CN111440205B - 一种联硼酸二醇酯、其制备方法、其中间体及其应用 - Google Patents
一种联硼酸二醇酯、其制备方法、其中间体及其应用 Download PDFInfo
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- CN111440205B CN111440205B CN201910041561.9A CN201910041561A CN111440205B CN 111440205 B CN111440205 B CN 111440205B CN 201910041561 A CN201910041561 A CN 201910041561A CN 111440205 B CN111440205 B CN 111440205B
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- Prior art keywords
- alkyl
- halogen
- compound
- substituted
- diol
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- -1 diol ester Chemical class 0.000 title claims abstract description 57
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- 239000002253 acid Substances 0.000 title claims abstract description 13
- 150000002009 diols Chemical class 0.000 claims abstract description 63
- 238000005859 coupling reaction Methods 0.000 claims abstract description 29
- 150000004985 diamines Chemical class 0.000 claims abstract description 22
- 229910052717 sulfur Inorganic materials 0.000 claims description 70
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 52
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 48
- 229910052736 halogen Chemical group 0.000 claims description 47
- 150000002367 halogens Chemical group 0.000 claims description 47
- 239000002904 solvent Substances 0.000 claims description 44
- 150000001875 compounds Chemical class 0.000 claims description 41
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 23
- 238000005886 esterification reaction Methods 0.000 claims description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 239000003153 chemical reaction reagent Substances 0.000 claims description 14
- 239000000460 chlorine Substances 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 239000011737 fluorine Substances 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 239000002808 molecular sieve Substances 0.000 claims description 9
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 9
- 229940125782 compound 2 Drugs 0.000 claims description 8
- 229940126214 compound 3 Drugs 0.000 claims description 8
- 230000008878 coupling Effects 0.000 claims description 8
- 238000010168 coupling process Methods 0.000 claims description 8
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 6
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 239000011630 iodine Substances 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 229940125904 compound 1 Drugs 0.000 claims description 5
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 24
- 125000001033 ether group Chemical group 0.000 claims 5
- 125000003118 aryl group Chemical group 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 3
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000001072 heteroaryl group Chemical group 0.000 claims 1
- 125000002346 iodo group Chemical group I* 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 35
- 239000000758 substrate Substances 0.000 abstract description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 abstract description 9
- 238000006578 reductive coupling reaction Methods 0.000 abstract description 7
- 238000004440 column chromatography Methods 0.000 abstract description 5
- 238000011084 recovery Methods 0.000 abstract description 5
- 229910021529 ammonia Inorganic materials 0.000 abstract description 4
- 150000002466 imines Chemical class 0.000 abstract description 4
- 230000001939 inductive effect Effects 0.000 abstract description 4
- 238000001953 recrystallisation Methods 0.000 abstract description 4
- 239000012295 chemical reaction liquid Substances 0.000 abstract description 3
- 125000006239 protecting group Chemical group 0.000 abstract description 3
- 238000000746 purification Methods 0.000 abstract description 3
- 230000009467 reduction Effects 0.000 abstract description 3
- 238000006722 reduction reaction Methods 0.000 abstract description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract 1
- 239000007791 liquid phase Substances 0.000 description 76
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 70
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 64
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- 239000007787 solid Substances 0.000 description 43
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 31
- 239000000047 product Substances 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 12
- 238000001035 drying Methods 0.000 description 11
- 239000007788 liquid Substances 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 238000005406 washing Methods 0.000 description 9
- 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 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 5
- SKOWZLGOFVSKLB-UHFFFAOYSA-N hypodiboric acid Chemical compound OB(O)B(O)O SKOWZLGOFVSKLB-UHFFFAOYSA-N 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000000375 direct analysis in real time Methods 0.000 description 4
- 238000012063 dual-affinity re-targeting Methods 0.000 description 4
- 239000012065 filter cake Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000001476 alcoholic effect Effects 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- PONXTPCRRASWKW-ZIAGYGMSSA-N (1r,2r)-1,2-diphenylethane-1,2-diamine Chemical compound C1([C@@H](N)[C@H](N)C=2C=CC=CC=2)=CC=CC=C1 PONXTPCRRASWKW-ZIAGYGMSSA-N 0.000 description 2
- AMKCOERXORDHFY-HZPDHXFCSA-N (4R,5R)-4,5-bis(4-methoxyphenyl)imidazolidin-2-one Chemical compound COC1=CC=C(C=C1)[C@@H]2[C@H](NC(=O)N2)C3=CC=C(C=C3)OC AMKCOERXORDHFY-HZPDHXFCSA-N 0.000 description 2
- IOEPOEDBBPRAEI-UHFFFAOYSA-N 1,2-dihydroisoquinoline Chemical compound C1=CC=C2CNC=CC2=C1 IOEPOEDBBPRAEI-UHFFFAOYSA-N 0.000 description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 2
- 229960001756 oxaliplatin Drugs 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000004537 pulping Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
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- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 1
