Diastereoselective Synthesis of β-Hydroxy Allylic Tertiary Sulfides via Nickel/Photoredox Cooperative Catalysis

Abstract

β-Hydroxy allylic sulfides represent privileged motifs in bioactive molecules but remain challenging to synthesize owing to sulfurmediated catalyst poisoning and stereocontrol issues. We report a nickel/photoredox cooperative catalysis system for the diastereoselective allylation of aldehydes with sulfur-substituted allylic acetates. Using an organic photocatalyst 4CzIPN under 450 nm blue light at room temperature, this protocol affords diverse β-hydroxy allylic tertiary sulfides in good yields with excellent diastereoselectivities (up to >20:1 dr). Broad substrate scope, mild conditions, and good functional group tolerance are demonstrated.Sulfur is an essential element in living organisms, and organosulfur compounds have gained pivotal importance in pharmaceutical and materials science. 1-4 β-hydroxy sulfides and allylic sulfides are prevalent in bioactive natural products, exhibiting antibacterial, antitumor, anti-allergic and other pharmacological activities, while also serving as versatile synthetic intermediates (Scheme 1a). 5-18 Various routes to β-hydroxy sulfides have been developed, including epoxide ring-opening, alkene hydroxysulfenylation, and nucleophilic addition of sulfur-stabilized carbanions (Scheme 1b). 19-33 Shibasaki's group further realized asymmetric synthesis of β-hydroxy tertiary sulfides via aldol reactions (Scheme 1c). 34 While allylic sulfides are also well-studied, 35-41 the chemistry of β-hydroxy allylic sulfides remains underdeveloped; Zhao's group reported a palladium-catalyzed approach toward sulfone-bearing quaternary stereocenters (Scheme 1d). 42 Recently Visible-light photoredox/transitional metal dual catalysis has become a mild, efficient strategy for aldehyde allylation to construct homoallylic alcohols. 43-51 However, e) This work, alylation reaction of ethylthioallyl ester and aldehyde a) Natural products and pharmaceuticals with β-hydroxy sulfide and allylic sulfide b)The synthesis of β-hydroxy sulfides 2