CN116082401A - Alpha-carbon chiral phosphine compound and preparation method thereof - Google Patents
Alpha-carbon chiral phosphine compound and preparation method thereof Download PDFInfo
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- CN116082401A CN116082401A CN202310064532.0A CN202310064532A CN116082401A CN 116082401 A CN116082401 A CN 116082401A CN 202310064532 A CN202310064532 A CN 202310064532A CN 116082401 A CN116082401 A CN 116082401A
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- phosphine
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- -1 phosphine compound Chemical class 0.000 title claims abstract description 73
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 title claims abstract description 62
- 229910000073 phosphorus hydride Inorganic materials 0.000 title claims abstract description 49
- 229910052799 carbon Inorganic materials 0.000 title claims abstract description 39
- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- 238000006243 chemical reaction Methods 0.000 claims abstract description 90
- 239000003446 ligand Substances 0.000 claims abstract description 47
- 239000003054 catalyst Substances 0.000 claims abstract description 35
- 150000001875 compounds Chemical class 0.000 claims abstract description 35
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 claims abstract description 25
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims abstract description 23
- 229910052796 boron Inorganic materials 0.000 claims abstract description 23
- 230000005588 protonation Effects 0.000 claims abstract description 21
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 20
- 239000000654 additive Substances 0.000 claims abstract description 15
- 230000000996 additive effect Effects 0.000 claims abstract description 15
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 13
- 239000003495 polar organic solvent Substances 0.000 claims abstract description 7
- BMQDAIUNAGXSKR-UHFFFAOYSA-N (3-hydroxy-2,3-dimethylbutan-2-yl)oxyboronic acid Chemical compound CC(C)(O)C(C)(C)OB(O)O BMQDAIUNAGXSKR-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000012298 atmosphere Substances 0.000 claims abstract description 6
- 230000001681 protective effect Effects 0.000 claims abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 125000003107 substituted aryl group Chemical group 0.000 claims description 16
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 15
- 239000010949 copper Substances 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 5
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical group [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 150000007514 bases Chemical class 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- IVDFJHOHABJVEH-UHFFFAOYSA-N HOCMe2CMe2OH Natural products CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 claims description 3
- 239000004327 boric acid Substances 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 abstract description 3
- 238000001308 synthesis method Methods 0.000 abstract description 3
- 238000007036 catalytic synthesis reaction Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 165
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 143
- 238000005481 NMR spectroscopy Methods 0.000 description 115
- 235000019439 ethyl acetate Nutrition 0.000 description 73
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 71
- 239000003208 petroleum Substances 0.000 description 67
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 66
- 238000004440 column chromatography Methods 0.000 description 65
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 56
- 239000003480 eluent Substances 0.000 description 56
- 239000000741 silica gel Substances 0.000 description 55
- 229910002027 silica gel Inorganic materials 0.000 description 55
- 238000004009 13C{1H}-NMR spectroscopy Methods 0.000 description 54
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 54
- 239000007787 solid Substances 0.000 description 45
- 239000000047 product Substances 0.000 description 40
- 238000004128 high performance liquid chromatography Methods 0.000 description 34
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 26
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
- 239000011734 sodium Substances 0.000 description 19
- 239000002904 solvent Substances 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 15
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 description 12
- AUONHKJOIZSQGR-UHFFFAOYSA-N oxophosphane Chemical compound P=O AUONHKJOIZSQGR-UHFFFAOYSA-N 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 150000003003 phosphines Chemical class 0.000 description 11
- 239000012043 crude product Substances 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 239000004305 biphenyl Substances 0.000 description 7
- 235000010290 biphenyl Nutrition 0.000 description 7
- 125000006267 biphenyl group Chemical group 0.000 description 7
- 238000006555 catalytic reaction Methods 0.000 description 7
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 7
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000032798 delamination Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 239000012295 chemical reaction liquid Substances 0.000 description 3
- 229910052802 copper Inorganic materials 0.000 description 3
- CSHQDFGRFMLWRA-UHFFFAOYSA-N copper(1+);prop-1-ene Chemical compound [Cu+].[CH2-]C=C CSHQDFGRFMLWRA-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- REJGOFYVRVIODZ-UHFFFAOYSA-N phosphanium;chloride Chemical compound P.Cl REJGOFYVRVIODZ-UHFFFAOYSA-N 0.000 description 3
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 3
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- VHHAZLMVLLIMHT-CUPIEXAXSA-N (2s,5s)-1-[2-[(2s,5s)-2,5-diphenylphospholan-1-yl]ethyl]-2,5-diphenylphospholane Chemical compound C1([C@@H]2CC[C@H](P2CCP2[C@@H](CC[C@H]2C=2C=CC=CC=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=CC=C1 VHHAZLMVLLIMHT-CUPIEXAXSA-N 0.000 description 2
- UWNADWZGEHDQAB-UHFFFAOYSA-N 2,5-dimethylhexane Chemical group CC(C)CCC(C)C UWNADWZGEHDQAB-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 2
- 238000005885 boration reaction Methods 0.000 description 2
- FZQBLSFKFKIKJI-UHFFFAOYSA-N boron copper Chemical compound [B].[Cu] FZQBLSFKFKIKJI-UHFFFAOYSA-N 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 150000001993 dienes Chemical class 0.000 description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- NITUNGCLDSFVDL-UHFFFAOYSA-N 3-phenylprop-2-yn-1-ol Chemical compound OCC#CC1=CC=CC=C1 NITUNGCLDSFVDL-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- AFCIMSXHQSIHQW-UHFFFAOYSA-N [O].[P] Chemical group [O].[P] AFCIMSXHQSIHQW-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000001503 aryl iodides Chemical class 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- QHRVFPPZMPHYHA-UHFFFAOYSA-N bis(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1PC1=CC=CC=C1C QHRVFPPZMPHYHA-UHFFFAOYSA-N 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- WILFNLHOTDCRAO-UHFFFAOYSA-N copper(1+);2-methylpropan-2-olate Chemical group [Cu+].CC(C)(C)[O-] WILFNLHOTDCRAO-UHFFFAOYSA-N 0.000 description 1
- RFKZUAOAYVHBOY-UHFFFAOYSA-M copper(1+);acetate Chemical compound [Cu+].CC([O-])=O RFKZUAOAYVHBOY-UHFFFAOYSA-M 0.000 description 1
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
- YOPUATYREUZXIO-UHFFFAOYSA-N copper;methanol Chemical compound [Cu].OC YOPUATYREUZXIO-UHFFFAOYSA-N 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- SQRXMWYMVOILDH-UHFFFAOYSA-N diphenylphosphanyloxy(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)OP(C=1C=CC=CC=1)C1=CC=CC=C1 SQRXMWYMVOILDH-UHFFFAOYSA-N 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- DYUWQWMXZHDZOR-UHFFFAOYSA-N methyl 4-iodobenzoate Chemical compound COC(=O)C1=CC=C(I)C=C1 DYUWQWMXZHDZOR-UHFFFAOYSA-N 0.000 description 1
- KTMKRRPZPWUYKK-UHFFFAOYSA-N methylboronic acid Chemical compound CB(O)O KTMKRRPZPWUYKK-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 150000008300 phosphoramidites Chemical class 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- TWBSQLRYTAQHCV-UHFFFAOYSA-N prop-2-enylidenephosphane Chemical compound C=CC=P TWBSQLRYTAQHCV-UHFFFAOYSA-N 0.000 description 1
- QHJWOSHIGFDANE-UHFFFAOYSA-N prop-2-enylphosphane Chemical compound PCC=C QHJWOSHIGFDANE-UHFFFAOYSA-N 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
Images
Classifications
-
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Abstract
The invention belongs to the technical field of asymmetric catalytic synthesis, and particularly relates to an alpha-carbon chiral phosphine compound and a preparation method thereof. In the protective gas atmosphere, carrying out asymmetric boron protonation reaction on a dienylphosphine oxide compound with a structure shown in a formula II, pinacol borate, a copper (I) catalyst, a chiral ligand, an organic alkaline compound and a proton additive in a polar organic solvent to obtain an alpha-carbon chiral phosphine compound with the structure shown in the formula I; the chiral ligand is a cyclic phosphine ligand (S, S) -Ph-BPE or a cyclic phosphine ligand (R, R) -Ph-BPE. The preparation method provided by the invention can synthesize the alpha-carbon chiral phosphine compound with the structure shown in the formula I with high yield and excellent enantioselectivity, the synthesis method is simple and low in cost, and the alpha-carbon chiral phosphine compound can be further converted into a new optical active product.
Description
Technical Field
The invention belongs to the technical field of asymmetric catalytic synthesis, and particularly relates to an alpha-carbon chiral phosphine compound and a preparation method thereof.
Background
Chiral phosphine compounds have important applications in the fields of organic synthesis, pharmaceutical chemistry or material science, etc. Chiral phosphine compounds play a significant role in the synthesis of chiral compounds as ligands in organic catalysts or asymmetric catalysis of transition metals. However, the synthesis of chiral phosphine compounds at present mainly depends on a method using a stoichiometric chiral auxiliary reagent or chiral resolution, and the effective chiral reagent has few types, large dosage and limited application range; the chiral resolution method is complicated, the resolution effect is unstable, and the synthesis and the application of chiral phosphine compounds with various structures and multiple functions are greatly limited.
The chiral phosphine compound is synthesized by utilizing an asymmetric catalysis method, and has the advantages of environmental protection, adjustable catalysis system, capability of obtaining various chiral types, diversified structures and the like. Asymmetric boration of phosphine compounds containing unsaturated bonds using transition metal catalysis is an effective method for constructing chiral centers. For example, phosphine compounds containing carbon-carbon double bonds can be prepared into beta-, gamma-or delta-carbon chiral phosphine compounds by asymmetric borohydride under the catalysis of copper or rhodium.
However, the above-described asymmetric boration reaction method is not effective for synthesizing an α -carbon chiral phosphine compound.
Disclosure of Invention
The invention aims to provide an alpha-carbon chiral phosphine compound and a preparation method thereof, wherein the alpha-carbon chiral phosphine compound with a structure shown in a formula I is synthesized through an asymmetric boron protonation reaction with high yield and high enantioselectivity by adopting a copper (I) catalyst as a catalyst, the synthesis method is simple and low in cost, and the alpha-carbon chiral phosphine compound can be further converted into a new optical active product.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides an alpha-carbon chiral phosphine compound, which has a structure shown in a formula I:
in the formula I, the R 1 Is C 1～8 Alkyl, C of (2) 3～8 Cycloalkyl, C 1～8 Alkoxy, amino, aryl or substituted aryl groups, said R 1 The substituent on the substituted aryl is fluorine, chlorine, bromine, nitro, trifluoromethyl, C 1～4 Alkyl and C of (C) 1～4 At least one of the alkoxy groups of (a);
the R is 2 Is C 1～4 Alkyl, aryl, substituted aryl or thienyl, R 2 The substituent on the substituted aryl is fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl, C 1～4 Alkyl, C of (2) 1～4 Alkoxy, C 1～4 At least one of an alkoxy group, an ester group and a cyano group.
Preferably, said R 1 Is phenyl group,
MeO-, etO-, or +.>
The R is 2 Is phenyl, naphthyl,
Preferably, the alpha-carbon chiral phosphine compound has any one of the following structures:
the invention provides a preparation method of an alpha-carbon chiral phosphine compound, which comprises the following steps:
in a protective gas atmosphere, carrying out asymmetric boron protonation reaction on a dienylphosphine oxide compound with a structure shown in a formula II, pinacol boric acid ester, a copper (I) catalyst, a chiral ligand, an organic alkaline compound and a proton additive in a polar organic solvent to obtain the alpha-carbon chiral phosphine compound; the chiral ligand is a cyclic phosphine ligand (S, S) -Ph-BPE or a cyclic phosphine ligand (R, R) -Ph-BPE;
preferably, the copper (I) catalyst is CuCl, cuBr, cuI, cuOAc, cuTc and Cu (CH) 3 CN) 4 PF 6 One or more of the following.
Preferably, the temperature of the asymmetric boron protonation reaction is-30 to-60 ℃.
Preferably, the organic basic compound is sodium t-butoxide.
Preferably, the proton additive is methanol.
Preferably, the mole ratio of the dienylphosphine oxide compound with the structure shown in the formula II and the pinacol borate is 1 (1-2);
the mol ratio of the alkenyl phosphine oxide compound with the structure shown in the formula II to the copper (I) catalyst is 1:0.05;
the mol ratio of the dienylphosphine oxide with the structure shown in the formula II to the chiral ligand is 1:0.06;
the mol ratio of the alkenyl phosphine oxide compound with the structure shown in the formula II to the proton additive is 1:2;
the molar ratio of the alkenyl phosphine oxide compound with the structure shown in the formula II to the organic alkaline compound is 1:0.2.
Preferably, the copper (I) catalyst is CuOAc; the temperature of the asymmetric boron protonation reaction is-55 ℃.
The invention provides an alpha-carbon chiral phosphine compound, which has a structure shown in a formula I, wherein R is 1 Is C 1～8 Alkyl, C of (2) 3～8 Cycloalkyl, C 1～8 Alkoxy, amino, aryl or substituted aryl groups, said R 1 The substituent on the substituted aryl is fluorine, chlorine, bromine, nitro, trifluoromethyl, C 1～4 Alkyl and C of (C) 1～4 At least one of the alkoxy groups of (a); the R is 2 Is C 1～4 Alkyl, aryl, substituted aryl or thienyl, R 2 The substituent on the substituted aryl is fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl, C 1～4 Alkyl, C of (2) 1～4 Alkoxy, C 1～4 At least one of an alkoxy group, an ester group and a cyano group. The boron functionalized chiral allylphosphine oxide compound with the structure shown in the formula I can be further converted into a new optical active product, so that the synthesis method of the chiral phosphine compound is expanded, and the application of the chiral phosphine oxide compound in the synthesis of the chiral compound is widened.
