CN113666962B - Nitrogen-phosphorus ligand and preparation method and application thereof - Google Patents
Nitrogen-phosphorus ligand and preparation method and application thereof Download PDFInfo
- Publication number
- CN113666962B CN113666962B CN202110944796.6A CN202110944796A CN113666962B CN 113666962 B CN113666962 B CN 113666962B CN 202110944796 A CN202110944796 A CN 202110944796A CN 113666962 B CN113666962 B CN 113666962B
- Authority
- CN
- China
- Prior art keywords
- nmr
- cdcl
- ligand
- phenyl
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000003446 ligand Substances 0.000 title claims abstract description 94
- YUWBVKYVJWNVLE-UHFFFAOYSA-N [N].[P] Chemical compound [N].[P] YUWBVKYVJWNVLE-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 55
- 239000001257 hydrogen Substances 0.000 claims abstract description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 28
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 14
- 150000002367 halogens Chemical class 0.000 claims abstract description 14
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical group C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 3
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 39
- -1 amino, nitro, phenyl Chemical group 0.000 abstract description 36
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 20
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 18
- 125000003545 alkoxy group Chemical group 0.000 abstract description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 12
- 125000003342 alkenyl group Chemical group 0.000 abstract description 12
- 125000000304 alkynyl group Chemical group 0.000 abstract description 12
- 150000002431 hydrogen Chemical class 0.000 abstract description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 10
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 abstract description 10
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 9
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 abstract description 8
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 abstract description 7
- 150000002148 esters Chemical class 0.000 abstract description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 5
- 239000000126 substance Substances 0.000 abstract description 5
- 125000002252 acyl group Chemical group 0.000 abstract description 4
- 125000004185 ester group Chemical group 0.000 abstract description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 abstract description 4
- 150000001408 amides Chemical class 0.000 abstract description 3
- 125000003396 thiol group Chemical class [H]S* 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 161
- 238000012512 characterization method Methods 0.000 description 60
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 25
- 125000004432 carbon atom Chemical group C* 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 125000003118 aryl group Chemical group 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical group CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 7
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 6
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
- 125000003504 2-oxazolinyl group Chemical group O1C(=NCC1)* 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical group [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
- 239000002841 Lewis acid Substances 0.000 description 4
- 150000001718 carbodiimides Chemical class 0.000 description 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000006880 cross-coupling reaction Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 150000007517 lewis acids Chemical class 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 230000001590 oxidative effect Effects 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001345 alkine derivatives Chemical group 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 239000011574 phosphorus Substances 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 235000005074 zinc chloride Nutrition 0.000 description 3
- 239000011592 zinc chloride Substances 0.000 description 3
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 2
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- BWRRWBIBNBVHQF-UHFFFAOYSA-N 4-(3-pyridin-2-yl-1,2,4-oxadiazol-5-yl)butanoic acid Chemical compound O1C(CCCC(=O)O)=NC(C=2N=CC=CC=2)=N1 BWRRWBIBNBVHQF-UHFFFAOYSA-N 0.000 description 1
- ROMPPAWVATWIKR-UHFFFAOYSA-N 4-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]butanoic acid Chemical compound O1C(CCCC(=O)O)=NC(C=2C=CC(Cl)=CC=2)=N1 ROMPPAWVATWIKR-UHFFFAOYSA-N 0.000 description 1
- LAGNMUUUMQJXBF-UHFFFAOYSA-N 4-ethynylbenzonitrile Chemical group C#CC1=CC=C(C#N)C=C1 LAGNMUUUMQJXBF-UHFFFAOYSA-N 0.000 description 1
- 125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
- 235000021513 Cinchona Nutrition 0.000 description 1
- 241000157855 Cinchona Species 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 1
- KUXDQQMEFBFTGX-UHFFFAOYSA-N [N].P Chemical compound [N].P KUXDQQMEFBFTGX-UHFFFAOYSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 238000010691 alkyne synthesis reaction Methods 0.000 description 1
- 125000000746 allylic group Chemical group 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001743 benzylic group Chemical group 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000005510 but-1-en-2-yl group Chemical group 0.000 description 1
- 125000005514 but-1-yn-3-yl group Chemical group 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 238000006772 olefination reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000006238 prop-1-en-1-yl group Chemical group [H]\C(*)=C(/[H])C([H])([H])[H] 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- CITILBVTAYEWKR-UHFFFAOYSA-L zinc trifluoromethanesulfonate Substances [Zn+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F CITILBVTAYEWKR-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
- C07F9/653—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
- C07F9/653—Five-membered rings
- C07F9/65324—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of organic chemical ligands, and discloses a nitrogen-phosphorus ligand, which has a structure shown in a general formula I or a tautomer, an enantiomer or a diastereoisomer thereof:
R 1 、R 5 each independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, alkenyl, alkynyl, hydroxyl, aldehyde, carboxyl, ester, halogen, trifluoromethyl, cyano, acyl, amide, amino, nitro, phenyl, benzyl, sulfonyl, sulfonic, and mercapto; r 2 Selected from one of the following structures: alkyl, alkoxy, cycloalkyl, alkenyl, alkynyl, phenyl, benzyl, phenethyl, naphthylmethyl, -CHPh 2 Ester group, -CH 2 OBn, or substituted phenyl or benzyl, or R 2 And R 4 Connected to form a five-membered ring and an acene ring; the R is 3 Selected from hydrogen or alkyl; said R is 4 Selected from hydrogen, alkyl, alkoxy, alkenyl, alkynyl, phenyl, benzyl; w is PR 2 Or P (O) R 2 And R is selected from phenyl, naphthyl, cyclohexyl and substituted phenyl. The invention also discloses a preparation method and application of the nitrogen-phosphorus ligand.
Description
Technical Field
The invention belongs to the field of organic chemical ligands, and particularly relates to a nitrogen-phosphorus ligand, and a preparation method and application thereof.
Background
The chiral oxazoline skeleton widely exists in a chiral ligand structure and has important application in asymmetric reaction catalyzed by transition metal. Besides the common chiral skeleton types such as bisoxazoline and trioxazoline, the chiral oxazoline skeleton can also form a bi/multidentate ligand together with other different heteroatoms. In recent years, chiral P, N-bidentate ligands composed of aryl/alkyl phosphine are widely applied to various types of asymmetric chemical reactions catalyzed by metal palladium, iridium, cobalt, copper and the like.
In recent years, with the development of radical asymmetric chemistry, the development of chiral ligands with different framework types is urgently needed to effectively regulate and control the stereoselectivity of radical intermediates. Chiral bisoxazoline ligands, nitrogen and phosphorus ligands derived from cinchona alkaloid and the like are successfully applied to asymmetric cross coupling reaction related to free radical intermediates, asymmetric 1,2 bifunctional reaction of olefin and oxidation type asymmetric coupling reaction of alkyl carbon-hydrogen bonds. Due to the diversity of the types of free radical reactions, more types of chiral ligands need to be developed to suit the needs of different reactions.
Disclosure of Invention
The invention aims to provide a nitrogen-phosphorus ligand which is based on a chiral oxazoline skeleton and has a novel structure.
The invention also aims to provide a preparation method of the nitrogen-phosphorus ligand.
The invention also aims to provide the application of the nitrogen and phosphorus ligand.
In order to achieve one of the purposes, the invention adopts the following technical scheme;
a nitrogen phosphorus ligand having the structure of formula i or a tautomer, enantiomer, or diastereomer thereof:
R 1 selected from the group consisting of hydrogen, alkyl, alkoxy, cycloalkyl, alkenyl, alkynyl, hydroxyl, aldehyde, carboxyl, ester, halogen, trifluoromethyl, cyano, acyl, amide, amino, nitro, phenyl, benzyl, sulfonyl, sulfonic, mercapto;
R 2 selected from one of the following structures:
alkyl, alkoxy, cycloalkyl, alkenyl, alkynyl, phenyl, benzyl, phenethyl, naphthylmethyl, -CHPh 2 Ester group, -CH 2 OBn, or
Phenyl or benzyl substituted by alkyl, alkoxy, alkenyl, alkynyl, phenyl, halogen, trifluoromethyl, ester, trifluoromethylphenyl, or
R 2 And R 4 Are linked to form a five-membered ring and an acene ring, i.e. form
Structure (c); />
Said R is 3 Selected from hydrogen or alkyl, and R 3 And R 2 Different;
said R is 4 Selected from hydrogen, alkyl, alkoxy, alkenyl, alkynyl, phenyl, benzyl, or
R 4 And R 2 Connected to form a five-membered ring and an acene ring, i.e. formation
Structure;
R 5 selected from hydrogen, alkyl, alkoxy, cycloalkyl, alkenyl, alkynyl, hydroxyl, aldehyde, carboxyl, ester, halogen, trifluoromethyl, cyano, acyl, amide, amino, nitro, phenyl, benzyl, sulfonyl, sulfonic, thiol, or
Benzene and substituted benzene ring-side forming a naphthalene ring, i.e. forming
Structure;
w is PR 2 Or P (O) R 2 ，
R is selected from phenyl, naphthyl, cyclohexyl,
Wherein R is 6 Selected from alkyl, alkoxy, trifluoromethyl, halogen, phenyl, phenoxy and dimethylphenyl, m represents an integer of 1 to 5, and when m is not less than 2, more than 2R are present 6 The same or different.
Further, said R 1 Selected from hydrogen, (C1-C4) alkyl, (C1-C4) alkoxy, halogen, trifluoromethyl, cyclohexyl, cyclopentyl, ethenyl, ethynyl、-OH、-CHO、-COOH、-CN、-NH 2 、-NO 2 Phenyl, benzyl.
Further, said R 1 Selected from hydrogen, (C1-C4) alkyl, (C1-C4) alkoxy, halogen, trifluoromethyl, ethenyl, ethynyl, -OH, -CHO, -COOH, -CN and phenyl.
Further, said R 1 Selected from hydrogen, halogen, trifluoromethyl, alkoxy.
Further, said R 1 Selected from hydrogen, fluorine, chlorine, bromine, trifluoromethyl and (C1-C4) alkoxy.
Further, said R 1 Selected from hydrogen, fluorine, trifluoromethyl and methoxy.
Further, said R 2 Selected from one of the following structures:
alkyl, cycloalkyl, phenyl, benzyl, phenethyl, naphthylmethyl, -CHPh 2 Ester group, -CH 2 OBn, or
Phenyl or benzyl substituted by alkyl, phenyl, halogen, trifluoromethyl, ester, trifluoromethylphenyl, or
R 2 And R 4 Connected to form a five-membered ring and an acene ring.
Further, said R 2 Selected from one of the following structures:
(C1-C6) alkyl, cyclopentyl, cyclohexyl, phenyl, benzyl, phenethyl, naphthylmethyl, -CHPh 2 、-CO 2 t Bu、-CH 2 OBn, or
From (C1-C6) alkyl, phenyl, halogen, trifluoromethyl, -CO 2 Et, trifluoromethylphenyl-substituted phenyl or benzyl, or
R 2 And R 4 Connected to form a five-membered ring and an acene ring.
Further, said R 2 Selected from one of the following structures:
(C1-C6) alkyl, cyclopentyl, cyclohexyl, phenyl, benzyl, phenethyl, naphthylmethyl, -CHPh 2 、-CO 2 t Bu、-CH 2 OBn, or
From (C1-C6) alkyl, phenylHalogen, trifluoromethyl, -CO 2 Et, trifluoromethylphenyl-substituted benzyl, or
R 2 And R 4 Connected to form a five-membered ring and an acene ring.
