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

• Published in: Chemistry : a European journal 2018-04, Vol.24 (19), p.4909-4915
• Main Authors: Hayashi, Yujiro, Saitoh, Takanobu, Arase, Hiromu, Kawauchi, Genki, Takeda, Naohiro, Shimasaki, Yasuharu, Sato, Itaru
• Format: Article
• Language: English
• Subjects: Aldehydes; asymmetric synthesis; Cascade chemical reactions; Catalysis; Chemical synthesis; Chemistry; Diols; domino reactions; Enantiomers; Ketones; Michael reaction; organocatalysis; Reagents; synthesis design
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201705930

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. Natural products in two pots: A two‐pot synthetic method to construct the chiral syn‐1,3‐diol unit has been developed from three aldehydes and Wittig reagent through an organocatalyst‐mediated aldol reaction, Bi(OTf)3‐mediated domino acetalization, and oxy‐Michael reaction as key steps (see scheme; OTf= trifluoromethanesulfonate).