Haloboration of terminal alkynes

2 Cross-coupling of Organoboron Compounds with Organic Halides 

The addition of tribromoborane to acetylene first may give a cw-adduct, which then isomerizes to the /ram-isomer during its isolation. This two-step procedure is useful for achieving a formal carboboration of alkynes with a variety of organic groups. 

Haloboration of terminal alkynes yielded stereodefined (Z)-2-halo-l-alkenylboron compounds e.g., 114, 115 that allowed further functionalization of the resulting C-Br or G-B bond. 2,2-Disubstituted-l-alkenylboronic esters were stereoselectively obtained when the haloboration was followed by cross-coupling with 1-alkynylzinc chlorides (Equation (18)).192 The iodoboration-conjugate addition sequence gave alkenyl iodides that were used as intermediate for the total synthesis of deoxyepothilone derivatives (Equation (19)).193-195 

The haloboration-coupling sequence provided simple access to the stereochemically pure 3,3-disubstituted allylboron compounds 116 via one carbon homologation of the alkenylboron intermediates (Equation (20)).196 Bromoboration of allene afforded 117 which was converted into a tartrate for asymmetric allylboration (Equation (21)).197 

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The haloboration reaction of terminal alkynes has been recently demonstrated to provide useful synthetic procedures for various halogen derivatives, which will be discussed later. 

A most useful haloboration agents, B-bromo-9-borabicyclo[3.3.1]nonane and BBr3, react readily with terminal alkynes via Markovnikov syn addition of the Hlg-B moiety to the carbon-carbon triple bond in an uncatalyzed process. The haloboration reaction occurs regio- and chemoselectively at terminal triple bonds, but for other types of unsaturated compounds it is nonselective 639... 

Haloboration Reactions. The haloboration of carbon-carbon triple bonds provides another entry point for the synthesis of organoboranes. A wide variety of haloboranes including BBrs, 9-BBN-Br, and 9-BBN-l has been found to react with terminal alkynes to produce (Z)-2-halo-l-aIkenylboranes. The reaction occurs in a stereo-, regio-, and chemoselective fashion specifically with terminal alkynes and has been used to synthesize numerous substituted olefins and related compounds. Diboration reactions of alkynes with B2CI4 are also well known. However, more convenient transition-metal-catalyzed procedures with the less reactive aUcoxy substituted diboranes B2(OR)4 have recently been developed. 

Haloboranes add to terminal alkynes in a cis /in-Markovnikov manner however, the bromoboration of acetylene itself exceptionally provides a trans adduct [28] (eq (17)). A sequence of haloboration with boron tribromide and then cross-coupling with organozincs is useful for a formal carboboration of alkynes with various organic groups. Addition of boron triboromide to allene is convenient for the synthesis of (2-bromo-2-propeny])borate [29] (eq (18)). 

Stereoselective addition of B-Br across a terminal acetylene (haloboration) was first reported by Blackborow (66). Suzuki and coworkers examined the intermediate obtained from the haloboration of alkynes with B-bromo and 5-iodo-9-borabicyclo[3.3.1]nonanes for various organoborane reactions. Suzuki has reviewed the applications of haloboration for organic syntheses (67-69). A recent application involving the 1,4-addition of a halovinyl-9-BBN to methyl vinyl ketone (70) for the synthesis of a promising anti-cancer agent, 12,13-desoxyepothilone B due to Danishefsky and coworkers is shown in Figure 19 (77). 

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