Elimination enantioselective epoxidation

Other Enantioselective Reactions. Enantioselective epoxide elimination by chiral bases has been demonstrated. More recently, the enantioselective [2,3]-Wittig rearrangement of a 13-membered propargylic ally lie ether has been performed using the lithium amide of (f ,f )-(l) as the base for deprotonation (eq 15). For this particular substrate, THF is a better solvent than ether, although pentane produces better results in a related transformation (eq 16). In fact, a change in solvent in this type of reaction has been shown to lead to a reversal of the stereoselectivity of the transformation. ... 

Astonishingly enough, enantioenriched lithiated cyclooctene oxides 142, originating from (—)-sparteine-mediated lithiation of 124 by i-BuLi/(—)-sparteine (11), could be trapped by external electrophiles, resulting in substituted epoxides 143 (equation 31) ° . Again, the use of i-PrLi furnished better enantioselectivities (approx. 90 10). Lithiated epoxides, derived from tetrahydrofurans and A-Boc-pyrrolidines, undergo an interesting elimination reaction . ... 

Discrepancies in the enantioselectivity reported for the same lithium amide and reaction conditions may be due to different enantiomeric purity of the lithium amides (Table 6, entries 1 -3,4-6 and 7-9 and Table 7, entries 3-5) . Interestingly, for the elimination of the cw-epoxides enantioselectivity is higher in benzene than in tetrahydrofuran (Table 6, entries 1 and 3.12 and 13 and 14 and 15) whereas for that of the trans-epoxide the situation is reversed (Tabic 7, entries 2 and 6). The enantioselectivity of the elimination of the /rans-epoxide can be raised significantly through addition of DBU (Table 7, entries 6 and 7). 

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 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. 

It should be noted that addition of DBU (or HMPT) has often - particularly for the catalytic procedures - proven beneficial in terms of enantioselectivity. This effect has been attributed to the breaking-up of active but less enantioselective base aggregates [50, 56, 62-64]. Interestingly, when solid-phase-bound stoichiometric (achiral) bases were used instead of LDA, no addition of DBU was necessary [58, 59]. (An example of the stoichiometric use of a chiral solid-phase bound base is given elsewhere [52].) Both experimental and theoretical investigations [66-68] indicate that the base-induced isomerization of epoxides proceeds as a syn elimination, with the lithium ion of the base acting as a Lewis acid (Scheme 13.31). 

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. 

Ring-opening of epoxides by P-elimination, on reaction with strong bases, such as lithium amides, or combinations of trimethylsilyl triflate with diazabicycloundecane, ° is a useful synthetic method to prepare allylic alcohols, particularly as it can be carried out enantioselectively. ... 

Epoxide 303 has been used an an enantioselective synthesis of the methylenecyclopropa-neacetic acid (514a) portion of (methylenecyclopropyl)acetyl-CoA (514b), a mammalian metabolite of hypoglycines A and B. Addition of the anion derived from phenyl 2-(tri-methylsilyl)ethyl sulfone to 303 produces a 3 1 mixture of threo and erythro diastereomers 509. Either diastereomer cyclizes to the same cyclopropane 511 upon treatment with LDA, which suggests that epimerization at C-5 must be occurring prior to cyclization. Selective removal of the TBPS group followed by oxidation of the alcohol to an acid and elimination affords the desired product 514a (Scheme 73) [126,127]. 

In the above case no P-elimination can occur. Reversibility observed during the a-deprotonation of such an epoxide with a lithium amide (vide supra) might result in lowering the ee when using a chiral lithium amide, since reversible deprotonation could compromise the kinetic control in enantioselective deprotonation. Nevertheless deprotonation of exo-norbornene oxide 91 with lithiiun (S,S)-bis(l-phenyl)ethylamide 11 [Eq. (7)] gave tricyclanol 92 in good yield (73%) and moderate ee (49%) (Scheme 16). When the rearrangement of exo-norbornene oxide 91 is carried out with s-BuLi in pentane from -78°C to room... 

A new thiophen synthesis is based on deprotonation and cyclization of the resultant carbanion (65) of a keten dimethylthioacetal. Other applications of cr-(phenylthio)- or cr-(alkylthio)-alkyl-lithiums include preparations of disparlure (the sex pheromone of the gypsy moth) and other chiral epoxides,of an anti-peptic-ulcer diterpene from Croton sublyratus, of carbene-thiometal chelates through reaction with fCr(CO)gl or fW(CO)jl, of olefins via )ff-hydroxy-sulphides, and of Michael adducts of enones. In other work, the chiral solvent l,4-dimethylamino-2,3-dimethoxybutane is employed in enantioselective addition reactions of cr-thio-carbanions with ketones and Michael acceptors. a,P -Elimination of cr-thio-carbanions such as (66) provides a useful synthesis of olefins, and a 2-(lithiomethylthio)-A -oxazoline (67) has been used to prepare a C-labelled thiiran for a microwave study of the valence tautomerism of allene episulphide. ... 

In addition to asymmetric deprotonation. Cope observed that cyclic epoxides in the presence of base give rise to products derived from transannular reactions [110], Boeckman carried out a study of oxiranes fused to medium-size rings and noted that the more commonly observed deprotonation of oxiranes can be suppressed at low temperature, permitting the formation of bi-cyclic structures [118]. In such cases, a-lithiation of an epoxide followed by 1,1-elimination generates a carbene that participates in a subsequent CH-insertion process (cf. 131). An enantioselective version of this reaction was investigated by Hodgson (Scheme 9.15) [119]. Thus, in the presence of sparteine (130), treatment of cyclooctene oxide 129 with i-PrLi affords bicyclic alcohol 132 in 84% ee. 

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