Nucleophile generation via decarboxylation: asymmetric construction of contiguous trisubstituted and quaternary stereocenters through a Cu(I)-catalyzed decarboxylative Mannich-type reaction.
The first catalytic asymmetric decarboxylative Mannich-type reaction between aldimines and cyanocarboxylic acids was developed. Alpha,alpha,beta-trisubstituted beta-amino nitriles containing contiguous trisubstituted and all-carbon quaternary stereocenters were produced with moderate to high enantio- and diastereoselectivity using 5 mol % CuOAc-(R)-DTBM-SEGPHOS complex as an asymmetric catalyst. This reaction proceeds through Cu(I)-catalyzed decarboxylative nucleophile generation followed by the addition of the resulting chiral Cu ketenimide to imines. Because the reaction proceeds under very mild conditions at nearly neutral pH, the reaction is applicable to a wide range of substrate combinations, including both aromatic and aliphatic imines. The products were converted to beta(2,2,3)-amino acid derivatives through simple acidic hydrolysis without any racemization or epimerization. Therefore, this is a general catalytic asymmetric method for the synthesis of beta(2,2,3)-amino acid derivatives, a group of important chiral building blocks for pharmaceutical lead compounds.
Yin
Liang
L
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kanai
Motomu
M
Shibasaki
Masakatsu
M
D000596:Amino Acids / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D003653:Decarboxylation; D008352:Mannich Bases / Q000737:chemistry*
D000596:Amino Acids; D008352:Mannich Bases; D003300:Copper