Asymmetric Synthesis of Substituted Pyrans by Enantioselective Intramolecular [2+2+2] Cyclization of Yne‐enones

Comprehensive Summary Substituted pyrans are prevalent structural motifs in natural products and bioactive molecules, and their enantioselective synthesis remains an important objective in organic chemistry. Herein, we report a rhodium(I)‐catalyzed enantioselective intramolecular [2+2+2] cyclization of yne‐enones for the efficient construction of chiral substituted pyrans. Using a commercially available SDP ligand, this transformation proceeds under mild conditions and exhibits good substrate scope, delivering bicyclic pyran derivatives in moderate to good yields with excellent enantioselectivities (up to 98% ee). The transformation proceeds via Rh(I)‐mediated oxidative cyclization to form a chiral rhodacycle, followed by carbonyl insertion and reductive elimination to deliver the pyran scaffold. The synthetic utility of this methodology is further demonstrated by a one‐pot cyclization/hydrolysis sequence. Treatment of the in situ generated pyran intermediates with Sc(OTf)₃ enables efficient conversion to optically enriched 1,5‐diketones bearing two contiguous stereocenters, with high enantioselectivity and moderate diastereoselectivity. Control experiments support a stepwise process involving pyran formation followed by Lewis acid‐promoted ring opening. Overall, this work provides an efficient and versatile strategy for the asymmetric synthesis of substituted pyrans and related chiral 1,5‐dicarbonyl compounds. The combination of high enantioselectivity, operational simplicity, and broad applicability highlights the potential of this methodology for applications in complex molecule synthesis and asymmetric catalysis.