4-Acetoxyazetidin-2-one

An intermolecular carbenoid reaction followed by intramolecular displacement of acetate gives the clavulanic acid derivative (112) in one step from 4-acetoxyazetidin-2-one (91) (80CC1257). Carbene-induced reactions of penicillins and cephalosporins have been reviewed (75S547, 78T1731). 

Treatment of the 1,2-oxazines 52 with carbon monoxide at 1000 psi in the presence of cobalt carbonyl brings about insertion of carbon monoxide to form the 1,3-oxazepines S3 <96TL2713>. A convenient route to P-lactams fused to oxepines is made available by alkene metathesis. Thus reaction of 4-acetoxyazetidin-2-one with ally alcohol in the presence of zinc acetate, followed by iV-allylation of the nitrogen affords the derivative 54 which cyclises by RCM to form the oxazepinone 55 <96CC2231>. The same communication describes a similar synthesis of 1,3-dioxepines. 

Campbell, M.M. and Carruthers, N., Synthesis of a-aminophosphonic and a-aminophosphinic acids and derived dipeptides from 4-acetoxyazetidin-2-ones, Chem. Commun., 730, 1980. 

Silane, trimethyl[(1-phenylethenyl)oxy]- (13735-81-4), 65, 12 4-ACETOXYAZETIDIN-2-ONE 2-AZETIDINONE, 4-HYDROXY-ACETATE (ESTER) 2-AZETIDINONE, 4-(ACETYLOXY)- (28562-53-0), 65, 135... 

Cainelli and coworkers have reported the synthesis of a class of 4-(2-oxoethy-lidene)azetidin-2-ones (IV, Fig. 14) that could be carried out by a novel Lewis acid mediated reactions of 4-acetoxyazetidin-2-ones with a-diazocarbonyl compounds [277]. 

Within the current synthetic effort in beta-lactam chemistry, 4-acetoxyazetidin-2-one and its derivatives play an important role in the total synthesis of many conventional beta-lactams and their analogues.There is therefore a requirement for a simple large-scale preparative method for this key intermediate. This synthesis is a modification of that reported by Clauss et al.7... 

Thin layer chromatographic analysis of 4-acetoxyazetid1n-2-one was carried out on E. Merck Silica gel F254 plates by elution with ethyl acetate. The hexane-soluble impurity (Rf 0.67) was detected by shortwave UV. 4-Acetoxyazetidin-2-one (Rf 0.38) was detected by exposure of the plate for 5 min to chlorine gas followed by spraying with TDM solution (Note 9) and heating with a hot air gun. 

Acetoxyazetidin-2-one 2-Azetidinone, 4-hydroxy-acetate (ester) (8) 2-Azetidinone, 4-(acetyloxy)- (9) (28562-53-0)... 

The ester group of 3-substituted 4-acetoxyazetidin-2-ones is replaceable in reactions with /3-(l-cyclohexenyl)dialk-ylboranes to form 3-cyclohexenylazetidin-2-ones in a varying cis-trans ratio <1995JA9604>. Transformations of the 4-acetoxy group to a CH(Me)COOH group <1996TL4967> are also known. 

UV. 4-Acetoxyazetidin-2-one (Rf 0.38) was detected by exposure of the plate for 5 min to chlorine gas followed by spraying with TDM solution (Note 9) and heating with a hot air gun. 

This has been nicely demonstrated and exploited by Woodward s syntheses of bicyclic systems of the penem type. They are typically formed in moderate to good yields upon refluxing the requisite substituted starting -lactams in toluene or xylene for extended periods. The key step is the introduction of the ylidic moiety into the 1-position of a 4-functionalized azetidin-2-one which itself can be obtained as a relay substance by degradation of natural penicillins or from easily available 4-acetoxyazetidin-2-one. The ester ylide function is built up by reaction first with alkyl hemiacetals of glyoxylates to give a hemiaminal and then successive replacement of the OH-group of the latter by Cl with thionyl chloride and finally of the chlorine atom by triphenylphosphane under basic conditions. 

A similar carbenoid route to the fused / -lactam 5 involves reaction of ethyl diazoacetoacetate with 4-acetoxyazetidin-2-one (4) catalyzed by rhodium(Il) acetate. Rhodium(II) acetate may also promote the cyclization step.6 For another route to compounds related to 5 see 8, 36-37. 

Janecki. T.. A novel route to substituted trienes and teti aenes. Synth. Commun., 23, 641, 1993. Campbell. M.M.. and Carrulhcrs. N.. Synthesis of a-aminophosphonic and a-aminophosphinic acids and derived dipeptides from 4-acetoxyazetidin-2-ones. J. Chem. Soc., Chem. Commun., 730, 1980. Campbell. M.M.. Carruthcrs. N.I.. and Mickel. S.J.. Aminophosphonic and aminophosphinic acid analogues of aspai tic acid. Tetrahedron, 38. 2513. 1982. 

Diastereoselective Additions to Chiral Imines, Nitrones and 4-Acetoxyazetidin-2-ones... 

The TiCU-mediated reaction of enol silanes with imines was first introduced by Ojima and coworkers in 1977. The reaction was then extended to several similar substrates, i.e. nitrones, ot-methoxycarba-mates, aminals, 4-acetoxyazetidin-2-one, 40 anj to different Lewis acids, i.e. SnCU, TiCU-(0PH)2, catalytic ZnX2, catalytic TMSOTf, ° to give good yields of the addition products with low levels ( 80 20) or a complete lack of simple stereoselection. Moderate to good anti selectivities were reported in the addition of silyl ketene acetals to imines under particular reaction conditions (equation 9) significant results are summarized in Table 4. 

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