The invention provides a preparation method of an alpha-carbon chiral phosphine compound, which comprises the following steps: in the atmosphere of protective gas, the dienylphosphine oxide compound with the structure shown in the formula II and pinacol borate (B) 2 pin 2 ) Carrying out asymmetric boron protonation reaction on copper (I) catalyst, chiral ligand, organic alkaline compound and proton additive in polar organic solvent to obtain the alpha-carbon chiral phosphine compound; the chiral ligand is a cyclic phosphine ligand (S, S) -Ph-BPE or a cyclic phosphine ligand (R, R) -Ph-BPE. The preparation method provided by the invention generates the copper (I) complex in situ by chiral ligand and copper (I) catalyst under the action of organic alkaline compound, and then the copper (I) complex and B 2 pin 2 Generating metal conversion reactionAn active copper boron complex; the alkenyl phosphine oxide compound with the structure shown in the formula II and the copper boron complex undergo a borocupnization reaction to form an allyl copper intermediate; finally, the allyl copper intermediate and the proton additive are protonated to obtain the target product alpha-carbon chiral phosphine compound, and the copper (I) catalyst is regenerated. The preparation method provided by the invention has regioselectivity in the process of inducing the diene boronation due to the electron-withdrawing property of the phosphorus oxygen group, and the obtained allyl copper intermediate is a key step for realizing higher enantioselectivity. The preparation method provided by the invention can synthesize the alpha-carbon chiral phosphine compound with the structure shown in the formula I with high yield and excellent enantioselectivity.
Drawings
FIG. 1 is a diagram of compound 2a in example 1 of the present invention 1 H NMR spectrum;
FIG. 2 shows a single crystal diffraction structure of Compound 6 in the application example of the present invention.
Detailed Description
The invention provides an alpha-carbon chiral phosphine compound, which has a structure shown in a formula I:
in the formula I, the R 1 Is C 1～8 Alkyl, C of (2) 3～8 Cycloalkyl, C 1～8 Alkoxy, amino, aryl or substituted aryl groups, said R 1 The substituent on the substituted aryl is fluorine, chlorine, bromine, nitro, trifluoromethyl, C 1～4 Alkyl and C of (C) 1～4 At least one of the alkoxy groups of (a);
the R is 2 Is C 1～4 Alkyl, aryl, substituted aryl or thienyl, R 2 The substituent on the substituted aryl is fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl, C 1～4 Alkyl, C of (2) 1～4 Alkoxy, C 1～4 At least one of an alkoxy group, an ester group and a cyano group.
In the present invention, the R 1 Preferably phenyl,
MeO-, etO-, or +.>
In the present invention, the R 2 Preferably phenyl, naphthyl,
In the present invention, the α -carbon chiral phosphine compound preferably has any one of the following structures:
the invention provides a preparation method of an alpha-carbon chiral phosphine compound, which comprises the following steps:
in a protective gas atmosphere, carrying out asymmetric boron protonation reaction on a dienylphosphine oxide compound with a structure shown in a formula II, pinacol boric acid ester, a copper (I) catalyst, a chiral ligand, an organic alkaline compound and a proton additive in a polar organic solvent to obtain the alpha-carbon chiral phosphine compound; the chiral ligand is a cyclic phosphine ligand (S, S) -Ph-BPE or a cyclic phosphine ligand (R, R) -Ph-BPE;
in the present invention, all preparation materials/components are commercially available products well known to those skilled in the art unless specified otherwise.
The invention has no special requirement on the source of the alkenyl phosphine oxide compound with the structure shown in the formula II, and the alkenyl phosphine oxide compound is prepared by a preparation method well known to a person skilled in the art.
In the invention, the structural formula of the cyclic phosphine ligand (S, S) -Ph-BPE is shown in a formula III:
in the invention, the structural formula of the cyclic phosphine ligand (R, R) -Ph-BPE is shown in a formula IV:
in the present invention, the copper (I) catalyst is preferably CuCl, cuBr, cuI, cuOAc, cuTc and Cu (CH) 3 CN) 4 PF 6 More preferably CuOAc.
In the present invention, the organic basic compound is sodium t-butoxide.
In the present invention, the proton additive is methanol.
In the invention, when the proton additive is methanol, the chiral ligand and the copper (I) catalyst generate an alkoxy copper (I) complex in situ under the action of the organic alkaline compound, wherein the alkoxy copper (I) complex is tert-butoxycopper generated by the copper catalyst and alkali tert-butoxide sodium when the catalytic reaction is started, or is reacted with methanol in a catalytic cycle to generate methoxy copper after protonation.
In the present invention, the polar organic solvent is preferably at least one selected from tetrahydrofuran, methyl tert-butyl ether, diethyl ether and toluene, more preferably toluene.
In the present invention, the molar ratio of the alkenylphosphine oxide compound of the structure represented by formula II to the pinacol borate is preferably 1 (1-2), more preferably 1 (1-1.7), and most preferably 1 (1-1.5).
In the present invention, the molar ratio of the alkenylphosphine oxide compound of the structure represented by formula II to the copper (I) catalyst is preferably 1:0.05.
In the present invention, the molar ratio of the dienylphosphine oxide of the structure of formula II to the chiral ligand is preferably 1:0.06.
In the present invention, the molar ratio of the alkenylphosphine oxide compound of the structure represented by formula II to the proton additive is preferably 1:2.
In the present invention, the molar ratio of the alkenylphosphine oxide compound of the structure represented by formula II to the organic basic compound is preferably 1:0.2.
The invention has no special requirement on the dosage of the polar organic solvent, and ensures that the asymmetric boron protonation reaction is smoothly carried out.
In the present invention, the temperature of the asymmetric boron protonation reaction is-30 to-60 ℃, more preferably-55 ℃. In the invention, the heat preservation time of the asymmetric boron protonation reaction is preferably 12-24 h. In the present invention, the asymmetric boron protonation reaction is preferably carried out under stirring.
In the present invention, the shielding gas is preferably nitrogen.
In the present invention, the mixing sequence of the raw materials for the asymmetric boron protonation reaction is preferably as follows: in the atmosphere of protective gas, stirring and mixing the copper (I) catalyst, chiral ligand, organic alkaline compound and polar organic for 30min at room temperature, cooling to the temperature of the asymmetric boron protonation reaction, and sequentially adding pinacol borate, the dienylphosphine oxide compound with the structure shown in the formula II and a proton additive.
In the invention, the reaction liquid is obtained after the asymmetric boron is protonated, and the invention preferably carries out post-treatment on the reaction liquid to obtain the alpha-carbon chiral phosphine compound. In the present invention, the post-treatment preferably includes the steps of: concentrating the reaction liquid to obtain a concentrate; and (3) performing column chromatography purification on the concentrate to obtain the alpha-carbon chiral phosphine compound. In the invention, the eluent used for the column chromatography purification is preferably a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is preferably 1:1.
The technical solutions provided by the present invention are described in detail below with reference to the drawings and examples for further illustrating the present invention, but they should not be construed as limiting the scope of the present invention.
In the examples of the present invention, both the reagents and solvents used were commercially available analytical grade. The reaction solvent was distilled under standard conditions to give anhydrous and oxygen-free solvent, and the MTBE, THF and toluene used in the reaction were dried over sodium reflux. The product is purified by using petroleum ether (60-90 ℃) and ethyl acetate as eluent and 200-300 meshes of silica gel. NMR measurements were performed on JEOL 400 and JEOL 600 nuclear magnetic resonance spectrometers with CDCl 3 As solvent in CDCl 3 (delta (1H): 7.26ppm; delta (13C): 77.16 ppm) is the chemical shift reference. Enantioselectivity was analyzed by liquid chromatography.
Wherein, the preparation method of the allenylphosphine oxide compound comprises the following steps:
(1) Preparation of alkynols:
method A:
according to the reaction scheme shown in formula 1: to a Schlenk flask, a magneton was added, vacuum was applied and replaced with nitrogen, phenylacetylene (1 equiv) and tetrahydrofuran (0.1M) were sequentially added three times, n-BuLi (2.5M in hexane,1equiv) was added dropwise over 30min at 0℃after the addition was completed, the reaction was stirred at 0℃for one hour, then paraformaldehyde (1.4 equiv) was added, and the reaction was allowed to warm to room temperature and stirred overnight. After the reaction was completed, saturated ammonium chloride was slowly added to quench the reaction, the mixture was allowed to stand for delamination, the organic phase was removed by a separating funnel, the aqueous phase was extracted 3 times with ethyl acetate, the organic phase was combined, the organic phase was washed with a saturated sodium chloride solution, and finally, the organic phase was dried over anhydrous sodium sulfate. Concentration by filtration and isolation of the crude product by column chromatography (petroleum ether: ethyl acetate=2:1, v: v) gave 3-phenyl-2-propyn-1-ol in 86% yield.
Method B:
according to the reaction scheme shown in formula 2: adding magneton into Schlenk bottle, vacuumizing, replacing with nitrogen, repeating for three times, adding Pd (PPh) 3 ) 2 Cl 2 (1 mol%) and CuI (2 mol%) followed by sequential addition of Et 3 N (0.25M), aryl iodide (1 equiv) and propynyl alcohol (1.1 equiv), the reaction was heated to 60 ℃ and stirring was continued for 5 hours. After the reaction was completed, cooled to room temperature, the reaction solution was filtered, and the solid residue was taken up in Et 3 N washing, combining the washing and organic phases, removing the solvent by rotary evaporator, and separating the crude product by column chromatography (petroleum ether: ethyl acetate=2:1, v: v) to give the product. Propargyl alcohol as shown in Table 1 was obtained according to method B.
Table 1 propargyl alcohol obtained in method B
(2) Preparation of phosphine chloride:
according to the reaction scheme shown in formula 3: a250 mL three-necked flask equipped with a reflux condenser and a magnetic stirring bar was evacuated to displace nitrogen three times, magnesium (Mg) chip (1.2 equiv) and a small amount of tetrahydrofuran were sequentially added, followed by adding a small amount of elemental iodine and heating the mixture with a heat gun until the color disappeared. A solution of R-Br (1 equiv) in tetrahydrofuran (1.0M) was added dropwise, with reflux maintained throughout the addition. After the addition was completed, the reaction was heated with an oil bath at 60 ℃ for 4 hours, and then cooled to room temperature.
According to the reaction scheme shown in formula 4: nitrogen protectionUnder the condition of adding Et 2 NPCl 2 (1 equiv) and tetrahydrofuran (0.67M), cooled to 0deg.C, and Grignard reagent (RMgBr, 2.05 equiv) was added dropwise, and the reaction was stirred at 0deg.C for 3 hours and then the solvent was removed on a rotary evaporator to leave a brown slurry. Cyclohexane was added to the slurry and filtered through a sand core funnel, and then anhydrous HCl gas was bubbled into the solution with continuous stirring for 1 hour, and the resulting reaction solution was filtered under nitrogen protection and the solvent was removed on a rotary evaporator and immediately used for the next reaction. The phosphine chloride shown in table 2 was prepared as described above.
TABLE 2 preparation of phosphine chloride according to the flow chart shown in formula 4
(3) Preparation of the diene:
according to the reaction scheme shown in formula 5: adding the magneton into a Schlenk bottle, vacuumizing and replacing with nitrogen, repeating for three times, adding alkynol (1 equiv), triethylamine (1.5 equiv) and tetrahydrofuran (0.33M), cooling to-78deg.C, and cooling to-78deg.C 1 2 The solution of PCl (1.2 equiv) in tetrahydrofuran was slowly added dropwise to the reaction flask, after the dropwise addition was completed, the reaction was warmed to room temperature (3 i and 3j were heated to 60 ℃ for further reaction), after the completion of the reaction, the reaction was quenched by slowly adding dilute HCl (0.1M), allowed to stand for delamination, the organic phase was removed by a separating funnel and the aqueous phase was extracted 3 times with ethyl acetate, the organic phases were combined, washed with saturated sodium chloride solution, and finally dried over anhydrous sodium sulfate. Concentration by filtration and separation of the crude product by column chromatography (petroleum ether: ethyl acetate=1:1, v: v) gives the dienylphosphino-oxy compounds shown in table 3.
