Catalytic Anti-Markovnikov Hydroallylation of Terminal and Functionalized Internal Alkynes: Synthesis of Skipped Dienes and Trisubstituted Alkenes.

We have developed catalytic anti-Markovnikov hydroallylation of terminal and functionalized internal alkynes. In this article, we describe the development of the reaction, exploration of the substrate scope, and a study of the reaction mechanism. Synthesis of skipped dienes through the hydroallylation of terminal alkyl and aryl alkynes with simple allyl phosphates and 2-substituted allyl phosphates is described. The hydroallylation of functionalized internal alkynes leads to the formation of skipped dienes containing trisubstituted alkenes. We demonstrate that the hydroallylation of internal alkynes can be used in the regio- and diastereoselective synthesis of complex trisubstituted alkenes. A mechanism of the hydroallylation reaction is proposed, and experimental evidence is provided for the key steps of the catalytic cycle. Stoichiometric experiments demonstrate an unexpected role of lithium alkoxide in the carbon-carbon bond-forming step of the reaction. A study of the hydrocupration of internal alkynes provides new insight into the structure, stability, and reactivity of alkenyl copper intermediates, as well as insight into the source of the regioselectivity in reactions of internal alkynes.