Asymmetric Pd(II)-catalyzed Ring-forming Reactions

描述（由申请人提供）：手性杂环化合物通常表现出有趣的生物活性，并且通常在上市药品中发现。本研究的广泛目的是开发新的合成方法来制备手性杂环化合物，否则很难获得。本研究的第一部分涉及以C-H酸为亲核试剂的不对称Pd（ll）催化Sn2'取代前手性烯丙基三氯酰酸酯。随后，该方法将应用于以立体选择的方式制备高内酯C的连续四元立体中心。本研究的最后一部分将应用手性Pd(ll)-催化剂在级联反应中制备有用的杂环化合物。与公共卫生相关的许多新药在过去10年推出的单对映体药物上市。此外，许多这些化合物含有杂环结构。拟议的研究将为科学家，主要是制药工业的药物化学家，提供制备单对映异构体杂环化合物和发现新药的新合成工具。

DESCRIPTION (provided by applicant): Chiral heterocyclic compounds typically display interesting biological activity, and are commonly found in marketed pharmaceuticals. The broad aim of this research is to develop new synthetic methods for preparing chiral heterocyclic compounds that are difficult to access otherwise. The first part of this research involves the development of an asymmetric Pd(ll)-catalyzed Sn2' displacement of prochiral allylic trichloroimidates with C-H acids as nucleophiles. Subsequently, this methodology will be applied to prepare the contiguous quaternary stereocenters of Hyperolactone C in a stereoselective fashion. The final section of the proposed research will apply chiral Pd(ll)-catalysts in cascade reactions to prepare useful heterocyclic compounds. PUBLIC HEALTH RELEVANCE Many new pharmaceuticals introduced in the last 10 years are marketed as single-enantiomer drugs. Further, many of these compounds contain heterocyclic structures. The proposed research will provide scientists, primarily medicinal chemists in the pharmaceutical industry, new synthetic tools for the preparation of single-enantiomer heterocyclic compounds and for the discovery of new drugs.