Kinetic resolution racemic allylic alcohols

Similarly,110 (lR,2S )-ephedrine is an effective poison in the kinetic resolution of allylic alcohols using racemic BINAP instead of the expensive (R)-BINAP. (/ )-2-cycIohexenoI can thus be obtained in >95% ee using a racemic... 

The lipase-catalysed enantioselective acylation of allylic alcohols in an ionic liquid solvent was demonstrated by Itoh et al. [16] (Fig. 7.7). They found that the acylation rate was strongly dependent on the counter anion of the imidazolium salt, while the lipase-catalysed acylation proceeded with high enantioseleclivity in all ionic liquid tested. Good results were obtained when the reaction was carried out in [bmimT [PFg ] or [bmun" ][BF ]. Other examples of kinetic resolution of allylic alcohols catalysed by lipases in ionic liquids were also reported by these authors [71, 72]. The transesterification of 5-phenyl-l-penten-3-ol under reduced pressure at 27 hPa and 40°C was carried out using methyl phenylthioacetate as acyl donor in [bmim+] [PF ] and [bdmim ][BF ], for obtaining the corresponding acylated compound in optically pure form [71], The acetylation of methyl mandelate catalysed by immobilised P5L in [bdmim ][BF ] is another example reported by these authors about the successful application of ionic liquids as reaction media in racemic resolutions... 

Another ruthenium catalyst was used for the dynamic kinetic resolution of allylic alcohols [reaction (24)] by acylation yielding allylic acetates. Again a redox process should be responsible for the racemization. 

Enzymatic hydrolysis of A/-acylamino acids by amino acylase and amino acid esters by Hpase or carboxy esterase (70) is one kind of kinetic resolution. Kinetic resolution is found in chemical synthesis such as by epoxidation of racemic allyl alcohol and asymmetric hydrogenation (71). New routes for amino acid manufacturing are anticipated. 

The application of the AE reaction to kinetic resolution of racemic allylic alcohols has been extensively used for the preparation of enantiomerically enriched alcohols and allyl epoxides. Allylic alcohol 48 was obtained via kinetic resolution of the racemic secondary alcohol and utilized in the synthesis of rhozoxin D. Epoxy alcohol 49 was obtained via kinetic resolution of the enantioenriched secondary allylic alcohol (93% ee). The product epoxy alcohol was a key intermediate in the synthesis of (-)-mitralactonine. Allylic alcohol 50 was prepared via kinetic resolution of the secondary alcohol and the product utilized in the synthesis of (+)-manoalide. The mono-tosylated 3-butene-1,2-diol is a useful C4 building block and was obtained in 45% yield and in 95% ee via kinetic resolution of the racemic starting material. 

Stopping the reaction before completion. This method is very similar to the asymmetric syntheses discussed on page 132. A method has been developed to evaluate the enantiomeric ratio of kinetic resolution using only the extent of substrate conversion. An important application of this method is the resolution of racemic alkenes by treatment with optically active diisopinocampheylborane, since alkenes do not easily lend themselves to conversion to diastereomers if no other functional groups are present. Another example is the resolution of allylic alcohols such as (56 with one... 

The great selectivity of Ru-BINAP species is also evident when they are used in kinetic resolution of enantiomers. When a racemic allylic alcohol reacts with H2 in the presence of Ru-(A)-BINAP, the (R)-alcohol reacts preferentially, thus leaving the (S)-enantiomer unreacted (Equation (7)).71... 

Kinetic resolution ofallylic alcohols. The (R)- and (S)-BINAP-Ru diacetate complexes can resolve racemic allylic alcohols, both acyclic and cyclic, with high enantiomeric selectivity. Thus hydrogenation of ( )-2 catalyzed by (S)-l at 76% conversion provides (S)-2 (>99% ee) and anti-3 (49 1, 39% ee). Hydrogenation of (S)-2 catalyzed by either (R)- or (S)-l provides anti-3 (>23 1). Similar results obtain with ( )-4. 

In principle, any reaction with a racemate using a chiral reagent can be used to effect a kinetic resolution. Kagan (56) has recently given an analysis of the relationship between the extent of reaction and die enantiomeric excess that can be achieved, while Sharpless (57) has applied kinetic resolution successfully to racemic allyl alcohols using his titanium alkoxide tartrate epoxidation reaction. 

The combination of the preceding method of obtaining allyl alcohols with the Sharpless kinetic resolution (SKR) of secondary allyl alcohols allows conversion of the original racemic allyl alcohol into a pure enantiomer with a 100% theoretical yield. By this procedure, the glycidol obtained by the SKR epoxidation of the secondary allyl alcohol is converted into the corresponding mesylate and then treated with the Te ion, furnishing the allylic alcohol with the same configuration of the enantiomer in the SKR which... 

Scheme 21). Scheme 22 illustrates an example of kinetic resolution of a racemic allylic alcohol with a 1,3-hydrogen shift. When racemic 4-hydroxy-2-cyclopentenone is exposed to a cationic (/ )-BINAP-Rh complex in THF, the S enantiomer is consumed five times faster than the R isomer (32). The slow-reacting stereoisomer purified as the crystalline ferf-butyldimethylsilyl ether is an intermediate in prostaglandin synthesis (33). These isomerizations may occur via initial Rh-olefinic bond interaction (34). 

