Sulfoxide‐Based Enantioselective Nazarov Cyclization: Divergent Syntheses of (+)‐Isopaucifloral F, (+)‐Quadrangularin A, and (+)‐Pallidol

Abstract

The synthesis of enantiomerically pure 3-aryl substituted indanones is developed using an enantioselective sulfoxide-based Knoevenagel condensation/Nazarov cyclization procedure. After the reductive desulfonation of the methyl para-tolyl sulfoxide-containing chiral auxiliary under mild conditions, selected enantiomerically pure indanone is used for the divergent total syntheses of three resveratrol natural products (+)-isopaucifloral F, (+)-quadrangularin A, and (+)-pallidol.

Transition‐Metal‐Free Synthesis of 1‐Indanone Skeleton: A Brief Update

“…The potential use of this protocol was applied in the enantioselective synthesis of anticancer agents. Sun group also carried out similar type of stereoselective reactions to access enantiopure indanones [40] …”

Recent Applications in the Use of Sulfoxides as Chiral Auxiliaries for the Asymmetric Synthesis of Natural and Biologically Active Products

“…By this 4 conrotatory ring closure the control of the sense of conrotation (torquoselectivity) allows cyclization to occur with high stereoselectively. In this context, in 2016 Sun 26 and Salom-Roig 27 proposed a new approach involving a chiral sulfoxide to control the torquoselectivity in the Nazarov reaction. As an example, alkylidene Nazarov substrate 139 underwent a AlCl 3 -promoted cyclization yielding the 3-arylindanone 140 (Scheme 27).…”

“…Analogously, the 3-arylindanone 143 was obtained from the corresponding alkylidene Nazarov substrate by Sun and co-workers 26 to access (+)-isopaucifloral F, (+)-quadrangularin A, and (+)-pallidol, which were found to exhibit antiosteoporosis, neuroprotective, and estrogen-like activities, respectively (Scheme 28).…”

Efficient kinetic resolution in the asymmetric transfer hydrogenation of 3-aryl-indanones: applications to a short synthesis of (+)-indatraline and a formal synthesis of (R)-tolterodine

“…1). [4][5][6][7] Typical examples of this type are (+)-indatraline used for the treatment of depression and cocaine addiction, [8][9][10] the antihypertensive agent (+) irindalone, 11 the neuroprotective agent (+)-quadrangularin A, 12 (+)-isopaucioral F used for the treatment of osteoporosis 12 and a-diisoeugenol that has cytotoxic and antioxidant activities. 13 An example of a bioactive indane bearing a 3-alkenyl group is (+)-multisianthol, which has antitumor activity.…”