Catalytic asymmetric mannich-type reaction of N-alkylidene-α-aminoacetonitrile with ketimines

Shaoquan Lin; Yuji Kawato; Naoya Kumagai; Masakatsu Shibasaki

doi:10.1002/anie.201412377

Catalytic asymmetric mannich-type reaction of N-alkylidene-α-aminoacetonitrile with ketimines

Angew Chem Int Ed Engl. 2015 Apr 20;54(17):5183-6. doi: 10.1002/anie.201412377. Epub 2015 Mar 3.

Authors

Shaoquan Lin¹, Yuji Kawato, Naoya Kumagai, Masakatsu Shibasaki

Affiliation

¹ Institute of Microbial Chemistry (BIKAKEN), Tokyo (Japan), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021 (Japan).

PMID: 25736268
DOI: 10.1002/anie.201412377

Abstract

Optically active vicinal diamines are versatile chiral building blocks in organic synthesis. A soft Lewis acid/hard Brønsted base cooperative catalyst allows for an efficient stereoselective coupling of N-alkylidene-α-aminoacetonitrile and ketimines to access this class of compounds bearing consecutive tetra- and trisubstituted stereogenic centers. The strategic use of a soft Lewis basic thiophosphinoyl group for ketimines is the key to promoting the reaction, and aliphatic ketimines serve as suitable substrates with as little as 3 mol % catalyst loading.

Keywords: Mannich reaction; asymmetric catalysis; copper; ketimines; nitriles.