Racemic acetates

Amino alcohols can be resolved by a number of pathways including hydrolysis, esterification, and transesterification. For example, hydrolysis of Ai,0-diacet5l-2-amino-l-butanol with PPL followed by recrystallization results in (80a) with 95% ee (108). Hydrolysis of racemic acetates or butyrates of 2-[(aLkoxycarbonyl)amino]-l-aLkanols with PFL gives (R)-alcohol (81) with 95% ee (109). (3)-(81) can be obtained by transesterification of the racemic (81) with ethyl acetate which also serves as the reaction medium (109). 

The force-area curves for racemic and (5)-(+)-2-tetracosanyl acetate recorded with a barrier speed of 5 cm/min are shown in Figures 17 and 18, respectively. Again, both enantiomers showed identical monolayer behavior. The film balance behavior of the racemic acetate was indistinguishable from that of the pure enantiomers at temperatures above about 27°C however, below this temperature the force-area curves differed markedly even at low surface pressures, which indicates that racemic compound formation occurs at relatively large areas per molecule. 

Since the oxidation of (96) proceeds through the acyliminium ions (97) (Scheme 36), where the positive charge is stabilized by the adjacent nitrogen atom, it should lead to racemic acetals (98) from enantioenriched acids (96). In fact, the electrolysis of A/-benzoylated L-proline (113) gave racemic N, O-acetal (114) regardless of the anode material used (Scheme 41) [129]. 

Ikeda and co-workers examined ferrocene-based ligands 11a and 11b in the same allyhc substitution reaction of racemic acetate 136 (Fig. 9.44, Table 9.24). This catalytic system resulted in quantitative yield of 137 with ee of 96 and 99%, respectively. 

Chemical synthesis of racemates and subsequent resolution via crystallization of diastereomeric salts is employed in the preparation of rf-biotin and tocopherol (vitamins), dexchlorpheniramine (antihistaminic), levomepromazine (neuroleptic), levorphanol (analgesic), and naproxen (antiphlogistic), to note some examples4, threo-2-Amino-1 -(4-nitro-phenyl)-l,3-propanediol, an intermediate in the production of chloramphenicol, is resolved by crystallization with entrainment or via crystallization of the salt with camphorsulfonic acid4. Enzymatic resolutions are increasingly employed, normally via deacetylation of racemic acetates. This method has recently been used in the synthesis of carbacyclin derivatives5. 

The ee value of acetate Idb, which was >98% at the beginning, decreased with increasing conversion (Fig. 2.1.4.3). At approximately 50% conversion only the racemic acetate rac-ldb could be detected. From here on, the mismatched acetate... 

Etodolac is a racemic acetic acid derivative with an intermediate half-life (Table 36-1). Etodolac does not undergo chiral inversion in the body. The dosage of etodolac is 200-400 mg three to four times daily. 

The reverse reaction was consisting of lipase-catalyzed hydrolysis of the racemic acetate afforded the (R)-alcohol in high enantiomeric excess (>99% ee). 

Lindell and co-workers reported [91JCS(P1)2603] that imidazole 67 reacts with a mixture of racemic acetates 68 and 69 containing 12% of trans isomers to afford isomers ds-70 and trans-71 in the same ratio as that obtaining in the cis-trans mixture of starting materials (Scheme 16). It should be pointed out that both 68 and 69 produce the same intermediate... 

The mixture of the (R)-HMPC and the (S)-acetate 4 from the enzymatic hydrolysis was esterified with methanesulfonyl choride and triethylamine to afford a mixture of the corresponding (R)-sulfonate 5a and the (S)-acetate 4. The (S)-acetate 4 was unaffected by the sulfonation conditions. The resultant mixture of two esters, 4 and 5a, was hydrolyzed in the presence of a small amount of calcium carbonate. The (R)-sulfonate 5a was converted into the (S)-HMPC 6 as a result of inversion of configuration. On the other hand, the (S)-acetate 4, was hydrolyzed with retention of configuration. Consequently, all of the racemic acetate J3, was converted with maximum efficiency to the desired (S)-HMPC 6, by the sequence enzymatic hydrolysis and sulfonation followed by inversion of the chiral center in (R)-HMPC without separation of the (S)-acetate Similar transformations could also be carried out via nitrate ester intermediate 5b obtained from the reaction of the (R)-HMPC with nitric acid and acetic anhydride. 

In contrast to the case of HMPC, most lipases hydrolyze the racemic acetate of CPBA 9 to give a mixture of the insecticidally active (S)-CPBA 2 and the (R)-acetate 1J). Thus, the desired (S)-CPBA J2 could be separated from the (R)-acetate 10 by means of a continuous counter-current extraction using n-heptane solvent at 80°C. However, it is important to utilize the recovered (R)-acetate W for an efficient process. Fortunately, since the proton of the asymmetric carbon of the cyanohydrin acetate is labile, the antipodal (R)-acetate is easily racemized by treatment with weak organic base such as triethylamine without any side reactions. The racemized acetate J9 thus obtained was recycled as shown in Figure 6. Therefore, all of the racemic acetate 9 was converted to the desired (S)-CPBA 2 in this recycling process. The (S)-CPBA 2 obtained was esterified with (S)-2-(4-chlorophenyl)-3-methylbutyryl chloride to produce the most insecticidally active stereoisomer V2 of fenvalerate, namely esfenvalerate. The relative biocidal activities between... 