TABLE 3 Bisphinoxy Compounds used in the examples of the invention
Example 1
According to the reaction scheme shown in formula 6: taking 25mL Schlenk tube, adding cuprous acetate (accounting for 5mol% of the dienylphosphine oxide) and (S, S) -Ph-BPE (accounting for 6mol% of the dienylphosphine oxide) under the protection of nitrogen, stirring for 30min at room temperature, cooling to-55deg.C, adding sodium tert-butoxide (accounting for 20mol% of the dienylphosphine oxide) and toluene (2 mL), adding B 2 pin 2 (1.2 equiv), followed by addition of a dienylphosphino-oxy compound (0.2 mmol,1.0 equiv) and methanol (2 equiv). After the reaction is finished, the reaction solution is quenched by an ammonium chloride solution and is directly concentrated, and the crude product is separated by column chromatography (petroleum ether: ethyl acetate=1:1, v: v) to obtain a target product, namely the alpha-carbon chiral phosphine compound with the structure shown in the formula I; wherein the dienylphosphino compound is a dienylphosphino compound of the above-described method, which is designated 1a,1b,1c,1d,1e,1f,1g,1h,1i,1j,1k,1l,1m,1n,1o,1p,1q,1r,3a,3b,3c,3d,3e,3f,3g,3h,3i,3j or 3k of Table 3;
the α -carbon chiral phosphine compounds prepared in this example are specifically α -carbon chiral phosphine compounds having the structure shown in formula I and designated as 2a,2b,2c,2d,2e,2f,2g,2h,2I,2j,2k,2l,2m,2n,2o,2p,2q,2r,4a,4b,4c,4d,4e,4f,4g,4h,4I,4j or 4k in tables 4 and 5;
TABLE 4 specific Structure, yield and ee values of partial alpha-carbon chiral phosphine Compounds a
TABLE 5 specific Structure, yield and ee values of the remaining alpha-carbon chiral phosphine compounds a
From tables 4 and 5, it can be derived that:
when the para-position is halogen substituent (F, cl and Br), the reactants are smoothly subjected to asymmetric boron protonation, giving 2b-d in excellent yields and high ee values. The reactants with electron donating groups also gave the corresponding products 2e-g in excellent yields and ee values of greater than 96%, while the electron withdrawing groups reduced the enantioselectivity (2 h-j). When the α -benzene ring bears a meta substituent, the dienyl diphenylphosphine oxide reactant was successfully converted to the corresponding products 2k and 2l in 99%, 81% yield and 95%, 93% ee, respectively. When the alpha-phenyl group contains ortho-substitution, the effect of steric hindrance is observed, giving the products 2m and 2n in moderate yields, with ee values of 76% and 89%, respectively, whereas the naphthyl-substituted substrate gives the product 2o in 60% yield and 44% ee value. Thienyl substituted dienyldiphenylphosphinoxide was obtained in 95%, 85% yield and 94%, 81% ee value for the corresponding products 2p and 2q, respectively. Boron protonation of the α -methyl-dienyl diphenylphosphino oxide gives the corresponding product 2r in 68% yield and 79% ee. When the phosphorus atom contains an aromatic substituent which is para, meta or ortho, the asymmetric boron protonation proceeds smoothly to give the products 4a-f in 50-83% yield and 78-96% enantioselectivity. Under these conditions, the dicyclohexyl-or diisobutyl-substituted dienylphosphinoxide compound gave the desired product (4 g-h) in moderate yield and good enantiomeric excess (80-86% ee). The dienylphosphonate is also suitable for this reaction, with yields of 45% and 88% for 4i and 4j, respectively, and ee values of 94% and 95%, respectively. Product 4k was obtained from the dienylphosphindiamide in moderate yields and ee values.
Example 2
100mL Schlenk tube was taken and charged with copper acetate (19.6 mg,5 mol%) respectively, (S, S) -Ph-BPE (97.3 mg,6 mol%), sodium tert-butoxide (20 mol%) and toluene (30 mL) under nitrogen, stirred at room temperature for 30min, cooled to-55deg.C, and charged with B 2 pin 2 (0.98 g,3.84 mmol) followed by 1a (1.0 g,3.2 mmol) and methanol (2 equiv). To be reacted to completionAfter that, the reaction solution was directly concentrated, and the crude product was separated by column chromatography (petroleum ether: ethyl acetate=1:1, v:v) to give the objective product 2a.
This implementation examined gram-scale reaction of asymmetric boron protonation of 1a, and 2a was obtained in 96% yield and 96% ee value, demonstrating the effectiveness of the preparation method provided by the present invention.
Example 3
The present example screens for the types of chiral ligands:
according to the reaction scheme shown in formula 7, the present example uses substrates 1a and B 2 pin 2 The reaction of (2) is to optimize the kind of chiral ligand for the model. At room temperature, cu (CH) 3 CN) 4 PF 6 The ligand used in the reaction was screened using tetrahydrofuran as the solvent, sodium tert-butoxide as the base and methanol as the proton additive, and the experimental parameters are shown in table 6.
TABLE 6 kinds of chiral ligands and specific reaction conditions used in example 3
Appendix 1:1a (0.2 mmol), B 2 pin 2 (0.24mmol),Cu(CH 3 CN) 4 PF 6 (5 mol% of 1 a), L1-8 (6 mol% of 1 a), L9-10 (12 mol% of 1 a), naO t Bu (20 mol% of 1 a), meOH (0.4 mmol), THF (2 mL).
Appendix 2: and (5) separating and purifying to obtain the yield.
L1 to L10 in Table 6 are respectively:
the results in Table 6 show that when (S) -BINAP is used as ligand, the yield and enantioselectivity of the reaction are relatively low, 20% and 13% ee (Table 6, SEQ ID NO: 1), respectively, and then the present example tries again to try ligand L2 of BINAP skeleton, while the yield is increased, the ee value is still low (Table 6, SEQ ID NO: 2). When highly sterically hindered L3 was used as ligand, the yield was 49% (Table 6, SEQ ID NO: 3). When ligand L4 was used, the product was obtained in 72% yield and 13% ee (Table 6, SEQ ID NO: 4). The cyclic phosphine ligand (S, S) -Ph-BPE (L5) promotes the reaction, the yield and the enantioselectivity are obviously improved, and the ee value of the product is 63% (Table 6, sequence number 5). When L5 was replaced with ligand L6 of the same backbone, the reaction was almost enantioselective (Table 6, SEQ ID NO: 6). No reaction occurred when L7 was used as ligand (table 6, no. 7), and the ee value of the product was 35% when L8 was used as ligand (table 6, no. 8). Further screening showed that the product was obtained in similar yields but without enantioselectivity when using other ligands such as (R) -MeO-MOP and phosphoramidite ligands (Table 6, SEQ ID NO: 9, 10). As is clear from the results in Table 6, ligand L5 was the best ligand.
Example 4
The present example screens the copper (I) catalyst species:
example 3 the optimum chiral ligand was determined and the effect of the copper (I) catalyst on the reaction was investigated in accordance with the reaction scheme shown in equation 8 and the reaction conditions in table 7 by lowering the reaction temperature to-30 c in order to further increase the enantioselectivity of the reaction, and the results are shown in table 7.
As is clear from the results in Table 7, when the reaction temperature was lowered from room temperature to-30 ℃, the yield and the enantioselectivity were significantly improved. This example first investigated the effect of cuprous salts on the reaction catalysis. When Cu (CH) 3 CN) 4 PF 6 As a catalyst, the yield and ee value were increased to 77% and 85%, respectively (Table 7, SEQ ID NO: 1). When CuCl was used as catalyst, the product was obtained with a similar ee (table 7, serial No. 2). When CuBr or CuI was used as the catalyst, the yields could be about 80%, but the ee values were relatively low, only 48% and 37%, respectively (Table 7, SEQ ID NO: 3, 4). CuOAc as catalyst gave the product in 88% yield and 90% ee (table 7, no. 5). While when CuTc is used as a catalyst, the yield is 80 percent, and the ee value is87% (Table 9, number 6). When using CuCl 2 As a catalyst, the productivity was significantly lowered, but the ee value was maintained at 80% or more (Table 7, SEQ ID NO: 7). When using CuBr 2 As a catalyst, the ee value was only 33% (Table 7, SEQ ID NO: 8). Cu (OAc) 2 、Cu(CF 3 SO 3 ) 2 Similar yields and poor enantioselectivities were obtained as catalysts (Table 7, ser. No. 9, 10). Thus CuOAc is the best catalyst.
TABLE 7 screening of copper (I) catalysts 1
Appendix 1:1a (0.2 mmol), B 2 pin 2 (0.24mmol),Cu catalyst(5mol％),(S,S)-Ph-BPE(6mol％),NaO t Bu(20mol％),MeOH(0.4mmol),THF(2mL)。
Appendix 2: and (5) separating and purifying to obtain the yield.
Example 5
The reaction conditions were screened in this example;
the reaction was carried out according to the reaction scheme described in formula 9 and the reaction conditions of Table 10, and the results are shown in Table 8.
As can be seen from the results in Table 10, the enantioselectivity of the product did not show a significant change when the temperature was lowered to-40 ℃ (Table 8, SEQ ID Nos. 1, 2). When KO is used t Bu instead of NaO t No reaction occurred when Bu was reacted (table 8, no. 3); when using LiO t Bu as the base of the reaction gave an ee value of only 43% (Table 8, SEQ ID NO: 4). With NaO t Bu was used as the base for the reaction, and the yield and ee value of the product were significantly reduced as the temperature was further reduced to-50 ℃ (Table 8, SEQ ID NO: 5). Insoluble solids were observed in the examples during the reaction, which is presumably due to the low solubility of the reactants and products. To further increase the enantioselectivity, a different approach was followedToluene, diethyl ether and methyl tertiary butyl ether. The yield of the product was 93% with toluene as solvent, the ee value was 93% (Table 8, SEQ ID NO: 6), whereas the yields were only 60% and 40% with diethyl ether and methyl tert-butyl ether, respectively (Table 8, SEQ ID NO: 7, 8). The desired product was obtained in 99% yield and 98% ee at-55℃with toluene as a solvent by further lowering the temperature (Table 8, SEQ ID NO: 9). When the temperature was lowered to-60 ℃, the yield was 92% (Table 8, SEQ ID NO: 10). Thus, the present invention determines the optimal conditions for the reaction: 5mol% CuOAc as catalyst, 6mol% (S, S) -Ph-BPE as ligand, 20mol% sodium tert-butoxide as base, toluene as solvent, the reaction is carried out at-55 ℃.
TABLE 8 optimization of reaction conditions 1
Appendix 1:1a (0.2 mmol), B 2 pin 2 (0.24mmol),CuOAc(5mol％),(S,S)-Ph-BPE(6mol％),base(20mol％),MeOH(0.4mmol),solvent(2mL)。
Appendix 2: and (5) separating and purifying to obtain the yield.
The structural characterization data of the dienylphosphine oxide compound with the structure shown in the formula II and the alpha-carbon chiral phosphine compound with the structure shown in the formula I, which are prepared in the embodiment of the invention, are specifically as follows:
diphenyl(1-(4-(trifluoromethoxy)phenyl)propa-1,2-dien-1-yl)phosphine oxide(1g):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,1.17g,74％yield,white solid,m.p.90-91℃. 1 H NMR(400MHz,CDCl 3 )δ7.77-7.72(m,4H),7.64(d,J＝8.8Hz,2H),7.54-7.50(m,2H),7.48-7.42(m,4H),7.10(d,J＝8.4Hz,2H),4.92(d,J＝10.8Hz,2H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ213.5(d,J＝6.6Hz),148.6,132.2(d,J＝2.3Hz),131.85(d,J＝9.7Hz),131.8(d,J＝105.7Hz),130.7(d,J＝5.9Hz),129.8(d,J＝4.5Hz),128.5(d,J＝12.6Hz),121.1,120.8,99.8(d,J＝10.0Hz),79.0(d,J＝12.2Hz). 31 P NMR(162MHz,CDCl 3 )δ29.3. 19 F NMR(376MHz,CDCl 3 )δ-57.8.HRMS(ESI-MS)m/z calcd.for C 22 H 17 F 3 O 2 P[M+H] + :401.0913,found:401.0918.
methyl 4-(1-(diphenylphosphoryl)propa-1,2-dien-1-yl)benzoate(1h):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,0.86g,84％yield,white solid,m.p.156-157℃. 1 H NMR(400MHz,CDCl 3 )δ7.91(d,J＝8.4Hz,2H),7.77-7.68(m,6H),7.51(dt,J＝7.6,1.2Hz,2H),7.45-7.41(m,4H),4.95(d,J＝10.4Hz,2H),3.86(s,3H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ214.0(d,J＝6.3Hz),166.8,136.9(d,J＝5.4Hz),132.1(d,J＝2.2Hz),131.8(d,J＝9.6Hz),131.76(d,J＝100Hz),129.9,129.1,128.5(d,J＝12.6Hz),128.2(d,J＝4.6Hz),100.6(d,J＝100.5Hz),79.2(d,J＝12.2Hz),52.2. 31 P NMR(162MHz,CDCl 3 )δ29.2.HRMS(ESI-MS)m/z calcd.for C 23 H 19 O 3 PK[M+K] + :413.0703,found:413.0702.
diphenyl(1-(4-(trifluoromethyl)phenyl)propa-1,2-dien-1-yl)phosphine oxide(1i):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,0.77g,39％yield,white solid,m.p.89-90℃. 1 H NMR(400MHz,CDCl 3 )δ7.77-7.72(m,6H),7.55-7.39(m,8H),4.96(d,J＝10.8Hz,2H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ213.9(d,J＝6.2Hz),135.9(d,J＝2.9Hz),132.3,132.1,131.8(d,J＝9.6Hz),131.6(d,J＝99.9Hz),129.6(q,J＝32.7Hz),128.55,128.54(d,J＝12.2Hz),125.6(d,J＝3.6Hz),124.1(q,J＝273.2Hz),100.2(d,J＝99.8Hz),79.3(d,J＝11.9Hz). 31 P NMR(162MHz,CDCl 3 )δ29.1. 19 F NMR(376MHz,CDCl 3 )δ-62.7.HRMS(ESI-MS)m/z calcd.for C 22 H 17 F 3 OP[M+H] + :385.0964,found:385.0964.
4-(1-(diphenylphosphoryl)propa-1,2-dien-1-yl)benzonitrile(1j):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,1.47g,91％yield,white solid,m.p.150-151℃. 1 H NMR(400MHz,CDCl 3 )δ7.76-7.71(m,6H),7.56-7.54(m,4H),7.45(dt,J＝7.6,2.8Hz,4H),4.99(d,J＝10.8Hz,2H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ214.0(d,J＝6.3Hz),137.3(d,J＝5.6Hz),132.40,132.36(d,J＝2.6Hz),131.8(d,J＝9.6Hz),131.5(d,J＝108.3Hz),128.8(d,J＝4.5Hz),128.6(d,J＝12.6Hz),118.8,111.2,100.3(d,J＝100.2Hz),79.5(d,J＝11.8Hz). 31 P NMR(162MHz,CDCl 3 )δ29.0.HRMS(ESI-MS)m/z calcd.for C 22 H 17 NOP[M+H] + :342.1042,found:342.1032.
