Enantioselective Intermolecular Murai-Type Alkene Hydroarylation Reactions

Abstract

Strategies that enable the efficient assembly of complex building blocks from feedstock chemicals are of paramount importance to synthetic chemistry. Building upon the pioneering work of Murai and co-workers in 1993, C–H-activation-based enantioselective hydroarylations of alkenes offer a particularly promising framework for the step- and atom-economical installation of benzylic stereocenters. This short review presents recent intermolecular enantioselective Murai-type alkene hydroarylation methodologies and the mechanisms by which they proceed.1 Introduction2 Enantioselective Hydroarylation Reactions of Strained Bicyclic Alkenes3 Enantioselective Hydroarylation Reactions of Electron-Rich Acyclic Alkenes4 Enantioselective Hydroarylation Reactions of Electron-Poor Acyclic Alkenes5 Enantioselective Hydroarylation Reactions of Minimally Polarized Acyclic Alkenes6 Conclusion and Outlook

A directed enolization strategy enables by-product-free construction of contiguous stereocentres en route to complex amino acids

“…More broadly, our study is important because enantioselective C(sp 3 )-H additions to alkenes are achieved by exploiting 'native' directing functionality. This has a clear parallel to Murai's seminal ortho-directed alkene hydroarylations 49 , a report that ignited the field of metal-catalysed C(sp 2 )-H functionalization, and has led to an emerging family of by-product-free enantioselective cross-couplings 50 . Our laboratory is now focused on developing a complementary set of C(sp 3 )-H-based cross-couplings by harnessing the design principles outlined here.…”

Directing Group Repositioning Strategy Enabled Site- and Enantioselective Addition of Heteroaromatic C–H Bonds to Acyclic Internal Alkenes

“…This pioneering breakthrough has spurred the subsequent development of the catalytic addition of C–H bonds to alkenes using a variety of transition-metal catalysts . Because tertiary benzylic stereocenters are ubiquitous in drugs, agrochemicals, and bioactive compounds, recent efforts have been directed to the development of the enantioselective Murai-type reactions . These atom- and step-economical synthetic protocols nicely complement the classical methods for the installation of alkyl groups to arenes such as the Friedel–Crafts reaction, radical addition, or prefunctionalization of the arenes, where they suffer from limitations including reaction efficiency, substrate scope, and product selectivity. , Through the innovation of catalytic systems, branch and enantioselective hydroarylation of terminal alkenes has begun to emerge recently …”

Ir-Catalyzed Distal Branch-Selective Hydroarylation of Unactivated Internal Alkenes with Benzanilides via C–H Activation along with Consecutive Isomerization

“…Among the methods used for alkene transformation, metal-catalyzed C–H addition to alkenes has been proven to be a powerful strategy for the transformation of organic molecules. , The influential work by Murai on the C–H hydroarylation of vinyl silanes led to significant advances in the transformation of alkenes . Despite extensive investigations, the site-selectivity of the hydrofunctionalization of alkenes remained challenging . In 2012, our group successfully controlled the regioselectivity in the cationic iridium-catalyzed hydroarylation of terminal alkenes with indole derivatives and achieved the selective synthesis of branched and linear isomers, respectively .…”