Highly Enantioselective Direct Aldol Reaction Catalyzed by Organic Molecules

Abstract

We have demonstrated that a new class of l-proline-based organic compounds catalyzed the direct aldol reaction between aldehydes and acetone to provide beta-hydroxy ketones in good yields. The reaction is efficient, and 5-10 mol % of the catalyst and excellent enantioselectivities (97-99% ee) were obtained in both aromatic and aliphatic aldehydes. The presence of a gem-diphenyl group at the beta-carbon is necessary for high enantioselectivity.

Novel Prolinamide‐Supported Polystyrene as Highly Stereoselective and Recyclable Organocatalyst for the Aldol Reaction

“…[4b] has been reacted with commercial (2S)-2-amino-1,1,2-triphenylethanol (4) in the presence of ethyl chloroformate [14] to afford the corresponding prolinamide derivative 5. Secondly, due to the presence of a styrenic moiety in its structure, 5 can be promptly linked to a commercially available mercaptomethyl-functionalized polystyrene (1% cross-linked with DVB, spherical beads, particle size 100-200 mesh) via a radical reaction in the presence of AIBN.…”

Enantioselective Aldol Reactions of Aliphatic Aldehydes with Singh’s Catalyst

“…There are only few studies where aldol reactions between two aliphatic aldehydes have been described [2][3][4][5][6][7][8][9][10][11][12][13][14]. In these reactions different amino acids [9], especially L-proline and its derivatives [15][16][17][18], diarylprolinols [11,14] and imidazolidinones [5], have been used as catalysts. Singh et al designed an L-proline based chiral catalyst with a gemdiphenyl group at the β-carbon, which is essential for high enantioselectivities [17].…”

“…In these reactions different amino acids [9], especially L-proline and its derivatives [15][16][17][18], diarylprolinols [11,14] and imidazolidinones [5], have been used as catalysts. Singh et al designed an L-proline based chiral catalyst with a gemdiphenyl group at the β-carbon, which is essential for high enantioselectivities [17]. So far, this catalyst has been used in aldol reactions only between an aldehyde and a ketone [19][20][21][22][23][24][25].…”

“…Since aldehyde oxygen forms hydrogen bonds with the NH and OH groups of catalyst 1, the new C-C bond is formed from its Re face [17]. The thermodynamically favorable E-enamine is mainly formed by giving syn-aldol products [27].…”

Hydroxy-L-prolines as asymmetric catalysts for aldol, Michael addition and Mannich reactions

“…High activity and enantioselectivity were observed for prolinamide derivatives with chiral auxiliaries. 23,[33][34][35][36] Another thought was to exchange the carboxylate group with other functional groups. An improvement in the activity and stereoselectivity was observed in many cases.…”