Resolution of allenes

Like the resolution of allenes, the separate existence of cis and trans isomers of cumulated trienes was not verified until many years after van t Hoff s original predictions, but a separation finally was achieved, in 1954, by R. Kuhn and K. Scholler for compounds 3 and 4 ... 

Resolution of allenic sulfanes. The allenic sulfone buta-l,2-dienyl /i-tolyl sulfone, CHgC6H4S02CH=C=CHCH3, can be resolved to the extent of 70% by treatment with 0.5 equiv. of (R)-a-phenylethylamine, ao +40°, in ether at 25°. The recovered sulfone is optically active. ... 

An alternative means of resolution depends on the differences in rates of reactions of enantiomers with a chiral reagent. The transition state energies for reaction of one chiral molecule with another can be different for each enantiomer. If a racemic mixture R molecule -h 5 molecule) reacts with an optically active reagent (R reagent), the two transition states R molecule / reagent) and (5 molecule i reagent) bear a diastereomeric relationship to each other. Kinetic resolution is the term used to describe the separation of enantiomers by selective reaction with an optically active reagent. A very useful application of this technique is the resolution of allenes by preferential reaction of one enantiomer with an optically active borane. Hydroboration of the allenes occurs at different rates, and the reaction mixture becomes enriched in the less reactive enantiomer. An allene that has been partially resolved by this technique was presented as an example of an axially dissymmetric molecule in Scheme 2.1 68 entry 2,1,3-dimethylallene). ... 

Long before chiral allenes were known (Problem 9.72), the resolution of 4-methylcyclohexylideneacetic acid into two enantiomers had been carried out. Why is it chiral What geometric similarity does it have to allenes ... 

A3. Allen, S., and Muirhead, H Refined three-dimensional structure of cat-muscle (Ml) pyruvate kinase at a resolution of 2.6 A. Acta Crystallogr., Sect. D Biol. Crystallogr. D52, 499-504 (1996). 

Resolution of a racemic mixture is still a valuable method involving fractional crystallization [113], chiral stationary phase column chromatography [114] and kinetic resolutions. Katsuki and co-workers demonstrated the kinetic resolution of racemic allenes by way of enantiomer-differentiating catalytic oxidation (Scheme 4.73) [115]. Treatment of racemic allenes 283 with 1 equiv. of PhIO and 2 mol% of a chiral (sale-n)manganese(III) complex 284 in the presence of 4-phenylpyridine N-oxide resulted... 

Scheme 4.73 Kinetic resolution of racemic allenes 283 by enantiomer-differentiating oxidation.

The chiral furan 120, prepared from 119, underwent a Diels-Alder reaction with racemic 110b (4equiv.) at -100 °C. Kinetic resolution of the allenic diester efficiently occurred to afford the oxabicydic enamine adduct 121 stereoselectively [100], The adduct was transformed to (+)-cydophellitol. 

Tius and co-workers elegantly applied a variant of the Nazarov reaction to the preparation of cyclopentenone prostaglandins (Scheme 19.39) [46]. Moreover, it was demonstrated that the chirality of non-racemic allenes is transferred to an sp3-hybridized carbon atom. Preparation of allenic morpholinoamide 214 and resolution of the enantiomers by chiral HPLC provided (-)- and (+)-214. Compound (-)-214 was exposed to the vinyllithium species 215 to afford a presumed intermediate which was not observed but spontaneously cyclized to give (+)- and (—)-216 as a 5 1 mixture. Compound (+)-216 was obtained with an 84% transfer of chiral information and (-)-216 was obtained in 64% ee. The lower enantiomeric excess of (—)-216 indicates that some Z to E isomerization took place. This was validated by the conversion of 216 to 217, where the absolute configuration was established. The stereochemical outcome of this reaction has been explained by conrotatory cyclization of 218 in which the distal group on the allene rotates away from the alkene to give 216. 

