Isai Ramakrishna

Bio: Isai Ramakrishna is an academic researcher from Indian Institute of Technology Madras. The author has contributed to research in topics: Amino acid & Aldol reaction. The author has an hindex of 11, co-authored 60 publications receiving 276 citations.

Copper-Catalyzed 8-Amido Chelation-Induced Remote C−H Amination of Quinolines

Abstract: A copper-catalyzed 8-amide chelation-induced remote C-H amination of quinolines has been developed. This direct amination with readily available azodicarboxylates proceeded with perfect C5-regioselectivity offering amino-substituted 8-aminoquinolines, important bioactive molecular scaffolds, in very high yields (up to 96%). A single-electron transfer (SET)-mediated mechanism with kH /kD =1.1 was proposed after trapping of the radical intermediate.

Nickel-Catalyzed Direct Alkenylation of Methyl Heteroarenes with Primary Alcohols.

Abstract: An efficient nickel-catalyzed acceptorless dehydrogenative coupling of methyl-substituted heteroarenes with primary alcohols is achieved using an in situ generated complex of inexpensive NiBr2 and readily available 8-aminoquinoline picolinic amide ligand. The protocol is operationally simple and scalable and furnishes a series of high-value 2-alkenylheteroarenes in good yields (up to 88%) with exclusive E-selectivity. The reaction proceeds with the release of water and molecular hydrogen, which was analyzed through gas chromatography to validate the reaction mechanism.

Metal-free switchable ortho/ipso-cyclization of N-aryl alkynamides: divergent synthesis of 3-selenyl quinolin-2-ones and azaspiro[4,5]trienones.

Abstract: A selenium radical triggered switchable ortho/ipso-cyclization cascade of N-aryl alkynamides has been devised under metal-free conditions to access 3-selenyl quinolin-2-ones and 3-selenospiro[4,5]trienones in high yields (up to 98%). The simple protocol is scalable and the mechanistic studies suggest that the radical cascade proceeds through a spirocyclic intermediate which is formed via an intramolecular ipso-cyclization route.

Metal-Involving Synthesis and Reactions of Oximes

Abstract: This review classifies and summarizes the past 10–15 years of advancements in the field of metal-involving (i.e., metal-mediated and metal-catalyzed) reactions of oximes. These reactions are diverse in nature and have been employed for syntheses of oxime-based metal complexes and cage-compounds, oxime functionalizations, and the preparation of new classes of organic species, in particular, a wide variety of heterocyclic systems spanning small 3-membered ring systems to macroheterocycles. This consideration gives a general outlook of reaction routes, mechanisms, and driving forces and underlines the potential of metal-involving conversions of oxime species for application in various fields of chemistry and draws attention to the emerging putative targets.

o-Silylaryl Triflates: A Journey of Kobayashi Aryne Precursors.

Abstract: Arynes are among the most active organic intermediates and have found numerous applications in expeditious preparation of substituted arenes. In the past 20 years, chemists have witnessed a resurgence in aryne chemistry, which is mainly attributed by the extensive utilization of Kobayashi's method, a fluoride-induced removal of the TMS group with concomitant departure of its ortho OTf group on o-silylaryl triflates. Nowadays, o-silylaryl triflates are the most frequently employed aryne precursors. This review provides an overview of the history of Kobayashi's method, its methodological achievements, and its applications in the synthesis of natural products, bioactive molecules, and polycyclic aromatic hydrocarbons.

A first example of cobalt-catalyzed remote C-H functionalization of 8-aminoquinolines operating through a single electron transfer mechanism

Abstract: The development of new C[BOND]H functionalization protocols based on inexpensive cobalt catalysts is currently attracting significant interest. Functionalized 8-aminoquinoline compounds are high-potential building blocks in organic chemistry and pharmaceutical compounds and new facile routes for their preparation would be highly valuable. Recently, copper has been applied as catalyst for the functionalization of 8-aminoquinoline compounds and found to operate through a single electron transfer (SET) mechanism, although requiring elevated reaction temperatures. Herein, we described the first example of a cobalt-catalyzed remote C[BOND]H functionalization of 8-aminoquinoline compounds operating through a SET mechanism, exemplified using a practical and mild nitration protocol. The reaction uses inexpensive cobalt nitrate hexahydrate [Co(NO3)2⋅6 H2O] as catalyst and tert-butyl nitrite (TBN) as nitro source. This methodology offers the basis for the facile preparation of many new functionalized 8-aminoquinoline derivatives.

A general method for the metal-free, regioselective, remote C–H halogenation of 8-substituted quinolines

Abstract: An operationally simple and metal-free protocol for geometrically inaccessible C5–H halogenation of a range of 8-substituted quinoline derivatives has been established. The reaction proceeds under air, with inexpensive and atom economical trihaloisocyanuric acid as a halogen source (only 0.36 equiv.), at room temperature. Exceptionally high generality with respect to quinoline is observed, and in most instances, the reaction proceeded with complete regioselectivity. Quinoline with a variety of substituents at the 8-position gave, exclusively, the C5-halogenated product in good to excellent yields. Phosphoramidates, tertiary amides, N-alkyl/N,N-dialkyl, and urea derivatives of quinolin-8-amine as well as alkoxy quinolines were halogenated at the C5-position via remote functionalization for the first time. This methodology provides a highly economical route to halogenated quinolines with excellent functional group tolerance, thus providing a good complement to existing remote functionalization methods of quinolin-8-amide derivatives and broadening the field of remote functionalization. The utility of the method is further showcased through the synthesis of several compounds of biological and pharmaceutical interest.

Chemo- and Stereoselective Transition-Metal-Free Amination of Amides with Azides.

Abstract: The synthesis of α-amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we present a stereoselective α-amination of amides employing simple azides that proceeds under mild conditions with release of nitrogen gas. The amide is used as the limiting reagent, and through simple variation of the azide pattern, various differently substituted aminated products can be obtained. The reaction is fully chemoselective for amides even in the presence of esters or ketones and lends itself to preparation of optically enriched products.