I. Enantioselective synthesis of (+)-zaragozic acid C. II. Nitridomanganese(V) complexes: design, preparation, and use as novel nitrogen atom-transfer reagents

Citation

Du Bois, Justin (1997) I. Enantioselective synthesis of (+)-zaragozic acid C. II. Nitridomanganese(V) complexes: design, preparation, and use as novel nitrogen atom-transfer reagents. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/ZK7H-DY11. https://resolver.caltech.edu/CaltechETD:etd-12022004-163242

Abstract

NOTE: Text or symbols not renderable in plain ASCII are indicated by [...]. Abstract is included in .pdf document. An enantioselective synthesis of the potent squalene synthase inhibitor (+)-zaragozic acid C is described. Zaragozic acid C constitutes one member of a family of natural products which possess a unique, highly functionalized 2,8-dioxabicyclo[3.2.1]octane core. An efficient route has been delineated which allows for the preparation of multigram quantities of this structural unit. Conversion of the bicyclooctane to the target molecule requires installing three carboxylic acids at C(8), C(9), and C(10), which has been accomplished by simultaneous oxidation of the corresponding tri-aldehyde. Additional highlights and supporting studies from this work include: (1) the use of [...] for the stereoselective reduction of ynones to trans enones; (2) an investigation of the diastereoselective dihydroxylation of [gamma]-alkoxy-[alpha,beta]-unsaturated ketones; (3) the effect of amine cosolvents on the nucleophilic addition of TMSC[...]CLi to a key dioxabicyclooctanone intermediate; and (4) stereospecific formation of the C(5) quaternary center by a chelation-controlled ketone addition reaction. The chemical transformations which have been developed should prove useful for the preparation of synthetic and semi-synthetic analogues of this important class of molecules. The design and preparation of novel nitridomanganese(V) Schiff base-derived complexes which function as nitrogen atom-transfer reagents for olefin amination has been described. X-ray crystallography has been employed to establish the structures of these unique [...] complexes, ORTEP figures of which are presented. The utility of these reagents has been demonstrated in reactions with silyl enol ethers and carbohydrate glycals to give [alpha]-amino ketones and 2-amino saccharides, respectively. Yields for these processes typically range from 60-80%, and, in all cases, the olefin starting material is employed as the limiting reagent. Moreover, the amine products isolated are conveniently protected as their N-trifluoroacetyl derivatives. Efforts to prepare additional reagents which display nitrogen transfer activity with unfunctionalized alkenes have led to the development of mild, efficient, and general protocols for the preparation of Mn[...]N systems. These complexes function competently as nitrogen transfer agents with styrene.

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