Enantioselective Organocatalysis of Strecker and Mannich Reactions Based on Carbohydrates

Abstract

Efficient organocatalysts for enantioselective Strecker and Mannich reactions were constructed from glucosamine as a readily accessible chiral scaffold. A variety of aromatic aldimines were subjected to hydrocyanation with good to excellent yield (72-98 %) and, in part, high enantioselectivity (69-95 % ee). Influence of the catalyst architecture on the enantioselectivity obviously arises from restrictions imposed on the conformational flexibility of the monosaccharidic backbone. In the asymmetric Mannich reaction moderate yields (up to 76 %) and enantioselectivities (up to 58 % ee) have been achieved with the described catalyst.

Novel carbohydrate-based bifunctional organocatalysts for nucleophilic addition to nitroolefins and imines

“…First, commercial D-glucosamine was converted into the 1-azido-2-Nallyloxycarbonyl derivative 1 as previously described. 6 Next, Zemplèn O-deacetylation of glycosyl azide 1 provided 2, and the 3, 4, and 6-hydroxyls were suitably functionalised with various protecting groups, in order to modulate the polarity, the rigidity and the hydrogen-bonding ability of the saccharide scaffold, and to evaluate their influence on the behaviour of the resulting organocatalysts. Accordingly, the highly polar O-acetylated scaffold 1, and its deacetylated derivative 2, both suitable to act as hydrogen-bonding acceptors, were employed for the synthesis of organocatalysts 10 and 13, respectively.…”

“…To the best of our knowledge, there is only one report describing the use of D-glucosamine as starting material for the synthesis of a new class of bifunctional catalysts able to promote the Strecker and Mannich reaction with imines. 6 In this pioneering work Kunz et al explored the preparation of carbohydrate-based organocatalysts, where the monosaccharide effectively replaced the more frequently used 1,2-diamino cyclohexane scaffold and was the only stereocontrolling element present in the molecule.…”

“…Based on these considerations and inspired by the seminal work by Kunz et al, 6 we decided to investigate the synthesis of a new family of (thio)urea-amine organocatalysts, 10 where both catalytic residues were connected by an enantiomerically pure saccharide-based scaffold, as an alternative chiral skeleton to diamino cyclohexane (Fig. 1).…”

Preparation of new type of organocatalysts having a carbohydrate scaffold

“…Organocatalysts based on a D-glucosamine scaffold carrying urea and imine as catalytic functionalities were described by Kunz in 2007. 5 Enantioselective Strecker and Mannich reactions were performed using these catalysts. 5 Thiourea-amine type bifunctional organocatalysts containing a monosaccharide unit were prepared and their catalytic activities were investigated recently.…”

“…5 Enantioselective Strecker and Mannich reactions were performed using these catalysts. 5 Thiourea-amine type bifunctional organocatalysts containing a monosaccharide unit were prepared and their catalytic activities were investigated recently. 6 In these cases, the carbohydrate moiety was located on the periphery of the catalyst molecule and not in-between the two catalytic centers (compounds D and E, Figure 2).…”