Organocatalytic Enantioselective Vinylogous Aldol Reaction of Allyl Aryl Ketones to Activated Acyclic Ketones

Abstract

The first catalytic asymmetric vinylogous aldol reaction of activated allyls to activated acyclic ketones is disclosed. A variety of activated acyclic ketones, such as trifluoromethyl ketones, α-ketoesters, and α-keto phosphonates, were found to be involved forming diverse γ-selective aldol adducts with high enantioselectivities (up to >99% ee). The method provides an effective, general strategy to access valuable chiral electron-withdrawing group-substituted tertiary hydroxyl-based carboxylic acids.

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

“…An initial catalyst screening was performed in dichloromethane, based on our previous experiences with this type of Michael additions [ 18 ]. We have employed a range of squaramide and thiourea organocatalysts C1 – C7 [ 18 , 27 – 34 ], as well as two newly synthesized binaphthol-squaramide catalysts ( S a ,R,R )- C8 , and ( S a ,S,S )- C8 ( Scheme 3 ). Results of the initial catalyst screening are summarized in Table 1 .…”

Lewis acid-catalyzed asymmetric reactions of β,γ-unsaturated 2-acyl imidazoles

“…T he exploration of reaction diversity from β,γ-unsaturated carbonyl compounds is interesting and of great synthetic value. These compounds and their analogs bearing one potential enolization have been demonstrated as highly active nucleophiles in a number of catalytic asymmetric reactions for the synthesis of natural products and bioactive compounds [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] . Especially, γ-addition as dienolate pronucleophiles with either metal catalysis [17][18][19][20][21][22][23][24][25][26][27][28] or organocatalysis [29][30][31][32][33][34][35][36] has been widely documented during the past several years, and the maintained πconjugation of γ-addition process leading to thermodynamically stable conjugated products (Fig.…”

Direct Catalytic Asymmetric Aldol Reaction of α‐Alkoxyamides to α‐Fluorinated Ketones

“…Surprisingly,t he direct catalytic enantioselective aldol reaction [3,4] engaging a-fluorinated ketones and a-oxygenated carbonyl compounds is little explored. [6][7][8][9] Whereas amides and carboxylic acids,w hich are regarded as more challenging aldol donor substrates in terms of reluctant enolization, have been incorporated in the direct aldol reaction manifold, [10] no enantioselective variants have been reported (Scheme 1b). [6][7][8][9] Whereas amides and carboxylic acids,w hich are regarded as more challenging aldol donor substrates in terms of reluctant enolization, have been incorporated in the direct aldol reaction manifold, [10] no enantioselective variants have been reported (Scheme 1b).…”

“…[5] Precedents of the direct catalytic asymmetric aldol reaction of a-fluorinated ketones using methyl ketones or acetaldehydes indicate that a-fluorinated ketones are sufficiently reactive in the aldol reaction, and the thus obtained tertiary alcohols are reluctant to undergo the undesired retro-aldol reaction (Scheme 1a). [6][7][8][9] Whereas amides and carboxylic acids,w hich are regarded as more challenging aldol donor substrates in terms of reluctant enolization, have been incorporated in the direct aldol reaction manifold, [10] no enantioselective variants have been reported (Scheme 1b). [11,12] Herein, we report an enantio-and diastereoselective direct catalytic aldol reaction of a-fluorinated ketones 2 and a-hydroxylated 7-azaindoline amides 1 (Scheme 1c).…”