Azetidines, bicyclic

Other interactions of /3-lactams with electrophiles include the oxidative decarboxylation of the azetidin-2-one-4-carboxylic acid (85) on treatment with LTA and pyridine (81M867), and the reaction of the azetidin-2-one-4-sulfinic acid (86) with positive halogen reagents. This affords a mixture of cis- and trans-4-halogeno-/3-lactams (87), the latter undergoing cyclization to give the bicyclic /3-lactam (88) (8UOC3568). 

Azetidines, 7, 237-284, 238-246 addition compounds with trimethylboron, 7, 240 AT-alkylation, 7, 240 applications, 7, 246 AT-arylation, 7, 240 azetidin-2-ones from, 7, 263 bicyclic... 

Azetidin-2-one, l-benzyl-3,3,4-triphenyl-, 7, 249 Azetidin-2-one, l-(2-bromophenyl)-X-ray crystallography, 7, 247 Azetidin-2-one, 3-carboxy-synthesis, 7, 262 Azetidin-2-one, 3-halo-synthesis, 7, 77 ring contraction, 7, 81-82 Azetidin-2-one, 4-imino-IR spectroscopy, 7, 248 Azetidin-2-one, 1-phenyl-irradiation, 7, 255 Azetidin-2-one, 4-phenyl-reductive ring cleavage, 7, 252 Azetidin-2-one, 4-thio-IR spectroscopy, 7, 248 Azetidinones bicyclic, 7, 348-356 C NMR, 7, 348 H NMR, 7, 348 reactivity, 7, 356-358 spectroscopy, 7, 357 structure, 7, 349 synthesis, 7, 358-359 fused ring... 

Irradiation of methacrylonitrile and 2-alkoxy-3-cyano-4,6-dimethylpyridine mixture causes [2+2]photocycloaddition across the C(2)-C(3) bond of the latter to give the bicyclic azetine 4 (45-55%) via an azacyclooctatetraene intermediate <96CC1349>. The [2+2]cycloaddition of )V-acylaldimines and allyltriisopropylsilane to give 2,4-disubstituted azetidines is catalysed by Lewis acids <95CL789>. 

P-Lactams have been used as a synthon for the preparation of a vast array of compounds. It has been reported that the reduction of 4-(haloalkyl)azetidin-2-ones with LiAlhL is a powerful method for the synthesis of stereodefined aziridines and azetidines <06OL1101>. However, reduction of 4-(haloalkyl)azetidin-2-ones with chloroalane afforded 2-(haloalkyl)azetidines, which were rearranged to 3,4-cw-disubstituted pyrrolidines and piperidines 32 <060L1105>. During these rearrangements, bicyclic azetidinium intermediates were formed which were ring opened by halides. The synthesis of a peptide-... 

A novel route to 3,4-disubstituted piperidines 206 via ring transformation of 2-(haloalkyl)azetidines 207 is shown below. During these reactions, bicyclic azetidinium intermediates are formed and then ring opened by a variety of nucleophiles generating stereospecific substituted piperidines in excellent yields <06OLl 105>. 

For the most part the parent unsubstituted bicyclic azetidines have not been reported. Those unsubstituted ring systems which have been reported are l-azabicyclo[2.2.0]hexane (4) (64HCA2145), l-azabicyclo[4.2.0]octane (5) (60JA2609) and the cis- and trans-6-azabicyclo[4.2.0]octanes (6) (66JOC1372). 

Several bicyclic azetidine systems have been synthesized via photochemically induced valence bond isomerization of a heterocycle. Photolysis of 2-amino-5-chloropyridine in... 

The most widely used method for synthesizing bicyclic azetidines is by photoaddition reactions, primarily of the [2 + 2] type. Scheme 3 lists several examples of this method (37) (81JA3136), (38) (75JA7288), (39) (77TL431), (40) (74JHC453). Cycloadditions to carbon-nitrogen double bonds have been reviewed (78MI51200). 

Photochemical excitation of cyclic a-amino ketones (41 and 43) leads to the formation of bicyclic azetidines and azetidinols by abstraction of a hydrogen y to the ketone followed by cyclization. Production of (42) (72CC1108) and (44) (75TL2463) is believed to occur as a singlet state reaction. 

Examples of preparations for a number of bicyclic azetidines are summarized in Tables 1-3. 

Table 1 Bicyclic Azetidines having a Carbon-containing Fused Ring Ring system Systematic name Substituents Yield (%) Ref.

Table 2 Bicyclic Azetidines containing One Heteroatom in the Fused Ring...

Under appropriate thermal conditions bicyclic azetidinones can undergo valence bond tautomerism in a behavior similar to that described for bicyclic azetidines in Section 5.12.2.2.1. Thus, the position of equilibrium illustrated in equation (4) strongly favors the... 

The discovery of the norcardicins and monobactams demonstrated for the first time that a conformationally constrained bicyclic structure was not necessary for antibacterial activity of (3-lactams [12, 13]. In recent years, various natural and unnatural monocyclic-(3-lactams have been shown to exhibit high biological activity, suggesting that the biological activity of the particular ring is influenced by the type of substitution attached to the azetidin-2-one ring (Fig. 2). 

Recently discovered antitumor monocyclic and bicyclic (3-lactam systems [40-42] are, in general, in good agreement with the phenomenon of azetidin-2-one pharmacophore of inexhaustible pharmacological potential on account of the specific ability of its numerous derivatives to inhibit not only bacterial transpeptidase, but also mammalian serin and cystein proteases [43]. As a measure of cytotoxicity, some compounds have been assayed against nine human cancer cell lines. 

The radical cyclization of A/-acrylate-4-(2-bromoethyl)azetidin-2-ones [247] has been reported to form a bicyclic (3-lactam (III, Fig. 3). 

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