Benzylic C(sp3)–H/C(sp2)–H cross-dehydrogenative coupling

Hydroacylation of alkenes, hydroamination, hydroalkylation, hydroalkoxylation, hydrocarboxylation

Functionalization reaction of C (sp2) -H bonds

Selective functionalization of one specific C(sp2 )–H bond in a complex molecule without the assistance of a directing group represents the state of the art in organic synthesis and will be a dynamic topic in future. In the past decade, many excellent methods have been developed to accomplish this goal with transition metal catalysts and even under metal-free conditions. Aldehydes with electron-withdrawing groups gave good yields of the corresponding products. Aldehydes with electron-donating groups gave a slightly lower yield of the product presumably due to the difficult C–H bond cleavage of aldehyde.

Proximity-driven metalation has been extensively exploited to achieve reactivity and selectivity in carbon-hydrogen (C-H) bond activation. Despite the substantial improvement in developing more efficient and practical directing groups, their stoichiometric installation and removal limit efficiency and, often, applicability as well

Transition-metal-catalyzed C–H bond functionalization directed by heteroatom directing groups is one of the most powerful tools in recent organic synthesis for the regioselective formation of carbon–carbon and carbon–heteroatom bond

sp2(C)– sp(C)coupling

Non directed sp2(C)– sp2(C)coupling

Directed sp2(C)– sp2(C)coupling

(Arene and olefin or olefin and olefin or aldehyde and olefin)

The olefination of unreactive aryl C–H bonds catalyzed by transition metals is among the most significant chemical transformations in organic syntheses The olefination of arene via the C–H activation have been accomplished by noble metal catalyst such as ruthenium,rhodium,palladium,cobalt,and iridium,with high temperature and organic solvents. These catalysts generally show high reactivity and broad substrate scope. Selective olefination, for instance Mono- and di-olefination via C–H activation has been of great interest and could be controlled by changing the solvent, catalyst or substrate. Selective synthesis of mono- and di-olefinated products at room temperature is yet to be developed. Many volatile and environmentally toxic organic solvents are commonly applied in the C–H olefination. In recent years, many researchers have paid attention to the replacement of these harmful solvents with an eco-friendly medium to meet the requirement of green chemistry. Though water and polyethylene glycol are extensively studied in some chemical transformations, their applications are significantly restricted by the low solubility of starting compounds and metal catalysts. Considering this, it is preferable to find an excellent medium to allow the C–H olefination to perform smoothly under mild conditions and reuse the metal catalyst.

For eg selective mono and di-olefination of 2-phenylpyridines and related arenes using styrenes utilising ([Cp*RhCl2]2); (Cp*Rh(OAc)2); ([Cp*CoCl2]2); ([Ru(p-cymene)Cl2]2) catalysts

Functionalization reaction of C (sp) -H bonds

Hydroacylation reactions

(alkene or alkyne and carbonyl group- sp2 C-H aor sp C-H and sp2 C activations)

Hydroacylation is a reaction in which alkene or alkyne or a carbonyl group is inserted into a formyl C-H bond. (the formal addition of an aldehyde CH bond across an unsaturated C-C bond), The product may be a ketone or chalcones. The hydroacylation begins with oxidative addition of the aldehydic carbon-hydrogen bond. The resulting acyl metal hydride complex next binds the alkene, the alkene inserts into either the metal-acyl or the metal-hydride bonds. In the final step, the resulting alkyl-acyl or beta-ketoalkyl-hydride complex undergoes reductive elimination .

Transition metal-catalyzed alkene hydroacylation, has emerged as a powerful, catalytic process to synthesize ketones, greatly expanded the scope and synthetic utility of these hydroacylation reactions in recent years. Intramolecular alkene hydroacylation reactions are now well-established methods to synthesize carbocyclic and heterocyclic ketones, often with high enantioselectivities.

These transformations generally occur in the presence of transition-metal or NHC catalysts, and the selection of the specific catalyst type determines the regiochemical outcome of the reaction. NHC-catalyzed intramolecular hydroacylations occur with exoselectivity (formal Markovnikov selectivity), while transition metal-catalyzed hydroacylations can occur with either endo-selectivity (formal anti-Markovnikov selectivity) or exo-selectivity. In addition, the development of intermolecular hydroacylations of new combinations of alkenes and alkynes with aldehydes continues to rapidly expand and provide direct routes to new ketones from simple starting materials.

Aldehyde- alkyne metathesis (sp2 C- and sp C-H activation)

An intramolecular ring-closing alkyne–carbonyl metathesis reaction has received much attention, since valuable functionalized hetero- and carbocycles can be readily formed under mild conditions. Moreover, such reactions are highly efficient and atom-economical by nature, unfortunately, and have been less explored. Notably, this reaction has been mostly employed for the synthesis of five- or six- membered heterocycles or carbocycles and seven-membered heterocycles

This reaction normally proceeds through a [2 + 2] cycloaddition and cycloreversion processes by the activation of the carbonyl group by formation of σ-complex or activation of alkyne by formation of π-complex or activation of both simultaneously depending on the catalyst.

Generally, this reaction is initiated either by Brønsted acids or Lewis acids such as TfOH, HBF4, BF3·OEt2, , In(OTf)3, AgSbF6, AuCl3, and a combination of AuCl3/AgSbF6 acting as a catalyst for this process. During our ongoing interest in the area of development of Deep eutectic system catalyzed reactions, has employed an intramolecular alkyne–carbonyl metathesis strategy in developing an alternative process for the efficient construction of carbo- and heterocycles

Furthermore, DES is inexpensive and environmentally friendly so it is highly desirable in organic synthesis. Keeping in mind these facts, we envisioned that the alkyne–carbonyl metathesis strategy could also be applied to the synthesis of functionalised seven-membered oxygen heterocycles such as ------ from easily available starting materials

Late stage-diversification through direct C-H activation and functionalization strategy

late stage C–H Direct arylation, late stage C–H heteroarylation, late stage C–H alkynylation, late stage C-H amination late-stage aroylation,

C–C/C–N/C-O/C-S bond formation via C–H C-C, C-N activation & functionalization

Activation of abundant C-O, C-N and C-C bonds via oxidative addition of a low-valent, electron-rich transition metal. nickel(0), rhodium(I), ruthenium(0) and iron catalysts for electronically activated substrates, sometimes assisted by chelating functional groups

allylic alkylation with alkynes, hydroallylation, hydroamination, hydroalkylation, hydroalkoxylation, hydrocarboxylation of alkynes as redox-neutral allyl precursors, allylation of tautomerizable heterocycles with alkynes

Transesterification, transamidation, decarboxylative chemoselective Amination of Aryl Acetic Acids, deaminative alkynylation of amines,

decarboxylative Csp3-Csp3 (utilizing nitromethane), Csp3-Csp2 (utilizing indole) , and Csp3-Csp utilizing(alkynes) coupling of amines (pyrrolidine carboxylic acid)