RESUMO
Direct coupling of enolizable aldehydes with C-alkynyl imines is realized affording the corresponding propargylic Mannich adducts of syn configuration, thus complementing previous methods that gave access to the anti-isomers. The combination of proline and a urea Brønsted base cocatalyst is key for the reactions to proceed under very mild conditions (3-10â mol % catalyst loading, dichloromethane as solvent, -20 °C, 1.2â molar equivalents of aldehyde) and with virtually total stereocontrol (syn/anti ratio up to 99:1; ee up to 99 %). Some possibilities of further chemical elaboration of adducts are also briefly illustrated.
RESUMO
An effective asymmetric route to functionalized 1,6- and 1,7-enynes has been developed based on a direct cross-aldol reaction between ω-unsaturated aldehydes and propargylic aldehydes (α,ß-ynals) promoted by combined α,α-dialkylprolinol ether/Brønsted acid catalysis. This synergistic activation strategy is key to accessing the corresponding aldol adducts with high stereoselectivity, both enantio- and diastereoselectivity. The aldol reaction also proceeds well with propargylic ketones (α,ß-ynones) thus enabling a stereocontrolled access to the corresponding tertiary alcohols. The utility of these adducts, which are difficult to prepare through standard methodology, is demonstrated by their transformation into trisubstituted bicyclic enones using standard Pauson-Khand conditions.