Enantioselective synthesis of (1R,4S)-1-amino-4-(hydroxymethyl)-2- cyclopentene, a precursor for carbocyclic nucleoside synthesis

Article abstract of DOI:10.1021/jo00081a019

(1R,4S)-1-Amino-4-(hydroxymethyl)-2-cyclopentene, an important precursor for the synthesis of carbocyclic nucleosides, has been prepared from D- glucono-δ-lactone in enantiomerically pure form (er > 99/1). The synthesis proceeded from the lactone via the diisopropylidene-2-amino-2-deoxymannonate and hydrolysis of the terminal isopropylidene group. Selective oxidation of the primary alcohol and esterification gave the corresponding mannarate which was deoxygenated at C5. Further transformations by regiospecific eliminative cleavage of the ketal and hydrogenation gave dimethyl (2S,3R)-2-amino-3- hydroxyadipate. Dieckmann cyclization through specific carbanion formation at C5 led to the aminohydroxy(methoxycarbonyl)cyclopentanone which was readily converted in a series of high-yielding steps to the target cyclopentene. Throughout the synthesis, stereo- and regioselectivities were strongly influenced by the sterically demanding 9-phenyl-9-fluorenyl protecting group on nitrogen.