UC Irvine

Hydrofunctionalizations are an attractive method for functionalizing olefins, forging new bonds in an atom-economic and sustainable fashion. We developed a variety of Rh–H catalysts that can couple heteroatom nucleophiles with olefin coupling partners. Choice of bisphosphine ligands for the Rh catalysts is important for achieving selectivity when the hydrofunctionalization has many potential outcomes. In the first example, we developed an intermolecular anti-Markovnikov hydroamination of 1,3-dienes to form homoallylic amines. In this case, the regioselectivity of the hydroamination is under both catalyst and substrate control, since the choice of ligand and diene substitution pattern are both critical for anti-Markovnikov regioselectivity. Mechanistic studies highlight the importance of the carboxylic acid additive for achieving reactivity between the Rh catalyst and the amine nucleophile.In the second example, we developed a divergent hydrothiolation of cyclopropenes. Depending on the choice of bisphosphine ligand on the Rh–H catalyst, either direct hydrothiolation occurs to from cyclopropyl sulfide products, or ring-opening of the cyclopropenes occurs to form allylic sulfide products. Mechanistic studies suggest that the two reaction pathways share a common cyclopropyl-Rh(III) intermediate. Another way to form Rh–H intermediates is through the activation of aldehyde C–H bonds by a Rh catalyst. One pathway from this Rh–H intermediate is to cleave the aldehyde C–C bond through dehydroformylation and form an olefin. Given Rh’s ability to catalyze transfer hydrogenation reactions, we expand this dehomologation to primary alcohols. This oxidative-dehydroformylation cascade to dehomologate primary alcohols to olefins is enabled by the addition of N,N-dimethylacrylamide as a hydrogen acceptor. The use of different acceptors for dehydroformylation inspired a collaboration with Chevron Phillips, where we tried to find new conditions for dehydroformylation to make it amenable towards industrial scale chemical synthesis. Another reaction that takes advantage of Rh activation of aldehyde C–H bonds is hydroacylation, where aldehydes and olefins are coupled to form ketones in a direct and atom-economical manner. Our lab previously developed a dynamic kinetic resolution of aldehydes through intramolecular hydroacylation. A bulky primary amine co-catalyst was used to selectively racemize the aldehyde starting material over epimerizing the cyclopentanone product. By further activating the Rh catalyst through hydrogenation and employing acrylamides as the coupling partner, we extend this dynamic kinetic resolution of aldehydes through intermolecular hydroacylation. Future studies include exploring the substrate scope and determining the rate of racemization.