Synthesis of Halides via Hydroboration

Organic halides are important synthetic intermediates in numerous reactions. They are also important due to the variety of radiohalogen-containing pharmaceuticals that have been developed in recent years [1-3]. The trialkylboranes prepared via hydroboration are conveniently converted to alkyl halides when 1 equiv of sodium hydroxide or sodium methoxide in methanol is added to a mixture of 1 mol of organoborane and 1 mol of iodine. The reaction becomes instantaneous and affords the corresponding alkyl halides. A second mole of iodine and base react similarly (Eq. 13.1) [4-6], ljut the third alkyl resists the reaction under these conditions. 

These difficulties are circumvented to some extent for the synthesis of secondary alkyl bromides by the action of bromine, in dark conditions, on the B-alkyl-9-BBN derivatives (Eqs. 13.2, 13.3) [7]. 

It is interesting to note that the reaction does not proceed through a direct rupture of the boron-carbon bond, but involves a highly selective free radical substitution of the a-hydrogen of the sec-alkyl group by bromine. Protonolysis of the intermediate by hydrogen bromide gives the final product (Chart 13.1) [8]. 

B-Isopropyl-9-BBN is 5.5 times more reactive as compared with the a position in cumene and some 660 times more reactive than is the tertiary position 

The remarkable activation of sec-alkyl of B-sec-alkyl-9-BBN is attributed to the stabilization of the free radical, owing to the interaction of the odd electron with the vacant p orbital of boron atom [8]. Attack on the two a-bridgehead positions is less facile because in these positions the odd electron would necessarily occupy an orbital that is orthogonal to the vacant p orbital on boron. 

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