- LSFATDHBTHDVOG-ZIAGYGMSSA-N (1R,2R)-1,2-bis(2-bromophenyl)ethane-1,2-diamine Chemical compound N[C@@H]([C@H](N)c1ccccc1Br)c1ccccc1Br LSFATDHBTHDVOG-ZIAGYGMSSA-N 0.000 description 1
- BMALUZKOHRPBTN-ZIAGYGMSSA-N (1R,2R)-1,2-bis(2-chlorophenyl)ethane-1,2-diamine Chemical compound C1([C@@H](N)[C@H](N)C=2C(=CC=CC=2)Cl)=CC=CC=C1Cl BMALUZKOHRPBTN-ZIAGYGMSSA-N 0.000 description 1
- JASPNOWTBVYYLF-ZIAGYGMSSA-N (1R,2R)-1,2-bis(3-chlorophenyl)ethane-1,2-diamine Chemical compound N[C@@H]([C@H](N)c1cccc(Cl)c1)c1cccc(Cl)c1 JASPNOWTBVYYLF-ZIAGYGMSSA-N 0.000 description 1
- XURRKKYAGFWNPT-ZIAGYGMSSA-N (1R,2R)-1,2-bis(4-bromophenyl)ethane-1,2-diamine Chemical compound N[C@@H]([C@H](N)c1ccc(Br)cc1)c1ccc(Br)cc1 XURRKKYAGFWNPT-ZIAGYGMSSA-N 0.000 description 1
- UQUZLWQGLCLOBD-HZPDHXFCSA-N (1R,2R)-1,2-bis(4-methylphenyl)ethane-1,2-diamine Chemical compound C1=CC(C)=CC=C1[C@@H](N)[C@H](N)C1=CC=C(C)C=C1 UQUZLWQGLCLOBD-HZPDHXFCSA-N 0.000 description 1
- CTMKVJFFLNHDQE-HZPDHXFCSA-N (1r,2r)-1,2-bis(2-methoxyphenyl)ethane-1,2-diamine Chemical compound COC1=CC=CC=C1[C@@H](N)[C@H](N)C1=CC=CC=C1OC CTMKVJFFLNHDQE-HZPDHXFCSA-N 0.000 description 1
- HHPPUZSHKRJDIW-ZIAGYGMSSA-N (1r,2r)-1,2-bis(4-chlorophenyl)ethane-1,2-diamine Chemical compound C1([C@@H](N)[C@H](N)C=2C=CC(Cl)=CC=2)=CC=C(Cl)C=C1 HHPPUZSHKRJDIW-ZIAGYGMSSA-N 0.000 description 1
- DWKHQEHNAPMAGG-ZIAGYGMSSA-N (1r,2r)-1,2-bis(4-fluorophenyl)ethane-1,2-diamine Chemical compound C1([C@@H](N)[C@H](N)C=2C=CC(F)=CC=2)=CC=C(F)C=C1 DWKHQEHNAPMAGG-ZIAGYGMSSA-N 0.000 description 1
- ZWMPRHYHRAUVGY-HZPDHXFCSA-N (1r,2r)-1,2-bis(4-methoxyphenyl)ethane-1,2-diamine Chemical compound C1=CC(OC)=CC=C1[C@@H](N)[C@H](N)C1=CC=C(OC)C=C1 ZWMPRHYHRAUVGY-HZPDHXFCSA-N 0.000 description 1
- PTSMQSGOXVGOTJ-OAQYLSRUSA-N (2R)-2-(2-chlorophenyl)-1,1-bis(4-methoxyphenyl)ethane-1,2-diol Chemical compound COC1=CC=C(C=C1)C(C2=CC=C(C=C2)OC)([C@@H](C3=CC=CC=C3Cl)O)O PTSMQSGOXVGOTJ-OAQYLSRUSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HBAJNQDYMXPGGO-UHFFFAOYSA-N 1-(2-methylphenyl)ethane-1,2-diamine Chemical compound CC1=CC=CC=C1C(N)CN HBAJNQDYMXPGGO-UHFFFAOYSA-N 0.000 description 1
- YALQMYSEXQRFQU-UHFFFAOYSA-N 1-(4-methoxyphenyl)-2-phenylethane-1,1-diol Chemical compound C1=CC(OC)=CC=C1C(O)(O)CC1=CC=CC=C1 YALQMYSEXQRFQU-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- POCXSZQENPZZJP-ZIAGYGMSSA-N C1=CC(=CC(=C1)C(F)(F)F)[C@H]([C@@H](C2=CC(=CC=C2)C(F)(F)F)N)N Chemical compound C1=CC(=CC(=C1)C(F)(F)F)[C@H]([C@@H](C2=CC(=CC=C2)C(F)(F)F)N)N POCXSZQENPZZJP-ZIAGYGMSSA-N 0.000 description 1
- AZVDCJGWJYFYLH-UHFFFAOYSA-N CC1=CC(C(CC2=CC=CC=C2)(O)O)=C(C)C=C1 Chemical compound CC1=CC(C(CC2=CC=CC=C2)(O)O)=C(C)C=C1 AZVDCJGWJYFYLH-UHFFFAOYSA-N 0.000 description 1
- BINWNCAJJXIWIE-UHFFFAOYSA-N CC1=CC(C)=C(C(CC2=CC=CC=C2)(O)O)C=C1 Chemical compound CC1=CC(C)=C(C(CC2=CC=CC=C2)(O)O)C=C1 BINWNCAJJXIWIE-UHFFFAOYSA-N 0.000 description 1
- ZSCDLIHCSZAKPZ-UHFFFAOYSA-N CC1=CC(C)=CC(C(CC2=CC=CC=C2)(O)O)=C1 Chemical compound CC1=CC(C)=CC(C(CC2=CC=CC=C2)(O)O)=C1 ZSCDLIHCSZAKPZ-UHFFFAOYSA-N 0.000 description 1
- 101100391174 Dictyostelium discoideum forC gene Proteins 0.000 description 1
- 238000003747 Grignard reaction Methods 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
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- GEKCWQCHNDIFMO-UHFFFAOYSA-N N'-[4-(trifluoromethoxy)phenyl]ethane-1,2-diamine Chemical compound NCCNC1=CC=C(OC(F)(F)F)C=C1 GEKCWQCHNDIFMO-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229930003756 Vitamin B7 Natural products 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
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Abstract
本发明公开了一种联硼酸二醇酯、其制备方法、其中间体及其应用。该联硼酸二醇酯可用于诱导底物为亚胺的还原偶联反应，底物可由醛及氨反应得到，非常易得且成本相当低廉；产物仅需酸碱操作，即可从反应体系中分离而来，无需柱色谱纯化，后处理方式便捷，易于操作；所得产物产率较高且无需保护基操作。该联硼酸二醇酯具备手性，所述还原偶联反应的立体选择性普遍优秀，仅需简单重结晶既可以得到99％ee的手性二胺。该联硼酸二醇酯可使用二醇可与联硼酸二醇酯反应获得，该二醇制备方便，易于放大，且其经过简单的酸碱操作，可以从反应液中回收重复利用，回收率达95％，进一步节约了制备成本。
Description
技术领域
本发明涉及一种联硼酸二醇酯、其制备方法、其中间体及其应用。
背景技术
联硼酸二醇酯具有无毒、稳定、易于操作等优点，在有机合成中具有广泛的用途。其按照二醇的来源不同，可分为非手性联硼酸二醇酯和手性联硼酸二醇酯。其中非手性联硼酸二醇酯，最早被广泛应用于Miyaura偶联反应制备有机硼酸酯化合物(Org.Synth.2000,77,176-185)。随着近几年有机化学的发展，其还被逐渐应用于对烯烃、炔烃、醛(酮)、亚胺等化合物的加成以及芳香化合物的C-H硼取代反应中(Chem.Rev.2016,116,9091)。相较于非手性联硼酸二醇酯，由于手性二醇的来源有限，且价格普遍昂贵，这导致手性联硼酸二醇酯的研究相对较少，仅有为数不多的报道其应用于共轭二烯的双硼化反应(J.Chem.Soc.,Dalton Trans.,1998,1431)以及烯烃的双硼化反应(J.Am.Chem.Soc.2016,138,2508)。前不久，汤文军教授小组报道了首例采用联硼酸二醇酯诱导的异喹啉类化合物的还原偶联反应(J.Am.Chem.Soc.2017,139,9767)。他们经过研究发现当采用已知的手性联硼酸(二氢化苯偶姻)酯为手性诱导试剂时，能够制备一系列手性联二氢异喹啉骨架衍生物，其产率中等到优秀，且对映选择性最高达99％。
然而，该反应只适用于异喹啉类化合物的还原偶联，仅适用于制备手性联二氢异喹啉类产物，即其原料及产物都限制于特定的环状结构。相较于上述特定的手性联二氢异喹啉骨架产物，手性1,2-二胺结构更多的广泛存在于具有生物活性的天然产物及药物分子中，如：维生素H，对人体脂肪和蛋白质代谢有着不可或缺的作用。奥沙利铂(Oxaliplatin)作为一种新型的抗肿瘤药物，对多种癌种有效，其分子中也具有1,2-二胺结构。除此之外，手性1,2-二胺还被广泛的应用于制备有机化学的手性催化剂中，如手性1,2-二胺与金属络合生成具有高反应活性和选择性的催化剂，应用于各种各样的类型的反应当中。手性的1,2-二胺结构也可以作为手性拆分试剂对醛的对映体进行拆分。因此，1,2-二胺的合成一直是化学家们研究的热点。
传统的合成手性1,2-二胺的方法可以归纳为如下几种方式：1)通过消旋体拆分；2)手性辅助基团诱导的不对称合成；3)手性二醇底物亲核取代反应；4)不同类型的手性有机小分子催化反应。
通过上述已知报道的方法，人们制备出了一系列手性的1,2-二胺产物，并应用于一系列手性催化剂及手性试剂的开发中去。然而，上述方法都有其一定的缺陷，如1)通过消旋体拆分方式需要繁琐的拆分试剂筛选及结晶条件考察，通常不同的产物往往需要不同类型的手性拆分试剂，而且拆分势必造成其理论收率最高仅为50％，目前已报道方法，其产率普遍不理想(J.Org.Chem.2008,73,133；Org.Lett.2003,5,595)。2)手性辅助基团诱导的还原偶联的最大缺陷是用到当量昂贵的手性辅助试剂，手性辅剂在反应中完全消耗，这导致该方式成本较高(Org.Lett.2004,6,4747；J.Am.Chem.Soc.2008，130，12185)。3)采用手性二醇为底物进行亲核取代反应制备手性的1,2-二胺，不仅手性二醇的制备方法有限，而且亲核试剂用到剧毒且易爆炸的NaN3，通常从非手性的底物出发到最终的手性1,2-二胺要经过3-5步反应，性价比较低(Chem.Rev.1994,94,2483.)。4)通过有机手性小分子催化制备的方法，其优点是底物种类多样，并且可以制备不对称的手性1,2-二胺，但不同的方法通常对映选择性波动较大，普遍用到较为昂贵的手性催化剂，且底物通常需要预先修饰才能得到较高的立体选择性，这就需要产物后续的脱保护基等附加步骤，反应不易放大，适用于实验室内克级规模以下制备。
因此，本领域亟需一种高效制备1,2-二胺化合物的方法。
发明内容
本发明所要解决的技术问题是现有的联硼酸二醇酯的结构单一，故而，本发明提供了一种联硼酸二醇酯、其制备方法、其中间体及其应用。该联硼酸二醇酯可用于诱导底物为亚胺的还原偶联反应，底物可由醛及氨反应得到，非常易得且成本相当低廉；产物仅需酸碱操作，即可从反应体系中分离而来，无需柱色谱纯化，后处理方式便捷，易于操作；所得产物产率较高且无需保护基操作。该联硼酸二醇酯具备手性，所述还原偶联反应的立体选择性普遍优秀，仅需简单重结晶既可以得到99％ee的手性二胺。该联硼酸二醇酯可使用二醇可与联硼酸二醇酯反应获得，该二醇制备方便，易于放大，且其经过简单的酸碱操作，可以从反应液中回收重复利用，回收率达95％，进一步节约了制备成本。
本发明提供了一种如式1所示的联硼酸二醇酯；
其中，C1和C2同时为R构型碳原子或S构型碳原子；
