Propargylic alcohols, kinetic resolution

Tao B, Ruble JC, Hole DA, Fu GC (1999) Nonenzymatic kinetic resolution of propargylic alcohols by a planar-chiral DMAP Derivative crystallographic characterization of the acylated catalyst. J Am Chem Soc 121 5091-5092... 

Benzotetramisole 213 has been identified as an effective catalyst for kinetic resolution of sec-benzylic and propargylic alcohols 214 to give 215 in excellent enantioselectivity O60L1351 06OL4859>. The benzotetramisole-catalyzed kinetic resolution has been extended to 2-oxazolidinone 217 via enantioselective /V-acylation <06JA6536>. 

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. 

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). 

As summarized in Schemes 12.9 and 12.10, kinetic resolution of propargylic [21] and allylic [22] alcohols work equally well. The DMAP-ferrocene hybrid 21c was also used for kinetic resolution of racemic diols and for the desymmetrization of meso diols [20]. These two applications are discussed in Section 13.3. 

Resolution by transesterification. Using vinylic acetates to esterify allyl alcohols, propargyl alcohols, 2-phenylthiocycloalkanols, a-hydroxy esters," methyl 5-hydroxy-2-hexenoates, and 2-substituted 1,3-propanediols, the enantioselective esterification provides a means of separation of optical isomers. Vinyl carbonates are also resolved by lipase-mediated enantioselective conversion to benzyl carbonates. Other esters that have also been used in the kinetic resolution include 2,2,2-tri-fluoroethyl propionate. There is a report on a double enantioselective transesterification" of racemic trifluoroethyl esters and cyclic meso-diols by lipase catalysis. 

The ophcally active Pd complex with a chiral allenyl ligand undergoes epimer-izahon in the presence of a catalytic amount of Pd(0) complex. This reaction does not involve the isomerization to the propargyl complex, but takes place via a dinuclear intermediate as depicted in Scheme 5.39. The -allenyl ligand in the dinuclear palladium intermediate may racemize via a vinyl-vinyidene intermediate. This type of reaction is prohahly involved in a kinetic resolution of racemic propargyl alcohols promoted hy chiral transihon metal complex [203]. The intermolecular allyl ligand transfer from Pd to Ee complexes occurs under... 

Tanaka et al. developed a Rh-catalyzed asymmetric one-pot transesterification and [2+2+2] cyclotrimerization using nonracemic ligand 415 in the synthesis of enantio-enriched 3,3-disubstituted phthalides (R R ) (Scheme 2-39)P The chiral Rh complex with 415 efficiently desymmetrized dipropargyl alcohols 413 (R = R -OC-) in the reaction with 412 to give phthalides 414 (R = R -C=C-) in up to 87% yield and 93% ee. Also, the kinetic resolution of racemic tertiary propargylic alcohols... 

The greatest advantage of this approach is the circumvention of the use of optically active tertiary propargylic alcohols. The chiral Rh complex could efficiently desymmetrize the achiral alcohol to give the 3,3-disubstituted phthalides products in up to 87% isolated yield and 93% ee. The kinetic resolution of racemic tertiary propargylic alcohols provided disubstituted phthalides with up to 89% 3deld and up to 93% ee. 

Scheme 41.4 Kinetic resolution of propargylic alcohols by Birman et al...

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