1,3-Dipolar Cycloadditions of (4R*,5R*)-1-Arylmethylidene- 4-benzamido-3-oxo-5-phenylpyrazolidin-1-ium-2-ides to Di-(–)-menthyl Maleate

Lidija Pezdirc, David Bevk, Samo Pirc and Jurij Svete*

Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, P.O. Box 537, SI-1000 Ljubljana, Slovenia

* Corresponding author: E-mail: jurij.svete@fkkt.uni-lj.si

1,3-Dipolar cycloadditions of racemic (1Z,4R*,5R*)-arylmethylidene-4-benzamido-5-phenyl-3-pyrazolidinon-1-azomethine imines 3 to enantiopure di-(–)-menthyl maleate (4) afforded mixtures of diastereomeric cycloadducts 5/5'–7/7'. Selectivity as well as stereochemistry of cycloadditions were dependent on the substituents at the 1'-Ar residue of dipoles 3. Thus, reactions of dipoles 3a–j with at least one free ortho-position gave either di-(–)-menthyl (1R*,2S*,3R*,5R*,6R*)-3-aryl-6-benzamido-7-oxo-5-phenylhexahydropyrazolo[1,2-a]pyrazole-1,2-dicarboxylates 5/5’ (the endo-isomers) and/or di-(–)-menthyl (1S*,2R*,3R*,5R*,6R*)-3-aryl-6-benzamido-7-oxo-5-phenylhexahydropyrazolo[ 1,2-a]pyrazole-1,2-dicarboxylates 6/6' (the exo-isomers) with syn-oriented 3-H and 5-H, whilst reactions of 4 with ortho-disubstituted dipoles 3k,l gave (1S*,2R*,3S*,5R*,6R*)-diastereomers 7/7'k,l with anti-oriented 3-H and 5-H. Separation of diastereomeric cycloadducts 5/5'–7/7' by crystallization and/or MPLC furnished isomerically pure compounds 5a,b,d,g, 5'b,d,h, 6c,d,j, and 6'c,d,f and purified mixtures of diastereomers 5/5'e, 6/6'e,h, and 7/7'k,l in 1–42% yields. The relative configuration of the pyrazolo[1,2-a]pyrazolone structural element in the products 5/5'–7/7' was determined by NMR.

Keywords: 1,3-dipolar cycloadditions, (–)-menthol, pyrazolidin-3-ones, azomethine imines, pyrazolo[1,2-a]pyrazoles,