Experimental and DFT Studies on Cp*Co(III)-Catalyzed Selective C8-Olefination and Oxyarylation of Quinoline N-Oxides with Terminal Alkynes

Herein we report Cp*Co(III)-catalysed site-selective (C8)-H olefination and oxyarylation of quinoline N-oxides with terminal alkynes. The selectivity for C8-olefination and oxyarylation is sterically and electronically controlled. In case of quinoline N-oxides (unsubstituted at C2-position), only olefination product is obtained irrespective of the nature of alkynes. In contrast, majorly oxyarylation is observed when 2-substituted quinoline N-oxides are reacted with bulkier alkynes such as 9-ethynyl phenanthrene. However, alkynes with electron-withdrawing groups provided only olefination products with 2-substituted quinoline N-oxides also. The developed strategy allowed a facile functionalization of naturally derived quinoline N-oxides and terminal alkynes to deliver corresponding olefinated and oxyarylated products. In the developed protocol, the 'N-O’ bond played a dual role i.e., as a traceless directing group and an oxygen atom source (in case of oxyarylation), which is confirmed by 18O-labeling and crossover experiments. In addition, control experiments, deuterium labeling experiments, KIE studies and DFT studies are performed to understand the mechanism and origin of selectivity for different substrates. DFT studies revealed that the alkyne addition into Co-C bond is the rate limiting step. The observed product selectivity is reproduced by DFT methods. Furthermore, the energy decomposition analysis is performed to understand the origin of selec-tivity.

Cost-efficient and user-friendly 17O/18O labeling procedures of fatty acids using mechanochemistry

Two mechanochemical procedures for 17O/18O-isotope labeling of fatty acids are reported: a carboxylic acid activation/hydrolysis approach and a saponification approach.

Late-Stage 18O Labeling of Primary Sulfonamides via a Degradation-Reconstruction Pathway

A late-stage ¹⁸O labeling approach of sulfonamides that employs the corresponding unlabeled molecule as the starting material was developed. Upon deamination of the sulfonamide, a sulfinate intermediate was isotopically enriched using eco-friendly reagents H₂¹⁸O and ¹⁵NH₃(aq) to afford a M+5 isotopologue of the parent compound. This degradation-reconstruction approach afforded isolated yields of up to 96% for the stable isotope labeled (SIL) sulfonamides, and was compatible with multiple marketed therapeutics, including celecoxib, on a gram scale. The SIL products also exhibited no ¹⁸O/¹⁶O back exchange under extreme conditions, further validating the utility of this green strategy for drug labeling for both <i>in vitro</i> and <i>in vivo</i> use. This procedure was also adapted to include pharmaceutically relevant methyl sulfones by using ¹³CH₃, affording M+5 isotopic enrichment, thereby illustrating the broad utility of this methodology.

Late-Stage 18O Labeling of Primary Sulfonamides via a Degradation-Reconstruction Pathway

A late-stage ¹⁸O labeling approach of sulfonamides that employs the corresponding unlabeled molecule as the starting material was developed. Upon deamination of the sulfonamide, a sulfinate intermediate was isotopically enriched using eco-friendly reagents H₂¹⁸O and ¹⁵NH₃(aq) to afford a M+5 isotopologue of the parent compound. This degradation-reconstruction approach afforded isolated yields of up to 96% for the stable isotope labeled (SIL) sulfonamides, and was compatible with multiple marketed therapeutics, including celecoxib, on a gram scale. The SIL products also exhibited no ¹⁸O/¹⁶O back exchange under extreme conditions, further validating the utility of this green strategy for drug labeling for both <i>in vitro</i> and <i>in vivo</i> use. This procedure was also adapted to include pharmaceutically relevant methyl sulfones by using ¹³CH₃, affording M+5 isotopic enrichment, thereby illustrating the broad utility of this methodology.

Applications of Rozen’s Reagent in Oxygen-Transfer and C–H Activation Reactions

Rozen’s reagent (hypofluorous acid–acetonitrile complex, HOF·MeCN) is a robust nonspecific oxygen-transfer reagent and became a proven tool for the oxidation of difficult-to-oxidize molecules. It has been applied to instant oxygen transfers to functional groups such as alkenes, alkynes, and aromatic hydrocarbons, epoxidation, oxidation of alcohols, amines, and alkynes, oxygen-transfer reactions with nitrogen, phosphorus, and sulfur-containing substrates, and α-hydroxylation of carbonyl groups. Apart from being a potential green oxidizing agent, the complex has applications in 18O-labeling and C–H functionalization strategies. Recent uses of Rozen’s reagent in developing nanomaterials and oxidized expanded graphite indicate the enormous potential of the reagent. These aspects are discussed in this review.1 Introduction2 Synthesis and Physical Properties3 Safety and Handling4 Oxygen-Transfer Reactions4.1 General Mechanism of Oxygen Transfer4.2 Epoxidation4.3 Oxidation of Alkynes4.4 Oxidation of Aromatic Alcohols and Phenols4.5 Oxidation of Nitrogen-Containing Compounds4.6 Conversion of Aldehydes into Nitriles4.7 Oxidation of Alcohols and Ethers4.8 Oxidation of Sulfur-Containing Compounds4.9 Oxygen-Transfer Reaction with Phosphine, Phosphite, and Phosphinite Compounds5 C–H Activation Reactions5.1 Hydroxylation of Nonactivated Tertiary Saturated Carbon Center5.2 Hydroxylation of Aromatic Carbon Center5.3 α-Hydroxylation of Carbonyl Group5.4 Activation of α-Hydrogens of α-Amino Acids6 Other Uses7 Green Chemistry and Rozen’s Reagent8 Experimental Problems9 Further Applications10 Conclusions