Allenic racemization

Enantioselective chemistry see Enantioselectivity) has been also developed with imido complexes. The stereospecific reaction of rac-(ebthi)(thf)Zr=NAr with racemic symmetrically or unsymmetrically 1,3-disubstituted allenes (1,3-diphenylallene, 3,4-heptadiene, 4,5-nonadiene or 1,2-cyclononadiene) provides at room temperature a single diastereoisomeric azazirconacycle (equation 8). In certain cases, this system allows conversion of an allene racemate into a mixtme emiched in one enantiomer. 

S,3,)-(EBIH)Zr(=NAr)(THF)2 promotes highly enantioselective cycloaddition reactions with allenes and, in certain cases, this system allows conversion of an allene racemate into a mixture enriched in one enantiomer. Mechanistic studies about the enantioselective cycloaddition and stereoinversion of allenes mediated by imidozirconocenes have revealed that the initial [2 + 2]-cycloaddition to form the azazirconacyclobutane is stereospecific and is not involved in the racemization process.728 The reactive zirconocene imido precursor r -(EBIH)Zr(NHBut)(Me) 958 has been shown to activate a variety of hydrocarbons R-H with primary alkyl, alkenyl, and aryl G-H bonds to form the corresponding alkyl derivative r -(EBIH)Zr(NHBut)(R) 959 with concomitant elimination of methane729 (Scheme 240). Mechanistic experiments support the proposal of intramolecular elimination of methane followed by hydrocarbon G-H addition. 

As typical examples of crystal-to-crystal thermal reactions, the cyclization of allene derivatives to four-membered ring compounds and the transformation of a racemic complex into a conglomerate complex are described. 

Scheme 5. Proposed biosynthesis of allene oxide 64 from 8i -lipoxygenase initiated metabolism of arachidonic acid and subsequent non-enzymatic transformations to racemic cyclopenteone 30 [86]...

A reasonable route for the formation of this racemic cyclopentenone (30) was proposed from 8.R-HPETE (29), which involves the non-enzymatic hydrolysis of an allene oxide (64) intermediate (Scheme 5 ) [86]. Biochemical precedence for these transformations was provided by earlier work with plants [90] and C. 

At the CASSCF(8,8)/6-31G level, 1 A"-4b is predicted to be a transition state for the enantiomerization of 3b. The CASPT2 calculated barrier for this process is ca. 21 kcal/mol (Fig. 12). This predicted value for the barrier to enantiomerization of 3b is essentially the same as that calculated for the racemization of 3a,55,57 which, as already noted, is approximately half of the experimental value of ca. 42 kcal/mol for racemization of allene.73... 

Initial attempts to perform the 1,5-substitution enantioselectively with chiral enyne acetates proceeded disappointingly. For example, treatment of the enantio-merically pure substrate 51 with the cyano-Gilman cuprate tBu2CuLi LiCN at -90 °C provided vinylallene 52 as a 1 3 mixture of E and Z isomers with 20 and 74% ee, respectively (Scheme 2.19) [28], As previously described for the corresponding Sn2 substitution of propargylic electrophiles, this unsatisfactory stereoselection may be attributed to a racemization of the allene by the cuprate or other organome-... 

Spino and Frechette reported the synthesis of non-racemic allenic alcohol 168 by a combination of Shi s asymmetric epoxidation of 166 and its organocopper-mediat-ed ring-opening reaction (Scheme 4.43) [74]. Reduction of the ethynyl epoxide 169 with DIBAL-H stereoselectively gave the allenic alcohol 170, which was converted to mimulaxanthin 171 (Scheme 4.44) [75] (cf. Section 18.2.2). The DIBAL-H reduction was also applied in the conversion of 173 to the allene 174, which was a synthetic intermediate for peridinine 175 (Scheme 4.45) [76], The SN2 reduction of ethynyl epoxide 176 with DIBAL-H gave 177 (Scheme 4.46) [77]. 

The enantioselective synthesis of an allenic ester using chiral proton sources was performed by dynamic kinetic protonation of racemic allenylsamarium(III) species 237 and 238, which were derived from propargylic phosphate 236 by the metalation (Scheme 4.61) [97]. Protonation with (R,R)-(+)-hydrobcnzoin and R-(-)-pantolactone provided an allenic ester 239 with high enantiomeric purity. The selective protonation with (R,R)-(+)-hydrobenzoin giving R-(-)-allcnic ester 239 is in agreement with the... 

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 kinetic resolution using a chiral zirconocene-imido complex 286 took place with high enantioselectivity to result in chiral allenes 287 (up to 98% ee) (Scheme 4.74) [116]. However, a potential drawback of these methods is irreversible consumption of half of the allene even if complete recovery of the desired enantiomer is possible. Dynamic kinetic resolutions avoid this disadvantage in the enantiomer-differentiating reactions. Node et al. transformed a di-(-)-L-menthyl ester of racemic allene-l,3-dicarboxylate [(S)- and (RJ-288] to the corresponding chiral allene dicarbox-ylate (R)-288 by an epimerization-crystallization method with the assistance of a catalytic amount of Et3N (Scheme 4.75) [117]. 

Chiral Lewis acids are also applicable in the deracemization of racemic allene dicarboxylates 289. Treatment of dimethylallene-l,3-dicarboxylate 289 with a chiral organoeuropium reagent, (+)-Eu(hfc)3, gave the corresponding optically active allene in 79% ee (Scheme 4.76) [118]. Unfortunately the chiral allene could not be isolated from the reaction mixture without loss of its optical purity. 

For other pioneering work including the synthesis of racemic or achiral allenes, see ... 

The allene moiety of the products 70b, 72 and 75 is in each case chiral and, furthermore, an additional chiral center is created in 72a,b and 75b,e-g, thereby leading to the possible formation of diastereomers. However, the concerted nature of such sigmatropic processes should result in suprafacial migrations and formation of the racemate of only one diastereomer in each case, as shown for 74 — 75 in Scheme 7.10. High stereoselectivity can really be found for the reaction of (fc)-71a and 74b,e,f, but not for other examples of type 71 and for 74g, which lead to mixtures of diastereomers. 

Based on nucleophilic addition, racemic allenyl sulfones were partially resolved by reaction with a deficiency of optically active primary or secondary amines [243]. The reversible nucleophilic addition of tertiary amines or phosphanes to acceptor-substituted allenes can lead to the inversion of the configuration of chiral allenes. For example, an optically active diester 177 with achiral groups R can undergo a racemization (Scheme 7.29). A 4 5 mixture of (M)- and (P)-177 with R = (-)-l-menthyl, obtained through synthesis of the allene from dimenthyl 1,3-acetonedicar-boxylate (cf. Scheme 7.18) [159], furnishes (M)-177 in high diastereomeric purity in 90% yield after repeated crystallization from pentane in the presence of catalytic amounts of triethylamine [158], Another example of a highly elegant epimerization of an optically active allene based on reversible nucleophilic addition was published by Marshall and Liao, who were successful in the transformation 179 — 180 [35], Recently, Lu et al. published a very informative review on the reactions of electron-deficient allenes under phosphane catalysis [244]. 

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