(1-(3-chloro-4-fluorophenyl)propa-1,2-dien-1-yl)diphenylphosphine oxide(1k):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,1.47g,86％yield,white solid,m.p.133-134℃. 1 H NMR(400MHz,CDCl 3 )δ7.76-7.71(m,4H),7.63(dd,J＝6.8,2.0Hz,1H),7.58-7.50(m,3H),7.47-7.42(m,4H),7.01(t,J＝8.8Hz,1H),4.93(d,J＝10.8Hz,2H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ213.3(d,J＝6.9Hz),157.5(d,J＝251.3Hz),132.2(d,J＝2.1Hz),131.8(d,J＝9.7Hz),131.5(d,J＝107.8Hz),130.3(d,J＝5.2Hz),129.3,129.24,129.2,128.5(d,J＝12.6Hz),128.1(dd,J＝6.8,4.7Hz),121.2(d,J＝18.2Hz),116.7(d,J＝21.4Hz),99.2(d,J＝100.7Hz),79.3(d,J＝12.2Hz). 31 P NMR(162MHz,CDCl 3 )δ29.1. 19 F NMR(376MHz,CDCl 3 )δ-116.4.HRMS(ESI-MS)m/z calcd.for C 21 H 16 ClFOP[M+H] + :369.0606,found:369.0616.
(1-(3-methoxyphenyl)propa-1,2-dien-1-yl)diphenylphosphine oxide(1l):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,1.41g,69％yield,viscous oil. 1 H NMR(400MHz,CDCl 3 )δ7.79-7.78(m,1H),7.77-7.75(m,2H),7.74-7.73(m,1H),7.52-7.47(m,2H),7.45-7.40(m,4H),7.21-7.13(m,3H),6.76-6.73(m,1H),4.89(d,J＝10.8Hz,2H),3.70(s,3H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ213.6(d,J＝6.9Hz),159.7,133.3(d,J＝5.5Hz),132.2(d,J＝107.7Hz),132.0(d,J＝2.9Hz),131.9(d,J＝9.6Hz),129.7,128.4(d,J＝12.6Hz),120.9(d,J＝5.0Hz),113.8,113.5(d,J＝5.1Hz),100.8(d,J＝101.0Hz),78.6(d,J＝12.5Hz),55.3. 31 P NMR(162MHz,CDCl 3 )δ28.9.HRMS(ESI-MS)m/z calcd.for C 22 H 20 O 2 P[M+H] + :347.1195,found:347.1183.
(1-(2-chlorophenyl)propa-1,2-dien-1-yl)diphenylphosphine oxide(1m):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,0.64g,37％yield,white solid,m.p.107-108℃. 1 H NMR(400MHz,CDCl 3 )δ7.83-7.78(m,4H),7.77-7.75(m,1H),7.51-7.47(m,2H),7.44-7.40(m,4H),7.34-7.32(m,1H),7.18-7.12(m,2H),4.86(d,J＝10.8Hz,2H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ213.7(d,J＝6.3Hz),133.9(d,J＝5.9Hz),132.0(d,J＝2.4Hz),131.8(d,J＝9.6Hz),131.6(d,J＝107.2Hz),131.1(d,J＝1.9Hz),130.7(d,J＝5.9Hz),130.1,129.2,128.3(d,J＝12.5Hz),127.0,97.5(d,J＝101.7Hz),77.9(d,J＝12.1Hz). 31 P NMR(162MHz,CDCl 3 )δ28.8.HRMS(ESI-MS)m/z calcd.for C 21 H 17 ClOP[M+H] + :351.0700,found:351.0704.
(1-(2-iodophenyl)propa-1,2-dien-1-yl)diphenylphosphine oxide(1n):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,1.21g,87％yield,white solid,m.p.106-107℃. 1 H NMR(400MHz,CDCl 3 )δ7.86-7.79(m,5H),7.69(dt,J＝8.0,1.2Hz,1H),7.52-7.47(m,2H),7.45-7.40(m,4H),7.24-7.22(m,1H),6.89(dt,J＝7.6,1.2Hz,1H),4.96(d,J＝10.4Hz,2H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ213.1(d,J＝6.7Hz),140.0,135.7(d,J＝5.9Hz),132.02(d,J＝9.2Hz),132.01,131.4(d,J＝99.5Hz),130.2,129.5,128.4,128.3(d,J＝12.5Hz),103.7(d,J＝100.9Hz),100.7(d,J＝5.6Hz),79.3(d,J＝12.0Hz). 31 P NMR(162MHz,CDCl 3 )δ27.9.HRMS(ESI-MS)m/z calcd.for C 21 H 17 IOP[M+H] + :443.0056,found:443.0061.
(1-(naphthalen-1-yl)propa-1,2-dien-1-yl)diphenylphosphine oxide(1o):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,0.63 g,54％yield,white solid,m.p.141-142℃. 1 H NMR(400MHz,CDCl 3 )δ8.14(d,J＝8.0Hz,1H),7.82-7.77(m,5H),7.72(d,J＝8.0Hz,1H),7.67(d,J＝7.2Hz,1H),7.51-7.43(m,4H),7.40-7.33(m,5H),4.91(d,J＝10.8Hz,2H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ213.6(d,J＝6.7Hz),134.1,132.0,131.9(d,J＝9.5Hz),131.8(d,J＝4.6Hz),131.78(d,J＝106.6Hz),129.2(d,J＝4.9Hz),128.6(d,J＝9.1Hz),128.3(d,J＝12.5Hz),127.6(d,J＝3.7Hz),126.3,125.9,125.4,125.1,98.3(d,J＝98.7Hz),76.9(d,J＝15.7Hz). 31 P NMR(162MHz,CDCl 3 )δ28.0.HRMS(ESI-MS)m/z calcd.for C 25 H 20 OP[M+H] + :367.1246,found:367.1250.
diphenyl(1-(thiophen-3-yl)propa-1,2-dien-1-yl)phosphine oxide(1p):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,0.57g,66％yield,reddish solid,m.p.133-134℃. 1 H NMR(400MHz,CDCl 3 )δ7.78-7.73(m,4H),7.54-7.50(m,3H),7.46-7.42(m,4H),7.23-7.21(m,1H),7.16(d,J＝5.2Hz,1H),4.89(d,J＝11.2Hz,2H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ213.0(d,J＝6.6Hz),132.1(d,J＝2.4Hz),131.9(d,J＝9.6Hz),131.8(d,J＝107.6Hz),131.2(d,J＝5.7Hz),128.4(d,J＝12.5Hz),127.3(d,J＝5.9Hz),125.5,123.8(d,J＝2.9Hz),96.6(d,J＝102.2Hz),78.7(d,J＝12.5Hz). 31 P NMR(162MHz,CDCl 3 )δ29.3.HRMS(ESI-MS)m/z calcd.for C 19 H 16 OPS[M+H] + :323.0654,found:323.0650.
diphenyl(1-(thiophen-2-yl)propa-1,2-dien-1-yl)phosphine oxide(1q):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,1.32g,83％yield,yellow solid,m.p.111-112℃. 1 H NMR(400MHz,CDCl 3 )δ7.80-7.79(m,1H),7.78-7.76(m,2H),7.75-7.74(m,1H),7.55-7.50(m,2H),7.47-7.42(m,4H),7.28-7.27(m,1H),7.18(d,J＝5.2Hz,1H),6.89-6.87(m,1H),4.95(d,J＝10.8Hz,2H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ212.3(d,J＝5.9Hz),134.1(d,J＝8.7Hz),132.2(d,J＝2.4Hz),131.9(d,J＝9.7Hz),131.6(d,J＝108.2Hz),128.4(d,J＝12.7Hz),127.9,127.6(d,J＝2.6Hz),125.7,96.5(d,J＝100.7Hz),79.5(d,J＝11.9Hz). 31 PNMR(162MHz,CDCl 3 )δ28.7.HRMS(ESI-MS)m/z calcd.for C 19 H 16 OPS[M+H] + :323.0654,found:323.0662.
bis(4-fluorophenyl)(1-phenylpropa-1,2-dien-1-yl)phosphine oxide(3a):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,0.53g,31％yield,yellow solid,m.p.98-99℃. 1 H NMR(400MHz,CDCl 3 )δ7.86-7.74(m,2H),7.57(d,J＝6.8Hz,4H),7.30-7.11(m,7H),4.92(d,J＝10.8Hz,2H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ213.6(d,J＝7.0Hz),165.2(dd,J＝254.4,3.0Hz),134.4,134.3,134.2,131.7(dd,J＝29.2,5.5Hz),128.9,128.7(d,J＝65.1Hz),128.3(d,J＝4.9Hz),128.0(dd,J＝111.4,3.0Hz),115.9(dd,J＝21.6,13.9Hz),100.9(d,J＝102.7Hz),78.9(d,J＝12.6Hz). 31 P NMR(162MHz,CDCl 3 )δ27.7. 19 F NMR(376MHz,CDCl 3 )δ-106.3.HRMS(ESI-MS)m/z calcd.for C 21 H 16 F 2 OP[M+H] + :353.0901,found:353.0892.
bis(3,5-dimethylphenyl)(1-phenylpropa-1,2-dien-1-yl)phosphine oxide(3b):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,0.86g,46％yield,white solid,m.p.125-126℃. 1 H NMR(400MHz,CDCl 3 )δ7.57(d,J＝8.0Hz,2H),7.35(d,J＝12.4Hz,4H),7.26-7.22(m,2H),7.16(t,J＝7.2Hz,1H),7.10(s,2H),4.89(d,J＝10.8Hz,2H),2.30(s,12H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ213.6(d,J＝6.8Hz),137.9(d,J＝13.2Hz),133.7(d,J＝2.6Hz),132.2(d,J＝5.2Hz),131.9(d,J＝106.5Hz),129.4(d,J＝9.7Hz),128.6,128.4(d,J＝4.6Hz),127.5,100.8(d,J＝99.8Hz),78.3(d,J＝12.3Hz),21.4. 31 P NMR(162MHz,CDCl 3 )δ30.4.HRMS(ESI-MS)m/z calcd.for C 25 H 25 OPNa[M+Na] + :395.1535,found:395.1530.
(1-(4-bromophenyl)propa-1,2-dien-1-yl)bis(3,5-dimethylphenyl)phosphine oxide(3c):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,1.28g,61％yield,white solid,m.p.67-68℃. 1 H NMR(400MHz,CDCl 3 )δ7.47(d,J＝8.4Hz,2H),7.36-7.31(m,4H),7.11(s,2H),4.89(d,J＝10.8Hz,2H),2.30(s,12H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ213.4(d,J＝6.7Hz),138.1(d,J＝13.2Hz),133.8(d,J＝2.5Hz),131.7,131.6(d,J＝106.6Hz),131.4(d,J＝5.2Hz),130.0(d,J＝4.6Hz),129.4(d,J＝9.6Hz),121.7,100.2(d,J＝99.5Hz),78.8(d,J＝12.0Hz),21.4. 31 P NMR(162MHz,CDCl 3 )δ30.4.HRMS(ESI-MS)m/z calcd.for C 25 H 24 BrOPNa[M+Na] + :475.0623,found:475.0618.
bis(3-methoxyphenyl)(1-(p-tolyl)propa-1,2-dien-1-yl)phosphine oxide(3d):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,0.54g,46％yield,yellow viscous oil. 1 H NMR(400MHz,CDCl 3 )δ7.47(d,J＝8.0Hz,2H),7.37(d,J＝1.6Hz,1H),7.34-7.29(m,3H),7.26-7.22(m,2H),7.07-7.00(m,4H),4.88(d,J＝10.8Hz,2H),3.79(s,6H),2.67(s,3H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ213.4(d,J＝6.7Hz),159.5(d,J＝15.4Hz),137.6,133.5(d,J＝107.0Hz),129.51(d,J＝14.9Hz),129.49,129.1,128.9(d,J＝5.4Hz),128.2(d,J＝4.7Hz),124.2(d,J＝9.8Hz),118.3(d,J＝1.4Hz),116.5(d,J＝10.5Hz),100.5(d,J＝101.3Hz),78.5(d,J＝12.8Hz),55.5,21.3. 31 P NMR(162MHz,CDCl 3 )δ30.2.HRMS(ESI-MS)m/z calcd.for C 24 H 23 O 3 PNa[M+Na] + :413.1277,found:413.1274.
bis(2-methoxyphenyl)(1-phenylpropa-1,2-dien-1-yl)phosphine oxide(3e):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,0.42 g,22％yield,white solid,m.p.118-119℃. 1 H NMR(400MHz,CDCl 3 )δ7.70(dd,J＝7.6,1.2Hz,1H),7.66(dd,J＝7.6,1.2Hz,1H),7.62(d,J＝7.6Hz,2H),7.44(t,J＝7.6Hz,2H),7.22(t,J＝7.2Hz,2H),7.15(t,J＝7.2Hz,1H),6.99-6.95(m,2H),6.84(dd,J＝8.0,5.2Hz),4.87(d,J＝11.2Hz,2H),3.63(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ213.3(d,J＝6.7Hz),161.4(d,J＝2.1Hz),134.5(d,J＝8.4Hz),133.7,133.0(d,J＝5.7Hz),128.4,128.2(d,J＝4.8Hz),127.2,120.45(d,J＝110.5Hz),120.40(d,J＝12.6Hz),110.9(d,J＝6.9Hz),100.2(d,J＝107.9Hz),77.2(d,J＝14.3Hz),55.6. 31 P NMR(162MHz,CDCl 3 )δ27.9.HRMS(ESI-MS)m/z calcd.for C 23 H 21 O 3 PNa[M+Na] + :399.1121，found:399.1121.
