Catalytic Asymmetric Acylcyanation of Imines

Abstract

The less problematic acetyl cyanide can be used instead of toxic HCN for the highly enantioselective acyl‐Strecker‐type reaction. In the presence of an N‐benzylimine and a catalytic amount of Jacobsen's catalyst 1, the desired α‐amidonitrile is obtained in excellent enantioselectivity and yield.

One-Step Synthesis of Chiral Oxindole-type Analogues with Potent Anti-inflammatory and Analgesic Activities

“…Inspired by the bifunctional catalytic system-based asymmetric synthesis 16 17 18 , we rationalized that isatylidene malononitrile can be activated by two thiourea hydrogen atoms through weak hydrogen bonds. This can be achieved by the nucleophilic attack of enolate, which is promoted by the HOMO energy raised from the interaction between the tertiary amine moiety of catalyst and the carbonyl group of benzoylacetonitrile.…”

The First Catalytic, Enantioselective Aza‐Henry Reaction of an Unactivated Cyclic Imine

“…The exception is Itoh’s methodology for the allylation of dihydroisoquinoline13 and Ohsawa’s Mannich reaction on electron‐deficient dihydro‐beta‐carbolines14 which prima facie require no activation of the imine. The aza‐Henry reaction (Scheme , A ) employs nitromethane as nucleophile, a reagent with great potential as a replacement for cyanide in asymmetric Strecker‐like processes 15,16. Yet, beyond our recent report of the racemic addition of nitromethane to 3,4‐dihydroisoquinoline (DHIQ)17 the addition of nitromethane to cyclic imines (Scheme , B ) has not been shown beyond a racemic addition to activated isoquinoline18 and a recent addition to electron‐deficient trifluoromethyl ketimines 19…”

Organocatalysis in the Asymmetric Synthesis of Nitrogen-Containing Compounds: How and Why

“…High yields ranging from 80-96% and excellent eesupto97% were achievede mploying 5a with aw ide range of aromatic N-Boc imines. Some time after this first report, twon ew catalytic, intermolecular asymmetric Friedel-Crafts 44 reactions based again on the activation of imines with phosphoric acids of type 5 appeared. In both cases, indole wasc hosen as the nucleophilic reaction partner.I nt he first report, (Scheme 4, top) activated Ntosyl imines were found to undergo av ery efficient reaction with aseries of differently substituted indoles, using the phosphoric acid 5b bearing 1-naphthyl substituent as the Ar group.…”

“…[43] Shortly after,t wo different and more convenient cyanide sources based on simple organic molecules such as acetyl cyanide and acetone cyanohydrin were disclosed. Surprisingly,o nly in 2007 acetyl cyanide has been used for the first time in an organocatalytic asymmetric Strecker reaction, [44] in combination with the chiral thiourea derivative 8a (see Fig. 9) similar to the catalysts introduced by Jacobsen and co-workers for their Strecker reaction using HCN and the asymmetric hydrophosphonylation of imines.…”