Asymmetric ketone-catalyzed

Bis(pyrazolyl)borate copper complex 47 has been employed as a catalyst in the homogeneous and heterogeneous styrene epoxidation reactions <00JCS(CC)1653>. Pyrazole palladacycles 48 have proven to be stable and efficient catalysts for Heck vinylations of aryl iodides <00JCS(CC)2053>. An asymmetric borane reduction of ketones catalyzed by N-hydroxyalkyl-/-menthopyrazoles has been reported <00JHC983>. 

The first example of asymmetric rhodium-catalyzed 1,4-addition of organoboron reagents to enones was described in 1998 by Hayashi and Miyaura. Significant progress has been made in the past few years. This asymmetric addition reaction can be carried out in aqueous solvent for a broad range of substrates, such as a,/ -unsaturated ketones, esters, amides, phosphonates, nitroalkenes. The enantioselectivity is always very high (in most cases over 90% ee). This asymmetric transformation provides the best method for the enantioselective introduction of aryl and alkenyl groups to the / -position of these electron-deficient olefins. 

Fig. 32.49 Hydrogenation of ketones catalyzed by racemic BINAP-Ru complexes and (S,S)-DPEN asymmetric activation.

Chiral Ketone-Catalyzed Asymmetric Oxidation of Unfunctionalized Olefins... 

TABLE 6-8. Asymmetric Hydrogenation of Simple Ketones Catalyzed by Rh-PennPhos... 

In summary, many attempts have been made at achieving enantioselective reduction of ketones. Modified lithium aluminum hydride as well as the ox-azaborolidine approach have proved to be very successful. Asymmetric hydrogenation catalyzed by a chiral ligand-coordinated transition metal complex also gives good results. Figure 6-7 lists some of the most useful chiral compounds relevant to the enantioselective reduction of prochiral ketones, and interested readers may find the corresponding applications in a number of review articles.77,96,97... 

Scheme 18. Ru-catalyzed asymmetric ketone reduction used by Schreiber in the total syntheses of immunosuppressive agents FK506 and rapamycin (1990, 1993).

Table 4.8 Asymmetric transfer hydrogenation of aromatic ketones, catalyzed by [lrH(CO)(PPh3)3]/83 under base-free conditions.

Table 5.4 Asymmetric transfer hydrogenation of prochiral ketones catalyzed by 12 giving (S)-alcohols. ...

Table 5.5 Asymmetric transfer hydrogenation of aromatic ketones catalyzed by preformed chiral catalysts and KO Bu system in 2-propanol. ...

Figure 1.13. Asymmetric hydrogenation of functionalized ketones catalyzed by BINAP-Ru complexes.

Figure 1.17. Asymmetric hydrogenation of simple ketones catalyzed by BINAP/1,2-diamine-Ru complex.

Figure 1.21. Asymmetric hydrogenation of rerr-alkyl ketones catalyzed by BINAP/ PICA-Ru complex.

Figure 1.23. Asymmetric transfer hydrogenation of ketones catalyzed by chiral arene-Ru...

Figure 1.26. Asymmetric Meerwein-Ponndorf-Verley-type reduction of ketones catalyzed by a Sm complex.

The first asymmetric enamine-catalyzed Mannich reactions were described by List in 2000 [208]. Paralleling the development of the enamine-catalyzed aldol reactions, the first asymmetric Mannich reactions were catalyzed by proline, and a range of cyclic and acyclic aliphatic ketones were used as donors (Schemes 24 and 25). In contrast to the aldol reaction, however, most Mannich reactions are syn selective. This is presumably due to the larger size of the imine acceptor, forcing the imine and the enamine to approach each other in a different manner than is possible with aldehyde acceptors (Scheme 23). 

Scheme 28 Asymmetric enamine-catalyzed Michael additions with ketone donors...

Tab. 3.1 Asymmetric conjugate addition of organoboronic acids to a,j8-unsaturated ketones catalyzed by RhjacacjjCjHJj/jSj-BINAP [6],...