R1为苯基、或、卤素取代的苯基{所述的卤素的个数可为1个、2个、3个、4个或5个，当存在2个以上的卤素时，所述的卤素相同或不同；所述的卤素可独立地为氟、氯、溴或碘，又可为氯；所述的卤素可独立地与所述的C1互为邻位、间位或对位，又可与所述的C1互为邻位；所述的“卤素取代的苯基”例如2-氯苯基}；
R2与R1相同；
C3为非手性碳原子；
R3-1为R3-1-1取代的苯基{所述的R3-1-1的个数可为1个、2个、3个、4个或5个，当存在2个以上的R3-1-1时，所述的R3-1-1相同或不同；所述的R3-1-1可独立地与所述的C3互为邻位、间位或对位，又可与所述的C3互为邻位或间位；所述的“R3-1-1取代的苯基”例如2-甲基苯基、4-甲氧基苯基、2,4-二甲基苯基、2,5-二甲基苯基或3,5-二甲基苯基，又例如2,5-二甲基苯基}；所述的R3-1-1独立地为C1～C3的烷基{例如甲基、乙基、正丙基或异丙基，又例如甲基}或C1～C3的烷氧基{例如甲氧基、乙氧基、正丙氧基或异丙氧基，又例如甲氧基}；
R3-2与R3-1相同；
C4为非手性碳原子；
R4-1为R4-1-1取代的苯基{所述的R4-1-1的个数可为1个、2个、3个、4个或5个，当存在2个以上的R4-1-1时，所述的R4-1-1相同或不同；所述的R4-1-1可独立地与所述的C4互为邻位、间位或对位，又可与所述的C4互为邻位或间位；所述的“R4-1-1取代的苯基”例如2-甲基苯基、4-甲氧基苯基、2,4-二甲基苯基、2,5-二甲基苯基或3,5-二甲基苯基，又例如2,5-二甲基苯基}；所述的R4-1-1独立地为C1～C3的烷基{例如甲基、乙基、正丙基或异丙基，又例如甲基}或C1～C3的烷氧基{例如甲氧基、乙氧基、正丙氧基或异丙氧基，又例如甲氧基}；
R4-2与R4-1相同。
在某一方案中，所述的联硼酸二醇酯1的某些基团的定义可如下所述，未涉及的基团的定义如上任一方案所述：
R1与R2均为苯基。
在某一方案中，所述的联硼酸二醇酯1的某些基团的定义可如下所述，未涉及的基团的定义如上任一方案所述：
所述的R3-1-1的个数为1个或2个，所述的R4-1-1的个数为1个或2个。
在某一方案中，所述的联硼酸二醇酯1的某些基团的定义可如下所述，未涉及的基团的定义如上任一方案所述：
所述的R3-1-1独立地为C1～C3的烷基；所述的R4-1-1独立地为C1～C3的烷基。
在某一方案中，所述的联硼酸二醇酯1的某些基团的定义可如下所述，未涉及的基团的定义如上任一方案所述：
R3-1和R4-1相同。
在某一方案中，所述的联硼酸二醇酯1的某些基团的定义可如下所述，未涉及的基团的定义如上任一方案所述：
R1与R2均为苯基；
所述的R3-1-1的个数为1个或2个，所述的R4-1-1的个数为1个或2个；
所述的R3-1-1独立地为C1～C3的烷基；所述的R4-1-1独立地为C1～C3的烷基；
R3-1和R4-1相同。
在某一方案中，所述的联硼酸二醇酯1可为以下任一化合物：
本发明还提供了一种如式2所示的二醇；
其中，C2、R2、C4、R4-1和R4-2的定义如上所述。
在某一方案中，所述的二醇2可为以下任一化合物：
本发明还提供了一种上述的联硼酸二醇酯1的制备方法，其包括下述步骤：在溶剂中，将化合物2、化合物3与化合物4进行酯化反应，得到所述的联硼酸二醇酯1即可；
其中，C1、R1、C2、R2、C3、R3-1、R3-2、C4、R4-1和R4-2的定义如上所述；
R5-1和R5-2独立地为氢或C1～C3的烷基{例如甲基、乙基、正丙基或异丙基}，或者，R5-1和R5-2连接形成-(CR5-1-1R5-1-2)n-{例如-CH2C(CH3)2CH2-}；n为1、2或3，所述的R5-1-1和R5 -1-2独立地为氢或C1～C3的烷基{例如甲基、乙基、正丙基或异丙基，又例如甲基}；
R5-3和R5-4独立地为氢或C1～C3的烷基{例如甲基、乙基、正丙基或异丙基}，或者，R5-3和R5-4连接形成-(CR5-3-1R5-3-2)m-{例如-CH2C(CH3)2CH2-}；m为1、2或3，所述的R5-3-1和R5 -3-2独立地为氢或C1～C3的烷基{例如甲基、乙基、正丙基或异丙基，又例如甲基}。
所述的酯化反应可在氮气或惰性气体的存在下进行。
所述的酯化反应可在分子筛的存在下进行。所述的分子筛可为4A分子筛。
所述的溶剂可为本领域该类酯化反应常规的溶剂，例如醚类溶剂。所述的醚类溶剂可为本领域该类酯化反应常规的醚类溶剂，例如四氢呋喃。
所述的溶剂与所述的化合物4的体积摩尔比可为该类酯化反应常规的体积摩尔比，例如3.0～3.5L/mol。
所述的化合物2与所述的化合物4的摩尔比可为该类酯化反应常规的摩尔比，例如(1～1.2)：1。
所述的化合物3与所述的化合物4的摩尔比可为该类酯化反应常规的摩尔比，例如(1～1.2)：1。
所述的酯化反应的温度可为本领域该类酯化反应常规的温度，例如60～70℃，又例如66℃。
所述的酯化反应的进程可以采用本领域中常规监测方法(例如TLC、HPLC、NMR或GC)进行监测，一般以化合物4不再反应时为反应终点，反应时间可为4小时～8小时。
在某一方案中，所述的联硼酸二醇酯1的制备方法的某些参数可如下所述，未涉及的参数如上任一方案所述：
R5-1、R5-2、R5-3和R5-4独立地为C1～C3的烷基。
在某一方案中，所述的联硼酸二醇酯1的制备方法的某些参数可如下所述，未涉及的参数如上任一方案所述：
R5-1和R5-2连接形成-(CR5-1-1R5-1-2)n-，且R5-3和R5-4连接形成-(CR5-3-1R5-3-2)m-。
在某一方案中，所述的联硼酸二醇酯1的制备方法的某些参数可如下所述，未涉及的参数如上任一方案所述：
化合物4为四羟基二硼或
本发明还提供了一种如式A所示的二胺的制备方法，其包括下述步骤：在溶剂中，将化合物B与偶联试剂进行偶联反应，得到所述的二胺A即可；
所述的偶联试剂为上述的化合物1或偶联试剂组合物，所述的偶联试剂组合物为化合物2、化合物3和化合物4；
其中，C1、R1、C2、R2、C3、R3-1、R3-2、C4、R4-1、R4-2、R5-1、R5-2、R5-3和R5-4的定义如上所述；
C5为手性碳原子，其构型与C1相同；C6为手性碳原子，其构型与C2相同；
R6-1为氢或C1～C3的烷基{例如甲基、乙基、正丙基或异丙基，又例如甲基}；
R6-2为苯基、萘基{例如1-萘基或2-萘基}、“杂原子数为1～2个，杂原子选自N、O和S中的一种或多种的5～6元杂芳基”{例如呋喃基或噻吩基；所述的呋喃基又例如呋喃-2-基；所述的噻吩基又例如噻吩-2-基或噻吩-3-基}、或、R6-2-1取代的苯基{所述的R6-2-1的个数可为1个、2个、3个、4个或5个，当存在2个以上的R6-2-1时，所述的R6-2-1相同或不同；所述的R6-2-1可独立地与所述的亚胺双键互为邻位、间位或对位；所述的“R6-2-1取代的苯基”例如4-甲基苯基、4-甲氧基苯基、4-三氟甲氧基苯基、4-甲氧酰基苯基、4-氟苯基、2,4,6-三氟苯基、4-氯苯基、4-溴苯基、2-甲氧基苯基、2-甲基苯基、2-氯苯基、2-溴苯基、3-三氟甲基苯基、2-苯基-苯基、3-氯苯基或3-氯苯基}；
所述的R6-2-1独立地为-C(＝O)-O-C1～C3的烷基{其中，所述的“C1～C3的烷基”例如甲基、乙基、正丙基或异丙基}、卤素{例如氟、氯、溴或碘}、C1～C3的烷基{例如甲基、乙基、正丙基或异丙基}、卤素取代的C1～C3的烷基{所述的卤素的个数可为1个、2个、3个、4个或5个，当存在2个以上的卤素时，所述的卤素相同或不同；所述的卤素可独立地为氟、氯、溴或碘，又可为氟；所述的C1～C3的烷基例如甲基、乙基、正丙基或异丙基；所述的“卤素取代的C1～C3的烷基”例如三氟甲基}、C1～C3的烷氧基{例如甲氧基、乙氧基、正丙氧基或异丙氧基}、或、卤素取代的C1～C3的烷氧基{所述的卤素的个数可为1个、2个、3个、4个或5个，当存在2个以上的卤素时，所述的卤素相同或不同；所述的卤素可独立地为氟、氯、溴或碘，又可为氟；所述的C1～C3的烷氧基例如甲氧基、乙氧基、正丙氧基或异丙氧基；所述的“卤素取代的C1～C3的烷氧基”例如三氟甲氧基}。
所述的偶联反应可在氮气或惰性气体的存在下进行。
所述的溶剂可为本领域该类偶联反应常规的溶剂，例如醚类溶剂和/或醇类溶剂。所述的醚类溶剂可为本领域该类偶联反应常规的醚类溶剂，例如四氢呋喃。所述的醇类溶剂可为本领域该类偶联反应常规的醇类溶剂，例如甲醇。所述的醚类溶剂和所述的醇类溶剂的体积比可为5：1。
所述的溶剂与所述的化合物B的体积摩尔比可为该类偶联反应常规的体积摩尔比，例如15～25L/mol，又例如18～22L/mol。
所述的化合物1与所述的化合物B的摩尔比可为该类偶联反应常规的摩尔比，例如(0.5～0.6)：1，又例如0.55：1。
所述的化合物2与所述的化合物B的摩尔比可为该类偶联反应常规的摩尔比，例如(0.2～1.0)：1。
所述的化合物3与所述的化合物B的摩尔比可为该类偶联反应常规的摩尔比，例如(0.2～1.0)：1。
所述的化合物4与所述的化合物B的摩尔比可为该类偶联反应常规的摩尔比，例如(0.7～0.8)：1，又例如0.75：1。
所述的偶联反应的温度可为本领域该类偶联反应常规的温度，例如20-30℃，又例如25-30℃。
所述的偶联反应的进程可以采用本领域中常规监测方法(例如TLC、HPLC、NMR或GC)进行监测，一般以化合物B不再反应时为反应终点，反应时间可为12～24小时。
在某一方案中，所述的二胺A的制备方法的某些参数可如下所述，未涉及的参数如上任一方案所述：
所述的二胺A可为以下任一化合物：
本发明还提供了一种二胺A，其为下述任一化合物：
本发明还提供了一种化合物B，其为
在不违背本领域常识的基础上，上述各优选条件，可任意组合，即得本发明各较佳实例。
本发明所用试剂和原料均市售可得。
如无特别说明，本发明中的“室温”是指20-30℃，例如25℃。
本发明的积极进步效果在于：该联硼酸二醇酯可用于诱导底物为亚胺的还原偶联反应，底物可由醛及氨反应得到，非常易得且成本相当低廉；产物仅需酸碱操作，即可从反应体系中分离而来，无需柱色谱纯化，后处理方式便捷，易于操作；所得产物产率较高且无需保护基操作。该联硼酸二醇酯具备手性，所述还原偶联反应的立体选择性普遍优秀，仅需简单重结晶既可以得到99％ee的手性二胺。该联硼酸二醇酯可使用二醇可与联硼酸二醇酯反应获得，该二醇制备方便，易于放大，且其经过简单的酸碱操作，可以从反应液中回收重复利用，回收率达95％，进一步节约了制备成本。
具体实施方式
下面通过实施例的方式进一步说明本发明，但并不因此将本发明限制在所述的实施例范围之中。下列实施例中未注明具体条件的实验方法，按照常规方法和条件，或按照商品说明书选择。
制备例1手性二醇的制备
选取合适的三口瓶，称取表面光洁干燥的镁屑(19.5g,0.81mol,1.5eq)抽换氮气三次，氮气保护下加入重蒸THF(200ml)和两粒碘，然后加入适量的芳基溴试剂(共0.54mol,1.0eq)，然后电吹风加热使得格氏试剂引发，溶液黄色褪去变无色，继续加入芳基溴，保持反应体系微沸，说明格氏反应引发完成，加完芳基溴后，将未取代或取代的R-扁桃酸甲酯(0.11mol,0.2eq)溶于重蒸THF(50mL)溶液中，滴加入格氏试剂当中，反应加热回流，反应约4小时后已经完成，将反应冷至室温，倒入饱和氯化铵溶液淬灭，调pH在7以下，乙酸乙酯萃取，合并有机相，无水硫酸钠干燥，柱层析得到含有产物的混合体系，石油醚重结晶得到干净产物，产率为60％。
(R)-1,1-二(4-甲氧基苯基)-2-苯基乙二醇(报道于Supermolecular.1998,9,85-98)
白色固体；99％ee；ee值由高压手性液相测定；高压液相条件：手性PC1柱，乙腈/水：80/20,25℃,流速0.7mL/min,7.13min(R),7.72min(S).旋光:[α]D 29＝200.0°[c＝0.5,CHCl3].1H NMR(500MHz,CDCl3):δ7.58(m,2H),7.17(m,3H),7.05(m,2H),7.00(m,2H),6.95(m,2H),6.64(m,2H),5.52(d,J＝3.2Hz,1H),3.82(s,3H),3.71(s,3H),3.01(s,1H),2.42(d,J＝3.2Hz,1H).13C NMR(125MHz,CDCl3):158.9,158.4,139.2,137.5,136.2,128.5(2C),128.3(2C),127.8,127.7(2C),127.6(2C),114.0(2C),113.1(2C),80.5,78.5,55.5,55.3.HRMS(ESI)calcd.for C22H22NaO4[M+Na]+:373.1410；found:373.1414.
(R)-2-(2-氯代苯基)-1,1-二(4-甲氧基苯基)乙二醇
黄色固体；99％ee；ee值由高压手性液相测定；高压液相条件：手性OJ-H,正己烷/异丙醇：90/10,25℃,流速0.7mL/min,55.13min(R),46.65min(S).旋光:[α]D 29＝4.84°[c＝0.5,CHCl3].1H NMR(500MHz,CDCl3):δ7.68(dd,J＝7.8,1.7Hz,1H),7.57(m,2H),7.23(ddd,J＝8.1,7.0,1.7Hz,1H),7.13(m,2H),6.96(m,4H),6.59(m,2H),6.12(dd,J＝4.3,1.6Hz,1H),3.83(s,3H),3.69(s,3H),3.21(m,1H),2.40(m,1H).13C NMR(125MHz,CDCl3):159.0,158.6,137.5,137.3,135.5,134.4,130.2,129.1,128.9,128.6(2C),128.4(2C),126.5,113.9(2C),112.8(2C),80.6,73.1,55.5,55.3.HRMS(ESI)calcd.for C22H21ClNaO4[M+Na]+:407.1021；found:407.1023.
