Bart Herlé, PhD student under the supervision of Prof. Antonio M. Echavarren (ICIQ), has defended his PhD Thesis entitled “Stereoselective Cyclopropanation via Gold(I)-Catalyzed retro-Buchner Reactions” (assigned to the Organic and Analytical Chemistry Department of the Universitat Rovira i Virgili) publicly on May 16th at the ICIQ Auditorium.
The members of the evaluation committee were: Prof. Mar Gómez Gallego (Universidad Complutense de Madrid), Prof. Rubén Martín (ICIQ) and Prof. Syuzanna Harutyunyan (University of Groningen)
The formation of aryl gold(I) carbenes from 7-substituted cycloheptatrienes via a retro-Buchner reaction has recently emerged as a safe and versatile alternative to decomposition of diazo compounds. However, the carbene formation takes places at high temperatures, which puts a limit on its application. This thesis summarizes the work done to overcome this drawback and enhance the versatility of this transformation.
Free carbenes can be generated from light-induced decomposition of 1H-cyclopropa[l]phenanthrenes, which bear great resemblance to the norcaradiene tautomer of cycloheptatriene. Therefore, the propensity to form gold(I) carbenes via the retro-Buchner reaction of phenanthrene derivatives was investigated, albeit without finding significant improvements over the cycloheptatriene derivatives.
The formation of vinyl gold(I) carbenes from 7-alkenyl cycloheptatrienes takes place at significantly lower temperatures. Based on this observation, a highly cis-selective olefin cyclopropanation reaction has been developed, affording vinylcyclopropanes and vinyl-aminocyclopropanes in moderate to good yield. The 7-alkenyl cycloheptatriene derivatives can be formed in a single step from aldehydes and ketones by a novel Julia-Kocienski reagent.
The mechanisms of the gold(I)-mediated retro-Buchner, cyclopropanation, and epimerization reactions for vinylcyclopropanes have been studied experimentally and computationally, which led to the development of an advanced stereochemical model for gold(I)-catalyzed cyclopropanation reactions.
Owing to the mechanistic insights, and the improved strategy for the synthesis of cycloheptatriene reagents, a sterically encumbered cycloheptatriene derivative was developed, which allows the formation of gold(I) carbenes at room temperature, paving the way for a broad-scope enantioselective cyclopropanation reaction.