Synthesis of (±)-cis-6-methyltetrahydropyran-2-ylacetic acid, a natural product from Viverra civetta, using organoselenium-mediated cyclisation reactions

Abstract

Two highly stereoselective syntheses of the natural product (±)-cis-6-methyltetrahydropyran-2-ylacetic acid (1) are described. The shorter of these is a three-step synthesis involving kinetic alkylation of the dianion derived from benzyl acetoacetate with 4-bromobut-1-ene, followed by organoselenium mediated cyclisation with N-phenylselenophthalimide, to give benzyl 6-phenylselenomethyl-5,6-dihydro-4H-pyran-2-ylacetate (11) and benzyl 6-phenylselenomethyltetrahydropyran-2-ylideneacettate (12), which upon reaction with Raney nickel under 100 atm of hydrogen directly affords compound (1).