Further, said R 2 Selected from one of the following structures:
ethyl, propyl, butyl, pentyl, cyclohexyl, phenyl, benzyl, phenethyl, naphthylmethyl, -CHPh 2 、-CO 2 t Bu、-CH 2 OBn, or
From methyl, butyl, phenyl, fluoro, trifluoromethyl, -CO 2 Et, p-trifluoromethylphenyl-substituted benzyl, or
R 2 And R 4 Connected to form a five-membered ring and an acene ring.
Further, said R 2 Selected from one of the following structures:
ethyl, isopropyl, sec-butyl, isobutyl, tert-butyl, -CH 2 t Bu, cyclohexyl, phenyl, benzyl, phenethyl, naphthylmethyl, -CHPh 2 、-CO 2 t Bu、-CH 2 OBn, or
R 2 And R 4 Connected to form a five-membered ring and an acene ring.
Further, said R 3 Selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl.
Further, said R 3 Selected from hydrogen or methyl.
Further, said R 4 Selected from hydrogen, (C1-C4) alkyl, methoxy, ethoxy, ethenyl, ethynyl, phenyl, benzyl, or
R 4 And R 2 Connected to form a five-membered ring and an acene ring.
Further on toSaid R is 4 Selected from hydrogen, (C1-C4) alkyl, phenyl, or
R 4 And R 2 Connected to form a five-membered ring and an acene ring.
Further, said R 4 Selected from hydrogen, methyl, ethyl, phenyl, or
R 4 And R 2 Connected to form a five-membered ring and an acene ring.
Further, said R 5 Selected from hydrogen, (C1-C4) alkyl, (C1-C4) alkoxy, cyclopentyl, cyclohexyl, vinyl, ethynyl, -OH, -CHO, -COOH, halogen, trifluoromethyl, -CN, -NH 2 、-NO 2 Phenyl, benzyl, or
Benzene ring and substituted benzene ring phase form naphthalene ring.
Further, said R 5 Selected from hydrogen, (C1-C4) alkyl, (C1-C4) alkoxy, cyclopentyl, cyclohexyl, ethenyl, ethynyl, -OH, -CHO, -COOH, halogen, trifluoromethyl, -CN, -NH 2 、-NO 2 Phenyl, benzyl, or
Benzene ring and substituted benzene ring phase form naphthalene ring.
Further, said R 5 Selected from hydrogen, (C1-C4) alkyl, or
Benzene ring and substituted benzene ring phase form naphthalene ring.
Further, said R 5 Selected from hydrogen, methyl, or
Benzene ring and substituted benzene ring phase form naphthalene ring.
Further, R is selected from phenyl, naphthyl,
Wherein R is 6 Selected from (C1-C4) alkyl, (C1-C4) alkoxy, trifluoromethyl, phenyl and dimethylphenyl.
Further, said R 6 Selected from methyl, ethyl, propyl, butyl, methoxy, trifluoromethyl, phenyl, and dimethylphenyl.
Further, R is selected from Ph, 2-Me-Ph, 3-Me-Ph, 4-Me-Ph,2-Et-Ph、3-Et-Ph、4-Et-Ph、2- i Pr-Ph、3- i Pr-Ph、4- i Pr-Ph、2- t Bu-Ph、3- t Bu-Ph、4- t Bu-Ph、2-Ph-Ph、3-Ph-Ph、4-Ph-Ph、2-CF 3 -C 6 H 4 、3-CF 3 -C 6 H 4 、4-CF 3 -C 6 H 4 、2,6-Me 2 -C 6 H 3 、3,5-Me 2 C 6 H 3 、2,6-Et 2 -C 6 H 3 、3,5-Et 2 C 6 H 3 、2,6- i Pr 2 -C 6 H 3 、3,5- i Pr 2 -C 6 H 3 、2,6- t Bu 2 -C 6 H 3 、3,5- t Bu 2 -C 6 H 3 、2,6-Ph 2 -C 6 H 3 、3,5-Ph 2 -C 6 H 3 、2,6-(CF 3 ) 2 -C 6 H 3 、3,5-(CF 3 ) 2 -C 6 H 3 、2,6-(OMe) 2 C 6 H 3 、3,5-(OMe) 2 C 6 H 3 、2,6-(3,5-Me 2 C 6 H 3 ) 2 -C 6 H 3 、2,6-(2,6-Me 2 C 6 H 3 ) 2 -C 6 H 3 、3,5-(3,5-Me 2 C 6 H 3 ) 2 -C 6 H 3 、3,5-(2,6-Me 2 C 6 H 3 ) 2 -C 6 H 3 、2,4,6-Me 3 -C 6 H 2 、2,4,6-Et 3 -C 6 H 2 、2,4,6- i Pr 3 -C 6 H 2 、2,4,6- t Bu 3 -C 6 H 2 、2,4,6-Ph 3 -C 6 H 2 、2,4,6-(CF 3 ) 3 -C 6 H 2 、2,4,6-(OMe) 3 -C 6 H 2 、3,5-di t Bu 2 -4-OMe-Ph, 1-naphthyl, 2-naphthyl.
Further, R is selected from Ph, 2-Me-Ph, 2- i Pr-Ph、4-CF 3 -C 6 H 4 、2,6-Me 2 -C 6 H 3 、3,5-Me 2 C 6 H 3 、3,5-Ph 2 -C 6 H 3 、3,5-(OMe) 2 C 6 H 3 、3,5- t Bu 2 -C 6 H 3 、3,5- i Pr 2 C 6 H 3 、3,5-(CF 3 ) 2 -C 6 H 3 、2,4,6-Et 3 -C 6 H 2 、3,5-di t Bu 2 -4-OMe-Ph、3,5-(3,5-Me 2 C 6 H 3 ) 2 -C 6 H 3 1-naphthyl.
Further, the nitrogen phosphorus ligand is selected from one of the following structures:
a preparation method of a nitrogen phosphine ligand comprises the following steps:
reacting the compound S1 with the compound S2 to obtain an intermediate S3;
reacting the intermediate S3 with the compound S4 to obtain a product;
R 1 、R 2 、R 3 、R 4 、R 5 w is as defined above.
Further, when W is PR 2 When the method is used, the method also comprises the step of reacting the compound with an oxidant to oxidize the compound into P (O) R 2 The method comprises the following steps:
further, the preparation method comprises the following steps:
reacting the compound S1 with Lewis acid and a compound S2 to obtain an intermediate S3;
and reacting the intermediate S3 with a carbodiimide condensing agent, a catalyst and a compound S4 to obtain a product.
Carbodiimide-based condensing agents refer to the following compounds: dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), and 1- (3-dimethylaminopropyl) -3-Ethylcarbodiimide (EDCI); the catalyst refers to the following compounds: pyridine, triethylamine, diethylamine; lewis acids refer to the following compounds: ferric chloride, aluminum chloride, zinc chloride, and trifluoromethanesulfonate.
Further, the lewis acid is zinc chloride; the carbodiimide condensing agent is EDCI, and the catalyst is DMAP. EDCI means 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and DMAP means 4-dimethylaminopyridine.
Further, the preparation method comprises the following steps:
the compound S1 and Lewis acid and the compound S2 are mixed according to a molar ratio of 1: (1-3): (1-3) reacting in chlorobenzene at 100-150 ℃, and performing post-treatment to obtain an intermediate S3;
the intermediate S3, a carbodiimide condensing agent, a catalyst and a compound S4 are mixed according to a molar ratio of 1: (2-6): (1.5-3): (1.1-3) reacting in dichloromethane at room temperature, and carrying out post-treatment to obtain the product.
Further, the oxidizing agent is an aqueous hydrogen peroxide solution.
Further, compound I was mixed with a 30wt% aqueous hydrogen peroxide solution at a molar ratio of 1: (1-4) reacting in dichloromethane at room temperature, and carrying out post-treatment to obtain the product.
The ligand of the invention is applied to asymmetric reactions, in particular to asymmetric cross-coupling alkyne synthesis reactions.
As used herein, "alkyl" refers to a saturated aliphatic hydrocarbon group which is a straight or branched chain group containing 1 to 20 carbon atoms, preferably an alkyl group containing 1 to 12 carbon atoms, more preferably an alkyl group containing 1 to 6 carbon atoms. Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-methylpentyl.
As used herein, "cycloalkyl" refers to a non-aromatic carbocyclic ring, typically having from 3 to 8 ring carbon atoms. The rings may be saturated or have one or more carbon-carbon double bonds. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, and cyclohexenyl.
"alkoxy" as used herein refers to the groups-O- (alkyl) and-O- (cycloalkyl) wherein alkyl, cycloalkyl is defined as described herein, said alkyl group containing from 1 to 20 carbon atoms and said cycloalkyl group containing from 3 to 8 carbon atoms. Non-limiting examples of alkoxy groups include: methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, pentyloxy, 2-pentyloxy, isopentyloxy, neopentyloxy, hexyloxy, 2-hexyloxy, 3-methylpentyloxy, cyclopropyloxy, cyclobutoxy, cyclopentyloxy, cyclohexyloxy. Alkoxy groups typically have 1 to 7 carbon atoms connected by an oxygen bridge.
As used herein, "alkenyl" refers to an unsaturated branched or straight chain alkyl group having at least one carbon-carbon double bond derived by the removal of one molecule of hydrogen from an adjacent carbon atom of the parent alkyl group. Alkenyl groups having 2 to 20 carbon atoms are preferred, and alkenyl groups having 2 to 6 carbon atoms are more preferred. The groups may be in either the cis or trans configuration with respect to one or more double bonds. Typical alkenyl groups include, but are not limited to, vinyl; propenyl, such as prop-1-en-1-yl, prop-1-en-2-yl, prop-2-en-1-yl (allyl), prop-2-en-2-yl; butenyl, such as but-1-en-1-yl, but-1-en-2-yl, 2-methyl-prop-1-en-1-yl, but-2-en-2-yl, but-1, 3-dien-1-yl, but-1, 3-dien-2-yl.
As used herein, "alkynyl" refers to an unsaturated, branched or straight chain alkyl group having at least one carbon-carbon triple bond derived by the removal of two molecules of hydrogen from adjacent carbon atoms of the parent alkyl group. Alkynyl groups having 2 to 20 carbon atoms are preferred, and alkynyl groups having 3 to 6 carbon atoms are more preferred. Typical alkynyl groups include, but are not limited to, ethynyl; propynyl groups such as prop-1-yn-1-yl, prop-2-yn-1-yl; butynyl, e.g. but-1-yn-1-yl, but-1-yn-3-yl, but-3-yn-1-yl.
As used herein, "hydroxy" refers to the group-OH; as used herein, "aldehyde" refers to the group-CHO.
As used herein, "carboxy" refers to the group-COOH.
As used herein, "ester group" refers to-C (O) O (alkyl) or-C (O) O (phenyl), wherein alkyl, phenyl are as defined herein, and said alkyl contains 1 to 20 carbon atoms. For the ester-substituted phenyl group, it may be formed either from the phenolic hydroxyl group of the phenyl ring and a carboxylic acid, such as PhOCOCH 3 PhOPiv, or from the carboxyl group of the phenyl ring with an alcohol, e.g. PhCOOCH 3 。
The term "halogen" as used herein refers to fluorine, chlorine, bromine and iodine.
As used herein, "trifluoromethyl" refers to-CF 3 (ii) a As used herein, "cyano" refers to-CN.
As used herein, "aryl" refers to a 6-membered carbocyclic aromatic ring, such as benzene; bicyclic ring systems in which at least one ring is carbocyclic and aromatic, such as naphthalene, indane and 1,2,3, 4-tetrahydronaphthalene; and tricyclic ring systems in which at least one ring is carbocyclic and aromatic, such as fluorene.