(1-phenylpropa-1,2-dien-1-yl)di-o-tolylphosphine oxide(3f):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,0.34g,18％yield,white solid,m.p.107-108℃. 1 H NMR(400MHz,CDCl 3 )δ7.73(d,J＝8.0Hz,2H),7.43-7.38(m,4H),7.31-7.20(m,5H),7.16-7.13(m,2H),4.82(d,J＝10.8Hz,2H),2.58(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ212.7(d,J＝6.9Hz),143.3(d,J＝7.8Hz),132.9(d,J＝12.5Hz),132.3(d,J＝4.8Hz),132.0(d,J＝2.3Hz),131.8(d,J＝11.0Hz),130.5(d,J＝105.3Hz),128.8,128.5(d,J＝4.4Hz),127.7,125.4(d,J＝13.3Hz),100.3(d,J＝99.1Hz),77.8(d,J＝12.5Hz),21.8(d,J＝3.8Hz). 31 P NMR(162MHz,CDCl 3 )δ36.4.HRMS(ESI-MS)m/z calcd.for C 23 H 21 OPNa[M+Na] + :367.1222，found:367.1226.
diisobutyl(1-phenylpropa-1,2-dien-1-yl)phosphine oxide(3h):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,0.61g,74％yield,white oil. 1 H NMR(400MHz,CDCl 3 )δ7.61(d,J＝8.0Hz,2H),7.34-7.30(m,2H),7.26-7.23(m,1H),5.16(d,J＝10.0Hz,2H),2.19-2.06(m,2H),1.91-1.83(m,2H),1.78-1.70(m,2H),1.03-1.00(m,12H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ211.3(d,J＝6.6Hz),132.6(d,J＝4.9Hz),128.7,128.4(d,J＝3.8Hz),127.7,100.9(d,J＝86.7Hz),77.9(d,J＝11.1Hz),38.7(d,J＝69.1Hz),24.7(d,J＝8.6Hz),23.8(d,J＝3.7Hz). 31 P NMR(162MHz,CDCl 3 )δ40.9.HRMS(ESI-MS)m/z calcd.for C 17 H 25 OPNa[M+Na] + :277.1716,found:277.1715.
dimethyl(1-phenylpropa-1,2-dien-1-yl)phosphonate(3i):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝2:1)as eluent,0.70g,62％yield,green solid,m.p.117-118℃. 1 H NMR(400MHz,CDCl 3 )δ7.52(d,J＝8.0Hz,1H),7.34-7.30(m,2H),7.26-7.21(m,1H),5.32(d,J＝3.2Hz,2H),3.76(d,J＝11.2Hz). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ214.0(d,J＝4.5Hz),128.9(d,J＝22.6Hz),128.7,127.9,127.6(d,J＝6.1Hz),96.1(d,J＝190.6Hz),78.5(d,J＝14.7Hz),53.3(d,J＝6.1Hz). 31 P NMR(162MHz,CDCl 3 )δ18.3.HRMS(ESI-MS)m/z calcd.for C 11 H 14 O 3 P[M+H] + :225.0675,found:225.0673.
(3k):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝2:1)as eluent,0.81g,53％yield,brown solid,m.p.47-48℃. 1 H NMR(400MHz,CDCl 3 )δ7.70(d,J＝8.0Hz,2H),7.32-7.29(m,2H),7.21(d,J＝7.2Hz,1H),5.11(d,J＝11.2Hz,2H),3.12-3.04(m,8H),1.04(t,J＝7.2Hz,12H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ212.6(d,J＝4.4Hz),133.1(d,J＝6.1Hz),128.3,128.1(d,J＝4.9Hz),127.2,100.2(d,J＝150.8Hz),76.7(d,J＝12.9Hz),39.5(d,J＝4.4Hz),14.2(d,J＝1.3Hz). 31 P NMR(162MHz,CDCl 3 )δ28.0.HRMS(ESI-MS)m/z calcd.for C 17 H 28 N 2 OP[M+H] + :307.1934,found:307.1930.
diphenyl(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphine oxide(2a):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,87.8mg,99％yield,98％ee,white solid,m.p.159-160℃. 1 H NMR(400MHz,CDCl 3 )δ7.91-7.87(m,2H),7.52-7.41(m,7H),7.32(t,J＝7.2Hz,1H),7.26-7.22(m,2H),7.18-7.10(m,3H),6.68(br,1H),6.11(t,J＝2.4Hz,1H),4.63(d,J＝7.6Hz,1H),1.15(s,6H),1.10(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ137.0(d,J＝5.2Hz),135.9(d,J＝9.2Hz),133.9(d,J＝4.8Hz),132.9(d,J＝4.6Hz),131.381(d,J＝1.7Hz),131.379(dd,J＝44.3,8.7Hz),130.2(d,J＝6.7Hz),128.251,128.250(dd,J＝34.7,11.5Hz),126.7,84.0,47.6(d,J＝66.2Hz),24.9,24.6. 31 P NMR(162MHz,CDCl 3 )δ31.0.[α] D 20 ＝-83.3(c＝1.5,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 27 H 31 BO 3 P[M+H] + :445.2103,found:445.2118.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝13.4min(minor),20.0min(major).
(1-(4-fluorophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide(2b):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,83.2mg,90％yield,97％ee,white solid,m.p.196-197℃. 1 H NMR(400MHz,CDCl 3 )δ7.90-7.85(m,2H),7.51-7.44(m,5H),7.37-7.32(m,3H),7.27-7.24(m,2H),6.85(t,J＝8.8Hz,2H),6.64(br,1H),6.09-6.08(m,1H),4.61(d,J＝6.8Hz,1H),1.15(s,6H),1.09(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ161.9(d,J＝246.2Hz),135.8(d,J＝8.7Hz),133.7(d,J＝17.8Hz),132.8,132.6(d,J＝3.8Hz),131.8,131.7,131.6,131.5,131.3,131.1(d,J＝8.6Hz),128.3(d,J＝32.1,11.3Hz),115.1(d,J＝21.3Hz),84.1,47.0(d,J＝66.4Hz),24.9,24.6. 31 P NMR(162MHz,CDCl 3 )δ32.6. 19 F NMR(376MHz,CDCl 3 )δ-116.2.[α] D 20 ＝-53.3(c＝1.5,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 27 H 30 BFO 3 PNa[M+Na] + :485.1828,found:485.1830.HPLC(AD-H,n-hexane/isopropanol＝90/30,flow rate＝1.0mL/min,l＝220nm)tR＝6.5min(minor),8.8min(major).
(1-(4-chlorophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide(2c):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,91.9mg,96％yield,97％ee,yellow solid,m.p.179-180℃. 1 H NMR(400MHz,CDCl 3 )δ7.89-7.84(m,2H)，7.53-7.42(m，5H)，7.36-7.33(m，3H)，7.29-7.25(m，2H)，7.13(d，J＝8.4Hz，2H)，6.64-6.63(m，1H)，6.10-6.09(m,1H),4.60(d,J＝7.6Hz,1H),1.15(s,6H),1.09(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ136.1(d,J＝9.0Hz),135.5(d,J＝5.2Hz),133.6(d,J＝9.5Hz),132.7,132.6(d,J＝9.5Hz),131.6,131.5,131.41,131.37,131.1(d,J＝8.6Hz),128.40,128.39(dd,J＝25.8,11.7Hz),84.1,47.1(d,J＝66.2Hz),24.9,24.6. 31 P NMR(162MHz,CDCl 3 )δ32.0.[α] D 20 ＝-70.0(c＝1.0,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 27 H 30 BClO 3 P[M+H] + :479.1713,found:479.1704.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝16.2min(minor),39.9min(major).
(1-(4-bromophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide(2d):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,103.6mg,99％yield,96％ee,white solid,m.p.183-184℃. 1 H NMR(400MHz,CDCl 3 )δ7.86-7.81(m,2H),7.51-7.40(m,5H),7.33(t,J＝7.2Hz,1H),7.26-7.14(m,6H),6.61(br,1H),6.08-6.07(m,1H),4.58(d,J＝6.8Hz,1H),1.13(s,6H),1.07(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ136.13(d,J＝3.7Hz),136.06,133.5(d,J＝7.7Hz),132.5(d,J＝7.9Hz),131.8(d,J＝6.6Hz),131.55,131.46,131.3,131.1(d,J＝8.7Hz),128.4(d,J＝23.9,11.5Hz),120.9(d,J＝1.5Hz),84.1,47.1(d,J＝66.0Hz),24.9,24.6. 31 P NMR(162MHz,CDCl 3 )δ32.2.[α] D 20 ＝-75.0(c＝2.0,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 27 H 29 BBrO 3 PNa[M+Na] + :547.1011,found:547.1010.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝17.0min(minor),50.5min(major).
diphenyl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(p-tolyl)allyl)phosphine oxide(2e):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,69.7mg,76％yield,98％ee,white solid,m.p.155-156℃. 1 H NMR(400MHz,CDCl 3 )δ7.89-7.85(m,2H),7.56-7.40(m,5H),7.34-7.31(m,3H),7.27-7.23(m,2H),6.97(d,J＝8.0Hz,2H),6.65-6.63(m,1H),6.10-6.08(m,1H),4.63(d,J＝7.6Hz,1H),2.24(s,3H),1.15(s,6H),1.10(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ136.3,135.9(d,J＝9.3Hz),133.8(d,J＝4.7Hz),132.8(d,J＝2.1Hz),131.37(dd,J＝38.5,8.8Hz),131.35(d,J＝1.3Hz),129.9(d,J＝6.7Hz),129.0,128.4(d,J＝11.5Hz),128.1(d,J＝11.5Hz),84.0,47.0(d,J＝66.7Hz),24.9,24.6,21.1. 31 P NMR(162MHz,CDCl 3 )δ32.3.[α] D 20 ＝-160.0(c＝1.0,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 28 H 33 BO 3 P[M+H] + :459.2260,found:459.2263.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝14.0min(minor),46.1min(major).
(1-(4-methoxyphenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide(2f):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,85.4 mg,90％yield,97％ee,white solid,m.p.156-157℃. 1 H NMR(400MHz,CDCl 3 )δ7.89-7.85(m,2H),7.52-7.41(m,5H),7.35-7.31(m,3H),7.27-7.24(m,2H),6.71(d,J＝8.4Hz,2H),6.63-6.61(m,1H),6.08-6.07(m,1H),4.59(d,J＝7.6Hz,1H),3.72(s,3H),1.15(s,6H),1.09(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ158.4,135.5(d,J＝9.2Hz),133.9(d,J＝9.4Hz),133.0(d,J＝8.1Hz),131.6(d,J＝8.6Hz),131.4,131.2,131.1,128.8(d,J＝4.9Hz),128.3(d,J＝30.9,11.3Hz),113.7,84.0,55.2,46.7(d,J＝66.8Hz),24.9,24.7. 31 PNMR(162MHz,CDCl 3 )δ32.8.[α] D 20 ＝-100.0(c＝1.0,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 28 H 33 BO 4 P[M+H] + :475.2210,found:475.2210.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝20.7min(minor),54.5min(major).
diphenyl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(4-(trifluoromethoxy)phen-yl)ally-l)phosp hine oxide(2g):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,88.8mg,84％yield,96％ee,white solid,m.p.142-143℃. 1 H NMR(400MHz,CDCl 3 )δ7.90-7.86(m,2H),7.51-7.45(m,5H),7.40(d,J＝8.4Hz,2H),7.36-7.32(m,1H),7.27-7.23(m,2H),7.00(d,J＝8.4Hz,2H),6.67-6.66(m,1H),6.11-6.10(m,1H),4.62(d,J＝7.2Hz,1H),1.16(s,6H),1.09(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ148.2,136.0(d,J＝8.8Hz),135.6(d,J＝4.9Hz),133.5(d,J＝24.5Hz),132.5(d,J＝24.0Hz),131.6,131.53,131.48,131.4,131.1(d,J＝8.5Hz),128.4(dd,J＝34.7,11.3Hz),121.8,120.6,119.2,84.1,47.2(d,J＝66.1Hz),24.9,24.6. 31 P NMR(162MHz,CDCl 3 )δ32.2. 19 F NMR(376MHz,CDCl 3 )δ-57.9.[α] D 20 ＝-100.0(c＝1.5,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 28 H 29 BF 3 O 4 PNa[M+Na] + :551.1746,found:551.1749.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝13.0min(minor),39.8min(major).
methyl 4-(1-(diphenylphosphoryl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)benzoate(2h):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,90.4mg,90％yield,77％ee,white solid,m.p.173-174℃. 1 H NMR(400MHz,CDCl 3 )δ7.90-7.85(m,2H),7.83(d,J＝8.0Hz,2H),7.51-7.43(m,7H),7.35-7.31(m,1H),7.26-7.22(m,2H),6.69-6.68(m,1H),6.13-6.11(m,1H),4.68(d,J＝7.2Hz,1H),3.85(s,3H),1.14(s,6H),1.09(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ167.2,142.5(d,J＝4.9Hz),136.4(d,J＝8.9Hz),133.4(d,J＝5.4Hz),132.5(d,J＝5.4Hz),131.6,131.5,131.4(d,J＝1.4Hz),131.1(d,J＝8.8Hz),130.2(d,J＝6.2Hz),129.5,128.4(dd,J＝28.9,11.4Hz),84.1,52.1,47.9(d,J＝65.4Hz),24.9,24.6. 31 P NMR(162MHz,CDCl 3 )δ31.4.[α] D 20 ＝-20.0(c＝2.0,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 29 H 32 BO 5 PNa[M+Na] + :525.1978,found:525.1975.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝25.1min(minor),51.2min(major).
diphenyl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(4-(trifluoromethyl)phenyl)allyl)-phosphi ne oxide(2i):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,92.2 mg,90％yield,83％ee,white solid,m.p.149-150℃. 1 H NMR(400MHz,CDCl 3 )δ7.90-7.85(m,2H),7.54-7.45(m,7H),7.41(d,J＝8.4Hz,2H),7.34(t,J＝6.8Hz,1H),7.28-7.25(m,2H),6.69-6.67(m,1H),6.14-6.12(m,1H),4.69(d,J＝7.6Hz,1H),1.15(s,6H),1.10(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ141.2(d,J＝4.4Hz),136.5(d,J＝8.7Hz),133.3(d,J＝9.1Hz),132.4(d,J＝9.9Hz),131.65,131.56,131.5,131.0(d,J＝8.6Hz),130.4(d,J＝6.3Hz),128.5(dd,J＝26.2,11.5Hz),125.1(d,J＝3.5Hz),84.2,47.6(d,J＝65.7Hz),24.9,24.6. 31 P NMR(162MHz,CDCl 3 )δ32.0. 19 F NMR(376MHz,CDCl 3 )δ-62.5.[α] D 20 ＝-90.0(c＝2.0,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 28 H 29 BF 3 O 3 PNa[M+Na] + :535.1797,found:535.1791.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝12.9min(minor),29.6min(major).
