Epoxides disubstituted

Scheme 14. Resolution of a czs-2,3-disubstituted epoxide and synthesis of (+)-disparlure...

The reactions of 2,3-disubstituted epoxides with hydroxylamines and hydroxamates tend to proceed more slowly, giving variable yields of ring-opening products. Catalysis with chiral Lewis acids 20 was reported to allow asymmetric opening of me o-epoxide 19 in a good yield and (equation 13). 

Heterogenous metal tartrates were screened for their efficacy in the catalysis of the asymmetric ring opening of me o-2,3-disubstituted epoxides with thiols, aniline, and trimethylsilyl azide [72]. Whereas the enantioselectivity of Zn(II) tartrates is in the 15-85 % ee range, selectivity with the Mn(II), Fe(II), and Co(II) tartrates was lower (< 40 % ee). With Nugent s Zr(Of-Bu)4/C3-symmetric tetradentate ligand catalyst... 

Carbonylation. The title reagent (as THF complex) mediates carbonylation of monosuhstituted and 2,3-disubstituted epoxides to give succinic anhydrides (22 examples, 90-99% conversion). 

Bacterial enzymes (in particular derived from Actinomycetes such as Rhodococ-cus and Nocardia sp.) are the catalysts of choice for more highly substituted 2,2- and 2,3-disubstituted epoxides. 

Table 2.3 Microbial resolution of 2,3-disubstituted epoxides (for substrate structures see Scheme 2.91)...

Jacobsen also showed that 2,2-disubstituted epoxides underwent kinetic resolution catalyzed by (salen)Cr-N3 complex 3 under conditions virtually identical to those employed with monosubstituted epoxides (Scheme 7.34) [64]. Several epoxides in this difficult substrate class were obtained with high ees and in good yields, as were the associated ring-opened products. The kinetic resolution of TBS-... 

Figure 6.71 Enantioconvergent hydrolysis of a 2,2-disubstituted epoxide by combined bio- and chemocatalysts.

When gem-disubstituted epoxides (122) are treated with Grignard reagents (and sometimes other epoxides), the product may be 123, that is, the new alkyl group may appear on the same carbon as the OH. In such cases, the epoxide is isomerized to an aldehyde or a ketone before reacting with the Grignard reagent. Halohydrins are often side products. 

While alkylation of terminal epoxides is reliable, attempted alkylations of 1,2-disubstituted epoxides have proved capricious. An unsuccessful approach to the swinholides, which called for the alkylation of cyanohydrin 47 with epoxide 48, is one such example. In the event, alkylation cleanly produced imidate 49, rather than the expected product 50 [27] (Eq. 14). 

Under some circumstances, acid-catalyzed ring opening of 2,2-disubstituted epoxides by sulfuric acid in dioxane goes with high inversion at the tertiary center.116... 

An additional example of an oxonium ion generated via the acid catalyzed rearrangement has been used to prepare a dihydropyran <06TL6149>. The oxonium ion 54 generated by the reaction of an epoxide with ZrCl4 can be trapped by a nucleophile such as butynol to prepare dihydropyran 55. A variety of mono- and disubstituted epoxides have been used in this reaction. 

For 1,2-disubstituted epoxides, the regiochemical outcome of nucleophilic attack becomes less predictable. However, in the case of epoxy ethers chelation control can be used to deliver the nucleophile preferentially to the epoxide carbon away from the ether moiety. Thus, treatment of epoxy ether 61 with an imido(halo)metal complex, such as [Cr(N-t-Bu)Cl3(dme)], leads to the clean and high-yielding production of the chlorohydrin 64. The regioselectivity is rationalized in terms of initial formation of a chelated species (62), followed by attack at C-3 to form the more stable 5-membered metallacyclic alkoxide 63 <00SL677>. 

Experimentally, the reactions of 1,1-disubstituted epoxides were not studied to address these issues because the predicted differences in selectivity... 

The table, which collects representative examples, shows that monosubstituted epoxides afford homoaUyhc alcohols resulting from the attack to the less substituted carbon atom (runs 1, 5 and 7). HomoaUyhc alcohols are useful intermediates in several important total synthesis." Disubstituted epoxides fail to react (run 4). Styrene oxide leads to a mixture of homoaUyhc alcohols (run 2) and ally lie epoxides give mixture of 1,2- and 1,4-opening product, with predominance of the 1,4 product (run 3, 6 and 8). 

