DIASTEREOSELECTIVE AND ENANTIOSELECTIVE SYNTHESIS OF 1,2-TRANS-SUBSTITUTED CYCLOALKANECARBOXYLATES AND SULFONES BY MICHAEL-INITIATED CYCLIZATION VIA SAMP RAMP HYDRAZONES

An efficient and flexible synthesis of 1,2-trans-substituted cycloalkanecarboxylates and sulfones of high diastereo- and enantiomeric purity is described. The key step of the procedure is a Michael-initiated ring closure (MIRC) reaction employing the SAMP/RAMP hydrazone method. Depending on the chain length of the omega-bromo(iodo)enoates 2, 3 and the type of ketone SAMP-hydrazone 1, 3-, 5-, 6- and 7-membered cycloalkane-carboxylates 4-7 or cyclopentanesulfones 24 bearing two or three stereogenic centers are formed with very high asymmetric induction. In the same manner, MIRC reactions with omega-(ethoxycarbonyl)enoate 26 give rise to 3-substituted cyclopentanone-2-carboxylates 27, but with lower overall chemical yields. The relative and absolute configurations are based on X-ray structure analyses, spectroscopic and mechanistic investigations.