Stereocontrol in asymmetric phospho-aldol catalysis. Chirality relaying in action

The enantioselective addition of diorgano-H-phosphonates to aldehydes, the phospho-aldol reaction, is catalysed by both ( R,R )-salcyen and ( R,R )-salcyan complexes of aluminium at room temperature under aerobic conditions. However, whilst the former ligand system favours one absolute configuration of product α-hydroxyphosphonate ester, to the extent of <50%, the latter ligand framework favours the opposite configuration < 60%, despite both ligand systems having the same absolute backbone configuration! Structure–activity, single-crystal X-ray and computational studies shed light about these differences and provide important clues as to how to increase stereoselectivity.