Unsaturated secondary alcohols resolution

Efficient kinetic resolution of chiral unsaturated secondary alcohols by irreversible enzyme-mediated acylation (with vinyl acetate as acylating agent, a crude preparation of Pseudomonas AK, and hexane as solvent) is possible, provided one relatively large and one small substituent are attached to the carbinol carbon. However, the method can be used to resolve substrates that are not amenable to asymmetric epoxidation (see examples 23, 25, 27, 29, where the double bond is either deactivated by an electron-withdrawing substituent, or is of the propargyl alcohol type). Acylation of the / -enantiomer consistently proceeds faster than that of the 5-enantiomer. An example of an allenic alcohol was also reported248. 

The enantioselective esterification of unsaturated secondary alcohols has been extensively studied [182] and has found several successful additional applications with substrates containing double bonds [183-188]. The results have been collected in Table 2 and Scheme 40, whereas Scheme 41 shows interesting examples of the resolution of hydroxy compounds that contain a triple bond in the molecule [189,190]. 

Various racemic secondary alcohols with different substituents, eg, a-hydroxyester (60), are resolved by PFL neady quantitatively (75). The effect of adjacent unsaturation on enzyme-catalyzed kinetic resolutions was thoroughly studied for a series of allylic (61), propargylic (62), and phenyl-substituted 2-alkanols (76,77). Excellent selectivity was observed for (E)-allylic alcohols whereas (Z)-isomers showed poor selectivity (76). 

A variety of unfunctionalized secondary alcohols, including saturated and unsaturated carbinols, are resolved by catalyst 25 with moderate to high selectivi-ties (fcrei=4 to >50, see Scheme 5) [25]. Octapeptide 25 was discovered by screening a split-pool library of peptide catalyst candidates for acylation of 1-phe-nylethanol (3), using a reactivity-based fluorescence screen [26], followed by structure optimization with directed libraries. While substrates with increased steric bulk about the alcohol are resolved with highest selectivities, even 2-butanol is resolved with modest selectivity (fcrei=4). Peptide-based catalysts have also been applied to the resolution of tertiary alcohols, a relatively unexplored area of nonenzymatic asymmetric acylation catalysis [27-29], By using a fluores-... 

Kinetic Resolution by Direct Esterification. This is the least common strategy for kinetic resolution and is most commonly executed on racemic alcohols with carboxylic acids in organic solvents. Reports include several alicyclic secondary alcohols such as menthol and various aliphatic secondary alcohols. Kinetic resolution of a variety of racemic saturated, unsaturated, and a-substituted carboxylic acids has also been effected by direct esterification with various alcohols. ... 

Dehydrogenative oxidation of secondary alcohols in the presence of acetone is the reverse process of transfer hydrogenation of ketones with 2-propanol [87b, 95b]. Kinetic resolution of racemic secondary alcohols is possible using this process with an appropriate chiral catalyst and suitable reaction conditions. As exemplified in Scheme 45, a variety of racemic aromatic or unsaturated alcohols can be effectively resolved in acetone with a diamine-based Ru(II) complex 42 or 50 [129]. Chiral alcohols with an excellent optical purity are recovered at about... 

Fu and co-workers have detailed the use of planar chiral DMAP and PPY analogs as catalysts for the resolution of secondary unsaturated alcohols (Fig. 1) [15]. Both ferrocene and ruthenocene-based catalysts have been examined, with the iron-based catalysts generally proving less reactive but more selective [16]. Catalysts are prepared in racemic form and are subsequently resolved by preparative chiral HPLC. 

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