Oxidative cycloaddition reactions of arylboron reagents via a one-pot formal dehydroboration sequence

Abstract

Arylboron compounds are widely available and synthetically useful reagents in which the boron group is typically substituted. Herein, we show that the boron group and the ortho-hydrogen atom are substituted in a formal cycloaddition reaction. This transformation is enabled by a one-pot sequence involving diaryliodonium and aryne intermediates. The scope of arylboron reagents and arynophiles is demonstrated and the method is applied to the formal synthesis of an investigational drug candidate.

Oxidative Cycloaddition Reactions of Arylboron Reagents via a One-pot Formal Dehydroboration Sequence

“…As such, they are ubiquitous building blocks and act as nucleophilic components in a variety of useful metal-free and metal-catalyzed substitution reactions (Scheme a). − In most applications, boron-based functional groups act as an electrofuge departing without the C aryl B bonding pair of electrons (Scheme a), which is consistent with their C -nucleophilic character and results in ipso -substitution. Herein, we demonstrate that arylboron reagents can be used as the starting point for oxidative cycloaddition reactions with dienes and 1,3-dipoles and thereby expand the value of arylboron reagents in synthesis by affording both ipso- and ortho -functionalization of the ring (Scheme b) . The key to developing a formal cycloaddition reaction of arylboron reagents is the intermediacy of a highly reactive aryne via formal dehydroboration.…”