(R)-1,1-二(3,5-二甲基苯基)-2-苯基乙二醇
白色固体；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱PC1,乙腈/水：80/20,25℃,流速0.7mL/min,10.88min(R),14.62min(S).旋光:[α]D 29＝176.0°[c＝0.5,CHCl3].1H NMR(500MHz,CDCl3):δ7.32(s,2H),7.17(m,3H),7.06(m,2H),6.96(s,1H),6.75(m,3H),5.57(d,J＝3.2Hz,1H),2.99(s,1H),2.45(s,J＝3.2Hz,1H),2.37(s,6H),2.16(s,6H).13C NMR(125MHz,CDCl3):δ145.0,143.4,139.0,138.1(2C),137.1(2C),129.2,128.5,128.3,127.7,127.5,124.8,124.2,80.9,78.2,21.8(2C),21.6(2C).HRMS(ESI)calcd.for C24H26NaO2[M+Na]+:369.1825；found:369.1828.
(R)-1,1-二(2,5-二甲基苯基)-2-苯基乙二醇
白色固体；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱PC3,乙腈/水：80/20,25℃,流速0.7mL/min,5.91min(R),6.69min(S).旋光:[α]D 30＝151.5°[c＝1.13,CHCl3].1H NMR(500MHz,CDCl3):δ7.67(s,1H),7.13(m,1H),7.08(m,2H),7.04(dd,J＝7.7,1.7Hz,1H),6.99(m,3H),6.90(s,1H),6.74(dd,J＝7.7,1.8Hz,1H),6.70(d,J＝7.7Hz,1H),5.64(s,1H),3.16(s,1H),2.68(s,1H),2.43(s,3H),2.05(s,3H),1.96(s,3H),1.77(s,3H).13C NMR(125MHz,CDCl3):δ142.6,140.6,140.3,136.0,134.3,132.9,131.6,128.9,128.8,128.3,128.0,127.6,127.4,127.3,21.7,27.6,21.2,21.1.HRMS(ESI)calcd.for C24H26NaO2[M+Na]+:369.1825；found:369.1828.
(R)-1,1-二(2,4-二甲基苯基)-2-苯基乙二醇
无色固体结晶；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱PC1,乙腈/水：80/20,25℃,流速0.7mL/min,7.27min(R),9.94min(S).旋光:[α]D 20＝-452.8°[c＝1.30,CHCl3].HRMS(ESI)calcd.for C24H26NaO2[M+Na]+:369.1825；found:369.1830.
(R)-2-苯基-1,1-邻二甲苯基乙二醇
白色固体；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱PC1,乙腈/水：80/20,25℃,流速0.7mL/min,7.27min(R),9.94min(S).旋光:[α]D 29＝223.8°[c＝0.5,CHCl3].1H NMR(500MHz,CDCl3):δ7.87(d,J＝7.6Hz,1H),7.28(m,1H),7.23(m,1H),7.16(m,1H),7.10(m,4H),6.96(m,3H),6.83(m,2H),5.67(s,1H),3.28(brs,1H),1.98(s,3H),1.83(s,3H).13C NMR(125MHz,CDCl3):δ140.8,140.2,139.2,133.1,131.7,128.3,128.1(2C),127.8(2C),127.7(2C),127.4(2C),126.8,125.1(2C),22.1,21.6.HRMS(ESI)calcd.forC22H22NaO2[M+Na]+:341.1512；found:341.1516.
制备例2手性二硼DB4～DB7的制备
选取一合适的Schlenk管，加入diol 5(30g,86mmol,2.0eq)，四羟基二硼(3.9g,43mmol,1.0eq)和适量的4A分子筛，抽换氮气三次，氮气保护下加入重蒸THF(150ml)，体系置于70℃油浴中回流，反应约4小时完成。将反应体系冷至室温，硅藻土过滤，二氯甲烷洗涤，滤液旋干，用石油醚洗涤，再次过滤，滤饼白色固体粉末即为双硼产物28.7g,产率为94％。(DB4)。
白色固体；94％产率；旋光:[α]D 29＝275.2°[c＝1.10,CHCl3].1H NMR(400MHz,CDCl3):δ7.70(s,2H),7.26(s,2H),7.07-6.99(m,14H),6.73(m,2H),6.59(m,4H),2.45(s,6H),2.14(s,6H),1.92(s,6H),1.53(s,6H).13C NMR(100MHz,CDCl3):δ141.1(2C),138.7(2C),137.5(2C),135.8(2C),134.7(2C),134.2(2C),132.7(2C),131.1(2C),131.0(2C),128.6(2C),128.5(2C),127.7(2C),127.6(2C),127.4(4C),127.3(4C),126.1(2C),91.8(2C),84.3(2C),21.7(2C),21.4(2C),21.3(2C),21.0(2C).11B NMR(CDCl3,128MHz):δ31.4.HRMS(DART)calcd.for C48H49O4 10B2[M]+:709.3884；found:709.3881.
选取一合适的Schlenk管，加入diol 4(3.2g,10mmol,2.0eq)，四羟基二硼(0.45g,5.0mmol,1.0eq)和适量的4A分子筛，抽换氮气三次，氮气保护下加入重蒸THF(15ml)，体系置于70℃油浴中回流，反应约4小时完成。将反应体系冷至室温，硅藻土过滤，二氯甲烷洗涤，滤液旋干，用石油醚洗涤，再次过滤，滤饼白色固体粉末即为双硼产物3.1g,产率为95％。(DB5)。
白色固体；95％产率；1H NMR(400MHz,CDCl3):7.91(d,J＝7.6Hz,2H),7.30(m,2H),7.26(m,2H),7.20(m,2H),7.14(m,8H),7.04(m,6H),6.88(m,4H),6.58(s,2H),1.98(s,6H),1.73(s,6H).11B NMR(CDCl3,128MHz):δ30.4.HRMS(DART)calcd.for C48H40O4 10B2[M]+:654.4200；found:654.4205.
选取一合适的Schlenk管，加入diol 6(350mg,1.0mmol,2.0eq)，四羟基二硼(45mg,0.50mmol,1.0eq)和适量的4A分子筛，抽换氮气三次，氮气保护下加入重蒸THF(5ml)，体系置于70℃油浴中回流，反应约4小时完成。将反应体系冷至室温，硅藻土过滤，二氯甲烷洗涤，滤液旋干，用石油醚洗涤，再次过滤，滤饼白色固体粉末即为双硼产物330mg,产率为92％。(DB6)。
白色固体；92％产率；1H NMR(500MHz,CDCl3):δ7.62(m,4H),7.21(m,6H),7.15(m,4H),7.06(m,4H),6.99(m,4H),6.70(m,4H),5.58(d,J＝3.2Hz,2H),3.88(s,6H),3.75(s,6H).11B NMR(CDCl3,128MHz):δ28.5.HRMS(DART)calcd.for C44H40O8 10B2[M]+:718.2909；found:718.2903.
选取一合适的Schlenk管，加入diol 8(346mg,1.0mmol,2.0eq)，四羟基二硼(45mg,0.50mmol,1.0eq)和适量的4A分子筛，抽换氮气三次，氮气保护下加入重蒸THF(5ml)，体系置于70℃油浴中回流，反应约4小时完成。将反应体系冷至室温，硅藻土过滤，二氯甲烷洗涤，滤液旋干，用石油醚洗涤，再次过滤，滤饼白色固体粉末即为双硼产物333mg,产率为94％。(DB8)。
白色固体；94％产率；HRMS(DART)calcd.for C48H48O4 10B2[M]+:710.3739；found:710.3743.
实施例1芳香亚胺不对称还原偶联底物拓展
在干净干燥的shlenk管中，加入芳基醛(0.2mmol,1.0eq)，体系抽换氮气三次，氮气保护，在氮气保护下，加入氨甲醇溶液(7.0M,3.0mmol,15.0eq)，加溶剂重蒸四氢呋喃(2mL)，体系密封，反应室温搅拌1h，在氮气保护下，加入DB4(0.11mmol,0.55eq)，室温(20-30℃)下搅拌12-24h。体系旋蒸除去多余氨气，加入1mL甲醇，加入盐酸(3.0M，1mL)调pH至3左右，二氯甲烷洗涤，将有机相浓缩后用正己烷打浆回收手性二醇diol5(95％回收率)。而水相加入氢氧化钠溶液调pH至12左右，二氯甲烷萃取，合并有机相，无水硫酸钠干燥，有机相旋干即得到产物。
1a(1R,2R)-1,2-二苯基乙二胺
白色固体；82％产率；95％ee(其中，过量的对映体的绝对构型如结构式所示，本发明全文同此)；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,14.66min(S,S),17.54min(R,R),该保留时间与购得的(1S,2S)-1,2-二苯基乙二胺、(1R,2R)-1,2-二苯基乙二胺在同一条件下的保留时间相同.旋光:[α]D 21＝36.0°[c＝1.04,CHCl3].1H NMR(500MHz,CDCl3):δ7.30-7.15(m,10H),4.09(s,2H),1.58(s,4H).13C NMR(125MHz,CDCl3):δ143.4(2C),128.2(4C),127.0(2C),126.9(4C),61.9(2C).HRMS(ESI)calcd.for C14H16N2[M+H]+:213.1390；found:213.1386.
2a(1R,2R)-1,2-二(4-甲基苯基)乙二胺
无色液体；71％产率；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,12.57min(S,S),14.11min(R,R).旋光:[α]D 21＝-41.3°[c＝1.02,CHCl3].1H NMR(500MHz,CDCl3):δ7.19-7.06(m,8H),4.07(s,2H),2.31(s,6H),1.82(s,4H).13C NMR(125MHz,CDCl3):δ140.2(2C),136.5(2C),128.9(4C),126.8(4C),61.4(2C),21.0(6C).HRMS(ESI)calcd.for C16H20N2[M+H]+:241.1702；found:241.1699.
3a(1R,2R)-1,2-二(4-甲氧基苯基)乙二胺
白色固体；68％产率；99％ee；ee值由其衍生物(4R,5R)-4,5-二(4-甲氧基苯基)2-咪唑烷酮测定所得.旋光:[α]D 22＝43.0°[c＝1.64,CHCl3].1H NMR(500MHz,CDCl3):δ7.18(d,J＝7.50Hz,2H),7.12(t,J＝7.80Hz,2H),6.81(t,J＝7.50Hz,2H),6.76(d,J＝8.20Hz,2H),4.47(s,2H),3.79(s,6H),2.32(s,4H).13C NMR(125MHz,CDCl3):δ156.8(2C),131.3(2C),128.2(2C),127.8(2C),120.3(2C),110.3(2C),55.5(2C),55.2(6C).HRMS(ESI)calcd.for C16H20N2O2[M+H]+:273.1598；found:273.1598.
衍生化操作：将手性二胺(27.2mg,0.1mmol)和Et3N(0.044ml,0.3mmol)溶于DCM(4.0mL)中，三光气(10mg,0.033mmol)溶于DCM(2.0ml)，滴加到上述体系中，使温度保持在5摄氏度以下。滴加完成后，让温度上升到室温后，搅拌3-4小时，反应完成(由薄层色谱监测)。二胺完全消耗后，用水淬灭反应(2.0mL),DCM萃取，有机相合并，无水硫酸钠干燥，柱层析得到白色固体。
(4R,5R)-4,5-二(4-甲氧基苯基)2-咪唑烷酮
白色固体；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：70/30/0.1,23℃,流速1.0mL/min,250nm,18.36min(S,S),38.57min(R,R).旋光:[α]D 27＝115.48°[c＝0.40,CHCl3].1H NMR(500MHz,CDCl3):δ7.17(d,J＝8.3Hz,4H),6.87(d,J＝8.3Hz,4H),5.16(s,2H),4.49(s,2H),3.80(s,6H).13C NMR(125MHz,CDCl3):δ162.5(1C),159.6(2C),131.8(2C),127.7(4C),114.1(4C),65.85(2C),55.3(6C).HRMS(ESI)calcd.for C17H18N2O3[M+H]+:299.1395；found:299.1590；[M+Na]+:321.1214；found:321.1210.
