2-Azetidinones, preparation

AZEnDINONE-4,4-DIMETHYL-l-SULFO-NYL CHLORIDE AND 2-AZETIDI-NONE-4,4-DniETHYL, 46, SI 2-Azetidinones, preparation of, 46, S6 e-Azidobiphenyls, decomposition to ni-trenes and cydization to carba-zoles, 46,88... 

The azetidinone ring system 43 is an important structural feature of the powerful b-lactam famiUes of antibiotics and appears in many other natural products such as clavulanic acid. Free radical-based routes to this ring system are remarkable for their variety and range. Four distinct radical-based disconnections have been investigated for azetidinone preparation. Disconnection a impUes closure of a carbamoyl-type radical onto an imsaturated acceptor group. Disconnection b imphes a closure of an amidoalkyl (a-carbamoyl) radical onto an enamide acceptor. Disconnection c points to an amidyl radical ring closure onto an alkene acceptor. Finally, disconnection d connotes ring closure of an acyl radical onto an imine acceptor (Scheme 11). 

Azetidinone , preparation, OSS Azetinee, 016-7 Azetinone structures, 0SO Aridu ion. roaction with epoxidsH 428-30... 

NYL CHLORIDE AND 2 AZETIDINONE 4 4-dimethyl, 46,51 2- Azetidmones, preparation of, 46,56 o Azidobiphenyls, decomposition to m-trenes and cyclization to carba-zoles, 46, 88... 

The first observation of the uncommon phenomenon of desmotropy in seven-membered heterocycles was reported for the prototropic annular tautomers 128 and 129. These dihydro-4,1-benzothiazepines, which were prepared (via the non-isolated intermediates 130 and 131 from the fused azetidinone 127 on treatment with NaOEt), could be isolated in pure form by column... 

The same group has developed the enantiospecffic synthesis of a-hydroxy [5-lactams 224 from readily available carbohydrates (Scheme 9.72) [123]. Microwave-assisted chemical reactions have been utilized for the preparation of these 3-hydroxy-2-azetidinones 224 and their subsequent conversion to enantiomeric forms of intermediates for natural products. 

JPR269>. 1,3,5-TriaIIyl-hexahydro-l,3,5-triazine has been used in the preparation of a C-4 unsubstituted azetidinone which is the starting material for the synthesis of penems and cephams <00S289>. A novel method for the preparation of AfW-disubstituted-Af"-nitroguanidines via 2-nitroimino-hexahydro-1,3,5-triazine derivatives has been studied <00TL7187>. 

Correspondingly, 4-acetoxy-2-azetidin-one (102) was prepared from 4-carboxy-2-azetidinone (101) by a non-Kolbe reaction (Eq. 13) [123],... 

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. 

The diazo ketones that are synthesized as intermediates are not only useful for the preparation of p-amino acids but may serve as versatile starting materials in different reactions, e.g. preparation of 3-azetidinones or 2-aminocyclopentanones. ... 

Azetidinones on a solid support 49 have been prepared in high yield by Staudinger reaction of a supported imine with an acid chloride in the presence of a base. The liberated p-lactams were of high purity <99TL1249>. Cycloaddition of a ketene intermediate, derived fi"om an azo compound, to an imine having an oxidatively cleavable chiral auxiliary N-substituent was used to obtain p-lactams 50. The trans. cis ratio which varied between 69 31 and 93 7, depended on the nature of the substituents R and R <99S650>. 

Examples of the synthesis of fused-ring azetidines by ring closure onto a preformed azetidine are uncommon, in contrast to approaches used for the preparation of fused ring azetidinones (see Sections 5.12.3, 5.11.4.4 and 5.10.4.3). The l,3-diazabicyclo[3.2.0]hep-tane derivative (48) was prepared (72JOC516) by cyclization with DCC of the carbamoyl-azetidine followed by thermal rearrangement of the intermediate thiazolidinone (Scheme 6). 

In contrast to the synthesis of bicyclic azetidinones containing a carboxyl group on the atom adjacent to the lactam nitrogen (see Section 5.12.3.4), few examples are reported in which bicyclic azetidinones without this carboxyl group are prepared from azetidinone precursors. One unique approach, however, utilized a free radical ring closure to obtain 6-oxa-l-azabicyclo[5.2.0]nonan-9-one (116) in modest yield (81TL2689). 

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). 

---