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-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.
Ramesh
Namakkal G.
NG
Department of Organic Chemistry, NSR Center for Molecular Structure, Design and Synthesis, University of Nijmegen, Toernooiveld, 6525 ED Nijmegen, The Netherlands.
Klunder
Antonius J. H.
AJ
Zwanenburg
Binne
B