Synthesis of Highly Functionalized Bismacycles via Post-Transmetallation Modification of Arylboronic Acids

Abstract

Bismacycles featuring a sulfone-bridged scaffold have recently been developed as versatile and convenient electrophilic arylating agents. Here, we report that the exocyclic aryl group, which is ultimately transferred to a nucleophilic coupling partner, can be functionalized through cross-coupling, heteroatom substitutions, oxidations and reductions, and protecting group manipulations. This “postsynthetic modification” approach provides concise and divergent access to complex aryl bismacycles. The utility of the functionalized bismacycles in electrophilic arylation of C–H and O–H bonds is demonstrated.

Development and Scale-Up of a New Sulfone-Based Bismacycle as a Universal Precursor for Bi(V)-Mediated Electrophilic Arylation

“…Excellent chemoselectivity and functional group compatibility are achieved by using the bismacycle in a stoichiometric, telescoped fashion that temporally separates the oxidant from the transmetallating agent and the nucleophilic partner. The practicality of this strategy relies on the ready accessibility of aryl bismacycles 2 from a general, bench-stable bismacycle precursor 1-OTs via B-to-Bi transmetalation and benefits further from the ability to synthetically manipulate the aryl group following its installation at bismuth . Use of the bismacycle in a stoichiometric fashion is ultimately offset by its efficient recovery and recycling (as 1-X ; typically >90%).…”

“…The practicality of this strategy relies on the ready accessibility of aryl bismacycles 2 from a general, bench-stable bismacycle precursor 1-OTs via B-to-Bi transmetalation and benefits further from the ability to synthetically manipulate the aryl group following its installation at bismuth. 20 Use of the bismacycle in a stoichiometric fashion is ultimately offset by its efficient recovery and recycling (as 1-X ; typically >90%).…”