Cooperative Assistance in Bifunctional Organocatalysis: Enantioselective Mannich Reactions with Aliphatic and Aromatic Imines

Abstract

Hold them tight: Guided by X-ray structures, bifunctional thiourea catalysts containing an activating intramolecular hydrogen bond were redesigned. The new catalysts were used to effect a highly enantioselective Mannich reaction between malonates and both aliphatic and aromatic imines (see scheme; Boc=tert-butoxycarbonyl).

2.16 The Bimolecular and Intramolecular Mannich and Related Reactions

“…162 They reported the direct Mannich reaction of malonate with N-Boc aldimine to furnish the corresponding adducts with excellent enantioselectivities. A thiourea catalyst 84 was found to be the catalyst of choice for aldimines derived from aromatic aldehyde, and 85 was suitable for aldimines derived from aliphatic aldehydes.…”

Organocatalysis

“…15 The group found that catalysts that contain a rigid trans-1,2-aminoindanol scaffold and a urea group that activates the thiourea group through intramolecular hydrogen bonds (such as 9) promote the enantioselective Mannich reaction between malonates and both aliphatic and aromatic imines. This offers a useful direct route to a wide variety Scheme 9 of protected β 3 -amino acids.…”

Conformational properties and folding analysis of a series of seven oligoamide foldamers

“…1,2 Foldamers are generally considered as artificial models for molecular folding, 3 but they may also find use in enzyme-like functions, for example as biomimetic receptors 4 and catalysts 5,6,7 . The most common bond type in foldamers is the amide bond with directional and relatively stable hydrogen bonding properties.…”