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Oxime ethers are extensively present as key components in numerous active pharmaceutical ingredients and many other synthetically viable organic compounds. Herein, we present a metal, base and additive free mild C-O bond formation strategy for the synthesis of oxime ethers from various oxime derivatives and tertiary and secondary aryl alcohols. The reaction is carried out in the presence of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as the green solvent at 30 °C. The reaction tolerates both aldoximes and ketoximes including ketoximes bearing heteroatoms, furnishing high yields (up to 99%). The formation of a triphenylmethyl carbocation as an intermediate is supported via UV-Vis spectroscopy. Successful gram-scale synthesis of the oxime ether, low energy input and simple reaction conditions further highlight the potential of this reaction to effectively transition from the laboratory scale to industrial production. A broad substrate scope compatibility was also observed.

A system utilizing palladium(II)-PEG has been devised for the intramolecular Heck cyclization of N -vinyl and N -allyl-2-haloanilines. The synthesis of a variety of indoles, including 2,3-diester substituted ones and 3-methyl indoles, has been accomplished using this catalytic system. The N -vinyl starting materials are obtained by the aza-Michael addition of 2-haloanilines with alkynecarboxylate esters, which, upon cyclization, yield ester-substituted indoles. Conversely, N -allyl-2-haloanilines yield 3-methylated indoles as the major products. The high activity of the system is owed to the in situ generation of Pd nanoparticles.

Molecular-iodine catalyzed access to an important class of bio-relevant indole derivatives, cyclopenta[ b ]indoles, has been achieved via a cascade addition/intramolecular cyclization reaction of indoles and acetone. Explorations of diverse substitution patterns revealed an essential substrate-control in the reaction. The high-density electronic core of indole is pivotal in favouring the formation of indolyl-cyclopenta[ b ]indole derivatives; in contrast, the electron deficiency of the core hindered the cyclization process, directing the formation of bis(indolyl)propanes. Investigations on the mechanistic pathway revealed that bis(indolyl)alkanes were the intermediates for the addition-cyclization process. This simple experimental method provides sustainable synthetic access to cyclopentannulated indoles.

Halogen bonding triggered by the Lewis basic nature of acetonitrile catalyzes the site-selective C-3 triaryl methylation of indoles and N -triaryl methylation of imidazoles with trityl chlorides under catalyst-, metal-, and additive-free conditions at room temperature. This method generates a quaternary carbon centre appended to a heterocyclic moiety. UV-Vis and FT-IR analyses indicate the existence of halogen bonding which is the driving force of the reaction. This approach is suitable for a wide range of substrates, furnishing moderate to excellent yields (up to 100%) of triaryl methylated products under ambient reaction conditions. Equimolar amounts of reactants are sufficient to obtain the optimum yield and in some cases pure products can be obtained without column chromatography.

N , N '-Dimethylurea (DMU) is introduced as a ligand to aid the Chan-Lam N -arylation of primary amides, amines, and 3-aminophenols with arylboronic acids and its ester derivative as the arylating associate. The developed methodology is catalyzed by Cu and its in situ complexation with DMU brings about efficient synthesis of N -arylated anilines, 3-aminophenols, and primary amides in moderate to good yields (50-90%). The [Cu 2 (OAc) 4 (DMU) 2 ] complex is synthesized and characterized by single crystal structure elucidation. The catalyst is cheap, free from prior synthesis of a metal complex, provides chemoselectivity towards the N -arylation of 3-aminophenols, and is suitable for mono-arylation of primary amides. The synthetic utility of the methodology is tested in the post-modification of two active pharmaceutical ingredients (APIs). The developed catalytic system extends the scope of N , N '-dimethylurea as an auxiliary in inexpensive and versatile Cu catalysis.

Facilitated by the dual role of Ceric Ammonium Nitrate (CAN), herein we report a cost-effective approach for the cyanation of aryl iodides/bromides with CAN-DMF as an addition to the existing pool of combined cyanation sources. In addition to being an oxidant, CAN acts as a source of nitrogen in our protocol. The reaction is catalyzed by a readily available Cu(ii) salt and the ability of CAN to generate ammonia in the reaction medium is utilized to eliminate the additional requirement of a nitrogen source, ligand, additive or toxic reagents. The mechanistic study suggests an evolution of CN- leading to the synthesis of a variety of aryl nitriles in moderate to good yields. The proposed mechanism is supported by a series of control reactions and labeling experiments.