An efficient and highly enantioselective total syntheses of MS-153 and manzacidin C are described. Synthetic efforts have led to the development of silicon Lewis acid promoted [3+2] cycloadditions of acylhydrazones with methallyl ethers along with the development of a new silane reagent. MS-153 was synthesized in three steps from the acetylaldehyde derived hydrazone in 70% overall yield and in ≥98% ee. A rapid and highly stereoselective synthesis of manzacidin C was achieved from an isopropyl glyoxylate derived N-acyl hydrazone in six steps, 94% ee, >15:1 dr, and 26% overall yield. An unexpected stereochemical switch was observed in the key silver triflate mediated cycloaddition leading to the hypothesis of a chiral hexacoordinate silicon transition state. This new avenue of reactivity led to the development of an enantioselective Friedel-Crafts cycloadditions of 2-pyridylbenzoylhydrazones. Absolute stereochemical proof of the substrates led to an adjustment in our stereochemical model of hexacoordinate silicon intermediates involving 2-pyridine as the Lewis basic binder.
|Advisor:||Leighton, James L.|
|School Location:||United States -- New York|
|Source:||DAI-B 71/02, Dissertation Abstracts International|
|Keywords:||Acylhydrazones, Manzacidin, Silicon Lewis acids|
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