4-Acetoxy azetidinone

This asymmetric alkylation of cyclic acylimines can provide optically active precursors to carbapenems.2 Thus reaction of the 4-acetoxy-2-azetidinone 5 with the chiral 3-acyl-(4S)-ethyl-l,3-thiazolidine-2-thione 6 provides the substituted aze-tidinone 7, an intermediate in a total synthesis of (- )-l-(3-methylcarbapenem. 

A monoacetoxylation may be obtained via an electrodecarboxylation of heterocycles ()3-lactam [193, 194] or oxazo-lidine derivatives [195]) having a carboxylic group in a-position, as shown in Scheme 106 for the preparation of 4-acetoxy-2-azetidinones. 

Indium mediated allylation of 4-acetoxy-2-azetidinones gave the products 57 in high yield <99SL447> and similar reactions with azetidin-2,3-diones gave 3-substituted 3-hydroxy-P-lactams 58 <98H97>. 

The free existence in solution of l-azetin-4-one has been demonstrated for the first time by using the three-phase test (90JOC434). The intermediate was generated from a 4-polymeric sulfonate 2-azetidinone, which is able to act as its nonpolymeric analogue 4-acetoxy-2-azetidinone in reactions with nucleophilic compounds. 

Indium-mediated allylation of 4-acetoxy-2-azetidinones affords 4-allyl-substituted azetidinones with retention of the stereochemistry (Equation (82)).320 An aminoalkoxy titanium complex is readily allylated with allylindium reagents to give homoallylic amines (Scheme 86).321... 

Transfer into a single-necked round-bottomed flask (100 mL), 4-acetoxy-2-azetidinone (1.32 g, 10.2 mmol) and a magnetic stirrer bar. Pour acetone (1 mL) and water (3.5 mL) into the flask under a stream of nitrogen and equip the flask with a pressure-equalizing addition funnel (50 mL) containing a solution of potassium ethyl trithiocarbonate (2.25 g, 1.28 mol-eq.) in water (12 mL). 

Similarly, starting from 4-acetoxy-2-azetidinone (12), 4-phenylthio-2-azetidinone (13) is formed in 79% yield with 38% optical purity9. 

Synthesis of selenopenams starts with commercially available 4-acetoxy-2-azetidinone derivatives which are reacted with sodium benzylselenoate, prepared by treatment of dibenzyl diselenide with sodium borohydride, to give 4-(benzylseleno)-2-azetidinones 97. The radical precursor 98 prepared from 97 was irradiated or heated, and the selenopenams 99 were thus obtained (Scheme 24) <20040BC2612, 2004MOL466, 2001TL4737>. 

A new efficient methodology for the preparation of a chiral 2-azetidinone intermediate applicable to the total synthesis of (+)-thienamycin and l)S-substituted carbapenems has been developed (86JAa673). This is based on the highly diastereoselective aldol-type reaction employing C4-chiral 3-acyl-l,3-thiazolidine-2-thiones and 4-acetoxy-2-azetidinones. 

A THF solution of 4-acetoxy-2-azetidinone (60) at -40°C was added to tin(II) enolate 59a, which was prepared from 3-acetyl-(4S)-ethyl-l,3-thia-zolidine-2-thione (40a). After stirring at 0°C for 1 hr, the reaction mixture... 

Diasterbo-Controlled Alkylation of 4-Acetoxy-2-azetidinone (60) with Tin(II) Enolates 65a-e... 

Determined by HPLC analysis (U V, 305 nm). Based on 4-acetoxy-2-azetidinone (60). 

Optically active 3-substituted 4-acetoxy-2-azetidinone (78) was similarly allowed to react with chiral tin(II) enolates 59a and b or achiral tin(II) enolates 79 and 80 in THF at 0°C for 1 hr to furnish the desired ) -methyl products, 81 (80% yield) in a 90 10 (81/other isomers) ratio, 82 (74% yield) in a 91 9 ratio (82/other isomers), 83 in a 79 21 ratio (83/other isomers), and 84 in a 88 12 ratio (84/other isomers), respectively (Scheme 15) (86JA4673). Each minor product separated from a mixture with the corresponding ) -(/ )-methyl product was proved to be an a-(S)-methyl derivative, which was formed from the -type tin(II) enolate of 3-propanoylthiazolidine-2-thiones. 

Mori used the anodic decarboxylative acetoxylation for the synthesis of the valuable penem precursors 4-acetoxy-2-azetidinones. Thus, 4-carboxy-2-azetidinone was electrolyzed in acetonitrile/AcOH (3 1) in the presence of NaOAc (4.5 equivalents) to give the desired product in 76% yield. Starting from the enantiopure 4-carboxy-3-[l-(t-butyldi-methylsilyloxy)ethyl]-2-azetidinone, the enantiopure 4-acetoxy compound was obtained in 85% yield [Eq. (48)] [244]. 

Acylation of quinoline with methylchloroformate (Scheme 5.2.69) generates the A-acyliminium ion in situ, which is efficiently trapped by allenyltri-n-butylstannane to give the 1,2-dihydroquinoline 322 in excellent yield. A potentially important Se substitution is illustrated by the reaction of 4-acetoxy-2-azetidinone 323 with the mixture of diastereomers 324 (Scheme 5.2.69) in the presence of BFj OEt2. Generation of the reactive A-acyliminium species leads to formation of jS-lactam 325 with moderate diastereoselection.ioo... 

Indium-mediated allylation of 4-acetoxy-2-azetidinones affords 4-aUyl-substituted... 

Greengrass, C.W., and Hoople, D.W.T., Reaction of 4-acetoxy-2-azetidinone with tertiary carbanions. Preparation of 4-alkyl- and 4-alkyhdene-2-azetidinones, Tetrahedron Lett., 22, 1161, 1981. 

Diastereo-Controlled Alkylation of 4-ACETOXY-2-AZETIDINONE (60) WITH... 

S. Mickel, 4-Acetoxy-2-Azetidinone A Useful Heterocyclic Synthon, Aldrichimica Acta, 1985, 95. 

It was discovered that the A -formimidoyl derivative both stabilised the molecular and enhanced the antipseudomonal activity [7]. The basic starting material for both imipenem and meropenem is 4-acetoxy-2-azetidinone (4-AA) (8), a well known heterocycle synthon which can readily be converted to 9 [8]. 

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