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 Michael addition-intramolecular aldol cyclization to give, in synthetically useful yields (30-99%), highly substituted, stereodefined and optically active 2-hydroxybicyclo[3.2.1]octan-8-ones 3-19. A generally separable mixture of isomers, in which the one bearing an equatorial hydroxy group predominates, is obtained with simple aldehydes. In the case of prostereogenic Michael accepters one diastereomer usually prevails from as little as 75% to as much as >97%. This high axial-C-4 stereoselectivity 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 transformations. 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.