Azetidinone derivatives, a process for their preparation and their use as intermediates in the preparation of carbapenem antibiotics

A process for preparing a compound of the formula (IV):

• ##STR41## which comprises reacting a compound of the formula (II):
• ##STR42## with a compound of the formula (III):
• P(R.sup.6).sub.3 (III)
• and cyclising the product of this reaction to prepare said compound of the formula (IV);
• wherein:
• R.sup.1 represents hydrogen or a hydroxy-protecting group;
• R.sup.2 and R.sup.3 may be the same or different and each represents hydrogen, a C.sub.1 -C.sub.6 alkyl group or a phenyl group;
• R.sup.4 represents a C.sub.1 -C.sub.6 alkyl group;
• a non-aromatic heterocyclic group having from 4 to 8 ring carbon atoms and having one or two ring nitrogen atoms and optionally containing an oxygen atom, a sulphur atom, a sulphinyl group, a sulphonyl group or a carbonyl group, and optionally having one or more substituents attached to the carbon atoms or to any nitrogen atom, selected from the group consisting of (1) substituents for attachment to the ring carbon atoms selected from the group consisting of C.sub.1 -C.sub.6 alkyl groups, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl groups, C.sub.2 -C.sub.8 alkoxyalkyl groups, methoxycarbonylmethyl, ethoxycarbonylmethyl, t-butoxycarbonylmethyl, benzyloxycarbonylethyl, methoxycarbonylpropyl groups, C.sub.2 -C.sub.7 cyanoalkyl groups, C.sub.1 -C.sub.6 haloalkyl groups, C.sub.1 -C.sub.6 alkoxy groups, halogen atoms, C.sub.1 -C.sub.6 aliphatic acyloxy groups, C.sub.1 -C.sub.6 aliphatic acylamino groups, cyano group, azido group, carboxy group, C.sub.2 -C.sub.7 alkoxycarbonyl groups, carbamoyl group, C.sub.1 -C.sub.6 alkylthio groups, C.sub.1 -C.sub.6 alkylsulphonyl groups, C.sub.1 -C.sub.6 alkylsulphonyl groups, nitro group;
• and (2) substituents for attachment to said ring nitrogen atom(s) selected from the group consisting of C.sub.1 -C.sub.6 alkyl groups, C.sub.1 -C.sub.6 alkenyl groups, C.sub.2 -C.sub.6 alkynyl groups, C.sub.3 -C.sub.8 cycloalkyl groups, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, 2-cyclopentylethyl, 2-cyclohexylethyl, 3-cyclopentylpropyl, 2-cyclopentylpropyl, 3-cyclohexylpropyl, 2-cyclohexylpropyl, 4-cyclopentylbutyl, 3-cyclohexylbutyl, phenyl, naphthyl groups, benzyl, phenylethyl, 3-phenylpropyl, C.sub.1 -C.sub.6 aliphatic acyl groups, cycloponanecarbonyl, cyclobutanecarbonyl, cyclopentanecarbonyl, cyclohexanecarbonyl, cyclopropylacetyl, cyclobutylacetyl, cyclopentylacetyl, cyclohexylacetyl, 3-cyclopentylpropionyl, 3-cyclohexylpropionyl, 4-cyclopentylbutyryl, 4-cyclohexylbutyryl, benzoyl, 1-naphthoyl, 2-naphthoyl groups, phenylacetyl, 1-naphthylacetyl, 3-phenylpropionyl, hydratropoyl, cinnamoyl, phenylpropioloyl, furoyl, thenoyl, nicotinoyl, isonicotinoyl, 4-thiazolecarbonyl, 5-pyrimidinecarbonyl, 2-pyrazinecarbonyl, 2-thienylacetyl, 3-(2-thienyl)propionyl, 4-thiazolylacetyl, 2-pyridylacetyl, 4-pyridylacetyl, 5-pyrimidinylacetyl, 1-aziridinylacetyl, 1-azetidinylacetyl, 3-azetidinylacetyl, 1-pyrrolidinylacetyl, 2-pyrrolidinylacetyl, 3-pyrrolidinylacetyl, 