2‐Trifluoroacetyl‐1‐methoxycycloalkenes: A convenient precursor for the synthesis of geminated polymethylene trifluoromethyl substituted heterocycles

Abstract

This article describes the methodology that allows the simultaneous introduction of a trifluoromethyl group and a 7-, 8-, and 10-membered cycloalkane ring fused to heterocyclic derivatives. A series of 10 geminated polymethylene trifluoromethyl substituted isoxazolines, pyrazoles, pyrimidinones, and a pyrazolyl-quinoline were obtained in moderate to good yields from the reaction of three 2-trifluoroacetyl-1-methoxycycloalkenes derived from cycloheptanone, cyclooctanone, and cyclododecanone with hydroxylamine hydrochloride, hydrazine hydrochloride, urea, and 7-chloro-4-hydrazinoquinoline.

Regioselective Preparation of Saturated Spirocyclic and Ring-Expanded Fused Pyrazoles

“…Saturated bicyclic pyrazoles are typically prepared by the Knorr condensation of a hydrazine derivative with a 1,3-dicarbonyl compound − ,− (Scheme a) or an equivalent substrate. ,− Alternative procedures involve variations of the 1,3-dipolar cycloaddition (Scheme b). − ,− The main drawback of these methods lies in the often laborious preparation of the required starting materials, which can limit the available functionality in the product and precludes the late-stage introduction of structural diversity. In addition, some saturated heterocyclic systems have been noted to give unexpected rearrangement products under Knorr condensation conditions …”