Epoxides base-induced

It is appropriate at this juncture to address some of the more useful transformations of 2,3-epoxy alcohols.913 A 2,3-epoxy alcohol such as compound 14 possesses two obvious electrophilic sites one at C-2, and the other at C-3. But in addition, C-l of a 2,3-epoxy alcohol also has latent electrophilic reactivity. For example, exposure of 14 to aqueous sodium hydroxide solution results in the formation of triol 19 in 79% yield (see Scheme 5). In this interesting transformation, hydroxide ion induces the establishment of an equilibrium between 2,3-epoxy-l-ol 14 and the isomeric 1,2-epoxy-3-ol 18. This reversible, base-induced epoxide migration reaction is a process known as the Payne rearrangement.14... 

Tetrahydropyran epoxides 12, the synthesis of which involves a RCM, undergo a base-induced rearrangement to 3,4-dihydro-2//-pyran-4-ols 13. These compounds are converted stereospecifically to 3,6-dihydropyrans 14 on treatment with allyltrimethylsilane (Scheme 6) <00EJO3145>. 

BASE-INDUCED REARRANGEMENT OF EPOXIDES TO ALLYLIC ALCOHOLS trans-Pinocarveol,... 

Building on Inoue s pioneering work and using Andersson s versatile diamine, Kozmin and coworkers have described a catalytic base-induced isomerization of silacyclopentene oxide 139 [Eq. (10.41)] as a potential route to acyclic polyol domains, important components of a number of natural products. Epoxida-tion of 140, epoxide ring opening, and oxidation of the C—Si bonds provides tetra-ols in good overall yield and selectivity ... 

BASE-INDUCED REARRANGEMENT OF EPOXIDES T 0 ALLYLIC ALCOHOLS trans- PINOCARVEOL... 

The latter, on reaction with methylamine yielded via the P-epoxide 373, the trans-a aminoalcohol 374, which was N-acylated to the amide 375. Acid-catalysed dehydration of the tertiary alcohol 375, led to the olefin 375, from which the key radical precursor, the chlorothioether377 was secured in quantitative yield by reaction with N-chlorosuccinimide. In keeping with the earlier results recorded for structurally related compounds, 377 on heating in the presence of ruthenium dichloride and triphenylphosphine also underwent a 5-exo radical addition to generate the cyclohexyl radical 378 which recaptured the chlorine atom to furnish the a-chloro-c/5-hydroindolone 379. Oxidation of thioether 379 gave the corresponding sulfoxide 380, which on successive treatment with trifluoroacetic anhydride and aqueous bicarbonate led to the chloro-a-ketoamide 381. The olefin 382 resulting from base induced dehydrochlorination of 381, was reduced to the hydroxy-amine 383, which was obtained as the sole diastereoisomer... 

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). 

Aliphatic or aromatic alcohols can be alkylated by epoxides under either basic or acidic reaction conditions. Reaction of aliphatic alcoholates with epoxides can be complicated by base-induced rearrangement or oligomerization of the epoxide, because alcoholates are strongly basic and because the product of epoxide ring opening is again an alcoholate. These side reactions can be suppressed by using only catalytic amounts of base (Scheme 4.78). The examples sketched in Scheme 4.78 show that under basic reaction conditions nudeophilic attack occurs preferentially at the sterically most accessible carbon atom. 

The direction of the base induced ring opening of oxaspiropentanes proved to be highly depending on the nature of the base and solvent. Thus the epoxide 100 opened either mainly to l-(l-cyclopropenyl) cyclohexanol 106 on reaction with lithium di-isopropylamide in ether or mainly to the expected l-(l-cyclohexenyl) cyclopropanol 105 on reaction with lithium diethylamide in pentane, Eq. (31)57). 

