Copper‐Catalyzed Oxidative α‐Alkylation of α‐Amino Carbonyl Compounds with Ethers via Dual C(sp³)‐H Oxidative Cross‐ Coupling

Abstract

A novel copper‐catalyzed oxidative alkylation of α‐amino carbonyl compounds with ethers has been established for the selective synthesis of α‐etherized α‐amino carbonyl compounds. This oxidative alkylation is achieved by dual C(sp3)H bond oxidative cross‐coupling, and its scope is expanded to α‐amino ketones, α‐amino esters and α‐amino amides.magnified image

Auto‐Oxidative Coupling of Glycine Derivatives

“…After that, some progress has been reported in this context 4. These reactions were mostly catalyzed by copper4a–e or iron salts4f–i in combination with stoichiometric amounts of chemical oxidants such as TBHP, DTBP, DDQ, or TEMPO oxoammonium salt 4a–i. Dioxygen is an environmentally benign oxidant and an atom‐efficient reagent in synthetic chemistry 5.…”

Cu‐Catalyzed Aerobic Oxidative Cyclizations of 3‐N‐Hydroxyamino‐1,2‐propadienes with Alcohols, Thiols, and Amines To Form α‐O‐, S‐, and N‐Substituted 4‐Methylquinoline Derivatives

“…The use of IPrCuCl in toluene resulted in compound 2 a in an excellent yield (92 %, entry 7). With TBHP ( tert ‐butyl hydroperoxide) and DTBP (di‐ tert ‐butyl peroxide) as oxidants (3 equiv), IPrCuCl gave β‐oxoamide 2 a in only 65–70 % yield, together with tert ‐butoxy‐β‐oxoamide 3 (30–35 %) as a side product (entries 8 and 9) 11. The use of H 2 O 2 and IPrCuCl yielded β‐oxoamide 2 a in 62 % yield (entry 10). …”

Recent Developments in Transition Metal‐Catalyzed Cross‐Dehydrogenative Coupling Reactions of Ethers and Thioethers

“…The α‐alkylation of α‐amino carbonyl compounds with ethers was reported by Wei, Li and co‐workers in 2014 (Scheme ) . Traditional α‐C−H alkylation of these substances requires strong base and organohalides as well as N ‐protection.…”

“…A plausible mechanism for the reaction between ethers and α‐aminocarbonyl compounds is shown in Scheme . It is assumed that the copper catalyst plays two roles: it splits TBHP into a tert ‐butoxyl radical and Cu 2+ (OH) under the influence of heat and Cu 2+ (OH) can abstract a proton from the product of the reaction between the tetrahydrofuranyl radical and the aminoketone to yield the final product.…”