The dehydroformylation of aldehydes to generate olefins occurs during the biosynthesis of various sterols, including cholesterol in humans. Here, we implement a synthetic version that features the transfer of a formyl group and hydride from an aldehyde substrate to a strained olefin acceptor. A Rh(Xantphos)(benzoate) catalyst activates aldehyde C–H bonds with high chemoselectivity to trigger C–C bond cleavage and generate olefins at low loadings (0.3 to 2 mol%) and temperatures (22 to 80 °C). This mild protocol can be applied to various natural products and was used to achieve a three step synthesis of (+)-yohimbenone. A study of the mechanism reveals that the benzoate counterion acts as a proton-shuttle to enable transfer hydroformylation.

We report an enantioselective coupling between α-branched aldehydes and alkynes to generate vicinal quaternary and tertiary carbon stereocenters. The choice of Rh and organocatalyst combination allows for access to all possible stereoisomers with high enantio-, diastereo-, and regioselectivity. Our study highlights the power of catalysis to activate two common functional groups and provide access to divergent stereoisomers and constitutional structures.

In this article, we expand upon the catalytic hydrothiolation of 1,3-dienes to afford either allylic or homoallylic sulfides with high regiocontrol. Mechanistic studies support a pathway where regioselectivity is dictated by the choice of counter-ion associated with the Rh-center. Noncoordinating counter-ions, such as SbF 6 − , allow for η 4-diene coordination to Rh-complexes and result in allylic sulfides. In contrast, coordinating counter-ions, such as Cl − , favor neutral Rhcomplexes where the diene binds η 2 to afford homoallylic sulfides. We propose mechanisms that rationalize a fractional dependence on thiol for the 1,2-Markovnikov hydrothiolation while accounting for an inverse dependence on thiol in the 3,4-anti-Markovnikov pathway. Through the hydrothiolation of an essential oil (β-farnesene), we achieve the first enantioselective synthesis of (−)-agelasidine A.

By using tandem ruthenium-catalysis, internal alkynes can be coupled with aldehydes for the synthesis of β,γ-unsaturated ketones. The catalyst promotes alkyne transformations with high regioselectivity, with examples that include the differentiation of a methyl versus ethyl substituent on the alkyne. Mechanistic studies suggest that the regioselectivity results from a selective allene formation that is governed by allylic strain.

We report an enantioselective coupling between alkynes and indoles. A Rh-hydride catalyst isomerizes alkynes to generate a metal-allyl species that can be trapped with both aromatic and heteroaromatic nucleophiles.