Method for synthesis of secondary alcohols
View Patent ↗A method for synthesis of secondary alcohols is provided for pharmaceutical secondary alcohol by addition of organoboronic acids with aldehydes in presence of the cobalt ion and bidentate ligands as the catalyst. In addition, an enantioselective synthesis method for secondary alcohols is also herein provided in the present invention. The present invention has advantages in using less expensive cobalt ion and commercially available chiral ligands as the catalyst, wide scope of organoboronic acids and aldehydes compatible with this catalytic reaction and achieving excellent yields and/or enantiomeric excess.
1. A method for synthesis of secondary alcohols, comprising:
reacting an organoboronic acid and an aldehyde in a reaction reagent to obtain a secondary alcohol, wherein the reaction reagent comprises a cobalt ion and a bidentate ligand.
2. The method as claimed in claim 1 , wherein the organoboronic acid is an arylboronic acid.
3. The method as claimed in claim 1 , wherein the organoboronic acid is a phenylboronic acid represented by a structure formula (1):
wherein R 1 is a member selected from the group consisting of H, halo, cyano, trifluoromethyl, amino, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -C 20 cycloalkyl, C 3 -C 20 cycloalkenyl, C 1 -C 20 heterocycloalkyl, C 1 -C 20 heterocycloalkenyl, aryl and heteroaryl.
4. The method as claimed in claim 1 , wherein the aldehyde is represented by a structure formula (2):
wherein R 2 is a member selected from the group consisting of C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -C 20 cycloalkyl, C 3 -C 20 cycloalkenyl, C 1 -C 20 heterocycloalkyl, C 1 -C 20 heterocycloalkenyl, aryl and heteroaryl.
5. The method as claimed in claim 1 , wherein the bidentate ligand contains phosphor.
6. The method as claimed in claim 5 , wherein the bidentate ligand comprises DPPE, (R)-Prophos, (R)-Tol-BINAP, (S)-BINAP, (S,S)-Chiraphos, (R,R)-Ph-BPE, (R)-Quinap, (R)-MOP, (S,S)-DIPAMP, (R)-Monophos, (R,R)-BDPP or (S,S)-DIOP.
7. The method as claimed in claim 1 , wherein the cobalt ion is Co 2+ .
8. The method as claimed in claim 1 , wherein the cobalt ion is provided by Co(acac) 2 , CoI 2 , CoBr 2 or CoCl 2 .
9. The method as claimed in claim 1 , wherein the reaction reagent is basic.
10. The method as claimed in claim 9 , wherein the basic reaction reagent is provided by K 2 CO 3 .
11. An enantioselective method for synthesis of secondary alcohols, comprising:
reacting an organoboronic acid and an aldehyde in an organic reagent to obtain an enantioselective secondary alcohol, wherein the organic reagent comprises a cobalt ion and a chiral bidentate ligand.
12. The method as claimed in claim 11 , wherein the organoboronic acid is an arylboronic acid.
13. The method as claimed in claim 11 , wherein the organoboronic acid is a phenylboronic acid represented by a structure formula (1):
wherein R 1 is a member selected from the group consisting of H, halo, cyano, trifluoromethyl, amino, C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -C 20 cycloalkyl, C 3 -C 20 cycloalkenyl, C 1 -C 20 heterocycloalkyl, C 1 -C 20 heterocycloalkenyl, aryl and heteroaryl.
14. The method as claimed in claim 11 , wherein the aldehyde is represented by a structure formula (2):
wherein R 2 is a member selected from the group consisting of C 1 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -C 20 cycloalkyl, C 3 -C 20 cycloalkenyl, C 1 -C 20 heterocycloalkyl, C 1 -C 20 heterocycloalkenyl, aryl and heteroaryl.
15. The method as claimed in claim 11 , wherein the bidentate ligand contains phosphor.
16. The method as claimed in claim 15 , wherein the bidentate ligand comprises (R)-Prophos, (R)-Tol-BINAP, (S)-BINAP, (S,S)-Chiraphos, (R,R)-Ph-BPE, (R)-Quinap, (R)-MOP, (S,S)-DIPAMP, (R)-Monophos, (R,R)-BDPP or (S,S)-DIOP.
17. The method as claimed in claim 11 , wherein the cobalt ion is Co 2+ .
18. The method as claimed in claim 11 , wherein the cobalt ion is provided by Co(acac) 2 , CoI 2 , CoBr 2 or CoCl 2 .
19. The method as claimed in claim 11 , wherein the organic reagent is basic.
20. The method as claimed in claim 19 , wherein the basic organic reagent is provided by K 2 CO 3 .