Accessing C2‐Functionalized 1,3‐(Benz)azoles through Transition Metal‐Catalyzed C−H Activation

Abstract

The skeletal presence of 1,3-azoles in a variety of bioactive natural products, pharmacophores, and organic materials demands the derivatization of such heteroarenes regioselectively. Plenty of cross-coupling as well as cyclocondensation reactions have been performed to build up these skeletons but remained commercially unrealizable. A couple of severe drawbacks are faced by these traditional protocols that require a more straightforward strategy to obviate them. Transition metal-catalyzed CÀ H functionaliza-tion has emerged as a superior alternative in that context. 1,3-Azoles and their benzo counterparts have been extensively functionalized exploiting both noble and earth-abundant transition metals. Lately, C-2 functionalization have gained much traction due to the ease of attaining high regioselectivity and installation of synthetically manipulative functionalities. This critical review presents a bird's eye view of all major C-2 functionalization of (benz)azoles catalyzed by a diverse set of metals performed over the past 15 years.

Development and Validation of a Chemoinformatic Workflow for Predicting Reaction Yield for Pd-Catalyzed C-N Couplings with Substrate Generalizability

“…oxazoles, imidazoles, thiazoles) which can be activated by palladium. 24 The goal of this limited reactant scope was to take the universe of N-H containing compounds and define a microcosm of representative examples for this study. In a similar manner, 50 (hetero)aryl bromides were selected to broadly represent many building blocks of interest to pharmaceutical development as well as their ability to represent a range of electronic and steric properties.…”

Ligandless Palladium-catalyzed Direct C-5 arylation of azoles Promoted by Benzoic Acid in Anisole

“…ESI-MS m/z 204 [M+H] + . EI-MS, m/z (%): 203 (100), 173 (19), 130 (17), 103 (16), 89 (32). 1 H NMR (400 MHz, CDCl3) δ 8.32 -8.28 (m, 2H), 7.61 -7.55 (m, 3H), 7.27 (s, 1H), 3.76 (s, 3H).…”

Transition-metal-catalyzed C–H bond alkylation using olefins: recent advances and mechanistic aspects

“…1–11 Within the domain, transition metal catalysis forms the largest, ever expanding subset contributing to the broad spectrum of applications that ranges from organic synthesis to petrochemical processing. 12–20 In this context, the development of novel methods to access arylation, 21–24 alkenylation 25–27 and alkynylation of C–H bonds 28 has gained tremendous attention. In comparison, alkylative C–H functionalizations have remained fairly scarce in the realm of transition metal catalysis due to the inert nature of the C–H bond, the large kinetic barrier for the C–H bond cleavage and its ubiquitous nature.…”