3-(2-pyrrolidinyl)propionyl, piperidinoacetyl, 2-piperidinylacetyl, 4-piperidinylacetyl, morpholinoacetyl, 1-aziridinecarbonyl, 1-azetidinecarbonyl, 3-azetidinecarbonyl, 1-pyrrolidinecarbonyl, 2-pyrrolidinecarbonyl, 3-pyrrolidinecarbonyl, 1-piperidinecarbonyl, 2-piperidinecarbonyl, 4-piperidinecarbonyl, 4-morpholinecarbonyl, phenacyl group, sulpho group, C.sub.1 -C.sub.6 alkylsulphonyl groups, C.sub.1 -C.sub.6 alkylsulphonyl groups, C.sub.2 -C.sub.6 alkylsulphonyl groups, C.sub.2 -C.sub.6 alkylsulphonyl groups, cyclopropylsulphonyl, cyclobutylsulphonyl, cyclopentylsulphonyl, cyclohexylsulphonyl, cyclopropylmethylsulphonyl, cyclobutylmethylsulphonyl, cyclopentylmethylsulphonyl, cyclohexylmethylsulphonyl, 2-cyclopentylethylsulphonyl, 2-cyclohexylethylsulphonyl, 3-cyclopentylpropylsulphonyl, 2-cyclopentylpropylsulphonyl, phenylsulphonyl, 1-naphthylsulphonyl, 2-naphthylsulphonyl, benzylsulphonyl, phenethylsulphonyl, 3-phenylpropylsulphonyl, 2-phenylpropylsulphonyl, 2-thienylsulphonyl, 4-thiazolylsulphonyl, 2-pyridylsulphonyl, 4-pyridylsulphonyl, 2-thienylmethylsulphonyl, 3-(2-thienyl)propylsulphonyl, 4-thiazolylmethylsulphonyl, 2-pyridylmethylsulphonyl, 4-pyridylmethylsulphonyl group, groups of the formula ##STR43## wherein R.sup.10 represents a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group and R.sup.11 represents a hydrogen atom, allyloxycarbonyl, 2-methylallyloxycarbonyl, 2-chloroallyloxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2,2,2-tribromoethoxycarbonyl, p-nitrobenzyloxycarbonyl or o-nitrobenzyloxycarbonyl,
• groups of the formula ##STR44## wherein R.sup.12 and R.sup.13 are the same or different and each represents a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group and Y represents an oxygen atom, a sulphur atom or an imino group which may be optionally substituted with a C.sub.1 -C.sub.4 alkyl group,
• C.sub.2 -C.sub.7 alkoxycarbonyl groups, benzyloxycarbonyl, phenethyloxycarbonyl, p-nitrobenzyloxycarbonyl and o nitrobenzyloxy carbonyl group;
• and
• the substituents attached to the nitrogen atoms of the non-aromatic heterocyclic groups may be substituted with one or more groups selected from the group consisting of C.sub.1 -C.sub.4 alkyl groups, C.sub.1 -C.sub.4 alkoxy groups, hydroxy, amino, halogen, C.sub.1 -C.sub.5 aliphatic acyloxy groups, C.sub.1 -C.sub.5 aliphatic acylamino groups, cyano, azido, carboxy, C.sub.2 -C.sub.5 alkoxycarbonyl groups, the carbamoyl group, C.sub.1 -C.sub.4 alkylthio group, C.sub.1 -C.sub.4 alkylsulphonyl groups, C.sub.1 -C.sub.4 alkylsulphonyl groups, nitro group, and groups of formula ##STR45## wherein R.sup.14 and R.sup.15 are the same or different and each represents a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group;
• a substituted alkyl group, said substituted alkyl groups being selected from the group consisting of a hydroxyalkyl group,
• a protected hydroxy alkyl group, an aminoalkyl group, and a protected aminoalkyl group;
