Hydroxylamines, intermolecular nitrone cycloaddition reactions

Further examples of the endocychc nitrone route to spirocychc adducts are the total syntheses of (—)-histrionicotoxin (230) by Holmes and of cyhndricines by Weinreb. Histrionicotoxin is one of many spiropiperidine alkaloids isolated from the poison-arrow frog Dendrobates histrionicus and has been the subject of many attempted total syntheses by a nitrone cycloaddition strategy that failed to provide the desired regioisomer, possibly through unfavorable steric interactions (265-268). Unlike these reports, Holmes and co-workers (101) found that the intermolecular reaction of nitrone (231), prepared by the 1,3-APT of the corresponding alkynyl-hydroxylamine carrying Oppolzer s chiral sultam auxiliary, afforded the styrene... 

The in situ formation of nitrones from oximes by 1,3-APT or 1,2-prototropy is clearly a powerful synthetic strategy but conventional nitrone generation, in particular hydroxylamine-carbonyl condensation, has been applied to numerous syntheses, in intra- and intermolecular mode (258). Accordingly, the ring systems similar to those synthesized using 1,3-APT/intramolecular nitrone-alkene cycloaddition (INAC) methodology by Heaney (313-315) (see Section 1.11.2) or Padwa and Norman (340) have been made using conventionally prepared nitrones (Scheme 1.67). As with the previous examples, once formed, the nitrones are suitably placed for a spontaneous intramolecular cycloaddition reaction with the... 

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