Enantioselective Synthesis of 4-Acetylaminocyclopent-2-en-1-ols from Tricyclo[5.2.1.02,6]decenyl Enaminones. Precursors for 5‘-Norcarbocyclic Nucleosides and Related Antiviral Compounds

Abstract

An efficient synthesis of both (1S,4R) and (1R,4S)-4-N-acetylamino-1-benzoylcyclopent-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 15. N-Acetylation of both 15 and 14 followed by single electron-transfer reduction using lithium in liquid ammonia afforded diastereomeric mixtures of beta-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 group as the chiral auxiliary. Thermolysis of the respective diastereomic mixtures of 26 and 27 in the gas phase (FVT) or in solution afforded 4-N-acetylaminocyclopent-2-ene-1-ones 30 in high optical and chemical yields. Acidic hydrolysis of (+)-30 gave (R)-(+)-4-aminocyclopentenone 31 as its hydrochloride. Stereoselective reduction of 30 using sodium borohydride and cerium chloride heptahydrate furnished amido alcohol 32, which was isolated and characterized as its benzoyl derivative 33.