The reaction of 2-(α,β-unsaturated)acyl-3-phenyl-l-menthopyrazoles (9) with dienes gave Diels−Alder adducts in good yield. The addition of MgBr2·OEt2 or ZnCl2 accelerated these reactions through the formation of chelating bonds such as N···Mg···OC or N···Zn···OC. The structural fixation by these catalysts also promoted the endo and diastereoselectivities of the Diels−Alder addition on the Re-face of the dienophiles. These results were supported by PM3 calculations, in which the heats of formation of the transition states anticipated the remarkable differences between the Re- and Si-facial attacks of the dienes.

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. 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=D...

The reaction of 1‐acyl‐3,5‐dimethylpyrazoles 1 with CN compounds was kinetically controlled with syn stereoselectivity through a lithium enolate intermediate using lithium diisopropylamide. In contrast, the anti stereoselective reaction of 1 was caused by the action of diisopropylethylamine in the presence of magnesium bromide under the thermodynamic control. Reaction of 2‐acyl‐3‐phenyl‐l‐menthopyrazoles 12 with CN compounds was observed in higher chemical and optical yields with the predominant 2′S configuration. An especially diastereomerically pure product was isolated in the reaction of 2‐propanoyl‐3‐phenyl‐l‐menthopyrazole (12a) with N‐benzylidene‐4‐toluenesulfonamide (2). The products from N‐acyl‐pyrazoles and CN compounds were further cyclized into β‐lactams directly or with short conversion steps.

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The conjugate additions of N‐(α,β‐unsaturated)acylpyrazoles were carried out by the treatment with Grignard reagents in the presence of cuprous halides. The reaction of 2‐(α,β‐unsaturated)acyl‐3‐phenyl‐l‐menthopyrazoles 3a‐h occurred in higher chemical yields and with asymmetric inductions on β‐position, where the addition of magnesium bromide as a Lewis acid influenced to the yields and the diastereoselectivities. In the case of α‐methylated 2‐(α,β‐unsaturated)acyl‐3‐phenyl‐l‐menthopyrazoles 3i‐n, the excellent asymmetric induction on the α‐position was also observed through the diastereofacial protonation.

N‐Acylpyrazoles formed the 5‐membered C=O‐Mg‐N‐2 chelate complexes with magnesium bromide which afforded the Claisen condensation products by the action of tertiary amine through the corresponding enolate.

heterocyclic 4-membered rings heterocyclic 4-membered rings R 0055 -096Synthesis of Optically Active β-Lactams by the Reaction of 2-Acyl-3-phenyl-l-menthopyrazoles with C=N Compounds.-Reaction of 1-acyl-3,5-dimethylpyrazoles (I) with imines in the presence of iPr 2 NEt and MgBr 2 proceeds under thermodynamic control to furnish the expected N-(β-amino)acylpyrazoles with high anti-stereoselectivity.Reaction under kinetic control through a lithium enolate intermediate decreases or even inverts anti-selectivity. Chemical and optical yields can be significantly enhanced by using 3-phenyl-l-menthopyrazole as a new chiral auxiliary [→ (IX)/(X)]. The products from N-acylpyrazoles and C=N compounds are cyclized into β-lactams directly or in short steps [→ (V), (VII)]. -(KASHIMA, C.; FUKUSAKA, K.; TAKAHASHI, K.; J. Heterocycl. Chem. 34 (1997) 5, 1559-1565; Dep. Chem., Univ. Tsukuba, Tsukuba, Ibaraki 305, Japan; EN)

Stereocontrolled Aldol Reaction of N-Acylpyrazoles with AldehydesUsing LDA or MgBr 2 -DIEA. -1-Acyl-3,5-dimethylpyrazoles (I) undergo a kinetically controlled aldol reaction with aldehydes in the presence of LDA. In general, the syn-products (III) are obtained as major products. In the presence of iPr 2 NEt/MgBr 2 thermodynamic control provides mainly the anti-products (IV). The chiral version of the reaction by application to the menthopyrazole (V) proceeds with moderate diastereoselectivities. -(KASHIMA, C.; FUKUCHI, I.; TAKAHASHI, K.; FUKUSAKA, K.; HOSOMI, A.; Heterocycles 47 (1998) 1, 357-365; Dep. Chem., Univ. Tsukuba, Tsukuba, Ibaraki 305, Japan; EN)