The Kulinkovich Cyclopropanation of Carboxylic Acid Derivatives

Abstract

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.

Modern Developments in the Chemistry of Homoenolates

“…The use of cyclopropanols and homoenolates in natural product and pharmaceutical synthesis has previously been reviewed. [9,108] This section will highlight selected applications of homoenolate reactivity towards the synthesis of complex targets, as well as the recent use of electrophilic homoenolates in synthesis.…”

Palladium-Catalyzed 2-(Neopentylsulfinyl)aniline Directed C-H Acetoxylation and Alkenylation of the Arylacetamides

“…Exploring alkenylation of 2-(neopentylsulfinyl)-arylacetamides 3, 8j, 8k, and 8q we wondered whether 1-substituted cyclopropanols 18 could be employed in this reaction as a source of functionalized vinyl ketones 19. Cyclopropanols are easily available from esters by means of the Kulinkovich reaction [20] and under the palladium catalysis, undergo smooth transformation to enones in the presence of an oxidant. [21] Successfully employed in the rhodium-catalyzed reactions, [22] cyclopropanols have never been utilized as coupling partners in C-H functionalization under the palladium catalysis.…”

Carbocyclic Amino Ketones by Bredt's Rule‐Arrested Kulinkovich–de Meijere Reaction

“…[a] Reagents and conditions: Ti(Oi-Pr)4 , c-C 5 H 9 MgBr,THF, rt. [a] Reagents and conditions: Ti(Oi-Pr)4 , c-C 5 H 9 MgBr,THF, rt.…”