Regioselectivity in C–H activation: reagent control in cyclometallation of 2-(1-naphthyl)-pyridine

Abstract

2-(1-Naphthyl)-pyridine () possesses sp(2) C-H bonds in both the γ- and δ-positions and is therefore a suitable substrate for studying the cyclometallation selectivity with different reagents and conditions. Such selectivity studies are reported. Based on deuterium-exchange experiments it is concluded that cycloruthenation with RuCl2(p-cymene) dimer is reversible with kinetic and thermodynamic preference for γ-substitution. Electrophilic cycloborylation, on the other hand, shows unusual δ-substitution. The previously published cyclopalladation and cycloauration of the substrate was studied in detail and was shown to be irreversible; they proceed under kinetic control and give γ- and δ-substitution for palladium and gold, respectively.

Intramolecular (directed) electrophilic C–H borylation

“…the selective formation of 96 from borylation at the more nucleophilic naphthyl peri position (Scheme 44, bottom). 89,90 In contrast, applying comparable borylation conditions to related systems five membered boracycles are formed exclusively, e.g. 97, with no compound O observed (97 forms despite the presence of strain arising from close HÁ Á ÁH contacts causing non-planarity in the polycyclic aromatic).…”

Regioselective C−H Functionalization of Naphthalenes: Reactivity and Mechanistic Insights

“…A very interesting example has been published by the group of Wendt who used 2‐(1‐naphthyl)‐pyridine 57 as substrate. In function of the metal used, the metallacycle could be formed in C2 or C8 position (Scheme ) . For instance, using palladium diacetate or a ruthenium complex allowed the formation of a palladacycle in C2 position whereas the reaction with a gold complex showed a full C8 selectivity.…”

Site‐Selective C(sp3)−H and C(sp2)−H Functionalization of Amines Using a Directing‐Group‐Guided Strategy

“…Most common directed reactions proceed via five membered metallocycles formed during the CÀ H activation. [52] In contrast, four membered metallocycles are rare due to strained ring formation that is thermodynamically less favored. This is the reason that β-CÀ H activation is more challenging and has required meticulously tuned reaction conditions to be successful.…”