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.