2.3- Disubstituted epoxides products

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-... 

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). 

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>. 

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). 

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). 

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. 

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... 

In the case of 1,2-disubstituted epoxides, such as compounds 200 and 201, the reaction with 2-lithio-l,3-dithiane 161 takes place diastereoselectively to afford products 202291 and 203292, respectively (Scheme 57). 

Treatment of 1,1-disubstituted epoxides of the gibberellin family with sulfuiyl chloride results in the formation of the corresponding a,3-enal in good yield, as shown in equation (31). Four examples were reported in which alcohols, esters, lactones and sdkenes survive. The postulated mechanism involves an electrophilic opening of the epoxide with elimination, followed by oxidation of the primary chlorosulfate ester. A steroidal 3-spirooxirane also undergoes this reaction, but the yield is poor and several products are obtained, suggesting that the overall scope of this reaction may be limited. 

As expected on the basis of the epoxy halide results just discussed, die displacement of a primary tosyl-ate can be smoothly accomplished in the presence of an adjacent disubstituted epoxide,and this reaction has been utilized in syntheses of disparlure and of other insect pheromones. On the other hand, a recently reported reaction of a cyclic glucopyranose-derived epoxide with either Me2CuLi or MeMgCl-CuBr afforded in high yield the desired ring-opened product, leaving intact an exocyclic primary mesylate. 

The 1,1-disubstituted epoxide (100 equation 40) undergoes ring expansion rather than hydride migration, to afford materials such as (101) and related products. It is conceivable that an aldehyde was generated in this instance, which then rearranged to the isolated products. This kind of behavior is seen with (102 equation 41) which upon brief treatment with BF3 afforded aldehyde (103) and ketone (104) in nearly equal amounts. When resubjected to the reaction conditions the aldehyde (103) gave a new ketone (105). Compound (103) was used as a precursor to the hydrocarbon cuparene, which has the structure of (103) modified by reduction of CHO to Me in spite of the modest yield, this proved a convenient approach to a structure with two adjacent quaternary carbons. ... 

Acyloins are sometimes formed in moderate yield when 1,2-disubstituted epoxides are treated with BFj in dimethyl sulfoxide solvent. A curious report of highly temperature dependent nonoxidative rearrangement of 2,3-epoxycyclododecanone indicates that a 1,2-dione is formed at 85 °C, whereas a 1,3-dione is the product at 150 °C. All of these applications require heating, since the Lewis acidity of BF3 is strongly attenuated in dimethyl sulfoxide. O ... 

Given the difficulties encountered in the epoxidation of frans-olefins by Mn(salen) complexes, it is intriguing that a wide range of trisubstituted olefins are outstanding substrates for asymmetric epoxidation (Scheme 7) [62,76]. The absolute stereochemistry of the epoxide products is inverted at the benzylic carbon when compared with the sense of induction seen with cfs-disubstituted olefins. A qualitative transition state model has been suggested wherein the trisubstituted substrate reacts with the metal-oxo complex via a skewed side-on approach (Fig. 12). The distortion of trisubstituted olefins from planarity resulting from Aj 2 or Aj 3 interactions may be critical in this context. 

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