Diols dynamic kinetic resolution

When 5-aryl l,3-dioxolane-2,4-diols were employed instead of the 5-alkyl substituted substrates rac-15, additional racemization of the anhydrides occurred, resulting in overall dynamic kinetic resolution. This reaction is covered in Section... 

Additions to prochiral ketenes [13.2] Desymmetrization of meso-diols [13.3] Dynamic kinetic resolution of azlactones rearrangement of O-acyl azlactones, O-acyl oxindoles, O-acyl benzofuranones [13.6]... 

A salen-cobalt complex has been appended to the PASSflow monolith system to form catalyst 42 and used for the dynamic kinetic resolution of epibromohydrin, 43. Because 43 undergoes rapid racemization under the conditions used, all the starting materials can theoretically be converted to the desired diol 44 (Scheme 4.75). The... 

Figure 18.24. Microbial dynamic kinetic resolution of the racemic diol 65 to (5)-dioL...

Instead of starting with racemic starting material it is also possible to use symmetric substrates [25]. The hydrolase selectively catalyses the hydrolysis of just one of the two esters, amides or nitriles, generating an enantiopure product in 100% yield (Scheme 6.7). No recycling is necessary, nor need catalysts be combined, as in the dynamic kinetic resolutions, and no follow-up steps are required, as in the kinetic resolutions plus inversion sequences. Consequently this approach is popular in organic synthesis. Moreover, symmetric diols, diamines and (activated) diacids can be converted selectively into chiral mono-esters and mono-amides if the reaction is performed in dry organic solvents. This application of the reversed hydrolysis reaction expands the scope of this approach even further [22, 24, 27]. 

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). ... 

In this chapter, we attempt to review the current state of the art in the applications of cinchona alkaloids and their derivatives as chiral organocatalysts in these research fields. In the first section, the results obtained using the cinchona-catalyzed desymmetrization of different types of weso-compounds, such as weso-cyclic anhydrides, meso-diols, meso-endoperoxides, weso-phospholene derivatives, and prochiral ketones, as depicted in Scheme 11.1, are reviewed. Then, the cinchona-catalyzed (dynamic) kinetic resolution of racemic anhydrides, azlactones and sulfinyl chlorides affording enantioenriched a-hydroxy esters, and N-protected a-amino esters and sulftnates, respectively, is discussed (Schemes 11.2 and 11.3). 

A straightforward extension of DKR to polymer chemistry is the use of diols and diesters (AA-BB monomers) or ester-alcohols (AB monomers) as substrates (Scheme 11.13, routes a and b). Such reactions have been referred to as dynamic kinetic resolution polymerizations (DKRP) and inevitably lead to the formation of oligomers/polymers because of the bifunctional nature of the reagents. The extension of DKR to polymer chemistry is not trivial since side reactions that are relatively unimportant in DKR (dehydrogenation, hydrolysis) have a major impact on the rate of polymerization and attainable chain lengths since the stoichiometry of the reactants is an important issue. As a result, the reaction conditions and catalyst combinations used in a typical DKR process will not a priori lead to chiral... 

Hilker et al (44) combined dynamic kinetic resolution with enzymatic polycondensation reactions to synthesize chiral polyesters from dimethyl adipate and racemic secondary diols. The concept offered an efficient route for the one-pot synthesis of chiral polymers from racemic monomers. Palmans at al (18,43) generalized the approach to Iterative Tandem Catalysis (ITC), in which chain growth during polymerization was effected by two or more intrinsically different catalytic processes that were compatible and complementary. 

Biocatalytic Dynamic Kinetic Resolution of (R,S)-1- 2,3-Dihydrobenzo[b]Furan-4-yl -Ethane-1,2-Diol. Most commonly used biocatalytic kinetic resolution of racemates often provide compounds with high e.e., although the maximum theoretical yield of product is only 50%. In many cases, the reaction mixture contains a roughly 50 50 mixture of reactant and product which have only slight differences in physical properties (e.g., a hydrophobic alcohol and its acetate), and thus separation may be very difficult. These issues with kinetic resolutions can be addressed by employing a Dynamic Kinetic Resolution process involving a biocatalyst or biocatalyst with metal-catalyzed in situ racem-ization (26,27). 

