Cyclopropyl building blocks for organic synthesis, 53 - Convenient syntheses of novel alpha- and beta-amino acids with spiropentyl groups

Racemic spiropentylglycine (8) has been synthesized by sodium borohydride r eduction of benzyl (E/Z)-2-chloro-2-spiropentylideneacetate (5-Bn), nucleop hilic substitution of the chlorine in the product 6 with azide and hydrogen olytic deprotection of the resulting 7 (overall yield 15%). An alternative approach to 8 consisted of the coupling of the higher-order cuprate 10, gen erated by halogen-metal exchange from bromospiropentane (9), with the elect rophilic glycine equivalent II 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% f rom 5-Me) were obtained from the Michael adduct 14-Me of (4R,5S)-4,5-diphen yloxazolidin-2-one (13) and methyl (E/Z)-2-chloro-2-spiropentylideneacetate (5-Me). Racemic 1-aminospiropentanecarboxylic acid (R/S-23) was prepared b y rhodium-catalyzed addition of dimethyl diazomalonate to methylenecyclopro pane and subsequent Curtius degradation of the halfester 28 via the azide 2 9 (overall yield 14%). Upon standing in aqueous solution, 23 underwent comp lete rearrangement to the new 1-amino-2-methylene-cyclobutanecarboxylic aci d (24). The interesting derivative of azabicyclo[3.1.0]hexane-1-carboxylate 34 with an annelated spiropentane moiety and a beta-amino acid fragment wa s incidentally obtained in a one-step intermolecular domino reaction starti ng with the addition of lithium benzylamide to methyl 2-chloro-2-cyclopropy lideneacetate (32, 41% yield).