Expedient synthesis of α,α-dimethyl-β-hydroxy carbonyl scaffolds via Evans' aldol reaction with a tertiary enolate

An efficient synthetic methodology for 3-hydroxy-2,2-dimethyloctynoic acid (DHOYA) and several variants, which are increasingly common fragments encountered in bioactive marine cyanobacterial metabolites, was developed. These fragments were obtained in three steps via a tertiary aldol reaction utilizing an Evans' chiral auxiliary to afford the desired stereochemistry at the β-hydroxy carbon. Thus far, this methodology has been successfully applied in determination of the absolute stereochemistry of eight cyanobacterial natural products, including the VGSC activator palymramide A.