4-(1-(diphenylphosphoryl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)benzonitrile(2j):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,71.3mg,76％yield,66％ee,white solid,m.p.172-173℃. 1 H NMR(400MHz,CDCl 3 )δ7.89-7.84(m,2H),7.50-7.43(m,9H),7.38-7.34(m,1H),7.29-7.25(m,2H),6.68-6.67(m,1H),6.14-6.12(m,1H),4.65(d,J＝7.6Hz,1H),1.15(s,6H),1.08(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ142.6(d,J＝5.4Hz),136.6(d,J＝8.9Hz),133.0(d,J＝22.1Hz),132.2,131.9,131.7(dd,J＝18.1,1.4Hz),131.4(d,J＝8.8Hz),130.9(d,J＝18.0Hz),130.87(d,J＝2.5Hz),128.5(dd,J＝26.0,11.6Hz),119.0,110.6,84.2,48.0(d,J＝64.9Hz),24.9,24.6. 31 P NMR(162MHz,CDCl 3 )δ31.3.[α] D 20 ＝-112.0(c＝2.5,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 28 H 30 BNO 3 P[M+H] + :470.2056,found:470.2052.HPLC(AD-H,n-hexane/isopropanol＝70/30,flow rate＝1.0mL/min,l＝220nm)tR＝8.0min(minor),15.9min(major).
(1-(3-chloro-4-fluorophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide(2k):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,98.4mg,99％yield,95％ee,white solid,m.p.159-160℃. 1 H NMR(400MHz,CDCl 3 )δ7.85(dd,J＝10.8,7.2Hz,2H),7.53-7.43(m,5H),7.38-7.26(m,5H),6.93(t,J＝8.8Hz,1H),6.64(br,1H),6.11-6.10(m,1H),4.56(d,J＝4.0Hz,1H),1.16(s,6H),1.11(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ157.2(d,J＝249.1Hz),136.3(d,J＝8.1Hz),134.0,133.3(d,J＝16.6Hz),132.4(d,J＝17.4Hz),132.1(d,J＝5.9Hz),131.55(d,J＝19.3Hz),131.53,131.1(d,J＝8.3Hz),129.9,129.81,129.75,128.5(dd,J＝23.4,11.4Hz),120.4(d,J＝17.8Hz),116.2(d,J＝21.0Hz),84.2,46.9(d,J＝64.1Hz),24.9,24.6. 31 P NMR(162MHz,CDCl 3 )δ31.4. 19 F NMR(376MHz,CDCl 3 )δ-118.4.[α] D 20 ＝-45.0(c＝2.0,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 27 H 29 BClFO 3 P[M+H] + :497.1619,found:497.1621.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝14.2min(minor),22.2min(major).
(1-(3-methoxyphenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide(2l):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,76.8mg,81％yield,93％ee,white solid,m.p.81-82℃. 1 H NMR(400MHz,CDCl 3 )δ7.89-7.85(m,2H),7.56-7.51(m,2H),7.48-7.41(m,3H),7.34-7.31(m,1H),7.27-7.23(m,2H),7.09-6.99(m,3H),6.69-6.65(m,2H),6.11(dd,J＝3.2,2.4Hz,1H),4.61(d,J＝7.6Hz,1H),3.68(s,3H),1.15(s,6H),1.10(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ159.3,138.5(d,J＝4.9Hz),136.0(d,J＝8.9Hz),133.9(d,J＝5.6Hz),132.9(d,J＝5.4Hz),131.6(d,J＝8.7Hz),131.4,131.22,131.17,131.1,129.1,128.3(dd,J＝29.8,11.5Hz),122.6(d,J＝6.8Hz),115.2(d,J＝6.8Hz),112.9,84.0,55.2,47.5(d,J＝66.4Hz),24.9,24.6. 31 P NMR(162MHz,CDCl 3 )δ32.9.[α] D 20 ＝-63.6(c＝2.2,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 28 H 32 BO 4 PNa[M+Na] + :497.2028,found:497.2023.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝23.4min(minor),49.1min(major).
(1-(2-chlorophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide(2m):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,50.7mg,53％yield,76％ee,white oil. 1 H NMR(400MHz,CDCl 3 )δ8.21(d,J＝7.6Hz,1H),7.88-7.83(m,2H),7.61-7.57(m,2H),7.49-7.42(m,3H),7.36-7.33(m,1H),7.28-7.25(m,2H),7.20-7.14(m,2H),7.05(t,J＝7.6Hz,1H),6.46-6.44(m,1H),6.18(dd,J＝4.0,2.0Hz,1H),5.32(d,J＝8.0Hz,1H),1.08(s,6H),1.03(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ137.3(d,J＝8.5Hz),136.1,134.1(d,J＝9.1Hz),133.5(d,J＝9.2Hz),132.5(d,J＝7.5Hz),132.0,131.9,131.4(d,J＝4.0Hz),131.1(d,J＝8.8Hz),129.2,128.3(dd,J＝11.5,5.1Hz),128.0,127.0,83.9,43.0(d,J＝66.9Hz),25.2,24.2. 31 P NMR(162MHz,CDCl 3 )δ32.0.[α] D 20 ＝+40.0(c＝2.5,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 27 H 29 BClO 3 PNa[M+Na] + :501.1533,found:501.1532.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝20.4min(minor),31.6min(major).
(1-(2-iodophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide(2n):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,58.2mg,51％yield,89％ee,white solid,m.p.137-138℃. 1 H NMR(400MHz,CDCl 3 )δ8.22(d,J＝7.6Hz,1H),7.90-7.86(m,2H),7.68(d,J＝7.6Hz,1H),7.56-7.45(m,5H),7.35(t,J＝7.2Hz,1H),7.28-7.24(m,3H),6.81(t,J＝7.6Hz,1H),6.44(br,1H),6.20(br,1H),5.13(d,J＝8.4Hz,1H),1.08(s,6H),1.05(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ140.8,139.5,137.2(d,J＝8.5Hz),132.3(d,J＝9.9Hz),132.0(d,J＝8.7Hz),131.8(d,J＝4.3Hz),131.5,131.4,131.3,128.5,128.4,128.3,128.2,103.1(d,J＝10.4Hz),83.9,51.2(d,J＝65.4Hz),25.3,24.3. 31 P NMR(162MHz,CDCl 3 )δ32.3.[α] D 20 ＝+32.0(c＝2.5,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 27 H 29 BIO 3 PNa[M+Na] + :593.0889,found:593.0887.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝13.6min(minor),19.8min(major).
(1-(naphthalen-1-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)diphenylphosphine oxide(2o):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,59.3mg,60％yield,44％ee,white solid,m.p.154-155℃. 1 H NMR(400MHz,CDCl 3 )δ8.46(d,J＝5.6Hz,1H),8.35(d,J＝8.0Hz,1H),7.85-7.78(m,3H),7.66-7.64(m,3H),7.48-7.44(m,5H),7.35(t,J＝6.8,1H),7.27-7.24(m,1H),7.19-7.17(m,2H),6.45(br,1H),6.23(br,1H),5.52(d,J＝8.0Hz,1H),1.09(s,6H),1.07(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ138.3(d,J＝5.8Hz),135.7,134.0,132.1(d,J＝8.1Hz),131.8(d,J＝8.2Hz),131.3(d,J＝2.3Hz),131.1(d,J＝7.6Hz),129.0,128.4,128.3,128.2,128.0(d,J＝4.4Hz),127.3,125.9,125.7(d,J＝54.8Hz),84.0,41.7(d,J＝63.8Hz),25.3,24.2. 31 P NMR(162MHz,CDCl 3 )δ32.3.[α] D 20 ＝+26.9(c＝2.6,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 31 H 32 BO 3 PNa[M+Na] + :517.2080,found:517.2081.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝23.8min(minor),29.2min(major).
diphenyl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(thiophen-3-yl)allyl)phosphine oxide(2p):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,85.6mg,95％yield,94％ee,white solid,m.p.144-145℃. 1 H NMR(400MHz,CDCl 3 )δ7.84(t,J＝8.4Hz,2H),7.57(m,2H),7.49-7.39(m,3H),7.36(d,J＝7.2Hz,1H),7.31-7.26(m,3H),7.14-7.12(m,1H),7.06(d,J＝4.8Hz,1H),6.56(br,1H),6.14-6.13(m,1H),4.84(d,J＝7.2Hz,1H),1.15(s,6H),1.10(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ136.7(d,J＝5.8Hz),136.3(d,J＝8.8Hz),133.7(d,J＝34.9Hz),132.7(d,J＝34.8Hz),131.4(dd,J＝53.8,8.8Hz),131.37(dd,J＝15.4,1.2Hz),129.2(d,J＝5.5Hz),128.3(dd,J＝20.0,10.5Hz),124.9,123.7(d,J＝7.7Hz),84.0,43.1(d,J＝66.9Hz),24.9,24.7. 31 P NMR(162MHz,CDCl 3 )δ32.1.[α] D 20 ＝-66.7(c＝1.5,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 25 H 29 BO 3 PS[M+H] + :451.1667,found:451.1666.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝16.0min(minor),20.3min(major).
diphenyl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(thiophen-2-yl)allyl)phosphine oxide(2q):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,76.5mg,85％yield,81％ee,brown solid,m.p.148-149℃. 1 H NMR(400MHz,CDCl 3 )δ7.87-7.82(m,2H),7.68-7.63(m,2H),7.48-7.38(m,4H),7.35-7.31(m,2H),7.07-7.06(m,2H),6.82(t,J＝4.4Hz,1H),6.64-6.62(m,1H),6.19-6.18(m,1H),4.97(d,J＝8.8Hz,1H),1.15(s,6H),1.11(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ139.0(d,J＝5.8Hz),136.9(d,J＝8.5Hz),133.3(d,J＝7.9Hz),132.3(d,J＝7.4Hz),131.5(dd,J＝43.0,8.8Hz),131.3(dd,J＝7.7,1.8Hz),128.3(dd,J＝14.4,11.8Hz),127.3(d,J＝6.5Hz),126.8,124.7(d,J＝1.1Hz),84.1,42.5(d,J＝66.2Hz),24.9,24.6. 31 P NMR(162MHz,CDCl 3 )δ30.9.[α] D 20 ＝-66.7(c＝1.5,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 25 H 28 BO 3 PSNa[M+Na] + :473.1482,found:473.1452.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝21.1min(minor),29.0min(major).
diphenyl(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-en-2-yl)phosphine oxide(2r):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,52mg,68％yield,79％ee,white oil. 1 H NMR(400MHz,CDCl 3 )δ7.89-7.84(m,2H),7.76-7.71(m,2H),7.47-7.44(m,3H),7.42-7.33(m,3H),6.23-6.21(m,1H),6.11-6.09(m,1H),3.53-3.46(m,1H),1.32(dd,J＝16.4,7.6Hz,3H),1.11(s,6H),1.08(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ134.9(d,J＝8.7Hz),133.6(d,J＝37.7Hz),132.6(d,J＝33.8Hz),131.45(dd,J＝27.1,8.8Hz),131.35(dd,J＝24.6,1.4Hz),128.4(dd,J＝35.8,11.0Hz),83.8,35.0(d,J＝67.4Hz),24.9,24.7,15.1(d,J＝2.4Hz). 31 P NMR(162MHz,CDCl 3 )δ34.1.[α] D 20 ＝+32.0(c＝2.5,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 22 H 29 BO 3 P[M+H] + :383.1946,found:383.1944.HPLC(IC,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝31.3min(minor),39.3 min(major).
bis(4-fluorophenyl)(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphine oxide(4a):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,79.7mg,83％yield,96％ee,white oil. 1 H NMR(400MHz,CDCl 3 )δ7.90-7.83(m,2H),7.49-7.43(m,2H),7.39-7.37(m,2H),7.20-7.12(m,5H),6.94(dt,J＝8.6,2.0Hz,2H),6.65-6.64(m,1H),6.12-6.11(m,1H),4.55(d,J＝7.6Hz,1H),1.16(s,6H),1.11(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ136.5(d,J＝5.6Hz),136.2(d,J＝9.4Hz),134.1,134.0,133.9,133.7,133.6,133.5,130.1(d,J＝6.8Hz),128.4,127.0,116.1,115.94,115.85,115.7,115.6,115.5,115.4,84.1,47.9(d,J＝67.4Hz),24.9,24.6. 31 P NMR(162MHz,CDCl 3 )δ31.3. 19 F NMR(376MHz,CDCl 3 )δ-107.5,-107.6.[α] D 20 ＝-60.0(c＝1.5,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 27 H 29 BF 2 O 3 P[M+H] + :481.1915,found:481.1918.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝12.1min(minor),26.5min(major).
bis(3,5-dimethylphenyl)(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphine oxide(4b):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,79.1mg,79％yield,92％ee,whitesolid,m.p.77-78℃. 1 H NMR(400MHz,CDCl 3 )δ7.46(d,J＝11.2Hz,2H),7.39(d,J＝8.0Hz,2H),7.18-7.09(m,4H),7.03(d,J＝11.6Hz,2H),6.92(s,1H),6.67(br,1H),6.10(t,J＝2.8Hz,1H),4.55(d,J＝7.6Hz,1H),2.34(s,6H),2.16(s,6H),1.16(s,6H),1.09(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ137.7(dd,J＝42.2,12.0Hz),137.2(d,J＝5.1Hz),135.7(d,J＝9.0Hz),133.6(d,J＝15.2Hz),133.0(dd,J＝30.9,2.3Hz),132.7(d,J＝14.4Hz),130.2(d,J＝6.5Hz),129.0(dd,J＝35.5,8.8Hz),128.1,126.6,83.9,47.7(d,J＝65.8Hz),25.0,24.4,21.5,21.3. 31 P NMR(162MHz,CDCl 3 )δ33.2.[α] D 20 ＝-80.0(c＝2.0,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 31 H 39 BO 3 P[M+H] + :501.2730,found:501.2725.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝6.5min(minor),10.4min(major).
