Wiley InterScience Backfile Collection 1832-2000
Chemistry and Pharmacology
Racemic spiropentylglycine (8) has been synthesized by sodium borohydride reduction of benzyl (E/Z)-2-chloro-2-spiropentylideneacetate (5-Bn), nucleophilic substitution of the chlorine in the product 6 with azide and hydrogenolytic deprotection of the resulting 7 (overall yield 15%). An alternative approach to 8 consisted of the coupling of the higher-order cuprate 10, generated by halogen-metal exchange from bromospiropentane (9), with the electrophilic glycine equivalent 11 followed by deprotection (overall yield 47%). Enantiomerically pure (1′-aminospiropentyl)acetic acid [(R)-16] (overall yield 16% from 5-Me) and 1-aminospiropentanecarboxylic acid [(R)-23] (29% from 5-Me) were obtained from the Michael adduct 14-Me of (4R,5S)-4,5-diphenyloxazolidin-2-one (13) and methyl (E/Z)-2-chloro-2-spiropentylideneacetate (5-Me). Racemic 1-aminospiropentanecarboxylic acid (R/S-23) was prepared by rhodium-catalyzed addition of dimethyl diazomalonate to methylenecyclopropane and subsequent Curtius degradation of the halfester 28 via the azide 29 (overall yield 14%). Upon standing in aqueous solution, 23 underwent complete rearrangement to the new 1-amino-2-methylenecyclobutanecarboxylic acid (24). The interesting derivative of azabicyclo[3.1.0]hexane-1-carboxylate 34 with an annelated spiropentane moiety and a β-amino acid fragment was incidentally obtained in a one-step intermolecular domino reaction starting with the addition of lithium benzylamide to methyl 2-chloro-2-cyclopropylideneacetate (32, 41% yield).
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