• a group represented by the formula ##STR46## wherein R.sup.7, R.sup.8, and R.sup.9 are the same or different and each represents hydrogen, methyl, ethyl, an amino-protecting group, or R.sup.7 and R.sup.8 or R.sup.8 and R.sup.9, together with the atom or atoms to which they are attached, form a ring and when R.sup.8 and R.sup.9 form a ring, they together represent ethylene, trimethylene, tetramethylene, pentamethylene or hexamethylene, and when R.sup.7 and R.sup.8 form a ring, R.sup.7 and R.sup.8 together represent ethylene or trimethylene;
• an aryl-substituted alkyl group, selected from the group consisting of benzyl, p-methoxybenzyl, m-nitrobenzyl, o-methylbenzyl, p-bromobenzyl and p-aminobenzyl;
• furfuryl;
• an alkyl group having a non-aromatic heterocyclic substituent, the alkyl group of which is a C.sub.1 -C.sub.4 alkyl, and the non-aromatic heterocyclic substituent is selected from the substituted or unsubstituted non-aromatic heterocyclic groups within the definition hereinbefore of R.sup.4 ;
• an alkenyl group or a substituted alkenyl group, selected from the group consisting of vinyl, allyl, 1-propenyl and 2-butenyl;
• an alkynyl group or a substituted alkynyl group selected from the group consisting of ethynyl, 2-propynyl and 1-propynyl;
• and when R.sup.4 represents a substituted alkenyl or alkynyl group as defined above, the substituents are selected from the group consisting of the formula --NR.sup.16 R.sup.17 wherein R.sup.16 and R.sup.17 are the same or different and each represents hydrogen, methyl, ethyl, propyl, isopropyl group, formyl, acetyl, propionyl, isobutyryl, chloroacetyl, trifluoroacetyl, benzoyl group or an amino-protecting group;
• groups of the formula --CONHR.sup.18, wherein R.sup.18 represents a hydrogen, methyl, ethyl, propyl, or an amino-protecting group;
• groups of the formula --NHCONHR.sup.18 ;
• groups of the formula --COOR.sup.19 wherein R.sup.19 represents hydrogen, methyl, ethyl, propyl or a carboxy-protecting group;
• groups of the formula --SR.sup.20, wherein R.sup.20 represents hydrogen, methyl, ethyl, propyl, allyl, vinyl, 1-methylvinyl, 1-propenyl, ethynyl, 2-propynyl, 1-propynyl, cyclopropyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopentylmethyl, 2-cyclohexylethyl, 2-cyclopentylethyl, benzyl, phenylethyl, p-methoxybenzyl, p-bromobenzyl, phenyl, p-tolyl, p-methoxyphenyl, thienyl, furyl, imidazolyl, pyridyl, thienylmethyl, 2-thienylmethyl, pyridylmethyl, imidazolylmethyl and thiazolylmethyl;
• groups of the formula --S(:O)R.sup.20 ;
• groups of the formula --SO.sub.2 R.sup.21 wherein R.sup.21 represents any of the groups defined for R.sup.20 or methoxy, ethoxy or propoxy;
• groups of formula --OSO.sub.2 R.sup.20 ;
• cyano;
• nitro;
• and azido groups;
• R.sup.5 represents hydrogen, or a carboxy-protecting group;
• R.sup.6 represents an alkoxy group having from 1 to 6 carbon atoms, or a phenoxy group selected from the group consisting of phenoxy, p-methylphenoxy, p-methoxyphenoxy groups, and a dialkylamino group wherein each alkyl group has from 1 to 6 carbon atoms, or two R.sup.6 groups together represent an o-phenylenedioxy group, and the other R.sup.6 represents any other R.sup.6 group, or the three R.sup.6 groups together represent a group of the formula CH.sub.3 --(CH.sub.2 --O--).sub.3.