Modern Developments in the Chemistry of Homoenolates

• Published in: European journal of organic chemistry 2019-01, Vol.2019 (1), p.8-26
• Main Authors: Mills, L. Reginald, Rousseaux, Sophie A. L.
• Format: Article
• Language: English
• Subjects: Carbonyls; Chemical synthesis; Cyclopropane; Cyclopropanol; Homoenolate; Natural products; Organic chemistry; Synthetic intermediates; Umpolung reactions
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201801312

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. This microreview highlights recent strategies for the synthesis of homoenolates and cyclopropanols, as well as protocols for homoenolate functionalization, both as nucleophilic and electrophilic reagents. The unique reactivity and synthetic utility of metal homoenolates is further showcased in recent examples of their use in natural product and pharmaceutical synthesis.