Kinetic Resolution of -Primary Alcohols

Preparation of epoxide 2R,3S)-5, which was converted to ieuco-maiure (the pheromone of the satin moth). 

Preparation of epoxide (2S,3/ )-23, which was converted to the pheromone of the Colorado potato beetle. 

Preparation of the enantiomers of y-cyclohomogeraniol (24), which was converted to two terpenoids. 

Preparation of (/ )-26, which was converted to (+)-hippospongic acid (a marine triterpenoid). 

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Figure 11 Representative kinetic resolution of primary alcohol ( )-10 using chiral acyl donor ( )-ll.

Mezetti, A. Keith, C. Kazlauskas, J., R. Highly enantioselective kinetic resolution of primary alcohols of the type Ph-X-CH(CH3)-CH2OH by Pseudomonas cepacia lipase effect of acyl chain lengh and solvent. Tetrahedron Asymmetry 2003, 14, 3917-3924. 

Sakai T, Hayashi K, Yano F, Takami M, Ino M, Korenaga T, Ema T (2003) Enhancement of the efficiency of the low temperature method for kinetic resolution of primary alcohols by optimizing the organic bridges in porous ceramic-immobilized lipase. Bull Chem Soc Jpn 76 1441-1446... 

The kinetic resolution of primary alcohols (RCH2OH) by enzymatic acylation is often demanding because of the remote position of the asymmetric center firom the reaction site. Moreover, special attention is needed to keep the acyl transfer irreversible and to prevent hydrolysis of the acylated product. 

Table 9.6 Kinetic resolution of primary alcohols 21a-c and secondary alco hols 23a-r by acylation in hydrol lase-filled conti nuous-flow reactors. ... 

Figure 9.8 Hydrolase-catalyzed kinetic resolution of primary alcohols 21a-c by acylation in continuous-flow PBR.

Striibing, D., Krumlinde, P, Piera, J., and Backvall, J.-E. (2007). Dynamic kinetic resolution of primary alcohols with an unfunctionalized stereogenic center in the (J-jxrsition. Adv. Synth. Catal., 349,1577-1581. 

Oxidative kinetic resolution of secondary alcohols mediated with a catalytic amount of optically active binaphthyl-type iV-oxyl has been performed with high selectivity". Also, it has mediated oxidative asymmetric desymmetrization of primary alcohols with good selectivity (equation 25)". ... 

Fig. 5 Enzymatic kinetic resolution of primary allenic alcohols...

Deska J, Backvall J-E (2009) Enzymatic kinetic resolution of primary allenic alcohols. Application to the total synthesis and stereochemical assignment of striatisporolide A. Org Biomol Chem 7 3379-3381... 

The immobilized catalyst provided good enantioselectivity and activity in the heterogeneous catalysis of the oxidative kinetic resolution of secondary alcohols and can be recovered and recycled for four times without obvious loss of enantioselectivity and activity. Oxidative kinetic resolutions of meso-diols, hydroxyl esters, and primary alcohols were also studied using this catalytic system. 

Dynamic Resolution. Lipase-catalyzed acyl transfer has become a well-established and popular method for the kinetic resolution of primary and secondary alcohols. In order to circumvent the limitations of kinetic resolution (i.e., a 50% theoretical yield of both enantiomers), several strategies have been developed, which achieve a more economic dynamic resolution process and allow the formation of a single stereoisomer as the sole product (for the theoretical background see Sect. 2.1.1). In contrast to compounds bearing a chiral center adjacent to an electron-withdrawing... 

Optically active 5-(hydroxymethyl)-3-phenyl-2-isoxazoline 13 is a versatile key intermediate for the syntheses of /3-hydroxy ketones, y-amino alcohols,and y-amino acids. However, the Upase-catalyzed kinetic resolution of isoxazoline ( )-13 has not been reported so far probably because of the low enantioselectivity expected for primary alcohols (Scheme 3). The enantioselectivity was found to be very low E value = 4-5 in /-Pr20) at room temperature however, it could be markedly improved up to an value of 249 at —60°C by using lipase PS-C 11 in acetone, which was the best solvent among those tested (THF, /-Pt20) 1 )-... 

An effective deoxygenation using enantiomerically pure epoxides from primary allylic alcohols ( Sharpless epoxides ) [44] to give enantiomerically pure secondary allylic alcohols was described by Yadav [45]. This approach circumvented a kinetic resolution of secondary allylic alcohols that implies a maximum yield of 50% ( Scheme 5). 

Table 14. Kinetic Resolution of Racemic Primary Allylic Alcohols via Sharplcss Epoxidation...

The improvement of the enantioselectivity E in kinetic resolution of a primary alcohol (10) through lipase-catalyzed transesterification was studied using a chiral acyl donor 11. The combination of the lipase, solvent and acyl donor was effective for the enantioselectivity.62... 

Acylases have also been applied to the kinetic resolution of amines. Aminoacylase I from Aspergillus melleus was used for the resolution of a range of arylalkylamines and amino alcohols via acylation with methyl 2 methoxyacetate (Figure 14.13) [19]. Excellent chemoselectivity was also observed in all cases, as the amino group was preferentially acylated in the presence of a primary alcohol functionality. However, poor to moderate enantioselectivity was observed, with values <10. The best result (E = 9.3) was obtained with 1 aminoindane 10 during the conversion to ester 38. 

TBDMSCl, DMAP, EtjN, DMF, 25°C, 12 h. These conditions were used to silylate selectively a primary over a secondary alcohol. In the silylation of carbohydrates, it was shown that these conditions inhibit silyl migration whereas the use of imidazole as base causes migration." Besides DMAP, other catalysts such as 1,1,3,3-tetramethylguanidine, l,8-diazahicyclo[5.4.0]undec-7-ene (83-99%), l,5-diazabicyclo[4.3.0]non-5-ene, and ethyldiisopropyl-amine have also been used. A chiral guanidine has been used to give modest kinetic resolution of chiral secondary alcohols with TBDMSCl and TIPSCl. ... 

A similar chiral substituent effect is also observed in kinetic resolution of racemic primary allylic alcohols (Scheme 8). For example, both the enantiomers of racemic E-allylic alcohol are epoxidized at almost the same rate, while efficient kinetic resolution occurs in the epoxidation of racemic Z- and 2-substitut-ed allylic alcohols [49]. 

Kinetic Resolution by Oxidation of Primary Alcohols Catalyzed by Whole Cells from Rhodococcus erythropolis (E.C. l.X.X.X) l43 45 ... 

Kinetic Resolution by Oxidation of Primary Alcohols Catalyzed by Whole... 

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