Ag-Catalyzed Asymmetric Mannich Reactions of Enol Ethers with Aryl, Alkyl, Alkenyl, and Alkynyl Imines

Abstract

An efficient catalytic and enantioselective method (up to >98% ee) for Mannich reactions between trimethylsilyl enol ethers derived from acetone and acetophenone and aryl, alkenyl, alkynyl, and alkyl imines is disclosed. A large variety of beta-amino ketones can be synthesized in the presence of 1-5 mol % AgOAc and an inexpensive and readily available amino acid-derived phosphine. All Ag-catalyzed asymmetric Mannich reactions can be run in undistilled THF and air. The o-anisyl activating groups of product amines can be removed in >70% isolated yield through a single vessel operation. The synthetic utility of the catalytic asymmetric method is illustrated by a four-pot synthesis of optically pure alkaloid (-)-sedamine.

Coupling Reactions Promoted by Silver

“…This transformation gave a b-aminoketone in 56% yield with enantiomeric excess higher than 98%. 39 Under similar conditions, the same authors were able to control two stereogenic centers in an asymmetric vinylogous Mannich reaction. Indeed, treatment of imines derived from aryl a-ketoesters with siloxyfuran under related conditions gave functionalized g-butenolides with high diastereo-and enantioselectivities (Scheme 10.21).…”

“…7d, 37 In related reactions, Snapper and Hoveyda et al reported an asymmetric version of Mannich-type reactions catalyzed by silver acetate. 38,39 Propargyl imines proved to be susceptible to nucleophilic addition of silylenol ethers derived from acetate esters in the presence of silver acetate and a ligand derived from an amino acid (Table 10.3). In this reaction,chiralb-aminoesterswere obtainedin highyieldandgoodenantioselectivity.…”

Aldol and Related Processes

“…25 Moreover, Hoveyda and coworkers have demonstrated that Mannich reactions between silyl enol ethers and aldimines are promoted by the chiral complex that was generated from AgOAc and an iso-Leu-derived phosphine ligand. 26 When the reaction was conducted with trimethylsilyl enol ether and aldimine in the presence of AgOAc, iso-Leu-derived phosphine ligand and 2-PrOH, the b-aminoketone was obtained with high enantioselectivity (Schemes 9.15 and 9.16).…”

A New Method for the Synthesis of Multisubstituted Pyrroles of Biological Interest by Double Nucleophilic Addition to α,β‐Unsaturated Imines

“…The PMP group was converted into an easily removable protecting group [10] at an earlier stage of the synthesis. We first attempted to replace the PMP group with an acetyl group, but the acetamide was obtained in only 5 % yield.…”