Synthesis of Heterocycles via Chemoselective Geminal Acylation of 2-Methoxyoxazolidines, E/Z Isomerization in the Metathesis of Allyl Alcohol Derivatives with a First-Generation Ruthenium Catalyst, and Interception of Nazarov Reaction Intermediates of Allenyl Vinyl Ketones with Arenes

Abstract

Heterocycles were prepared through the geminal acylation of 2-methoxyoxazolidines with 1,2-bis(trimethylsilyloxy)cyclobutene. It was found that when water was excluded from the standard reaction conditions, regioselectivity of the ring expansion step was reversed, resulting in preferential rupturing of the endocyclic C-O bond instead of the C-N bond. Further cyclization resulted in the generation of 6,5-fused ring systems. The aqueous procedure was found to be applicable to 1,2-bis(trimethylsilyloxy)cyclopentene, resulting in the analogous 6,6-fused ring systems, while the anhydrous procedure failed to promote ring expansion. Tricyclic 6,5,6-fused ring systems were obtained with meso-7,8-bis(trimethylsilyloxy)bicyclo[4.2.0]oct-7-ene using the anhydrous procedure, while the intermediate generated under aqueous conditions failed to undergo ring closing. Allylic alcohol derivatives were subjected to homodimerization in the presence of a first-generation ruthenium catalyst. Previous work suggested that thermodynamic equilibration to the E-isomer was not a significant process for first-generation catalysts. However, product E/Z ratios were, in general, observed to increase significantly over time. In addition, an atmosphere of ethylene promoted reversion to the terminal olefins, leading to rapid E/Z equilibration, albeit at the expense of yield. Brief exposure to ethylene over the course of reaction resulted in a high E/Z ratio in a moderate yield. A 6,6,5-fused ring system was synthesized via the tandem Nazarov cyclization-intramolecular Friedel-Crafts alkylation of the corresponding allenyl vinyl ketone. The presence of electron donating substituents on the arene, as well as a two-carbon tether linking the arene to the allenyl vinyl ketone, were crucial to the success of the reaction. The intermolecular trapping of an allenyl vinyl ketone with substituted arenes was also investigated. Trapping occurred primarily at the electronically preferred position a, while sterically encumbered substrates tended to trap preferentially at the less hindered position c. Surprisingly, 1,3,5-trisubstituted arenes trapped almost exclusively at position a, having overcome significant steric crowding, demonstrated by hindered rotation about the newly formed carbon-carbon bond.