Two‐Pot Synthesis of Chiral 1,3‐syn‐Diols through Asymmetric Organocatalytic Aldol and Wittig Reactions Followed by Domino Hemiacetal/Oxy‐Michael Reactions

Abstract

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 NaClO and a catalytic amount of Bi(OTf) (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.

Diaryl Prolinols in Stereoselective Catalysis and Synthesis: An Update

“…More recently, Hayashi and coauthors exploited the asymmetric diarylprolinol catalyzed cross‐aldol reaction as key‐step for the synthesis of chiral syn ‐1,3‐diols . These important synthons, which are constituents of many natural products and drugs, were obtained starting from three readily accessible aldehydes in a two‐pot process (Scheme <pschr16<).…”

Enantio‐ and Diastereoselective Synthesis of Latanoprost using an Organocatalyst

“…To control the stereochemistry at C9, we employed domino acetalization/oxy‐Michael reactions developed by our group. Thus, upon treating alcohol 8 with 3,4‐dinitrobenzaldehyde, 50 mol % Bi(OTf) 3 , and NaClO 4 , domino acetalization followed by a stereoselective oxy‐Michael reaction proceeded to afford acetal 7 , in which the stereochemistry at C9 was completely controlled in the desired manner even though starting alcohol 8 was a mixture of C7 diastereomers. Diastereoselective reduction of ketone 7 at C11 proceeded stereoselectively from the convex face to provide 27 in 86 % yield.…”

Water‐Compatible Synthesis of 2‐Trifluoromethyl‐1,3‐Dioxanes

“…Acetals have been used as protecting groups for alcohols and diols for many years. The most commonly used for diols are aromatic (phenyl and p ‐methoxyphenyl) and aliphatic (acetonide); however, other groups coming from highly activated aldehydes have also been reported as alternative protecting groups for 1,3‐diols, such as the 3,4‐dinitrophenyl and trichloromethyl groups . In consequence, the stability of acetals is well established particularly under basic conditions.…”