A catalytic amount of ketone 26 was used to investigate the substrate scope of the asymmetric epoxidation. High enantioselectivities can be obtained for a wide variety of trans- and trisubstituted olefins (Table 3, entries 1 ) [54]. Simple trans-olefins, such as franx-7-tetradecene, can be epoxidized in high yield and enantiomeric excess, indicating that this asymmetric epoxidation is generally suitable for frani-olefms. 2,2-Disubstituted vinyl silanes are epoxidized in high ees (Table 3, entries 5, 6) and enantiomerically enriched 1,1-disubstituted epoxides can be... 

Stabilized ketene 6S. For l, 2 -disubstituted epoxide, species 6S undergoes 6-endo-dig electrocyclization (path b) [24] to form the six-membered ketone 66, ultimately giving naphthol products. l, 2, 2 -Trisubstituted epoxide species 6S undergoes 5-endo-dig cyclization (path a) to give the ketone species 67, finally producing l-alkylidene-2-indanones. The dialkyl substituent of the epoxide enhances the 5-endo-dig cyclization of species 65 via formation of a stable tertiary carbocation 67. We observed similar behavior for the cyclization of (o-styryl)ethynylbenzenes [15, 16]. Formation of 2,4-cyclohexadien-l-one is explicable according to 6-endo-dig cyclization of a ruthenium-stabilized ketene, vhich ultimately afforded the observed products [25]. 

For 2,2-disubstituted epoxides 68a-d bearing a 2-phenyl substituent, their corresponding catalytic cyclizations gave good yields of l-phenyl-2-methyl-lH- indenes 69a-c using the same ruthenium catalyst under similar conditions [25]. It is interesting to note that the same product 69c vas obtained for different epoxides 68c and 68d, bearing a fiuoro substituent at their phenyl C4 and C5, respectively. 

Generally monosubstituted and dx-l,2-disubstituted epoxides are good substrates for EH while tri-, tetra or tra s-l,2-disubstituted ones are poor or non-substrates. Resolutions of epoxides using microsomal epoxide hydrolases, mEHs show that cis-2-alkyl substituted styrene oxides gave very high E-values when R=Me or Et (Figure 2.18a). A series of cis-... 

In the realm of hydrolytic reactions, Jacobsen has applied his work with chiral salen complexes to advantage for the kinetic resolution of racemic epoxides. For example, the cobalt salen catalyst 59 gave the chiral bromohydrin 61 in excellent ee (>99%) and good yield (74%) from the racemic bromo-epoxide 60. The higher than 50% yield, unusual for a kinetic resolution, is attributed to a bromide-induced dynamic equilibrium with the dibromo alcohol 62, which allows for conversion of unused substrate into the active enantiomer <99JA6086>. Even the recalcitrant 2,2-disubstituted epoxides e.g., 64) succumbed to smooth kinetic resolution upon treatment with... 

Oxidatively generated oxocarbenium ions have been used for intramolecular epoxide activation. Cascade reactions to form oligotetrahydrofuran products that demonstrated a strong preference for the exo-cyclization pathway were achieved in good yields when disubstituted epoxides were used as substrates. High stereoselectivity was observed in these reactions, with complementary diastereomers being formed from diastereomeric (g) epoxides.257... 

Interestingly, 1,2-disubstituted epoxides led to a,a-disubstituted propargyl alcohols, indicating that 1,2 shifts and therefore epoxide-to-aldehyde rearrangements occurred during the reactions (Scheme 10.12). Mechanistic studies by NMR validated this rearrangement and also supported the transmetallation-abstraction mechanism as already proposed (Scheme 10.13).8... 

Figure 9.1 Structure of epoxide polymers of various tacticity obtained from mono- and disubstituted epoxides...

Note that stereoregular polymers of disubstituted epoxides with a threo-diisotactic and eryt/zro-disyndiotactic structure have not been synthesised. 

Oxazolines.1 Reaction of 1,1-disubstituted epoxides with nitriles and SiF4 (1 equiv.) provides fluorohydrins, which oti further exposure to SiF4 are converted into 2-oxazolines, in which the nitrogen is attached to the substituted carbon. In the example cited, the yield is increased to 81% from reactions conducted at 80°. 

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