4a(1R,2R)-1,2-二(4-甲氧羰基苯基)乙二胺
黄色固体；55％产率；81％ee；ee值由其衍生物测定所得.旋光:[α]D 21＝87.7°[c＝1.01,CHCl3].1H NMR(500MHz,CDCl3):δ7.92(d,J＝7.6Hz,4H),7.29(d,J＝8.0Hz,4H),4.14(s,2H),3.89(s,6H),1.96(s,4H).13C NMR(125MHz,CDCl3):δ166.8(2C),129.6(4C),129.2(2C),127.5(2C),127.0(4C),61.9(2C),52.1(6C).HRMS(ESI)calcd.for C18H20N2O4[M+H]+:329.1498；found:329.1496.
(1R,2R)-1,2-二(4-甲氧羰基苯基)2-咪唑烷酮
将手性二胺(32.8mg,0.1mmol)和Et3N(0.044ml,0.3mmol)溶于DCM(4.0mL)中，三光气(10mg,0.033mmol)溶于DCM(2.0ml)，滴加到上述体系中，使温度保持在5摄氏度以下。滴加完成后，让温度上升到室温后，搅拌3-4小时，反应完成(由薄层色谱监测)。二胺完全消耗后，用水淬灭反应(2.0mL),DCM萃取，有机相合并，无水硫酸钠干燥，柱层析得到黄色固体。
黄色固体；81％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：70/30/0.1,23℃,流速1.0mL/min,250nm,10.22min(S,S),14.77min(R,R).旋光:[α]D 26＝64.74°[c＝1.03,CHCl3].1H NMR(500MHz,CDCl3):δ8.04(d,J＝8.5Hz,4H),7.33(d,J＝8.0Hz,4H),5.28(s,2H),4.62(s,2H),3.93(s,6H).13C NMR(125MHz,CDCl3):δ166.5(1C),162.2(2C),144.3(2C),130.6(2C),130.3(4C),126.5(4C),65.6(2C),52.3(6C).HRMS(ESI)calcd.for C19H18N2O5,[M+H]+:355.1290；found:355.1288.
5a(1R,2R)-1,2-二(4-溴代苯基)乙二胺
无色液体；78％产率；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,23.16min(S,S),30.59min(R,R).Optical rotation:[α]D 20＝78.80°[c＝1.06,CHCl3].1H NMR(500MHz,CDCl3):δ7.40-7.36(m,4H),7.11-7.06(m,4H),4.02(s,2H),2.15(s,4H).13C NMR(125MHz,CDCl3):δ141.5(2C),131.4(4C),128.7(4C),121.2(2C),61.4(2C).HRMS(ESI)calcd.forC14H14Br2N2[M+H]+:368.9600；found:368.9597.
6a(1R,2R)-1,2-二(4-氟代苯基)乙二胺
无色液体；78％产率；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,15.43min(S,S),18.15min(R,R).Optical rotation:[α]D 25＝45.9°[c＝1.04,CHCl3].1H NMR(500MHz,CDCl3):δ7.16(dd,J＝8.40,5.40Hz,4H),6.93(t,J＝8.50Hz,4H),4.00(s,2H),1.76(s,4H).13C NMR(125MHz,CDCl3):δ161.8(d,J＝243.8Hz,2C),138.8(d,J＝3.2Hz 2C),128.4(d,J＝7.8Hz,4C),115.0(d,J＝21.0Hz,4C),61.6(2C).19F NMR(376MHz,CDCl3):δ-115.51(m,2F).HRMS(ESI)calcd.for C14H14F2N2[M+H]+:249.1202；found:249.1198.
7a(1R,2R)-1,2-二(4-氯代苯基)乙二胺
无色液体；58％产率；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,20.19min(S,S),26.58min(R,R).旋光:[α]D 21＝83.2°[c＝1.03,CHCl3].1H NMR(500MHz,CDCl3):δ7.22(d,J＝8.50Hz,4H),7.14(d,J＝8.50Hz,4H),4.05(s,2H),2.23(s,4H).13C NMR(125MHz,CDCl3):δ140.9(2C),133.0(2C),128.5(4C),128.4(4C),61.3(2C).HRMS(ESI)calcd.forC14H14Cl2N2[M+H]+:281.0609；found:281.0607.
8a(1R,2R)-1,2-二(2,4,6-三取代苯基)乙二胺
无色液体；66％产率；93％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,13.77min(S,S),17.29min(R,R).旋光:[α]D 21＝23.5°[c＝1.00,CHCl3].1H NMR(500MHz,CDCl3):δ6.48(t,J＝8.80Hz,4H),4.41(s,2H),2.04(s,4H).13C NMR(125MHz,CDCl3):δ161.6(d,J＝124.0Hz,2C),161.0(d,J＝124.0Hz,4C),114.7(t,J＝15.8Hz,2C),100.2(t,J＝26.8Hz,2C),52.0(2C).19F NMR(376MHz,CDCl3):δ-108.6(p,J＝7.40Hz,2F),-110.7(t,J＝7.50Hz,4F).HRMS(ESI)calcd.for C14H10F6N2[M+H]+:321.0826；found:321.0821.
9a(1R,2R)-1,2-二(2-甲氧基苯基)乙二胺
白色固体；74％产率；95％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,13.63min(S,S),14.97min(R,R).旋光:[α]D 20＝37.2°[c＝1.07,CHCl3].1H NMR(500MHz,CDCl3):δ7.18(d,J＝7.50Hz,2H),7.12(t,J＝7.80Hz,2H),6.81(t,J＝7.50Hz,2H),6.76(d,J＝8.20Hz,2H),4.47(s,2H),3.79(s,6H),2.32(s,4H).13C NMR(125MHz,CDCl3):δ156.8(2C),131.3(2C),128.2(2C),127.8(2C),120.3(2C),110.3(2C),55.5(2C),55.2(6C).HRMS(ESI)calcd.forC16H20N2O2[M+H]+:273.1598；found:273.1598.
10a(1R,2R)-1,2-邻甲苯基乙二胺
无色液体；71％产率；70％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,12.6min(S,S),18.5min(R,R).旋光:[α]D 21＝14.4°[c＝1.00,CHCl3].1H NMR(500MHz,CDCl3):δ7.60(d,J＝7.65Hz,2H),7.19(t,J＝7.60Hz,2H),7.09(t,J＝7.50Hz,2H),7.00(d,J＝7.50Hz,2H),4.38(s,2H),2.10(s,6H),2.01(s,4H).13C NMR(125MHz,CDCl3):δ141.4(2C),135.3(2C),130.3(2C),126.8(2C),126.7(2C),126.0(2C),55.8(2C),19.5(6C).HRMS(ESI)calcd.forC16H20N2[M+H]+:241.1703；found:241.1699.
11a(1R,2R)-1,2-二(2-氯代苯基)乙二胺
白色固体；76％产率；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,13.24min(S,S),16.62min(R,R).旋光:[α]D 27＝-28.43°[c＝1.47,CHCl3].1H NMR(500MHz,CDCl3):δ7.57(d,J＝7.50Hz,2H),7.28(d,J＝7.50Hz,2H),7.23(t,J＝7.50Hz,2H),7.14(t,J＝7.50Hz,2H),4.76(s,2H),2.00(s,4H).13C NMR(125MHz,CDCl3):δ140.2(2C),133.0(2C),129.6(2C),128.6(2C),128.3(2C),126.8(2C),55.2(2C).HRMS(ESI)calcd.for C14H14Cl2N2[M+H]+:281.0615；found:281.0607.
12a(1R,2R)-1,2-二(2-溴代苯基)乙二胺
白色固体；65％产率；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,14.63min(S,S),18.16min(R,R).旋光:[α]D 27＝-49.0°[c＝1.00,CHCl3].1H NMR(500MHz,CDCl3):δ7.54(d,J＝7.90Hz,2H),7.46(d,J＝8.00Hz,2H),7.24(d,J＝8.00Hz,2H),7.04(t,J＝7.70Hz,2H),4.67(s,2H),1.78(s,4H).13C NMR(125MHz,CDCl3):δ142.2(2C),132.9(2C),128.8(2C),128.6(2C),127.5(2C),123.7(2C),58.1(2C).HRMS(ESI)calcd.for C14H14Br2N2[M+H]+:368.9601；found:368.9597.
13a(1R,2R)-1,2-二(2-取代呋喃)乙二胺
无色液体；77％yield；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,20.86min(S,S),23.13min(R,R).旋光:[α]D 21＝20.9°[c＝1.04,CHCl3].1H NMR(500MHz,CDCl3):δ7.33(s,2H),6.28(d,J＝1.95Hz,2H),6.15(d,J＝3.20Hz,3H),4.27(s,2H),1.87(s,4H).13C NMR(125MHz,CDCl3):δ155.9(2C),141.6(2C),110.2(2C),106.0(2C),54.0(2C).HRMS(ESI)calcd.for C10H12N2O2[M+H]+:193.0966；found:193.0972.[M+Na]+:215.0785；found:215.0791.
14a(1R,2R)-1,2-二(2-取代噻吩)乙二胺
无色液体；71％产率；96.5％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,18.58min(S,S),19.38min(R,R).旋光:[α]D 27＝39.8°[c＝1.80,CHCl3].1H NMR(500MHz,CDCl3):δ7.20(d,J＝5.0Hz,2H),6.94(d,J＝4.4Hz,2H),6.90(d,J＝3.4Hz,2H),4.43(s,2H),1.81(s,4H).13CNMR(125MHz,CDCl3):δ147.3(2C),126.7(2C),124.1(2C),123.8(2C),58.4(2C).HRMS(ESI)calcd.for C10H12N2S2[M+H]+:225.0512；found:225.0515.
15a(1R,2R)-1,2-二(3-取代噻吩)乙二胺
无色液体；81％产率；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,21.55min(S,S),22.68min(R,R).旋光:[α]D 27＝9.2°[c＝1.53,CHCl3].1H NMR(500MHz,CDCl3):δ7.28-7.25(m,2H),7.12(d,J＝2.4Hz,2H),6.98(d,J＝5.0Hz,2H),4.23(s,2H),1.67(s,4H).13C NMR(125MHz,CDCl3):δ144.6(2C),126.3(2C),125.7(2C),121.0(2C),57.7(2C).HRMS(ESI)calcd.for C10H12N2S2[M+H]+:225.0512；found:225.0515.
