Synthesis of Unsymmetrical Trisulfides from S-Substituted Sulphenylthiosulphates.

Trisulfide unit is widely found in natural products and has garnered attention due to the unique pharmacological and physiochemical properties. However, despite limited progress, widely applicable approaches for constructing unsymmetrical trisulfides have so far remain scarce. In this work, an easy-to-prepare, solid-state and scalable reagent, S-substituted sulphenylthiosulphate, has been developed for the divergent synthesis of unsymmetrical trisulfides. Alkyl electrophile substrates, including bromides, chlorides, iodides and tosylates, with diverse substituents are smoothly converted to the corresponding trisulfides with S-substituted sulphenylthiosulphates and thiourea as another sulfur source. Furthermore, the late-stage modification of drug molecules was successfully achieved through this method.

Bilateral Unsymmetrical Disulfurating Reagent Design for Polysulfide Construction.

Polysulfides are significant compounds in life science, pharmaceutical science, and materials science. Therefore, polysulfide construction is in great demand. The controllable sequential installation of groups on both ends of a S-S motif faces an enormous challenge owing to the reversible nature of the covalent S-S bond. A library was established with two divergent mask groups for bilateral unsymmetrical disulfurating reagents (R1O-SS-SO2R2). Sequential coupling with preferential activation of the S-SO2 bond (37.6 kcal/mol) and controllable activation of the S-O bond (54.8 kcal/mol) in the presence of the S-S bond (62.0 kcal/mol) enabled successive reactions at each end of the S-S motif to afford unsymmetrical disulfides and trisulfides, even for the cross-linkage of natural products, pharmaceuticals, peptides, and a protein (bovine serum albumin).

Construction of C-S and C-Se Bonds from Unstrained Ketone Precursors under Photoredox Catalysis.

A mild photoredox catalyzed construction of sulfides, disulfides, selenides, sulfoxides and sulfones from unstrained ketone precursors is introduced. Combination of this deacylative process with SN 2 or coupling reactions provides novel and convenient modular strategies toward unsymmetrical or symmetric disulfides. Reactivity studies favor a bromine radical that initiates a HAT (Hydrogen Atom Transfer) from the aminal intermediate resulting in expulsion of a C-centered radical that is intercepted to make C-S and C-Se bonds. Gram scale reactions, broad substrate scope and tolerance towards various functional groups render this method appealing for future applications in the synthesis of organosulfur and selenium complexes.

Access to Polysulfides through Photocatalyzed Dithiosulfonylation.

In this study, we outline a general method for photocatalyzed difunctionalization of alkenes, a diene, alkynes, 1,3-enynes, and [1.1.1]propellane using dithiosulfonate reagents (ArSO2 -SSR) with improved atom economy. Both "ArSO2 -" and "-SSR" on the dithiosulfonate are transferred under mild conditions with broad substrate scope, high stereoselectivity, and complete regioselectivity. Significantly, the resulting dithiosulfonylated styrene is a general and practical nucleophilic disulfuration reagent, reacting with a variety of electrophiles efficiently. Both reactions can be conducted on gram scale, rendering the approach highly valuable.

Catalytic Asymmetric Disulfuration by a Chiral Bulky Three-Component Lewis Acid-Base.

A three-component Lewis acid-base (Lewis trio) involving a bulky chiral primary amine, B(C6 F5 )3 and a bulky tertiary amine has been developed as an effective enamine catalyst for enantioselective disulfuration reactions. The bulky tertiary amine was found to activate a bulky primary-tertiary diamine-borane Lewis pair for enamine catalysis via frustrated interaction. The resulted chiral bulky Lewis trio (BLT) allows for the construction of chiral disulfides via direct disulfuration with ß-ketocarbonyls or α-branched aldehydes in a practical and highly stereocontrolled manner.

New Design of a Disulfurating Reagent: Facile and Straightforward Pathway to Unsymmetrical Disulfanes by Copper-Catalyzed Oxidative Cross-Coupling.

A novel reagent, which introduces two sulfur atoms in one step, was designed and used for the construction of diverse disulfanes by copper-catalyzed oxidative cross-coupling under mild reaction conditions. By applying this stable and readily prepared reagent, late-stage modification of pharmaceuticals and natural products can be achieved straightforward. The scaled-up experiments further indicated the practicality of this protocol. The pH value of the system plays a key role in achieving highly selective cleavage of the C-S bond instead of a S-S bond in the transformation.