Xuefeng Jiang

Transfer of sulfur: from simple to diverse.

The introduction of sulfur atoms onto target molecules is an important area in organic synthesis, in particular in the synthesis of pharmaceutical compounds, and a wide variety of sulfuration agents have been developed for thionation reactions over the past few decades. In this Focus Review, we collect and summarize the C-S bond-formation reactions that have been used to construct C-S bonds in natural products and pharmaceutical compounds.

Sulfur Containing Scaffolds in Drugs: Synthesis and Application in Medicinal Chemistry.

The impact of the development of sulfur therapeutics is instrumental to the evolution of the pharmaceutical industry. Sulfur-derived functional groups can be found in a broad range of pharmaceuticals and natural products. For centuries, sulfur continues to maintain its status as the dominating heteroatom integrated into a set of 362 sulfur-containing FDA approved drugs (besides oxygen or nitrogen) through the present. Sulfonamides, thioethers, sulfones and Penicillin are the most common scaffolds in sulfur containing drugs, which are well studied both on synthesis and application during the past decades. In this review, these four moieties in pharmaceuticals and recent advances in the synthesis of the corresponding core scaffolds are presented.

Efficient Access to 1,4-Benzothiazine: Palladium-Catalyzed Double C–S Bond Formation Using Na2S2O3 as Sulfurating Reagent∥

A novel Pd-catalyzed double C-S bond formation coupling reaction has been developed. This protocol, in which Na2S2O3 was used as sulfurating reagent in metal-catalyzed reactions, provides an efficient method for the synthesis of substituted 1,4-benzothiazine derivates, which are structural elements of numerous bioactivity molecules rendering this protocol attractive to both synthetic and medicinal chemistry.

Direct Cross-Coupling Access to Diverse Aromatic Sulfide: Palladium-Catalyzed Double C–S Bond Construction Using Na2S2O3 as a Sulfurating Reagent

The Pd-catalyzed cross-coupling of aryl halides, alkyl halides, and Na2S2O3·5H2O to deliver aromatic thioethers is described. Pyridine, furan, thiophene, benzofuran, benzoxazole, benzothiophene, benzothiazole, and pyrazine are all amenable to this protocol. The odorless and stable solid Na2S2O3·5H2O was used as a convenient and environmentally friendly source of sulfur. Pd-catalyzed cross-couplings without thiols or thiophenols to build C-S bonds have not previously been achieved, which renders our observation more striking.

Transition-Metal-Free Aerobic Oxidative Cleavage of CC Bonds in α-Hydroxy Ketones and Mechanistic Insight to the Reaction Pathway†

Clear cut: For the title reaction, O(2), the ideal oxidant, was used as the only oxidizing reagent. The dimer intermediate (see scheme) and isotopic labeling control experiments with (18)O(2) partially disclosed the reaction mechanism.

A highly efficient Cu-catalyzed S-transfer reaction: from amine to sulfide.

A highly efficient Cu-catalyzed dual C-S bonds formation reaction, proceeding in alcohol and water under air, is reported, in which inodorous stable Na2S2O3 is used as a sulfurating reagent. This powerful strategy provides a practical and efficient approach to construct thioethers, using readily available aromatic amines and alkyl halides as starting materials. Sensitive and synthetic useful functional groups could be tolerated. Furthermore, pharmaceuticals, glucose, an amino acid, and a chiral ligand are successfully furnished by this late-stage sulfuration strategy.

Ligand Controlled Regiodivergent C1 Insertion on Arynes for Construction of Phenanthridinone and Acridone Alkaloids

A palladium-catalyzed regiodivergent C1 insertion multicomponent reaction involving aryne, CO, and 2-iodoaniline is established to construct the scaffolds of phenanthridinone and acridone alkaloids. Regioselective control is achieved under the guidance of selective ligands. The phenanthridinones are solely obtained under ligand-free condition. In comparison, application of the electron-abundant bidentate ligand dppm afforded the acridones with high efficiency. The release rate of the aryne from the precursor assists the regioselectivity of insertion as well, which was revealed through interval NMR tracking. A plausible mechanism was suggested based on the control experiments. Representative natural products and two types of natural product analogues were synthesized divergently through this tunable method.

Total synthesis and biological evaluation of monorhizopodin and 16-epi-monorhizopodin.

For many years, polyketide natural products have provided the scientific community with a rich source of novel molecular architectures, many of which have become important therapeutics for clinical use.[1] In 1993, the polyketide rhizopodin was isolated from the myxobacterium Myxococcus stipitatus.[2] It was shown to display an interesting array of biological properties, including potent anti-tumor activity against a range of cancer cell lines in the low nanomolar range and the ability to inhibit the polymerization of actin.[2,3] Despite its original structural assignment as the 19-membered monomeric lactone 1a (monorhizopodin), recent studies revealed dimeric structure 2 to be the correct architecture of rhizopodin (Figure 1).[4] These molecules have started to attract attention from the synthetic community, although no total syntheses have been reported to date.[5]

Ligand-Controlled Divergent Cross-Coupling Involving Organosilicon Compounds for Thioether and Thioester Synthesis

A divergent cross-coupling for both thioether and thioester construction from organosilicon compounds has been developed. Predominant selectivity for Hiyama-type coupling and C1 insertion reaction was achieved under the guidance of ligands. Thioether was obtained under ligand-free conditions in which disulfide generated from homocoupling could be prevented. Meanwhile, application of bidentate phosphine ligands under carbon monoxide atmosphere (CO balloon) afforded the thioester with little decomposition, which was revealed through interval NMR tracking.

Palladium-catalyzed atom transfer radical cyclization of unactivated alkyl iodide

A palladium-catalyzed atom transfer cyclization of unactivated alkyl iodide has been developed. A radical chain mechanism has been proposed for this transformation, which might not involve an alkylpalladium intermediate.