As used herein, "acyl" refers to the groups (alkyl) -C (O) -, (cycloalkyl) -C (O) -, (aryl) -C (O) -, wherein the groups are attached to the parent structure through a carbonyl function, and wherein alkyl, cycloalkyl, and aryl are as described herein, the alkyl contains 1 to 20 carbon atoms, and the cycloalkyl is 3 to 8 carbon atoms.
As used herein, "amido" refers to the group-CONR b R c Wherein R is b Selected from hydrogen, alkyl, cycloalkyl, aryl, R c Selected from alkyl, cycloalkyl, aryl; or R b And R c And together with the nitrogen to which they are attached form a 5-to 8-membered nitrogen-containing heterocycloalkyl group optionally containing 1 or 2 additional heteroatoms selected from O, N and S in the heterocycloalkyl ring. Alkyl, cycloalkyl, aryl are as defined hereinThe alkyl group has 1 to 20 carbon atoms, and the cycloalkyl group has 3 to 8 carbon atoms.
As used herein, "amino" refers to-NH 2 (ii) a As used herein, "nitro" refers to-NO 2 。
As used herein, "phenyl" means
As used herein, "phenoxy" refers to PhO-.
As used herein, "sulfonyl" refers to the following groups: -S (O) 2 ) - (alkyl), -S (O) 2 ) - (aryl), -S (O) 2 ) - (amino). Alkyl, aryl, amino groups are as defined herein, said alkyl groups containing from 1 to 20 carbon atoms.
As used herein, "sulfonic acid group" means-SO 3 H; "mercapto" as used herein refers to-SH;
as used herein, "dimethylphenyl" refers to a phenyl group having two methyl substituents, which may be 2,3, 2,4, 2,5, 2,6, 3,4, 3,5, 3,6, 4,5, 4,6, 5,6 substitutions.
As used herein, "naphthylmethyl" refers to
"benzyl" as used herein refers to PhCH 2 -; as used herein, "phenylethyl" refers to PhCH 2 CH 2 -。
As used herein, "trifluoromethylphenyl-substituted phenyl or benzyl" refers to p-trifluoromethylphenyl, o-trifluoromethylphenyl, m-trifluoromethylphenyl-substituted phenyl or benzyl.
The "substitution" of "substituted phenyl", "substituted benzyl" as defined herein is mono-or polysubstituted, for example, "substituted phenyl" includes: (1) a benzene ring has a substituent; (2) The benzene ring has two or more substituents which may be the same or different. The substituted position may be any of positions of benzene rings 2,3,4, 5, 6.
The invention has the following beneficial effects:
the chiral oxazoline and amido phosphine are used as core skeletons, nitrogen phosphorus compounds with novel structures are synthesized through derivation, and can be used as ligands of asymmetric reaction, particularly, the electronic effect and steric hindrance effect of phosphorus on the ligands can be regulated and controlled, the electronic effect and steric hindrance effect of chiral oxazoline substituent can also be regulated and controlled, and the chiral oxazoline and amido phosphine compound has unique advantages in free radical asymmetric reaction: high catalytic efficiency, wide substrate application range, high yield and good enantioselectivity. The ligand of the invention can be widely applied to oxidation type asymmetric cross-coupling reactions of different types of alkyl carbon-hydrogen bonds and terminal alkynes, and has important significance for developing a novel catalytic system to solve other types of radical asymmetric reactions.
Detailed Description
All reactions were carried out under an argon atmosphere. Unless otherwise stated, chemicals were purchased from commercial products and were not further purified. Chlorobenzene and dichloromethane used in the experiment are anhydrous solvents. Thin Layer Chromatography (TLC) used 60F254 silica gel plates. The silica gel column chromatography uses Qingdao marine silica gel (particle size 0.040-0.063 mm). TLC color development was performed with UV light (254 nm) or iodine. NMR spectra were characterized using a Bruker DPX 400 nuclear magnetic resonance apparatus, 1 the H NMR was 400MHz and the molecular weight of the polymer, 31 p NMR was 162MHz, the solvent was deuterated chloroform, and Tetramethylsilane (TMS) was used as an internal standard. Chemical shifts are in ppm and coupling constants are in Hz. In that 1 In H NMR, δ represents chemical shift, s represents singlet, d represents doublet, t represents triplet, q represents quartet, p represents quintet, m represents multiplet, br represents broad.
General synthesis of ligands:
step 1: compound S1 (20 mmol), compound S2 (20-60 mmol, preferably 20 mmol), anhydrous zinc chloride (20-60 mmol, preferably 40 mmol) were placed in a 100mL sealed tube, argon was replaced three times, 40mL chlorobenzene was added, followed by stirring at 100-150 deg.C (preferably 130 deg.C) for 24-72 hours, and detection by TLC was performed until complete disappearance of compound S1. And (3) post-treatment: cooling to room temperature, adding water and ethyl acetate, adding 2mL of ethylenediamine, stirring until the system is clear, followed by extraction with ethyl acetate, separation of the organic layer, drying, filtration and vacuum concentration, the residue thus obtained is purified by silica gel column to give intermediate S3 (40-80% yield).
Step 2: a solution of intermediate S3 (10 mmol) and compound S4 (11-20 mmol, preferably 12 mmol) in 50mL of dichloromethane was added EDCI (20-60 mmol, preferably 30 mmol) and DMAP (15-30 mmol, preferably 20 mmol). The reaction was stirred at room temperature for 24 hours and quenched by addition of water. The organic layer was separated, dried, filtered and concentrated in vacuo. The residue thus obtained was purified by silica gel column to give the product (60-80% yield).
When W is PR 2 When the method is used, the method also comprises the step of oxidizing the compound into P (O) R by reacting the compound with aqueous hydrogen peroxide solution 2 The steps of (1):
to a solution of ligand (1 mmol) in 10mL of dichloromethane was added 30wt% aqueous hydrogen peroxide (containing 1-4 mmol hydrogen peroxide, preferably 2 mmol), the reaction was stirred at room temperature for 12 hours, concentrated in vacuo, and the residue thus obtained was purified by silica gel column to give oxidized ligand (90-98% yield).
Example 1
Characterization data for ligand 1: 1 H NMR(400MHz,CDCl 3 ) 1 H NMR(400MHz,CDCl 3 )δ12.91(s,1H),8.82(d,J＝8.4Hz,1H),7.94–7.80(m,2H),7.50–7.26(m,13H),7.21–7.05(m,2H),4.42(dd,J＝8.6,7.7Hz,1H),4.20–4.03(m,2H),1.76(dq,J＝13.3,6.7Hz,1H),0.93(dd,J＝6.7,3.7Hz,6H)。 13 C NMR(100MHz,CDCl 3 )δ167.4,163.63,141.63,141.40,140.12,138.65,138.47,138.42,138.40,138.35,138.29,134.78,134.07,133.99,133.87,133.79,132.52,130.34,129.01,128.50,128.43,128.41,128.37,128.30,127.51,127.47,122.38,120.05,113.40,72.84,69.52,33.21,19.04,18.74。 31 P NMR(162MHz,CDCl 3 )δ-8.21。
example 2
Characterization data for ligand 2: 1 H NMR(400MHz,CDCl 3 )δ12.84(s,1H),8.80(d,J＝8.4Hz,1H),7.94(dd,J＝7.9,1.3Hz,1H),7.68(dd,J＝7.3,3.8Hz,1H),7.48(t,J＝7.4Hz,1H),7.42–7.23(m,15H),7.13(t,J＝7.6Hz,1H),7.05–6.95(m,2H),5.55–5.37(m,1H),4.81(dd,J＝10.0,8.6Hz,1H),4.31(t,J＝8.5Hz,1H)。 13 C NMR(100MHz,CDCl 3 )δ167.22,164.74,141.68,141.02,140.21,138.91,138.67,138.58,138.26,134.78,134.12,133.91,133.86,133.66,132.88,130.32,129.17,128.87,128.39,128.32,128.27,127.85,127.59,127.55,126.63,122.47,120.26,113.19,73.21,69.91。 31 P NMR(162MHz,CDCl 3 )δ-7.84。
