The SmI₂-mediated reductive coupling reaction between non-conjugated aldehydes and two 2-(dialkylamido)aryl 2,3-disubstituted α,β-unsaturated esters has been investigated. In contrast to the corresponding 2- or 3-monosubstituted esters investigated in prior work, the disubstituted substrate has not yet been used in this reaction despite offering the potential to selectively forge three adjacent stereogenic centers in one step. Preliminary study on the aldehyde scope and limitations of the reaction has been conducted; high diastereoselectivity and good to high yields have been achieved for most of the investigated non-conjugated aldehydes. The only observed systematic exceptions are the reactions of the 2-methyl-3-phenyl-substituted acrylate with α-branched aldehydes that afforde...[ Read more ]

The SmI₂-mediated reductive coupling reaction between non-conjugated aldehydes and two 2-(dialkylamido)aryl 2,3-disubstituted α,β-unsaturated esters has been investigated. In contrast to the corresponding 2- or 3-monosubstituted esters investigated in prior work, the disubstituted substrate has not yet been used in this reaction despite offering the potential to selectively forge three adjacent stereogenic centers in one step. Preliminary study on the aldehyde scope and limitations of the reaction has been conducted; high diastereoselectivity and good to high yields have been achieved for most of the investigated non-conjugated aldehydes. The only observed systematic exceptions are the reactions of the 2-methyl-3-phenyl-substituted acrylate with α-branched aldehydes that afforded drastically decreased selectivity and in case of the highly sterically demanding pivaldehyde a very low yield. Exemplary use of the chiral esters to form the enantiomerically enriched products is presented, although a generally low and highly substrate-dependent enantioselectivity was observed. Finally, viability of the reaction in the synthesis of natural products is indicated by utilizing it for a short total synthesis of phaseolinic acid. Interpretation of the reaction results was attempted by proposing a new mechanism which might explain the observed diastereoselectivity but will need further experimental evidence for confirmation or correction.