Lithium/Element Exchange as an Efficient Tool for Accessing Atropo-enriched Biaryls via Arynes

Abstract

This account documents the development of transition metal-free, aryne-mediated aryl-aryl coupling, the 'ARYNE coupling', which began in 2001 in Lausanne. ortho,ortho'-Di-, tri- and even tetrasubstituted biphenyls have now become accessible on a multi-gram scale. The reaction is perfectly regioselective and the obtained polybromobiphenyls can be submitted to regioselective bromine/lithium interconversions. The access to enantiopure biphenyls is now possible using enantiopure sulfoxides as chiral auxiliaries, which allow for subsequent chemoselective sulfoxide/metal exchange on each atropo-diastereoisomer with configurational stability of the intermediate biaryllithiums. Direct atropo-diastereoselective ARYNE coupling has been reported more recently.

Transition‐Metal‐Free Heterobiaryl Synthesis via Aryne Coupling

“…In this context, Leroux et al reported an efficient transition metal free aryl‐aryl coupling protocol, the so‐called “Aryne coupling” reaction . Very recently, we extended the reaction to the construction of hetaryl‐aryl backbones, developing thus the “(Het)‐Aryne” version of the reaction (Scheme ) .…”

“…In this context, Leroux et al reported an efficient transition metal free aryl-aryl coupling protocol, the so-called "Aryne coupling" reaction. [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] Very recently, we extended the reaction to the construction of hetaryl-aryl backbones, developing thus the "(Het)-Aryne" version of the reaction (Scheme 1). [44] However, our study essentially focused on the thiophene ring as a model partner.…”

Enantiospecific Generation and Trapping Reactions of Aryne Atropisomers

“…Chirality at the molecular scale is a property of growing importance in chemical and physical sciences, as well as in medicine and technology. 10 Various additions to the electrophilic triple bond of ortho-arynes have largely been employed for the synthesis of chiral biaryls through the formation of the biaryl C(sp 2 )−C(sp 2 ) single bond, 1,8,9,11 and some helicenes have also been derived from arynes. 12,13 Recently, the palladium-catalyzed cyclotrimeriza-tion of rac-7,8- [5]helicyne (1, Figure 1b) was reported for the stereoselective syntheses of chiral nanographenes embedding up to six [5]helicene units.…”

“…Chirality at the molecular scale is a property of growing importance in chemical and physical sciences, as well as in medicine and technology . Various additions to the electrophilic triple bond of ortho -arynes have largely been employed for the synthesis of chiral biaryls through the formation of the biaryl C­(sp 2 )–C­(sp 2 ) single bond, ,,, and some helicenes have also been derived from arynes. , Recently, the palladium-catalyzed cyclotrimerization of rac- 7,8-[5]­helicyne ( 1 , Figure b) was reported for the stereoselective syntheses of chiral nanographenes embedding up to six [5]­helicene units. − rac -7,8-[5]­Helicyne ( 1 ) is an inherently chiral ortho -aryne, the first of its kind, and no enantioenriched inherently chiral aryne is known. Herein, we propose to extend the synthetic chemistry of arynes to chiral and enantioenriched aryne atropisomers 2 bearing a biaryl stereogenic axis vicinal to the reactive aryne triple bond (Figure b).…”