Asymmetric Synthesis with Chiral Heteroalkyl Radicals

点击翻译按钮获取中文摘要

The Organic Synthesis Program supports Professor Philip P. Garner, of the Department of Chemistry of Case Western Reserve University, in his studies of the development of a new class of recyclable chiral auxiliaries for asymmetric synthesis with chiral heteroalkyl radicals. Prototype hydroxyalkyl radical equivalents contain a chiral acetal group derived from either carbohydrates or terpenes. General methods, including radical translocation, for the formation of chiral acetaloxyalkyl radicals are under development for the preparation of these materials. Systematic variation of the auxiliary structure, coupled with ab initio transition state structure modeling, addresses the nature of the interactions responsible for asymmetric induction and facilitates their optimization. Both inter- and intramolecular variants of atom/group transfer reactions as well as additions to carbon-carbon double bonds are explored, as is methodology to permit the efficient removal and reuse of the chiral auxiliaries. Bidirectional and iterative versions of asymmetric `radical aldol` reactions promise stereocontrolled access to 1,3-polyols. In contrast to the often well-defined chemistry of compounds containing even numbers of electrons, compounds containing an unpaired electron (radicals) are often so reactive that their reaction chemistry is difficult to harness. Lack of reaction control is a particular problem in the attempted synthesis via radicals of compounds displaying the property of chirality, wherein a molecule differs from another in the same way a right hand differs from a left. With the support of the Organic Synthesis Program, Professor Philip P. Garner, of the Department of Chemistry of Case Western Reserve University, is developing chemical approaches which allow the exploitation of the intrinsic reactivity of radicals while maintaining a high level of control over the chirality of the resulting products. These approaches offer new routes for the synthesis of biologically active compounds, which are often chiral.