A One-Pot Method for the Stereoselective Introduction of a Vinyl Group via an Atom-Transfer Radical-Cyclization Reaction with a Diphenylvinylsilyl Group as a Temporary Connecting Tether. Synthesis of 4‘α-<i>C</i>-Vinylthymidine, a Potent Antiviral Nucleoside¹

Abstract

A one-pot method for the stereoselective introduction of a vinyl group at the β-position of a hydroxyl group in halohydrins or α-phenylselenoalkanols via an atom-transfer radical-cyclization reaction was developed. When a solution of the diphenylvinylsilyl ether of (±)-trans-2-iodoindanol (2a) and (Bu3Sn)2 in benzene was irradiated with a high-pressure mercury lamp, the corresponding atom transfer 5-exo-cyclization product was produced, which in turn was treated with tetrabutylammonium fluoride to give cis-2-vinylindanol (3) in 82% yield from 2a. Similar reactions with diphenylvinylsilyl ethers of (±)-trans-1-phenylselenoindan-2-ol (4), trans-2-iodocyclopentanol (6), and trans-2-iodocyclohexanol (8) gave the corresponding vinyl derivatives. Furthermore, this reaction was successfully applied to the synthesis of 4‘α-C-vinylthymidine, a potent antiviral nucleoside.