American Chemical Society
jo0c00531_si_002.cif (399.53 kB)

Accessing Dihydro-1,2-oxazine via Cloke–Wilson-Type Annulation of Cyclopropyl Carbonyls: Application toward the Diastereoselective Synthesis of Pyrrolo[1,2‑b][1,2]oxazine

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posted on 2020-05-07, 13:08 authored by Pankaj Kumar, Rakesh Kumar, Prabal Banerjee
A convenient additive-free synthesis of dihydro-4H-1,2-oxazines via a Cloke–Wilson-type ring expansion of the aryl-substituted cyclopropane carbaldehydes with the hydroxylamine salt is introduced. Comparatively less active cyclopropyl ketones also follow a similar protocol if supplemented by catalytic p-toluene sulfonic acid monohydrate. The transformation is performed in an open-to-air flask as it shows negligible sensitivity toward air/moisture. Dihydro-4H-1,2-oxazines when subjected to cycloaddition with the cyclopropane diester afford a trouble-free formulation of the valued hexahydro-2H-pyrrolo­[1,2-b]­[1,2]­oxazine derivatives. A cascade one-pot variant of this two-step strategy offers a comparable overall yield of the final product.