Ruthenium(II)-Catalyzed C–H Bond Activation and Functionalization

To improve the atom- and step-economy of organic syntheses, researchers would like to capitalize upon the chemistry of otherwise inert carbon–hydrogen (C–H) bonds. During the past decade, remarkable progress in organometallic chemistry has set the stage for the development of increasingly viable metal catalysts for C–H bond activation reactions. Among these methods, oxidative C–H bond functionalizations are particularly attractive because they avoid the use of prefunctionalized starting materials. For example, oxidative annulations that involve sequential C–H and heteroatom–H bond cleavages allow for the modular assembly of regioselectively decorated heterocycles. These structures serve as key scaffolds for natural products, functional materials, crop protecting agents, and drugs. While other researchers have devised rhodium or palladium complexes for oxidative alkyne annulations, my laboratory has focused on the application of significantly less expensive, yet highly selective ruthenium complexes.This Ac...

Carboxylate-assisted ruthenium-catalyzed alkyne annulations by C-H/Het-H bond functionalizations.

Synthetically useful functional groups, including ketones, amides, carbamates, carboxylic acids, aldehydes or ethers, have been identified as weakly coordinating directing groups in efficient ruthenium(II)-catalyzed CH functionalizations. This strategy set the stage for versatile CH bond olefinations, oxygenations, nitrogenations and oxidative alkyne annulations among others. Thereby, step-economical access to diversely decorated arenes and heteroarenes was provided in a sustainable fashion.

Weakly Coordinating Directing Groups for Ruthenium(II)‐ Catalyzed CH Activation

6.1. Oxadiazoles 4154 6.2. Diazaphospholes 4154 7. Six-Membered Heterocycles with One Heteroatom 4155 7.1. Pyridines 4155 7.2. Pyridinones 4155 7.3. Quinolines 4156 7.4. Quinolinones 4157 7.5. Isoquinolines 4157 7.6. Acridines 4158 7.7. Pyranones 4158 7.8. Flavones 4159 8. Six-Membered Heterocycles with Two Heteroatoms 4159 8.1. Pyridazinones 4159 8.2. Pyrimidines 4159 8.3. Pyrimidinones 4160 8.4. Quinazolines 4162 8.5. Quinazolinones 4162 8.6. Quinoxalines 4164 8.7. Quinoxalinediones 4165 8.8. Oxazines 4165 8.9. Oxazinones 4166 8.10. Thiazines 4166 9. Six-Membered Heterocycles with Three Heteroatoms 4166

Solvent-free heterocyclic synthesis.

The use of coordinating moieties as directing groups for the functionalisation of aromatic carbon–hydrogen (C–H) bonds has become an efficient strategy for the selective construction of new carbon–carbon (C–C) and carbon–heteroatom (C–X) bonds in arenes. However many directing groups cannot be easily removed/modified from the products after C–H functionalisation, thus limiting the structural diversity of the products. This limitation can be overcome by employing removable/modifiable or traceless directing groups which can be easily attached to the starting materials and detached from the products. In this tutorial review, we give an overview of recent advances in this emerging field which have dramatically increased the synthetic applicability of C–H functionalisation processes.

Arene C–H functionalisation using a removable/modifiable or a traceless directing group strategy

1,5-Benzothiazepine, a versatile pharmacophore: a review.

Ruthenium-catalyzed C-H bond arylations of arenes bearing removable directing groups via six-membered ruthenacycles.

Diversity oriented design of various hydrazides and their in vitro evaluation against Mycobacterium tuberculosis H37Rv strains.

Synthesis, anti-tubercular activity and 3D-QSAR study of coumarin-4-acetic acid benzylidene hydrazides.

In continuation of our research program on new antitubercular agents, this article is a report of the synthesis of 97 various symmetrical, unsymmetrical, and N-substituted 1,4-dihydropyridines. The synthesized molecules were tested for their activity against M. tuberculosisH37Rv strain with rifampin as the standard drug. The percentage inhibition was found in the range 3–93%. In an effort to understand the relationship between structure and activity, 3D-QSAR studies were also carried out on a subset that is representative of the molecules synthesized. For the generation of the QSAR models, a training set of 35 diverse molecules representing the synthesized molecules was utilized. The molecules were aligned using the atom-fit technique. The CoMFA and CoMSIA models generated on the molecules aligned by the atom-fit method show a correlation coefficient (r2) of 0.98 and 0.95 with cross-validated r2(q2) of 0.56 and 0.62, respectively. The 3D-QSAR models were externally validated against a test set of 19 molecules (aligned previously with the training set) for which the predictive \({r^{2} (r^{2}_{\rm pred})}\) is recorded as 0.74 and 0.69 for the CoMFA and CoMSIA models, respectively. The models were checked for chance correlation through y-scrambling. The QSAR models revealed the importance of the conformational flexibility of the substituents in antitubercular activity.

Atul Manvar

Papers

1,5-Benzothiazepine, a versatile pharmacophore: a review.

Ruthenium-catalyzed C-H bond arylations of arenes bearing removable directing groups via six-membered ruthenacycles.

Diversity oriented design of various hydrazides and their in vitro evaluation against Mycobacterium tuberculosis H37Rv strains.

Synthesis, anti-tubercular activity and 3D-QSAR study of coumarin-4-acetic acid benzylidene hydrazides.

Synthesis, in vitro antitubercular activity and 3D-QSAR study of 1,4-dihydropyridines