An elegant combination of monomers with the components of a dynamic kinetic resolution (DKR) permitted the conversion of a racemic diol into a polymer consisting of enantioenriched units that could be recovered by polymer hydrolysis [28]. Diol 5 and achiral diester 6 were combined with a well-known system of lipase and ruthenium catalyst (see Chapters 4 and 5 for more on this). The esterification of the free hydroxyl groups is very selective (for the R) configuration) but as the polymerization proceeds, the (S) stereocentres are racemized. Upon 92% conversion of the hydroxy groups and hydrolysis of the polymer, an enantioenriched sample of the diol was obtained that contained essentially none of the (S,S)-isomer. 

Fig. 16 Dynamic kinetic resolution polymerization of a 1,4 diol and dimethyl adipate, and structures of Noyori (i) and Shvo (2) type racemization catalyst [140]...

For the synthesis of an optically active polyester from a racemic monomer, a new method of dynamic kinetic resolution was used. A mixture of stereoisomers of a secondary diol, a,a -dimethyl-l,4-benzenedimethanol, were enzymatically polymerised with dimethyl adipate (Scheme 12.6, [1]) [32]. 

In another context, Cao and Qu showed that an enantioselective acylation catalysed by a chiral thioamide modified 1-methylhistidine methyl ester (Scheme 2.19) in combination with a DABCO-mediated racemisation of the substrate led to the efficient dynamic kinetic resolution (DKR) of meso-1,2-diol monodichloroacetates. As shown in Scheme 2.19, both cyclic and acyclic meso-l,2-diol monodichloroacetates could be transformed to the corresponding enantiomerically enriched (15, 2R)-heterosubstituted diol esters in good yields and moderate enantioselectivities of up to 74% ee. 

Scheme 12.21 One-pot synthesis of the corresponding 1,3 diols through dynamic kinetic resolution of diketone 40.

Other examples include OKR of racemic secondary alcohols (Scheme 25A), oxidative desymmetrizations of meso-diols, etc. The kinetic resolution is generally defined as a process where two enantiomers of a racemic mixture are transformed to products at different rates. Thus, one of the enantiomers of the racemate is selectively transformed to product, whereas the other is left behind. This method allows to reach a maximum of 50% yield of the enantiopure remaining sec-alcohol. To overcome this fim-itation, a modification of the method, namely dynamic kinetic resolution (DKR), was introduced. In this case, the kinetic resolution method is combined with a racemization process, where enantiomers are interconverted while one of them is consumed (e.g., by esterification. Scheme 25B). Therefore, a 100% theoretical yield of one enantiomer can be reached due to the constant equifibrium shift. In most of the proposed DKR processes, several catalytic systems, e.g., enzymes and transition-metal catalysts, work together. Both reactions (transfer hydrogenation of ketones and the reverse oxidation of secondary alcohols using ketone as a hydrogen acceptor) can be promoted by a catalyst. The process can involve a temporary oxidation of a substrate with hydrogen transfer to a transition-metal complex. 

Persson, B. A., Huerta, F. E, and Backvall, J.-E. (1999). Dynamic kinetic resolution of secondary diols via coupled ruthenium and enzyme catalysis. /. Org. Chem., 64,5237-5240. 

Kim, M. J., Choi, Y. K., Choi, M. Y., Kim, M. and Park, J. (2001). Lipase/ruthenium-catalyzed dynamic kinetic resolution of hydroxy acids, diols, and hydroxy aldehydes protected with a bulky group.. Org. Chem., 66,4736-4738. 

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. 

Dynamic resolution of various sec-alcohols was achieved by coupling a Candida antarctica lipase-catalyzed acyl transfer to in-situ racemization based on a second-generation transition metal complex (Scheme 3.17) [237]. In accordance with the Kazlauskas rule (Scheme 2.49) (/ )-acetate esters were obtained in excellent optical purity and chemical yields were far beyond the 50% limit set for classical kinetic resolution. This strategy is highly flexible and is also applicable to mixtures of functional scc-alcohols [238-241] and rac- and mcso-diols [242, 243]. In order to access products of opposite configuration, the protease subtilisin, which shows opposite enantiopreference to that of lipases (Fig. 2.12), was employed in a dynamic transition-metal-protease combo-catalysis [244, 245]. 

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