Asymmetric Synthesis of Trisubstituted Tetrahydrothiophenes via in Situ Generated Chiral Fluoride-Catalyzed Cascade Sulfa-Michael/Aldol Reaction of 1,4-Dithiane-2,5-diol and α,β-Unsaturated Ketones

Abstract

A chiral fluoride-catalyzed asymmetric cascade sulfa-Michael/aldol condensation reaction of 1,4-dithiane-2,5-diol and a series of α,β-unsaturated ketones is described to access chiral trisubstituted tetrahydrothiophene derivatives. The target products, including the spiro tetrahydrothiophene derivatives bearing a five-, six-, and seven-membered ring, were highly functionalized and showed high ee value. This established protocol realized a highly enantioselective reaction with a catalytic amount of KF and Song's chiral oligoEG via in situ generated chiral fluoride to construct useful heterocyclic skeletons with great complexity.

Chemodivergent Preparation of Various Heterocycles via Phase‐Transfer Catalysis: Enantioselective Synthesis of Functionalized Piperidines

“…Thus, a truly general enantioselective methodology for the sulfa‐Michael addition of thiophenols to simple, unactivated β‐substituted‐α,β‐unsaturated esters is missing in the present literature, rendering our methodology a relevant contribution. To the best of our knowledge, enantioselective sulfa‐Michael additions under phase‐transfer conditions are an extremely rare process, with only one example reported so far, showing a chiral crown‐ether catalyzed sulfa‐Michael/aldol cascade . Finally, organocatalytic enantioselective sulfa‐Michael initiated cascade cyclizations are well‐established protocols .…”

Recent Advances in the Cycloaddition Reactions of 2‐Benzylidene‐1‐benzofuran‐3‐ones, and Their Sulfur, Nitrogen and Methylene Analogues

“…In 2017, using the same reactants (E)-2-(aryl)-2,3-dihydro-1H-inden-1-ones 5 and 1,4-dithiane-2,5-diol 6, Yan's group achieved a high-yield synthesis for compounds 9 through chiral fluoride catalyst Cat-1 (in situ) and reported this as highly functionalized with a high ee value (Scheme 1b). [9] More importantly, the spiro tetrahydrothiophene derivatives bearing a six-or seven-membered ring were also obtained.…”

1,4‐Dithiane‐2,5‐diol: An Attractive Platform for the Synthesis of Sulfur‐Containing Functionalized Heterocycles

“…[11] Moreover, derivatives 41a have been conveniently obtained in a diastereoselective fashion in the presence of triethylamine. [11,29] Replacement of the benzofuran-3(2H)-one with the benzothiophen-3(2H)-one moiety produced 42b with moderate enantioselectivity. [11,29] Replacement of the benzofuran-3(2H)-one with the benzothiophen-3(2H)-one moiety produced 42b with moderate enantioselectivity.…”