One Lump or Two? A Plurality of Pathways in Gold(III)-Catalyzed Cyclization Transforming Propargyl Acetates to a Carene-like Bicyclo[4.1.0]heptane

The
bicyclo­[4.1.0]­heptane substructure, featured in a number of
natural products, is economically formed via gold­(III)-mediated cycloisomerization
of a 5-acetoxy-1,6-enyne. This Ohloff–Rautenstrauch rearrangement
takes place with high regio- and stereocontrol and purportedly proceeds
through either of two pathways that differ in the order of major events:
cyclization followed by ester migration (“cyclization first”)
or its transpose (“migration first”). Implicit solvent-phase
(dichloroethane) electronic structure calculations [IEFPCM-B2PLYP-D3/def2-TZVP//IEFPCM-B2PLYP/6-31G­(d)-LANL2DZ]
aimed at elucidation of the minimum energy pathway corresponding to
the “cyclization first” and “migration first”
pathways are presented herein. Both pathways feature multiple steps
and are characterized by low-energy barriers, indicating that facile
interconversion of structures on the surface is possible. In addition,
the highest-energy structures for each of the two pathways are very
close in energy (ΔΔE⧧ < 3.0 kcal/mol). Relative turnover frequency (TOF) and degree
of TOF control (XTOF) calculations indicate
that although a cyclization first pathway may dominate, both cyclization
and acyl migration processes influence the rate of this reaction.