Enantioselective Cu-H catalyzed synthesis of cyclopropanes

Chiral cyclopropanes are compounds of interest in synthetic and medicinal chemistry as these are often found in biologically active molecules such as natural compounds and drugs. In this thesis, a new copper hydride-catalyzed cyclopropanation strategy enabled by a hydrocupration-alkylation sequence of bromocrotonate derivatives is presented. The starting materials required for this transformation are obtained via a general and convergent synthesis that starts from commodity chemicals and involves a common iodide-intermediate that undergoes different cross-coupling reactions to produce the functionalized allyl alcohols. The Appel reaction further converts these latter into the corresponding bromocrotonate derivatives. The cyclopropanation of these compounds proceeds with good generality and allows to access chiral cyclopropanes bearing aryl and alkyl substituents in good yields, complete trans-diastereoselectivity, and enantioselectivities up to 99:1 er.