title: Lithium Halomethylcarbenoids: Preparation and Use in the Homologation of Carbon Electrophiles.
abstract: α-Halomethyllithium carbenoids are useful homologating reagents which - reacting under proper reaction conditions as carbanions - enable the installation via nucleophilic addition of a reactive halomethyl fragment onto a preformed carbon-heteroatom bond. The pronounced thermolability represented - since seminal studies by Köbrich - the Achilles' heel of these reagents: the use of Barbier-type methodologies (i.e., the electrophile should be present in the reaction mixture prior to the formation of the carbenoid) was pivotal in order to suppress decomposition through α-elimination processes. Nowadays, the use of low temperatures (-78 °C) guarantees reliable procedures and, significantly, the employment of microreactor technologies allows external trapping to be performed even at higher temperatures as reported by Luisi. We will discuss the α-halomethyllithium-mediated homologations of a series of carbon electrophiles such as carbonyl compounds, imines, esters, Weinreb amides, and isocyanates.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14, A-1090, Vienna, Austria.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Pace
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14, A-1090, Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Holzer
authors.affiliation: Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering Ghent University, Coupure Links 653, B-9000, Ghent, Belgium.
authors.forename: Norbert
authors.initials: N
authors.lastname: De Kimpe
keywords: carbenoids; carbonyl compounds; homologation reactions; lithium; synthetic methods