Two-pot synthesis of chiral 1,3-syn-diols through asymmetric organocatalytic aldol and Wittig reactions, followed by domino hemiacetal/oxy-Michael reactions.

A two-pot synthetic method to construct the chiral syn-1,3-diol unit has been developed from three aldehydes and either Wittig or Horner-Wadsworth-Emmons reagents. In the first pot, chiral delta-hydroxy ,alpha,beta-unsaturated ketones are synthesized with excellent enantioselectivity by the organocatalyst-mediated asymmetric direct aldol reaction of two different aldehydes, followed by either Wittig or Horner-Wadsworth-Emmons reactions. In the second pot, domino acetalization with an aldehyde and subsequent oxy-Michael reaction proceeds in the presence of NaClO4 and a catalytic amount of Bi(OTf)(3) (OTf = trifluoromethanesulfonate) to provide the chiral 1,3-syn-diol derivative with excellent diastereoselectivity. DiosponginC and yashabushidiolA have been synthesized efficiently by using the present method as a key step.