Enantioselective Intermolecular Crossed‐Conjugate Additions between Nitroalkenes and α,β‐Enals through a Dual Activation Strategy

Abstract

Double the fun: The title reaction was developed by using a Lewis base/iminium activation strategy (see scheme). The reaction proceeded with excellent yields and ee values, and the products were additionally transformed into a single enantiomer of a substituted pyrrolidine with excellent retention of configuration.

Additive Effects on Asymmetric Catalysis

“…The influence of trimethyl phosphite additive on the yield and enantioselectivity of the crossed-conjugate addition between nitroalkenes and enals was reported by Shi et al (Scheme ). The cross-coupling afforded the product in a rather low yield of 12% without any additive because the epimerization process of the stereogenic center adjacent to the nitro group was easy to occur. However, addition of (MeO) 3 P, the product was obtained with an improved yield of 64% and ee of 90%.…”

Asymmetric Organocatalysis and the Nitro Group Functionality

“…An intriguing reaction, whereby the nitroalkene is effectively used as the Michael donor, has been reported by Shi and co-workers (Scheme 27). 41 In this reaction, the prolinol 59 is used as a Lewis base, generating a nitronate that undergoes 1,4-attack onto the conjugated iminium ion (thus, the reaction has a dual activation). Irreversible βhydride elimination followed by reduction then gives the alcohol 60 in essentially a 1:1 diastereomeric ratio.…”

Iminium Activation in Catalytic Enantioselective Conjugate Additions

“…However, the diastereoselectivity ratio remained between 3 : 1 and 3 : 2, even though the catalyst was seen to be an excellent promoter of the same reaction with simple nitromethane. This diastereoselectivity problem when using substituted nitroalkanes was also found in the reaction shown in Scheme 6.12 [36]. This consisted of a crossed Michael reaction between a nitroalkene and an α,β-unsaturated aldehyde, in which the cooperative use of two different catalytic species capable of activating (independently) the nucleophile and the electrophile (dual activation strategy) was applied.…”