A gold-catalysed enantioselective Cope rearrangement of achiral 1,5-dienes

Abstract

Since the discovery of the Cope rearrangement in the 1940s, no asymmetric variant of the rearrangement of achiral 1,5-dienes has emerged, despite the successes that have been achieved with its heteroatom variants (Claisen, aza-Cope, etc.). This article reports the first example of an enantioselective Cope reaction that starts from an achiral diene. The new gold(I) catalyst derived from double Cl−-abstraction of ((S)-3,5-xylyl-PHANEPHOS(AuCl)2), has been developed for the sigmatropic rearrangement of alkenyl-methylenecyclopropanes. The reaction proceeds at low temperature and the synthetically useful vinylcyclopropane products are obtained in high yield and enantioselectivity. Density functional theory calculations predict that: (1) the reaction proceeds via a cyclic carbenium ion intermediate, (2) the relief of strain in the methylenecyclopropane moiety provides the thermodynamic driving force for the rearrangement and (3) metal complexation of the transition-state structure lowers the rearrangement barriers.

Toward a Symphony of Reactivity: Cascades Involving Catalysis and Sigmatropic Rearrangements

“…To date, these are the most prevalent examples of catalyst control in asymmetric all-carbon Cope rearrangements. [6b,11] A recent example from the Davies group in the context of natural product total synthesis is shown in Scheme 2. Asymmetric cyclopropanation of triene 4 followed by Cope rearrangement, with transfer of chirality generated cycloheptadiene 7 in good yield and high enantiomeric excess.…”

Gold(I)-Catalyzed Formation of Bicyclo[4.2.0]oct-1-enes

“…17 This reaction is driven thermodynamically by the relief of ring strain in the cyclopropylidene moiety. 18,19 In this paper, we extend the scope of this rearrangement to cyclic substrates like 1 (R = Me, Ph) with the goal of using alkylidene cyclopropane strain release to access medium sized carbocycles, 20–22 which suffer from their own strain (Scheme 1).…”

Chiral [2.2]paracyclophane-based NAC- and NHC-gold(I) complexes

“…As demonstrated by Gagn e et al [8], the dinuclear PCPsubstituted gold complex delivers the best enantiomeric excess in Cope rearrangements. Thus, another target was the synthesis of a dinuclear NAC gold complex.…”

“…These complexes were used for the domino cyclization/nucleophile addition reactions of enynes in the presence of water, methanol, or electronrich aromatic derivatives, but the results concerning this reaction using the famous PhanePhos ligand were unsatisfactory. In 2012, however, Gagn e published a gold-catalyzed Cope rearrangement where the highest yield and enantiomeric excess were found for the PhanePhos ligand [8]. Both these innovative first investigations in homogeneous gold catalysis were conducted with PCPphosphane ligands.…”