Diversity-Oriented Synthesis of CF3-Functionalized Polycyclic Spiroisoxazolones via Organobase-Promoted Vinylogous
Ganesh Shantaram Khomane1, Chia-Chin Liu1, Chia-Yen Chang1
1Department of Chemistry, National Taiwan Normal University, 88, Sec. 4, Tingchow Road, Taipei 11677, Taiwan, R.O.C.
Abstract:
An organobase-controlled regiodivergent approach for the synthesis of CF3-containing polycyclic spiro-fused and -caged isoxazolone scaffolds is described. This is the first report demonstrating the reactivity of 4-alkylidene isoxazolones in VMA-based cascade reactions in combination with COCF3-tethered enediones. Additionally, the asymmetric variant of the spiro-fused isoxazolone scaffolds was also achieved using a bifunctional squaramide catalyst. Control experiments confirmed the reversibility and stability of the hemiketal and ketal groups in spiroisoxazolones. Gram-scale synthesis and derivatization further demonstrated the synthetic utility.
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