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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Computational Exploration of Anomalous Regioselectivities in Cycloadditions of Ketenes to Oxazolines
Ledong Zhu1, Mark A Maskeri1, Melissa Ramirez1
1Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.
Abstract:
Thermal (2 + 2) cycloadditions of several N-carboalkoxy (R)-2-tert-butyldihydrooxazoles with ketenes have been studied experimentally by the Ghosez group. Contrary to results from Seebach and co-workers that the electrophilic addition of acylating agents occurs β to dihydrooxazole nitrogen, Ghosez found major cycloadducts resulting from an attack of ketene carbonyl carbon β to oxygen. We investigate the potential energy surface for the cycloaddition of diphenyl- and phenylchloroketenes to two (R)-2-tert-butyldihydrooxazoles with ωB97X-D and mPW1PW91 density functional theory and DLPNO-CCSD(T) wave function theory. These (2 + 2) cycloadditions are concerted but highly asynchronous, and the selectivity trends in ketene addition cases are in good agreement with the experiment. We propose a model based on the buildup of charge in oxazoline to reconcile the regiochemical differences between Ghosez and Seebach's observations.
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