SmI2/Pd(0)-mediated intramolecular coupling between propargylic esters and tethered aldehydes or ketones

A SmI2/Pd(0)-promoted intramolecular coupling between propargylic esters and carbonyl compounds is described. The reaction affords homopropargyl cycloalkanol products. Cyclopentanols are formed in high yields when ketones are employed as the carbonyl components, but aldehydes are found not to be suitable partners in these reactions. Particularly remarkable is the efficient formation of products with adjacent functionalized quaternary centers. These cyclizations take place with low diastereoselectivity about the newly created propargylic and carbinol stereogenic centers except when these two centers are quaternary or in the presence of groups capable of both chelating trivalent samarium and facilitating retroaldol-aldol-type equilibria in the product. In this latter case, the strategic combination of chemoselective carbonyl addition and SmI2/Pd(0)-promoted cyclization provides ready and convenient stereocontrolled access to functionalized cyclopentanols from unprotected 1,5-dicarbonyl starting materials. The analogous formation of cyclohexanols is limited by low cyclization yields and lack of stereoselectivity.