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

Abstract

Naphthalene is a very important skeleton in chemistry as evidenced by the large number of active compounds that contain it. For this reason, methods that can achieve easy functionalization of naphthalene derivatives are of great importance. This Minireview summarizes reactions that allow regioselective functionalization of 1‐substituted naphthalenes based on directed C−H activation strategies. Indeed, over the past ten years, many research groups have tried to develop new methodologies to directly introduce different functional groups on every position of naphthalene. In addition to the possible reactions reported in the literature, special attention has been paid to mechanistic aspects in order to explain the observed regioselectivities.

Rhodaelectro‐Catalyzed peri‐Selective Direct Alkenylations with Weak O‐Coordination Enabled by the Hydrogen Evolution Reaction (HER)

“…Given the importance of 1,8-disubstituted (peri-substituted) naphthalene derivatives, there has been continuous strong interest in the C8 functionalization towards CÀ C formation by metal-catalyzed CÀ H functionalizations. [12] In this context, methods for the construction of the CÀ C bonds via peri-selective naphthalene functionalization have been developed, such as arylations, [13] alkenylations, [14] alkynylations [15] or annulations. [16] While the oxidative, peri-selective alkenylation with styrenes was enabled with chemical oxidants by difficult to remove sulfonamide directing groups [14a] (Scheme 1b), oxidative 1-naphthol alkenylations, either in a chemical or an electrochemical manner are yet to be developed.…”

Overcoming peri- and ortho-selectivity in C–H methylation of 1-naphthaldehydes by a tunable transient ligand strategy

“… 2 Although a few regioselective methylation methods are well-developed for the transition metal (TM)-catalyzed ortho -C–H functionalization of benzene, 3 the precise site-selectivity control on polyaromatic ring systems ( e.g. naphthalene) remains largely absent, 4 due to their possession of at least two proximal sites, the peri - and ortho -positions ( Fig. 1B ).…”

Rhodaelektro‐katalysierte peri‐selektive direkte Alkenylierungen mit schwacher O‐Koordination ermöglicht durch die Wasserstoffbildungsreaktion (HER)

“…Angesichts der Bedeutung von 1,8-disubstituierten (peri-substituierten) Naphthalin-Derivaten besteht ein anhaltend großes Interesse an der C8-Funktionalisierung zur CÀ C-Bindungsbildung durch metallkatalysierte CÀ H-Funktionalisierungen. [12] In diesem Zusammenhang wurden Methoden zum Aufbau von CÀ C-Bindungen durch peri-selektive Naphthalinfunktionalisierung entwickelt, unter anderem Arylierungen, [13] Alkenylierungen, [14] Alkinylierungen [15] und Anellierungen. [16] Während die oxidative, peri-selektive Alkenylierung mit Styrolen und chemischen Oxidationsmitteln mit schwer zu entfernenden Sulfonamidgruppen als dirigierenden Gruppen ermöglicht wurde [14a] (Schema 1b), stehen oxidative Alkenylierungen von 1-Naphthol, entweder auf chemischem oder elektrochemischem Wege, noch aus.…”