Transition Metal Catalyzed Hydrofunctionalization of Alkynes via 1,2-Boronate Rearrangements

Abstract

Hydrofunctionalization of alkynes has emerged as a useful synthetic strategy to buildmolecular diversity from simple and commercially available starting materials. Utilizing transition metal catalysis different regio and stereochemical products can be synthesized, providing access to E-, Z-, and 1-1 disubstituted alkenes with high selectivity and broad functional group tolerance. Herein we describe two new selective transition metal catalyzed hydroalkylations of terminal alkynes, to form alkenes with valuable allylic functionality. The first reaction, described in chapter 1, is the hydroalkylation of terminal alkynes tofurnish E-allylic alcohols. This transformation proceeds through a highly regio- and diastereoselective hydrocupration followed by the addition of the reactive alkenyl copper species to an α-halo boronic ester. The proposed mechanism proceeds through the formation of a boron- ate species that undergoes a stereospecific 1,2-metalite shift to give the allylic boronic ester, which is oxidized with stereochemical inversion to the corresponding alcohol. This method also allows for the selective synthesis of chiral allylic alcohols, from enantioenriched α-halo boronic esters. Following this development, chapter 2 describes the synthesis of Z‐Michael acceptors viahydroalkylation of conjugated alkynes. The reaction proceeds through the formation of silver acetylide followed by the addition to an alkyl borane species to form the corresponding boron- ate. This undergoes a stereospecific 1,2-metalite shift, which provides the excellent Z-selectivity for the reaction. This method is the first reported Z-selective hydroalkylation of conjugated terminal alkynes. The reaction provides access to (Z)-α,β-unsaturated esters, amides and ketones, with broad functional group compatibility and tolerance for α-branched boranes, yielding products that are challenging to synthesize via other methods. Key to the development of this reaction was the use of weak inorganic bases. The low solubility of these bases in hydrocarbon solvents limits their effective concentration, suppressing undesired side reactions.