A Designer Axially Chiral Amino Sulfonamide as an Efficient Organocatalyst for Direct Asymmetric anti-Selective Mannich Reactions and syn-Selective Cross-Aldol Reactions

✍ Scribed by Taichi Kano; Yukako Yamaguchi; Keiji Maruoka

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 365 KB
• Volume: 15
• Category: Article
• ISSN: 0947-6539
• DOI: 10.1002/chem.200900267

✦ Synopsis

Abstract

Amino sulfonamide catalyst: A distal proton of the axially chiral amino sulfonamide (S)‐1 realized the opposite diastereoselectivity in Mannich and cross‐aldol reactions compared with that observed in proline‐catalyzed reactions. The reactions catalyzed by (S)‐1 proceeded smoothly to give the anti‐Mannich and syn‐aldol adducts in excellent enantioselectivity (see scheme).magnified image

A direct asymmetric Mannich reaction using a novel axially chiral amino sulfonamide (S)‐3 that is highly anti‐ and enantioselective has been developed. For instance, in the presence of a catalytic amount of (S)‐3, the reactions between aldehydes and α‐imino esters proceeded smoothly to give anti Mannich products with a significantly higher anti/syn ratio and enantioselectivity than previously possible. By utilizing N‐Boc‐protected aromatic imines instead of α‐imino esters, the synthetically useful Boc protecting group and various aromatic or heteroaromatic substituents were installed into the anti Mannich products and consequently the substrate scope of the anti‐selective Mannich reaction and the synthetic utility of the anti Mannich products have been expanded. The axially chiral amino sulfonamide (S)‐3 has also been successfully applied to asymmetric direct cross‐aldol reaction between two different aldehydes. The catalyst (S)‐3 has the advantage of giving mainly syn products, whereas proline shows the opposite anti selectivity.