Bicyclic oximes

For a review of such ring enlargements, see Vinnik, M.I. Zarakhani, N.G. Russ. Ghem. Rev., 1967, 36, 51. For a review with respect to bicyclic oximes, see Ref. 254. 

Finally, a rather early (but from a mechanistic viewpoint a very interesting) sequence of radical reactions has been described by Pattenden and coworkers, in which an acetylenic oxime ether 3-312 was converted into the bicyclic oxime 3-319 in 70% yield (Scheme 3.78) [126]. Hydrolysis of 3-319 led to the bicyclic enone 3-320, which in fact can also more easily be synthesized by a Robinson annulation. 

The synthesis of amines from oximes is exemplified by the reduction of oxime 332 to 333 (99W032453) and of bicyclic oximes (derived from ketones 3 and 23a), for instance, of oxime 387 (Scheme 87) to amine 388 that is acylated to yield potential pharmaceutical agent 390 (92BML1147). Nucleophilic substitution of chloropyridine 384 generates morpholino derivative 385 (76IJB400). 

The first derivative of the 1,2,3-dithazepine template 70 was obtained as a minor product (<5% yield) of reaction between bicyclic oxime 67 and S2CI2 in the presence of Hiinig s base (Scheme 8) <1996JOC9178>. The structure of isolated dark-blue compound was confirmed by MS and NMR data. The compound 70 proved to be unstable and readily eliminated sulfur to yield 69. 

Bicyclic oximes also give the corresponding amines with high stereoselectivity, but in a manner different from the bicyclic imine of Eq. (23) the stereochemical feature of the electrochemical reduction is the same as that of the LiAlH4 reduction, but opposite that of the sodium reduction [182],... 

Another classical example is Stork s 1972 total synthesis of racemic byssochlamic acid (51), which constitutes the first application of a Beckmann fragmentation in the total synthesis of a complex natural product 1 Scheme S.131. Bicyclic oxime 49 underwent Beckmann fragmentation to generate the nine-membered intermediate 50, which was converted to ( )-byssochlamic acid (51) after ethyl substituent formation and conversion of the benzene rings to the two maleic anhydrides. 

In a series of different rearrangements, finally under the conditions of fragmentation of a carbon-carbon bond, the Beckman rearrangement of a bicyclic oxime 60 affords cis-chrysanthemonitril 61 (Reaction scheme 38) [68]. 

Phosphonic acid analogues of aspartic acid, glutamicacid C-benzy1g1ycine,191 and the phosphor inane (70)1 92 have been studied, also the oxime (71)193 a phosphonopiperidinol - with a very distorted chair structure,194 the phosphonate (72),195 a pyrazole,196 a thiocarbamoy1phosphonate, 97 and two iminobis-(methylphosphonic acids).198 Additionally there have been studies of the new bicyclic sulphur heterocycle (73),199 the oxazaphospho1idine (74)200 and a triaminophosphetanium aluminium betaine.201... 

Synthesis of novel bicyclic heterocyclic systems involving aziiidine ring formation has been described. The sodium salts of tosylhydrazones 11 decomposed by heating in benzene and gave aziridinopyrroloindoles 12 in yields up to 73% (equation 5) . Intramolecular cyclization of oxime ether 13 in the presence of base (for example, DBU) in acetonitrile afforded aziridinopyrrolidine 14 in yields up to 51% (equation 6) °. 

Bicyclic derivatives of furazan A-oxide are prepared by nitrile oxide dimerization reaction. Dioxime 272 (R, R = Me) undergoes cyclization to the corresponding 4,4-tetramethylperhydrocycloocta[c]furazan A-oxide 273 (84% yield) by treatment with NaOCl/HaO/CHaCla at 0°C and then refuxing in toluene (equation 117). However, in the cases of sterically less hindered oximes 272 (R = H, Me R = H) only complex mixtures of oligomerization and cyclization products could be obtained ". Interestingly, the reaction of pyridyl oxime -274 with TsCl afforded 1,2,5-oxadiazole 275 as single product (equation 118). On the other hand, the reaction of Z-isomer of oxime 274 leads only to 0-tosylated oxime. ... 

Since the migrating group retains its configuration, the use of enantiomerically enriched oximes provides a direct entry to enantiomerically pure lactams. These lactams may be used as a key building block for the synthesis of diverse compounds. Westermann and Gedrath applied this strategy to the stereoselective synthesis of enantiomerically pure o-.a-disubstituted a-amino acids (equation 135), bicyclic lactams and the spirocyclic framework of Histrionicotoxins (equation 136). 

Fragmentations of oximes of bicyclic compounds, e.g. camphor oxime, have been extensively studied, as the products can be used as chiral intermediates in enantiospecific syntheses. 

In a similar approach, Shishido et al. (241) used oxime 215 [derived from the monoterpene (+)-citronellal (214)] for the synthesis of (—)-mintlactone (218) and (+)-isomintlactone (219), sweet compounds isolated from some Mentha species (Scheme 6.89). Bicyclic isoxazoline 216 was obtained in good yield from the cycloaddition. As expected, the product possessing tra i-l,4-substimtion prevailed. Reductive hydrolysis of the major isomer of 216 using hydrogen-Raney Ni-trimethyl borate provided p-hydroxyketone 217. This compound was dehydrated to give an enone and this was followed by carbonyl reduction-lactonization to complete the synthesis of both lactones 218 and 219 (241). 

The synthesis of type I bicyclic peptides is the most simple as the two side-chain-to-side-chain cyclizations can be performed successively on the assembled peptide or more appropriately by condensation of the two monocyclic segments preferably in solution. As shown in Scheme 23 (path A), for the synthesis of suitably protected monocyclic peptides, side-chain attachment of Asp or Glu residues to the oxime resin is proposed,[436,43T which leads to the desired cyclization and release of the protected segments as Pac or preferably as A1 es-tersJ396 These are C-terminally deprotected, when required, and then assembled in solution into bi- or polycyclic peptides of type I. 

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