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 induced diastereoselectivity is determined by the chiral sulfinyl moiety of the substrate and not by the menthyl chirality, since a similar but opposed d.r. is obtained in sulfoxide 1 (and ee in the oxidized allenylsulfone 2) when the (-)-menthyl (S/ )-sulfinate is used rather than the ( — )-menthyl (SS)-sulfinate. The induced diastereoselectivity is fair to good, as deduced from the optical purity of the sulfones 2, however, inadvertent resolution of the diastereomers during the chromatographic separation of the allenic and acetylenic sulfoxides may have affected the figures. 

In practice, oxidations of this type have been observed and generally have been carried out with a substrate bearing a racemic secondary alcohol so that kinetic resolution is achieved. Although these oxidations are not strictly within the scope of this chapter, they are summarized briefly in Eqs. 6A.7-6A.9 to acquaint the reader with other potential uses for the Ti-tartrate catalytic complex. In the kinetic resolutions shown in Eqs. 6A.7 and 6A.8, the oxidations are controlled by limiting the amount of oxidant used to 0.6 equiv. Only modest resolution was attained for the acetylenic alcohol (Eq. 6A.7, 21% ee) [77] and the allenic alcohol (Eq. 6A.8, 40% ee) [77]. Resolutions of the furanols [142] or the thiophene alcohols [143] of Eq. 6A.9 generally are excellent (90-98% ee except when Rj is a I-butyl group). Only in the kinetic resolution of the furanols has the oxidation product been identified and, in that case, is a dihydropyranone. 

A 1,3-substituted allene, which has axial chirality instead of carbon central chirality, has been prepared by a palladium-catalyzed cross-coupling of 4,4-dimethylpenta-l,2-dienylzinc chloride (83) with phenyl iodide (5c) or by that of l-bromo-4,4-dimethylpenta- 1,2-diene (84) with phenylzinc chloride [60] (Scheme 8F.20). The highest enantiomeric purity (25% ee) of the allene (S)-85 was obtained in the former combination with (f ,/ )-diop (1) as chiral ligand. It is interesting that the enantiomeric purity was independent of the ratio of the reagents though the reaction seems to involve a kinetic resolution of the racemic 83. 

Subsequently, Grunthaner reexamined the ESCA spectrum of the 2-norbornyl cation on a higher-resolution X-ray photoelectron spectrometer using highly efficient vacuum techniques.884 The spectrum closely matches the previously published spectra. Furthermore, the reported ESCA spectral results are consistent with the theoretical studies of Allen and co-workers885 on the classical and nonclassical norbomyl cation at the STO-3G and STO-4.31G levels. Using the parameters obtained by Allen and co-workers, Clark and co-workers were able to carry out a detailed... 

Australian Penicillium striatisporum strain (Fig. 5) [68]. Before, neither a synthetic approach, nor the absolute configuration of this butenolide had been reported. Combining the enzymatic kinetic resolution with a palladium(II)-mediated racemization [69] could lead to a highly efficient dynamic kinetic resolution (DKR) of allenes. 

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

Carballeira JD, Krumlinde P et al (2007) Directed evolution and axial chirality optimization of the enantioselectivity of Pseudomonas aeruginosa lipase towards the kinetic resolution of a racemic allene. Chem Commun 43 1913-1915... 

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... 

Allenes, another class of compounds having interesting properties, have been also resolved by lipases, the kinetic resolution of a variety of racemic 1 -ethenyl and ethynyl-substituted 2,3-allenols was reported using a lipase from Candida antarctica type B (CAL-B) with vinyl acetate as acyl donors in organic solvent. The biocatalytic resolution afforded (S)-2,3-allenols (S)-98 and (i )-2,3-allenyl acetates (R)-99 in chemical yields up to 55% and an enantiomeric excess ee up to 99% for both enantiomers depending on the substituents.91... 

The separation of racemic mixture is the most difficult process and involves several steps. The selective hydroboration sequence provides a convenient procedure 199 200 for the resolution of 1,3-disubstituted allenes, while the process is tedious and lengthy by other methods201. Thus, the treatment of ( + )-1,3-dimethyl allene with 50 mol percent of (+)-IPC2BH provided unreacted (R)-(-)-l,3-dimethylallene (Eq. 128). The configuration of allenes is consistently R when resolved by ( + )-IPC2BH. As both forms of IPC2BH are available, it should be possible to obtain the allenes of opposite configuration. 

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