The first example of near-room-temperature α-arylation of benzo[ b]thiophenes is reported. The discovery rests on the observation of a switch in α-/β-regioselectivity at different loadings of Pd(dba)·CHCl in the coupling between benzo[ b]thiophene and 4-iodotoluene. We show that this unprecedented regioselectivity switch is driven by a Ag(I)-mediated C-H activation at the α-C-H position, which becomes the dominant mode of reactivity at low concentrations of Pd. Competition experiments, kinetic studies, KIE, and D/H scrambling experiments have been carried out supporting this mechanism.

Piperidine scaffolds are present in a wide range of bioactive natural products, and are therefore considered as highly valuable, privileged synthetic targets. In this manuscript, we describe a gold-catalyzed annulation strategy that allows a straightforward assembly of piperidines and piperidine-containing azabridged products from readily available alkene-tethered oxime ethers (or esters) and N-allenamides. Importantly, we demonstrate the advantages of using oxime derivatives over imines, something pertinent to the whole area of gold catalysis, and provide relevant mechanistic experiments that shed light into the factors affecting the annulation processes. Moreover, we also describe preliminary experiments demonstrating the viability of enantioselective versions of the above reactions.

Aldehydes can be α-alkylated with allenamides by the combined action of an organocatalyst and a gold complex. The reaction requires the simultaneous generation of an enamine and a gold-activated allenamide. Importantly, by using a chiral amine as organocatalyst it is possible to obtain aldehyde products featuring all-carbon quaternary stereocenter at their α-position, with moderate to good levels of enantioselectivity.