Formaldehyde SAMP-hydrazone as a neutral formyl anion equivalent: Asymmetric synthesis of substituted beta-formyl delta-lactones and furofuran lactones

An efficient asymmetric synthesis of alpha-substituted beta-formyl delta-la ctones 5 (de greater than or equal to 98%, ee = 80-95%) and 4-substituted f urofuran lactones 6 (de greater than or equal to 98%, ee = 80-->98%) in acc eptable overall yields is reported. Key steps of the new procedure are an a symmetric Michael addition of formaldehyde SAMP-hydrazone (1) to 5,6-dihydr o-2H-pyran-2-one (2) under neutral conditions, followed by trans-selective alpha-alkylation and subsequent cleavage of the auxiliary by ozonolysis or a hydrolytic domino reaction protocol, respectively. The absolute configura tions given for the title compounds are based on three X-ray structure anal yses and NOE measurements.