Experimental test of setting three contiguous stereogenic centers in water. Diastereoselective coupling of geometrically biased allylic bromides to alpha-oxy aldehydes with indium

Indium-promoted additions of (Z)-2-(bromomethyl)-2-butenoate to several alpha-(tert-butyldimethylsiloxy) and alpha-(benzyloxy) aldehydes in water have been examined in order to assess the direction and sense of asymmetric induction in these coupling reactions. High levels of the 3,4-syn;4,5-anti diastereomers were produced, reflecting the promising synthetic potential of this chemistry. This stereodifferentiation has been attributed to the strong geometric bias exercised by this allylindium reagent and adherence to a Felkin-Ahn transition-state alignment. Support for this interpretation was gained by comparing the fate of (E)-cinnamyl bromide under comparable circumstances. In this case, the 3,4-anti;4,5-anti diastereomer predominated as expected.