A general mechanistic map of organocatalytic hydroboration of alkynes: polarity controlled switchable selective pathways

Abstract

Although organocatalytic hydroboration of alkyne has achieved a breakthrough in synthesis chemistry, understanding the possible mechanism, origin of regioselectivity and stereoselectivity of these kinds of reactions is still a challenging issue in this field. Herein, a general mechanistic map for phosphine-catalyzed hydroboration of alkyne with HBpin involving multiple intermediates and competing pathways has been systematically studied by using density functional theory (DFT). The calculated results show that the Lewis base PBu₃ can even nucleophilically attack on either the α- or β-carbon of different alkyne substrates, and always strengthens the nucleophilicity of the other carbon towards HBpin. Then, the regioselective hydroboration of alkyne for generating either an α- or β-isomer undergoes the competing 1,2-proton transfer (PT) or 1,2-borotopic transfer (BT) pathway, respectively. For the ynamide substrate, 2H₂O-assisted 1,2-PT pathway is more energetically favorable when compared with the 1,2-BT pathway, but the case is reversed for the propiolonitrile substrate. Further analysis revealed that the intrinsic polarities of the regioselective transition states could be responsible for this phenomenon, and the π conjugated interactions play a crucial role for controlling the stereoselectivity. The insights obtained are not only important for understanding the origin of regio- and stereoselectivity, but are also useful for guiding the design of the organocatalytic hydroboration of alkynes with special regio- and stereoselectivity.