N-Prolinylanthranilamide Pseudopeptides as Bifunctional Organocatalysts for Asymmetric Aldol Reactions

Abstract

Proline anthranilamide-based pseudopeptides were shown to be effective organocatalysts for enantioselective direct aldol reactions of a selection of aldehydes with various ketones with excellent yield, enantioselectivity up to 99% and anti to syn diastereoselectivity up to 25:1.

Various Polar Tripeptides as Asymmetric Organocatalyst in Direct Aldol Reactions in Aqueous Media

“…Barbas and co‐worker studies showed that the simple L ‐prolinamide with the acidic nature of the –CONH proton is less, therefore it is an ineffective catalyst for the aldol rection . To overcome this problem a range of prolinamide derivatives including di‐ and tri‐peptides were developed to be excellent catalysts for asymmetric transformation . Synthetic peptides have the advantage of designable modularity, are readily available, and they are made up from the same chiral building blocks (amino acid residues) as enzymes.…”

Prolinamide‐Catalysed Asymmetric Organic Transformations

“…designed bifunctional pseudopeptides N ‐prolinylanthranilamide for direct asymmetric aldol reaction. The anthranilic acid core represents a very convenient template for structural motif, in the present case modification of the carboxylic acid by incorporation of an amino acid residue, which was found to be excellent organocatalyst for aldol reaction of 4‐nitrobenzaldehyde 10 with cyclohexanone 11 and anti aldol product 13 was obtained with (9:1) dr and 99% ee (Scheme ) …”

“…Pearson and Panda synthesised a series of N ‐prolinylanthranilamide pseudopeptides using L ‐proline and anthranilic acid core unit as organocatalysts for asymmetric aldol reaction of isatin with acetone. These organocatalysts also applicable for a variety of isatin derivatives and acetone to afforded corresponding aldol product in high yield and good enantioselectivity (Scheme ) …”

“…The anthranilic acid core represents a very convenient template for structural motif, in the present case modification of the carboxylic acid by incorporation of an amino acid residue, which was found to be excellent organocatalyst for aldol reaction of 4-nitrobenzaldehyde 10 with cyclohexanone 11 and anti aldol product 13 was obtained with (9:1) dr and 99% ee (Scheme 27). [60] Fotaras et al described the asymmetric aldol reaction in the presence of prolinamide bearing (1 S, 2 S)-diphenylethylenedi-amine and thiourea groups, anti-aldol product was obtained in a quantitative yield and high stereoselectivities (97:3 dr and 99% ee) (Scheme 28). [61] Considerable effect of the acid additive (4-nitrobenzoic acid) was encountered for both yield and enantioselectivity.…”

Stabilization of the transition structures of organocatalytic asymmetric direct aldol reaction in wet solvent free condition by the formation of water assisted supramolecular network: A DFT study

“…In this context, huge efforts have been made to modify L-proline and 4-hydroxy-L-proline to prepare organocatalyst for aqueous medium asymmetric aldol reaction. Primarily, three types of modifications on the basic skeletons of L-proline and 4-hydroxy-L-proline were reported [29][30][31][32]. Carboxylic acid moiety of L-proline, hydroxyl group of 4-hydroxy-L-proline individually or both groups simultaneously were reported to be modified in order to enhance the hydrophobicity of L-proline.…”