Jean-Pierre Demoute

Copper-Free Sonogashira Coupling of Cyclopropyl Iodides with Terminal Alkynes

The substrate scope of the copper-free Sonogashira coupling has been successfully extended to cyclopropyl iodides, allowing an efficient access to a wide variety of functionalized alkynyl cyclopropanes.

A Sonogashira cross-coupling/5-exo-dig cyclization/ionic hydrogenation sequence: synthesis of 4-substituted 3-azabicyclo[3.1.0]hexan-2-ones from 2-iodocyclopropanecarboxamides.

A variety of 4-substituted 3-azabicyclo[3.1.0]hexan-2-ones have been prepared from 2-iodocyclopropanecarboxamides by a three-step sequence involving a copper-free Sonogashira coupling with terminal aryl- or heteroarylalkynes, followed by a 5-exo-dig cyclization and an ionic hydrogenation.

Efficient Synthesis of Substituted 3‐Azabicyclo[3.1.0]hexan‐2‐ones from 2‐Iodocyclopropanecarboxamides Using a Copper‐Free Sonogashira Coupling

The copper-free Sonogashira coupling between N-substituted cis- 2-iodocyclopropanecarboxamides and terminal aryl-, heteroaryl-alkynes or enynes, followed by 5-exo-dig cyclization of the nitrogen amide onto the carbon-carbon triple bond, provides a remarkably efficient access to a variety of substituted 4-methylene-3-azabicyclo[3.1.0]hexan-2-ones in excellent yields. Protonation of these latter enamides generates bicyclic N-acyliminium ions that can be involved in Pictet-Spengler cyclizations leading to new 3-azabicyclo[3.1.0]hexan-2-ones, possessing a quaternary stereocenter at C4, with high diastereoselectivities. This strategy constitutes an attractive complementary alternative to the classical route that relies on the addition of organometallic reagents to cyclopropyl imides.

Synthesis of Functionalized Alkylidenecyclopropanes by Ireland–Claisen Rearrangement of Cyclopropenylcarbinyl Esters

Glycolates or glycinates derived from diversely substituted secondary cyclopropenylcarbinols have been involved for the first time in an Ireland-Claisen rearrangement. This reaction allows an efficient and stereoselective access to highly functionalized alkylidenecyclopropanes possessing an α-hydroxy or α-amino acid subunit, which in turn are valuable precursors of substituted cyclopropanes by diastereoselective hydrogenation of the exocyclic alkene.

Synthesis of Alkylidene(gem-Difluorocyclopropanes) from Propargyl Glycolates by a One-Pot Difluorocyclopropenation/Ireland–Claisen Rearrangement Sequence

A one-pot difluorocyclopropenation/Ireland-Claisen rearrangement sequence applied to readily available propargyl glycolates was developed as a route toward functionalized alkylidene(gem-difluorocyclopropanes). This strategy conveniently avoids the isolation of the unstable 3,3-difluorocyclopropenylcarbinyl glycolates arising from the difluorocyclopropenation. The Ireland-Claisen rearrangement proceeds with high diastereoselectivity and chirality transfer to afford alkylidene(gem-difluorocyclopropanes) incorporating a quaternary stereocenter and a protected glycolic acid moiety, which are useful building blocks for the preparation of functionalized gem-difluorocyclopropanes.

[3,3]-Sigmatropic Rearrangement of Cyclopropenylcarbinyl Cyanates: Access to Alkylidene(aminocyclopropane) Derivatives

Cyclopropenylcarbinyl cyanates, generated in situ by dehydration of the corresponding carbamates, underwent an efficient and stereoselective [3,3]-sigmatropic rearrangement leading to the corresponding alkylidene(isocyanatocyclopropanes), which could be converted into various alkylidene(aminocyclopropane) derivatives in a one-pot manner. This transformation complements the repertoire of sigmatropic rearrangements involving cyclopropenylcarbinol derivatives and in particular, the previously reported Overman rearrangement of cyclopropenylcarbinyl trichloroacetimidates.