Gold‐Catalyzed Oxidation of Internal Alkynes into Benzils and its Application for One‐Pot Synthesis of Five‐, Six‐, and Seven‐Membered Azaheterocycles

Abstract

Internal alkynes have been shown to undergo oxidation to substituted benzils (1,2‐diarylethane‐1,2‐diones) by α‐picoline N‐oxide in the presence of Ph3PAuNТf2 (5 mol‐%). In addition to the unsubstituted benzil, the method allows preparing, under markedly mild conditions (50 °C in chlorobenzene), various non‐symmetrical products, including heteroaromatic versions thereof which are much more difficult to obtain otherwise. This gold(I)‐catalyzed transformation was integrated into one‐pot reaction sequence delivering a range of 5‐ to 7‐membered ring systems (imidazoles, quinoxalines, 1,2,4‐triazines, pyrazines, and 1,4‐diazepines), thus linking these important heterocyclic motifs to the internal alkyne reagent space.

Transition Metal‐Catalyzed Synthesis of 1,2‐Diketones: An Overview

“…The major advantages of this approach are milder reaction conditions, broad substrate scope tolerance, and higher product yields. [35] Recently, the same group employed 2,3-dichloropyridine-Noxide 39 as the oxygen transfer reagent for the oxidation of alkynes 38 into 1,2-diketones 49 in the presence of 3 mol% of Au I catalyst Ph 3 PAuNTf 2 (Scheme 15). [36] Remarkably, this strategy is effective for a wide variety of alkynes 38 to obtain the corresponding 1,2-diketones 40 in good to excellent yields (56-99%).…”

Gold‐Catalyzed Oxidative Alkyne Functionalization by N−O/S−O/C−O Bond Oxidants

“…Recently Dubovtsev and coworkers & Kukushkin and coworkers also developed a series of gold-catalyzed 1,2-dicarbonylations of various terminal and internal alkynes where various pyridine N-oxides are used as an external oxidant. [27] Scheme 5 illustrates the development of benzils from unsubstituted diphenylacetylene and diarylacetylenes under mild reaction conditions in the presence of 2.5 equivalent of picoline Noxide and Ph 3 PAuNf 2 (5 mol%) and 2.0 equivalent of TfOH. Letter, by switching external oxidant to substituted by 2,3-dichloropyridine N-oxide and the desired 1,2-dicarbonyls were derived from a wide range of terminal-and internal alkynes, alkynyl ethers/ thioethers, and ynamides without any acid additives (Scheme 6).…”

Base-Promoted Annulation of Amidoximes with Alkynes: Simple Access to 2,4-Disubstituted Imidazoles

“…As depicted in Scheme 1, one of the classic approaches to synthesize 1,2,4,5-tetrasubstituted or 2,4,5-trisubstituted imidazoles is the three-component cyclization of α-diketone, aldehyde, and amine or ammonia sources catalyzed by transition metal complexes or under acidic conditions (Equation (1)). Recently, this protocol has been evolved using internal alkynes as starting materials via generating 1,2-diketones in situ by oxidation reaction [21][22][23][24]. On the other hand, the formal [3+2] annulation of substituted amidines with alkyne forming imidazole ring usually shows high atom-utilization, and two representative procedures are concluded in Scheme 1.…”