Novel olefination process to itaconate and succinate derivatives

A process for the preparation of a compound of the formula (IV), (V) or (VI):

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• wherein R is aryl, C3-8 cycloalkyl, C1-10 alkyl, (aryl)C1-10 alkylene, (C3-8 cycloalkyl)C1-10 alkylene, heterocyclyl, (heterocyclyl)C1-10 alkylene, (aryl)C3-8 cycloalkylene, (C3-8 cycloalkyl)arylene or (C1-10 alkylaryl)C1-10 alkylene,
• wherein “aryl” is a mono- or bicyclic partially or fully unsaturated carbocyclic ring system containing from 4 to 10 atoms, such as phenyl or naphthyl, or a partially or fully unsaturated mono- or bicyclic heterocyclic moiety having up to 10 atoms in the ring system and with up to 4 hetero-atoms in the said ring system each independently selected from N, O and S, said carbocyclic ring system and heterocyclic moiety being optionally substituted by one or more substituents each independently selected from halogen, NO2, NH2, CO2R9, phenyl, C1-6 alkyl(optionally substituted by one or more halogen), and C1-6 alkoxy(optionally substituted by one or more halogen), and “heterocyclyl” is a 3- to 8-membered mono or bicyclic saturated heterocyclic group having from 1 to 4 ring hetero-atoms each independently selected from N, O and S, optionally substituted by one or more substituents each independently selected from halogen, NO2, NH2, CO2R9, phenyl, C1-6 alkyl(optionally substituted by one or more halogen), and C1-6 alkoxy(optionally substituted by one or more halogen);
• R1 is C1-6 alkoxy;
• R2 is OH or O−M+;
• R9 is H or C1-6alkyl;
• and M+ is the cation of a metal such as sodium, lithium or potassium, or is a protonated amine moiety such as (mono-, di- or tri-C1-10 alkyl)ammonium, (mono-, di- or tri-C3-10 cycloalkyl)ammonium, (C1-10 alkyl)n1 (C3-10 cycloalkyl)n2ammonium, anilinium, benzylammonium, triethanolammonium, or (S)-α-methylbenzylammonium, where n1 and n2 are each independently selected from 1 or 2 with the proviso that the sum of n1 and n2 is not greater than 3;
• which comprises:
• formation of a compound of formula ( IV ) as defined above, by reaction of an aldehyde of formula RCHO, or a protected derivative thereof such as a hemiacetal or adduct thereof such as a bisulphite, wherein R is as defined above, with a phosphorus compound of formula (IX):
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• or a metal carboxylate salt thereof such as a sodium, lithium or potassium carboxylate salt thereof,
• wherein R1 is as defined above, and
• “P” is a phosphonate moiety of formula —P(O)(OR3)(OR4), wherein R3 and R4 are either each independently selected from H, C1-6 alkyl, benzyl and phenyl (optionally substituted by one or more C1-6 alkyl), or R3 and R4 taken together are C2-5 alkylene,
• or “P” is a phosphorane moiety of formula —(PR5R6R7)+X− wherein R5, R6 and R7 are each independently selected from C1-6 alkyl and phenyl, and X is bromine, chlorine or iodine, in the presence of a sodium, lithium or potassium C1-C6 alkoxide base, in an inert solvent, and at a temperature of from −80° C. to 20° C., said process being optionally followed by conversion of the product of formula (IV) where R2 is O−M+ wherein M+ is a metal such as Na, Li or K, to a compound of formula (IV) where R2 is OH by treatment with a proton source, which may optionally be converted to a compound of formula (IV) wherein R2 is O−M+ (where M+ is a protonated amine moiety as previously defined), by treatment with a corresponding amine, optionally followed by, if a compound of formula (V) or (VI) is desired, asymmetric reduction of a compound of formula (IV) to provide a compound of formula (V) or (VI).