Nitrones cyclizations

The intramolecular nitrone cyclization approach has been used to produce cycloadducts containing a central seven-membered ring in a manner analogous to that described in Section 10.21.9.3.2(ii) <1996T11265>. 

A very recent synthesis of ( )-pumiliotoxin C employed the nitrone cyclization product (29), obtained in 74% overall yield from the nitrone precursors.12b Reduction of (29) with zinc-acetic acid provided a trisubstituted piperidine which was converted in several steps to ( )-pumiliotoxin C. 

Cyclization of C-(cycloalkenyl)nitrones has been extensively investigated.13-15 For example, the cy-clohexenylnitrone (30) (an equilibrated 2 1 ( )/(Z) isomer mixture) afforded (31) in 56% yield (Scheme 7).13 Presumably the (Z)-nitrone cyclized exclusively based on the strained transition state required for cyclization of the ( )-nitrone. None of the isomeric bridged [4.2.1] product (32) was formed this is attributed to unfavorable nonbonded interaction between the carbonyl group and a ring methylene group in the required transition state. 

Nitrones can be generated by Michael reaction of oximes with appropriate conjugated substrates.25 If a generated nitrone has a built-in dipolarophile, cyclization can ensue (Scheme 15). There are three synthetic variations on this theme.25a,b First, the oxime may contain the dipolarophile as in (56). Reaction of (56) with phenyl vinyl sulfone provided a quantitative yield of the tandem product as one stereoisomer. Alternatively, die dipolarophile can reside in the Michael substrate as in (57). Reaction of (57) with cyclohexanone oxime produced two isoxazolidines from competitive cyclization of the intermediate nitrone through six- and seven-membered carbocyclic transition states. It is also possible to carry out an intramolecular Michael addition followed by an intramolecular nitrone cyclization as in thermolysis of (58) to produce a tricyclic isoxazolidine. Very recently several examples of a tandem Diels-Alder, Michael addition, nitrone cyclization sequence have been reported.250... 

INOC reactions are occasionally synthetic alternatives to nitrone cyclizations. The isoxazolines produced can substitute for isoxazolidines in a number of further transformations. Thus, isoxazolines, like isoxazolidines, can be converted to 7-amino alcohols.31 Isoxazolines can be converted to isoxazolidines and vice versa.32... 

Pseudocopsinine (215) was isolated from Vinca erecta. Parsons et al. devised a concise synthesis of the pseudocopsinine framework 214 utilizing a 5-exo/5-exo double tandem radical cyclization [83-84]. The cyclization precursor 213 was readily accessible via a [3 + 2] nitrone cyclization. As depicted in Scheme 40, reaction between the pyrrolidine aldehyde 210 ando-... 

The use of nitrones in the synthesis of anatoxin-a, very fast death factor. Tetrahedron 41, 3447-3453, and references therein about the regioselectivity of nitrone cyclization. 

Histrionicotoxin (340) and (-)-histrionicotoxin 235A (341) were synthesized from (S)-6-hydroxy-8-nonenoate, using an allylic epoxide cyclization to generate three of the required chiral centers [717]. A recent synthesis of the histrionicotoxin ring system employed a tandem Michael addition-nitrone cyclization [718]. GC-MS, GC-FT1R, and revised i3C NMR spectral data have been reported for a number of histrionicotoxins [719],... 

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