Epoxides alkylation

Scheme 4.17 Asymmetric domino alkylation epoxidation reactions.

On the basis of the above model compound studies, the reactivity of I can now be more clearly understood. The nucleophilic ester groups in I can interact intramolecularly with oxiranium ions formed by attack at either of the two alkylated epoxide groups to form dioxacarbenium ions XVIII, XIX and XXI which are less reactive than oxiranium ions XVII or XX. This is shown in Scheme 2. 

A difference in reaction efficiency was observed depending on the catalyst used. Imidazolium salt 305 provides the highest yield of desired product. When preformed complex 307 is subjected to the reaction conditions, fran -2-ethylcyclohex-anol is detected by gas chromatography in 76% yield (Eq. 30). Alkylation starting with free carbene 306 results in only 28% yield of desired alkylated epoxide. 

Finally, one example of trityl salt analogues in the phase-transfer catalysis is presented. The highly stable triazatriangulenium cations 62 [161, 162] were jnst recently introduced to the phase-transfer chemistry [163], Persistent to strongly basic and nncleophilic conditions, these salts revealed efficient catalytic activity in addition reactions (Scheme 64). Modification of the alkyl side chains on nitrogen allowed matching the fair hydro/lipophilicity with the optimised conditions in the alkylation, epoxidation, aziridination and cyclopropanation reactions. The results are comparable to those of tetrabutylammonium salts and in some cases showed even a better outcome. 

On the other hand, 1-pynylmagnesium bromide m reported7 to give a mixture of two isomeric alcohol In low yield (Eq. 827). TIm minor product, however, is formed simply by attack on the most-alkylated epoxide carbon, rather than by preliminary isomerization ( > propioneldehyde. 

There are numerous variations on the general mechanism outlined in Figure 7.10. Glutathione forms conjugates with a wide variety of xenobiotic species, including alkenes, alkyl epoxides (1,2-epoxyethylbenzene), arylepoxides (1,2-epoxynaphthalene), aromatic hydrocarbons, aromatic halides, alkyl halides (methyl iodide), and aromatic nitro compounds. The glutathione transferase enzymes required for the initial conjugation are widespread in the body. 

The industrial production of Crixivan (9 H2S04) took advantage of the chirality of (IS,2R)-aminoindanol to set the two central chiral centers of 9 by an efficient diastereoselective alkylation-epoxidation sequence.17 The lithium enolate of 12 reacted with allyl bromide to give 13 in 94% yield and 96 4 diastereoselective ratio. Treatment of a mixture of olefin 13 and V-chlorosuccinimide in isopropyl acetate-aqueous sodium carbonate with an aqueous solution of sodium iodide led to the desired iodohydrin in 92% yield and 97 3 diastereoselectivity. The resulting compound was converted to the epoxide 14 in quantitative yield. Epoxide opening with piperazine 15 in refluxing methanol followed by Boc-removal gave 16 in 94% yield. Finally, treatment of piperazine derivative 16 with 3-picolyl chloride in sulfuric acid afforded Indinavir sulfate in 75% yield from epoxide 14 and 56% yield for the overall process (Scheme 24.1).17-22... 

Bell, T. W. and Ciaccio, J.A. (1988). Alkylative epoxide rearrangement, application to stereoselective synthesis of chiral pheromone epoxides. Tetrahedron Lett., 29, 865-868. 

Another recent example by Peukert and Jacobsen (199) took advantage of the first polymer supported Jacobsen s catalyst 8.53 (Fig. 8.31) comparable with the soluble catalyst in asymmetric epoxidation and its full characterization (200, 201). The supported catalyst, prepared from the activated carbonate of hydroxymethyl PS and from a soluble phenolic catalyst (201), was used to catalyze the opening of racemic alkyl epoxides (Mi, Fig. 8.31) with substituted phenols and yielded the 50-member aryloxy alcohol library L15 with good enantiomeric purity (average >90%, never below 80% e.e.). 8.53 was also used to produce the chiral intermediate monomer set M3 (Fig. 8.31) which was used to make two 50-member chiral libraries L16 (1,4-diary-loxy 2-propanols) and L17 (3-aryloxy-2-hydroxy propanamines) with excellent enantiomeric excess following the straightforward synthetic schemes reported in Fig. 8.31. 

Simple alkyl epoxides 277 Arene oxides 277 Cyclic vinyl epoxides 279... 

Z.6Z)-m- (9S.I(lR)-cpoxy- 3.6-lienicosadiene Bihar hairy caterpillar (Diacrisia ohiiipta) Fs Alkylative epoxide rearrangement and stereoselective Wittig olelmation reactions 1 Lipasc-ealalyzed asymmetric acetylation of a (+)-epoxideh [142] [201 h... 

Z.6Z)-Alkylative epoxide rearrangement and stereoselective Wittig ole filiation [ I42J... 

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