Rhodium(III)-Catalyzed Nonaromatic sp² C–H Activation/Annulation Using NHC as a Directing and Functionalizable Group

Abstract

In parallel to the directing-group-assisted sp 2 C−H bond activation−functionalization of aromatic backbones, a similar exercise with nonaromatic sp 2 C−H bonds is also in high demand in synthetic chemistry despite several challenges pertinent to the latter process. In the presented protocol, Nheterocyclic carbene (NHC) motifs, appended to nonaromatic sp 2 C−H bond-containing organic molecules, have been used for developing a rhodium(III)-catalyzed annulation reaction with internal alkynes to synthesize a class of imidazo[1,2-a]pyridinium architectures. Mechanistic studies highlight the directing role of the NHC ligand during the C−H activation process and intermediacy of the C−H-activated Rh-NHC metallacycle in the catalysis.

C–H activation-annulation on the N-heterocyclic carbene platform

“…In this work, we succeeded in activating various non-aromatic sp 2 C-H bonds and coupling them with internal alkynes to form cationic annulated scaffolds (Scheme 9). 27 Interestingly, no intramolecular C-H activation/annulation of vinylic group was observed under these reaction conditions. Two protocols using AgOTf or Cu(OAc) 2 were achieved.…”

“…Upon successful exhibition of directing group behaviour of NHC to activate aromatic 17,19,21,24 and non-aromatic sp 2 C-H bonds at Rh-NHC platform, 27 we extrapolated our investigations to difficult-to-functionalise chelating organic molecules having strongly coordinating heteroatoms in suitable metalchelating positions. Thus, in early 2016, our group reported an unprecedented 'rollover' C-H activation-annulation of such chelating molecules based on 2-pyridylimidazolium halide motifs as NHC backbone.…”

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

“…A non-aromatic C(sp 2 )–H bond activation-functionalization of imidazolium salts 327 with internal alkynes catalyzed by Rh(III) was reported by Thenarukandiyil et al . to synthesize imidazo[1,2- a ]pyridinium salts 328 [179]. The same group has initially reported reactivity of N-heterocyclic carbenes (NHCs) as directing group for aromatic/heteroaromatic C−H activation with alkynes to construct positively charged π-conjugated organic materials.…”

“…However, the design and development of novel synthetic pathways through the exploration of non-aromatic C(sp 2 )−H containing organic substrates are of greater demand. Therefore, in the Rh(III)-catalyzed non-aromantic C(sp 2 )–H activation functionalization reaction, the role of NHC of N-heterocyclic motifs as a directing group along with the crucial involvement of copper/silver salts in this transformation has been envisaged (Scheme 108) [179]. Moreover, the annulation was substantially feasible with various substituents such as methyl, butyl, and benzyl in the imidazolium substrates in good yields.…”

Synthesis of [5,6]‐Bicyclic Heterocycles with a Ring‐Junction Nitrogen Atom: Rhodium(III)‐Catalyzed C−H Functionalization of Alkenyl Azoles

“…[2] However,d espite their pharmaceutical importance,only anarrow subset of [5,6]-bicyclic heterocycles with ar ing-junction nitrogen atom have been assembled by this approach, specifically with the rhodium(III)-catalyzed annulation of N-vinyl imidazoles and alkynes (Figure 1a). [3,4] Herein we describe general methods for the rhodium(III)catalyzed alkenyl C(sp 2 )ÀHf unctionalization of C-alkenyl azoles for the synthesis of fused [5,6]-bicyclic heterocycles which incorporate from two to four nitrogen atoms (Figure 1b,c). While previous reports have demonstrated C À H functionalization of C-aryl azoles for the synthesis of tricyclic and higher-order heterocycles, [5] to the best of our knowledge, this study represents the first investigation of C-alkenyl azole substrates.…”