Synthesis of cyclopentane and cyclohexane derivatives

In either case the products were obtained in good yields, high purity and excellent levels of diastereoselectivity. Only modest diastereoselectivities were observed when geminally disubstituted aldehydes were used. 

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Based on a domino Knoevenagel/cne reaction, Tietze and Steinmetz developed a stereoselective solid-phase synthesis of cyclopentane and cyclohexane derivatives of type 326 and 327 using a Merrifield resin modiiled with a propandiol linker 320 as shown in Scheme 4.6.3. Subsequent reaction with monomethyl malonoyl chloride 321 afforded the polymer-bound malonate 322, which, in a two-component domino reaction was treated with unsaturated aldehydes 323 in the presence of a catalytic amount of piperidinium acetate and zinc chloride. Except for a-substituted aldehydes, the initial Knoevenagel condensation occurred without addition of dehydrating agents and the subsequent intramolecular ene reaction gave cyclopentane and cyclohexane derivatives 325 after cleavage firom the resin either by reduction or transesterification. 

Tietze, L.F. and Steinmetz, A., Stereoselective solid phase synthesis of cyclopentane and cyclohexane derivatives by two component domino reactions Generation of combinatorial libraries, Angew. Chem. Int. Ed. Engl, 35 (1996) 651-652. 

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