Dynamic kinetic asymmetric hydrogenation

In 2015, Zhao and co-workers described the first dynamic kinetic asymmetric amination of alcohols via borrowing hydrogen methodology under the cooperative catalysis of iridium complex 25 and chiral phosphoric acid 27 (Schemes 31, 32) [179]. The authors proposed that, initially, the two stereocenters in the alcohols were both racemized to ketone by the first oxidation, followed by tautomerization of the iminium intermediates 28 and 30 through enamine intermediate 29. Then, the... 

Kejrwords Dynamic kinetic asymmetric transformation (DYKAT) Dynamic kinetic resolution (DKR) Hydrogenation Imine reduction Ketone reduction Mechanism of carbonyl reduction Mechanism of imine reduction Mechanism of dUiydrogen activation Ruthenium catalysis Shvo s catalyst Transfer hydrogenation... 

The Shvo catalyst 1 was successfully used in the transfer hydrogenation of 1,3-diones to the corresponding 1,3-diols with isopropanol as the hydrogen donor (2) [36, 37], This reaction is synthetically useful for the reduction of cyclic diones since reduction of these diketones by LiAlIli preferentially gives the aUyUc alcohol [36]. Also piperidine-3,5-diones were efficiently reduced to the corresptMiding diols by isopropanol using 1 as catalyst [37], and these diols were subsequently used in dynamic kinetic asymmetric transformatimis (DYKATs) to provide stereodefined 3,5-disubstituted piperidines [36, 37],... 

Dynamic Resolution of Chirally Labile Racemic Compounds. In ordinary kinetic resolution processes, however, the maximum yield of one enantiomer is 50%, and the ee value is affected by the extent of conversion. On the other hand, racemic compounds with a chirally labile stereogenic center may, under certain conditions, be converted to one major stereoisomer, for which the chemical yield may be 100% and the ee independent of conversion. As shown in Scheme 62, asymmetric hydrogenation of 2-substituted 3-oxo carboxylic esters provides the opportunity to produce one stereoisomer among four possible isomers in a diastereoselective and enantioselective manner. To accomplish this ideal second-order stereoselective synthesis, three conditions must be satisfied (1) racemization of the ketonic substrates must be sufficiently fast with respect to hydrogenation, (2) stereochemical control by chiral metal catalysts must be efficient, and (3) the C(2) stereogenic center must clearly differentiate between the syn and anti transition states. Systematic study has revealed that the efficiency of the dynamic kinetic resolution in the BINAP-Ru(H)-catalyzed hydrogenation is markedly influenced by the structures of the substrates and the reaction conditions, including choice of solvents. 

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... 

For examples of dynamic kinetic resolution, see Ohkuma T, Noyori R (1999) Hydrogenation of carbonyl groups. In Jacobsen EN, Pfaltz A, Yamamoto H (eds) Comprehensive asymmetric catalysis. Springer, Berlin Heidelberg New York, chap 6.1 Huerta FF.Minidis ABE, Backvall J-E (2001) Chem Soc Rev 30 321-331... 

Ruthenium catalysts that contain Cl-MeO-BIPHEMP have been used in the asymmetric hydrogenation of P-keto esters (99% ee)126 and the dynamic kinetic resolution of substituted P-keto esters (Scheme 12.33).121 The asymmetric hydrogenation of methyl 3,3-dimethyl-2-oxobutyrate to the corresponding a-hydroxy ester has been reported with ruthenium catalyst, RuBr2[(-)-Cl-MeO-BIPHEMP] 2 (Scheme 12.34).121... 

Notz W, Tanaka F, Watanabe S, Chaudari NS, Turner JM, Thayumanavan R, Barbas CF 3rd (2003) The direct organocatalytic asymmetric mannich reaction unmodified aldehydes as nucleophiles. J Org Chem 68 9624-9634 Noyori R (2002) Asymmetric catalysis science and opportunities (Nobel lecture). Angew Chem Int Ed Engl 41 2008-2022 Noyori R, Tokunaga M, Kitamura M (1995) Stereoselective organic synthesis via dynamic kinetic resolution. Bull Chem Soc Jpn 68 36-55 Ohkuma T, Kitamura M, Noyori R (2000) Asymmetric hydrogenation. In Ojima I (ed) Catalytic asymmetric synthesis, 2nd edn. Wiley-VCH, New York, p 1-110... 

Wilson RM, Jen WS, MacMillan DWC (2005) Enantioselective organocatalytic intramolecular Diels-Alder reactions. The asymmetric synthesis of solana-pyrone D. J Am Chem Soc 127 11616-11617 Xie JH, Zhou ZT, Kong WL, Zhou QL (2007) Ru-catalyzed asymmetric hydrogenation of racemic aldehydes via dynamic kinetic resolution efficient synthesis of optically active primary alcohols. J Am Chem Soc 129 1868-1869... 

Dynamic kinetic resolution is well known in pure chemical synthesis, as illustrated by work by Noyori et al. on the asymmetric hydrogenation of a-substituted /f-ketoesters. Noyori et al. [5], Ward [6] and Caddick et al. [7] have reviewed the chemical syntheses, and biocatalytic routes have been discussed by Faber et al. [8]. 

Rhodium and ruthenium complexes of CHIRAPHOS are also useful for the asymmetric hydrogenation of p-keto esters. Dynamic kinetic resolution of racemic 2-acylamino-3-oxobutyrates was performed by hydrogenation using ((5,5)-CHIRAPHOS)RuBr2 (eq 3). The product yields and enantiomeric excesses were dependent upon solvent, ligand, and the ratio of substrate to catalyst. Under optimum conditions a 97 3 mixture of syn and anti p-hydroxy esters was formed, which was converted to o-threonine (85% ee) and D-allothreonine (99% ee) by hydrolysis and reaction with propylene oxide. 

Zhou explored the asymmetric hydrogenation of 2,3 disubstituted quinolines. They thought that the hydrogenation mechanism of 2,3 disubstituted quinolines was somewhat different from that of 2 substituted quinolines (Scheme 10.20) [3]. For the hydrogenation of 2 substituted quinoline, the hydrogenation of C=N bond is the enantioselectivity controlled step (Scheme 10.19, H-I), while the enantioselectivity controlled step of 2,3 disubstituted quinolines is the isomerization of enamine to imine and the hydrogenation of C=N bond, which is in fact a dynamic kinetic... 

Example of Dynamic Kinetic Resolutions Dynamic Kinetic Resolution of 1,3-Dicarbonyl Compounds Through Asymmetric Hydrogenation... 

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. ... 

The application of dynamic kinetic discrimination to the ruthenium-catalysed hydrogenation of cyclic ketones such as 2-arylated cycloalkanones was reported by Noyori s group in 2004. Hence, the asymmetric hydrogenation of various 2-arylcycloalkanones with tra s -RuCl2(BINAP)(l, 2-diamine) and t-BuOK in ijo-propyl alcohol selectively gave the corresponding cis-2-arylcycloalkanols in excellent enantiomeric purity and quantitative yield, as shown in Scheme 2.25. 

Fig. 22 Diastereoselective asymmetric transfer hydrogenation of cyclic substrates with dynamic kinetic resolution...

---