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

Abstract

The mechanism of acetylene bromoboration in neat boron tribromide was studied carefully by means of experiment and theory. Besides the syn-addition mechanism through a four-center transition state, radical and polar anti-addition mechanisms are postulated, both triggered by HBr, which is evidenced also to take part in the Z/E isomerization of the product. The proposed mechanism is well supported by ab initio calculations at the MP2/6-31+G* level with Ahlrichs' SVP all-electron basis for Br. Implicit solvation in CH 2 Cl 2 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 E/Z mixtures of dibromo(bromovinyl)borane with the Z-isomer as a major product (up to 85%). Transformation to the corresponding pinacol and neopentyl glycol boronates and stereoselective decomposition of their E-isomer provided pure (Z)-(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.

Free Radical Isomerizations in Acetylene Bromoboration Reaction

“…Despite the theoretical drawbacks described, the radical mechanisms proposed in this work are consistent with available experimental data [ 9 ]. They thus offer a novel point of view on the mechanism of bromoboration and haloboration reactions and, in a wider context, on the isomerizations of substituted alkenes in general.…”

“…A 2013 joint experimental and theoretical study by Lawson et al reported the first successful haloboration/esterification of internal alkynes [ 8 ]. Finally, inspired by the previous work by Mazal and Vaultier [ 4 ], we concentrated on the stereoselective bromoboration of acetylene with boron tribromide as a route to ( Z )-Bromovinylboronates, with mechanistic studies supported by ab initio calculations [ 9 ].…”

“…In the latter study, we suggested—besides a syn -addition through a four-centered transition state—two other addition mechanisms yielding a thermodynamically more stable ( E )-isomer [ 9 ]. We further concentrated on the mechanism of Z / E -isomerization of the syn -adduct, ( Z )-dibromo(2-bromvinyl)borane, ( Z )- 1 , considering Wang and Uchyiama’s hypothesis of stereoconversion mediated by BBr 3 or HBr.…”

“…BBr 3 was taken for a catalyst of isomerization in many previous works [ 1 , 10 , 11 ]. Since BBr 3 -catalyzed isomerization with relatively high activation Gibbs energy (30 kcal mol −1 , [ 7 ]) did not apply under our experimental setup, but the catalytic effect of HBr was confirmed [ 9 ], we concentrated on understanding its mechanistic aspects. Knowing that, for the chloro-counterpart of ( Z )- 1 , a direct cis / trans isomerization and HCl-catalyzed conversion required as much as 55 and 45 kcal mol −1 , respectively [ 7 ], we analyzed several HBr-catalyzed mechanisms for ( Z )- 1 with a hope to establish a less-energy demanding route.…”

“…Thus, we concentrated on radical Z/E isomerization possibility. As formation of the vicinal isomer of dibromoethane in the reaction mixture indicated that HBr prefers a radical pathway for the addition to vinyl bromide in BBr 3 , we suggested a free radical mechanism of Z/E stereoconversion [ 9 ]. Several methodological questions arose, however, which were beyond the scope of our previous study; thus we formulate and respond them here: (1) Could our earlier MP2 radical isomerization reaction profiles be obtained at the DFT level of theory as well?…”