Pyridine-directed Rh-catalyzed C6-selective C–H acetoxylation of 2-pyridones

A Rh(III)-catalyzed C-H acetoxylation of 2-pyridones with phenyliodine(III) diacetate (PIDA) in a DCE/AcOH mixed solvent system has been developed using N-2-pyridyl function as directing group. The reaction occurs under mild conditions, typically in air at 40 oC, to selectively produce the corresponding C6-acetoxylated 2-pyridones in moderate to good yields.Hazra S., Hirano K., Miura M.. Pyridine-directed Rh-catalyzed C6-selective C–H acetoxylation of 2-pyridones. Heterocycles 101, 223 (2020); https://doi.org/10.3987/com-19-s(f)16

Solvent-Controlled Rhodium-Catalyzed C6-Selective C−H Alkenylation and Alkylation of 2-Pyridones with Acrylates

A solvent-controlled rhodium-catalyzed C6-selective alkenylation and alkylation of 2-pyridones with acrylates via a pyridine-directed C−H cleavage was developed. Using DMF as solvent, the C−H alkenylation with acrylates selectively occurs to deliver the corresponding C6-alkenylated 2-pyridones in good yields. On the other hand, the C6-alkylated products are predominantly formed in a more polar and protic solvent, HFIP. Thus, a single set of starting substrates can be divergently transformed to C6-functionalized 2-pyridones, which are of potent interest in medicinal and pharmaceutical chemistry.This is the accepted version of the following article:Hazra S., Hirano K., Miura M.. Solvent-Controlled Rhodium-Catalyzed C6-Selective C−H Alkenylation and Alkylation of 2-Pyridones with Acrylates. Asian Journal of Organic Chemistry 8, 1097 (2019), which has been published in final form at https://doi.org/10.1002/ajoc.201900190. This article may be used for non-commercialpurposes in accordance with the Wiley Self-ArchivingPolicy [https://authorservices.wiley.com/author-resources/Journal-Authors/licensing/self-archiving.html

N-Phosphine Oxide-Substituted Imidazolylidenes (PoxIms): Multifunctional Multipurpose Carbenes

This article discusses the concept of N-heterocyclic carbenes (NHCs) equipped with more than one functional moiety, which allows using these NHCs for multiple purposes. A pioneering example for such NHCs is N-phosphine oxide-substituted imidazolylidenes (PoxIms), and their synthesis and strategic use are highlighted. The utility of PoxIms by far exceeds the conventional use as multidentate ligands for metal complexes on account of the synergetic functions of the carbene and the N-phosphine oxide group(s).Hazra S., Hoshimoto Y., Ogoshi S.. N-Phosphine Oxide-Substituted Imidazolylidenes (PoxIms): Multifunctional Multipurpose Carbenes. Chemistry - A European Journal 23, 15238 (2017); https://doi.org/10.1002/chem.201703644

Rhodium-Catalyzed C4-Selective C-H Alkenylation of 2-Pyridones by Traceless Directing Group Strategy

A rhodium-catalyzed C4-selective C-H alkenylation of 3-carboxy-2-pyridones with styrenes has been developed. The carboxylic group at the C3 position works as the traceless directing group, and the corresponding C4-alkenylated 2-pyridones are obtained exclusively with concomitant decarboxylation. Unlike the reported procedures, the exclusive C4 selectivity is uniformly observed even in the presence of potentially more reactive C-H bonds at the C5 and C6 positions. By using this strategy, the multiply substituted 2-pyridone can be prepared via sequential C-H functionalization reactions.Hazra S., Hirano K., Miura M.. Rhodium-Catalyzed C4-Selective C-H Alkenylation of 2-Pyridones by Traceless Directing Group Strategy. Organic Letters. 23(4), 1388-1393, (2021), 19 February 2021; © 2021 American Chemical Society. https://doi.org/10.1021/acs.orglett.1c00050

Strategic Utilization of Multifunctional Carbene for Direct Synthesis of Carboxylic–Phosphinic Mixed Anhydride from CO2