16a(1R,2R)-1,2-二(3-三氟甲基苯基)乙二胺
无色液体；59％产率；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,13.39min(S,S),14.69min(R,R).Optical rotation:[α]D 27＝26.4°[c＝0.73,CHCl3].1H NMR(500MHz,CDCl3):δ7.51-7.34(m,8H),4.12(s,2H),1.63(s,4H).13C NMR(125MHz,CDCl3):δ143.9(2C),130.6(q,J＝34.14Hz,2C),130.3(2C),128.7(2C),124.4(q,J＝270.8Hz,2C),124.1(2C),123.8(2C),61.9(2C).19F NMR(376MHz,cdcl3):δ-62.7(2F).HRMS(ESI)calcd.forC16H14F6N2[M+H]+:349.1139；found:349.1134.
17a(1R,2R)-1,2-二(2-取代[1,1'-联苯基])乙二胺
白色固体；33％产率；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,8.43min(S,S),9.30min(R,R).旋光:[α]D 29＝33.7°[c＝0.50,CHCl3].1H NMR(500MHz,CDCl3):δ7.34-7.33(m,6H),7.15-7.00(m,6H),6.99-6.87(m,6H),4.24(s,2H),2.80(s,4H).13C NMR(125MHz,CDCl3):δ141.8(2C),140.7(2C),138.3(2C),129.7(2C),129.4(2C),129.1(2C),128.4(2C),128.0(2C),127.9(2C),126.9(2C),126.9(2C),126.8(2C),56.7(2C).HRMS(ESI)calcd.for C26H24N2,[M+H]+:365.2015；found:365.2012.
18a(1R,2R)-1,2-二(3-氯代苯基)乙二胺
黄色液体；65％产率；92％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：80/20/0.1,23℃,流速0.8mL/min,17.58min(S,S),18.29min(R,R).旋光:[α]D 27＝52.0°[c＝1.30,CHCl3].1H NMR(500MHz,CDCl3):δ7.29(s,2H),7.20(d,J＝4.60Hz,4H),7.12-7.09(m,2H),4.03(s,2H),1.59(s,4H).13C NMR(125MHz,CDCl3):δ145.2(2C),126.3(2C),134.3(2C),129.6(2C),127.4(2C),127.0(2C),125.1(2C),61.4(2C).HRMS(ESI)calcd.for C14H14Cl2N2[M+H]+:281.0607；found:281.0607.
19a(1R,2R)-1,2-二(2-取代萘基)乙二胺
白色固体；64％产率；99％ee；ee值由其衍生物所得.旋光:[α]D 27＝61.23°[c＝1.00,CHCl3].1H NMR(500MHz,CDCl3):δ7.83-7.68(m,8H),7.43(d,J＝6.6Hz,6H),4.46(s,2H),2.51(s,4H).13C NMR(125MHz,CDCl3):δ140.0(2C),133.2(2C),132.7(2C),128.0(2C),127.9(2C),127.6(2C),126.0(2C),125.7(4C),125.3(2C),61.3(2C).HRMS(ESI)calcd.forC22H20N2[M+H]+:313.1701；found:313.1699.
(4R,5R)-4,5-二(2-取代萘基)2-咪唑烷酮
将手性二胺(31.2mg,0.1mmol)和Et3N(0.044ml,0.3mmol)溶于DCM(4.0mL)中，三光气(10mg,0.033mmol)溶于DCM(2.0ml)，滴加到上述体系中，使温度保持在5摄氏度以下。滴加完成后，让温度上升到室温后，搅拌3-4小时，反应完成(由薄层色谱监测)。二胺完全消耗后，用水淬灭反应(2.0mL),DCM萃取，有机相合并，无水硫酸钠干燥，柱层析得到白色固体。
白色固体；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：70/30/0.1,23℃,流速1.0mL/min,230nm,18.70min(S,S),28.63min(R,R).Optical rotation:[α]D 27＝151.37°[c＝0.25,CHCl3].1H NMR(500MHz,CDCl3):δ7.87(t,J＝7.9Hz,4H),7.80-7.77(m,2H),7.71(s,2H),7.53-7.48(m,4H),7.44(dd,J＝8.5,1.8Hz,2H),5.05(s,2H),4.86(s,2H).13C NMR(125MHz,CDCl3):δ137.2(1C),133.4(2C),133.2(2C),129.0(2C),128.0(2C),127.8(2C),126.6(2C),126.4(2C),125.7(2C),124.0(2C),66.0(2C).HRMS(ESI)calcd.for C23H18N2O,[M+H]+:339.1496；found:339.1492,[M+Na]+:361.1315；found:365.1311.
20a(1R,2R)-1,2-二(1-取代萘基)乙二胺
白色固体；61％yield；73％ee；ee值由其衍生物所得.旋光:[α]D 27＝-32.88°[c＝1.20,CHCl3].1H NMR(500MHz,CDCl3):δ8.30(d,J＝8.50Hz,2H),7.88(d,J＝8.10Hz,2H),7.78(dd,J＝18.20,7.70Hz,4H).7.58(t,J＝7.60Hz,2H),7.48(dt,J＝15.50,7.60Hz,4H),5.12(s,2H),1.81(s,4H).13C NMR(125MHz,CDCl3):δ139.5(2C),133.9(2C),130.9(2C),129.1(2C),127.7(2C),126.0(2C),125.5(2C),125.4(2C),124.2(2C),122.9(2C),54.4(2C).HRMS(ESI)calcd.for C22H20N2[M+H]+:313.1701；found:313.1699.
(4R,5R)-4,5-二(1-取代萘基)2-咪唑烷酮
将手性二胺(31.2mg,0.1mmol)和Et3N(0.044ml,0.3mmol)溶于DCM(4.0mL)中，三光气(10mg,0.033mmol)溶于DCM(2.0ml)，滴加到上述体系中，使温度保持在5摄氏度以下。滴加完成后，让温度上升到室温后，搅拌3-4小时，反应完成(由薄层色谱监测)。二胺完全消耗后，用水淬灭反应(2.0mL),DCM萃取，有机相合并，无水硫酸钠干燥，柱层析得到白色固体。
白色固体；73％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：70/30/0.1,23℃,流速1.0mL/min,250nm,18.28min(S,S),29.19min(R,R).旋光:[α]D 27＝-77.78°[c＝0.55,CHCl3].1H NMR(500MHz,CDCl3):δ7.85(d,J＝8.2Hz,4H),7.80(d,J＝7.2Hz,2H),7.53(t,J＝7.7Hz,2H),7.40(dt,J＝15.0,8.1Hz,4H),7.11(t,J＝7.7Hz,2H),5.55(s,2H),5.43(s,2H).13C NMR(125MHz,CDCl3):δ162.6(1C),136.6(2C),133.9(2C),130.5(2C),129.0(2C),128.8(2C),126.1(2C),125.8(2C),125.6(2C),124.1(2C),122.8(2C),61.3(2C).HRMS(ESI)calcd.for C23H18N2O,[M+H]+:339.1496；found:339.1492,[M+Na]+:361.1315；found:365.1311.
实施例2甲基取代的芳香亚胺底物拓展
在干净干燥的shlenk管中，加入氮甲基取代的芳基亚胺(0.2mmol，1.0eq)，DB4(0.11mmol,0.55eq)，体系抽换氮气三次，氮气保护下，加入重蒸四氢呋喃2.0ml，密封，室温下搅拌12-24h。停止反应，加入盐酸(3.0M，1ml)调pH至3左右，二氯甲烷洗涤，有机相浓缩后经正己烷打浆回收diol 5(95％回收率)，水相加入氢氧化钠溶液调pH至12左右，二氯甲烷萃取，合并有机相，无水硫酸钠干燥，旋干即得到产物。
1c(1R,2R)-N1,N2-二甲基-1,2-二(4-甲基苯基)乙二胺
白色固体；75％yield；97％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：90/10/0.1,25℃,流速0.7mL/min,7.65min(S,S),8.26min(R,R).旋光:[α]D 28＝38.53°[c＝0.38,CHCl3].1H NMR(500MHz,CDCl3):δ6.99(d,J＝8.0Hz,4H),6.95(d,J＝8.0Hz,4H),3.52(s,2H),2.26(s,6H),2.24(s,6H),2.06(brs,2H).13C NMR(125MHz,CDCl3):δ138.0(2C),136.5(2C),128.8(2C),128.0(2C),70.7(2C),34.7(2C),21.3(2C).HRMS(ESI)calcd.for C18H25N2[M+H]+:269.2012；found:269.2011.
2c(1R,2R)-1,2-二(4-甲氧基苯基)-N1,N2-二甲基乙二胺
白色固体；76％产率；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：90/10/0.1,25℃,流速0.7mL/min,16.78min(R,R),21.54min(S,S).旋光:[α]D 28＝9.4°[c＝0.90,CHCl3].1H NMR(500MHz,CDCl3):δ6.95(d,J＝8.6Hz,4H),6.71(d,J＝8.6Hz,4H),3.74(s,6H),3.55(s,2H),2.27(s,6H).13C NMR(125MHz,CDCl3):δ158.7(2C),132.2(2C),129.2(4C),113.6(4C),70.2(2C),55.3(2C),34.3(2C).HRMS(ESI)calcd.for C18H25N2O2[M+H]+:301.1911；found:301.1918.
3c(1R,2R)-1,2-二(4-氟代苯基)-N1,N2-二甲基乙二胺
白色固体；55％产率；98％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：90/10/0.1,25℃,流速0.7mL/min,7.00min(R,R),10.20min(S,S).旋光:[α]D 28＝55.4°[c＝0.75,CHCl3].1H NMR(500MHz,CDCl3):δ6.94(m,4H),6.84(m,4H),3.45(s,2H),2.23(s,6H),2.13(s,2H).13C NMR(125MHz,CDCl3):δ162.9(2C),161.0(2C),136.6(d,J＝3.0Hz,2C),129.4(d,J＝8.0Hz,4C),115.0(d,J＝21.3Hz,4C),70.8(2C),34.6(2C).19F NMR(376MHz,CDCl3):δ-114.8(2F).HRMS(ESI)calcd.forC16H19F2N2[M+H]+:277.1511；found:277.1516.
4c(1R,2R)-1,2-二(4-氯代苯基)-N1,N2-二甲基乙二胺
白色固体；80％产率；98％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：90/10/0.1,25℃,流速0.7mL/min,7.70min(R,R),11.99min(S,S).旋光:[α]D 28＝89.7°[c＝0.08,CHCl3].1H NMR(500MHz,CDCl3):δ7.14(d,J＝8.1Hz,4H),6.94(d,J＝8.1Hz,4H),3.47(s,2H),2.23(s,6H).13C NMR(125MHz,CDCl3):δ139.3(2C),132.9(2C),129.4(4C),128.5(4C),70.6(2C),34.6(2C).HRMS(ESI)calcd.forC16H19Cl2N2[M+H]+:309.0920；found:309.0917.
5c(1R,2R)-1,2-二(4-溴代苯基)-N1,N2-二甲基乙二胺
白色固体；73％产率；98％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：90/10/0.1,25℃,流速0.7mL/min,8.55min(R,R),13.00min(S,S).旋光:[α]D 28＝64.8°[c＝1.0,CHCl3].1H NMR(500MHz,CDCl3):δ7.29(d,J＝8.3Hz,4H),6.88(d,J＝8.3Hz,4H),3.44(s,2H),2.22(s,6H),2.06(s,2H).13C NMR(125MHz,CDCl3):δ139.9(2C),131.4(4C),129.8(4C),121.1(2C),70.6(2C),34.6(2C).HRMS(ESI)calcd.for C16H19Br2N2[M+H]+:396.9910；found:396.9906.
