Catalytic Amination of Phenols with Amines

Abstract

Given the wide prevalence and ready availability of both phenols and amines, aniline synthesis through direct coupling between these starting materials would be extremely attractive. Herein, we describe a rhodium-catalyzed amination of phenols, which provides concise access to diverse anilines, with water as the sole byproduct. The arenophilic rhodium catalyst facilitates the inherently difficult keto–enol tautomerization of phenols by means of π-coordination, allowing for the subsequent dehydrative condensation with amines. We demonstrate the generality of this redox-neutral catalysis by carrying out reactions of a large array of phenols with various electronic properties and a wide variety of primary and secondary amines. Several examples of late-stage functionalization of structurally complex bioactive molecules, including pharmaceuticals, further illustrate the potential broad utility of the method.

Lignin-based Bisguaiacol diisocyanate: a green route for the synthesis of biobased polyurethanes

“…However, the direct amination of phenol derivatives, although very attractive, is usually difficult and requires harsh conditions and expensive transition-metal catalysts to achieve Scheme 1 Process for the preparation of MDI (A) and synthetic pathway of BGI (B) effective dearomative "hydrogen-borrowing strategy" (scheme 3A). [25][26][27][28][29][30] Scheme 2 Synthesis of BGF according to literature procedure 23 23 [25][26][27][28][29][30] Moreover, the substrate scope of such transformations is somewhat limited, especially when using ammonia as the nitrogen nucleophile. 26,27 Alternatively, the amination of phenols via transition-metal-free Smiles rearrangement has also been described (scheme 3B).…”

Integrated design of an amination process of lignin oxygenated model compounds to synthesize cyclohexylamine: catalyst nanostructure engineering and catalytic conditional strategy

“…Deng et al 131 demonstrated the potential of metal phosphides by successfully catalyzing the amination of furan alcohols. Shi et al 132 reported an efficient rhodium-catalyzed direct amination of phenols with amines without activating reagents or reductants/oxidants. Recently, Li et al 66 demonstrated a new strategy for the directional preparation of pyrimidines from lignin β-O-4 model compounds without transition-metal catalysis, using NaOH to facilitate a one-pot multi-component cascade reaction.…”

Regioselective C(sp2)–H imidation of arenes by redox neutral visible-light photocatalysis

“…The methodologies pertaining to this particular transformation have largely employed conventional nucleophilic substitution reactions 3 and transition metal-catalyzed C–N cross-coupling reactions. 4 However, these protocols suffer from serious drawbacks such as low yield, substrate specificity, 5 and many other limitations. 6 In the past few years, catalytic C(sp 2 )–H amination utilizing transition-metal as well as metal-free conditions using suitable directing groups has been reported.…”