Chiral Pyridoxal-Catalyzed Asymmetric Biomimetic Transamination of α-Keto Acids

Abstract

A series of chiral pyridoxals 8 and 9 have been developed from commercially available pyridoxine and (S)-α,α-diarylprolinols. The pyridoxals exhibited good catalytic activity in an asymmetric transamination of α-keto acids with 2,2-diphenylglycine (7f) as the amine source to give various α-amino acids in 29-85% yields with 53-80% ee's. The current asymmetric transamination has successfully mimicked a complete biological transamination process characterized by two half-transaminations, a small chiral pyridoxal molecule acting as the catalyst, and enantioselective control.

Enantioselective Carbonyl Catalysis Enabled by Chiral Aldehydes

“…Very recently,Z hao,Y uan and co-workers designed an ovel N-quaternized biaryl axially chiral pyridoxal catalyst 29 [19] based on previous developments [5a,b] and their interests in chiral pyridoxal catalyzed transformations (Scheme 8). [13] This biomimetic transformation provided the corresponding a,b-diamino acid ester products 28 in moderate to excellent yields,along with excellent diastereo-and enantioselectivities. This Mannich-type reaction featured av ery low catalyst loading (0.2-1 mol %), high catalytic efficiency, mild conditions and broad substrate scope.F or example,fused aromatic imine (for 28-A), heteroaromatic imines (for 28-B, 28-C)and multi-substituted phenyl imine (for 28-D)c ould undergo the Mannich-type reaction smoothly.I na ddition, a,b-diamino acid esters bearing potentially biologically active chiral moieties (e.g.…”

“…In 2015, Zhao and co-workers achieved biomimetic asymmetric transamination reactions of a-keto acids 17, catalyzed by chiral pyridoxal catalyst 20 (Scheme 4). [13] Va rious optically active a-amino acids 18 were obtained in moderate to good yields and enantioselectivities under mild Angewandte Chemie Kurzaufsätze conditions.For example,various aromatic substituted (for 18-A-18-C)a nd aliphatic substituted (for 18-D, 18-E) a-keto acids reacted smoothly in this reaction. Thea symmetric transamination of the chiral substrate (S)-4-(6-methoxynaphthalene-2-yl)-2-oxopentanic acid proceeded with excellent diastereocontrol (> 20:1 dr, 18-G).…”

Enantioselective Carbonyl Catalysis Enabled by Chiral Aldehydes

“…In 2015, Zhao and co‐workers achieved biomimetic asymmetric transamination reactions of α‐keto acids 17 , catalyzed by chiral pyridoxal catalyst 20 (Scheme ) . Various optically active α‐amino acids 18 were obtained in moderate to good yields and enantioselectivities under mild conditions.…”

“…Very recently, Zhao, Yuan and co‐workers designed a novel N ‐quaternized biaryl axially chiral pyridoxal catalyst 29 based on previous developments, and their interests in chiral pyridoxal catalyzed transformations (Scheme ) . This biomimetic transformation provided the corresponding α,β‐diamino acid ester products 28 in moderate to excellent yields, along with excellent diastereo‐ and enantioselectivities.…”

Aldehyde Catalysis: New Options for Asymmetric Organocatalytic Reactions

“…4 In nature, vitamin B6 bearing an aldehyde group can activate amino acids through a-functionalization, and it has been employed in a vast array of biochemical reactions. 5 Inspired by this biological process, synthetic chemists adopted this concept in the laboratory, and several biomimetic chiral pyridoxal analogs have been developed and employed in aldol reactions, 6 transaminations, 7 and Cope-type hydroaminations of allylic amines. 8 However, the development of efficient chiral aldehyde catalysts for the a-functionalization of primary amines is still a great challenge.…”