ONE-POT BASE-PROMOTED TANDEM MICHAEL ADDITION-INTRAMOLECULAR ALDOLIZATION - STEREOSELECTIVE SYNTHESIS AND REACTIVITY OF 2-HYDROXYBICYCLO[3.2.1]OCTAN-8-ONES

alpha-Substituted cyclopentanones 1 react with alpha,beta-unsaturated aldehydes 2 by a facile base-promoted (K2CO3, Cs2CO3, DBU) tandem Mich ael addition-intramolecular aldol cyclization to give, in syntheticall y useful yields (30-99%), highly substituted, stereodefined and optica lly active 2-hydroxybicyclo[3.2.1]octan-8-ones 3-19. A generally separ able mixture of isomers, in which the one bearing an equatorial hydrox y group predominates, is obtained with simple aldehydes. In the case o f prostereogenic Michael accepters one diastereomer usually prevails f rom as little as 75% to as much as >97%. This high axial-C-4 stereosel ectivity results from a diastereoselective Michael addition and can be easily reversed by simple adaptation of the reaction conditions. The structures of the products rest upon NMR spectroscopy and chemical tra nsformations. The synthetic potential of hydroxybicyclo[3.2.1]octanes is illustrated by transformations of 25-28, especially by their facile conversion to functionalized and stereodefined cycloheptanes 30, 32, 35-42.