Preparation of chiral pyrrolidinone derivatives

A process for the preparation of a compound of formula IIa or IIb:

• ##STR24## wherein R.sup.2, R.sup.3, R.sup.4 and R.sup.5 independently represent hydrogen or C.sub.1 -C.sub.4 alkyl;
• A is an aromatic or heteroaromatic ring system optionally substituted with one or more substituents selected from halogen, C.sub.1 -C.sub.10 hydrocarbyl, S(O).sub.p (C.sub.1 -C.sub.10 hydrocarbyl), cyano, nitro, SCN, SiR.sup.c.sub.3 where each R.sup.c is independently C.sub.1 -C.sub.4 alkyl or phenyl, COR.sup.8, CR.sup.8 NOR.sup.9, NHOH, ONR.sup.8 R.sup.9, SF.sub.5, COOR.sup.8, SO.sub.2 NR.sup.8 R.sup.9, OR.sup.10 and NR.sup.11 R.sup.12 ;
• and in which any ring nitrogen atom may be quaternised or oxidised;
• alternatively, any two substituents of the group A may combine to form a fused 5- or 6- membered saturated or partially saturated carbocyclic or heterocyclic ring in which any carbon or quaternised nitrogen atom may be substituted with any of the groups mentioned above for A or in which a ring carbon atom may be oxidised;
• p is 0, 1 or 2;
• R.sup.8 and R.sup.9 independently represent hydrogen or C.sub.1 -C.sub.10 hydrocarbyl;
• R.sup.10 is hydrogen, C.sub.1 -C.sub.10 hydrocarbyl, SO.sub.2 (C.sub.1 -C.sub.10 hydrocarbyl) CHO, CO(C.sub.1 -C.sub.10 hydrocarbyl), COO(C.sub.1 -C.sub.10 hydrocarbyl) or CONR.sup.8 R.sup.9 ;
• R.sup.11 and R.sup.12 independently represent hydrogen, C.sub.1 -C.sub.10 hydrocarbyl, O(C.sub.1 -C.sub.10 hydrocarbyl), SO.sub.2 (C.sub.1 -C.sub.10 hydrocarbyl), CHO, CO(C.sub.1 -C.sub.10 hydrocarbyl), COO(C.sub.1 -C.sub.10 hydrocarbyl) or CONR.sup.8 R.sup.9 ;
• any of the hydrocarbyl groups within the group A may optionally be substituted with halogen, hydroxy, SO.sub.2 NR.sup.a R.sup.b where R.sup.a and R.sup.b independently represent hydrogen or C.sub.1 -C.sub.6 alkyl, cyano, nitro, amino, mono- and dialkylamino in which the alkyl groups have from 1 to 6 or more carbon atoms, acylamino, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 haloalkoxy, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulphinyl, C.sub.1 -C.sub.6 alkylsulphonyl, carboxy, carboxyamide in which the groups attached to the N atom may be hydrogen or C.sub.1 -C.sub.10 hydrocarbyl optionally substituted with halogen, alkoxycarbonyl wherein the alkoxy group may have from 1 to 6 or more carbon atoms or aryl;
• the process comprising heating a compound of formula Va or Vb:
• ##STR25## wherein R.sup.2 and R.sup.3 are as defined for formulae IIa and IIb and R.sup.4 and R.sup.5 are hydrogen;
• with a compound of formula VI:
• ##STR26## wherein A is as defined for formulae IIa and IIb at a temperature of from about 100.degree. to 300.degree. C.

A process for preparing a compound of formula II so as to obtain an enantiomeric excess of a compound of formula IIa or IIb:

• ##STR27## wherein R.sup.2, R.sup.3, R.sup.4 and R.sup.5 independently represent hydrogen or C.sub.1 -C.sub.4 alkyl;
• A is an aromatic or heteroaromatic ring system optionally substituted with one or more substituents selected from halogen, C.sub.1 -C.sub.10 hydrocarbyl, S(O).sub.p (C.sub.1 -C.sub.10 hydrocarbyl), cyano, nitro, SCN, SiR.sup.c.sub.3 where each R.sup.c is independently C.sub.1 -C.sub.4 alkyl or phenyl, COR.sup.8, CR.sup.8 NOR.sup.9, NHOH, ONR.sup.8 R.sup.9, SF.sub.5, COOR.sup.8, SO.sub.2 NR.sup.8 R.sup.9, OR.sup.10 and NR.sup.11 R.sup.12 ;
• and in which any ring nitrogen atom may be quaternised or oxidised;
• alternatively, any two substituents of the group A may combine to form a fused 5- or 6- membered saturated or partially saturated carbocyclic or heterocyclic ring in which any carbon or quaternised nitrogen atom may be substituted with any of the groups mentioned above for A or in which a ring carbon atom may be oxidised;
• p is 0, 1 or 2;
• R.sup.8 and R.sup.9 independently represent hydrogen or C.sub.1 -C.sub.10 hydrocarbyl;
• R.sup.10 is hydrogen, C.sub.1 -C.sub.10 hydrocarbyl, SO.sub.2 (C.sub.1 -C.sub.10 hydrocarbyl) CHO, CO(C.sub.1 -C.sub.10 hydrocarbyl), COO(C.sub.1 -C.sub.10 hydrocarbyl) or CONR.sup.8 R.sup.9 ;
• R.sup.11 and R.sup.12 independently represent hydrogen, C.sub.1 -C.sub.10 hydrocarbyl, O(C.sub.1 -C.sub.10 hydrocarbyl), SO.sub.1 (C.sub.1 -C.sub.10 hydrocarbyl), CHO, CO(C.sub.1 -C.sub.10 hydrocarbyl), COO(C.sub.1 -C.sub.10 hydrocarbyl) or CONR.sup.8 R.sup.9 ;
• any of the hydrocarbyl groups within the group A may optionally be substituted with halogen, hydroxy, SO.sub.2 NR.sup.a R.sup.b where R.sup.a and R.sup.b independently represent hydrogen or C.sub.1 -C.sub.6 alkyl, cyano, nitro, amino, mono- and dialkylamino in which the alkyl groups have from 1 to 6 or more carbon atoms, acylamino, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 haloalkoxy, C.sub.1 -C.sub.6 alkylthio, C.sub.1 -C.sub.6 alkylsulphinyl, C.sub.1 -C.sub.6 alkylsulphonyl, carboxy, carboxyamide in which the groups attached to the N atom may be hydrogen or C.sub.1 -C.sub.10 hydrocarbyl optionally substituted with halogen, alkoxycarbonyl wherein the alkoxy group may have from 1 to 6 or more carbon atoms or aryl;
• the process comprising reacting a compound of formula VII:
• ##STR28## wherein R.sup.2, R.sup.3, R.sup.4, R.sup.5 and A are as defined for formulae IIa and IIb;
• with a base at a temperature from -100.degree. to 10.degree. C. followed by a sterically hindered chiral oxidising agent.