Azetidines conversion

The direct, stereoselective conversion of alkynes to A-sulfonylazetidin-2-imines 16 by the initial reaction of copper(l) acetylides with sulfonyl azides, followed, in situ, by the formal [2+2] cycloaddition of a postulated A-sulfonylketenimine intermediate with a range of imines has been described <06AG(E)3157>. The synthesis of A-alkylated 2-substituted azetidin-3-ones 17 based on a tandem nucleophilic substitution followed by intramolecular Michael reaction of primary amines with alkyl 5-bromo-4-oxopent-2-enoates has been... 

The cyclization of 7-aminoalcohols or 7-azidoalcohols can produce azetidines via activation with phosphines (81JOC3562,84JCS(P1)2415,85TL2809,92OPP209), as exemplified for the conversion (25) — (26) (83CC682, 84JCS(P1)2415>. 

Powdered crystals of 1, well ground and sandwiched by Pyrex glass plates, were irradiated with 500-W Hg lamp at 0 °C for 2 h, which led to the exclusive production of optically active / -thiolactam, l-benzyl-4-phenyl-azetidine-2-tliione-3-spiro-T-cyclohexane 2, in 96% yield at 58% conversion. The material was purified by column chromatography, and the structure was determined by spectroscopy. As expected, the thiolactam 2 showed optical activity ([a]D+109° c 1.0 CHC13, 94% ee). 

The possibility of the triazene linking system for the ester-enolate imine condensation was initially investigated on model compounds 110 and 111 (Scheme 35). Dibenzyltriazene 110 was used as a model compound for monobactam derivatives and prepared by diazotization of hippuric acid methyl ester. Dibenzyltriazene 111 was used as a model compound for 3-phenyl-substituted azetidin-2-ones and prepared by diazotization of 2-(4-aminophenyl)-propionic acid methyl ester and conversion with dibenzylamine in 64% overall yield. The low yields of /V-unsub-stituted lactams, during the model studies, hint at a problematic transfer to solid support. 

Sakamoto et al. found that. S -phenyl Y-benzoylfomiyl-A-tp-tolyljthiocarbamatc 54 crystallized in chiral space group P2i.[33] Photolysis of the chiral crystals in the solid-state gave optically active l-benzyl-4-phenyl-4-phenylthiooxazolidine-2,4-dione (55, 16% chemical yield, 21% ee) and cw-3,4-diphenyl-3-hydroxy-l-(thiophenylcarbonyl)-azetidin-2-one (56, 18% chemical yield, 23% ee) in 62 % conversion yield. Better optical purities were observed at low conversion (in 17% cov.), 46% ee for 55, and 32% ee for 56, respectively. 

The conversion of pyrrolidines (6) into 1,2-disubstituted azetidines (7) has been achieved using an extrusion reaction (93BSB719). 

The reaction of 3,3-dichloro-2-methoxyazetidine 35 with lithium aluminium hydride in ether afforded 3-chloro-azetidine 36 (Equation 8). The substitution of the methoxy group by hydride via an azetinium intermediate and subsequent conversion of the geminal dichloro derivative to the monochloroazetidine via a single electron transfer reaction yielded this compound <1998JOC6>. Treatment of 1-benzyl-3-hydroxyazetidine 37 with triphenylphos-phine in carbon tetrachloride yielded l-benzyl-3-chloroazetidine 38 (Equation 9) <2004JOC2703>. 

Azetidin-2-ones, 3-hydroxy-, conversion into tetramic acids, 57, 167 Azetine-2-thione, 4-dimethylamino-3-... 

Numerous examples of photorearrangements arising by 47r-electrocyclization pathways have been described. A 2-azabicyclo[2.2.0]hex-5-ene, prepared in this way, has been used in the synthesis of 3-azatricyclo[4.1.0.0 ]heptanes, and the conversion of the 4-acetoxypyrid-2-ones (10) into the azabicyclo[2.2.0]hexenones (11) is a vital step in a new synthesis of 4-(2 -hydroxyethyl)azetidin-2-ones. Irradiation of the 4-pyrimidinones (12) in acetic acid affords the 5-carboxypyrimidinium betaines (13) via the bicycles (14) these intermediates are stable in liquid ammonia-ether mixtures at —40°C. The l,3-diazabicyclo[2.2.0]hex-5-en-2-one (15) is... 

The conversion of secondary azetidines into amides, carbamates, sulfonamides and ureas is accomplished without difficulty by the usual procedures a number of these derivatives are listed in Tables 1, 2 and 3. An extensive survey of these reactions has been csxried out -with 3-phenylazetidine. T -Nitroso derivatives ore obtuned -with nitrous acid, and. y-mirofiO -S-phenylaeetidine has been reduced with lithium... 

In the course of studies on cyclopropanone—)5-lactam conversions, Wasserman and coworkers developed a route to the nocardicins by taking advantage of the reactivity of primary amines with cyclopropanone. The unusual susceptibility of the carbonyl group of cyclopropanone to attack by nucleophiles is well exemplified in this synthesis which involves the addition of the highly hindered malonate derivative (156) to generate the cyclopropanol adduct (157). The hindered amine (156) was previously found to be completely unreactive as a nucleophile in a displacement reaction with dibromoester (158) in an attempt to form the azetidine carboxylate (159). The further conversion of the amino malonate adduct (157) to the -lactam through a nitrenium ion rearrangement is illustrated in Scheme 59. 

Analogous intramolecular additions have also been described. The importance of the trifluoromethyl group in influencing the course of a photoreaction has again been demonstrated in the conversion of 3-(but-3-enyl)-2-trifluoromethyl-4(3H)-quinazolinone (100) into the intramolecular adduct (101) the corresponding 2-unsubstituted quinazolinone is reported to be photostable. Intramolecular azetidine formation has also been... 

In order to study possible side reactions which may reduce the yield in the Woodward method of annulation of azetidin-2-ones (Scheme 31) similar reactions of ylides (214), which do not contain groups capable of conversion to carbonyl by DMSO-acetic anhydride treatment, have been investigated. 30 A range of products, e.g. (215) and (216), were obtained. A mild, four-carbon homologation of the 4-formyl-substituted azetidinone (217) involving reaction with the phosphonium ylide (218) has been used to synthesize (219), a useful intermediate in the synthesis of carbacephem antibiotics. 3 ... 

Azetidine-2,4-diones can be prepared in good yield from aziridinones by carbonylation in the presence of a rtiodium catalyst (equation 54). This conversion can also be brought about using [Co2(CO)s], but in this case the reaction is not catalytic. 

Photorearrangement of o-nitrobenzyl derivatives is a well-established process and proceeds via intramolecular hydrogen abstraction. A pathway of this type is initially involved in the conversion of the 1-(o-nitrobenzyl)-2-acylpyrazolidin-3-ones (70) into the 1-(acylamino)azetidin-2-ones (71) as shown in Scheme 4, ... 

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