example 3
Characterization data for ligand 3: 1 H NMR(400MHz,CDCl 3 )δ12.79(s,1H),8.84(d,J＝8.3Hz,1H),7.89(d,J＝7.8Hz,1H),7.83(d,J＝3.4Hz,1H),7.47(t,J＝7.8Hz,1H),7.43–7.30(m,12H),7.29–7.18(m,5H),7.12(dd,J＝14.0,6.6Hz,2H),4.79–4.57(m,1H),4.39(t,J＝8.9Hz,1H),4.12(t,J＝8.0Hz,1H),3.11(dd,J＝13.8,6.6Hz,1H),2.84(dd,J＝13.8,7.4Hz,1H)。 13 C NMR(100MHz,CDCl 3 )δ167.37,164.11,141.39,141.17,140.14,138.90,138.67,138.58,138.46,137.63,134.94,134.07,133.98,133.87,133.77,132.69,130.43,129.07,128.62,128.42,128.33,127.44,127.40,126.66,122.44,120.16,113.34,70.81,67.74,42.14。 31 P NMR(162MHz,CDCl 3 )δ-8.02。
example 4
Characterization data for ligand 4: 1 H NMR(400MHz,CDCl 3 )δ0.83(d,J＝1.2Hz,9H),3.98–4.19(m,2H),4.30(dd,J＝9.6,8.1Hz,1H),7.01–7.11(m,2H),7.26–7.46(m,13H),7.75–7.89(m,2H),8.75(d,J＝8.4Hz,1H),12.83(s,1H)。 31 P NMR(162MHz,CDCl 3 )δ-8.42。
example 5
Characterization data for ligand 5: 1 H NMR(400MHz,CDCl 3 )δ12.75(s,1H),8.70(dd,J＝8.5,1.1Hz,1H),7.87(ddd,J＝7.8,3.9,1.3Hz,1H),7.82(dd,J＝7.9,1.7Hz,1H),7.54(td,J＝7.5,1.3Hz,1H),7.43(td,J＝7.6,1.3Hz,1H),7.40-7.18(m,15H),7.10(ddd,J＝7.8,3.9,1.2Hz,1H),7.02(td,J＝7.7,1.2Hz,1H),5.75(d,J＝7.9Hz,1H),5.42(ddd,J＝8.2,6.9,1.7Hz,1H),3.52(dd,J＝18.1,6.9Hz,1H),3.37(dd,J＝17.9,1.6Hz,1H)。 13 C NMR(101MHz,CDCl 3 )δ167.1,163.9,141.7,141.5,141.3,139.9,139.7,139.1,138.8,138.6,138.5,138.1,138.0,134.8,134.1,133.9,133.8,133.6,132.5,129.0,128.7,128.4,128.31,128.27,128.25,128.22,128.15,127.49,127.45,127.41,125.5,125.0,122.3,120.0,113.3,81.7,76.6,39.8。 31 P NMR(162MHz,CDCl 3 )δ-7.84。
example 6
Characterization data for ligand 6: 1 H NMR(400MHz,CDCl 3 )δ12.87(s,1H),8.77(d,J＝8.4Hz,1H),7.92–7.89(m,1H),7.84–7.82(m,1H),7.43–7.35(m,3H),7.34–7.27(m,10H),7.13–6.99(m,2H),4.43(t,J＝8.8Hz,1H),4.28–4.21(m,1H),3.95(t,J＝8.1Hz,1H),1.63(p,J＝7.4Hz,2H),0.93(t,J＝7.4Hz,3H)。 13 C NMR(101MHz,CDCl 3 )δ167.2,163.6,141.4,141.2,140.0,138.8,138.6,138.5,138.42,138.36,138.3,134.8,134.0,133.9,133.8,133.7,132.4,130.3,128.9,128.4,128.3,128.30,128.28,128.2,127.4,127.4,122.3,120.0,113.3,71.0,68.0,28.9,10.4。 31 P NMR(162MHz,CDCl 3 )δ-8.06。
example 7
Characterization data for ligand 7: 1 H NMR(400MHz,CDCl 3 )δ12.51(s,1H),8.59(d,J＝8.5Hz,1H),7.79(d,J＝7.8Hz,1H),7.74–7.71(m,1H),7.38–7.16(m,16H),7.04–7.00(m,2H),4.61(p,J＝7.5Hz,1H),4.32(t,J＝8.9Hz,1H),4.06(t,J＝8.1Hz,1H),3.10(dd,J＝13.8,6.3Hz,1H),2.77(dd,J＝13.8,7.7Hz,1H),1.22–1.17(m,36H)。 13 C NMR(101MHz,CDCl 3 )δ167.4,163.9,150.1,150.0,150.0,140.6,140.4,140.3,140.0,137.6,137.3,137.2,137.0,134.2,132.5,129.8,129.0,128.8,128.6,128.5,128.4,128.3,128.2,127.83,127.0,127.0,126.6,122.3,122.3,122.1,120.1,113.2,70.6,67.7,42.1,34.8,34.8,31.4,31.3。 31 P NMR(162MHz,CDCl 3 )δ-4.26。
example 8
Characterization data for ligand 8: 1 H NMR(400MHz,CDCl 3 )δ12.46(s,1H),8.68(d,J＝8.4Hz,1H),7.80(d,J＝7.8Hz,1H),7.72(dd,J＝7.6,4.7Hz,1H),7.38(t,J＝7.9Hz,1H),7.31(dd,J＝7.7,3.0Hz,1H),7.25–7.13(m,8H),7.02(t,J＝7.6Hz,1H),6.84–6.82(m,4H),4.61(dt,J＝14.2,7.2Hz,1H),4.34(t,J＝8.9Hz,1H),4.06(t,J＝8.0Hz,1H),3.05(dd,J＝13.8,6.2Hz,1H),2.79–2.48(m,15H),1.19(q,J＝7.5Hz,6H),0.83(q,J＝7.3Hz,12H)。 13 C NMR(101MHz,CDCl 3 )δ167.2,163.9,149.0,148.8,144.2,141.7,141.4,140.43,140.36,140.2,137.6,133.7,132.5,132.2,129.7,129.0,128.9,128.6,127.4,127.1,126.6,126.3,126.2,121.9,120.2,113.1,70.6,67.8,42.1,28.5,28.4,28.4,28.3,28.2,15.1,15.1。 31 P NMR(162MHz,CDCl 3 )δ-27.87。
example 9
Characterization data for ligand 9: 1 H NMR(400MHz,CDCl 3 )δ13.10(s,1H),8.69(d,J＝8.5Hz,1H),7.87(t,J＝8.7Hz,4H),7.71(t,J＝6.8Hz,4H),7.44(q,J＝7.8Hz,2H),7.32(t,J＝7.6Hz,1H),7.26–7.17(m,5H),7.11(t,J＝7.6Hz,1H),6.91(dd,J＝7.8,4.1Hz,1H),4.77–4.69(m,1H),4.41(t,J＝8.9Hz,1H),4.15(t,J＝8.0Hz,1H),3.09(dd,J＝13.8,7.0Hz,1H),2.87(dd,J＝13.8,7.3Hz,1H)。 31 P NMR(162MHz,CDCl 3 )δ-5.6。
example 10
Characterization data for ligand 10: 1 H NMR(400MHz,CDCl 3 )δ12.83(d,J＝4.5Hz,1H),8.75(dd,J＝8.6,3.9Hz,1H),7.86–7.81(m,2H),7.43–7.28(m,13H),7.09–7.04(m,2H),4.38(t,J＝8.8Hz,1H),4.14(q,J＝8.6Hz,1H),4.02(t,J＝8.3Hz,1H),1.55–1.44(m,2H),1.14–1.03(m,1H),0.86–0.78(m,6H)。 13 C NMR(101MHz,CDCl 3 )δ167.4,163.4,141.7,138.1,134.7,134.0,133.9,133.8,133.7,132.4,130.2,128.9,128.4,128.3,128.3,128.2,127.4,122.3,120.0,113.4,71.5,69.4,39.6,25.7,15.1,11.1。 31 P NMR(162MHz,CDCl 3 )δ-8.35。
example 11
Characterization data for ligand 11: 1 H NMR(400MHz,CDCl 3 )δ12.80(s,1H),8.80(d,J＝8.5Hz,1H),7.98–7.95(m,1H),7.83(d,J＝7.8Hz,1H),7.80–7.78(m,1H),7.69–7.63(m,2H),7.44(td,J＝8.1,7.2,4.2Hz,2H),7.37(t,J＝7.9Hz,1H),7.33–7.19(m,14H),7.09–6.99(m,3H),4.73(p,J＝7.3Hz,1H),4.24(t,J＝8.9Hz,1H),4.12(t,J＝7.8Hz,1H),3.50(dd,J＝14.2,6.4Hz,1H),3.10(dd,J＝14.2,7.8Hz,1H)。 13 C NMR(101MHz,CDCl 3 )δ167.0,163.9,140.9,140.7,140.0,138.8,138.6,138.5,138.4,134.7,133.8,133.8,133.7,133.6,133.6,133.5,132.5,131.7,130.2,128.9,128.8,128.2,128.2,128.1,128.1,127.3,127.1,126.7,126.0,125.6,125.3,123.2,122.2,119.9,113.0,71.0,66.6,39.3。 31 P NMR(162MHz,CDCl 3 )δ-7.89。
example 12
Characterization data for ligand 12: 1 H NMR(400MHz,CDCl 3 )δ12.72(s,1H),8.78(dt,J＝8.6,2.3Hz,1H),7.84(dq,J＝7.9,1.7Hz,1H),7.76–7.64(m,4H),7.61(s,1H),7.44–7.40(m,3H),7.31–7.28(m,11H),7.12–7.04(m,2H),6.97(ddd,J＝7.8,4.3,1.7Hz,1H),6.91(td,J＝7.5,1.4Hz,1H),4.74(dq,J＝9.4,7.2Hz,1H),4.38(t,J＝8.9Hz,1H),4.14(t,J＝8.0Hz,1H),3.19(dd,J＝13.8,7.0Hz,1H),2.97(dd,J＝13.8,7.2Hz,1H)。 13 C NMR(101MHz,CDCl 3 )δ167.1,163.9,140.8,140.6,139.9,138.4,138.4,138.3,135.0,134.6,133.8,133.7,133.6,133.5,133.3,132.4,132.0,130.0,128.9,128.2,128.1,128.0,128.0,127.4,127.3,127.2,127.0,125.9,125.3,122.2,119.8,113.1,70.6,67.5,42.1。 31 P NMR(162MHz,CDCl 3 )δ-8.04。
example 13
Characterization data for ligand 13: 1 H NMR(400MHz,CDCl 3 )δ12.87(s,1H),8.74(dd,J＝8.5,3.9Hz,1H),7.88–7.81(m,2H),7.43–7.29(m,13H),7.09–7.03(m,2H),4.42–4.33(m,1H),4.09–4.00(m,2H),1.73–1.59(m,5H),1.27–0.83(m,6H)。 13 C NMR(101MHz,CDCl 3 )δ167.4,163.3,141.7,141.5,140.0,138.3,138.2,138.2,134.6,134.0,133.9,133.8,133.7,132.4,130.1,128.8,128.3,128.3,128.2,127.4,127.4,122.3,120.0,113.4,71.8,69.5,42.9,29.6,29.2,26.3,25.9,25.8。 31 P NMR(162MHz,CDCl 3 )δ-8.39。
example 14
Characterization data for ligand 14: 1 H NMR(400MHz,CDCl 3 )δ12.74(s,1H),8.79(d,J＝8.4Hz,1H),7.83(d,J＝7.9Hz,1H),7.72(dd,J＝7.8,3.9Hz,1H),7.46(d,J＝7.5Hz,2H),7.42–7.27(m,16H),7.20–7.00(m,6H),4.61(p,J＝7.4Hz,1H),4.36(t,J＝8.9Hz,1H),4.06(t,J＝8.0Hz,1H),3.00(dd,J＝13.8,7.4Hz,1H),2.81(dd,J＝13.9,6.7Hz,1H)。 13 C NMR(101MHz,CDCl 3 )δ167.2,164.0,141.1,140.9,140.5,140.0,139.1,138.6,138.5,138.4,138.4,138.3,136.7,134.8,133.9,133.6,132.6,130.3,129.3,129.0,128.6,128.4,128.3,128.2,128.2,128.2,127.3,127.2,127.1,127.0,126.8,122.3,120.0,113.2,70.8,67.6,41.8。 31 P NMR(162MHz,CDCl 3 )δ-8.10。
example 15
Characterization data for ligand 15: 1 H NMR(400MHz,CDCl 3 )δ12.53(s,1H),8.38(d,J＝8.4Hz,1H),7.74(ddd,J＝7.7,3.7,1.3Hz,1H),7.52(td,J＝7.5,1.3Hz,1H),7.43(td,J＝7.6,1.3Hz,1H),7.37-7.12(m,13H),7.08(ddd,J＝7.8,4.0,1.2Hz,1H),7.07-6.94(m,2H),6.75(ddd,J＝11.5,8.3,1.1Hz,1H),5.65(d,J＝8.0Hz,1H),5.47(ddd,J＝8.2,6.7,1.8Hz,1H),3.49(dd,J＝18.1,6.7Hz,1H),3.39(dd,J＝18.2,1.7Hz,1H)。 13 C NMR(101MHz,CDCl 3 )δ167.1,162.8,162.3,162.2,160.2,141.3,141.2,140.9,140.7,140.6,139.6,138.8,138.6,137.9,137.8,137.7,137.6,134.6,134.1,133.88,133.85,133.7,133.0,132.9,130.3,128.6,128.5,128.33,128.31,128.28,128.2,128.12,128.05,127.4,127.3,127.20,127.16,125.5,125.3,125.2,124.9,115.99,115.96,110.6,110.3,103.3,103.2,82.4,75.0,39.7。 19 F NMR(376MHz,CDCl 3 )δ-106.56； 31 P NMR(162MHz,CDCl 3 )δ-7.61。
