Stereoselective Bromoboration of Acetylene with Boron Tribromide: Preparation and Cross-Coupling Reactions of ()-Bromovinylboronates.

The mechanism of acetylene bromoboration in neat boron tribromide was studied carefully by means of experiment and theory. Besides the -addition mechanism through a four-center transition state, radical and polar -addition mechanisms are postulated, both triggered by HBr, which is evidenced also to take part in the isomerization of the product. The proposed mechanism is well supported by calculations at the MP2/6-31+G* level with Ahlrichs' SVP all-electron basis for Br. Implicit solvation in CHCl has been included using the PCM and/or SMD continuum solvent models. Comparative case studies have been performed involving the B3LYP/6-31+G* with Ahlrichs' SVP for Br and MP2/Def2TZVPP levels. The mechanistic studies resulted in development of a procedure for stereoselective bromoboration of acetylene yielding mixtures of dibromo(bromovinyl)borane with the -isomer as a major product (up to 85%). Transformation to the corresponding pinacol and neopentyl glycol boronates and stereoselective decomposition of their -isomer provided pure ()-(2-bromovinyl)boronates in 57-60% overall yield. Their reactivity in a Negishi cross-coupling reaction was tested. An example of the one-pot reaction sequence of Negishi and Suzuki-Miyaura cross-couplings for synthesis of combretastatin A4 is also presented.