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

Abstract

A convenient additive-free synthesis of dihydro-4H-1,2-oxazines via a Cloke−Wilson-type ring expansion of the arylsubstituted 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.

[3+3]-Annulation of Cyclic Nitronates with Vinyl Diazoacetates: Diastereoselective Synthesis of Partially Saturated [1,2]Oxazino[2,3-b][1,2]oxazines and Their Base-Promoted Ring Contraction to Pyrrolo[1,2-b][1,2]oxazine Derivatives

“…The literature provides limited data on the preparation of pyrrolo[1,2- b ]oxazine derivatives [ 78 , 79 ], especially possessing an unsaturated pyrrole core [ 80 , 81 ]. Therefore, we elucidated the scope of the found transformation.…”

Cloke–Wilson rearrangement: a unique gateway to access five-membered heterocycles

“…4 Mostly, vinyl, carbonyl, imine, and alkylidene substituents are introduced to enhance the reactivity of cyclopropanes. 1,5 The substituted cyclopropanes undergo ring-opening/cyclization reactions to generate five-membered heterocycles, such as vinylcyclopropane to cyclopentene, 6 cyclopropyl-carbonyls to dihydrofurans, 7 cyclopropylimines to pyrroline, 8 and cyclopropyl thioketones to dihydrothiophenes. 9 Neureiter was the first chemist to report the synthesis of dichlorocyclopentene by the thermal rearrangement of dichlorovinylcyclopropane above 400 °C.…”

“…23,72–74 In 1947, Wilson reported the thermal rearrangement of cyclopropylcarbaldehyde to dihydrofuran. 7 a Besides its application in the synthesis of diverse heterocycles, 24 this rearrangement is also involved in the total synthesis of various natural products. 25 The [3 + 2] cycloaddition reaction of cyclopropanes with aldehydes results in the synthesis of furans, 26 a but the synthetic route to the furan moiety via the rearrangement of cyclopropyl ketone is a highly efficient and cost-effective protocol.…”

Deoxygenative Arylation of 5,6-Dihydro-4H-1,2-oxazine-N-oxides with Arynes

“…5,6-Dihydro-4 H -1,2-oxazines can be prepared via several synthetic routes (Scheme a), among which [4+2] cycloaddition of nitrosoalkenes (NSA) with electron-rich olefins, cyclization of γ-halooximes, and electrophile-induced cyclization of γ,δ-unsaturated oximes are most commonly used. , Very recently, some new methods emerged, namely, a Cloke–Wilson-type ring expansion of cyclopropyl oximes, asymmetric Pd-catalyzed carboetherification of γ,δ-alkenyl oximes, intramolecular iridium-catalyzed O-allylation of oximes, and electrochemical intermolecular [2+1+3] annulation . However, both conventional and new methods are used to prepare 1,2-oxazines having substituents at positions C-3 and C-6, while the introduction of substituents at positions C-4 and C-5 is challenging.…”