Dynamic kinetic resolution ketone ketones

Scheme 9.11 Successful dynamic kinetic resolution of ketone rac-13.

Fig. 4.116 Dynamic kinetic resolution of ketones using CHMO-containing recombinant E. coli.

Scheme 2.24 Dynamic kinetic resolution of ketone IPS catalyzed by CHMO-containing...

The ability to catalyze the asymmetric hydrogenation of aliphatic ketones provides an opportunity to extend the scope of these reactions to the dynamic kinetic resolution of ketones that contain a stereocenter in the enolizable a-position. The catalysts containing bisphosphine and diamine ligands are activated by base, and the base used to activate the metal catalyst can also catalyze the racemization of the ketone. An example of such a process is shown in Equation 15.76. ... 

Dynamic kinetic resolution of racemic ketones proceeds through asymmetric reduction when the substrate does racemize and the product does not under the applied experimental conditions. Dynamic kinetic resolution of a-alkyl P-keto ester has been performed through enzymatic reduction. One isomer, out of the four possible products for the unselective reduction (Figure 8.38), can be selectively synthesized using biocatalyst, and by changing the biocatalyst or conditions, all of the isomers can be selectively synthesized [29]. 

Another example of dynamic kinetic resolution is the reduction of a sulfur-substituted ketone. Thus, yeast reduction of (R/S)-2-(4-methoxyphenyl)-l, 5-benzothiazepin-3,4(2H, 5H)-dione gave only (2S, 3S)-alcohol as a product out of four possible isomers as shown in Figure 8.39c [29kj. Only (S)-ketone was recognized by the enzyme as a substrate and reduction of the ketone proceeded... 

The dynamic kinetic resolution (DKR) of a-sulfur-substituted ketones such as 31 and 33 was investigated. When the MOM protected mercaptol ketone 31 was treated with the BINOL-LiAlH4 complex, a moderate diastereoselectivity of 5 1 favoring the desired anti isomer was observed. The major diastereomer had 70%... 

Dynamic kinetic resolution is possible for a-alkyl or a-alkoxy cyclic ketones in the presence of KOH, which causes mutation of the stereogenic center syn-alco-hols were obtained selectively with high enantioselectivity using ruthenium-3,5-xyl-binap. Dynamic kinetic resolution of 2-arylcycloalkanones also proceeded with extremely high syn-selectivity and with high enantioselectivity using ruthenium-binap-diamine as catalyst (Table 21.23) [12, 139, 140]. 

The hydrogenation of a-amino ketones was also a key step for the synthesis of three more pharma actives (Fig. 37.25). Roche [95] divulged a pilot process involving the hydrogenation/dynamic kinetic resolution of a cyclic a-amino ketone using an optimized MeO-biphep ligand. The Ru-catalyzed reaction was carried out on a 9-kg scale with excellent enantio- and diastereoselectivities, and very... 

Enantioselective and Diastereoselective Enzyme-catalyzed Dynamic Kinetic Resolution of an Unsaturated Ketone... 

Dynamic Kinetic Resolutions (DKR) are documented in the chemical literature [17, 18], and it was envisaged that such a system was, in theory, possible with the aryl-substituted morpholinols 2. The morpholinol ring system may exist, in part, as the open chain hydroxyl ketone (see Scheme 10.1), and it has been reported [19,... 

As described above, the catalyst comprising RuC12 complex with a strong base is effective for the asymmetric hydrogenation through dynamic kinetic resolution. However, it is not suitable for static kinetic resolution of racemic a-substi-tuted ketones because of the basic conditions. The newly devised frans-RuHfri1-BH4)[(R)-XylBINAP][(S,S)-DPEN] without any additional base allows one to... 

A tandem 1,4-addition-Meerwein-Ponndorf-Verley (MPV) reduction allows the reduction of a, /i-unsaturated ketones with excellent ee and in good yield using a camphor-based thiol as reductant.274 The 1,4-addition is reversible and the high ee stems from the subsequent 1,7-hydride shift the overall process is thus one of dynamic kinetic resolution. A crossover experiment demonstrated that the shift is intramolecular. Subsequent reductive desulfurization yielded fiilly saturated compounds in an impressive overall asymmetric reductive technique with apparently wide general applicability. 

A dynamic kinetic resolution has been employed to achieve a catalytic asymmetric reductive amination of aldehydes.332 Reductive amination of ketones and aldehydes by sodium triacetoxyborohydride has been reviewed, highlighting its advantage over other reagents.333... 

It was mentioned at the beginning of this chapter that alkaloids were among the first catalysts to be used for asymmetric hydrocyanation of aldehydes. More recent work by Tian and Deng has shown that the pseudo-enantiomeric alkaloid derivatives 5/6 and 7/8 catalyze the asymmetric addition of ethyl cyanoformate to aliphatic ketones (Scheme 6.6) [50]. It is believed that the catalytic cycle is initiated by the alkaloid tertiary amine reacting with ethyl cyanoformate to form a chiral cyanide/acylammonium ion pair, followed by addition of cyanide to the ketone and acylation of the resulting cyanoalkoxide. Potentially, the latter reaction step occurs with dynamic kinetic resolution of the cyano alkoxide intermediate... 

Figure 5.15 a Generic scheme of dynamic kinetic resolution of alcohols b example of the resolution of a racemic 8-aminotetrahydroquinoline, where the racemization iscatalyzed by the organic ketone 8-aza-l-tetralone (the racemization cycle is highlighted in gray). 

DYNAMIC KINETIC RESOLUTION OF RACEMIC KETONES THROUGH ASYMMETRIC REDUCTION... 

Figure 28. Dynamic kinetic resolutions by reduction of ketones and aldehydes...

The remarkable activity of copper catalysts in carbonyl hydrogenation and alcohol dehydrogenation prompts their use also for the racemization of chiral secondary alcohols. Actually, since the first report on chemoenzymatic dynamic kinetic resolution [68], racemization of alcohols via the corresponding ketone has attracted considerably attention, owing to its role as backbone in this resolution [69, 70]. 

The first example of a dynamic kinetic resolution involving a CHMO-cata-lyzed BV oxidation was recently reported (Fig. 4.116) [321]. The reaction was performed with whole cells of CHMO-containing recombinant E. coli sp. at pH 9. Under these conditions the ketone substrate underwent facile racemization,... 

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