6c(1R,2R)-N1,N2-二甲基-1,2-二(4-三氟甲氧基苯基)乙二胺
白色固体；49％产率；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：90/10/0.1,25℃,流速0.7mL/min,8.55min(R,R),13.00min(S,S).旋光:[α]D 29＝22.8°[c＝0.48,CHCl3].1H NMR(500MHz,CDCl3):δ7.02(m,8H),3.59(s,2H),2.75(s,2H),2.29(s,6H).19F NMR(376MHz,CDCl3):δ-58.0(2F).HRMS(ESI)calcd.for C18H19F6N2O2[M+H]+:409.1345；found:409.1350.
7c(1R,2R)-1,2-二(2-甲氧基苯基)-N1,N2-二甲基乙二胺
白色固体；77％yield；80％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：90/10/0.1,25℃,流速0.7mL/min,8.07min(R,R),8.87min(S,S).旋光:[α]D 29＝44.4°[c＝0.30,CHCl3].1H NMR(500MHz,CDCl3):δ7.12(d,J＝7.4Hz,2H),7.03(ddd,J＝8.3,7.4,1.8Hz,2H),6.74(t,J＝7.4Hz,2H),6.61(dd,J＝8.2Hz,2H),4.04(s,4H),3.60(s,6H),2.58(brs,2H),2.25(s,6H).13C NMR(125MHz,CDCl3):δ158.0(2C),129.3(2C),127.6(2C),120.1(2C),110.2(2C)，110.1(2C),55.3(2C),34.7(2C).HRMS(ESI)calcd.for C18H25N2O2[M+H]+:301.1911；found:301.1912
8c(1R,2R)-N1,N2-二甲基-1,2-二邻甲苯基乙二胺
白色固体；67％产率；93％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：90/10/0.1,25℃,流速0.7mL/min,8.07min(R,R),8.87min(S,S).旋光:[α]D 28＝9.2°[c＝0.46,CHCl3].1H NMR(500MHz,CDCl3):δ7.49(dd,J＝7.8,1.3Hz,2H),7.15(t,J＝7.4Hz,2H),7.02(td,J＝7.4,1.3Hz,2H),6.87(d,J＝7.4Hz,2H),3.93(s,2H),2.33(brs,2H),2.24(s,6H),1.92(s,6H).13C NMR(125MHz,CDCl3):δ139.7(2C),137.1(2C),130.0(2C),126.9(2C),126.7(2C),125.9(2C),65.5(2C),34.4(2C),19.7(2C).HRMS(ESI)calcd.for C18H25N2[M+H]+:269.2012；found:269.2017.
9c(1R,2R)-1,2-二(3-氯代苯基)-N1,N2-二甲基乙二胺
白色固体；58％产率；99％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：90/10/0.1,25℃,流速0.7mL/min,8.07min(R,R),8.87min(S,S).旋光:[α]D 20＝-452.8°[c＝1.30,CHCl3].1H NMR(500MHz,CDCl3):δ7.16-7.08(m,6H),6.90(m,1H),3.58(s,2H),2.29(s,6H).HRMS(ESI)calcd.for C16H19Cl2N2[M+H]+:309.0920；found:309.0924.
10c(1R,2R)-1,2-二(3-氟代苯基)-N1,N2-二甲基乙二胺
白色固体；83％产率；98％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：90/10/0.1,25℃,流速0.7mL/min,7.31min(R,R),8.73min(S,S).旋光:[α]D 28＝13.4°[c＝1.05,CHCl3].1H NMR(500MHz,CDCl3):δ7.14-7.13(m,2H),6.85-6.78(m,6H),3.54(s 2H),2.65(brs,2H),2.27(s,6H).13C NMR(125MHz,CDCl3):δ163.9(2C),162.0(2C),143.0(2C),129.7(2C),123.8(2C),114.5(2C),70.7(2C),34.5(2C).19F NMR(376MHz,CDCl3):δ-113.4(2F).HRMS(ESI)calcd.for C16H19F2N2[M+H]+:277.1511；found:277.1517.
11c(1R,2R)-N1,N2-二甲基-1,2-二(1-取代萘基)乙二胺
白色固体；59％产率；70％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：90/10/0.1,25℃,流速0.7mL/min,8.07min(R,R),8.87min(S,S).旋光:[α]D 29＝-114.0°[c＝0.21,CHCl3].1H NMR(500MHz,CDCl3):δ8.19(m,2H),7.71-7.58(m,6H),7.37-7.33(m,6H),4.74(s,2H),2.36(s,2H),2.25(s,6H).13C NMR(125MHz,CDCl3):δ137.1(2C),133.9(2C),132.4(2C),128.8(2C),127.8(2C),125.6(2C),125.4(2C),125.2(4C),123.3(2C),35.0(2C).HRMS(ESI)calcd.for C24H25N2[M+H]+:341.2012；found:341.2014.
12c(1R,2R)-N1,N2-二甲基-1,2-二(2-取代萘基)乙二胺
白色固体；59％产率；90％ee；ee值由高压手性液相测定；高压液相条件：手性柱S-Chiral B,正己烷/异丙醇/二乙胺：90/10/0.1,25℃,流速0.7mL/min,8.07min(R,R),8.87min(S,S).旋光:[α]D 29＝80.0°[c＝0.31,CHCl3].1H NMR(500MHz,CDCl3):δ7.71(m,2H),7.66(d,J＝8.5Hz,2H),7.59(m,2H),7.39(m,4H),7.27(dd,J＝8.5,1.7Hz,2H),3.89(s,2H),2.29(s,6H),2.20(brs,2H).13C NMR(125MHz,CDCl3):δ138.3(2C),133.3(2C),132.9(2C),128.0(2C),127.9(2C),127.7(2C),127.3(2C),126.0(2C),125.9(2C),125.7(2C),70.9(2C),34.8(2C).HRMS(ESI)calcd.for C24H25N2[M+H]+:341.2012；found:341.2015.
实施例3
在干净干燥的shlenk管中，加入苯甲醛(0.2mmol,1.0eq)，体系抽换氮气三次，氮气保护，在氮气保护下，加入氨甲醇溶液(7.0M,3.0mmol,15.0eq)，加溶剂重蒸四氢呋喃(2mL)，体系密封，反应室温搅拌1h，在氮气保护下，加入{体系一：[双醇diol(1-8)(0.08mmol,0.4eq)和B2(neo)2(0.15mmol，0.75eq)]，或者，体系二：[DB(1-4)(0.11mmol,0.55eq)]}，室温(25-30℃)下搅拌12-24h。体系旋蒸除去多余氨气，加入1mL甲醇，加入盐酸(3.0M，1mL)调pH至3左右，二氯甲烷多次洗涤，水相加入氢氧化钠溶液调pH至12左右，二氯甲烷萃取，合并有机相，无水硫酸钠干燥，有机相旋干即得到产物。产率和ee值见表1。
表1
| 序号 | 联硼酸酯 | 溶剂 | 产率(％) | ee值(％) |
| 1 | DB 1 | MeOH | 35 | 45 |
| 2 | DB 1 | THF | 61 | 51 |
| 3 | DB 1 | Dioxane | 55 | 42 |
| 4 | DB 1 | Toluene | 35 | 48 |
| 5 | DB 1 | MTBE | 40 | 49 |
| 6 | DB 2 | THF | 72 | 57 |
| 7 | DB 3 | THF | 80 | 20 |
| 8 | DB 4 | THF | 82 | 95 |
| 9 | DB 5 | THF | 73 | 82 |
| 10 | DB 6 | THF | 68 | 72 |
| 11 | DB 7 | THF | 81 | 92 |
| 12 | diol 1+B<sub>2</sub>(neo)<sub>2</sub> | THF | 60 | 30 |
| 13 | diol 2+B<sub>2</sub>(neo)<sub>2</sub> | THF | <5 | Nd |
| 14 | diol 4+B<sub>2</sub>(neo)<sub>2</sub> | THF | 71 | 80 |
| 15 | diol 5+B<sub>2</sub>(neo)<sub>2</sub> | THF | 81 | 93 |
| 16 | diol 6+B<sub>2</sub>(neo)<sub>2</sub> | THF | 75 | 68 |
| 17 | diol 8+B<sub>2</sub>(neo)<sub>2</sub> | THF | 78 | 92 |
Claims (15)
1.一种如式1所示的联硼酸二醇酯；
其中，C1和C2同时为R构型碳原子或S构型碳原子；
R1为苯基、或、卤素取代的苯基；R2与R1相同；
C3为非手性碳原子；
R3-1为R3-1-1取代的苯基，所述的R3-1-1独立地为C1～C3的烷基或C1～C3的烷氧基；R3-2与R3 -1相同；
C4为非手性碳原子；
R4-1为R4-1-1取代的苯基，所述的R4-1-1独立地为C1～C3的烷基或C1～C3的烷氧基；R4-2与R4 -1相同。
2.如权利要求1所述的联硼酸二醇酯1，其特征在于，当所述的R1为卤素取代的苯基时，所述的卤素的个数为1个、2个、3个、4个或5个，当存在2个以上的卤素时，所述的卤素相同或不同；
和/或，当所述的R1为卤素取代的苯基时，所述的卤素独立地为氟、氯、溴或碘；
和/或，当所述的R1为卤素取代的苯基时，所述的卤素独立地与所述的C1互为邻位、间位或对位；
