Enantioselective hydrogenation enamines

Table 6.7 Enantioselective hydrogenation of enamines cata-lyzed by [(R,R,R)-(EBTHI)TiX2] [112],a)...

Early transition-metal complexes have been some of the first well-defined catalyst precursors used in the homogeneous hydrogenation of alkenes. Of the various systems developed, the biscyclopentadienyl Group IV metal complexes are probably the most effective, especially those based on Ti. The most recent development in this field has shown that enantiomerically pure ansa zirconene and titanocene derivatives are highly effective enantioselective hydrogenation catalysts for alkenes, imines, and enamines (up to 99% ee in all cases), whilst in some cases TON of up to 1000 have been achieved. 

Table 34.4 Selected results for the enantioselective hydrogenation of N-alkyl imines and enamines (for structures, see Fig. 34.7) Catalytic system, reaction conditions, enantioselectivity, productivity and activity.

Researchers at Merck Co. [35] who, together with scientists from Solvias, had developed the enantioselective hydrogenation of unprotected enamine amides and esters [36], reported a more recent example of product inhibition. The product amine amide or ester was found to be an inhibitor of the catalyst, and indeed instances of catalyst poisoning by amines have been reported several times (see later). The authors also found an excellent solution to this problem the addition of BOC-anhydride to the hydrogenation reaction neatly reacts away all the amine to form the BOC-protected amine, whereas the enamine was left unreacted (Scheme 44.4). This addition resulted in a remarkable rate enhancement [35]. 

Cyclic a-amino acids with an enamine pattern can be obtained upon enantioselective hydrogenation followed by a hydroformylation/cyclization sequence in a single-pot version Rh(I)-DuPHOS acts as a catalyst for both steps, the enantioselective hydrogenation of prochiral dienamides and the hydroformylation of the resulting homoallylic amines (Scheme 13) [52,53]. 

Scheme 13 Enantioselective Hydrogenation/hydroformylation/enamine formation...

General Procedure for the Enantioselective Hydrogenation/Hydroformylation/Enamine Formation. Synthesis of Cyclic Enamine Amino Acids. Prochiral dieneamide (1 eq) and... 

Olefinic double-bond isomerization is probably one of the most commonly observed and well-studied reactions that uses transition metals as catalysts [1]. However, prior to our first achievement of asymmetric isomerization of allylamine by optically active Co(I) complex catalysts [2], there were only a few examples of catalytic asymmetric isomerization, and these were characterized by very low asymmetric induction (<4% ee) [3], In 1978 we reported that an enantioselective hydrogen migration of a prochiral allylamine such as AVV-diethylgerany-lamine, (1) or N V-diethylnerylamine (2) gave optically active citronellal ( )-enamine 3 with about 32% ee utilizing Co(I)-DIOP [DIOP = 2,3-0-isopropylidene-2,3-dihydroxy-l,4-bis(diphenylphosphino)butane] complexes as the catalyst (eq 3.1). 

An enantioselective hydrogen migration of prochiral allylamines 188 and 190 to chiral enamines 189 was realized by use of chiral cobalt catalysts300 (equation 18). 

The formation of stereogenic C-N bonds by hydrogenation of the enamine structure is not only limited to amino acids. Likewise, chiral 1,2-aminoalcohols or 1,2-diamines can be produced by the enantioselective hydrogenation of dehydro-p-amino alcohols (or their esters) and of dehydro-a-amino aldoximes, respectively (eq 6 and eq 7, Thble 2). Esters and aldoximes thus obtained can be converted into the corresponding alcohols or diamines by standard methods. By this means, simple amines with one aryl group attached to the double bond can also be hydrogenated with high enantioselectivity. ... 

Enantioselective Hydrogenation of Enamines with Monodentate Phosphorus Ligands... 

S Enantioselective Hydrogenation of Enamines tvith Monodentate Phosphorus Ligands rR u -R... 

Only a few chiral catalysts based on metals other than rhodium and ruthenium have been reported. The titanocene complexes used by Buchwald et al. [109] for the highly enantioselective hydrogenation of enamines have aheady been mentioned in Section 3.4 (cf. Fig. 32). Cobalt semicorrin complexes have proven to be efficient catalysts for the enantioselective reduction of a,P-unsaturated carboxylic esters and amides using sodium borohydride as the reducing agent [ 156, 157]. Other chiral cobalt complexes have also been studied but with less success... 

---