Transfer hydrogenation process and catalyst
AssigneeAvecia Limited
InventorsAndrew John Blacker, Ben James Mellor
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Abstract
A catalytic transfer hydrogenation process is provided. The catalyst employed in the process is a metal cyclopentadienyl complex which is coordinated to defined bidentate ligands. Preferred metals include rhodium, ruthenium and iridium. Preferred bidentate ligands are diamines and aminoalcohols, particularly those comprising chiral centers. The hydrogen donor is advantageously a secondary alcohol or a mixture of triethylamine and formic acid. The process can be employed to transfer hydrogenate ketones and imines, which are preferably prochiral. Catalysts for use in such a process are also provided.
Claims15
A process for the transfer hydrogenation of a compound of formula (1) to produce a compound of formula (2);
- 6
- wherein:
- X represents CR3R4, NR5, (NR5R6)+Q−, O or S;
- R1, R2, R3, R4, R5 and R6each independently represents a hydrogen atom, an optionally substituted hydrocarbyl, a perhalogenated hydrocarbyl or an optionally substituted heterocyclyl group, one or more of R1 & R2, R1 & R3, R2 & R4, R3 & R4, R1 & R5, R2 & R6 and R5 & R6 optionally being linked in such a way as to form an optionally substituted ring(s);
- and
- Q− represents an anion;
- said process comprising reacting the compound of formula (1) with a hydrogen donor in the presence of a catalyst, characterised in that the catalyst has the general formula:
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- wherein:
- R7 represents an optionally substituted cyclopentadienyl group;
- A represents —NR8—, —NR9—, —NHR8 or —NR8R9 where R8 is H, C(O)R10, SO2R10, C(O)NR10R14, C(S)NR10R14, C(═NR14)SR15 or C(═NR14)OR15, R9 and R10 each independently represents an optionally substituted hydrocarbyl, perhalogenated hydrocarbyl or an optionally substituted heterocyclyl group, and R14 and R15 are each independently hydrogen or a group as defined for R10;
- B represents —O—, —OH, OR11, —S—, —SH, SR11, —NR11—, —NR12—, —NHR12 or —NR11R12 where R12 is H, C(O)R13, SO2R13, C(O)NR13R16, C(S)NR13R16, C(═NR16)SR17 or C(═NR16)OR17, R11 and R13 each independently represents an optionally substituted hydrocarbyl, perhalogenated hydrocarbyl or an optionally substituted heterocyclyl group, and R16 and R17 are each independently hydrogen or a group as defined for R13;
- E represents a linking group;
- M represents a metal capable of catalysing transfer hydrogenation;
- and
- Y represents an anionic group, a basic ligand or a vacant site;
- provided that when Y is not a vacant site that at least one of A or B carries a hydrogen atom.
A process according to any preceding claim, wherein the compound of formula (1) is prochiral and the catalyst is chiral, an enantiomerically and/or diastereomerically purified form of the catalyst being employed, whereby the compound of formula (1) is asymmetrically hydrogenated.
A process according to any one of the preceding claims, in which the process is carried out in presence of a base having a pKa of at least 8.0.
Dependencies are inferred from the claim text.