Abstract

Graphical Abstract by Bianca Bertolino

Cyclopropanes are characterized by high ring-strain energy and have been employed as useful building blocks in organic synthesis. The incorporation of a heteroatom donor substituent such as OH, OR, NR₂, or SR on the ring imparts enhanced reactivity. Hydroxycyclopropanes (cyclopropanols) in particular have been thoroughly studied due to their facile ring cleavage. Among several known methods, a new method for preparation of cyclopropanols involves dialkoxytitanacyclopropane-mediated cyclopropanation (the Kulinkovich cyclopropanation) of esters with Grignard reagent in the presence of titanium isopropoxide. The striking feature of this method is the facile formation of a three-membered ring from a simple Grignard reagent which acts as a 1,2-dicarbanion equivalent through a pivotal dialkoxytitana-cycloproapne intermediate. These reactions benefit from the availability of inexpensive reagents, ease of operation, and high selectivity for cis-dialkylcyclopropanols. This cyclopropanation reaction has since been extended to other carboxylic derivatives to provide convenient access to several heteroatom-substituted cyclopropanes. The objective of this chapter is to provide an updated, comprehensive coverage of the literature on the Kulinkovich cyclopropanation reaction and related processes. Key mechanistic issues are summarized.