Racemic allyl alcohols

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. 

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. 

Correlate reaction tellurium-mediated resolution of racemic allyl alcohols... 

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... 

One of the first optically active allenes reported was synthesized by enantioselective dehydration of a racemic allylic alcohol in the presence of (+)-10-camphorsulfonic acid as the chiral catalyst125,126. The initial optical rotation of the tetraarylallene is low, but can be increased to [a],2/1 +351 (cyclohexane) after several recrystallizations. 

The racemic acyclic allylic t-butylsulfinates roc-llaa and roc-llba were prepared both as 1 1 mixtures of diastereomers from the racemic allylic alcohols rac-lOa and roc-lOb, respectively, and racemic 2-t-butylsulfinyl chloride [18], in high yields (Scheme 2.1.4.13). 

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). 

Another example is the cyclization of the racemic allylic alcohol 232 at -80°C which furnished the racemic tetracyclic bis-olefin 233 in 70% yield (89, 90). Ozonolysis of 233 gave the bicyclic triketone aldehyde 234 which underwent under acidic conditions a double intramolecular aldol cyclodehydration to produce racemic 16,17-dehydroprogesterone 235. This represents the first synthesis of a steroid via the now so-called "biomimetic" polyene cyclization method. 

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... 

Geraniol or nerol can be converted to citronellol in 96-99% ee in quantitative yield without saturation of the C(6)-C(7) double bond (eq 6). The S C ratio approaches 50000. The use of alcoholic solvents such as methanol or ethanol and initial H2 pressure greater than 30 atm is required to obtain high enantioselectivity. Diastereoselective hydrogenation of the enantiomerically pure al-lylic alcohol with an azetidinone skeleton proceeds at atmospheric pressure in the presence of an (i )-BINAP-Ru complex to afford the (3-methyl product, a precursor of ip-methylcarbapenem antibiotics (eq 7). Racemic allylic alcohols such as 3-methyl-2-cyclohexenol and 4-hydroxy-2-cyclopentenone can be effectively resolved by the BINAP-Ru-catalyzed hydrogenation (eq 8). ... 

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. 

Reaction of racemic allyl alcohol and 10 mol of racemic complex 88 affords the produet with little selectivity. 

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. 

Resolution of racemic allyl alcohols (general procedure).Elemental powdered Te (2.0-2.5 equiv) andNaBH (4.0-5.0 equiv) in DMF (0.5-1.0 M in Te) are mixed nnder an inert atmosphere and heated to 70-80°C for 0.5 h. The grey suspension turns a deep purple colour. The reaction is cooled to room temperature and the glycidyl sulphonate (1.0 equiv based on Te) in DMF is added. The reaction is monitored by NMR analysis of reaction aliquots and is... 

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. 

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