Mechanistic Insights in Gold-Stabilized Nonclassical Carbocations: Gold-Catalyzed Rearrangement of 3-Cyclopropyl Propargylic Acetates

Abstract

The reaction of 3-cyclopropyl propargylic carboxylates with Au(I) and Au(III) catalysts affords selectively 5-(E)-alkylidenecyclopentenyl acetates via [3,3]-sigmatropic rearrangement of the carboxylic moiety followed by cyclopropyl ring opening and cyclization. DFT calculations have been performed, supporting a two-step no-intermediate mechanism along the cyclization coordinate. The stereoselective formation of the exocyclic alkenes is kinetically controlled in the first of these events. Although stereospecific in nature through a gold-stabilized nonclassical carbocation, the chirality transfer in these cyclopentannulations is not complete. Computational and experimental evidence is provided for a Au-promoted cyclopropyl ring opening/epimerization/ring closure in both cis- and trans-cyclopropyl settings, which competes with the cyclization event, thus eroding the stereochemical information transfer. When tertiary acetates were used, products of both 1,2- and 1,3-acyloxy migration processes could be isolated, supporting the competitive coexistence of these two pathways along the reaction profile, as suggested also by DFT calculations.

Gold‐Catalyzed Oxidative Ring Expansion of 2‐Alkynyl‐1,2‐Dihydropyridines or ‐quinolines: Highly Efficient Synthesis of Functionalized Azepine or Benzazepine Scaffolds

“…This could be followed by ring opening to furnish the azepine 2 (path b). [11,19] 13 may also be formed from 11 (path c).…”

Propargyl Claisen rearrangement: allene synthesis and beyond

“…Hence, substrates 87 and 89 accommodating the small-size ring directly bonded to the alkyne moiety were stirred with catalytic amounts of a gold catalyst at ambient temperature to deliver substituted cyclopentenes 88 and 90 in good yields and short periods of time (Scheme 24). 48 The domino process therefore included a [3,3]-sigmatropic rearrangement, a cyclopropyl ring opening and a cyclisation. A key to the success of the reaction was the presence of a substituent R that would aid in the delocalization of the d + generated upon cyclopropyl ring opening.…”

Gold‐Catalyzed Migrations and Ring Expansions

“…Although the cyclization process competes with a cyclopropyl opening/closure, which can erode the stereochemical information transfer from the starting material onto the final products, the reaction appears to be stereospecific in nature, so that enantiomerically enriched five-and six-membered rings could be obtained from the corresponding chiral starting materials as shown in Scheme 63 41,121 .…”