Azetidinones, also

Azeto[2,l-bjquinazolines. The intramolecular aza-Wittig reaction by treatment of A/-(o-azidobenzyl)azetidinones (also the A/-benzoyl analogs) with triorganophosphines R3P is only successful when R = Me (when R = Bu, Ph, complex reaction mixtures are generated which do not contain the desired products). 

Cyclization of (68) and depiotection tfien yield the monobactam nucleus (69) which may be coupled with various C-3 side chains (48). Direct alkylation of the JV-unsubstituted azetidinone (70) using fluorotetrazole [93607-94-4], CgH FN, also produced (69) after deprotection of (71) (49). 

A similar intramolecular nucleophilic capture of an allylic sulfenate generated thermally from the corresponding sulfoxide was also reported for the facile transformation of the azetidinone 61 into a new 3-acetylthio-2-thiacephem ring system 62 (equation 29)127. 

The electrophilicity of alane is the basis for its selective reaction with the amide group. Alane is also useful for reducing azetidinones to azetidines. Most nucleophilic hydride reducing agents lead to ring-opened products. DiBAlH, A1H2C1, and A1HC12 can also reduce azetinones to azetidines.100... 

With a 3,3-heterodihalogeno substitution of the (3-lactam ring, a selective interaction of each enantiomer of the chiral azetidinone with the enzyme active site is expected. The enantiomer 3R of the 3F, 3Br derivative indeed has a more favorable kinetic parameter k-JK, than the enantiomer 3S.33 The partition ratio kCA /kt (=k3/k4, Eq. 11.1) for the inactivation is also higher. Therefore, enantiomer 3R is a better suicide substrate for HLE since a lower partition ratio corresponds to abetter suicide substrate.20... 

Cationic Fp (olefin) complexes [Fp = f/5-C5H5Fe(CO)2] undergo regio-specific addition of heteroatomic nucleophiles.32 Subsequent ligand transfer (carbonyl insertion) occurs with retention of configuration at the migrating center (R—Fe—CO -> RCOFe).33 A combination of these processes has provided a novel stereospecific azetidinone synthesis which can also be applied to condensed systems.34... 

Scheme 11). Alternatively the quaternary salts can be converted thermally into acyliron chelate complexes which can then be oxidized to azetidinones (Scheme 12). Extension of the method to the synthesis of a condensed azetidinone is illustrated in Scheme 13, but the scope of the procedure has not been evaluated. It will also be of interest to assess the utility of other cationic organometallic complexes preliminary studies have shown that molybdenum complexes behave in an analogous manner but the oxidative cyclization is inefficient (Scheme 14). 

Lactams are named in several ways. They are named as alkanolactams by the IUPAC substitutive system, such as 3-propanolactam, 4-butanolactam, 5-pentanolactam, and 6-hexano-lactam, respectively, for the 4-, 5-, 6-, and 7-membered rings, respectively. An alternate IUPAC method, the specialist heterocyclic nomenclature system, names these lactams as 2-azetidinone, 2-pyrrolidinone, 2-piperidinone, and hexahydro-2f/-azepi n-2-one, respectively. These lactams are also known by the trivial names fl-propiolactam, a-pyrrolidone (y-butyrolactam), a-piperidone (8-valerolactam), and e-caprolactam, respectively. 

Reformatsky reactions of Af-(2-bromoalkanoyl)-l,3-benzoxazin-4-ones 267 and 272 and imines derived from aniline or /)-substituted anilines gave fra j -/3-lactams 273 with complete diastereoselectivity, and the l,3-benzoxazin-4-one auxiliary 269 could also be recycled. However, in the similar transformations of imines containing an o-methoxyphenyl substituent on the nitrogen, no cyclization to azetidinone occurred and /r -/3-aminocarboxamide derivatives 274 were the only products formed (Scheme 51) <2005S725>. 

Reduction of hydroxamic acids. Buffered TiC lj can reduce simple hydroxamic acids (equation I). Yields are high when R1 is an alkyl group when it is hydrogen, aldehydes are obtained as by-products. The reagent also reduces substituted N-hydroxy-2-azetidinones to /Mactams (equation 11). 

While these rearrangements are used most often to prepare large rings, the expansion of cyclopropanone to azetidinones is also practical (Scheme 24 CHEC 5.09.3.3.3). 

Arylation, olefins, 187, 190 Arylketimines, iridium hydrogenation, 83 Arylpropanoic acid, Grignard coupling, 190 Aspartame, 8, 27 Asymmetric catalysis characteristics, 11 chiral metal complexes, 122 covalently bound intermediates, 323 electrochemistry, 342 hydrogen-bonded associates, 328 industrial applications, 8, 357 optically active compounds, 2 phase-transfer reactions, 333 photochemistry, 341 polymerization, 174, 332 purely organic compounds, 323 see also specific complexes Asymmetric induction, 71, 155 Attractive interaction, 196, 216 Autoinduction, 330 Axial chirality, 18 Aza-Diels-Alder reaction, 220 Azetidinone, 44, 80 Aziridination, olefins, 207... 

Azetidinones are also formed on photolysis of cis-a-phenyl-cinnamanilide (361), but in addition a small quantity of a cis-trans mixture of 3,4-diphenyl-3,4-dihydroquinolin-2-one (362) was obtained. The yield of quinolinone was considerably increased in the photocyclization of alkyl-substituted acrylanilides.389 The anilide (363) of tiglic acid, for example, was converted into the anilide (364) of angelic acid by photochemical cis-trans isomerism, and into a mixture of cis- and [Pg.103]

Of the new methods of preparation of oxo derivatives of the 5,6-dihydro-4//-1,3-oxazines, the most important is that developed by Martin and co-workers 169 the reaction of acylisocyanates with enol ethers at room temperature under nitrogen yields 48 [Eq. (35)] (see also Arbuzov et a/.170-171) together with an isomeric azetidinone. The... 

The extension of the above radical intramolecular cyclization of /V-haloaryl-p-lactams to 2-azetidinones bearing the proradical center at C3 was also explored. The treatment of haloarenes 109a-c under similar conditions for the preparation of benzocarbapenems and benzocarbacephems 104—108 gave the fused tricyclic (1-lactams llOa-c (Scheme 37, Table 2). Compounds 110a and 110b were obtained as mixtures of diastereomers, which are epimers at the newly formed C5 stereocenter, while the amino derivative 110c could be prepared as a single isomer. 

The 1,2-functionalization of the allene moiety in 2-azetidinone-tethered alleny-nol derivatives has also been explored [96]. Carbamate 174 was selected as the starting material for the palladium(II)-catalyzed reaction. The above carbamate was prepared from the ot-allenic alcohol 171a by treatment with tosyl isocyanate. Reaction of compound 174 was carried out at room temperature in acetonitrile in the presence of 10 mol% of Pd(OAc)2, 5 equiv of LiBr, 2 equiv of Cu(OAc)2 and 1.2 equiv of K2CO3 under an atmospheric pressure of oxygen. The 1H-XMR spectrum of the crude material displayed neither signal corresponding to the allene... 

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