Tempering the Reactivities of Postulated α‑Oxo Gold Carbenes Using Bidentate Ligands: Implication of Tricoordinated Gold Intermediates and the Development of an Expedient Bimolecular Assembly of 2,4-Disubstituted Oxazoles

2,4-Oxazole is an important structural motif in various
natural
products. An efficient modular synthesis of this structure has been
achieved via a [3 + 2] annulation between a terminal alkyne and a
carboxamide using a gold-catalyzed oxidation strategy. The postulated
reactive intermediate, a terminal α-oxo gold carbene, previously
known to be highly electrophilic and hence unlikely to be trapped
by stoichiometric external nucleophiles, is coerced to react smoothly
with the carboxamide en route to the oxazole ring by a P,N- or P,S-bidentate
ligand such as Mor-DalPhos; in stark contrast, often-used ligands
such as monodentate phosphines and N-heterocyclic carbenes are totally
ineffective. The role of these bidentate phosphines in this reaction
is attributed to the formation of a tricoordinated gold carbene intermediate,
which is less electrophilic and hence more chemoselective when reacting
with nucleophiles. The success in using bidentate phosphine ligands
to temper the reactivities of in situ-generated gold carbenes is likely
to open many new opportunities to apply oxidative gold catalysis to
the development of novel methods, and the implication of tricoordinated
gold intermediates in homogeneous gold catalysis should stimulate
further advances in gold catalysis.