purity / 1,3-Dipolar cycloadditions / Methanamines, substituted / N-Oxides 389 stituent, contain a C-aromatic ring. In the present communication we report some of the results of this investigation'). Previously, we have been engaged in the preparation of a series of a novel class of antifungal agents, the cis/trans-5-substituted 3-aryl-3-[(1H)-imidazol-(or 1H-1,2,4-triazol)-l-ylmethyl]-2-methylisoxazolidines (7/8) '). The synthesis of 7/8 was accomplished by 1,3-dipolar cycloaddition reaction of a-substituted ketonitrones 5 with appropriate dienophiles (Scheme 1). The cycloaddition proceeded regioselectively under mild conditions, and the resulting cis/ trans diastereomeric mixture 7/8 was readily separated by flash chromatography on neutral silica gel. The a-substituted ketonitrones 5 were obtained in moderate to excellent yields by treating the corresponding 2-(I H-azol-1-y1)-I-phenylethanones 4 with Nmethylhydroxylamine hydrochloride in the presence of sodium acetate. Scheme 1 0 1 0 2 4 5 6 R? 6 c +
Results and Discussion
While it is well known that cyclic nitrones do not pose any problem in terms of configurational ambiguity, the acyclic nitrones may possess discrete (E) or ( Z ) configuration3). In spite of a relatively high barrier to isomerization of (E)and (Z)-ketonitrones4), it is possible that configurational alteration may still occur5). Thus, Koyano and Tanaka4") described the thermal isomerization of C,Ndiphenyl-C-cyano N-oxides in I-hutanol taking place with an E A value of 24.6 kcal . mol-' ' -C6H5 C6H4C1-(4) CH -3.63 5.27 -C6H4F-(4) CH -3.63 5.28 -CsHdOCH3-(4) CH -3.64 5.27 -C6H4CH3-(4) CH -3.64 5.28 -C6H4OCH3-(3) CH -3.65 5.27 -C6H4CH3-(3) CH -3.64 5.21 -C&3(CH3)C1-(3, 4) CH -3.64 5.26