A Direct Catalytic Asymmetric Mannich-type Reaction to syn-Amino Alcohols

Abstract

The Mannich reaction is one of the most widely utilized chemical transformations for the construction of nitrogen-containing compounds. With the increasing occurrence of nitrogen in drugs and natural products, highly asymmetric variants of the Mannich reaction are desirable. In this communication, we report the application of our dinuclear zinc catalyst to a highly asymmetric Mannich-type reaction to generate syn 1,2-amino alcohols.

Catalytic Enantioselective Mannich Reactions

“…On the other hand, syn-selective catalytic asymmetric direct Mannich reactions of 2-hydroxy-acetophenone derivatives with a-imino esters using a dinuclear zinc catalyst were reported. 28 It was also disclosed that diastereo-and enantioselective Mannich reactions of activated carbonyl compounds with a-imino esters proceeded smoothly in the presence of a catalytic amount of a chiral Lewis acid derived from Cu(OTf) 2 and bisoxazoline (BOX) ligand (Scheme 6.11). 29 Catalytic enantioselective addition of nitro compounds to imines, 30 a-amination reactions of 2-keto esters, 31 Mannich reactions of malonates or b-keto esters with imines, 32 and Mannich reactions of glycine derivatives with imines 33 also proceeded under similar reaction conditions.…”

Silica-Supported Boric Acid with Ionic Liquid: A Novel Recyclable Catalytic System for One-Pot Three-Component Mannich Reaction

“…The results (Table 4 6 ], is an excellent catalytic system for Mannich reaction. Generally, excellent yields of Mannich products were obtained for a variety of aldehydes including those bearing an electronwithdrawing group (Table 4, entries 4,6,7,9). Some of the earlier reported methods were not capable of giving Mannich products from aldehydes substituted with -NO 2 group.…”

“…These improved methodologies are mainly based on two-component reactions where the imine as electrophile was pre-formed and reacted with stable nucleophiles such as enolates, enol ethers and enamines. [6][7][8][9][10][11][12][13] However, the preferable route is the use of a one-pot threecomponent setup rather than a two step that allows a wide range of structure variations. 14) Numbers of catalysts have been employed for classical Mannich reaction of aldehydes, ketones and amines mainly involving acids like proline, [15][16][17] p-dodecyl benzenesulphonic acid (DBSA) 18) and some Lewis acids.…”

Asymmetric Catalysis: An Enabling Science

“…The systems of both Shibasaki and colleagues (128) and Trost and Yeh (129) also perform well for the so-called nitoaldol reaction, wherein the active methylene partners are nitroalkanes. Furthermore, the nitrogen analog of the carbonyl partner, i.e., imines (a Mannich-type process), also serves as a suitable partner with these same catalysts (130,131). These ligands create proximal multisite catalysts in contrast to the more common single-site catalysts.…”