Copper-Catalyzed Oxidative Dehydrogenative Carboxylation of Unactivated Alkanes to Allylic Esters via Alkenes

Abstract

We report copper-catalyzed oxidative dehydrogenative carboxylation (ODC) of unactivated alkanes with various substituted benzoic acids to produce the corresponding allylic esters. Spectroscopic studies (EPR, UV–vis) revealed that the resting state of the catalyst is [(BPI)Cu(O2CPh)] (1-O2CPh), formed from [(BPI)Cu(PPh3)2], oxidant, and benzoic acid. Catalytic and stoichiometric reactions of 1-O2CPh with alkyl radicals and radical probes imply that C–H bond cleavage occurs by a tert-butoxy radical. In addition, the deuterium kinetic isotope effect from reactions of cyclohexane and d12-cyclohexane in separate vessels showed that the turnover-limiting step for the ODC of cyclohexane is C–H bond cleavage. To understand the origin of the difference in products formed from copper-catalyzed amidation and copper-catalyzed ODC, reactions of an alkyl radical with a series of copper–carboxylate, copper–amidate, and copper–imidate complexes were performed. The results of competition experiments revealed that the relative rate of reaction of alkyl radicals with the copper complexes follows the trend Cu(II)–amidate > Cu(II)–imidate > Cu(II)–benzoate. Consistent with this trend, Cu(II)–amidates and Cu(II)–benzoates containing more electron-rich aryl groups on the benzamidate and benzoate react faster with the alkyl radical than do those with more electron-poor aryl groups on these ligands to produce the corresponding products. These data on the ODC of cyclohexane led to preliminary investigation of copper-catalyzed oxidative dehydrogenative amination of cyclohexane to generate a mixture of N-alkyl and N-allylic products.

Cobalt‐Catalyzed Dehydrogenative Coupling of Alcohols/Aldehydes and Amines: An Important Role for Imine Hydration

“…The reaction of 1a with 2a gave no product in the presence of I 2 (1.0equiv) and nBu 4 NOH (2.0 equiv;I O À and IO 2 À generated in situ, Scheme 7A). [26] We also conducted the reactioni nt he presence of 9,10-dihydroanthracene, ak nownt rap for tBuO· radicals, [27] which formsa nthracene as the exclusive product throughh ydrogen abstraction by alkoxy radicals (Scheme 7B). The potentially involved transient hyperiodite species [7,26] was found to be inert during the oxidative dehydrogenation (Scheme 7C).…”

Transition‐Metal‐Catalyzed Acyloxylation: Activation of C(sp2)–H and C(sp3)–H Bonds

“…Aldehydes and acids could also be regarded as coupling partners for the synthesis of unsymmetrical and allylic esters through copper‐catalyzed reactions starting from simple alkanes. The strength of the C–H bonds plays a determinant role in these reactions.…”

A Boron Protecting Group Strategy for 1,2-Azaborines

“…The experiments in Table 2 and Table S3 and the detailed mechanistic studies performed by others 18,20 prompt us to propose a tentative mechanism for the B -R to B -OR transformation using the system based on copper and DTBP (Figure 2). We propose an initial generation of a Cu(II) alkoxide species from the reaction of a Cu(I) species with the DTBP oxidant with concomitant formation of a tert-butoxide radical.…”

“…The lessons we learned from these aerobic reactions guided us to explore an alternate system. First, we used di- tert -butylperoxide (DTBP) 20 under a nitrogen atmosphere as the oxidant to potentially reduce the prevalence of unwanted side reactions between the azaborine substrate and molecular oxygen. Second, we examined the benzyl group as the boron leaving group, since it should impart the same stability toward cross coupling or other nucleophilic reaction conditions that n -butyl would, and it would become a relatively stable radical species in case this expulsion contributed to limiting the rate of the overall reaction.…”