Enantioselective Mukaiyama–Michael Reaction of Cyclic α-Alkylidene β-Keto Phosphine Oxide and Phosphonate and Asymmetric Synthesis of (R)-Homosarkomycin

Abstract

The asymmetric Mukaiyama-Michael reaction of cyclic α-alkylidene β-oxo phosphates and phosphine oxides that proceeds in a highly enantioselective manner is described. It is possible to carry out these reactions using a catalytic amount of a bisoxazoline-Cu(II) complex without decreasing the enantioselectivity, and one of the products has been successfully used for the first enantioselective synthesis of (R)-homosarkomycin.

Recent Advances in Metal-Catalyzed Asymmetric 1,4-Conjugate Addition (ACA) of Nonorganometallic Nucleophiles

“…The Nakada group developed a similar system for the ACA of silyl enol ethers to cyclic α-alkylidene β-oxo imides using complex L90a –Cu­(OTf) 2 as catalyst (Scheme b). They further extended the application of this catalyst system to cyclic α-alkylidene β-oxo phosphates and phosphine oxides by using complex L90b –Cu­(II) as catalyst (Scheme c) . It is worth noting that the potential of this method was illustrated in the synthesis of ( R )-homosarkomycin.…”

Metal-Controlled Switching of Enantioselectivity in the Mukaiyama–Michael Reaction of α,β-Unsaturated 2-Acyl Imidazoles Catalyzed by Chiral Metal–Pybox Complexes

“…An asymmetric Mukaiyama–Michael reaction is one of the potential chemical tools for the synthesis of enantioenriched 1,5-dicarbonyls. Considerable attention has been devoted to the development of an asymmetric Mukaiyama–Michael reaction. , However, access to both enantiomeric 1,5-dicarbonyls via the Mukaiyama–Michael reaction using the same chiral ligand or organocatalyst is a noble approach, but remains a formidable challenge. In this context, Bernardi described the counterion induced reversal of enantioselectivity in the Mukaiyama–Michael reaction of 2-carbomethoxy cyclopentenone promoted by chiral bisoxazoline-Cu­(II) complexes .…”

Enantioselective Organocatalytic Michael Addition Reactions Catalyzed by Proline/Prolinol/Supported Proline based Organocatalysts: An Overview

“…Several catalysts such as proline scaffolds, thiourea, [5–7] acids, [8,9] bi‐functional organocatalysts, [10–12] alkaloids, [13,14] crown ethers, [15,16] metal complexes, [17–19] pyrrolidine, [20–22] and phase transfer catalysts [23–25] have made outstanding contributions for the preparation of enantiomerically enriched molecules. One such forerunner catalyst among them is mono‐functional proline‐based organocatalyst, especially diarylprolinol TMS ether (also known as Hayashi‐Jorgensen catalyst) and its analogs have been extensively used in one‐pot asymmetric Michael addition reactions.…”