Catalysis enantiomerically pure complexes

Recently, Akiyama et al. reported an enantiocontrolled [3+2] cycloaddition of chirally modified Fischer alkenylcarbene complexes 180 with aldimines 181 under Lewis-acid catalysis (Sn(OTf)2) to afford enantiomerically pure 1,2,5-trisubstituted 3-alkoxypyrrolines 182 (Scheme 40) [121]. The mode of formation of these products 182 was proposed to be a [4+2] cycloaddition, with the complexes 180 acting as a 1-metalla- 1,3-diene with subsequent reductive elimination. Upon hydrolysis under acidic conditions, the enol ethers give the enantiomerically pure 3-pyrrolidinones 183 (Table 9). 

The production of enantiomerically pure products is of great importance in chemical industry. The most desirable way to obtain these products is by chiral catalysis. Homogeneous complexes can often be used as chiral catalysts however, because of their difficult regenerability, the development of heterogeneous chiral catalysts by immobilization of these complexes is difficult but highly desired. 

Enantiomerically pure copper and rhodium complexes enable enantioselective catalysis of carbene-mediated reactions. Such reactions will be discussed more thoroughly in Section 4.2. Experimental Procedure 4.1.1 describes the preparation of an enantiomerically pure rhodium(II) complex which has proven efficient for catalysis of different types of carbene complex-mediated C-C-bond-forming reactions with high asymmetric induction. 

Major breakthroughs can also be expected in asymmetric catalysis, because enantiomerically pure carbene complexes, with the source of asymmetry close to the metal center, will be accessible. 

Catalytic Michael additions of a-nitroesters 38 catalyzed by a BINOL (2,2 -dihydroxy-l,r-bi-naphthyl) complex were found to yield the addition products 39 as precursors for a-alkylated amino acids in good yields and with respectable enantioselectivities (8-80%) as shown in Scheme 9 [45]. Asymmetric PTC (phase transfer catalysis) mediated by TADDOL (40) as a chiral catalyst has been used to synthesize enantiomeri-cally enriched a-alkylated amino acids 41 (up to 82 % ee) [46], A similar strategy has been used to access a-amino acids in a stereoselective fashion [47], Using azlactones 42 as nucleophiles in the palladium catalyzed stereoselective allyla-tion addition, compounds 43 were obtained in high yields and almost enantiomerically pure (Scheme 9) [48]. The azlactones 43 can then be converted into the a-alkylated amino acids as shown in Scheme 4. 

In recent years the synthesis of chiral and achiral tripodal phosphines and their application in homogeneous catalysis has been studied in more detail [2]. Enantiomerically pure tripodal ligands were synthesized from the corresponding trichloro compounds and chiral, cyclic lithio-phosphanes, e.g. 17, (Scheme 6) [21,22], Using a rhodium(I) complex of ligand 18, an enantiomeric excess of 89 % was obtained in the asymmetric hydrogenation reaction of methyl acetami-docinnamate (19). 

In asymmetric catalysis a prochiral substrate binds to an enantiomerically pure catalyst to generate a pair of diastereomeric intermediates. The energy difference and the rate of exchange between them controls the optical yield (e.e.) of the final product. In the case of a-aminocinnamic acid derivatives, the acyl auxiliary on the nitrogen is required to enable the substrate to form a chelate complex with rhodium.12 The mechanism of this reaction is shown in Fig. 22-3 the ligand in this case is DIPAMP (22-XV). 

Another interesting approach to an NHC ligand with a chiral, bridging wingtip group was introduced by Perry et al. [45] and uses enantiomerically pure 1,2-diamino-cyclohexane as the scaffold. Reaction with chloroacetic acid chloride and subsequently with DIPP-imidazole yields the imidazolium salt that can be reacted with silver(I) oxide [46] to the respective silver(I) NHC complex. Subsequent carbene transfer to palladium(II) renders the chiral palladium(II) carbene transfer that can be used in catalysis (see Figure 5.9). 

The configurationally robust [CpRe(NO)(PPh3)X] complexes, easily obtained in an enantiomerically pure form (except for X = OR, NR2), were used as building blocks for new chiral hgands with spectator chiral-at-metal fragments. Both chiral diphosphine (117) and diamine ligands (118) have been prepared and successfully tested in catalysis. ... 

Enantiomerically pure bis-Gp derivatives with chiral Gp ligands have been used with success in the catalytic enantioselective opening of meso-epoxides via electron transfer (see Section 4.05.8). The structural features are of relevance for the understanding of activity and selectivity of these complexes in diastereoselective reactions and for the design of novel catalysts. A comparison of the structure of three of these bis-Gp Ti derivatives (Scheme 481) in the solid state and in solution determined by X-ray crystallography and NMR methods indicated that the structures in the crystal and in solution are the same, and that applications of these complexes in catalysis can de discussed on the basis of crystallographic data.1114 In a similar study, the 1-methylcyclohexyl-Cp, 1-butyl-1-methylbutyl-Cp, and cyclohexyl-Cp titanocene dichlorides (Scheme 481) have been prepared and their molecular structures compared. The use of these three compounds in radical addition reactions has been studied.1115... 

Enantioselective catalysis with nucleophiles that attack the metal of the intermediate rr-allylpal-ladium complexes prior to allylic C-C bond formation has met with only limited success so far30-31. Phenylation of the allyl acetates 1 and 4 via re-allyl complexes with a me,sY -7r-allyl ligand using phenylzinc chloride and enantiomerically pure monophosphines 231 or 53a yield 3 and 6 of low enantiomeric excess, respectively. 

The effect that homogeneous transition-metal catalysis has had on stereoselective synthesis is especially impressive. Using chiral ligands, it is possible to control hydrogenation of double bonds so that new chirality centers have a particular configuration. The drug L-dopa, used to treat Parkinsonism, is prepared in multiton quantities by enantio-selective hydrogenation catalyzed by an enantiomerically pure chiral rhodium complex. 

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