Noyori catalytic asymmetric hydrogenation ketones

The role of base in the Noyori s asymmetric hydrogenation of ketone catalysed by trans-RutdiphosphinejCMdiamine) has been evaluated. Several catalytic intermedi- ates have been characterized and a mechanism (Scheme 17) has been presented.338... 

The discovery by the recent Nobel-laureate, Ryoji Noyori, of asymmetric hydrogenation of simple ketones to alcohols catalyzed by raras-RuCl2[(S)-binap][(S,S)-dpen] (binap = [l,l -binaphthalene-2,2/-diyl-bis(diphenylphosphane)] dpen = diphenylethylenediamine) is remarkable in several respects (91). The reaction is quantitative within hours, gives enantiomeric excesses (ee) up to 99%, shows high chemoselecti-vity for carbonyl over olefin reduction, and the substrate-to-catalyst ratio is >100,000. Moreover, the non-classical metal-ligand bifunctional catalytic cycle is mechanistically novel and involves heterolytic... 

Homogeneous catalytic asymmetric hydrogenation has become one of the most efficient methods for the synthesis of chiral alcohols, amines, a and (3-amino acids, and many other important chiral intermediates. Specifically, catalytic asymmetric hydrogenation methods developed by Professor Ryoji Noyori are highly selective and efficient processes for the preparation of a wide variety of chiral alcohols and chiral a-amino acids.3 The transformation utilizes molecular hydrogen, BINAP (2,2 -bis(diphenylphosphino)-l,l -binaphthyl) ligand and ruthenium(II) or rhodium(I) transition metal to reduce prochiral ketones 1 or olefins 2 to their corresponding alcohols 3 or alkanes 4, respectively.4... 

More recently Noyori developed asymmetric hydrogenation of simple ketones with BlNAP/diamine-ruthenium complexes.In this system the catalytic process contrasted with the conventional mechanism of asymmetric hydrogenation of unsaturated bonds which requires metal-substrate 7t-complexation. In fact with BlNAP/diamine-ruthenium neither the ketone substrate nor the alcohol product interacted with the metallic centre during the catalytic cycle. The enantiofaces of the prochiral ketones were differentiated on the molecular surface of the coordinatively saturated RuH intermediate. 

The mechanism of the Meerwein-Pondorf-Verley reaction is by coordination of a Lewis acid to isopropanol and the substrate ketone, followed by intermolecular hydride transfer, by beta elimination [41]. Initially, the mechanism of catalytic asymmetric transfer hydrogenation was thought to follow a similar course. Indeed, Backvall et al. have proposed this with the Shvo catalyst [42], though Casey et al. found evidence for a non-metal-activation of the carbonyl (i.e., concerted proton and hydride transfer [43]). This follows a similar mechanism to that proposed by Noyori [44] and Andersson [45], for the ruthenium arene-based catalysts. By the use of deuterium-labeling studies, Backvall has shown that different catalysts seem to be involved in different reaction mechanisms [46]. 

KRs based on the oxidation of a chiral secondary alcohol to a prochiral ketone has been of considerable interest as the later can be usually recycled into the racemic starting material by simple hydride reduction [2d, 55]. The first broadly applicable method for this purpose was reported by Noyori et al. [56], under catalytic hydride transfer conditions similar to those employed for the asymmetric hydrogenation of ketones. For example, excellent results (s>50) have been reported for the KR of benzyhc alcohols by using a chiral diamine-ruthenium complex in the... 

Scheme 1.45 A revised catalytic cycle for the asymmetric hydrogenation of aromatic ketones in propan-2-ol by Noyori s (pre)catalyst 1 based on a computed MEp253 follows a H /H" " outer sphere hydrogenation mechanism (see text). KO-f-C4H9 free conditions X = Y = H. Under high KO-f-C4H9 concentration X = Y = K and/or H. Formation of the major enantiomeric product is shown. (Adapted from Dub, P. A. et al., /. Am. Chem. Soc., 136, 3505-3521. Copyright 2014 American Chemical Society.)...

Ikariya and Noyori et al. also reported the synthesis of new chiral Cp Rh and Cp Ir complexes (13 and 14) bearing chiral diamine ligands [(R,R)-TsCYDN and (R,R)-TsDPEN] (Scheme 5.10) these are isoelectronic with the chiral Ru complex mentioned above, and may be used as effective catalysts in the asymmetric transfer hydrogenation of aromatic ketones [42], The Cp Ir hydride complex [Cp IrH(R,R)-Tscydn] (14c) and 5-coordinated amide complex (14d), both of which would have an important role as catalytic intermediates, were also successfully prepared. 

Transfer hydrogenation is particularly good for the reduction of ketones and imines that are somewhat more difficult to reduce with Hj than are C—C bonds. BSckvall and co-workers have shown how RuCl fPPhj) is effective at 80°C with added base as catalyst promoter. The role of die base is no doubt to form the isopropoxide ion. which presumably coordinates to Ru and by elimination forms a hydride and acetone. Noyori and co-workers have has a remarkable asymmetric catalytic hydrogen transfer that goes without direct coordination of the C=0 bond to the metal. Instead, the metal donates a hydride to the C=0 carbon while the adjacent RU-NH2R group donates a proton to the C=0 oxygen. 

The principles of directed and asynunetric reactions were first developed for hydrogenation, as discussed in Section 9.2. Asymmetric hydrosilation of ketones can now be carried out catalytically with rhodium complexes of diop (9.22). The widely used chiral ligand Et-duPHOS, made by Burk at du Pont, allows chiral amination of ketones via Eq. 14.50. Note how the use of the hydrazone generates an amide carbonyl to act as a ligand, as is known to favor high e.e. (see Section 9.2). Noyori s powerful BINAP ligand has been applied to a very large number of asymmetric reactions. 

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