Enantioselectivity allylic elimination

Zirconium-Catalyzed Enantioselective Carbomagnesation-Elimination Tandem Reaction of Allylic Derivatives... 

Zireonitun-Catalyzed Enantioselective Carboalomination-Elimination Ihiidem Reaction Allylic Derivatives and Its Application to Kinetic Resolution... 

Reaction of allylic silanes with enantiomerically pure 1,3-dioxanes has been found to proceed with moderate enantioselectivity.104 The homoallylic alcohol can be liberated by oxidation followed by base-catalyzed (3-elimination. The alcohols obtained in this way are formed in 70 5% e.e. 

Although the asymmetric isomerization of allylamines has been successfully accomplished by the use of a cationic rhodium(l)/BINAP complex, the corresponding reaction starting from allylic alcohols has had a limited success. In principle, the enantioselective isomerization of allylic alcohols to optically active aldehydes is more advantageous because of its high atom economy, which can eliminate the hydrolysis step of the corresponding enamines obtained by the isomerization of allylamines (Scheme 26). 

Allylic substitution using hard nucleophiles proceeds through a different mechanism. Instead of attacking the allyl group of the 71 allyl-metal complex, hard nucleophiles attack the metal first and the product is subsequently formed by reductive elimination. Nickel(O) complexes have often been used for this purpose. Reports of good enantioselectivities in this type of reaction are limited. 

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. 

In view of the Zr-catalyzed enantioslective carbomagnesation-elimination tandem reaction of allylic derivatives discussed earlier, a similar process with EtjAl might be expected and has indeed been developed recently [29]. As a representative example, the reaction of 2,5-dihydro-furan with 3 equiv. of Et3Al in the presence of (i )-(EBTHI)Zr[B[NOL-(5)] (8) and (NMTHI)ZrCpCl2 (9) produced, after hydrolysis, (S)-2-ethyl-3-buten-1 -ol in 90 and 67% yields, respectively. The enantioselectivity observed with 8 was >99% ee, whereas that observed with 9 was 85-90% ee. Upon deuterolysis of the organoaluminum products, a mixture of monodeuterated and nondeuterated products was obtained and the extent of D incorporation increased to 94% with neat Et3Al without any solvent. The results indicate that the reaction must produce two organoaluminum products, 10 and 11 (Scheme 4.18). On oxidation with 02 only... 

Recent results indicate that Zr-catalyzed enantioselective ethylmctallation of allyl derivatives not accompanied by -elimination is feasible witb various allylamines, allyl sulfides, and even with allyl alcohol [29,36] (Table 4.5). Although both chemical yields and enantioselectivity are still generally modest, the following favorable examples appear to indicate that further improvements may be expected. In some cases (NMTHI)ZrCpCl2 (9) of C( symmetry and smaller overall steric requirements provide distinct advantages over sterically more demanding C2-symmetric complexes, such as 1, 3, and 8. 

Distinction between enantiodiscrimination by complexation and by alkylation of equilibrating intermediates is less clear in a number of related cases. It is likely that more than one type of chiral discrimination may be involved. For example, when a conformational ly flexible four-membered ring substrate is used for the same reaction, the enantioselectivity was only 56% ee (Eq. 8E.15) [175]. In this case, it has been proposed that equilibration via a tertiary e-palladium species may be possible, switching the origin of enantio-discrimination to the alkylation step. A more contrasting example involves the formation of an asymmetric diene via selective P-elimination of similar diastereomeric Jt-allyl intermediates (Eq. 8E.16). Evidence suggests that the enantio-determining elimination process occurs after the equilibration of the 7t-allyl intermediates [176]. 

The desymmetrization of meso-e poxides such as cyclohexene epoxide (55, Scheme 13.27) has been achieved both by enantioselective isomerization, e.g. to allylic alcohols (56, path A, Scheme 13.27) or by enantiotopos-differentiating opening by nucleophiles, affording trans-/ -substituted alcohols and derivatives (57, path B, Scheme 13.27). As indicated in Scheme 13.27, the allylic alcohols 56 can also be prepared from the ring-opening products 57 by subsequent elimination of the nucleophile. 

In their search for suitable synthetic applications of their methodology, Shibasaki and coworkers spared no efforts and carried out an 18-step synthesis of lactone 35, which represents an early intermediate of Danichefsky s synthesis of (-i-)-vernolepin (Scheme 10) [14]. First, the ester 31 is transformed via 32 into the allylic alcohol 33, which is then cyclized with good enantioselectivities to yield the enone 34 (which is initially formed as an enol by /i-H-elimination). 

An enantioselective method for the synthesis of 3-functionalized 2,3-dihydrobenzofuran derivatives via an intramolecular carbolithiation reaction of allyl 2-lithioaryl ethers uses (—)-sparteine as a chiral inductor. A variety of electrophiles can be reacted with the cyclized organolithium intermediate. With certain substrates, however, /3-elimination occurs instead (Equation 140) <2005CEJ5397>. 

A number of useful enantioselective syntheses can be performed by attaching a chiral auxihary group to the selenium atom of an appropriate reagent. Examples of such chiral auxiliaries include (49-53). Most of the asymmetric selenium reactions reported to date have involved inter- or intramolecular electrophilic additions to alkenes (i.e. enantioselective variations of processes such as shown in equations (23) and (15), respectively) but others include the desymmefrization of epoxides by ringopening with chiral selenolates, asymmetric selenoxide eliminations to afford chiral allenes or cyclohexenes, and the enantioselective formation of allylic alcohols by [2,3]sigmafropic rearrangement of allylic selenoxides or related species. 

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