Alkenes are common platforms for a variety of synthetically useful reactions. One particularly important mode of reactivity is olefin activation with electrophilic halogens;however, few of these transformations may be performed enantioselectively at this time. To address this deficiency, a method of asymmetric olefin activation by an activated complex of a planar-chiral heterocycle catalyst and a cationic halogen is proposed. Enantioselective functionalization of a number of simple alkene substrates will enable the synthesis of several bioactive target molecules relevant to public health, including cytoxazone (cytokine modulator), pleurotin (antibacterial, anticancer), prostaglandins (human hormones), the pumiliotoxin core (amphibian toxin), and a glucocorticoid receptor agonist (asthma, rheumatoid arthritis). Physical organic mechanistic studies will be employed to develop and improve the reactivity and selectivity of the catalyst, In addition to the explicit applications of the proposed transformations to the synthesis of bioactive molecules, this method will enable the synthesis of a wide variety of enantioenriched building blocks useful for a variety of synthetic purposes.
This proposal describes several related methods to transform common alkenes into valuable stereochemically defined products. These reactions will be useful for the laboratory preparation of many medicinally relevant substances that are otherwise difficult to access. Several specific examples of the application of these reactions in the synthesis of important bioactive molecules are described, including cytoxazone (cytokine modulator), pleurotin (antibacterial, anticancer), prostaglandins (human hormones), pumiliotoxins (amphibian toxins), and a glucocorticoid receptor agonist (asthma, rheumatoid arthritis).
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