example 16
Characterization data for ligand 16: 1 H NMR(400MHz,CDCl 3 )δ10.81(s,1H),8.44-8.40(m,1H),7.58(ddd,J＝7.5,3.6,1.6Hz,1H),7.50-7.32(m,4H),7.34-7.28(m,5H),7.25-7.16(m,4H),7.13-7.09(m,2H),7.06-7.01(m,1H),6.94(d,J＝7.6Hz,1H),6.77(td,J＝7.6,1.2Hz,1H),5.72(d,J＝7.8Hz,1H),5.48(ddd,J＝7.7,5.6,2.2Hz,1H),3.49-3.39(m,2H)。 13 C NMR(101MHz,CDCl 3 )δ167.0,162.3,141.0,140.5,140.3,139.5,138.7,138.6,138.4,137.6,137.5,137.4,134.53,134.51,134.2,134.1,134.0,133.9,131.1,130.6,130.0(q,J C-F ＝31.8Hz),128.8,128.7,128.6,128.5,128.5,128.3,128.2,127.5,127.3,127.2,125.5,124.7,124.6,123.6(q,J C-F ＝272.1Hz),121.7(q,J C-F ＝5.5Hz),114.3-114.2(m,1C),83.8,76.4,39.0。 19 F NMR(376MHz,CDCl 3 )δ-58.86。 31 P NMR(162MHz,CDCl 3 )δ-7.52。
example 17
Characterization data for ligand 17: 1 H NMR(400MHz,CDCl 3 )δ10.62(s,1H),7.99-7.86(m,2H),7.78-7.60(m,4H),7.52(ddd,J＝7.3,4.0,1.5Hz,1H),7.44-7.25(m,5H),7.24-7.12(m,5H),7.08(td,J＝7.4,3.1Hz,2H),6.87(dt,J＝8.2,4.1Hz,1H),6.80(d,J＝7.6Hz,1H),5.68(d,J＝7.6Hz,1H),5.48(ddd,J＝7.5,5.0,2.3Hz,1H),3.46(t,J＝3.3Hz,2H)。 13 C NMR(101MHz,CDCl 3 )δ166.3,166.2,161.6,141.0,140.5,140.4,139.3,137.9,134.5,134.4,132.5,132.4,132.14,132.11,132.0,131.9,131.8,131.6,131.5,131.39,131.37,131.2,131,1,130.9,130.5,130.0,129.90,129.85,129.5,128.8,128.2,128.1,127.90,127.86,127.8,127.6,125.3,124.6,124.4,122.0,121.9-121.6(m,1C),115.0,83.9,76.2,38.8。 19 F NMR(376MHz,CDCl 3 )δ-58.92。 31 P NMR(162MHz,CDCl 3 )δ29.95。
example 18
Characterization data for ligand 18: 1 H NMR(400MHz,CDCl 3 )δ12.21(s,1H),8.50(dd,J＝8.6,1.1Hz,1H),7.77(dd,J＝8.0,1.6Hz,1H),7.39(ddd,J＝7.8,3.7,1.3Hz,1H),7.33(tq,J＝4.3,1.8Hz,3H),7.28-7.11(m,12H),7.05-6.91(m,6H),5.14(td,J＝9.3,7.5Hz,1H),4.30(t,J＝9.1Hz,1H),4.05(dd,J＝8.7,7.5Hz,1H),3.98(d,J＝9.2Hz,1H),1.20(d,J＝8.4Hz,36H)。 13 C NMR(101MHz,CDCl 3 )δ167.5,164.2,150.08,150.05,150.02,149.98,141.8,141.5,139.9,134.2,132.4,129.6,128.8,128.7,128.4,128.31,128.29,128.2,128.1,127.0,126.7 126.4,122.3,122.2,122.1,120.3,113.3,70.1,70.1,56.7,34.8,34.7,31.33,31.31。 31 P NMR(162MHz,CDCl 3 )δ-4.35。
example 19
Characterization data for ligand 19: 1 H NMR(400MHz,CDCl 3 )δ11.95(s,1H),8.04-7.93(m,1H),7.77-7.69(m,2H),7.61(dd,J＝19.6,13.1Hz,4H),7.46(dd,J＝11.7,8.5Hz,3H),7.37-7.31(m,1H),7.30-7.26(m,1H),7.25-7.13(m,9.6H),7.07-6.99(m,3H),6.96(t,J＝7.6Hz,1H),5.18(q,J＝8.0Hz,1H),4.31(t,J＝9.1Hz,1H),4.03(t,J＝8.4Hz,1H),3.96(d,J＝9.7Hz,1H),1.20(d,J＝2.1Hz,36H)。 13 C NMR(101MHz,CDCl 3 )δ166.3,166.28,164.1,150.3,150.1,142.0,141.7,140.5,140.4,139.3,135.1,135.0,133.3,132.7,132.5,132.4,132.1,131.8,131.8,131.7,131.5,129.7,129.6,128.8,128.8,128.4,128.3,128.2,127.1,127.0,126.8,126.6,126.3,126.3,126.2,126.2,125.5,122.4,120.4,113.7,70.3,70.2,56.8,34.9,31.3。 31 P NMR(162MHz,CDCl 3 )δ32.34。
example 20
Characterization data for ligand 20: 1 H NMR(400MHz,CDCl 3 )δ12.47(s,1H),8.61(dd,J＝8.5,1.1Hz,1H),7.82-7.69(m,2H),7.48(td,J＝7.5,1.3Hz,1H),7.40(td,J＝7.6,1.4Hz,1H),7.38-7.17(m,9H),7.07-7.00(m,1H),6.96(td,J＝7.7,1.2Hz,1H),5.72(d,J＝8.0Hz,1H),5.44-5.32(m,1H),3.74-3.21(m,8H),1.28(d,J＝9.9Hz,36H)。 31 P NMR(162MHz,CDCl 3 )δ-5.64。
example 21
Characterization data for ligand 21: 1 H NMR(400MHz,CDCl 3 )δ12.86(s,1H),8.71(dd,J＝8.5,1.1Hz,1H),7.86(ddd,J＝7.8,3.9,1.3Hz,1H),7.81(dd,J＝7.9,1.7Hz,1H),7.77(t,J＝1.8Hz,1H),7.71-7.64(m,5H),7.58-7.49(m,9H),7.46(td,J＝7.6,1.3Hz,1H),7.37(ddt,J＝7.3,5.8,1.1Hz,8H),7.34-7.27(m,7H),7.25-7.19(m,3H),7.01(ddd,J＝8.1,7.4,1.2Hz,1H),5.56(d,J＝8.0Hz,1H),5.33(ddd,J＝8.3,7.0,1.7Hz,1H),3.48(dd,J＝18.1,7.0Hz,1H),3.32(dd,J＝18.2,1.7Hz,1H)。 31 P NMR(162MHz,CDCl 3 )δ-5.35。
example 22
Characterization data for ligand 22: 1 h NMR (400 MHz, chloroform-d) delta 12.80 (s, 1H), 8.63-8.57 (m, 2H), 8.49 (dd,J＝8.5,4.8Hz,1H),7.97-7.90(m,1H),7.88-7.74(m,5H),7.55(td,J＝7.6,1.3Hz,1H),7.50-7.27(m,11H),7.21-7.16(m,1H),7.09-6.92(m,4H),5.78(d,J＝8.0Hz,1H),5.45(ddd,J＝8.3,6.9,1.7Hz,1H),3.55(dd,J＝18.0,6.9Hz,1H),3.44-3.34(m,1H)。 31 p NMR (162 MHz, chloroform-d) delta-26.03.
Example 23
Characterization data for ligand 23: 1 h NMR (400 MHz, chloroform-d) Δ 12.59 (s, 1H), 8.64 (dd, J =8.5,1.1Hz, 1H), 7.90-7.75 (m, 2H), 7.50 (td, J =7.5,1.3Hz, 1H), 7.39 (td, J =7.6,1.3Hz, 1H), 7.36-7.29 (m, 2H), 7.29-7.23 (m, 4H), 7.23-7.17 (m, 3H), 7.07-6.96 (m, 3H), 6.92-6.73 (m, 3H), 5.70 (d, J =7.9hz, 1h), 5.39 (ddd, J =8.2,6.8,1.7hz, 1h), 3.88-3.70 (m, 2H), 3.50 (dd, J =18.0,6.8hz, 1h), 3.35 (dd, J =18.0,1.6hz, 1h), 1.13 (dt, J =12.7,6.5hz, 9h). 31 P NMR (162 MHz, chloroform-d) delta-28.64.
Example 24
Characterization data for ligand 24: 1 h NMR (400 MHz, chloroform-d) δ 12.54 (s, 1H), 8.59 (dd, J =8.5,1.1hz, 1h), 7.80 (dd, J =7.9,3.4hz, 2h), 7.49 (t, J =7.5hz, 1h), 7.40 (t, J =7.6hz, 1h), 7.37-7.28 (m, 4H), 7.26 (d, J =3.1hz, 3h), 7.19 (d, J =8.2hz, 4h), 7.07 (dd, J =7.8,4.0hz, 1h), 6.99 (dd, J =8.2,7.4hz, 1h), 5.71 (d, J =8.0hz, 1h), 5.39 (J, J =8.2, 7.0h), 3.50, 1h (J = 3.50, 10H), 1.17.17, 3.1h, 360, 3.1h, 19 (d, 17.34H, 19H), 1.17H, 19H, 1.3.3H, 18H, 19H, 1H). 31 P NMR (162 MHz, chloroform-d) delta-4.36.
Example 25
Characterization data for ligand 25: 1 h NMR (400 MHz, chloroform-d) delta 12.28 (s,1H),8.30–8.20(m,1H),8.06(dd,J＝8.5,1.2Hz,1H),7.83–7.63(m,6H),7.56–7.41(m,2H),7.36–7.20(m,8H),7.19–
7.08(m,1H),7.08–6.94(m,4H),5.69(d,J＝7.8Hz,1H),5.42(ddd,J＝8.0,6.8,1.5Hz,1H),3.53(dd,J＝18.1,6.8Hz,1H),3.39(dd,J＝18.1,1.5Hz,1H)。 31 P NMR (162 MHz, chloroform-d) delta 30.98.
Example 26
Characterization data for ligand 26: 1 h NMR (400 MHz, chloroform-d) δ 12.58 (s, 1H), 8.69 (dd, J =9.3,5.2hz, 1h), 7.84 (ddd, J =7.6,3.8,1.4hz, 1h), 7.62-7.49 (m, 2H), 7.44 (td, J =7.6,1.4hz, 1h), 7.36-7.14 (m, 15H), 7.12-7.04 (m, 2H), 5.77 (d, J =7.9hz, 1h), 5.45 (ddd, J =8.3,6.9,1.7hz, 1ddh), 3.54 (J =18.0,6.9hz, 1ddh), 3.38 (J =18.0,1.7hz, 1H). 19 F NMR (376 MHz, chloroform-d) delta-119.46. 31 P NMR (162 MHz, chloroform-d) delta-7.75.
Example 27
Characterization data for ligand 27: 1 h NMR (400 MHz, chloroform-d) δ 10.68 (s, 1H), 8.61-8.11 (m, 1H), 7.60-7.53 (m, 1H), 7.51-7.45 (m, 1H), 7.44-7.36 (m, 3H), 7.21 (dd, J =9.1,3.5hz, 3h), 7.18-7.08 (m, 4H), 7.08-7.03 (m, 2H), 7.02-6.97 (m, 1H), 6.94 (t, J =7.4hz, 1h), 6.85 (t, J =7.4hz, 1h), 6.77 (dd, J =7.7,4.2hz, 1h), 6.69-6.60 (m, 1H), 5.70 (d, J =7.8h, 1h), 5.45 =7.7,4.2hz, 1h), 6.69-6.60 (m, 1H), 5.70 (d, J =7.8h, 1H), 5.45 (J =7.8, 1H), 3.23, 3.8H, 3.23H), 3.23, 3H, 3.8H, 3.41H, 3H, 3.8H, 1H). 19 F NMR (376 MHz, chloroform-d) delta-58.87. 31 P NMR (162 MHz, chloroform-d) delta-24.20.
Example 28
Characterization data for ligand 28: 1 h NMR (400 MHz, chloroform-d) δ 10.55 (s, 1H), 8.14 (d, J =8.0hz, 1h), 7.49-7.27 (m, 6H), 7.24-7.17 (m, 3H), 7.15 (t, J =7.4hz, 1h), 7.10-7.03 (m, 2H), 6.96 (ddd, J =7.5,3.9,1.7hz, 1h), 6.91-6.80 (m, 3H), 6.68 (dd, J =7.7,4.0hz, 1h), 5.69 (d, J =7.8hz, 1h), 5.45 (ddd, J =7.8,6.0,1.8hz, 1h), 3.88 (q, J =7.2hz, 1h), 3.79-3.60 (m, 1H), 3.53-3.28 (m, 2H), 1.18 (d, J =6.8hz, 3h), 1.14 (d, J =6.7hz, 3h), 1.01 (d, J =6.8hz, 3h), 0.96 (d, J =6.8hz, 3h). 19 F NMR (376 MHz, chloroform-d) delta-58.90. 31 P NMR (162 MHz, chloroform-d) delta-29.37.