和/或，所述的R3-1-1的个数为1个、2个、3个、4个或5个，当存在2个以上的R3-1-1时，所述的R3-1-1相同或不同；
和/或，所述的R3-1-1独立地与所述的C3互为邻位、间位或对位；
和/或，当所述的R3-1-1为C1～C3的烷基时，所述的C1～C3的烷基为甲基、乙基、正丙基或异丙基；
和/或，当所述的R3-1-1为C1～C3的烷氧基时，所述的C1～C3的烷氧基为甲氧基、乙氧基、正丙氧基或异丙氧基；
和/或，所述的R4-1-1的个数为1个、2个、3个、4个或5个，当存在2个以上的R4-1-1时，所述的R4-1-1相同或不同；
和/或，所述的R4-1-1独立地与所述的C4互为邻位、间位或对位；
和/或，当所述的R4-1-1为C1～C3的烷基时，所述的C1～C3的烷基为甲基、乙基、正丙基或异丙基；
和/或，当所述的R4-1-1为C1～C3的烷氧基时，所述的C1～C3的烷氧基为甲氧基、乙氧基、正丙氧基或异丙氧基。
3.如权利要求2所述的联硼酸二醇酯1，其特征在于，当所述的R1为卤素取代的苯基时，所述的卤素的个数为1个或2个；
和/或，当所述的R1为卤素取代的苯基时，所述的卤素独立地为氯；
和/或，当所述的R1为卤素取代的苯基时，所述的卤素独立地与所述的C1互为邻位；
和/或，所述的R3-1-1的个数为1个或2个；
和/或，所述的R3-1-1独立地与所述的C3互为邻位或间位；
和/或，当所述的R3-1-1为C1～C3的烷基时，所述的C1～C3的烷基为甲基；
和/或，当所述的R3-1-1为C1～C3的烷氧基时，所述的C1～C3的烷氧基为甲氧基；
和/或，所述的R4-1-1的个数为1个或2个；
和/或，所述的R4-1-1独立地与所述的C4互为邻位或间位；
和/或，当所述的R4-1-1为C1～C3的烷基时，所述的C1～C3的烷基为甲基；
和/或，当所述的R4-1-1为C1～C3的烷氧基时，所述的C1～C3的烷氧基为甲氧基。
4.如权利要求3所述的联硼酸二醇酯1，其特征在于，当所述的R1为卤素取代的苯基时，所述的“卤素取代的苯基”为2-氯苯基；
和/或，所述的R3-1为2-甲基苯基、4-甲氧基苯基、2,4-二甲基苯基、2,5-二甲基苯基或3,5-二甲基苯基；
和/或，所述的R4-1为2-甲基苯基、4-甲氧基苯基、2,4-二甲基苯基、2,5-二甲基苯基或3,5-二甲基苯基。
5.如权利要求1所述的联硼酸二醇酯1，其特征在于，R1与R2均为苯基；
和/或，所述的R3-1-1独立地为C1～C3的烷基；所述的R4-1-1独立地为C1～C3的烷基；
和/或，R3-1和R4-1相同。
6.如权利要求1所述的联硼酸二醇酯1，其特征在于，R1与R2均为苯基；
所述的R3-1-1独立地为C1～C3的烷基；所述的R4-1-1独立地为C1～C3的烷基；
R3-1和R4-1相同。
7.如权利要求1所述的联硼酸二醇酯1，其特征在于，其为以下任一化合物：
8.一种二醇，其特征在于，其为以下任一化合物：
9.一种如权利要求1～7中任一项所述的联硼酸二醇酯1的制备方法，其特征在于，其包括下述步骤：在溶剂中，将化合物2、化合物3与化合物4进行酯化反应，得到所述的联硼酸二醇酯1即可；
其中，R5-1和R5-2独立地为氢或C1～C3的烷基，或者，R5-1和R5-2连接形成-(CR5-1-1R5-1-2)n-；n为1、2或3，所述的R5-1-1和R5-1-2独立地为氢或C1～C3的烷基；
R5-3和R5-4独立地为氢或C1～C3的烷基，或者，R5-3和R5-4连接形成-(CR5-3-1R5-3-2)m-；m为1、2或3，所述的R5-3-1和R5-3-2独立地为氢或C1～C3的烷基。
10.如权利要求9所述的联硼酸二醇酯1的制备方法，其特征在于，当所述的R5-1为C1～C3的烷基时，所述的C1～C3的烷基为甲基、乙基、正丙基或异丙基；
和/或，当所述的R5-2为C1～C3的烷基时，所述的C1～C3的烷基为甲基、乙基、正丙基或异丙基；
和/或，当所述的R5-1-1为C1～C3的烷基时，所述的C1～C3的烷基为甲基、乙基、正丙基或异丙基；
和/或，当所述的R5-1-2为C1～C3的烷基时，所述的C1～C3的烷基为甲基、乙基、正丙基或异丙基；
和/或，当所述的R5-3为C1～C3的烷基时，所述的C1～C3的烷基为甲基、乙基、正丙基或异丙基；
和/或，当所述的R5-4为C1～C3的烷基时，所述的C1～C3的烷基为甲基、乙基、正丙基或异丙基；
和/或，当所述的R5-3-1为C1～C3的烷基时，所述的C1～C3的烷基为甲基、乙基、正丙基或异丙基；
和/或，当所述的R5-3-2为C1～C3的烷基时，所述的C1～C3的烷基为甲基、乙基、正丙基或异丙基；
和/或，所述的酯化反应在氮气或惰性气体的存在下进行；
和/或，所述的酯化反应在分子筛的存在下进行；
和/或，所述的溶剂为醚类溶剂；
和/或，所述的溶剂与所述的化合物4的体积摩尔比为3.0～3.5L/mol；
和/或，所述的化合物2与所述的化合物4的摩尔比为(1～1.2)：1；
和/或，所述的化合物3与所述的化合物4的摩尔比为(1～1.2)：1；
和/或，所述的酯化反应的温度为60～70℃。
11.如权利要求10所述的联硼酸二醇酯1的制备方法，其特征在于，当所述的R5-1和R5-2连接形成-(CR5-1-1R5-1-2)n-时，所述的-(CR5-1-1R5-1-2)n-为-CH2C(CH3)2CH2-；
和/或，当所述的R5-3和R5-4连接形成-(CR5-3-1R5-3-2)m-时，所述的-(CR5-3-1R5-3-2)m-为-CH2C(CH3)2CH2-；
和/或，所述的酯化反应在4A分子筛的存在下进行；
和/或，所述的溶剂为四氢呋喃；
和/或，所述的酯化反应的温度为60～66℃。
12.一种如式A所示的二胺的制备方法，其特征在于，其包括下述步骤：在溶剂中，将化合物B与偶联试剂进行偶联反应，得到所述的二胺A即可；
所述的偶联试剂为化合物1或偶联试剂组合物，所述的偶联试剂组合物为化合物2、化合物3和化合物4；
其中，C1、R1、C2、R2、C3、R3-1、R3-2、C4、R4-1和R4-2的定义独立地如权利要求1～7中任一项所述；R5-1、R5-2、R5-3和R5-4的定义独立地如权利要求9～11中任一项所述；
C5为手性碳原子，其构型与C1相同；C6为手性碳原子，其构型与C2相同；
R6-1为氢或C1～C3的烷基；
R6-2为苯基、萘基、“杂原子数为1～2个，杂原子选自N、O和S中的一种或多种的5～6元杂芳基”、或、R6-2-1取代的苯基；
所述的R6-2-1独立地为-C(＝O)-O-C1～C3的烷基、卤素、C1～C3的烷基、卤素取代的C1～C3的烷基、C1～C3的烷氧基、或、卤素取代的C1～C3的烷氧基。
13.如权利要求12所述的二胺A的制备方法，其特征在于，当所述的R6-1为C1～C3的烷基时，所述的C1～C3的烷基为甲基、乙基、正丙基或异丙基；
和/或，当所述的R6-2为萘基时，所述的萘基为1-萘基或2-萘基；
和/或，当所述的R6-2为“杂原子数为1～2个，杂原子选自N、O和S中的一种或多种的5～6元杂芳基”时，所述的“杂原子数为1～2个，杂原子选自N、O和S中的一种或多种的5～6元杂芳基”为呋喃基或噻吩基；
和/或，当所述的R6-2为R6-2-1取代的苯基时，所述的R6-2-1的个数为1个、2个、3个、4个或5个，当存在2个以上的R6-2-1时，所述的R6-2-1相同或不同；
和/或，当所述的R6-2为R6-2-1取代的苯基时，所述的R6-2-1独立地与所述的亚胺双键互为邻位、间位或对位；
和/或，当所述的R6-2-1为-C(＝O)-O-C1～C3的烷基时，所述的“C1～C3的烷基为甲基、乙基、正丙基或异丙基；
和/或，当所述的R6-2-1为卤素时，所述的卤素为氟、氯、溴或碘；
和/或，当所述的R6-2-1为C1～C3的烷基时，所述的C1～C3的烷基为甲基、乙基、正丙基或异丙基；
和/或，当所述的R6-2-1为卤素取代的C1～C3的烷基时，所述的卤素的个数为1个、2个、3个、4个或5个，当存在2个以上的卤素时，所述的卤素相同或不同；
和/或，当所述的R6-2-1为卤素取代的C1～C3的烷基时，所述的卤素独立地为氟、氯、溴或碘；
和/或，当所述的R6-2-1为卤素取代的C1～C3的烷基时，所述的C1～C3的烷基为甲基、乙基、正丙基或异丙基；
和/或，当所述的R6-2-1为C1～C3的烷氧基时，所述的C1～C3的烷氧基为甲氧基、乙氧基、正丙氧基或异丙氧基；
和/或，当所述的R6-2-1为卤素取代的C1～C3的烷氧基时，所述的卤素的个数为1个、2个、3个、4个或5个，当存在2个以上的卤素时，所述的卤素相同或不同；
和/或，当所述的R6-2-1为卤素取代的C1～C3的烷氧基时，所述的卤素独立地为氟、氯、溴或碘；
和/或，当所述的R6-2-1为卤素取代的C1～C3的烷氧基时，所述的C1～C3的烷氧基为甲氧基、乙氧基、正丙氧基或异丙氧基；
和/或，所述的偶联反应在氮气或惰性气体的存在下进行；
和/或，所述的溶剂为醚类溶剂和/或醇类溶剂；
和/或，所述的溶剂与所述的化合物B的体积摩尔比为15～25L/mol；
和/或，所述的化合物1与所述的化合物B的摩尔比为(0.5～0.6)：1；
和/或，所述的化合物2与所述的化合物B的摩尔比为(0.2～1.0)：1；
和/或，所述的化合物3与所述的化合物B的摩尔比为(0.2～1.0)：1；
和/或，所述的化合物4与所述的化合物B的摩尔比为(0.7～0.8)：1；
和/或，所述的偶联反应的温度为20-30℃。
14.如权利要求13所述的二胺A的制备方法，其特征在于，当所述的R6-1为C1～C3的烷基时，所述的C1～C3的烷基为甲基；
和/或，当所述的R6-2为“杂原子数为1～2个，杂原子选自N、O和S中的一种或多种的5～6元杂芳基”时，所述的“杂原子数为1～2个，杂原子选自N、O和S中的一种或多种的5～6元杂芳基”为呋喃-2-基、噻吩-2-基或噻吩-3-基；
和/或，当所述的R6-2-1为卤素取代的C1～C3的烷基时，所述的“卤素取代的C1～C3的烷基”为三氟甲基；
和/或，当所述的R6-2-1为卤素取代的C1～C3的烷氧基时，所述的“卤素取代的C1～C3的烷氧基”为三氟甲氧基；
和/或，当所述的溶剂为醚类溶剂和/或醇类溶剂时，所述的醚类溶剂为四氢呋喃；
和/或，当所述的溶剂为醚类溶剂和/或醇类溶剂时，所述的醇类溶剂为甲醇；
和/或，当所述的溶剂为醚类溶剂和/或醇类溶剂时，所述的醚类溶剂和所述的醇类溶剂的体积比为5：1；
和/或，所述的溶剂与所述的化合物B的体积摩尔比为18～22L/mol；
和/或，所述的化合物1与所述的化合物B的摩尔比为0.55：1；
和/或，所述的化合物4与所述的化合物B的摩尔比为0.75：1；
和/或，所述的偶联反应的温度为25-30℃。
15.如权利要求12所述的二胺A的制备方法，其特征在于，所述的二胺A为以下任一化合物：
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