Enantioselective Synthesis of (1R,4S)-1-Amino-4-(hydroxymethyl)-2-cyclopentene, a Precursor for Carbocyclic Nucleoside Synthesis

Abstract

(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 syn- thesis proceeded from the lactone via the diisopropylidene-2-amino- 2-deoxy-mannonate 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 transfor- mations by regiospecific eliminative cleavage of the ketal and hydroge- nation gave dimethyl (2S,3R)-2-amino-3-hydroxyadipate. Dieckmann cycli- zation through specific carbanion formation at C5 led to the aminohy- droxy(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