Example 29
Characterization data for ligand 29: 1 h NMR (400 MHz, chloroform-d) δ 12.90 (s, 1H), 8.85 (dd, J =8.5,1.2hz, 1h), 8.06 (dd, J =7.9,1.6hz, 1h), 7.72 (ddd, J =7.8,3.9,1.3hz, 1h), 7.51 (ddd, J =8.8,7.3,1.7hz, 1h), 7.34-7.23 (m, 11H), 7.16 (dtd, J =10.9,7.6,1.3hz, 2h), 7.12-7.01 (m, 6H), 7.00-6.88 (m, 6H), 5.99 (d, J = 10.1h), 5.80 (d, J =10.0hz, 1h). 31 P NMR (162 MHz, chloroform-d) delta-7.89.
Example 30
Characterization data for ligand 30: 1 h NMR (400 MHz, chloroform-d) δ 12.90 (s, 1H), 8.85 (dd, J =8.6,1.2hz, 1h), 8.07 (dd, J =7.9,1.6hz, 1h), 7.72 (dd, J =7.3,3.9hz, 1h), 7.51 (ddd, J =8.8,7.4,1.7hz, 1h), 7.34-7.21 (m, 11H), 7.17 (dtd, J =10.8,7.5,1.3hz, 2h), 7.11-7.01 (m, 5H), 6.94 (dtd, J =8, 7.8,3.3hz, 6h), 6.00 (d, J =10.1hz, 1h), 5.80 (d, J = 10.1h). 31 P NMR (162 MHz, chloroform-d) delta-7.90.
Example 31
Characterization data for ligand 31: 1 h NMR (400 MHz, chloroform-d) δ 12.33 (s, 1H), 8.68 (dd, J =8.5,1.2hz, 1h), 7.80 (dd, J =7.9,1.6hz, 1h), 7.47-7.41 (m, 1H), 7.40-7.36 (m, 1H), 7.31 (d, J =3.6hz, 7h), 7.28-7.18 (m, 15H), 7.18-7.10 (m, 3H), 7.08-6.88 (m, 5H), 5.14 (td, J =9.2,6.9hz, 1h), 4.33 (t, J =9.1hz, 1h), 4.10 (dd, J =8.8,7.2hz, 1h), 4.04-3.94 (m, 1H). 31 P NMR (162 MHz, chloroform-d) delta-8.12.
Example 32
Characterization data for ligand 32: 1 H NMR(400MHz,CDCl 3 )δ12.21(s,1H),8.55(dd,J＝8.4,1.2Hz,1H),7.78(dd,J＝8.0,1.6Hz,1H),7.40–7.33(m,2H),7.29–7.15(m,9H),7.09–6.89(m,12H),5.13(td,J＝9.2,7.6Hz,1H),4.33(t,J＝9.1Hz,1H),4.07(dd,J＝8.8,7.4Hz,1H),3.98(d,J＝9.3Hz,1H),2.82–2.70(m,4H),1.15(dd,J＝7.2,2.0Hz,12H),1.11(dd,J＝7.2,6.0Hz,12H)。 31 P NMR(162MHz,CDCl 3 )δ-5.92。
example 33
Characterization data for ligand 33: 1 H NMR(400MHz,CDCl 3 )δ12.25(s,1H),8.71(dd,J＝8.6,1.1Hz,1H),7.82(dd,J＝7.9,1.7Hz,1H),7.73–7.67(m,4H),7.65(dd,J＝7.7,1.7Hz,2H),7.39(ddd,J＝8.7,7.2,1.7Hz,1H),7.32–7.28(m,5H),7.27–7.14(m,11H),7.11–7.05(m,3H),7.03–6.89(m,10H),4.81(td,J＝9.5,7.8Hz,1H),4.16(t,J＝9.0Hz,1H),3.99–3.91(m,1H),3.80(d,J＝9.8Hz,1H),2.35(s,12H),2.34(s,12H)。 31 P NMR(162MHz,CDCl 3 )δ-5.96。
example 34
Characterization data for ligand 34: 1 H NMR(400MHz,CDCl 3 )δ12.34(s,1H),8.69(d,J＝8.5Hz,1H),7.80(dd,J＝7.9,1.6Hz,1H),7.77–7.69(m,2H),7.65(ddd,J＝9.5,7.6,1.7Hz,4H),7.53(dd,J＝7.0,1.8Hz,8H),7.39(td,J＝7.9,7.4,2.1Hz,8H),7.35–7.26(m,6H),7.24–7.08(m,6H),7.06–6.99(m,4H),6.93(t,J＝7.4Hz,2H),6.87(t,J＝7.2Hz,1H),4.92(td,J＝9.4,7.5Hz,1H),4.22(t,J＝9.0Hz,1H),3.99(t,J＝8.1Hz,1H),3.84(d,J＝9.6Hz,1H)。 31 P NMR(162MHz,CDCl 3 )δ-5.74。
example 35
Characterization data for ligand 35: 1 H NMR(400MHz,CDCl 3 )δ12.33(s,1H),8.78(d,J＝8.5Hz,1H),7.83(dd,J＝7.9,1.6Hz,1H),7.49–7.38(m,2H),7.33(t,J＝7.5Hz,1H),7.30–7.12(m,8H),7.11–7.01(m,4H),6.99(t,J＝7.2Hz,1H),6.49(ddd,J＝14.4,8.1,2.3Hz,4H),6.42(t,J＝2.3Hz,2H),5.13(td,J＝9.4,7.3Hz,1H),4.35(t,J＝9.1Hz,1H),4.09(dd,J＝8.7,7.3Hz,1H),3.97(d,J＝9.4Hz,1H),3.70(s,6H),3.69(s,6H)。 31 P NMR(162MHz,CDCl 3 )δ-4.70。
example 36
Characterization data for ligand 36: 1 H NMR(400MHz,CDCl 3 )δ12.25(s,1H),8.66(d,J＝8.4Hz,1H),7.79(dd,J＝8.0,1.6Hz,1H),7.38(td,J＝6.6,6.1,1.8Hz,2H),7.30(td,J＝7.6,1.3Hz,1H),7.26–7.15(m,5H),7.15–7.06(m,4H),7.06–6.92(m,6H),6.89(dd,J＝7.6,3.8Hz,4H),5.07(td,J＝9.3,7.3Hz,1H),4.31(t,J＝9.1Hz,1H),4.06(dd,J＝8.7,7.4Hz,1H),3.95(d,J＝9.2Hz,1H),2.22(s,6H),2.19(s,6H)。 31 P NMR(162MHz,CDCl 3 )δ-8.27。
example 37
Characterization data for ligand 37: 1 H NMR(400MHz,CDCl 3 )δ10.48–10.37(m,1H),8.17(dd,J＝7.8,1.9Hz,1H),7.42–7.31(m,7H),7.21(dd,J＝8.5,1.8Hz,3H),7.19–7.07(m,5H),7.04–6.93(m,2H),5.72(d,J＝7.9Hz,1H),5.47(ddd,J＝8.0,6.3,1.9Hz,1H),3.44(dd,J＝18.1,6.3Hz,1H),3.40–3.33(m,1H),1.22(s,18H),1.18(s,18H). 19 F NMR(376MHz,CDCl 3 )δ-58.91。 31 P NMR(162MHz,CDCl 3 )δ-4.92。
example 38
Characterization data for ligand 38: 1 H NMR(400MHz,CDCl 3 )δ12.68(s,1H),8.75(d,J＝8.4Hz,1H),7.84(dd,J＝7.9,1.7Hz,1H),7.70(ddd,J＝7.7,3.9,1.3Hz,1H),7.46–7.38(m,1H),7.38–7.31(m,2H),7.29–7.20(m,10H),7.14–7.00(m,4H),6.81(t,J＝8.6Hz,2H),4.41–4.35(m,1H),4.04(q,J＝7.0Hz,1H),2.93(dd,J＝13.9,7.5Hz,1H),2.75(dd,J＝13.9,6.7Hz,1H),1.29(d,J＝6.3Hz,3H)。 19 F NMR(376MHz,CDCl 3 )δ-116.29。 31 P NMR(162MHz,CDCl 3 )δ-8.30。
example 39
Characterization data for ligand 39: 1 H NMR(400MHz,CDCl 3 )δ12.69(s,1H),8.76(d,J＝8.5Hz,1H),7.85(d,J＝7.9Hz,1H),7.69(dd,J＝7.8,3.9Hz,1H),7.41(t,J＝7.9Hz,1H),7.38–7.19(m,12H),7.08(dd,J＝8.1,5.1Hz,4H),6.80(t,J＝8.5Hz,2H),4.21(q,J＝6.3Hz,1H),4.09(q,J＝6.8Hz,1H),2.91(dd,J＝13.8,7.5Hz,1H),2.74(dd,J＝13.8,6.4Hz,1H),1.67–1.49(m,2H),0.92(t,J＝7.4Hz,3H)。 19 F NMR(376MHz,CDCl 3 )δ-116.30。 31 P NMR(162MHz,CDCl 3 )δ-8.32。
example 40
Characterization data for ligand 40: 1 H NMR(400MHz,CDCl 3 )δ12.58(s,1H),8.77(d,J＝8.5Hz,1H),8.00(d,J＝7.2Hz,1H),7.85(d,J＝7.9Hz,1H),7.45–7.29(m,13H),7.07(d,J＝6.9Hz,2H),4.85(t,J＝9.4Hz,1H),4.54(dt,J＝25.6,9.1Hz,2H),1.39(s,9H)。 31 P NMR(162MHz,CDCl 3 )δ-7.94。
example 41
Characterization data for ligand 41: 1 H NMR(400MHz,CDCl 3 )δ12.67(s,1H),8.72(d,J＝8.4Hz,1H),7.82(t,J＝8.0Hz,2H),7.48–7.27(m,13H),7.06(t,J＝7.6Hz,2H),4.49(t,J＝8.8Hz,1H),4.33(dq,J＝9.4,4.6,2.8Hz,1H),3.86(t,J＝8.4Hz,1H),1.68(dd,J＝14.0,6.6Hz,1H),1.45(d,J＝6.0Hz,1H),0.84(s,9H)。 31 P NMR(162MHz,CDCl 3 )δ-8.66。
example 42
Characterization data for ligand 42: 1 H NMR(400MHz,CDCl 3 )δ12.87(s,1H),8.77(d,J＝8.5Hz,1H),7.86–7.79(m,1H),7.75(dd,J＝7.8,1.6Hz,1H),7.41(ddd,J＝8.7,7.3,1.7Hz,1H),7.36–7.28(m,11H),7.22(td,J＝7.5,1.3Hz,1H),7.15–7.08(m,5H),7.08–7.01(m,2H),4.28(d,J＝8.3Hz,1H),3.99(d,J＝8.3Hz,1H),2.89(s,2H),1.40(s,3H)。 31 P NMR(162MHz,CDCl 3 )δ-7.58。
example 43
Characterization data for ligand 43: 1 H NMR(400MHz,CDCl 3 )δ12.60(s,1H),8.77(d,J＝8.5Hz,1H),7.85(t,J＝9.2Hz,3H),7.69(dd,J＝7.8,3.9Hz,1H),7.46(t,J＝7.9Hz,1H),7.38–7.29(m,11H),7.23(d,J＝7.7Hz,3H),7.09(q,J＝5.8,3.8Hz,2H),4.66(p,J＝7.4Hz,1H),4.43(t,J＝9.0Hz,1H),4.35(dt,J＝13.8,6.3Hz,2H),4.10(t,J＝8.0Hz,1H),3.04(dd,J＝13.9,7.6Hz,1H),2.91(dd,J＝13.9,6.4Hz,1H),1.37(t,J＝7.1Hz,3H)。 31 P NMR(162MHz,CDCl 3 )δ-8.30。
example 44
Characterization data for ligand 44: 1 H NMR(400MHz,CDCl 3 )δ12.91(s,1H),8.76(dd,J＝8.5,1.1Hz,1H),7.90–7.81(m,2H),7.56(dd,J＝8.0,5.8Hz,4H),7.44(ddd,J＝8.7,7.4,1.7Hz,1H),7.38(ddd,J＝7.7,5.8,4.0Hz,5H),7.31(td,J＝7.5,1.2Hz,1H),7.24–7.14(m,5H),7.09(td,J＝7.6,1.2Hz,1H),7.00(ddd,J＝7.7,3.9,1.3Hz,1H),4.66(dt,J＝9.5,7.2Hz,1H),4.39(t,J＝8.9Hz,1H),4.12(dd,J＝8.5,7.4Hz,1H),3.08(dd,J＝13.8,6.8Hz,1H),2.83(dd,J＝13.8,7.3Hz,1H)。 19 F NMR(376MHz,CDCl 3 )δ-62.72。 31 P NMR(162MHz,CDCl 3 )δ-8.06。
