Synlett

We report a straightforward, metal-free, efficient protocol for the synthesis of 2-phenylnaphthalenes from 1-phenylethane-1,2-diols under mild conditions. In this strategy, 1,1,1,3,3,3-hexafluoro-2-propanol is used as a solvent that stabilizes the reaction intermediate. An in situ IR experiment revealed that the reaction proceeds through the formation of phenylacetaldehyde followed by a [4+2] Diels–Alder reaction. Several control experiments were performed to gain mechanistic insights into the reaction.

A new protocol for the catalytic denitrative generation of radicals from nitroalkanes was disclosed. 9-Fluorenol acts as a single-electron transfer catalyst that reduces nitroalkanes to promote the C-NO2 bond cleavage, followed by the formation of alkyl radicals. The obtained radicals participate in diverse transformations such as hydrogenation, Giese addition, spirocyclization, and Minisci reactions by using appropriate trapping reagents. The present system outperforms conventional methods using tin hydrides in terms of cost, toxicity, and experimental operations.

A visible-light-driven α-hydroxymethylation of ketones to generate the corresponding alcohols was achieved under continuous-flow conditions. MeOH was used as a green and renewable C1 source and solvent to enable the α-C(sp3)–H functionalization of ketones under irradiation by white LEDs. A flow microreactor operated under optimized conditions permitted this oxidation to proceed with a higher efficiency and a shortened reaction time of 215 minutes, which was improved ten times compared with the batch parallel reaction (36 h). Mechanism studies indicate the reaction proceeds by a radical pathway.

A practical method for synthesizing 7-azaserotonin and 7-azamelatonin was developed by using 3-bromo-5-methoxy-1-tosyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-2-ol as a starting material. This compound is a useful reactant for the formal C3-electrophilic reaction. The lactone derivative obtained by the reaction with Meldrum’s acid was used as a key intermediate, in which the C2 unit was introduced into the 7-azaindole skeleton.

A concise stereoselective synthesis of (Z)-1,2-bis(arylsulfanyl)ethenes by the reaction of arylsulfonyl chlorides with calcium carbide in the presence of cuprous iodide as a catalyst is described. The salient features of this protocol are its use of an inexpensive and easily handled solid alkyne source as a surrogate for flammable and explosive gaseous acetylene, its commercially available starting materials, its high stereoselectivity, and its simple workup procedures. The stereochemical structure of a selected product was determined by single-crystal X-ray diffraction. This method can be extended to a gram scale.

Bottromycin is a structurally complex cyclic peptidic compound isolated from Streptomyces bottropensis and related organisms and belongs to the RiPP family of natural products (ribosomally synthesized and post-translationally modified peptides). It exhibits potent antibacterial properties against gram-positive pathogens (including drug resistant strains such as MRSA, MIC 1 μg/mL and VRE, MIC 0.5 μg/mL) and mycoplasma. Bottromycin blocks the binding of the aminoacyl-tRNA to the A-site on the 50S ribosome and hence inhibits protein synthesis. Bottromycins contain structurally diverse post-translational modifications (PTMs) on a small peptide (GPVVVFDC) including a unique macrocyclic amidine, rare β-methylation, terminal thiazole heterocycle, oxidative decarboxylation, and Asp epimerization, among others. It exhibits a precursor peptide organization with a C-terminal follower peptide and a N-terminal core peptide. There are several new studies reported recently which gave detailed insights into the bottromycin biosynthesis pathway. This Account highlights the current advancements in understanding the biosynthetic pathway of bottromycin focusing mainly on the biochemically and structurally characterized enzymes and intricate details of the peptide–protein biophysical interactions. These studies have provided a strong foundation for conducting combinatorial biosynthesis and synthetic biological studies to create novel bottromycin variants for therapeutic applications.1 Introduction2 Biosynthetic Pathway for Bottromycin3 Enzymology of Bottromycin Biosynthesis3.1 Cleavage of Methionine (BotP)3.2 Radical SAM Methyltransferases (BotRMT1, BotRMT2, BotRMT3)3.3 ATP-Dependent YcaO Enzymes3.3.1 Thiazoline Formation by BotC3.3.2 Macrolactamidine Formation by BotCD3.4 Follower Peptide Hydrolysis (BotAH)3.5 Aspartate Epimerization (BotH)3.6 Oxidative Decarboxylation (BotCYP)3.7 O-Methyltransferase (BotOMT)4 Heterologous Bottromycin Production and Analogue Preparation5 Summary and Outlook

An efficient approach for the photosynthesis of various arylated 2-aryl-2H-indazoles (38 examples) in moderate to good yields (up to 87% yield) under mild conditions was developed by employing 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) as an inexpensive photocatalyst. This protocol features wide substrate scope, good functional group tolerance, and operational simplicity. In addition, the strategy was successfully applied to the late-stage modification of drug molecules, and the meaningful introduction of complex drugs to the skeleton of 2H-Indazole was achieved for the first time.

A transition-metal-free synthesis of 3-ethynylcoumarins from salicylaldehyde-derived alkynoates was developed involving a DBU-promoted intramolecular Morita–Baylis–Hillman-type reaction/dehydration/isomerization cascade. A wide variety of alkynoates were employed to deliver 3-ethynylcoumarins in moderate to good yields.

We report a catalyst-free method for the alkylation/annulation of N-arylacrylamides to give the corresponding 3-alkyl-2-oxo-2,3-dihydro-1H-indoles by using alkyl iodides as precursors of alkyl radicals. These reactions occur at moderate temperatures and are mediated by easily accessible K2S2O8 and Bu3N.

As a promising pharmacophore, sulfondiimines have drawn increasing attention in recent years, but their uptake in medicinal chemistry is jeopardized by the scarcity of related transformations. Herein, we report a facile and mild N-alkylation protocol of NH-diphenyl sulfondiimines with alkyl halides to prepare a myriad of N-alkylated diphenyl sulfondiimines. Owing to air atmosphere, room temperature, as well as mild reaction conditions, this protocol has exhibited great potential in organic synthesis and medicinal chemistry by the late-stage functionalization of natural products.