Diastereoselective 1,3-Dipolar Cycloaddition of 2-(a,b-Unsaturated) Acyl-3-phenyl-l-menthopyrazoles (1997)

A b s t r a c t The 1,3-dipolar cycloadducts of N-(a,B-unsaturated) acylpyrazoles(2) with benzonitrile oxide or nitrones were afforded in good yield.In the cases of nitrones, the addition of MgBQ or ZnBr2 promoted the stereoselectivity as well as the acceleration of the reaction rate.In the reaction of 2f and 2g, the big jump on the diastereoselectivity was accomplished by the addition of MgBn, and(3'S,4'R,5'S)-8 was obtained as optically pure form in over 90% yield.These isoxazolidinecarbonylpyrazoles were converted into azetidinones in moderate yield with the retention of their stereo structures.Recently we have developed the preparation and the utilities of 3-phenyl-1-menthopyrazole (1) as a new c h i d auxiliary,' which has some unique structure and properties different from the conventional c h i d auxiliarie~:~The most important characteristic of this auxiliary is that the substrate terminates to heteroaromatic pyrazole ring and is surrounded by the chiral atmosphere.Especially the steric hindrance of 1 is relaxed by twisting the benzene ring, which overlays on one side of the terminal nitrogen atom.'This structural characteristic causes the diastereofacial effect in the reactions on the substrate moiety.Moreover, lone pair electrons of adjacent nitrogen take a role of Lewis base to form the chelation of N.-Mg...O=C in the mixture of N-acylpyrazoles and MgBQ.' Similar chelation of N-,Li-0 is perceived in the lithium enolate derived from N-acylpyrazoles.These chelations freeze the bond rotation of acyl group fixing to Z-configuration.As the result, the chirality of (4R)t ?his paper is dediied to Professor Shigeru Oae on thc occasion of his 77th birthday for his brilliant achievement in Ule field of heteroatom a ~d heterocyclic chemist~y.290 HETEROCYCLES.Vol.44.No. 1.1997 methyl group of 1 causes the high asymmetric induction in the reactions on acyl group of 2-acyl-3-phenyl-lmenthopyrazoles such as a-alkylation4 and a-~ulfenylation.~Otherwise, N-acyl substituted heteroaromatics such as N-acyliidazoles are easily convelted into various acyl derivatives by the action of nucleophiles especially under acidic conditions6 he similar chemical behaviors are observed likely in the reactions of Nacylpyrazoles with alcohol^,^ a m i n e ~, ~ Grignard reagents,9 or organozinc compound^'^ under very mild conditions.These facts demonstrated the excellent utility of 1 as a new c h i d auxiliary.For the further extension of the utility of 1, a wide variety of the diastereoselective reaction on the acyl moiety of 2-acyl-3-phenyl-lmenthopyrazoles is highly desired.Here, we report the diastereofacial 1,3-dipolar cycloaddition of a nitrile oxide and nitrones on 2-(a,p-unsaturated) acyl-3-phenyl-I-menthopyrazoles (2, Xc=MP).Firstly 1-(a,b-unsaturated) acyl-3,s-dimethylpyrazoles (2, Xc=DMP) were treated with benzonitrile oxide, which was generated in sihr from 1-chlorobenzaldoxime and triethylamine.In the short readion time at chilled temperature, 1,3-dipolar cycloaddi-tion of 1-acryloyl-3,s-dimethyl-pyrazole (2a) was performed regioselectively a: Xc=DMP, R=H