Premium
Lithium Halomethylcarbenoids: Preparation and Use in the Homologation of Carbon Electrophiles
Author(s) -
Pace Vittorio,
Holzer Wolfgang,
De Kimpe Norbert
Publication year - 2016
Publication title -
the chemical record
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.61
H-Index - 78
eISSN - 1528-0691
pISSN - 1527-8999
DOI - 10.1002/tcr.201600011
Subject(s) - electrophile , carbenoid , nucleophile , reagent , carbanion , chemistry , combinatorial chemistry , lithium (medication) , heteroatom , carbon fibers , decomposition , organic chemistry , catalysis , materials science , ring (chemistry) , medicine , rhodium , composite number , composite material , endocrinology
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.