Novel Multiple-Component X-C/C-C Formation Reactions

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DESCRIPTION (provided by applicant): This NIH R15 proposal is intended to develop novel X-C/C-C bond formation reactions and Diels-Alder cyclization using 1-iodo-3-siloxy-l,3-butadiene (Danishefsky-type diene). The asymmetric catalytic versions of these reaction will be investigated. These reactions can provide efficient approaches to numerous chemically and biologically important compound. For example, a novel lead structure made by the Pl's group has been found to be active toward colon cancer, non-small cell lung cancer and Melanoma as tested by NCI. In the past few years, the PI's group have obtained a substantial amount of preliminary results for the multiple-component X-C/C-C bond formation reaction. The asymmetric halo aldol reaction is the first asymmetric catalytic carbonyl addition of allenolates to aldehydes. Based on our preliminary results, the new asymmetric halo aldol reactions will be carried out by 1,4-robust activation and 1,2-tandem functionalization of alpha,beta-alkylenic ketones. New chiral phosphoramides and polymer beads-attached chiral phosphoramides are designed and will be synthesized as the Lewis base catalysts. Meanwhile, a series of chiral Lewis acid catalysts will be obtained and utilized to control the chirality for the halo aldol and Diels-Alder reactions. The 1,2-difuctionalization of alpha,beta-acetylenic ketones and esters will result in beta-halo Baylis-Hillman adducts which are multiple functionalized. The new catalysts and catalytic systems will result in high regioselectivity, stereoselectivity, chemoselectivity, as well as the scope of substrates for the new reactions. Besides the asymmetric catalysis, chiral p-toluene and tert-butanesulfinimines will also be utilized as the chiral auxiliaries and electrophiles for the novel X-C/C-C bond formation reactions. So far, the PI has trained 21 undergraduates, and fourteen of them achieved publications as co-authors. Most of these students have successfully entered medical or graduate schools in the US. In addition, 6 graduate students have been or are still being trained by PI's synthesis projects. This R15 grant application is very important for the PI to continue his teaching and research activities at Texas Tech.