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 orthohydrogen 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.

An efficient and chemoselective method to generate arynes

“…Finally, we compared the compatibility of functionalized nitrones with 1b and other basic conditions (NaO t -Bu or K 2 CO 3 ), 10 H ,11 i or other aryne precursors ( 4 and 5 ). The functionalized nitrones included those with an acetanilide 2g , terminal alkyne 2h , and boronate ester 2i (Scheme 7 and Table 2).…”

“…8 As such, onium groups have the potential to activate a proton in the ortho -position for deprotonation with a relatively weak and mild base ultimately leading to arynes (Scheme 1b). The use of onium leaving groups to generate arynes has been known for some time, 9 and although recent advances include more robust synthetic protocols and expanded scope, 10 they still require relatively strong bases ( e.g. NaO t -Bu or LiHMDS).…”