Enantioselective isomerization can be advantageously used for the kinetic resolution of racemic allyl alcohols. For example treatment of 4-hydroxy-2-cyclopente-none (rac-28) in the presence of Rh[(R)-BINAP](MeOH)2 + gives rise to the enan-tiomerically enriched allyl alcohol (R)-29 (Scheme9) [13]. This unsaturated hydroxy ketone is an important building block for the synthesis of prostaglandins... 

The combination of the chemistry shown in Scheme 22,100 with the Sharpless kinetic resolution (SKR) of secondary allylic alcohols 46101 provides a method for the conversion of racemic allylic alcohols 46 into a single enantiomer with 100% theoretical yield.102 The reaction of sodium telluride with the mesylate 48 derived from 47 affords 46a. In this way, a single enantiomer of the allylic alcohol 46 is obtained in high yield (Scheme 23).102... 

In the hydrogenation of racemic allylic alcohols catalyzed by a chiral Rh catalyst, at most, 20 1 discrimination has been attained for some acyclic substrates. BINAP-Ru complexes have been used for kinetic resolution of chiral acyclic and cyclic secondary alcohols with up to 74 1 differentiation between the enantiomeric alcohols (equation 15). ... 

When C-I of the allylic alcohol (attached close to the OH group) is a stereogenic center the asymmetric epoxidation will proceed with substantially different rates for the two enantiomers, allowing kinetic resolution of the racemic allylic alcohol. 

Application of the Sharpless procedure for the kinetic resolution of racemic allyl alcohols [Ti(0/Pr)4 BuOOH and L- or D-DET] to such a process provided an optically active dihy-drop)Tan together with enantiomerically pure unreacted furylcarhinol [6]. The Casiraghi approach leads to 2,3-unsaturated furanoses (or amino furanoses) hy an acid-catalyzed reaction of 2-(trimethylsilyloxy)furan with sugar aldehydes or aminoaldehydes. 

Resolution of Racemic Mixtures ofAllylic Alcohols.An important application of the SAE reaction is the kinetic resolution of racemic mixtures of secondary allylic alcohols. In this case, the chiral catalyst reacts faster with one enantiomer than with the other since the two transition states are diastereomeric. Thus, using 0.5 mole of r-BuOOH for each mole of racemic allylic alcohol, the faster-reacting enantiomer will consume the r-BuOOH to furnish the epoxide. This leaves behind the unreacted slower-reacting allylic alcohol in high enantiomeric excess, which is then separated from the epoxide via chromatography. 

On the other hand, when an epoxy alcohol is the desired product, the reaction must be stopped before the fast isomer is consumed completely. Usually the reaction is stopped at 40 to 45% conversion. Although the direct epoxidation of racemic allylic alcohols gives the epoxides in good enantiomeric excesses, the epoxidation of the recovered unreacted allylic alcohols obtained by kinetic resolution provides epoxides of much high enantiopurity. 

Synthesis of Chiral Oxirans. The recently introduced Katsuki-Sharpless reagent (titanium alkoxide with tartrate) has proved highly effective for the maiden introduction of chirality into prochiral allylic alcohols. An interesting development of this procedure has afforded the possibility of kinetic resolution of racemic allylic alcohols. The basis of the method involves the... 

Using a racemic allylic alcohol, one can take advantage of this rate differential to selectively epoxidize the more reactive 5 isomer in the presence of its antipode. This procedure is known as a Sharpless kinetic resolution (KR) [13,36]. The KR has very wide applicability for the preparation of both 1,2-anti epoxy alcohols and the unreacted allylic alcohol, often with very high enantioselectivities (note that the diastereomeric 1,2-syn series is not generally available by this technique). In general terms, carrying out the reaction to lower conversions will maximize the yield and... 

Representative examples are shown in Scheme 9. The Sharpless AE of geraniol (57) with (+)-diethyl tartrate (DET) gave a-epoxide 58 with 95% ee. In a double asymmetric induction, epoxidation of allylic alcohol 59 with (—)- and (+)-DET provided a- and P-epoxides, 60 and 61, in ratios of 40 1 and 1 14, respectively [23]. It is noteworthy that high asymmetric selectivity was induced even in the mismatched case. The Sharpless AE is also effective for the kinetic resolution of racemic allylic alcohols. In the reaction of 62 with 0.6 equiv. of t-BuOOH and... 

Martin VS, oodard SS, Katsuki T et al (1981) Kinetic resolution of racemic allylic alcohols by enantioselective epoxidation - a route to substances of absolute enantiomeric purity. J Am Chem Soc 103 6237-6240... 

The kinetic resolution reaction can be used for the asymmetric synthesis of chiral secondary allylic alcohols or their corresponding epoxides. The yield of either is, of course, limited to 50%, starting from the racemic allylic alcohol, but the methodology has found widespread use in organic synthesis. For example, epoxidation of the racemic allylic alcohol 54 gave the epoxide 55, used to prepare the anticoccidial antibiotic diolmycin A1 (5.63). ... 

The crystal structures of two catalyst precursors have been determined, A-(/ )-[(8)Ru(02CR)2] and A-(5)-[(8)Ru(02CR)2]/ These complexes also achieve the kinetic resolution of racemic allylic alcohols by asymmetric hydrogenation of one isomer only see equation (14). The asymmetric reduction of functionalized... 

Using the same concept, Hoveyda and co-workers recently employed molybdenum derived chiral complexes to develop a net catalytic enantioselective, cross metathesis process based on either the kinetic resolution of racemic allylic alcohols or the asym-... 

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