BCl3 -Induced Annulative Oxo- and Thioboration for the Formation of C3-Borylated Benzofurans and Benzothiophenes

Abstract

BCl₃ -induced borylative cyclization of aryl-alkynes possessing ortho-EMe (E=S, O) groups represents a simple, metal-free method for the formation of C3-borylated benzothiophenes and benzofurans. The dichloro(heteroaryl)borane primary products can be protected to form synthetically ubiquitous pinacol boronate esters or used in situ in Suzuki-Miyaura cross couplings to generate 2,3-disubstituted heteroarenes from simple alkyne precursors in one pot. In a number of cases alkyne trans-haloboration occurs alongside, or instead of, borylative cyclization and the factors controlling the reaction outcome are determined.

Keywords: annulation; borylation; cross coupling; electrophilic cyclization; organoboranes.

Scheme 1

Borylative cyclization of substituted alkynes with B(C₆F₅)₃.

Scheme 2

Previous relevant borylative cyclization reactions and this work.

Figure 1

Trans‐haloboration of 1 with BCl₃. Top right, solid state structure of 2, thermal ellipsoids at 50 % probability and hydrogens omitted for clarity. Bottom, a previously reported alkyne trans‐haloboration.

Scheme 3

BCl₃‐induced borylative cyclization of 2‐alkynyl‐anisoles. Bottom right, solid state structure of 4 g, thermal ellipsoids at 50 % probability and hydrogens omitted for clarity. [a] 12 h. [b] 6 mmol scale to produce 1.16 g of 4 g. [c] Using non‐purified solvents under ambient atmosphere.

Scheme 4

Trans‐haloboration with strong electron‐withdrawing/bulky groups.

Scheme 5

Double BCl₃‐induced borylative cyclization.

Scheme 6

One pot borylative cyclization and Suzuki–Miyaura cross coupling.

Scheme 7

Borylative cyclization followed by demethylation/dehalogenation to form benzothienyl‐BCl₂ and then subsequent esterification.