Enantioselective synthesis of 4-acetylaminocyclopent-2-en-1-ols from tricyclo[5.2.1.0(2,6)]decenyl enaminones. Precursors for 5 '-norcarbocyclic nucleosides and related antiviral compounds

An efficient synthesis of both (1S,4R) and (1R,4S)-4-N-acetylamino-1-benzoy lcyclopent-2-enes 33 has been accomplished starting from enantiopure 5-(1'- phenylethylamino)-endo-tricyclo[5.2.1.0(2,6)]-deca-4,8-dien-3-ones 14 and 1 5. N-Acetylation of both 15 and 14 followed by single electron-transfer red uction using lithium in liquid ammonia afforded diastereomeric mixtures of p-amino ketones 26 and 27 and of ent-26 and ent-27 in high yields and with high diastereoselectivity. In this reduction process, the enaminone double bond is reduced with the concomitant removal of the alpha-methylbenzyl grou p as the chiral auxiliary. Thermolysis of the respective diastereomic mixtu res of 26 and 27 in the gas phase (FVT) or in solution afforded 3-N-acetyla minocyclopent-2-ene-1-ones 30 in high optical and chemical yields. Acidic h ydrolysis of (+)-30 gave (R)-(+)-4-aminocyclopentenone 31 as its hydrochlor ide. Stereoselective reduction of 30 using sodium borohydride and cerium ch loride heptahydrate furnished amido alcohol 32, which was isolated and char acterized as its benzoyl derivative 33.