American Chemical Society
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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

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journal contribution
posted on 2017-02-03, 22:29 authored by Jeremy M. Hines, Jesse J. Eason, Matthew R. Siebert
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.