The Intramolecular Buchner Reaction of α-Diazo-β-Ketonitriles: Development and Application to the Total Synthesis of (+)-Salvileucalin B

Citation

Nani, Roger Rauhauser (2013) The Intramolecular Buchner Reaction of α-Diazo-β-Ketonitriles: Development and Application to the Total Synthesis of (+)-Salvileucalin B. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/2KGP-7X92. https://resolver.caltech.edu/CaltechTHESIS:06062013-031825238

Abstract

Since its discovery in 1896, the Buchner reaction has fascinated chemists for more than a century. The highly reactive nature of the carbene intermediates allows for facile dearomatization of stable aromatic rings, and provides access to a diverse array of cyclopropane and seven-membered ring architectures. The power inherent in this transformation has been exploited in the context of a natural product total synthesis and methodology studies.

The total synthesis work details efforts employed in the enantioselective total synthesis of (+)-salvileucalin B. The fully-substituted cyclopropane within the core of the molecule arises from an unprecedented intramolecular Buchner reaction involving a highly functionalized arene and an α-diazo-β-ketonitrile. An unusual retro-Claisen rearrangement of a complex late-stage intermediate was discovered on route to the natural product.

The unique reactivity of α-diazo-β-ketonitriles toward arene cyclopropanation was then investigated in a broader methodological study. This specific di-substituted diazo moiety possesses hitherto unreported selectivity in intramolecular Buchner reactions. This technology was enables the preparation of highly functionalized norcaradienes and cyclopropanes, which themselves undergo various ring opening transformations to afford complex polycyclic structures.

Finally, an enantioselective variant of the intramolecular Buchner reaction is described. Various chiral copper and dirhodium catalysts afforded moderate stereoinduction in the cyclization event.

Thesis Files