Catalytic Aerobic Cross-Dehydrogenative Coupling of Phenols and Catechols

Abstract

We describe a selective, catalytic aerobic cross-dehydrogenative coupling (CDC) reaction of phenols and catechols that creates aryl ethers. To avoid challenges of selectivity, we employ copper (Cu) coordination to confine substrate redox to the inner coordination sphere of the metal. This minimizes nonselective radical processes to provide high levels of selectivity for cross over homo coupling, by C–O instead of C–C bond formation. The method remains efficient on synthetically useful substrates and scales and enables a convergent synthesis of the tetrahydroisoquinoline alkaloid (S, S)-thalicarpine featuring diaryl ether formation in the late stages of the synthesis. Related molecules are difficult to prepare by traditional Ullman-type coupling and provide a benchmark for evaluating the potential utility of our methodology.

Cross dehydrogenative C–O coupling catalysed by a catenane-coordinated copper(i)

“…Moreover, multiple substituted phenols, including those with bulky ortho-substituents (e.g. -NO 2 and t Bu), performed equally well in the CDC (Table 2, entries [16][17][18][19], demonstrating a wide substrate scope of the CDC. When catechol was used as the phenolic substrate, a double substituted ve-membered ring product was obtained (Table 2, entry 20).…”

“…13,14 Currently, there are only few reports of C(sp 2 )-O dehydrogenative coupling of phenols with anilines, 15 formamides, 16 acrylates 17 and catechols. 18 C(sp 3 )-O cross coupling is even more challenging, and the use of a hypervalent iodine oxidant 19 or a metal-free condition are among the few reported examples of C(sp 3 )-O cross coupling in the literatures. 20 Preliminary mechanistic studies on the catenane-supported Cu(I) suggest the CDC involves a mononuclear, radicalinvolving pathway.…”

8-, 9-, and 11-Aryloxy Dimeric Aporphines and Their Pharmacological Activities

“…In 2019, Jean-Philip Lumb and coworkers reported a catalytic aerobic cross-dehydrogenative coupling reaction of phenols and catechols, and its application in thalicarpine (43) synthesis in 20% overall yield over 11 steps (longest linear sequence). As depicted in Scheme 8, the coupling of phenol 126 and catechol 127 using CuCl under an atmosphere of O 2 generated intermediate 128 in a 76% yield, which, after methylation and reduction, afforded thalicarpine (43) in a 74% yield over two steps [189]. On the other hand, the syntheses of naturally-occurring C9-aryloxy aporphines of the pakistanine-type dimers 101-107 were mainly achieved through the acid-catalyzed rearrange-ment of the naturally occurring proaporphine-benzylisoquinoline dimers of the pakistanaminetype dimers.…”

Spectrophotometric Determination of carvedilol Via Oxidative Coupling Reaction

“…Catechol and resorcinol are phenolic compounds and are widely used in tanning, cosmetics, the pharmaceutical industry and in developing photo-graphs [1] [2]. These compounds are harmful to humans and animals even in very low concentration.…”