Direct synthesis of carboxylic–phosphinic mixed anhydrides has been achieved by treating carbon dioxide with N-phosphine oxide-substituted imidazolylidenes (PoxIms) that contain both nucleophilic carbene and electrophilic phosphorus moieties. This novel mixed anhydride was efficiently derivatized into an ester, an amide, and an unsymmetrical ketone via transformation into its corresponding imidazolium salt followed by a dual substitution reaction. The presented work used well-designed multifunctional carbene reagents to establish a novel utility for carbon dioxide in organic synthesis.Hoshimoto Y., Asada T., Hazra S., et al. Strategic Utilization of Multifunctional Carbene for Direct Synthesis of Carboxylic–Phosphinic Mixed Anhydride from CO2. Angewandte Chemie - International Edition 55, 16075 (2016); https://doi.org/10.1002/anie.201609710

Solvent-Controlled Rhodium-Catalyzed C6-Selective C−H Alkenylation and Alkylation of 2-Pyridones with Acrylates

This is the accepted version of the following article:Hazra S., Hirano K., Miura M.. Solvent-Controlled Rhodium-Catalyzed C6-Selective C−H Alkenylation and Alkylation of 2-Pyridones with Acrylates. Asian Journal of Organic Chemistry 8, 1097 (2019), which has been published in final form at https://doi.org/10.1002/ajoc.201900190. This article may be used for non-commercialpurposes in accordance with the Wiley Self-ArchivingPolicy [https://authorservices.wiley.com/author-resources/Journal-Authors/licensing/self-archiving.html]A solvent-controlled rhodium-catalyzed C6-selective alkenylation and alkylation of 2-pyridones with acrylates via a pyridine-directed C−H cleavage was developed. Using DMF as solvent, the C−H alkenylation with acrylates selectively occurs to deliver the corresponding C6-alkenylated 2-pyridones in good yields. On the other hand, the C6-alkylated products are predominantly formed in a more polar and protic solvent, HFIP. Thus, a single set of starting substrates can be divergently transformed to C6-functionalized 2-pyridones, which are of potent interest in medicinal and pharmaceutical chemistry

Comparison of analgesic effect of intra-articular administration of levobupivacaine and clonidine versus ropivacaine and clonidine in day care knee arthroscopic surgery under spinal anesthesia

Introduction: Intra-articular (IA) local anesthetics are often used for the management and prevention of pain after arthroscopic knee surgery. Clonidine prolongs the duration of local anesthetics. In this study, analgesic effect of intra-articular administration of levobupivacaine and clonidine was compared with ropivacaine and clonidine in knee joint arthroscopic surgery under spinal anesthesia. Method: 88 patients, aged between 15 to 55 years, ASA I and II undergoing knee arthroscopy under spinal anesthesia were assigned into two equal groups (n = 44) in a randomized double blind protocol. Patients in Group L received 10 ml of 0.50% levobupivacaine and 1 mcg/kg clonidine and Group R received 10 ml of 0.75% ropivacaine and 1 mcg/kg of clonidine through intra-articular route at the end of the procedure. In the post-operative period, pain intensity was assessed by VAS (Visual Analogue Scale) Score recorded at 1 st , 5 th , 8 th , 12 th , 18 th post-operative hours. Duration of analgesia, total rescue analgesic dose in first 18 hours and any side effects were also recorded. Result: Group L experienced significantly longer duration of effective postoperative analgesia and lesser rescue analgesic compared to group R. Group R had higher mean VAS score at 5 th and 12 th post-operative hours (P < 0.05). No side effects were observed among the groups. Conclusion: Intra-articular administration of levobupivacaine and clonidine give better post-operative pain relief by increasing duration of analgesia, and decreasing need of rescue analgesic compared to intra-articular ropivacaine and clonidine

Total Synthesis of Coprinol

The first synthesis of coprinol has been achieved from 2-methoxy-3,5-dimethylbenzaldehyde via the intermediacy of an indanone derivative where dialkylation, Friedel–Crafts acylation, demethylation, and regioselective formation of a primary −OH group from a chloroacetyl group are the key steps