Asymmetric hydrogen transfer reduction

Leautey, M. Jubault, P. Pannecoucke, X. Quirion, J.-C. Synthesis and evaluation of a broad range of new chiral (aminoalkyl)phos-phane ligands for asymmetric hydrogen-transfer reduction of prochiral ketones. Eur. J. Org. Chem. 2003, 3761-3768. 

Asymmetric alkylation of benzaldehyde can be performed in a toluene/FC-72 biphasic system with Ti(0-iPr)4 and the fluorous BINOL ligand 7 (Figure 2) with reasonable yield and enantioselectivity [24]. The asymmetric hydrogen-transfer reduction of ketones works fairly... 

Merck reported the synthesis and isolation of (7 )-3,5-bistrifluoromethylphenylethanol (170) in high yields and enantiomeric excess by asymmetric hydrogen transfer. Reduction of 3,5-bistrifluoro-acetophenone (128, Ar = 3,5-(CF3)2C6H3, R = Me) with catalyst 169, prepared in situ from [RuCl2(p-cymene)]2 and (I S,2R)-cA-l-aminoindan-2-ol, produced the chiral alcohol 170 in 91-93% ee (Scheme 12.67).213... 

Finally, the use of S/P ligands derived from (i )-binaphthol has been considered by Gladiali et al. in the asymmetric rhodium-catalysed hydrogen-transfer reduction of acetophenone performed in the presence of i-PrOH as the hydrogen donor.It was noted that racemisation occurred when the reaction time increased and consequently the corresponding alcohol was obtained in only low enantioselectivities (< 5% ee) as shown in Scheme 9.21. Similar results were more recently reported by these authors by using iridium combined with the same ligands. ... 

In Figure 13.19 we have shown a route to L-699,392 published by Merck involving three steps based on homogeneous catalysts, viz. two Heck reactions and one asymmetric hydrogen transfer reaction, making first an alcohol and subsequently a sulphide [21], Stoichiometric reductions for the ketone function have been reported as well [22] and the Heck reaction on the left-hand side can be replaced by a classic condensation reaction. L-699,392 is used in the treatment of asthma and related diseases. 

Asymmetric hydrogen transfer shows promise for use at industrial scale because ruthenium complexes that contain chiral vicinal diamino 164 or amino alcohol 165 ligands allow the reductions of substrates such as aryl ketones and imines to be achieved under mild conditions.13 207... 

The progress in development and application of asymmetric hydrogen transfer has continued, albeit not at the same pace as reductions with molecular hydrogen.23 188-208 209 Several examples of asymmetric hydrogen transfer have been reported at large scale, such as the preparation of (A )-l-tetralol, (S)-4-fluorophenylethanol, and (A )-l-mcthylnaphthylaminc with CATHy based catalysts (166-168), whereas (f )-3,5-bistrifluoromethylphenylethanol has been made with m-aminoindanol-Ru(/>cymene) complex (169) (see also Chapter 17). 

Kadyrov R, Riermeier TH (2003) Highly enantioselective hydrogen-transfer reductive amination catalytic asymmetric synthesis of primary amines. Angew Chem Int Ed Engl 42 5472-5474 Kang Q, Zhao ZA, You SL (2007) Highly enantioselective Friedel-Crafts reaction of indoles with imines by a chiral phosphoric acid. J Am Chem Soc 129 1484-1485... 

One place to look for good alcohol racemization catalysts is in the pool of catalysts that are used for hydrogen transfer reduction of ketones. One class of complexes that are excellent catalysts for the asymmetric transfer hydrogenation comprises the ruthenium complexes of mono sulfonamides of chiral diamines developed by Noyori and coworkers [20, 21]. These catalysts have been used for the asymmetric transfer hydrogenation of ketones [20] and imines [21] (Fig. 9.9). 

Aqueous ammonia was found to increase the yield of the alcohol but not of the amine in the highly enantioselective hydrogen-transfer reductive amination of acetophenone, as recently described by Kadyrov et al. [18]. AU these reactions were performed in methanol/NHj with [((Kj-tol-binapjRuClJ as catalyst with a best asymmetric induction of 98% ee. 

Asymmetric transfer hydrogenation of ketones in the presence of soluble transition metal catalysts has been developed [8-10], enantioselectivities up to 99% ee being obtained using a ruthenium catalyst bearing mono-N-tosylated diphenyl-ethylenediamine as a ligand. Iridium complexes associated with fluorous chiral diimines 3a-3c or diamines 4a—4b have also been shown to be effective catalysts in hydrogen-transfer reduction of ketones [11,12]. 

Pan et al. give an extensive review of immobilized asymmetric catalysts according to reaction classes and the land of support [9]. Saluzzo and Lemaire reviewed the use of polymer-supported BINAP for hydrogenation and hydrogen-transfer reduction with diamines or amino alcohols, respectively [10]. The immobilization and recycling of chiral catalysts was the topic of a recent book [11]. Dendritic catalysts... 

The three major catalytic reduction procedures which have emerged are enantioselective hydride reduction, hydrogenation and hydrogenation transfer reduction (HTR) close to the hydrosilylation which represent only few examples in asymmetric polymer-supported catalyst. 

Simple reductions, hydrogenation, transfer hydrogenation, and asymmetric hydrogen transfer reactions are discussed in this section. 

Another method of enantioselective hydrogenation of 15 to 16 en route to montelukast was studied by Noyori et al. using Ru(II)-catalyzed asymmetric hydrogen transfer and formic acid as the source of hydrogen [26]. The catalytic complex 19 and the reductive process are presented in Scheme 11.6. 

Isopropanol can be used in the asymmetric hydrogen transfer reactions for two purposes first, as a cosolvent for improving the substrate solubility and second, as a cosubstrate for cofactor regeneration (substrate-coupled approach). For example, in the reduction of acetophenone by Candida viswanathii cells, addition of 10% (v/v) isopropanol led to a great increase of the substrate tolerance and a conversion of 90% compared to 9% in the control at a substrate concentration of 70 mM after lh[8]. 

As with hydrogenation, hydrogen transfer of imines is a poorly developed field.126-130 However, recent arene-Ru11 systems bearing chiral 1,2-diamine co-ligands have been found to be excellent catalysts for asymmetric reduction of imines with formic acid as donor.31,131-134... 

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