Regio- and Stereo- selective Methods for the Borylation of Substituted Alkynes

Abstract

Organoboron derivatives represent an important class of compounds due to the versatility of the carbon-boron bond in a variety of chemical reactions. Boron-containing compounds have garnered increasing attention as synthetic intermediates and medicinal agents. Therefore, the introduction of carbon-boron bonds to organic molecules continues to be an important field of study. This dissertation describes novel methodology for the regio- and stereo-selective introduction of carbon-boron bonds to generate β-borylacrylonitrile and 1-boryl-1,3-enyne products. Propiolonitriles are intriguing research targets due to the electron-withdrawing nature of the cyano group on the adjacent alkyne. In this dissertation, we developed a phosphine-catalyzed regio- and stereo-selective hydroboration of propiolonitriles to generate novel β-borylacrylonitriles in up to 89% yield and 97:3 (E)-selectivity. These products were converted to the corresponding postassium 1,2-vinylcyanotrifluoroborate salts and demonstrated applications in oxidation and Suzuki-Miyaura cross-coupling reactions. Interestingly, 31P and 13C NMR studies suggest that this hydroboration reaction proceeds in a 1,2-phosphine addition pathway instead of a canonical 1,4-conjugate addition pathway. We also developed a transition metal-free cis hydroboration of 1,3-diyne substrates. In the presence of catalytic amounts of tri-n-butylphosphie and the unsymmetric diboron reagent pinBBdan, 1-boryl-1,3-enyne products were generated in up to 63% and >99:1 (Z)-selectivity. These 1,8-diaminonaphthalene products can be converted to the corresponding pinacolboranes or trifluoroborate salts. They also demonstrated applications in protodeboronation and Suzuki-Miyaura cross-coupling reactions. We propose that this hydroboration occurs via a nucleophilic boron addition mechanism.