Noyori origin

Ru-diphosphine-diamine complexes developed originally by Noyori for the hydrogenation of aryl ketones are also suitable for the hydrogenation of imines. The best results are obtained for N-aryl imines where a Ru-duphos-diamine complex achieved up to 94% ee, albeit with relatively low activity and productivity (entry 3.7) (for data relating to cyclic imines, see Table 34.5). 

Imine 5a is also hydrogenated with good ee and TON using a Ru-dipho-sphine-diamine complex originally developed by Noyori (entry 4.7). An unusual... 

B uilding on the original proposal by Yates, the mechanism of this reaction is believed to involve the formation of copper carbenoids as intermediates, Scheme 1. Beyond the fact that copper, its ligands, the carbenoid fragment, and alkene are involved in the stereochemistry-determining event, as evidenced by Noyori et al. (2) and later by Moser (11, 12), little definitive mechanistic information has been acquired for this process. The basics of the mechanism will be discussed in this section. In subsequent sections detailing enantioselective variants, specific factors that have added to the understanding of this reaction will be addressed as will the models used to rationalize the observed stereochemistry. 

The catalyst system reported by Nozaki and Noyori was developed into a commercial process by Aratani and co-workers (14) at Sumitomo. The original salicyl-... 

Since the original report, about 12 other reagents have been reported to catalyze this reaction, but this reagent of Noyori (1) and that of Oguni (15,268) seem to be the most effective. In addition, both can effect chiral amplification, an increase of enan-tioselectivity over that of the catalyst. Noyori suggests that the alkyl transfer reaction involves a dinuclear Zn complex such as 3, whose structure has been established by... 

The most fully understood system in this class of reactions, however, is the DAIB-catalyzed addition of diethylzinc to aldehydes, due to the very detailed mechanistic studies performed by Noyori et al.32-37 They were able to determine the structure of several intermediates involved in the reaction and established the kinetic law. Part of the catalytic cycle is depicted in Scheme 13. The origin of the asymmetric amplification lies in the formation of dimers of DAIB-zinc alkoxides. The heterochiral dimer is quite stable in the concentration range of the experiment (2 x 10 1 to 5 x 10 1 M in toluene for DAIB), whereas the homodimers are prone to dissociation and react further with diethylzinc to give a di-zinc complex that is the active species in the catalytic cycle. They react with benzaldehyde and give rise to the asymmetric transfer of the ethyl group. The final product, as a zinc alkoxide, does not interfere with the reaction (and hence there is no autoinduction), since it... 

The Mukaiyama aldol reaction of carbonyl substrates with silyl enol ethers is the most widely accepted of Lewis acid-promoted reactions. Many Lewis acids for the reaction have been developed and used enantioselectively and diastereoselectively. In 1980, catalytic amounts of la were found by Noyori et al. to effect aldol-type condensation between acetals and a variety of silyl enol ethers with high stereoselectivity [2c,20]. Unfortunately, la has poor Lewis acidity for activation of aldehydes in Mukaiyama s original aldol reaction [21]. Hanaoka et al. showed the scope and limitation of 11-cat-alyzed Mukaiyama aldol reaction, by varying the alkyl groups on the silicon atom of silyl enol ethers [22]. Several efforts have been since been made to increase the reactivity and/or the Lewis acidity of silicon. One way to enhance the catalyst activity is to use an additional Lewis acid. 

One compound which did not work well in our system was our original model, a-phenylacrylic acid. A number of these aryl propionic acids are valuable as nonsteroidal antiarthritics. Here, as is typically the case, only one enantiomer is active and thus a process to prepare one isomer directly was needed. We tried hard to solve this problem, even using ruthenium-ligand systems, but without success. It took Professor Noyori with his BINAP-ruthenium complex to solve this problem [4]. This is just another example in the history of invention. The one who makes the first discovery seldom makes the second. On a grander stage, this may explain why there are so few double Nobel Laureates. 

Curve A in Scheme 6, represents an example of the asymmetric ampHfication obtained by Noyori et al. [12], which still remains the highest (-i-)-NLE known. The authors found that the reaction is first-order with respect to the catalyst and that the asymmetric ampHfication originates from the accumulation of unreactive meso-dimers of the zinc alcoholate of (-)-DAIB. The (-l-)-NLE maybe seen as the consequence of a reservoir, weakly coupled to the catalytic cycle and storing some racemic Hgand. 

By this route, Monsanto researchers were able to obtain both (S)-naproxen 22 and (S)-ibu-profen 57 by exploiting the Ru/BINAP-catalyzed hydrogenation originally developed by Noyori and his group. In the synthesis of both drugs the required acrylic acid was obtained by the relevant procedure outlined in Fig. 20. 

Troponoids (5, 222-223). The reaction of a,a -dibromo ketones with diiron nonacarbonyl to generate an oxyallyl-Fe(II) species originally suffered one limitation only secondary and tertiary dibromo ketones reacted satisfactorily. For example, reaction of a,a -dibromoacetone, BrCH2COCH2Br, fails. Noyori et al. have presented a solution to this limitation. The reaction is carried out with a polybromo ketone and the bromine atoms in the adduct are removed with Zn-Cu couple. The synthesis of 8-oxabicyclo[3.2.11oct-6-ene-3-one (1) is... 

To enable the attachment to a polymer, the original Gao-Noyori catalyst was tethered as shown in Eq. (2) and described in the literature [4]. As polymer backbone a polysiloxane polymer was chosen simply because the attachment of the monomer through its vinylic functionality by means of a hydrosilylation reaction could easily be achieved [Eq. (2)]. 

M. Yamakawa, I. Yamada, R. Noyori, CWn Attraction the origin of enantioselectivity in transfer hydrogenation of aromatic carbonyl compounds catalyzed by chiral 77 -arene-ruthenium(II) complexes, Angew. Chem. Int. Ed., 2001, 40, 2818-2821. 

Another original synthesis of tetrahydrolipstatin comes from Stephen Davies. [278] The two central building blocks are on the one hand an enantio-mericaUypure )S-hydroxyaldehyde, which is accessible by acylation of Meldrum s acid with dodecanoyl chloride, followed by an enantioselective hydrogenation of the -keto-ester along Noyori s method, and on the other hand an enantio-mericallypure acyl-iron complex [279], which is obtained by alkylation ofthe acetyl complex. [280] It is noteworthy that from the beginning the aldehyde component possesses the correct absolute configuration. The side-specific course ofthe anh-aldol addition is exclusively determined by the iron complex. First, the iron complex is deprotonated with butyl-lithium, then transmetallated with diethylaluminium chloride, and finally reacted with the aldehyde. The re-... 

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