Enantiomerically enriched ethers bearing multiple vicinal stereogenic centers are prevalent among natural products and drugs. Therefore, the synthesis of chiral ether is crucial. Such moieties can be accessed by stereoselective transformations of alkyl enol ethers; however, the cumbersome synthesis and limited access are some of the significant challenges that remain to be addressed. We envisioned a combination of a chiral Cu-based complex and a trityl-containing compound first enables the generation of a broad scope of enol ethers through oxidation of significantly more accessible and otherwise stable alkyl ethers. Subsequently, organocopper promotes the stereoselective union of the in situ generated enol ethers with a wide range of coupling partners. Specifically, we surmised that the treatment of ether 1 and beta,gamma-unsaturated ketoester 2 with 5.0 mol % of [t-BuBOX-Cu](SbF6)2 and Ph3COAc would afford the a broad array of dihydro-2H pyrans containing three vicinal stereogenic centers. This process is proposed to proceed through Ph3C+-mediated hydride abstraction to form an oxocarbenium ion I which then undergoes deprotonation by a suitable base to furnish enol ether II. The subsequent organocopper-catalyzed hetero Diels-Alder reaction between II and beta,gamma-unsaturated ketoester 2 could form dihydro-2H pyran 3.

Organocopper-catalyzed enantioselective ether C1-H and C2-H functionalization

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