Use of Silyl Glyoxylates in Tandem Vinylation/Brook Rearrangement/Adol Reactions

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DESCRIPTION (provided by applicant): Tandem reactions and multicomponent couplings have long been a desirable goal for organic synthesis, as they quickly and efficiently fashion complex molecules from simpler starting materials. The long term goal of this project is to devise diastereo- and enantioselective reactions that can be used in the synthetic design of natural products and pharmaceutically relevant building blocks. This proposal focuses on the generation of a,(3-dihydroxy, v-chiral carbonyl compounds from the domino reaction of silylglyoxylates, vinyl Grignard, and aldehydes. Specifically the strategy presented is to: i) examine induction of enantioselectivity by making a chiral silylglyoxylate via the ester functionality such as usage of 8-phenyl-menthol, valinol, and phenylalaninol; ii) examine induction of enantioselectivity via chiral Grignard ligands such as (-)-sparteine, trans- 1,2-diaminocyclohexane, and /V,A/-dimethylpseudoephedrine. iii) assess the potential for addition to prochiral aldehydes (e.g. tiglic aldehyde) followed by enantioselective hydroxyl-directed hydrogenation using cationic rhodium or iridium species; iv) utilize the aforementioned methodology in the most concise synthesis to date of the antifungal, phytotoxic natural product alternaric acid. A wide number of therapeutics are either natural products themselves or derived from natural products, most often with specific orientations (stereochemistry) of bonds and functional groups. This research aims to access portions of these would-be Pharmaceuticals in a succinct manner via assembly of multiple segments at one time, complete with stereochemical integrity. Through rapid construction of these components, potential medicines can be synthesized more quickly for further study.