A novel asymmetric protonation of metal enolates is achieved via ligand-enabled asymmetric cooperative gold catalysis, leading to the efficient formation of versatile chiral cyclopentenones with good to excellent enantioselectivities. The prochiral cyclopentadienyl carbonate A – the precursor for the gold-catalyzed enantioselective protonation – is formed from enynyl carbonates via IPrAu+-catalyzed [3,3]-sigmatropic rearrangement and the Nazarov cyclization. In the presence of the chiral tertiary amino group-functionalized ligand L, A undergoes soft propargyl deprotonation of the dienyl carbonate by the tethered pendant tertiary amine moiety of the ligand, which is followed by decarboxylative elimination to form the gold enolate B. The observed enantioselectivity is attributed to the ligand, which features a chiral center at the C1-position of the ligand tetrahydroisoquinoline moiety. The steric shielding of the methyl group during the soft propargyl deprotonation step dictates that only one face of the basic nitrogen would be in close enough proximity to the substrate to be catalytically active. Rotation about the fluxional biphenyl axis would cause the nitrogen lone pair to be blocked by the methyl group and is therefore catalytically inactive. Subsequently, the proton transfer from the chiral quaternary ammonium group to the dienyloxy gold species occurs preferentially on one prochiral face, as outlined in the structure B, enabling asymmetric α-protonation. This rapid access to chiral cyclopentenones constitutes a two-step, one-pot method from acyclic precursors which can be prepared readily from commodity reagents.

Asymmetric synthesis of cyclopentenones via enantioselective protonation enabled by cooperative gold catalysis

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