Enantioselective Organocopper-Catalyzed Hetero Diels–Alder Reaction through in Situ Oxidation of Ethers into Enol Ethers

Abstract

We disclose a catalytic method for the enantio- and diastereo­selective union of alkyl ethers and heterodienes. We demonstrate that a chiral Cu–BOX complex catalyzes the efficient oxidation of ethers into enol ethers in the presence of trityl acetate. Then, the organocopper promotes stereoselective hetero Diels–Alder reaction between the in situ generated enol ethers and β,γ-unsaturated ketoesters, allowing for rapid access to an array of dihydropyran derivatives possessing three vicinal stereogenic centers.

Synthetic applications of hydride abstraction reactions by organic oxidants

“…212 Yesilcimen and co-workers employed the trityl cation to form dienophiles in asymmetric inverse electron-demand hetero Diels-Alder reactions from simple ethers. 213 Oxidizing tetrahydrofuran to form dihydrofuran in the presence of enone 356 and catalyst 357 results in the production of adduct 358 in excellent yield and with high stereocontrol. The use of TrOAc as the oxidant was necessary to maintain the concentration of trityl cation at a low level since it catalyzes a background racemic hetero Diels-Alder reaction.…”

IronIII-catalyzed asymmetric inverse-electron-demand hetero-Diels–Alder reaction of dioxopyrrolidines with simple olefins

“…HOMO-raising strategies, employing enamine 8 or enolate activation 9 with organocatalysts, further broaden the scope of dienophiles. The generation of active dienophiles in situ , exemplified by the conversion of 3-cyclopropylideneprop-2-enone into cyclobutene-fused furans 10 or the oxidation of ethers, 11 facilitates rapid and alternative access to cycloaddition products. In contrast, IEDHDA reaction of simple alkenes is generally challenging 12,14 and achievable only by lowering the LUMO of hetero-dienes.…”

Asymmetric Double Oxidative [3 + 2] Cycloaddition for the Synthesis of CF3-Containing Spiro[pyrrolidin-3,2′-oxindole]

“…These transformations feature a high degree of step economy and no intermediate purification steps. However, the asymmetric double oxidative cycloadditions have not been documented in the literature probably due to the oxidation ability of oxidants to oxidize both substrates simultaneously, compatibility issues between oxidants and chiral catalysts, and undesired overoxidation, although some groups have contributed to the oxidation of one of the substrates and the subsequent enantioselective transformations . Therefore, we hypothesized that three-atom or four-atom saturated substances A and cheap alkane-based substances B could be simultaneously transformed to 1,3-dipoles or (hetero)­dienes IA and alkenes IB , respectively, in the same oxidative system (Figure A).…”