A synergistic gold/iron catalytic system was developed for sequential alkyne hydration and vinyl gold addition to aldehydes or ketones. Fe(acac)3 was identified as an essential co-catalyst in preventing vinyl gold protodeauration and facilitating nucleophilic additions. Effective C-C bond formation was achieved under mild conditions (r.t.) with excellent regioselectivity and high efficiency (1% [Au], up to 95% yields). Extending reaction scope to intramolecular fashion achieved successful macrocyclization (16-31 ring sizes) with excellent yields (up to 90%, gram-scale) without extended dilution (0.2 M), which highlighted the great potential of this new crossed-aldol strategy in challenging target molecule synthesis.
Keywords: Aldol reaction; gold catalysis; iron catalysis; macrocyclization; synergistic catalysis.