Enantioselective Organocatalytic Conjugate Addition of Aldehydes to Nitrodienes

Abstract

The asymmetric organocatalyzed Michael addition of aldehydes to alpha,beta-gamma,delta-unsaturated nitro compounds has been accomplished using only 5 mol % of (S)-diphenylprolinol silyl ether and 2 equiv of aldehyde in a mixture of ethanol and water (5% v/v). The Michael adducts were obtained in good yields, diastereoselectivities up to 94/6, and ee's up to 99%. This process provides synthetically useful compounds which can easily lead to more complex molecules, as exemplified with substituted tetrahydropyran or cyclohexene.

Enantioselective Organocatalytic Michael Additions of Oxyacetaldehydes to Nitroolefins

“…[16] Alexakis described nitrodienes as acceptors in the addition of aldehydes and only 1,4-addition products have been obtained in high yields and with high enantioselectivities. [17] Michael addition of acetaldehyde, as the most reactive enolizable aldehyde, constitutes a special challenge. List solved this issue by slow addition of acetaldehyde to the nitroolefin and thus obtained good yields and enantioselectivities.…”

Direct Catalytic Asymmetric Doubly Vinylogous Michael Addition of α,β‐Unsaturated γ‐Butyrolactams to Dienones

“…[1,2] Recently,a symmetric organocatalysis has been successfully applied to the functionalization of unsaturated carbonyl compounds at their g-, d-, and e-positions with high stereo-and site-selectivity.…”

“…[6] In most studies as ingle vinylogous substrate,e ither the electrophilic or nucleophilic partner,w as used. [1,[3][4][5][6][7] In 2013 Jørgensen and co-workers reported the first organocatalytic doubly vinylogous Michael-type reaction, namely the 1,6-addition of alkylidene lactones to 2,4-dienals with the formation of an ew stereocenter (Scheme 1a).[8] It is significantly difficult to simultaneously activate the two vinylogous partners at their remote reactive sites whilst achieving high regio-, diastereo-, and enantiocontrol. Indeed, to the best of our knowledge there are no precedents for the catalytic, asymmetric doubly vinylogous Michael addition (DVMA) to 2,4-dienones,the much less reactive analogues of 2,4-dienals.…”

Enantioselective One‐Pot Organocatalytic Michael Addition/Gold‐Catalyzed Tandem Acetalization/Cyclization

“…Knowing the compatibility of amines and gold catalysts, [12] and our recent results on 1,4-additions of aldehydes to nitrodienes, [13] as well as goldcatalyzed transformations of functionalized alkynes, [14] we envisaged a one-pot process consisting of an enantioselective organocatalytic Michael addition of aldehydes 1 to nitroenyne 2, and a subsequent gold-catalyzed tandem acetalization/cyclization of the corresponding adduct 3 by electrophilic activation [3] of the triple bond. Herein we disclose our results on this one-pot reaction which leads to nitro-substituted tetrahydrofuranyl ethers 4 with high diastereo-and enantioselectivities (Scheme 1).…”