Resolution of alcohols

Naphthyl)ethyl isocyanate 2 for chromatographic resolution of alcohols, hydroxy esters thiols via diastereomenc derivatives. 

Scheme 5.11 Dynamic kinetic resolution of alcohol 18 by combination of enzymatic transesterification and ruthenium-catalyzed racemization.

The low-temperature method is effective not only in the kinetic resolution of alcohols but also in the enantioface-selective asymmetric protonation of enol acetate of 2-methylcyclohexanone (15) giving (f )-2-methylcyclohexanone (16). The reaction in H2O at 30°C gave 28% ee (98% conv.), which was improved up to 77% ee (82% conv.) by the reaction using hpase PS-C 11 in /-Pt20 and ethanol at 0°C. Acceleration of the reaction with lipase PS-C 11 made this reaction possible because this reaction required a long reaction time. The temperature effect is shown in Fig. 14. The regular temperature effect was not observed. The protons may be supplied from H2O, methanol, or ethanol, whose bulkiness is important. 

Scheme 10.6 Mechanism of aerobic oxidation catalysed by complex 13 [23] Table 10.2 Oxidative kinetic resolution of alcohols using (-)-sparteine [25]...

Axially chiral Pd-NHC complexes reported by Shi and co-workers [26-28] have shown high selectivity in the oxidative kinetic resolution of alcohols without the need of addition of a chiral base. Enantiomeric excesses of up to 99% were obtained (Scheme 10.7). 

Scheme 10.7 Oxidative kinetic resolution of alcohols using chiral bis-NHC hgands [26-28] 10.3.1.2 Anaerobic Oxidation...

In a lipase-catalyzed reaction, the acyl group of the ester is transferred to the hydroxyl group of the serine residue to form the acylated enzyme. The acyl group is then transferred to an external nucleophile with the return of the enzyme to its preacylated state to restart the catalytic cycle. A variety of nucleophiles can participate in this process. For example, reaction in the presence of water results in hydrolysis, reaction in alcohol results in esterification or transesterification, and reaction in amine results in amination. Kirchner et al.3 reported that it was possible to use hydrolytic enzymes under conditions of limited moisture to catalyze the formation of esters, and this is now becoming very popular for the resolution of alcohols.4... 

The empirical observation that (—)-sparteine 55 is necessary for catalysis implicates a base-promoted pathway in the mechanism. In the first step, a palladium alk-oxide is formed after alcohol binding, followed by p-hydride elimination of the alkoxide to yield a ketone product. On the basis of a kinetic study of the enantio-selective oxidation of 1-phenylethanol, it was revealed that (—)-sparteine plays a dual role in the oxidative kinetic resolution of alcohols, as a ligand on palladium and an exogeneous base " ... 

Reformatsky reaction, 1, 1 22, 4 Reimer-Tiemann reaction, 13, 2 28, 1 Reissert reaction, 70, 1 Resolution of alcohols, 2, 9 Retro-Diels-Alder reaction, 52, 1 53, 2 Ritter reaction, 17, 3... 

Lipase Catalyzed Kinetic Resolution of Alcohols via Chloroacetate Esters (-)-(lR,2S)-trans-2-Phenylcyclohexano1 and (+)-(lS,2R)-trans-2-Phenyl cyclohexanol... 

Even more interesting is the oxidative kinetic resolution of alcohols under aerobic conditions. The system Pd(lI)/sparteine/02 was reported to convert a racemic alcohol with high selectivity into the ketone and the alcohol [97-99]. This has also been shown to work with palladium carbene complexes (Scheme 16). 

Moreover, the already known abihty of iridium compounds to catalyze hydrogen transfer reactions has been excellently applied in Oppenauer-type and domino-type reactions for valuable organic chemicals and further developments, including asymmetric variants to kinetic resolution of alcohols and fine chemicals, can be expected. 

I.4.2. Enzymatic Kinetic Resolution of Alcohols and Carboxylic Acids... 

Compared to the chemo-catalyzed kinetic resolution of alcohols, there are few reports of similar reactions for amines. Building on other work, one elegant example from Berkessel uses bifunctional organocatalysts to enantioselectively hydrolyze a racemic azlactone, and the dynamic kinetic resolution (DKR) is achieved by in-situ acid-catalyzed racemization of the azlactone under mild conditions to give product N-acylarnino esters in, for example, 72% ee and 96% conversion with phenylalanine [6]. 

For a review of resolution of alcohols, see Klyashchitskii Shvets Russ. Chem. Rev. 1972, 41. 592-602. 

Resolution of alcohols (cf., l-(naphthyl)cthyl isocyanate, 8, 356 357). A practical synthesis of the methyl ester of (S)-5-HF,TF. (1) from arachidonic acid involves chromatographic separation of the diastereomeric urethanes preparecT from the Isocyanate derived from dehydroabietylamine (hydrogen chloride and phosgene).1 Urethanes from other chiral amines are less useful. The urethanes are cleaved with triethylamine and trichlorosilanc to give the corresponding pure enantiomeric esters, which can be hydrolyzed by base. 

LIPASE-CATALYZED KINETIC RESOLUTION OF ALCOHOLS VIA CHLOROACETATE ESTERS (-)-(1R,2S)-trans-2-PHENYLCYCLOHEXANOL AND (+)-(1S,2R)-trans-2-PHENYLCYCLOHEXANOL... 

Fig. 3. Peptide-based catalysts for kinetic resolution of alcohols...

For examples of kinetic resolution of alcohols using chiral acylating agents, see Evans DA, Anderson JC, Taylor MK (1993) Tetrahedron Lett 34 5563-5566 Vedejs E, Chen X (1997) J Am Chem Soc 119 2584-2585... 

To recycle a valuable amine acylation catalyst, Janda and co-workers10 attached a proline-based catalyst to a polymeric support for the enan-tioselective kinetic resolution of alcohols (entry 6). The resin-bound catalyst behaves similarly to the soluble catalyst, providing good yields of secondary alcohols and their corresponding esters with good to excellent enantioselectivities for various substrates. 

Steric effects were evaluated by a study of the DMAP-catalysed acylation of 1 y, 2y and 3y alcohols by acetic, propionic, isobutyric, isovaleric, and pivalic anhydrides in CH2C12 at 20 °C. In all cases the reaction kinetics could be described by rate laws containing a DMAP-catalysed term and an uncatalysed (background) term. Steric effects were evident in both reactions, but were generally greater for the DMAP-catalysed reaction. For example, the uncatalysed reactions between cyclohexanol and acetic and pivalic anhydrides differed about 500-fold, but for the corresponding DMAP-catalysed reactions the factor was 8000-fold. The implications of these findings for the kinetic resolution of alcohols were discussed.32... 

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