Ketones, enantioselective hydrogenation

Thomas C. Nugent of Jacobs University Bremen reported J. Org. Chem. 2008, 73, 1297) that added Yb(OAc)j improved the de in the reductive amination of ketones such as 22 with Raney Ni and 23. Yong-Gui Zhou of the Dalian Instimte of Chemical Physics found (Organic Lett. 2008,10, 2071) that cycUc sulfamidates such as 25 were easily prepared from the corresponding hydroxy ketone. Enantioselective hydrogenation of 25 gave... 

L = P(CH3)3 or CO, oxidatively add arene and alkane carbon—hydrogen bonds (181,182). Catalytic dehydrogenation of alkanes (183) and carbonylation of bensene (184) has also been observed. Iridium compounds have also been shown to catalyse hydrogenation (185) and isomerisation of unsaturated alkanes (186), hydrogen-transfer reactions, and enantioselective hydrogenation of ketones (187) and imines (188). 

Chitosan (Fig. 27) was deposited on sihca by precipitation. The palladium complex was shown to promote the enantioselective hydrogenation of ketones [80] with the results being highly dependent on the structure of the substrate. In the case of aromatic ketones, both yield and enantioselectiv-ity depend on the N/Pd molar ratio. Low palladium contents favored enan-tioselectivity but reduced the yield. Very high conversions were obtained with aliphatic ketones, although with modest enantioselectivities. More recently, the immobilized chitosan-Co complex was described as a catalyst for the enantioselective hydration of 1-octene [81]. Under optimal conditions, namely Co content 0.5 mmolg and 1-octene/Co molar ratio of 50, a 98% yield and 98% ee were obtained and the catalyst was reused five times without loss of activity or enantioselectivity. 

Since the initial work of Onto et al. (1) a considerable amount of work has been performed to improve our understanding of the enantioselective hydrogenation of activated ketones over cinchona-modified Pt/Al203 (2, 3). Moderate to low dispersed Pt on alumina catalysts have been described as the catalysts of choice and pre-reducing them in hydrogen at 300-400°C typically improves their performance (3, 4). Recent studies have questioned the need for moderate to low dispersed Pt, since colloidal catalysts with Pt crystal sizes of <2 nm have also been found to be effective (3). A key role is ascribed to the effects of the catalyst support structure and the presence of reducible residues on the catalytic surface. Support structures that avoid mass transfer limitations and the removal of reducible residues obviously improve the catalyst performance. This work shows that creating a catalyst on an open porous support without a large concentration of reducible residues on the Pt surface not only leads to enhanced activity and ee, but also reduces the need for the pretreatment step. One factor... 

Whereas general activities and selectivities for hydrogenations of ketones are similar to those of aldehydes, one big difference exists between the two. The hydrogenation of prochiral ketone carbonyls produces chiral carbons. Over symmetrical catalysts, racemic alcohols are formed however, over unsymmet-rical surfaces, enantioselectivity may occur. Enantioselective hydrogenations of ketones is an increasingly active research held and is covered in Chapter 3. Here we discuss that aspect of stereoselectivity associated with ring systems. 

In enantioselective hydrogenation of aromatic ketones, a catalytic system consisting of [RuC12-(BINAP)(dmf)ra], a chiral diamine such as (,S, S )-DPFN and KOH in a 1 1 2 ratio, affords the R alcohol with 97% ee and quantitative yield (Equation (lO)) 104... 

Excellent asymmetric hydrogenation of amino ketones has been applied for the syntheses of many chiral drugs. For example, the enantioselective hydrogenation of 3-aryloxy-2-oxo-l-propylamine derivatives can directly afford the l-amino-3-aryloxy-2-propanol derivatives as chiral / -adrenergic blocking agents. This has been successfully accomplished with a neutral MCCPM-Rh complex as the catalyst. With 0.01 mol.% of an (A,A)-MCCPM-Rh complex,... 

BPPM Scheme 1.17) was used as catalyst [60]. The enantioselective hydrogenation of functionalized ketones was also efficiently achieved by a series of rhodium(I) aminophosphine- and amidophosphine-phosphinite complexes [61]. 

Scheme 3.12 Enantioselective hydrogenation of a ketone by transfer from iso-propanol catalyzed by the hydride complex RuH( 6-arene)(NH2CHPhCHPhNTs) and the amido complex Ru(r 6-arene)(NHCHPhCHPhNTs) [94].

The concerted delivery of protons from OH and hydride from RuH found in these Shvo systems is related to the proposed mechanism of hydrogenation of ketones (Scheme 7.15) by a series of ruthenium systems that operate by metal-ligand bifunctional catalysis [86]. A series of Ru complexes reported by Noyori, Ohkuma and coworkers exhibit extraordinary reactivity in the enantioselective hydrogenation of ketones. These systems are described in detail in Chapters 20 and 31, and mechanistic issues of these hydrogenations by ruthenium complexes have been reviewed [87]. 

In this chapter, we review the growing family of phospholane-based chiral ligands, and specifically examine their applications in the field of enantioselective hydrogenation. In general, this ligand class has found its broadest applicability in the reduction of prochiral olefins and, to a significantly lesser extent, ketones and imines this is reflected in the composition of the chapter. Several analogous phosphacycle systems have also been included, where appropriate. 

Burk et al. showed the enantioselective hydrogenation of a broad range of N-acylhydrazones 146 to occur readily with [Et-DuPhos Rh(COD)]OTf [14]. The reaction was found to be extremely chemoselective, with little or no reduction of alkenes, alkynes, ketones, aldehydes, esters, nitriles, imines, carbon-halogen, or nitro groups occurring. Excellent enantioselectivities were achieved (88-97% ee) at reasonable rates (TOF up to 500 h ) under very mild conditions (4 bar H2, 20°C). The products from these reactions could be easily converted into chiral amines or a-amino acids by cleavage of the N-N bond with samarium diiodide. 

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