example 45
Characterization data for ligand 45: 1 H NMR(400MHz,CDCl 3 )δ12.77(s,1H),8.77–8.65(m,1H),7.84(td,J＝8.9,7.9,4.0Hz,2H),7.45–7.34(m,3H),7.34–7.27(m,10H),7.12–7.02(m,2H),4.46(ddd,J＝9.4,7.8,1.5Hz,1H),4.36(qd,J＝8.7,5.5Hz,1H),3.90(td,J＝7.9,1.5Hz,1H),1.66(ddd,J＝15.2,12.6,6.7Hz,1H),1.55(ddd,J＝13.9,9.0,5.5Hz,3H),1.35(ddd,J＝13.8,8.7,5.6Hz,1H),0.85(dd,J＝10.1,6.6Hz,6H)。 31 P NMR(162MHz,CDCl 3 )δ-8.27。
example 46
Characterization data for ligand 46: 1 H NMR(400MHz,CDCl 3 )δ12.61(s,1H),8.70(d,J＝8.4Hz,1H),7.81(dd,J＝7.9,1.6Hz,1H),7.72(d,J＝1.8Hz,2H),7.67(dt,J＝7.8,2.1Hz,5H),7.55–7.44(m,8H),7.42–7.27(m,16H),7.09–7.02(m,1H),6.99(dt,J＝8.6,4.2Hz,2H),6.85–6.73(m,2H),4.48–4.33(m,1H),4.29(t,J＝8.9Hz,1H),3.98(t,J＝7.9Hz,1H),2.83(dd,J＝13.9,7.0Hz,1H),2.66(dd,J＝14.0,6.8Hz,1H)。 19 F NMR(376MHz,CDCl 3 )δ-115.40。 31 P NMR(162MHz,CDCl 3 )δ-5.35。
example 47
Characterization data for ligand 47: 1 H NMR(400MHz,CDCl 3 )δ12.65(s,1H),8.78(dd,J＝8.5,1.1Hz,1H),7.83(dd,J＝7.9,1.6Hz,1H),7.63(dd,J＝4.5,1.8Hz,1H),7.40(ddd,J＝8.7,7.3,1.7Hz,1H),7.21(dd,J＝7.8,3.2Hz,1H),7.13–7.01(m,6H),6.94(td,J＝7.3,3.0Hz,4H),6.77–6.70(m,2H),4.59(dd,J＝9.4,7.1Hz,1H),4.38(t,J＝8.9Hz,1H),4.06(t,J＝8.0Hz,1H),2.97(dd,J＝13.8,6.9Hz,1H),2.83–2.73(m,1H),2.27(s,3H),2.10(s,6H),2.07(s,6H)。 19 F NMR(376MHz,CDCl 3 )δ-116.15。 31 P NMR(162MHz,CDCl 3 )δ-23.54。
example 48
Characterization data for ligand 48: 1 H NMR(400MHz,CDCl 3 )δ12.58(s,1H),8.73(d,J＝8.5Hz,1H),7.82(dd,J＝7.9,1.6Hz,1H),7.65(dt,J＝7.8,3.4Hz,1H),7.39(ddd,J＝8.6,7.2,1.7Hz,1H),7.21(td,J＝5.4,2.3Hz,1H),7.08(ddd,J＝8.5,4.9,2.2Hz,4H),7.06–7.00(m,1H),7.00–6.89(m,5H),6.83–6.74(m,2H),4.67–4.52(m,1H),4.39(t,J＝8.9Hz,1H),4.05(t,J＝8.0Hz,1H),2.94(dd,J＝13.9,7.5Hz,1H),2.84–2.76(m,1H),2.23(s,3H),2.09(s,6H),2.07(s,6H)。 19 F NMR(376MHz,CDCl 3 )δ-116.08。 31 P NMR(162MHz,CDCl 3 )δ-22.32。
example 49
Characterization data for ligand 49: 1 H NMR(400MHz,CDCl 3 )δ12.84(s,1H),8.78(d,J＝8.4Hz,1H),8.33(d,J＝4.6Hz,1H),7.85(dd,J＝7.9,1.6Hz,1H),7.77–7.73(m,1H),7.72(d,J＝3.2Hz,1H),7.66–7.61(m,1H),7.54–7.39(m,3H),7.16–7.04(m,3H),6.97(qd,J＝5.5,2.6Hz,6H),6.58–6.48(m,2H),4.60(dd,J＝9.4,7.2Hz,1H),4.39(t,J＝8.9Hz,1H),4.11–4.03(m,1H),2.96(dd,J＝13.9,6.8Hz,1H),2.77(dd,J＝13.9,6.8Hz,1H),2.13(s,6H),2.11(s,6H)。 19 F NMR(376MHz,CDCl 3 )δ-115.88。 31 P NMR(162MHz,CDCl 3 )δ-21.97。
example 50
Characterization data for ligand 50: 1 H NMR(400MHz,CDCl 3 )δ12.17(s,1H),8.65(d,J＝8.4Hz,1H),7.81(dd,J＝8.0,1.7Hz,1H),7.47–7.35(m,2H),7.28–7.16(m,9H),7.08–6.94(m,5H),6.91–6.80(m,4H),5.21(td,J＝9.3,7.3Hz,1H),4.38(t,J＝9.1Hz,1H),4.11(dd,J＝8.8,7.3Hz,1H),4.02(d,J＝9.1Hz,1H),2.61(tt,J＝14.6,9.1Hz,12H),1.23(q,J＝7.6Hz,6H),0.84(dt,J＝14.3,7.2Hz,12H)。 31 P NMR(162MHz,CDCl 3 )δ-27.78。
example 51
Characterization data for ligand 51: 1 H NMR(400MHz,CDCl 3 )δ10.88(s,1H),8.58(dd,J＝7.2,2.4Hz,1H),7.66–7.59(m,1H),7.53–7.41(m,2H),7.38–7.26(m,12H),7.16–7.08(m,2H),7.08–7.01(m,1H),6.94(t,J＝8.6Hz,2H),4.61–4.49(m,1H),4.44(t,J＝9.0Hz,1H),4.11(t,J＝8.2Hz,1H),2.97(dd,J＝14.0,6.8Hz,1H),2.72(dd,J＝14.0,7.3Hz,1H)。 19 F NMR(376MHz,CDCl 3 )δ-59.07,-116.18。 31 P NMR(162MHz,CDCl 3 )δ-8.04。
example 52
Characterization data for ligand 52: 1 H NMR(400MHz,CDCl 3 )δ12.79(s,1H),8.80(d,J＝8.5Hz,1H),7.88(ddd,J＝7.8,4.6,1.8Hz,2H),7.46(ddd,J＝8.7,7.4,1.7Hz,1H),7.40–7.28(m,14H),7.20–7.04(m,4H),4.74–4.57(m,1H),4.39(t,J＝8.9Hz,1H),4.12(t,J＝8.0Hz,1H),3.13(dd,J＝14.0,6.2Hz,1H),2.78(dd,J＝14.0,7.7Hz,1H),1.32(s,9H)。 31 P NMR(162MHz,CDCl 3 )δ-8.12。
example 53
Characterization data for ligand 53: 1 H NMR(400MHz,CDCl 3 )δ12.36(s,1H),8.68(d,J＝9.2Hz,1H),7.67(ddd,J＝7.8,3.8,1.3Hz,1H),7.37–7.26(m,11H),7.26–7.21(m,2H),7.11–7.03(m,3H),6.99(dd,J＝9.2,3.1Hz,1H),6.84–6.76(m,2H),4.56(dq,J＝9.5,7.2Hz,1H),4.37(t,J＝8.9Hz,1H),4.04(t,J＝8.0Hz,1H),3.79(s,3H),2.93(dd,J＝14.0,7.4Hz,1H),2.79(dd,J＝14.0,6.4Hz,1H)。 19 F NMR(376MHz,CDCl 3 )δ-116.25。 31 P NMR(162MHz,CDCl 3 )δ-8.41。
example 54
Characterization data for ligand 54: 1 H NMR(400MHz,CDCl 3 )δ12.75(s,1H),8.77(d,J＝8.4Hz,1H),7.85(ddd,J＝9.6,7.8,2.7Hz,2H),7.47–7.37(m,1H),7.29(q,J＝4.5,3.8Hz,17H),7.12–6.99(m,2H),4.60–4.49(m,3H),4.42(t,J＝9.0Hz,1H),4.25(t,J＝7.9Hz,1H),3.67(dd,J＝9.5,4.5Hz,1H),3.50(dd,J＝9.5,6.4Hz,1H)。 31 P NMR(162MHz,CDCl 3 )δ-7.81。
example 55
Characterization data for ligand 55: 1 H NMR(400MHz,CDCl 3 )δ12.58(s,1H),8.76(d,J＝8.5Hz,1H),7.84(d,J＝7.9Hz,1H),7.74–7.58(m,1H),7.37(d,J＝55.8Hz,15H),7.18(t,J＝7.8Hz,2H),7.07(t,J＝7.9Hz,2H),4.74–4.52(m,1H),4.40(t,J＝9.0Hz,1H),4.08(t,J＝8.1Hz,1H),3.04(dd,J＝14.0,7.3Hz,1H),2.88(dd,J＝14.1,6.7Hz,1H)。 19 F NMR(376MHz,CDCl 3 )δ-62.56。 31 P NMR(162MHz,CDCl 3 )δ-7.98。
example 56
Characterization data for ligand 56: 1 H NMR(400MHz,CDCl 3 )δ12.55(s,1H),8.75(d,J＝8.5Hz,1H),7.84(d,J＝7.9Hz,1H),7.67(dd,J＝7.7,3.1Hz,1H),7.43(t,J＝7.9Hz,1H),7.39–7.22(m,15H),7.18(t,J＝7.5Hz,1H),7.07(d,J＝7.3Hz,2H),4.60(p,J＝7.6Hz,1H),4.41(t,J＝8.9Hz,1H),4.05(t,J＝8.0Hz,1H),3.00(dd,J＝14.0,7.9Hz,1H),2.87(dd,J＝14.0,6.0Hz,1H)。 19 F NMR(376MHz,CDCl 3 )δ-62.29。 31 P NMR(162MHz,CDCl 3 )δ-8.12。
example 57
Characterization data for ligand 57: 1 H NMR(400MHz,CDCl 3 )δ12.77(s,1H),8.78(d,J＝8.5Hz,1H),7.90–7.70(m,2H),7.30(d,J＝9.7Hz,13H),7.06(dq,J＝15.2,7.8Hz,3H),6.96(d,J＝12.5Hz,3H),4.60(t,J＝7.9Hz,1H),4.31(t,J＝9.0Hz,1H),4.06(t,J＝8.0Hz,1H),3.03(dd,J＝13.8,6.3Hz,1H),2.72(dd,J＝13.8,7.9Hz,1H),2.25(s,3H)。 31 P NMR(162MHz,CDCl 3 )δ-7.82。
example 58
Characterization data for ligand 58: 1 H NMR(400MHz,CDCl 3 )δ12.72(s,1H),8.77(dd,J＝8.5,1.1Hz,1H),7.85(dd,J＝7.9,1.7Hz,1H),7.74(ddd,J＝6.8,3.8,1.9Hz,1H),7.46–7.41(m,1H),7.38(ddd,J＝6.2,5.3,3.2Hz,4H),7.29(dd,J＝5.7,2.5Hz,10H),7.23–7.12(m,6H),7.07(td,J＝7.6,1.2Hz,1H),7.02(ddd,J＝7.5,3.8,1.8Hz,1H),4.71–4.58(m,1H),4.41(dd,J＝9.4,8.5Hz,1H),4.12(dt,J＝8.5,6.3Hz,2H),3.05(dd,J＝13.9,7.2Hz,1H),2.84(dd,J＝13.8,6.8Hz,1H)。 19 F NMR(376MHz,CDCl 3 )δ-62.36. 31 P NMR(162MHz,CDCl 3 )δ-8.22。
example 59
Characterization data for ligand 59: 1 H NMR(400MHz,CDCl 3 )δ12.81(s,1H),8.74(d,J＝8.4Hz,1H),7.90(dd,J＝7.7,3.8Hz,1H),7.84(d,J＝7.9Hz,1H),7.47–7.25(m,13H),7.20(dd,J＝13.9,7.0Hz,3H),7.12–7.03(m,2H),6.99(d,J＝7.2Hz,2H),4.41(t,J＝8.8Hz,1H),4.27(p,J＝7.6Hz,1H),3.91(t,J＝8.1Hz,1H),2.70(dt,J＝14.4,7.3Hz,1H),2.59(dt,J＝13.8,8.1Hz,1H),1.88(q,J＝7.5Hz,2H)。 31 P NMR(162MHz,CDCl 3 )δ-8.44。
example 60
The ligand of the invention is applied to the reaction of synthesizing alkyne by free radical asymmetric oxidation Sonogashira cross coupling.