For the production of various pyrethroid insecticides the (S)-4-hydroxy-3-methyl-2-(2-propynyl)-2-cyclopenten-l-one was required. Arthrobacter lipase hydrolysed only the P-enantiomer of the racemic acetate and, after extraction, the mixture of the alcohol and acetate were submitted to methanesulfonyl chloride and triethylamine. The thus-obtained acetate/mesylate mixture was hydrolysed/ inverted yielding 82% of (S)-4-hydroxy-3-methyl-2-(2-propynyl)-2-cyclopenten-l-one with an ee of 90% (Scheme 6.17 B). The procedure was also proved to work with other secondary alcohols and instead of the mesylate a Mitsunobu inversion could be applied [35]. 

Methods for the capillary gas chromatographic separation of optical isomers of chiral compounds after formation of diastereoisomeric derivatives were developed. Analytical aspects of the GC-separation of diastereoisomeric esters and urethanes derived from chiral secondary alcohols, 2-, 3-, 4- and 5-hydroxy-acid esters, and the corresponding jf- and -lactones were investigated. The methods were used to follow the formation of optically active compounds during microbiological processes, such as reduction of keto-precursors and asymmetric hydrolysis of racemic acetates on a micro-scale. The enantiomeric composition of chiral aroma constituents in tropical fruits, such as passion fruit, mango and pineapple, was determined and possible pathways for their biosynthesis were formulated. 

The reduction of methylketones to the corresponding S-(+)-alkan-2-ols by actively fermenting baker s yeast (14,15) was used to determine the GC order of elution of R-T+)-MTPA esters of secondary alcohols (Figure 3). The asymmetric hydrolysis of racemic acetates by microorganisms is a further method to obtain optically pure alcohols (1 6). Capillary GC investigation of the R-(+)-MTPA derivatives revealed, that enzymic hydrolysis of racemic... 

Figure 3. Formation of optically pure alcohols by stereospecific reduction of ketones and asymmetric hydrolysis of racemic acetates (DB 210, 30 m/0.33 mm i.d.).

Asymmetric reduction of the ketone on a 1.0-g (4.0-mmol) scale to provide (R)-(-)-2,2-diphenylcyclopentanol (96% ee) has been reported employing (+)-( -chlorodiisopinocampheylborane however, the reaction is extremely slow and inefficient [70% yield, 5 days, 2.6 equiv of (+)-p-chlorodiisopinocampheylborane].5 Other efforts to obtain enantiomerically pure 1 by means of enzymatic hydrolysis of the corresponding racemic acetates using horse liver acetone powder (HLAP) and pig... 

Enzymatic Resolution Approach (eq 2) Ketone (R)-l can also be obtained by enzymatic resolution of racemic acetate ( )-2, which is prepared by reduction and acetylation of racemic ( )-l (prepared according to the direct synthesis approach). Oxidation of the resulting (R)-alcohol affords (R)-l in high enan-tioselectivity (> 99% ee). This method has been employed for large-scale synthesis of (R)-l. 

Acetone Powder Containing Esterase Activity. The main advantage in using crude homogenates or acetone powders of organs such as liver is to have a cheap source of different enzymes. If one of these is desired for a specific substrate, the crude enzymatic mixture can be used with some advantage, compared to the purified enzymes. Pig liver acetone powder (PLAP), together with other extracts, is commercially available or can be prepared from fresh pig liver. PLAP has been used for the enantioselective hydrolysis of the racemic acetate of rrans-2-phenylcyclohexanol... 

Cholesterol Esterase. This enzyme (EC 3.1.1.13 CAS 9026-00-0) physiologically catalyzes the hydrolysis of cholesterol esters, monoacylglycerols, and vitamin esters. It has also been used for several cyclie and noncyclic substrates with variable enantioselectivity. The resolution of racemic esters has been reported and an interesting example is the application to the racemic acetate of an hemiacetal (eq 14). ... 

Problem 28.17 (a) Drawing structures of the kind in Fig. 28.5 (p. 907), show how Cram s mechanism accounts for the conversion of optically active //ireo-3-phenyl 2-butyl tosylate into racemic acetate, (b) In contrast, optically active erythro tosylate yields optically active erythro acetate. Show that this, too, fits Cram s interpretation of the reaction. 

FIGURE 3.28. Hydrolytic kinetic resolution of racemic acetates using ChiroCLEC-PC... 

The rearrangement of sulfinate esters to sulfones has also been investigated. Detailed understanding of the mechanism results from the acetolysis of chiral (asymmetric sulfur and carbon) p-phenylbenzhydryl p-toluenesulfinate (120)ul Fava found that (120) undergoes epimerization at sulfur with complete retention at carbon. Sulfone (121) was formed in 33% optical purity, together with a small amount of racemic acetate. It appears that epimerization at sulfur is due to return from the intimate ion pair whereas sulfone (121) can form from both intimate and solvent-separated ion pairs. 

A bridged intermediate appears unlikely in the acetolysis of (338) since the solvolysis of the tertiary system (339) goes with neither aryl participation nor pheno-nium intermediates (cf. Section 7.3.3.). More direct evidence comes from the solvolysis of the chiral 2-methyl-2-phenyl-1-butyl system. Both the mesylate (340) and the amine (341) afford the product of phenyl migration, (342), with substantial racemization285. Similarly, the alkaline deamination of (343) yields largely racemic acetals (344)2S6 These stereochemical results clearly demonstrate the limits of phenonium ion intervention. 

A series of cyanohydrin acetates with an e.e. up to 98% has been prepared by enzymatic hydrolysis of their racemic acetates in the presence of an esterase from Pseudomonas spJ137]. Lipoprotein lipase from Pseudomonas sp. catalysed irreversible transesterification using enol esters was applied to the resolution of different aromatic cyanohydrins[138> 139). 

Enzymes were used for the chiral synthesis or resolution of side chains that can be coupled to 10-deacetylbaccatin 111 in the semisynthesis of paclitaxel and analogs. Racemic acetate 8 (Scheme... 

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