Reductive Cross-Aldol Reaction Using Bromoaldehyde and an Aldehyde Mediated by Germanium(II): One-Pot, Large-Scale Protocol

The reaction of α-bromoaldehyde with aldehyde in the presence of GeCl2−dioxane gave the syn-selective cross-aldol equivalent. A catalytic amount of Bu4NBr improved the yield and selectivity. The initially formed aldol adduct (β-germoxyaldehyde) did not suffer from over-reaction. This system enabled an intramolecular aldol reaction to give cyclic compounds effectively. One-pot synthetic methodology including bromination of aldehyde followed by cross-aldol reaction with the second aldehyde was successful on a large-scale.