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 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.