Modern Developments in the Chemistry of Homoenolates

Abstract

Homoenolates are unique synthetic intermediates which display umpolung reactivity. Homoenolates and homoenolate equivalents like cyclopropanols have seen a recent surge in popularity due to their particular utility for accessing β‐functionalized carbonyl derivatives. This popularity has been enabled by the development of protocols for facile access to cyclopropanols and homoenolates from a variety of readily available starting materials. This microreview will highlight common strategies for generating cyclopropanols and metal homoenolates, as well as procedures for homoenolate functionalization, with a particular emphasis on protocols that have appeared after 2003. As an amphoteric molecule, two main reactivity modes have been established: the homoenolate reacts as a carbon nucleophile for β‐functionalization reactions and/or as a carbonyl electrophile, a strategy which has only emerged in the past few years. This microreview will highlight the use of homoenolates as convenient intermediates for accessing especially challenging motifs. The use of homoenolate chemistry in the context of natural product and pharmaceutical synthesis will also be presented.

Selective Carbon–Carbon Bond Cleavage of Cyclopropanols

“…4,5 More recently, transitionmetal-catalyzed C−C and C−X bond-forming reactions of cyclopropyl alcohols have been covered in an excellent review by Nikolaev and Orellana, 6 and the synthesis of cyclopropyl alcohols and their use in homoenolate chemistry has been covered by us. 7 Other reviews pertinent to sections of this review will be mentioned where relevant.…”

Creating Stereocenters within Acyclic Systems by C–C Bond Cleavage of Cyclopropanes

“…Stereodefined enantio- and diastereomerically enriched cyclopropanols are amphoteric molecules possessing two main reactivity modes through reaction as a carbon nucleophile or as a carbonyl electrophile. Several methods have been reported for the preparation of cyclopropanols, including the Kulinkovich reaction and copper-catalyzed enantioselective carbomagnesiation followed by stereoretentive oxidation of the resulting cyclopropylmagnesium species . To promote the selective ring opening, it was proposed that particular nucleophilic species are required.…”

Metal-Catalyzed Transformations of Cyclopropanols via Homoenolates

“…7 More recently, Mills and Rousseaux compiled an excellent review on modern chemistry of metal homoenolates, which was organized by the synthetic methods for homoenolates and their reaction modes. 8 Dai and coworkers summarized the utility of cyclopropanols and their transformations in the synthesis of complex natural products. 9 Le Bras and Muzart have reviewed Pd-catalyzed reactions of cyclopropanols along with cyclobutanols and cyclobutenols, many of which involve homoenolate intermediates.…”