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)
Dr. Herlé with his supervisor, Prof. Antonio M. Echavarren, and the evaluation committee
Abstract
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.