Efficient Palladium-Catalyzed Homocoupling Reaction and Sonogashira Cross-Coupling Reaction of Terminal Alkynes under Aerobic Conditions

Abstract

An efficient method for palladium-catalyzed homocoupling reaction of terminal alkynes in the synthesis of symmetric diynes is presented. The results showed that both Pd(OAc)(2) and CuI played crucial roles in the reaction. In the presence of 2 mol % Pd(OAc)(2), 2 mol % CuI, 3 equiv of Dabco, and air, homocoupling of various terminal alkynes afforded the corresponding symmetrical diynes in moderate to excellent yields, whereas low yields were obtained without either Pd(OAc)(2) or CuI. Moreover, high TONs (turnover numbers; up to 940 000 for the reaction of phenylacetylene) for the homocoupling reaction were observed. Under similar reaction conditions, cross-coupling of 1-iodo-4-nitrobenzene with phenylacetylene was also carried out smoothly in quantitative yield. However, the presence of CuI disfavored the palladium-catalyzed Sonogashira cross-coupling reactions of the less active aryl iodides and bromides. In the presence of 0.01-2 mol % Pd(OAc)(2), a number of aryl iodides and bromides were coupled with terminal alkynes in good to excellent yields. It is noteworthy that this protocol employs mild, efficient, aerobic, copper-free, and ligand-free conditions.

Oxidative acetylenic coupling reactions as a surface chemistry tool

“…Ligand-free palladium-catalyzed homocoupling reactions under aerobic conditions have been developed by Xie and co-workers and been shown to result in moderate to excellent yields using air as the reoxidant. 45 This protocol not only tolerates a range of functional groups but also does not require any additives such as phosphine ligands. In order to optimize the reaction conditions for the attachment of alkyne 2 onto acetylenyl Si(100) monolayers (SAM-1) an analogous Pd-catalyzed protocol was initially evaluated (method A).…”

Concise and modular synthesis of regioisomeric haptens for the production of high-affinity and stereoselective antibodies to the strobilurin azoxystrobin

“…For rabbit immunization, the synthesized haptens were converted to NHS-active esters and covalently linked to bovine serum albumin (BSA) to afford bioconjugates with similar hapten-toprotein molar ratios (15)(16)(17)(18)(19)(20). After the fourth boost, all of the immunized animals gave rise to high titres (over 10 5 ) against the homologous ovalbumin (OVA) conjugate.…”

“…15 The cross-coupling reaction was carried out efficiently using Pd(OAc) 2 as the source of the palladium catalyst and 1,4-diazabicyclo[2.2.2]octane (DABCO) as the base in acetonitrile at room temperature. 16 The next and last step that completed the preparation of the required arylic a-ring synthon involved the hydrogenation of the acetylenic compound 12, using 10% palladium-on-carbon as the catalyst. Under these conditions, both complete hydrogenation of the triple bond and hydrogenolysis of the benzyl protecting group took place to afford the desired phenol 13 in almost quantitative yield.…”

“…The tricyclic carbon skeletal framework of the target hapten was completed via another nucleophilic substitution reaction of the chlorine atom of chloropyrimidine 15 with 2-cyanophenol (16). In this case, this chloride substitution reaction was much more difficult than the former and required heating of the reaction mixture at 85 ºC.…”

Palladium‐Catalyzed Aerobic Domino Oxidative Carbocyclization‐Alkynylation of Allenynes

“…[13] An initial challenge associated with the envisioned project was to reduce the tendency of terminal alkynes to undergo oxidative homocoupling under palladium catalysis. [14] An additional challenge would be to control the intrinsic reactivity of the substrate 1 when R = H. In this case, both reacting partners would be terminal alkynes and the possibility would exist for undesired heterocoupling of two alkynes under oxidative conditions. [15] For the initial studies, we chose the reaction of 1 a and phenylacetylene (9 a) in THF in the presence of 5 mol % of a Pd II catalyst and 2.0 equiv of benzoquinone.…”