Vicinal stereocenters via asymmetric allylic alkylation and Cope rearrangement: a straightforward route to functionally and stereochemically rich heterocycles

Abstract

An asymmetric allylic alkylation/Cope rearrangement (AAA/[3,3]) capable of stereoselectively constructing vicinal stereocenters has been developed. Strategically integrated 4-methylation on the 3,3-dicyano-1,5-diene controls stereoselectivity and drives Cope rearrangement equilibrium in the...

Pd-Catalysed asymmetric allylic alkylation of heterocycles: a user's guide

“…More recently, Grenning and co-workers reported the enantioselective allylation of piperidine-derived alkylidene malonitriles via a Pd-AAA/Cope rearrangement sequence (Scheme 45C). 54 The authors used 1,3-disubstituted allylic partners to form the corresponding enantioenriched 1,5-dienes through a kinetic resolution process, which relied on the Pd-AAA with ( S , S )-DACH-Ph ( L1 ). They also showed that the presence of a methyl substituent on the allyl partner was critical for the Cope rearrangement to proceed.…”

“…In their report on the enantioselective allylation of piperidine-derived alkylidene malonitriles, 54 Grenning and co-workers also investigated the transformation of bicyclic prochiral piperidine scaffolds, such as tropanes (Scheme 46B). On these systems, the Pd-AAA step delivered a 50 : 50 mixture of two diastereoisomers.…”

Palladium-Catalyzed Allylation of Endocyclic 1-Azaallyl Anions

“…However, this method requires multistep operation in one pot, and the aggregation of organolithium reagents in etherate solvent brings significant difficulty to achieve this reaction enantioselectively . Although transition-metal-catalyzed allylation has been extensively studied on various structural motifs, its utilization on the synthesis of 3-allyl cyclic amines remains rare . Very recently, the Stoltz group reported the tandem dearomatization/enantioselective allylic alkylation of pyridines (Scheme b) .…”