Dynamic kinetic asymmetric 1.5- diols

Silylated amino acid esters have been prepared by a dynamic kinetic asymmetric transformation of this type. Slow addition (by syringe pump) of (R,R) DPEC maintained insertion slow relative to interconversion and afforded the silyl-substituted amino acid esters in Eq. 36 with ee values of 80, 68, and 83%. The ester 38c (R=TMS) was too base-sensitive to permit removal of the chiral diol, but transesterification of the other /J-hydroxyethyl esters 38 to the corresponding methyl esters was straightforward [22]. 

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],... 

The enzyme-catalyzed kinetic asymmetric transformation (KAT) of a diastereomeric 1 1 syn anti mixture is limited to a maximum theoretical yield of 25% of one enantiomer. This important drawback has been overcome by the combination of the actions of a ruthenium complex and a lipase in a dynamic kinetic asymmetric transformation (DYKAT), the desymmetrization of racemic or diastereomeric mixtures involving interconverting diastereomeric intermediates, implying different equilibration rates of the stereoisomers. Thus, this strategy allows the preparation of optically active diols, widely employed in organic and medicinal chemistry, as they are an important source of chiral auxiliaries and ligands and they can be easily employed as precursors of much other functionality. 

Martin-Matute, B. and Backvall, J.-E. (2004). Ruthenium- and enzymedynamic kinetic asymmetric transformation of 1,4-diols Synthesis of gamma-hydroxy ketones. /. Org. Chem., 69,9191-9195. 

Leijondahl, K., Boren, L., Braun, R., and Backvall, J.-E. (2008). Enantiopure 1,5-diols from dynamic kinetic asymmetric transformation. Useful synthetic intermediates for the preparation of chiral heterocycles. Org. Lett, 10,2027-2030. 

Leijondahl K, Boren L, Braun R, Backvall J-E. Enzyme- and ruthenium-catalyzed dynamic kinetic asymmetric transformation of 1,5-diols. Application to the synthesis of (+)-solenop-sin A. J. Org. Chem. 2009 74 1988 1993. 

Fig. 8.33 DYKAT of 1,3-diols via lipase-catalyzed acyl-transfer in combination with Ru-catalyzed epimerization of hydroxyl groups. G=chiral carbon, convertible for equilibration and acyl migration, but not for the irreversible step H=chiral carbon, convertible for equilibration, acyl migration and the irreversible step l=chiral carbon, convertible for acyl migration, stable chirality. (From J. Steinreiber, K. Faber, H. Griengl, De-racemization of enantiomers versus de-epimerization of diastereomers-chssification of dynamic kinetic asymmetric transformations (DYKAT), Chemistry 14 (2(X)8), 8060. Copyright 2008 Wiley).

The first example of the asymmetric synthesis of P-chiral trialkyl phosphates (12) via trialkyl phosphite, in which the keystone is dynamic kinetic resolution in the condensation of a dialkyl phosphorochloridite (13) and an alcohol by the catalytic assistance of a chiral amine has been reported (Figure 2)." 2,4-Dinitrophenol (DNP) was employed as an activating reagent with ben-zyloxy-bis-(diisopropylamino) phosphite to synthesize the cyclic phosphate derivatives (14) from a series of alkane diols HO-(CH2)n-OH (n=2-6). Included was a cyclic phosphate derivative of carbohydrate (15). The mechanism of activation by 2,4-DNP and cyclization was also described (Figure 3). ... 

Cartigny D, Piintener K, Ayad T, Scalone M, Ratoveloma-nana-Vidal V. Highly diastereo and enantioselective synthesis of monodifferentiated iy -l,2-diol derivatives through asymmetric transfer hydrogenation via dynamic kinetic resolution. Org. Lett. 2010 12(17) 3788-3791. 

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