Expanding the Chiral Monoterpene Pool: Enantioselective Diels–Alder Reactions of α-Acyloxy Enones

Abstract

An enantioselective Diels–Alder (DA) reaction of α-acyloxy enones has been developed to synthesize chiral oxidized cyclohexenes. Yttrium­(III) triflate, in conjunction with a chiral pyridinebisimidazoline (PyBim) ligand, was found to catalyze the asymmetric [4 + 2] cycloaddition with a variety of dienes and α-acyloxy enone dienophiles. Using this method, terpinene-4-ol, a key intermediate in the synthesis of commercial herbicide cinmethylin, can be prepared in four steps from isoprene. A combination of kinetic data and NMR studies support a mechanism involving reversible binding of a dienophile to a yttrium catalyst followed by cycloaddition with a diene as the rate-determining step.

PyBox–La(OTf)3-Catalyzed Enantioselective Diels–Alder Cycloadditions of 2-Alkenoylpyridines with Cyclopentadiene

“…The selected attempts on ligand screening are listed in Table 1 (for more details, see Table S1 and Table S2 in the Supplementary Materials). Pyridine-2,6-bisimidazoline ligands PyBim-1 and PyBim-2 produced 3aA in 84:16 and 75:25 er, respectively [23][24][25]. In contrast, 3aA was produced in 94:6 and 68:32 er values when the respective pyridine-2,6-bisoxazoline ligands PyBox-1 and PyBox-2 were used.…”