2-Azetidinone chemistry

The N-desilylation of 1-trimethylsilyl- or 1 -(// rt-butyldimethylsilyl)-2-azctidinones is a commonly used process in 2-azetidinone chemistry. The leri-b11toxycarbonyI group is readily removed with trifluoroacetic acid, while the 4-methox-yphenyl protecting group is conveniently removed by ceric ammonium nitrate, or anodic oxidation (Scheme 87). 

Dehydrohalogenation of substituted acetyl chlorides via tertiary organic bases and the stereoselective construction of an azetidinone ring from an imine (the Staudinger reaction) has played an important part in the development of azetidinone chemistry, which has been reviewed <1993MI637>. The use of bicarbonates in the presence of a crown ether at — 10°C has been suggested as an economical alternative to tertiary amines <2003SL1937>. 

Interesting developments in simple azetidine chemistry continue to be reported. The apparently general acetylative dealkylation of Af-tert-butyl-3-substituted azetidines 6 (R = Bu ) in the presence of boron trifluoride provides a two-step route to azabicyclobutane 7 from 6 (R = Bu, R = Cl). An aqueous solution of 7 reacts with ethyl chloroformate to give 8. Relatively unexplored 3-azetidinones 9 (R = Ac or NO2) are available from 3-acetoxya2Ktidine 6 (R = Ac, R = OAc) which is obtained by acetylative dealkyation of 6 (R = Bu , R = OAc) <96JOC5453>. 3-Substituted azetidines can be utilized in the synthesis of polyfunctional y- and S-aminophosphonic acid derivatives <95TL9201>. 

The sulfonium ylide derived chemistry of penicillins continues to meet the interest of several research groups. It is well known that intermolecular carbenoid attack at the sulfur atom generates a sulfonium ylide which undergoes spontaneous opening of the thiazolidine ring to furnish a l,2-sm>-penicillin 326). Novel examples of this reaction type were found upon Rb2(0Ac)4-catalyzed decomposition of diazomalonic esters in the presence of various penicillins this transformation constituted the opening step of a synthetic sequence directed towards 2-alkoxycarbonyl-cephems 345 a) or modified penicillins 345 b). Similar to its reaction with 4-thio-2-azetidinone... 

Several reviews of P-lactam chemistry have appeared including a general survey with 407 references <99MI335>. Other reviews include discussions of thioester enolate-imine reactions , enantio- and diastereo-selective routes to azetidinones <99MI221>, the use of diazoketones in diastereoselective synthesis <99MI43>, and solid-phase and combinatorial syntheses of p-lactams <99MI955>. 

The formation of rings with more than seven atoms has unfavorable rates because the addition step is often too slow to allow it to compete successfully with other pathways open to the radical intermediate. In stannane based chemistry for example, premature hydrogen abstraction from the organotin hydride is difficult to avoid. However, Baylis-Hillman adducts 111 derived from enantiopure 1-alkenyl (or alkynyl)-4-azetidinone-2-carbaldehydes are used for the stereoselective and divergent preparation of highly functionalized bicycles 112 and 113 fused to medium-sized heterocycles (Scheme 38) [80, 81]. The Baylis-Hillman reaction using nonracemic protected a-amino aldehydes has been attempted with limited success due to partial racemization of the chiral aldehyde by DABCO after... 

After the discovery of penicillins and cephalosporins as classical (3-lactam antibiotics and clinically useful active agents, the past few decades have witnessed a remarkable growth in the field of (3-lactam chemistry [1, 2]. The need for potentially effective (3-lactam antibiotics as well as more effective (3-lactamase inhibitors has motivated synthetic organic and medicinal chemists to design new functionalized 2-azetidinones. Besides their clinical use as antibacterial agents, these compounds have also been used as synthons in the preparation of various heterocyclic compounds of biological significance [3-7]. The potential use of some... 

As exemplified by the chemistry of Af-[bis(trimethylsilyl)methyl]azetidinones, the bissilylmethyl group are stable to ozonolysis conditions, allowing chemical transformations to be carried out on the substituents at the 4-position of the ring.228,256... 

A review on the chemistry of 3-azetidinones, 3-oxetanones and 3-thietanones has appeared <02CRV29>. 

On account of its relevance to penicillin chemistry, a great deal of work has been carried out on -lactams, but only a flavor of that chemistry can be included here. The reaction of 2-azetidinones (-lactams) with nucleophilic reagents is accompanied by acylnitrogen fission, as is normal for amides (cf. 63 64), e.g., propiolactam yields -alanine (H2NCH2CH2C02H) on hydrolysis. 

Axenrod, T., Watnick, C., and Yazdekhasti, H. 1995. Synthesis of 1,3,3-trinitroazetidine via the oxidative nitrolysis of A-p-tosyl-3-azetidinone oxime. Journal of Organic Chemistry, 60(7) 1959-64. 

Palonao, C., Aizpurua, J. M. Azetidinone frameworks as chiral templates via asymmetric Staudinger reaction. Trends in Organic Chemistry 1993, 4, 637-659. 

Singh, G. S. Recent progress in the synthesis and chemistry of azetidinones. Tetrahedron 2003, 59, 7631-7649. 

Azetidinones. - This section only includes novel results on the preparation or reactions of the azetidinone nucleus. The chemistry of 3-lactam antibiotics is not included. 

Although the solid-phase formation of this clinically valuable pharmacophore occurred with high cis selectivity, the diastereoselectivity induced by the asymmetric center of the amino acid was only very moderate. Induction could be achieved, however, with an optically active ketene. By using this approach, a model library of 25 p-lactams of type 111/112 was initially formed in higher than 80% purity, and this chemistry was subsequently used to generate a combinatorial library of thousands of 3,4-bis-substituted 2-azetidinones of sufficient purity to be directly submitted for bioassays. 

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