Traditional and sustainable approaches for the construction of C-C bonds by harnessing C-H arylation.

Biaryl scaffolds are found in natural products and drug molecules and exhibit a wide range of biological activities. In past decade, the transition metal-catalyzed C-H arylation reaction came out as an effective tool for the construction of biaryl motifs. However, traditional transition metal-catalyzed C-H arylation reactions have limitations like harsh reaction conditions, narrow substrate scope, use of additives etc. and therefore encouraged synthetic chemists to look for alternate greener approaches. This review aims to draw a general overview on C-H bond arylation reactions for the formation of C-C bonds with the aid of different methodologies, majorly highlighting on greener and sustainable approaches.

Photoinduced Regioselective Olefination of Arenes at Proximal and Distal Sites.

The Fujiwara-Moritani reaction has had a profound contribution in the emergence of contemporary C-H activation protocols. Despite the applicability of the traditional approach in different fields, the associated reactivity and regioselectivity issues had rendered it redundant. The revival of this exemplary reaction requires the development of a mechanistic paradigm that would have simultaneous control on both the reactivity and regioselectivity. Often, the high thermal energy required to promote olefination leads to multiple site functionalizations. To this aim, we established a photoredox catalytic system constituting a merger of palladium/organo-photocatalyst (PC) that forges oxidative olefination in an explicit regioselective fashion with diverse arenes and heteroarenes. Visible light plays a significant role in executing "regioresolved" Fujiwara-Moritani reactions without the requirement of silver salts and thermal energy. The catalytic system is also amenable toward proximal and distal olefination aided by the respective directing groups (DGs), which entails the versatility of the protocol in engaging the entire spectrum of C(sp2)-H olefination. Furthermore, streamlining the synthesis of natural products, chiral molecules, drugs, and diversification through late-stage functionalizations underscore the importance of this sustainable protocol. The photoinduced attainment of this regioselective transformation is mechanistically established through control reactions and kinetic studies.

Imine as a linchpin approach for meta-C-H functionalization.

Despite the widespread applications of C-H functionalization, controlling site selectivity remains a significant challenge. Covalently attached directing groups (DGs) served as ancillary ligands to ensure ortho-, meta- and para-C-H functionalization over the last two decades. These covalently linked DGs necessitate two extra steps for a single C-H functionalization: introduction of DG prior to C-H activation and removal of DG post-functionalization. Here we report a temporary directing group (TDG) for meta-C-H functionalization via reversible imine formation. By overruling facile ortho-C-H bond activation by imine-N atom, a suitably designed pyrimidine-based TDG successfully delivered selective meta-C-C bond formation. Application of this temporary directing group strategy for streamlining the synthesis of complex organic molecules without any necessary pre-functionalization at the meta position has been explored.

Transient directing ligands for selective metal-catalysed C-H activation.

C-H activation is a 'simple-to-complex' transformation that nature has perfected over millions of years of evolution. Transition-metal-catalysed C-H activation has emerged as an expeditious means to expand the chemical space by introducing diverse functionalities. Notably, among the strategies to selectively cleave a particular C-H bond, the catalytic use of a small molecule as co-catalyst to generate a transient directing group, which provides a balance between step economy and chemical productivity, has gained immense attention in recent years. This allows one to convert a desired C-H bond irrespective of its geometrical or stereochemical configuration. This Review describes the various transient directing groups used in C-H activation and explains their mechanistic significance.