Organic & Biomolecular Chemistry最新文献

The incorporation of a sulfoximine group into parent molecules is of interest. In this work, we report a practical and efficient alkyldisulfanium salt-mediated α-sulfoximidation of alkenes with NH-sulfoximines. This method enables the synthesis of various thioether group-containing alkyl sulfoximines in moderate to good yields. Mild and catalyst-free conditions, readily available substrates and operational simplicity make this method quite attractive in organic synthesis.

We report herein a one-step three-component decarboxylative strategy for the construction of novel azatrithiapentalenes from readily available cinnamonitriles, arylacetic acids and elemental sulfur. The reaction was found to proceed in DMSO in the presence of DABCO as a basic promoter through an unusual disproportionate incorporation of three sulfur atoms into the carbon skeletons derived from two organic substrates. A comprehensive examination of the substrate scope demonstrated that the reaction conditions are broadly tolerant, including substrates bearing a diverse array of substituents with markedly different electronic and steric features. Control experiments demonstrated that elemental sulfur reacts independently with both starting organic substrates to yield two key intermediates that could combine together to yield azatrithiapentalenes. The reaction could be extended to phenylmethanethiols or dibenzyl disulfides in place of phenylacetic acids.

The replacement of N,N-dimethylformamide (DMF) in solid-phase peptide synthesis (SPPS) is critical for improving the sustainability and safety of peptide research. While N-butyl-2-pyrrolidinone (NBP) has emerged as a viable alternative for linear peptide synthesis, its applicability to post-linear synthesis modifications remains underexplored. Here, we demonstrate the use of NBP as an alternative solvent for key on-resin transformations required in peptidomimetic synthesis. Orthogonal protecting group strategies were successfully implemented, enabling selective removal of Cys(SIT), Cys(Acm), Cys(Trt), and Lys(Dde) under mild conditions. Notably, SIT deprotection achieved 92% conversion in a single 4-hour treatment, while Acm and Trt were selectively removed using iodine or N-halosuccinimides, respectively. Lys(Dde) was efficiently cleaved in the presence of Cys(Acm) using 4% hydrazine in NBP. Furthermore, on-resin cyclisation via disulfide bond and 1,4-disubstituted triazole formation proceeded effectively in NBP, as did N-terminal acetylation under mild conditions. These findings establish NBP as a practical and greener alternative to DMF for diverse post-linear synthesis modifications, supporting the development of sustainable SPPS protocols.

A copper-catalyzed multicomponent radical domino reaction of 1-allyl-2-ethynylbenzoimidazoles with Togni's reagent, amines and CO₂ was successfully developed. This method provides a convenient and efficient approach to access valuable trifluoromethyl- and carbamoyloxyl-substituted ring-fused benzimidazoles in satisfactory yields with good functional group tolerance and high regio- and stereo-selectivity. Additionally, it enables the conversion and utilization of CO₂ under mild conditions.

Herein, we report a new methodology for the electrochemical oxidative C-H trifluoromethylation of 4-phenylthiazol-2-amines in an undivided cell using a glassy carbon electrode (GCE) and sodium trifluoromethanesulfinate (CF₃SO₂Na; Langlois' reagent) as the CF₃ radical source. Using this tert-butyl hydroperoxide (TBHP)-mediated and transition metal-free effective approach, trifluo-romethylated 4-phenylthiazol-2-amines were synthesized in high yields (up to 97%).

The construction of spiro-iminoindoline-pyrazolines from readily available starting materials has garnered significant interest within the synthetic chemistry community. Herein, we report a chemo- and diastereoselective (2 + 3) and three-component formal (1 + 1 + 3) cascade cyclization strategy for their synthesis, demonstrating unprecedented CC chemoselectivity of nitrile imines toward α,β-unsaturated imines. This method delivers multifunctionalized products efficiently under mild conditions. Furthermore, preliminary antioxidant screening using the DPPH radical scavenging assay highlights their potential bioactivity.

Backbone construction and ionic modulation are effective strategies for improving energetic material performance. In this work, we report the successful synthesis and detailed characterization of a carbonyl-containing fused triazolotriazine compound (3). Its perchlorate salt (4) features a dense crystal lattice and exhibits a high density (1.90 g cm^-3) with good detonation performance (D = 8382 m s^-1; P = 30.74 GPa) and low mechanical sensitivities [impact sensitivity (IS) > 40 J; friction sensitivity (FS) > 360 N], surpassing those of TNT. Direct oxidation of the amino group in 3 using fuming HNO₃ yields the nitro compound 5, with HNO₃ as the sole oxidant. Among 4, 5, and its ammonium salt 6, the perchlorate salt 4 achieves the most favorable balance between energetic output and structural stability. This work highlights the synthesis and systematic characterization of these novel fused-triazolotriazine derivatives, offering a practical route toward high-energy, low mechanical sensitivity energetic materials.

A zinc-catalyzed method has been developed for the direct conversion of primary alcohols into alkenes under acceptorless dehydrogenation conditions. Utilizing a simple and Earth-abundant zinc catalyst, this approach enables the dehydrogenative coupling of primary alcohols with either diphenylphosphine oxide (to generate symmetric alkenes) or benzyl phosphine oxides (to generate asymmetric alkenes), affording a diverse range of alkenes in moderate to high yields with (E)-selectivity. This strategy provides a promising facile route for alkene synthesis directly from readily accessible alcohols, as evidenced by gram-scale reactions and the preparation of the biologically active compounds DMU-212 and resveratrol.

An electrochemically promoted primary benzylic C(sp³)-H directed dehydrogenative cascade cyclization for the synthesis of quinazolinones was developed under undivided electrolytic conditions. In this protocol, neither external chemical oxidants nor transition-metal catalysts were needed, and a broad range of substituted quinazolinones were efficiently synthesized from simple methyl arenes and 2-aminobenzamides in high efficiencies. The reaction mechanism was investigated using a series of control experiments and CV studies, which showed that the reaction likely proceeds via an aryl radical cation pathway.

Nickel catalyzed C-H oxygenation is a fundamentally important, but much less studied transformation. Herein, we report a nickel based catalyst that, in combination with catalytic DDQ, promotes the oxygenation of (aryl)(N-heteroaryl)methanes with molecular oxygen under neutral conditions. The strategy involves SET-induced formation of C-centered radicals giving access to (aryl)(N-heteroaryl)ketones and is extended to arylbenzyl ketones. The current approach has been successfully applied for the synthesis of an intermediate of AMG 579, an investigational drug candidate. A slightly modified catalyst system enables the synthesis of benzoxazinones directly starting from (aryl)(N-heteroaryl)methanes.