(1-(4-bromophenyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)bis(3,5-dimet-hylphe-nyl)ph osphine oxide(4c):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,76.5mg,66％yield,96％ee,green solid,m.p.79-80℃. 1 H NMR(400MHz,CDCl 3 )δ7.41(d,J＝11.2Hz,2H),7.28-7.26(m,2H),7.25-7.22(m,2H),7.08(s,1H),7.02(d,J＝11.6Hz,2H),6.94(s,1H),6.63(br,1H),6.08(t,J＝2.8Hz,1H),4.48(d,J＝7.6Hz,1H),2.32(s,6H),2.18(s,6H),1.15(s,6H),1.08(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ137.9(dd,J＝31.5,12.2Hz),136.3(d,J＝5.1Hz),136.0(d,J＝9.2Hz),133.25(d,J＝20.0Hz),133.18(dd,J＝22.2,2.4Hz),132.3(d,J＝20.2Hz),131.9(d,J＝6.5Hz),131.2,128.9(dd,J＝39.3,8.9Hz),120.8,84.0,47.1(d,J＝65.5Hz),25.0,24.5,21.5,21.4. 31 P NMR(162MHz,CDCl 3 )δ32.9.[α] D 20 ＝-77.3(c＝2.2,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 31 H 38 BBrO 3 P[M+H] + :579.1835,found:579.1830.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝7.0min(minor),14.0min(major).
bis(3-methoxyphenyl)(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(p-tolyl)allyl)phosphine oxide(4d):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,55mg,53％yield,94％ee,white solid,m.p.71-72℃. 1 H NMR(400MHz,CDCl 3 )δ7.44-7.30(m,5H),7.17(dt,J＝8.0,4.0Hz,1H),7.07-6.98(m,5H),6.86(dd,J＝8.0,2.0Hz,1H),6.64(br,1H),6.08(dd,J＝3.2,2.4Hz,1H),4.55(d,J＝8.0Hz,1H),3.82(s,3H),3.62(s,3H),2.25(s,3H),1.15(s,6H),1.10(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ159.3(dd,J＝45.7,14.0Hz),136.6(d,J＝50.4Hz),135.6(d,J＝9.5Hz),135.1(d,J＝24.5Hz),134.2(d,J＝23.9Hz),133.9(d,J＝5.7Hz),130.0(d,J＝6.7Hz),129.4(dd,J＝31.2,13.8Hz),129.0,123.4(dd,J＝38.2,9.1Hz),117.7,116.3(dd,J＝59.8,9.2Hz),84.0,55.4(d,J＝19.5Hz),47.2(d,J＝66.8Hz),25.0,24.6,21.1. 31 P NMR(162MHz,CDCl 3 )δ32.9.[α] D 20 ＝-40.9(c＝2.2,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 30 H 37 BO 5 P[M+H] + :519.2472,found:519.2471.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝22.8min(minor),53.6min(major).
bis(2-methoxyphenyl)(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphine oxide(4e):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,55.5mg,55％yield,88％ee,white solid,m.p.81-82℃. 1 H NMR(400MHz,CDCl 3 )δ7.91(ddd,J＝12.8,7.6,1.2Hz,1H),7.58(ddd,J＝12.4,7.6,1.2Hz,1H),7.44(d,J＝7.6Hz,2H),7.40-7.36(m,1H),7.26-7.22(m,1H),7.13-7.09(m,2H),7.06-6.97(m,2H),6.81-6.77(m,2H),6.67-6.64(m,2H),6.05-6.03(m,1H),5.10(d,J＝10.0Hz,1H),3.67(s,3H),3.53(s,3H),1.17(s,6H),1.08(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ160.3(dd,J＝67.3,3.3Hz),138.4(d,J＝5.2Hz),134.5(dd,J＝12.5,9.8Hz),134.2(d,J＝6.1Hz),132.8,132.6(d,J＝1.0Hz),130.2(d,J＝7.0Hz),127.8,126.2,123.0,122.0,120.3(d,J＝11.2Hz),110.8(dd,J＝33.6,6.7Hz),83.6,55.3(d,J＝8.3Hz),46.8(d,J＝70.1Hz),25.2,24.4. 31 PNMR(162MHz,CDCl 3 )δ31.1.[α] D 20 ＝-66.7(c＝1.5,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 29 H 35 BO 5 P[M+H] + :505.2315,found:505.2323.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝21.8min(minor),33.5min(major).
(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)di-o-tolylphosphine oxide(4f):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,47.2mg,50％yield,78％ee,yellow solid,m.p.75-76℃. 1 H NMR(400MHz,CDCl 3 )δ7.80(dd,J＝12.0,7.2Hz,1H),7.41-7.39(m,2H),7.36-7.29(m,2H),7.27-7.11(m,6H),7.01-6.95(m,2H),6.73(br,1H),6.20(t,J＝3.0Hz,1H),4.66(d,J＝7.6Hz,1H),2.33(s,3H),2.09(s,3H),1.15(s,6H),1.06(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ142.8(d,J＝46.2,7.4Hz),137.6(d,J＝4.9Hz),136.5(d,J＝8.6Hz),133.1(d,J＝10.3Hz),132.4(d,J＝24.8Hz),132.0(dd,J＝13.3,11.8Hz),131.5(d,J＝10.6Hz),131.2(dd,J＝26.4,2.0Hz),130.4(d,J＝6.4Hz),128.2,126.6,125.0(dd,J＝1.3Hz),124.9(d,J＝2.4Hz),83.9,47.0(d,J＝66.2Hz),25.0,24.4,21.5(d,J＝3.7Hz),20.9(d,J＝3.2Hz). 31 P NMR(162MHz,CDCl 3 )δ37.0.[α] D 20 ＝-34.6(c＝2.6,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 29 H 35 BO 3 P[M+H] + :473.2416,found:473.2421.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝7.3min(minor),9.3min(major).
dicyclohexyl(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphine oxide(4g):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝2:1)as eluent,59.3mg,65％yield,80％ee,viscous oil. 1 H NMR(400MHz,CDCl 3 )δ7.54(d,J＝8.0Hz,2H),7.29-7.25(m,2H),7.22-7.18(m,1H),6.72(t,J＝2.0Hz,1H),6.12(t,J＝2.8Hz,1H),3.97(d,J＝5.6Hz,1H),2.11-1.81(m,9H),1.72-1.56(m,5H),1.43-1.32(m,3H),1.22(s,12H),1.07-0.85(m,5H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ139.1(d,J＝5.2Hz),135.5(d,J＝7.1Hz),129.8(d,J＝6.1Hz),129.2(d,J＝16.7Hz),128.6,126.7,84.0,42.9(d,J＝55.1Hz),38.3(dd,J＝61.3,9.9Hz),27.5,27.37,27.35,27.22,27.16,27.13,27.11,27.10,27.04,26.97,26.9(d,J＝2.2Hz),26.4(d,J＝1.0Hz),26.2,25.0,24.8. 31 P NMR(162MHz,CDCl 3 )δ52.2.[α] D 20 ＝-100.0(c＝1.5,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 27 H 43 BO 3 P[M+H] + :457.3042,found:457.3052.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝8.5min(major),21.0min(minor).
diisobutyl(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphine oxide(4h):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝2:1)as eluent,42.9mg,53％yield,86％ee,white solid,m.p.76-77℃. 1 H NMR(400MHz,CDCl 3 )δ7.49-7.47(m,2H),7.30-7.26(m,2H),7.23-7.19(m,1H),6.53(br,1H),6.14(t,J＝2.8Hz,1H),3.78(d,J＝8.8Hz,1H),2.19-2.00(m,2H),1.83-1.62(m,2H),1.55-1.41(m,2H),1.21(s,6H),1.19(s,6H),1.06-1.02(m,6H),0.87(d,J＝11.6,6.4Hz,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ138.0(d,J＝4.8Hz),134.5(d,J＝8.3Hz),129.9(d,J＝6.4Hz),129.3(d,J＝103.7Hz),128.5,126.8,84.0,49.6(d,J＝59.4Hz),37.5(dd,J＝62.4,43.3Hz),25.2(dd,J＝16.2,9.6Hz),24.9,24.7,24.5(dd,J＝14.8,7.0Hz),23.9(dd,J＝31.4,3.7Hz). 31 P NMR(162MHz,CDCl 3 )δ48.0.[α] D 20 ＝-45.5(c＝2.2,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 23 H 39 BO 3 P[M+H] + :405.2730,found:405.2727.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝13.2min(minor),15.5min(major).
Dimethyl(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphonate(4i):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝2:1)as eluent,32mg,45％yield,94％ee,green oil. 1 H NMR(400MHz,CDCl 3 )δ7.44-7.42(m,2H),7.31-7.26(m,2H),7.24-7.20(m,1H),6.28-6.27(m,1H),6.12-6.10(m,1H),4.24(d,J＝24.0Hz,1H),3.71(d,J＝11.2Hz,3H),3.51(d,J＝10.4Hz,3H),1.20(s,6H),1.14(s,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ136.0(d,J＝5.6Hz),133.0(d,J＝10.0Hz),130.0(d,J＝7.6Hz),129.0(d,J＝22.4Hz),128.4,127.1(d,J＝1.3Hz),84.0,53.4(d,J＝6.9Hz),53.1(d,J＝7.0Hz),46.8(d,J＝137.6Hz),24.9,24.6. 31 PNMR(162MHz,CDCl 3 )δ29.1.[α] D 20 ＝-55.6(c＝1.8,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 17 H 26 BO 5 PNa[M+Na] + :375.1506,found:375.1505.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝5.5min(minor),6.6min(major).
diethyl(1-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)phosphonate(4j):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝2:1)as eluent,66.9mg,88％yield,95％ee,white oil. 1 H NMR(400MHz,CDCl 3 )δ7.44-7.42(m,2H),7.28-7.24(m,2H),7.21-7.17(m,1H),6.33-6.32(m,1H),6.10(dd,J＝3.6,2.4Hz,2H),4.19(d,J＝23.6Hz,1H),4.09-4.01(m,2H),3.94-3.86(m,1H),3.81-3.72(m,1H),1.26(t,J＝7.2Hz,3H),1.19(s,6H),1.12(s,6H),1.08(t,J＝6.8Hz,3H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ136.4(d,J＝5.8Hz),132.9(d,J＝9.8Hz),130.0(d,J＝7.6Hz),128.7,128.3,126.9(d,J＝1.7Hz),83.9,62.5(d,J＝6.9Hz),62.2(d,J＝7.0Hz),47.1(d,J＝137.3Hz),24.9,24.5,16.5(d,J＝6.0Hz),16.3(d,J＝5.9Hz). 31 P NMR(162MHz,CDCl 3 )δ26.7.[α] D 20 ＝-28.0(c＝2.5,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 19 H 31 BO 5 P[M+H] + :381.2002,found:381.2004.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝5.9min(minor),7.8min(major).
(4k):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝2:1)as eluent,54.7mg,63％yield,59％ee,white oil. 1 H NMR(400MHz,CDCl 3 )δ7.51-7.49(m,2H),7.23-7.19(m,2H),7.15-7.11(m,1H),6.78-6.77(m,1H),6.07-6.05(m,1H),4.08(d,J＝13.6Hz,1H),3.08-2.98(m,4H),2.75-2.67(m,4H),1.18(s,6H),1.15(s,6H),1.08(t,J＝7.2Hz,6H),0.76(t,J＝7.2Hz,6H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ138.9(d,J＝4.7Hz),134.0(d,J＝8.0Hz),130.3(d,J＝6.9Hz),128.8,128.0,126.3,83.8,45.1(d,J＝109.5Hz),39.5(d,J＝3.6Hz),38.9(d,J＝3.4Hz),25.0,24.6,14.5,14.3. 31 P NMR(162MHz,CDCl 3 )δ34.0.[α] D 20 ＝-66.7(c＝1.5,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 23 H 40 BN 2 O 3 PNa[M+Na] + :457.2766,found:457.2762.HPLC(IC,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min，l＝220nm)tR＝10.7min(minor)，11.5min(major).
application example
The present application example performed a series of transformations on compound 2a according to the general scheme of the reaction shown in formula 10, and found that the derivatization reaction shown in formula 10 was performed smoothly and a corresponding product with a retained configuration was obtained. The palladium-catalyzed Suzuki coupling gave product 5 in 92% yield and 97% ee value. On CH 3 B(OH) 2 Hydrolysis of 2a under HCl conditions gives the corresponding boronic acid compound 6 in 63% yield and 97% ee. FIG. 2 shows a single crystal diffraction structure of Compound 6. Chiral centers of Compound 6 were defined as R configuration by X-ray diffraction analysis. Under the action of copper (II) halide, the aqueous methanol is used as a solvent to obtain chloro and bromo products 7 and 8 in high yield. Under the aerobic condition, the 2a boron removal reaction catalyzed by silver is smoothly carried out.
