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 δ-hydroxy α,β-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. Diospongin C and yashabushidiol A have been synthesized efficiently by using the present method as a key step.
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