Ni/Chiral Sodium Carboxylate Dual Catalyzed Asymmetric O-Propargylation

Abstract

A highly enantioselective O-propargylation catalyzed by combining a phosphine–nickel complex and an axially chiral sodium dicarboxylate has been developed. The transformation features mild reaction conditions, a broad substrate scope, and excellent functional group tolerance, offering an efficient approach to an array of enantioenriched O-propargyl hydroxylamines. Mechanistic studies support the presumed role of the chiral carboxylate as a counterion for nickel catalysis enabling the discovery of highly stereoselective transformations. The power of this reaction is illustrated by its application in the asymmetric total synthesis of potent firefly luciferase inhibitors and (S)-dihydroyashabushiketol.

Catalytic Asymmetric Benzylation of Azomethine Ylides Enabled by Synergistic Lewis Acid/Palladium Catalysis

“…In light of the subtle role that the leaving group played in the oxidative addition and enantioselectivity-controlling step, ,, we first investigated the reaction performance of rac -alanine-derived imine ester 1a with a range of activated 2-naphthalenemethanol derivatives under the dual-metal cooperative catalysis of 5 mol % Cu­(I)/( S , S p )- L1 [( S , S p )-Ph-phosferrorx] complexes and [Pd­(PPh 3 )] 4 in dichloromethane at room temperature (Table , entries 1–5). With acetyl-protected 2-naphthalenemethanol as the electrophilic precursor, no desired benzylated product was observed (Table , entry 1).…”

“…Gratifyingly, with a switch in the activated groups from acetyl to carbonate ( 2b and 2c ) or phosphate ( 2d and 2e ), the corresponding asymmetric benzylation/reduction could occur smoothly, affording the desired product 3a in good yield with different levels of enantioselectivity (Table , entries 2–5). The diverse enantioselectivity may be due to the leaving groups being the counteranion for the metal catalyst to affect the stereoselectivity . CO 2 Me-protected 2-naphthalenemethanol 2b was selected as the electrophilic precursor for further optimization in terms of the yield and ee.…”

Nickel-Catalyzed Asymmetric Propargylation for the Synthesis of Axially Chiral 1,3-Disubstituted Allenes

“…Since the pioneering study by Tsuji and Kawatsura, significant effort has been devoted to nickel-catalyzed APS reactions with excellent levels of enantiocontrol for introducing the internal alkyne functionality. Our group recently developed a straightforward method for nickel-catalyzed highly enantioselective APS reactions to afford enantioenriched O -propargyl hydroxylamines . However, the development of versatile and practical N -sulfonylhydrazone reagents as diazo precursors that are utilized in APS synthesis of the critical propargylic hydrazide motif via the stereoselective formation of a C–N bond is in high demand, and the corresponding product could be further converted to synthetically valuable allenes in a predictable and programmable manner.…”

Asymmetric O-Propargylation of Hydroxylamines via Ni/Chiral Sodium Carboxylate Dual Catalytic System

“…图式 1 镍催化不对称炔丙基化 Scheme 1 Nickel-catalyzed asymmetric propargylation 近年来, 中国科学技术大学合肥微尺度物质科学国 家研究中心郭昌课题组 [6][7] 利用镍参与的双催化体系在 不对称炔丙基化反应研究中做了很多突出工作. 最近, 该课题组 [8] 在最优反应条件下考察了底物适用范围(表 1). 该 反应体系具有良好的官能团兼容性.…”