(1) A specific preparation method of the product 5 in the formula 10:
according to the reaction scheme shown in formula 11, a 25mL Schlenk tube was charged with magneton, evacuated and replaced with nitrogen, and repeated three times, while adding tetrakis triphenylphosphine palladium (5 mol%), cesium fluoride (2 equiv), 2a (0.1 mmol) and methyl p-iodobenzoate (0.12 mmol) under nitrogen atmosphere, 1.4-dioxane (2 mL)/water (0.1 mL) was added as a solvent, and the reaction was stirred at 90℃overnight. After completion of the reaction, the reaction was quenched with saturated sodium chloride (5 mL), allowed to stand for separation, the organic phase was separated with a separating funnel, and the aqueous phase was extracted with ethyl acetate (5 ml×3), the organic phases were combined, and finally dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporator and the crude product was separated by column chromatography (petroleum ether: ethyl acetate=1:1, v: v) to give the desired product 5.
(2) A specific preparation method of the product 6 in the formula 10:
according to the reaction scheme shown in formula 12, a 25mL Schlenk tube was charged with magneton, evacuated and replaced with nitrogen, and repeated three times, 2a (88.9 mg,0.2mmol,1.0 equiv), methylboronic acid (5-10 equiv) and hydrochloric acid/acetone (1 mL/1 mL) were sequentially added. The reaction was stirred at room temperature, after completion of the reaction, deionized water was added, allowed to stand for separation, the organic phase was separated with a separating funnel, and the aqueous phase was extracted with ethyl acetate (5 ml×3), the organic phases were combined, and finally dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporator and the crude product was isolated by column chromatography (petroleum ether: ethyl acetate=1:1, v: v) to give the product, which was then recrystallized from ethyl acetate and petroleum ether to give pure target product 6.
(3) Specific preparation methods of products 7 and 8 in formula 10:
according to the reaction scheme shown in formula 13, a 25mL Schlenk tube was charged with magneton, 2a (88.9 mg,0.2 mmol), copper halide (0.6 mmol, X=Cl or Br) and methanol/water (1 mL/1 mL) were sequentially added, and the reaction was stirred at 80℃for 6 hours. After the reaction was completed, the reaction was quenched with saturated sodium chloride solution (1 mL), allowed to stand for delamination, the organic phase was separated with a separating funnel, and the aqueous phase was extracted with ethyl acetate (5 ml×3), the organic phases were combined, and finally dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporator and the crude product was separated by column chromatography (petroleum ether: ethyl acetate=1:1, v: v) to give the desired products 7 and 8.
(3) A specific preparation method of the product 9 in the formula 10:
according to the reaction scheme shown in formula 14, a 25mL Schlenk tube was charged with magneton, and 2a (88.9 mg,0.2 mmol), silver nitrate (2.0 mg,6 mol%), triethylamine (20.2 mg,0.2 mmol) and ethanol/water (1 mL/1 mL) were sequentially added, and the reaction was stirred at 80℃for 3 hours. After the reaction was completed, the reaction was quenched with saturated sodium chloride solution (1 mL), allowed to stand for delamination, the organic phase was separated with a separating funnel, and the aqueous phase was extracted with ethyl acetate (5 ml×3), the organic phases were combined, and finally dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporator and the crude product was separated by column chromatography (petroleum ether: ethyl acetate=1:1, v: v) to give the desired product 9.
The structural characterization data of the compounds 5 to 9 prepared in the application example of the invention are specifically as follows:
methyl 4-(3-(diphenylphosphoryl)-3-phenylprop-1-en-2-yl)benzoate(5):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,41.6mg,92％yield,97％ee,yellow solid,m.p.183-184℃. 1 H NMR(400MHz,CDCl 3 )δ7.87(d,J＝8.4Hz,2H),7.81-7.76(m,2H),7.51-7.47(m,1H),7.43-7.35(m,5H),7.31-7.29(m,2H),7.27-7.23(m,2H),7.20-7.18(m,5H),6.39(d,J＝2.0Hz,1H),5.61(d,J＝1.6Hz,1H),4.55(d,J＝9.6Hz,1H),3.88(s,3H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ166.9,147.7(d,J＝8.6Hz),143.6(d,J＝3.4Hz),134.5(d,J＝6.1Hz),133.0(d,J＝7.1Hz),132.0(d,J＝5.4Hz),131.7(dd,J＝23.8,2.4Hz),131.3(dd,J＝16.5,8.9Hz),130.2(d,J＝5.4Hz),129.8,129.2,128.5,128.4(dd,J＝43.4,11.7Hz),127.5(d,J＝1.3Hz),126.3,121.4(d,J＝7.1Hz),52.3,51.6. 31 P NMR(162MHz,CDCl 3 )δ32.5.[α] D 20 ＝-56.5(c＝2.3,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 29 H 26 O 3 P[M+H] + :453.1614,found:453.1619.HPLC(IC,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝33.4min(major),37.6min(minor).
(3-(diphenylphosphoryl)-3-phenylprop-1-en-2-yl)boronic acid(6):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝5:1)as eluent,45.6mg,63％yield,97％ee,white solid,m.p.107-108℃. 1 H NMR(400MHz,CDCl 3 )δ7.85-7.80(m,2H),7.59-7.47(m,5H),7.41-7.28(m,7H),7.21-7.11(m,3H),5.76(t,J＝2.3Hz,1H),5.44(t,J＝3.0Hz,1H),4.35(d,J＝8.8Hz,1H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ136.1(d,J＝5.4Hz),132.9(d,J＝12.2Hz),132.1(dd,J＝17.4,2.0Hz),131.4(d,J＝28.5,8.7Hz),130.7,129.9(d,J＝51.0Hz),129.4(d,J＝7.0Hz),128.9,128.6(dd,J＝28.4,16.6Hz),127.2,57.3(d,J＝64.1Hz). 31 P NMR(162MHz,CDCl 3 )δ37.8.[α] D 20 ＝-60.0(c＝1.0,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 21 H 21 BO 3 P[M+H] + :363.1321,found:363.1319.HPLC(AD-H,n-hexane/ethanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝15.0min(minor),20.9min(major).
(2-chloro-1-phenylallyl)diphenylphosphine oxide(7):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,58.4mg,82％yield,97％ee,white solid,m.p.198-199℃. 1 H NMR(600MHz,CDCl 3 )δ7.97-7.93(m,2H),7.58-7.52(m,3H),7.37-7.32(m,3H),7.27-7.25(m,2H),7.23-7.17(m,5H),6.20(d,J＝1.2Hz,1H),5.43(br,1H),4.30(d,J＝9.6Hz,1H). 13 C{ 1 H}NMR(151MHz,CDCl 3 )δ137.5,132.9(d,J＝5.0Hz),132.4(d,J＝10.0Hz),132.1(d,J＝2.9Hz),131.8(d,J＝14.0Hz),131.7(d,J＝2.7Hz),131.4(d,J＝8.9Hz),131.2(d,J＝8.9Hz),130.2(d,J＝5.1Hz),128.9(d,J＝11.6Hz),128.4(d,J＝1.5Hz),128.2(d,J＝11.9Hz),127.9(d,J＝2.3Hz),118.7(d,J＝4.7Hz),56.1(d,J＝62.4Hz). 31 P NMR(162MHz,CDCl 3 )δ30.8.[α] D 20 ＝-340.0(c＝1.0,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 21 H 19 ClOP[M+H] + :353.0857,found:353.0858.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝18.1min(minor),31.2min(major).
(2-bromo-1-phenylallyl)diphenylphosphine oxide(8):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,78.7mg,99％yield,99％ee,white solid,m.p.212-213℃. 1 H NMR(600MHz,CDCl 3 )δ7.98-7.95(m,2H),7.61-7.54(m,3H),7.36-6.29(m,3H),7.23-7.18(m,7H),6.69(br,1H),5.70(d,J＝2.4Hz,1H),4.39(d,J＝9.0Hz,1H). 13 C{ 1 H}NMR(151MHz,CDCl 3 )δ132.6(d,J＝5.1Hz),132.3,132.2(d,J＝2.4Hz),131.7(d,J＝2.3Hz),131.6(d,J＝11.6Hz),131.3(d,J＝8.8Hz),131.0(d,J＝9.1Hz),130.1(d,J＝4.9Hz),129.0(d,J＝11.5Hz),128.4(d,J＝1.4Hz),128.2(d,J＝11.9Hz),127.9(d,J＝1.8Hz),127.6,123.4(d,J＝4.8Hz),57.9(d,J＝59.9Hz). 31 P NMR(162MHz,CDCl 3 )δ31.6.[α] D 20 ＝-185.0(c＝2.0,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 21 H 19 BrOP[M+H] + :397.0351,found:397.0352.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝17.1min(minor),30.5min(major).
diphenyl(1-phenylallyl)phosphine oxide(9):Purified by column chromatography on silica gel with petroleum ether/EtOAc(v/v＝1:1)as eluent,41.3mg,65％yield,86％ee,white solid,m.p.180-181℃. 1 H NMR(400MHz,CDCl 3 )δ7.89-7.84(m,2H),7.55-7.47(m,5H),7.37-7.34(m,1H),7.30-7.24(m,4H),7.22-7.14(m,3H),6.29-6.18(m,1H),5.15(dd,J＝10.0,2.8Hz,1H),5.04(dd,J＝16.8,4.0Hz,1H),4.24(t,J＝9.2Hz,1H). 13 C{ 1 H}NMR(101MHz,CDCl 3 )δ135.5(d,J＝6.2Hz),133.0(d,J＝6.8Hz),131.7(dd,J＝31.6,8.6Hz),131.6(d,J＝138.2Hz),131.5(dd,J＝49.1,2.7Hz),129.5(d,J＝5.8Hz),128.6,128.4(dd,J＝33.6,11.7Hz),127.2(d,J＝2.0Hz),119.8(d,J＝11.0Hz),52.9(d,J＝65.1Hz). 31 P NMR(162MHz,CDCl 3 )δ31.8.[α] D 20 ＝-48.0(c＝2.5,CHCl 3 ).HRMS(ESI-MS)m/z calcd.for C 21 H 20 OP[M+H] + :319.1252,found:319.1250.HPLC(AD-H,n-hexane/isopropanol＝90/10,flow rate＝1.0mL/min,l＝220nm)tR＝30.7min(major),38.2min(minor).
although the foregoing embodiments have been described in some, but not all embodiments of the invention, other embodiments may be obtained according to the present embodiments without departing from the scope of the invention.
Claims (10)
1. An alpha-carbon chiral phosphine compound, which is characterized by having a structure shown in a formula I:
in the formula I, the R 1 Is C 1～8 Alkyl, C of (2) 3～8 Cycloalkyl, C 1～8 Alkoxy, amino, aryl or substituted aryl groups, said R 1 The substituent on the substituted aryl is fluorine, chlorine, bromine, nitro, trifluoromethyl, C 1～4 Alkyl and C of (C) 1～4 At least one of the alkoxy groups of (a);
the R is 2 Is C 1～4 Alkyl, aryl, substituted aryl or thienyl, R 2 The substituent on the substituted aryl is fluorine, chlorine, bromine, iodine, nitro, trifluoromethyl, C 1～4 Alkyl, C of (2) 1～4 Alkoxy, C 1～4 At least one of an alkoxy group, an ester group and a cyano group.
2. The alpha-carbon chiral phosphine compound according to claim 1, wherein said R 1 Is phenyl group,
MeO-, etO-, or
The R is 2 Is phenyl, naphthyl,
3. The α -carbon chiral phosphine compound according to claim 2, wherein the α -carbon chiral phosphine compound has any one of the following structures:
4. a process for producing an α -carbon chiral phosphine compound according to any one of claims 1 to 3, which comprises the steps of:
in a protective gas atmosphere, carrying out asymmetric boron protonation reaction on a dienylphosphine oxide compound with a structure shown in a formula II, pinacol boric acid ester, a copper (I) catalyst, a chiral ligand, an organic alkaline compound and a proton additive in a polar organic solvent to obtain the alpha-carbon chiral phosphine compound; the chiral ligand is a cyclic phosphine ligand (S, S) -Ph-BPE or a cyclic phosphine ligand (R, R) -Ph-BPE;
5. the method according to claim 4, wherein the copper (I) catalyst is CuCl, cuBr, cuI, cuOAc, cuTc and Cu (CH) 3 CN) 4 PF 6 One or more of the following.
6. The method according to claim 4, wherein the temperature of the asymmetric boron protonation reaction is-30 to-60 ℃.
7. The process according to claim 4, wherein the organic basic compound is sodium t-butoxide.
8. The method of claim 4, wherein the proton additive is methanol.
9. The preparation method according to claim 4, wherein the molar ratio of the dienylphosphine oxide compound of the structure represented by formula II to the pinacol borate is 1 (1-2);
the mol ratio of the alkenyl phosphine oxide compound with the structure shown in the formula II to the copper (I) catalyst is 1:0.05;
the mol ratio of the dienylphosphine oxide with the structure shown in the formula II to the chiral ligand is 1:0.06;
the mol ratio of the alkenyl phosphine oxide compound with the structure shown in the formula II to the proton additive is 1:2;
the molar ratio of the alkenyl phosphine oxide compound with the structure shown in the formula II to the organic alkaline compound is 1:0.2.
10. The method of claim 6, wherein the copper (I) catalyst is CuOAc; the temperature of the asymmetric boron protonation reaction is-55 ℃.
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