2-Methylenetetrahydropyrans: Efficient Partners in the Carbonyl Ene Reaction

Abstract

The carbonyl ene reaction of 2-methylenetetrahydropyrans provides a rapid, high yielding route for the preparation of β-hydroxydihydropyrans under mild conditions. This process provides a new entry for the synthesis of 2-substituted tetrahydropyrans and for the direct introduction of oxygen heterocycles into molecular frameworks.

Aqueous ZnCl2 Complex Catalyzed Prins Reaction of Silyl Glyoxylates: Access to Functionalized Tertiary α-Silyl Alcohols

“…To further improve the product yield, other catalysts, including Fe salts, Al salts, Cu salts, Zn salts and Sc salts, were examined (Table , entries 2–10). The yield of desired product 3a is increased up to 48% by using an absolutely anhydrous commercially available ZnCl 2 (10 mol %) as a catalyst (Table , entry 11). To further improve the product yield, other solvents, including THF, EtOAc, DMF, CH 3 CN, DMSO, and toluene, were examined.…”

Studies toward the synthesis of spirastrellolide A. Preparation of a C31–C47 model

“…Synthesis of the requisite spiroketal commenced with the carbonyl ene reaction of the exocyclic enol ether 6 with ethyl glyoxylate (Scheme 2). 5 The resulting dihydropyran 7 was treated with aqueous HCl to give the corresponding spiroketals as a 2:1 mixture of diastereomers 8a and 8b that differ in stereochemistry at C37 (spirastrellolide numbering). 6 From here, the individual spiroketals were separated and converted to the corresponding exocyclic enol ethers 9a and 9b by protection of the secondary alcohol followed by treatment with the Petasis reagent.…”

“…Retrosynthetically, we anticipated incorporation of the side chain via a cross coupling reaction between a suitably functionalized vinyl halide 3 and a spiroketal 4 that contained an exocyclic methylene (Scheme 2). In turn, preparation of the spiroketal 4 was envisaged from an exocyclic enol ether 6 via a carbonyl ene reaction 5 and subsequent spirocyclization. Access to the vinyl halide 3 was expected from the corresponding aldehyde 5 that is readily available from (S)-malic acid.…”

Effects of Chiral Ligands on the Asymmetric Carbonyl-Ene Reaction

“…62 The carbonyl-ene reaction of 2-methylenetetrahydropyran with benzaldehyde was catalyzed by complex 73a to produce the corresponding -hydroxydihydropyran with excellent yield and moderate enantioselectivity (Scheme 45, c). 63 Jacobsen and coworkers examined Schiff base chromium(III) complex 74 in the intramolecular carbonyl-ene reaction. This dimeric structure contains two ligands and two Cr(III) centers which are bridged through indane-bound oxygens.…”