To a Schlenk tube equipped with a magnetic stir bar, oven dried, cuTc (cuprous thiophene-2-carboxylate, 10mol% equivalent), ligand L5 (15 mol%), 4-cyanophenylacetylene (1.0 equivalent), oxidant (3.0 equivalent), cesium carbonate (4.0 equivalent) were added, argon was replaced three times, followed by chlorobenzene (1.0 mL) and tetrahydronaphthalene (0.13ml, 10.0 equivalent). Then reacted at 0 ℃ for 120h. After completion of the reaction (monitored by TLC), the precipitate was filtered off and washed with solvent, then the solution was evaporated and purified by silica gel column chromatography (petroleum ether = 100) to give the product in 60% yield, 82% ee.
Characterization data of the product: HPLC conditions were Chiralcel OJ-H (n-hexane/isopropanol =98/2, flow rate 1.0mL/min, lambda =254 nm), t was a colorless oil R (minor)＝19.0min,t R (major)＝24.4min。 1 H NMR(400MHz,CDCl 3 )δ7.58-7.54(m,2H),7.50-7.45(m,3H),7.21-7.15(m,2H),7.14-7.08(m,1H),4.04(t,J＝6.4Hz,1H),2.87-2.78(m,2H),2.26-2.13(m,1H),2.13-1.94(m,2H),1.87-1.78(m,1H)。 13 C NMR(101MHz,CDCl 3 ) Delta 136.3,135.5,132.2,131.9,129.4,129.0,128.9,126.8,126.1,118.6,111.0,98.1,80.2,32.1,30.0,29.1,21.2.HRMS (ESI) m/z accurate mass calculation C 19 H 16 N[M+H] + 258.1277, found 258.1275.
The results of the ligands of the invention used in the above reactions are shown in the following table (L1 represents the ligand of example 1 and so on):
| ligands | Yield (%) | ee(％) | Ligands | Yield (%) | ee(％) |
| L1 | 47 | 49 | L12 | 49 | 54 |
| L2 | 51 | 66 | L13 | 53 | 51 |
| L3 | 62 | 48 | L14 | 52 | 61 |
| L4 | 41 | 38 | L15 | 61 | 87 |
| L5 | 60 | 82 | L16 | 65 | 92 |
| L6 | 47 | 32 | L17 | 60 | 92 |
| L7 | 46 | 58 | L18 | 45 | 43 |
| L8 | 22 | 15 | L19 | 44 | 40 |
| L9 | 33 | 52 | L20 | 52 | 91 |
| L10 | 50 | 72 | L21 | 55 | 90 |
| L11 | 57 | 52 |
Therefore, the ligand of the invention can be used as a catalyst together with copper salt for oxidizing Sonogashira C (sp) substrates of terminal alkyne and benzylic/allylic carbon-hydrogen bond substrates 3 ) Asymmetric cross coupling reaction, chiral carbon-carbon triple bond construction, good yield and excellent enantioselectivity.
The above description is only an embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (3)
1. A nitrogen phosphorus ligand having the structure of formula i or a tautomer, enantiomer, or diastereomer thereof:
R 1 selected from hydrogen, halogen, trifluoromethylThe base group is a group of a compound,
R 2 and R 4 Are linked to form a five-membered ring and an acene ring, i.e. form
In the structure of the utility model, the utility model has the advantages of simple structure,
R 3 is a hydrogen atom, and is,
R 5 is a hydrogen atom, and is,
w is PR 2 Or P (O) R 2 ，
R is selected from phenyl, naphthyl,
Wherein R is 6 Selected from methyl, propyl, butyl, methoxy and phenyl, m represents an integer of 1 to 5, when m is more than or equal to 2, more than 2R exist 6 The same or different.
2. The nitrogen phosphorus ligand of claim 1, selected from one of the following structures:
3. a method of preparing the nitrogen phosphorus ligand of claim 1 or 2, comprising the steps of:
reacting the compound S1 with the compound S2 to obtain an intermediate S3;
reacting the intermediate S3 with the compound S4 to obtain a product;
R 1 、R 2 、R 3 、R 4 、R 5 w is as defined in claim 1 or 2.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110944796.6A CN113666962B (en) | 2021-08-17 | 2021-08-17 | Nitrogen-phosphorus ligand and preparation method and application thereof |
| CN202211584497.7A CN116178431A (en) | 2021-08-17 | 2021-08-17 | Oxazoline phosphine ligand and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110944796.6A CN113666962B (en) | 2021-08-17 | 2021-08-17 | Nitrogen-phosphorus ligand and preparation method and application thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211584497.7A Division CN116178431A (en) | 2021-08-17 | 2021-08-17 | Oxazoline phosphine ligand and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113666962A CN113666962A (en) | 2021-11-19 |
| CN113666962B true CN113666962B (en) | 2023-03-31 |
Family
ID=78543358
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211584497.7A Pending CN116178431A (en) | 2021-08-17 | 2021-08-17 | Oxazoline phosphine ligand and preparation method thereof |
| CN202110944796.6A Active CN113666962B (en) | 2021-08-17 | 2021-08-17 | Nitrogen-phosphorus ligand and preparation method and application thereof |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211584497.7A Pending CN116178431A (en) | 2021-08-17 | 2021-08-17 | Oxazoline phosphine ligand and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN116178431A (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110590841B (en) * | 2019-08-29 | 2022-05-17 | 南方科技大学 | Nitrogen-phosphorus ligand and preparation method and application thereof |
-
2021
- 2021-08-17 CN CN202211584497.7A patent/CN116178431A/en active Pending
- 2021-08-17 CN CN202110944796.6A patent/CN113666962B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN116178431A (en) | 2023-05-30 |
| CN113666962A (en) | 2021-11-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5244149B2 (en) | Optically active quaternary ammonium salt having axial asymmetry and method for producing α-amino acid and derivatives thereof using the same | |
| CN110590841B (en) | Nitrogen-phosphorus ligand and preparation method and application thereof | |
| JP4556869B2 (en) | Asymmetric synthesis using chiral Bronsted acid as catalyst | |
| CN103936537B (en) | A kind of phenol of golden catalysis and the selectivity c h bond functionalization method of aniline | |
| JP2003507443A (en) | Chiral ligands, their transition metal complexes and their use in asymmetric reactions | |
| CN111606849B (en) | Synthetic method of 2- (2-aminophenyl) quinoline compound | |
| CN110256493B (en) | C2-phosphonoindole compound and preparation method thereof | |
| US6380392B1 (en) | Ligands based on chiral 2-amino-2′-hydroxy-1,1′-binaphthyl and related frameworks for asymmetric catalysis | |
| EP2045014B1 (en) | Polymer-supported metal complex catalyst | |
| JP4528123B2 (en) | Process for the production of nitrooxy derivatives of naproxen | |
| CN113666962B (en) | Nitrogen-phosphorus ligand and preparation method and application thereof | |
| Siva et al. | Syntheses of new dimeric-Cinchona alkaloid as a chiral phase transfer catalysts for the alkylation of Schiff base | |
| CN109836457B (en) | High-steric-hindrance chiral P, N, N ligand and preparation method and application thereof | |
| CN111187298B (en) | C2-phosphono methylene indole compound and preparation method and application thereof | |
| JPWO2008140074A1 (en) | Method for producing optically active carboxylic acid ester | |
| JP3789508B2 (en) | Optically active asymmetric diphosphine and method for obtaining optically active substance in the presence of the compound | |
| Liang et al. | Syntheses and resolutions of new chiral biphenyl backbones: 2-amino-2′-hydroxy-6, 6′-dimethyl-1, 1′-biphenyl and 2-amino-2′-hydroxy-4, 4′, 6, 6′-tetramethyl-1, 1′-biphenyl | |
| JP4779109B2 (en) | Optically active amino acid derivative having axial asymmetry and method for producing optically active compound using the amino acid derivative as an asymmetric catalyst | |
| Ferrand et al. | Hydrophilic diamine ligands for catalytic asymmetric hydrogenation of C O bonds | |
| JP2012082155A (en) | Triazolium salt and method for producing the same, and method for producing alkylated oxindol using azide alcohol and asymmetric reaction | |
| CN113149835B (en) | Preparation method for rapidly generating alpha-ketoester by iodine-mediated oxidation of alpha-diazo ester | |
| JPH029598B2 (en) | ||
| JP5546781B2 (en) | 2,2'-bis (dialkylphosphino) biphenyl compound, method for producing the same, and metal complex having the compound as a ligand | |
| Wei et al. | Novel atropisomeric bisphosphine ligands with a bridge across the 5, 5′-position of the biphenyl for asymmetric catalysis | |
| CN114957103B (en) | Axial chiral halogenated biaryl compound and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |