The nitro compound 4 was prepared in five steps with 33 % overall yield starting from the readily available 4benzyloxy 3-methoxy benzaldehyde 7 (scheme 2). PhCHZO 0 Q-Me0 I CHO ~PhCH~O+=j+_n,~~ PhCHIO+Noz Me0 Me0 a) (EtO)z P(O)CH2C02Et, NaH, DME, reflux, 24 h (75 %) ; b) LiAlH4, THF-ether : 1-2, room temp., 18 h (86 %) ; c) TsCl, pyridine, + 5Β°C 16 h (76 %) ; d) NaI, acetone, room temp., 21 h (86 %) ; e) AgN02, benzene, room temp., 64 h (78 %). Scheme 2 Compound 5 was obtained, as previously described for the racemic series (6). The Peterson olefination of the known chiral aldehyde 6 ([~]21~ = -79", c = 0.8, MeOH) (7) afforded the iron complexed triene 5 ([cx]~~D = + 241", c = 1.0, MeOH) in 71 % yield.
Addition of nitrile oxide 3 generated in situ from 4 @) to the dipolarophile 5 gave the diastereomeric isoxazolines 8 and 9 (IV9 : 89/l 1). The 8A ratio was assayed by integration of the oletinic protons Ha and Hb of the tH-NMR spectrum of the crude material (GD6, 300 MHz). The major, less polar adduct 8 was recovered in 75 % yield after silica gel chromatography (8:2 hexane'ethyl acetate). The stereochemistry of 8 (9) was based on previous cycloaddition results (6) and on the sign of the optical rotation of the final product 1.