Recent Advances in First‐Row Transition‐Metal‐Mediated C−H Halogenation of (Hetero)arenes and Alkanes

Abstract

The ubiquity of carbon halogen bonds in the structural core of numerous biomolecules and pharmaceuticals along with their role as synthetic precursors in various organic reactions makes the organic halides a crucial class of organic compounds. Consequently, the synthesis of organic halides with high regioselectivity is of paramount importance in synthetic chemistry. In nature, selective halogenation is achieved by metalloenzymes with high efficiency involving high-valent iron-oxo as active species. The high selectivity of halogenating enzymes attracted considerable attention leading to the development of several biomimetic approaches for CÀ H halogenation. Moreover, the emergence of transition metal (TM) catalyzed site-selective CÀ H halogenation protocols through the development of several directed strategies has also been impressive. There has been significant development in the first row TM catalyzed CÀ H halogenation reactions despite the dominance of late transition metals catalysts in this field. But in literature, there is no up-to-date recent review article that consolidates bio-mimetic as well as synthetic strategies of CÀ H halogenation (X = Cl, Br, I) containing organo-fluorination with all the first-row transition metals. Thus, we got motivated and have focused to elucidate the recent developments of first row TM-catalyzed CÀ H halogenation of (hetero)arenes and alkanes through biomimetic approaches as well as directed and undirected strategies in this present review. Additionally, this review covers the recent progresses in the CÀ H fluorination methodologies. Altogether, the review will provide a combined overview of all the strategies of first-row transition-metalmediated CÀ H halogenation reactions that may benefit the scientific community towards the development of new methodologies in this field.

Recent Advances in Alkenyl sp2 C–H and C–F Bond Functionalizations: Scope, Mechanism, and Applications

“…The carbon–halogen bond is one of the central functional groups in organic chemistry. With the ever-increasing efforts devoted toward transition-metal-catalyzed C–H functionalizations, the direct C–H halogenation has also gained considerable momentum in recent years. − For example, Glorius and co-workers in 2013 demonstrated a remarkable Cp*Rh­(III)-catalyzed alkenyl C­(sp 2 )–H bond halogenation of various α,β-unsaturated amides with readily available N -bromosccinimide and N -iodosuccinimide to obtain diverse Z -haloacrylamide derivatives in DCE at 60 °C (Scheme a) . Indeed, a large variety of synthetically useful and versatile functional groups are tolerated in this case.…”

Preparation and Characterization of a Formally NiIV–Oxo Complex with a Triplet Ground State and Application in Oxidation Reactions

“…High-valent first-row transition-metal–oxo species are active intermediates in oxidation reactions that are important in biology, oxidative chemical transformations, and water splitting for the generation of renewable energy carriers. , Fe– and Mn–oxo species are active intermediates in enzymes like cytochrome P450, methane monooxygenase, mononuclear non-heme iron enzymes, and photosystem II, to name a few examples. , While Fe, Mn, and Cu are the favored metals for biology–high-valent Cu intermediates have been proposed for some enzymes but are less studied − –outside of bioinorganic chemistry, similar species with other transition metals have been used in chemical oxidation reactions, that is, oxygen atom transfer (OAT) and C–H activation. − Metal–oxo moieties are also relevant for renewable energy-related reactions, like the oxidative side of water splitting, referred to as the oxygen evolution reaction (OER), and the reduction of O 2 to water in fuel cells. − A notable example of the former is Nocera’s artificial leaf, which catalyzes the OER via a high-valent Co–oxo intermediate . Additionally, though more recently developed, there are several molecular Ni-based OER catalysts that also likely operate through high-valent Ni–O intermediates …”

Copper-catalyzed regioselective C2–H chlorination of indoles with para-toluenesulfonyl chloride

“…Transition-metal-catalyzed directing-group assisted C–H functionalization has emerged as an atom-economic and powerful tool in organic synthesis. 8 With regard to this, a broad variety of transition-metal-mediated or catalyzed C–H chlorination of (hetero)arenes have been successfully developed, 9 in which NCS, 10 DCE, 11 a,b CuCl 2 11 c,d and others 12 were employed as the chlorinating reagents. However, to the best of our knowledge, there is only one such report for the synthesis of 2-chloroindoles (Scheme 1a).…”