Asymmetric elimination

A very interesting approach to chiral a unsaturated sulfoxides 39 based on a kinetic resolution was elaborated by Marchese (69), who found that asymmetric elimination of racemic j3-halogenosul-foxides 40 takes place in the presence of chiral tertiary amines. 

Asymmetric elimination with high induction has mainly been described for epoxides, halides and alcohols (using chiral bases), for chiral ketals (using achiral Lewis acids), and for chiral sulfoximines (using achiral bases)1 3. For each compound class only a few examples have been examined, thus, the scope of these methods has not yet been fully explored. The literature on asymmetric eliminations up to 1970 has been covered in a review article4. 

Asymmetric eliminations of mew-configurated epoxides to give chiral allyl alcohols may most successfully be achieved using the chiral lithium amides which are also successful for the asymmetric deprotonation of ketones (see previous section). Problems in interpretation of asymmetric induction are also similar to those found in deprotonation of the ketones finding the optimal chiral lithium amide and reaction parameters remains largely empirical. 

Asymmetric elimination of cis-A,5-epoxyoctane and cis-2,3-epoxybutane to the corresponding allyl alcohols with various chiral lithium amides proceeds only in moderate yield and enanliose-... 

Of the synthetically more useful substrates studied in such asymmetric eliminations, protected cis- and frans-3,4-epoxycyclopentanol are converted in excellent yield and with modest to high enantioselectivity to (lS /O-l -dihydroxycyclopentene derivatives, which are useful intermediates in the synthesis of prostaglandins66 (Tables 6 and 7)42 44 66a. 

Asymmetric elimination in epoxycyclopentenones bearing a chiral ketal group 1 with achiral lithium amides to give hydroxycyclopentenones has been examined due to the utility of the latter in prostaglandin synthesis67. When lithium diethylamide in diethyl ether and (3S, 5S )-2,6-dimeth-yl-3,5-heptanediol as chiral auxiliary are used, the diastereomeric cyclopentenol derivatives 2 are obtained in a ratio of 87.7 12.3 in 80 % yield. The absolute configuration is based on chemical correlation and the diastereomeric ratio on GC analysis. No further examples are reported. 

Asymmetric elimination of bicyclic wc.vr>-epoxides 3 to give the corresponding allyl alcohols (/ )-4 can be achieved in moderate yield and enantioselectivity by using vitamin B12, which is, in situ, reduced to catalytically active vitamin B12s [cob(I)alamin] with zinc in methanol68-70. This reaction fails for 1,2-epoxycyclooctane and also for monocyclic epoxides, e.g., 2,3-dimethyIoxi-rane gives (/ )-3-buten-2-ol in 57% yield but with low enantiomeric excess (26%)68-70. 

The bicyclo[3.3.0]octene skeleton is of interest due to its potential use as an intermediate in the synthesis of cyclopentanoid natural and nonnatural compounds. The bicyclo[3.3.0]octene skeleton can be prepared by asymmetric elimination of the corresponding alcohols on treatment with a variety of chiral amines80, S1. Bicyclic trifluoromethanesulfonales 1 on treatment with (5)-Ar,Ar-dimethyl-l-phenylethylaminc give the corresponding bicyclo[3.3.0]octenes 2 with 15,5/ -configuration with up to 89% enantiomeric excess in high yield. 

Asymmetric elimination in the -hydroxy sulfoximine of bicyclo[3.3.0]octane-2,5-dione monoethylene ketal 3, which is obtained in high yield and diastereoselectivity by addition of (S)-.S -lithiomethyl-A -methyl-S-phenylsulfoximine7, 72 to the latter, by sequential treatment with chlorotrimethylsilane and butyllithium, gives the diastereomeric alkenylsulfoximines (S1)-( )- and (Sy(Z)-4 in a ratio 98 273. 

Construction of an orbital correlation diagram (7) discloses that concerted cis elimination of R-R from ci -ML4RR is not forbidden by symmetry considerations thus, there appears to be no advantage for the asymmetric elimination... 

Axially chiral vinyl sulfoximines have been prepared with high diastereoselec-tivity (> 99 1) by asymmetric elimination of LiOSiMe3 from 3-siloxy sulfoximines.72 For example, addition of lithiated (+)-(S)-2a to ketone 94 gave the (3-hydroxy sulfoximines 95 with a 99 1 diastereoselectivity. When the dianion of 95 was quenched at -78 °C with chlorotrimethylsilane, the vinyl sulfoximine 97 was... 

In the presence of a Rh catalyst and a chiral BINAP, 3-(2-hydroxyphenyl)cyclobutanones 46 undergo a cascade reaction in which addition to the carbonyl group is followed by opening of the cyclobutane ring with asymmetric elimination of the p-carbon. The final product is a 3,4-dihydrocoumarin obtained in high yield and excellent ee <07JA12086>. 

The asymmetric elimination has so far generally been carried out by enan-tioselective deprotonation using chiral bases [15]. Therefore, if an elimination from optically active selenoxides gave optically active alkenes, the reaction may provide a new methodology for asymmetric elimination to form a carbon-carbon double bond under mild conditions. A few examples of asymmetric selenoxide elimination are described below. 

Z)-2-butenylene dicarbonate with dimethyl malonate gives a low yield (20—40%) of 2-vinylcyclopropane-l,l-dicarboxylate with up to 70% ee (Scheme 2-38) [54], Reaction with methyl acetoacetate or acetylacetone takes place in a different manner to give a dihydrofuran derivative (59% ee), which results from nucleophilic attack of enolate oxygen at the cyclization step, (c) Asymmetric elimination of an acetyl-acetate ester gives (R)-4-rerr-butyl-l-vinylcyclohexene of up to 44% ee (Scheme 2-39) [55]. (d) Palladium-catalyzed allylic silylation is also applied to asymmetric synthesis... 

Synthetic applications of the elimination of allylic carbonates have been reported by other groups,including steps in the synthesis of diterpenoid forskolint ° and triterpenoid azadirachtinP Asymmetric eliminations have been exploredP ... 

By using the same lithium salt (S)-201, asymmetric elimination to give 205 with high diastereotopic differentiation without loss of chirality was reported [15] (Scheme 7.32). This asymmetric carbonyl olefination allowed the selective synthesis of both the (Z)- and ( )-alkenylsulfoximides 208 and 210, which are useful... 

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