Oi and Inoue recently described the asymmetric rhodium-catalyzed addition of organosilanes [35]. The addition of aryl- and alkenyltriaUcoxysilanes to u,y9-unsaturated ketones takes place, in the presence of 4 mol% of a cationic rhodium catalyst generated from [Rh(COD)(MeCN)2]BF4 and (S)-B1NAP in dioxane/H20 (10 1) at 90°C, to give the corresponding conjugate addition products (Eq. 3). The enantioselectivity is comparable to that observed with the boronic acids, as the same stereochemical pathway is applicable to these reactions (compare Scheme 3.7). 

Figure 6.23 Proposed transition states of the asymmetric 72-catalyzed cyanosilylation of ketones describe two alternative mechanistic pathways for cooperative catalysis Addition via thiourea-bound ketone (TS 1, preferred) and addition via thiourea-bound cyanide (TS 2).

A novel and more general method to enable biocatalyzed conversion and synthesis of hydrophobic compounds involves the use of gel-stabilized aqueous-organic two-phase systems [8], Features, advantages, disadvantages, and perspectives of this method in asymmetric synthesis will be discussed in this chapter, illustrated for the stereoselective benzoin condensation and the reduction of ketones catalyzed by thiamine pyrophosphate (TPP)-dependent lyases and NAD(P)H-dependent alcohol dehydrogenases, respectively. 

Chiral ketone-catalyzed asymmetric epoxidation has received intensive interest since the first reported by Curci et al. in 1984. The reaction is performed with oxone (potassium peroxomonosulfate) as the primary oxidant which generates the chiral dioxirane catalytic species in situ, which in turn, transfers the oxygen... 

Lauret, C. and Roberts, S.M. Asymmetric Epoxidation of a, -Unsaturated Ketones Catalyzed by Poly(amino acids). Aldrichimica Acta 2002, 35(2), 47-51. 

Table 3.5 Asymmetric hydrogenation of ketones catalyzed by mthenium(II) complex selected results.

SCHEME 19. Asymmetric borane reduction of ketones catalyzed by an oxazaphos-pholidine-borane complex. 

Significant progress has been made on the asymmetric Pd-catalyzed aliylic alkylation of prochiral enolates, with a number of ligands now available that provide products with high ee. Trost was the first to demonstrate that high enantiomeric excesses were capable with ketoester substrates [29] now asymmetric aliylic alkylation of ketoesters and simple ketone substrates has been achieved in several more cases. Table 4 summarizes the ligands, substrates, and ee for recent examples. 

Fu reported the enantioselective addition of diphenylzinc to ketones catalyzed by chiral amino alcohol 6, and observed a slight asymmetric amplification [13]. Bolm also reported asymmetric amplification in enantioselective alkylations using diethylzinc promoted by a chiral 2-pyridyl alkanol 7 and (1-hydroxy sulfoximine 8 (Scheme 9.6) [14,15]. 

A brief review of procedures for asymmetric metal-catalyzed Baeyer-Villiger oxidations is given with asymmetric copper-catalyzed synthesis of 3-phenyl-2-oxepanone as representative of the enantioselective synthesis of lactones from cyclic ketones . 

S. Cheng, H. Wan, K. Tsai, andT. Ikariya, Asymmetric transfer hydrogenation of prochiral ketones catalyzed by chiral ruthenium complexes with aminophos-phine ligands, J. Mol. Cat. A Chemical 1999, 147, 105-111. 

The asymmetric aldol reaction is one of the most important topics in modern catalytic synthesis [54]. The products, namely />-hydroxy carbonyl compounds, have a broad range of applications and play a key role in the production of pharmaceuticals [55], Since the discovery of the catalytic asymmetric aldol reaction with enolsi-lanes by Mukaiyama et al. [56], steady improvements of the metal-catalyzed asymmetric aldol reaction have been made by many groups [57]. For this type of aldol reaction a series of chiral metal catalysts which act as Lewis acids activating the aldol acceptor have been shown to be quite efficient. It was recently shown by the Shibasaki group that the asymmetric metal-catalyzed aldol reaction can be also performed with unmodified ketones [57a], During the last few years, several new concepts have been developed which are based on use of organocatalysts [58], Enolates and unmodified ketones can be used as aldol donors. 

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