Based on the (/ )-specific ADH from L. kefir, a recombinant E. coli strain was constructed as a whole-cell biocatalyst, and co-expressed GDH was used for regeneration of NADPH [157]. These designer cells were applied for the reduction of 4-fluoroacetophenone to the corresponding optically active (/ )-4-fluorophe-nylethan-l-ol at 0.5 M educt concentration [158]. After a reaction time of 23 h, a conversion of >95% has been achieved, and the purified isolated chiral alcohol showed an ee value of >99% (87% yield). (S)-p-Halohydrins were obtained with this whole-cell catalyst by means of an enantioselective reduction of the corresponding ketones with both high conversions of >95% and enantioselectivities of >99% (Fig. 40). Base-induced cyclization of the [S-halohydrin led to enantiomeri-cally pure (S)-epoxides in high yield and enantiomeric purity (>99% ee) [159]. 

Fig. 40 Concept for the two-step synthesis of enantiomerically pure (S)-epoxides out of aliphatic 1-halogenated 2-ketones. The ketone was reduced by a recombinant whole-cell catalyst bearing alcohol dehydrogenase from Lactobacillus kefir (LKADH) and glucose dehydrogenase (GDH) for regeneration of NADPH. Base-induced cyclization of the enantiomerically pure (5)-(3-halohydrin intermediate gave the desired (S)-epoxides in high yield and enantiomeric purity (>99% ee)...

The efficiency of this method was demonstrated in a total synthesis of the antibiotic (-r)-tetrahy-drocerulenin 28 (Scheme 8) and (-h)-cerulenin [11]. Irradiation of complex 22 in the presence of the chiral iV-vinyl-oxazolidinone 24, which is easily prepared from the amino carbene complex 23 [12], leads to the cyclobutanone 25 with high diastereoselectivity. Regioselective Baeyer-Villiger oxidation followed by base-induced elimination of the chiral carbamate yields the butenolide 26 in high enantiomeric purity. This is finally converted, using Nozoe s protocol [13], to the target molecule 28 by diastereo-selective epoxidation (- 27) and subsequent aminolysis. 

A novel cyclofragmentation to form 3-arylbenzofurans with concomitant release from a solid-phase support has been developed <2000AGE1093>. Base-induced epoxide opening leads to an alkoxide intermediate that suffers a Grob fragmentation with extrusion of the sulfmate leaving group and formaldehyde (Scheme 90). 

Brimble, M.A., and Furkert, D.P 2004. Synthesis of the l,6,8-trioxadispiro[4.1.5.2]tetradec-l 1-ene ring system present in the spirolide family of shellfish toxins and its conversion into a l,6,8-fi ioxadispiro[4.1.5.2]-tetradec-9-en-12-ol via base-induced rearrangement of an epoxide. Org Biomol Chem 2, 3573—3583. 

C yclopropyl ketones. Substituted cyclopropyl ketones can be obtained by base-induced isomerization of y, -epoxy ketones. Thus treatment of the epoxide (2) of... 

A rather different approach to the hydroazulenic synthesis has been adopted by Hendrickson and Boeckman. Treatment of 1-cyclopentenylcarboxalde-hyde (411) with the pyrrolidine enamine of cyclopentanone (412) yielded the thermodynamically most stable adduct (413) which, on quaternization and base-induced fragmentation, gave the acid (414) in 25% yield. Furthermore, the acid (414) has been converted into the epoxide (415) and the (5-lactone (416), both of which are potential synthetic precursors of guaiane-type sesquiterpenoids, e.g. pseudoguaianolides. 

As mentioned in the previous section, the Peterson reaction proceeds by an irreversible addition of the silyl-substituted carbanion to a carbonyl. It has generally been assumed that an intermediate p-oxidosi-lane is formed and then eliminated. In support of this mechanistic hypothesis, if an anion-stabilizing group is not present in the silyl anion, the p-hydroxysilanes can be isolated fixrm the reaction, and elimination to the alkene carried out in a separate step. Recent studies by Hudrlik indicate that, in analogy to the Wittig reaction, an oxasiletane (304) may be formed directly by simultaneous C—C and Si—O bond formation (Scheme 43). The p-hyd xysilanes were synthesized by addition to the silyl epoxide. When the base-induced elimination was carried out, dramatically different ratios of cis- to rranr-alkenes were obtained than from the direct Peterson alkenation. While conclusions of the mechanism in general await further study, the Peterson alkenation may prove to be more closely allied with the Wittig reaction than with -elimination reactions. 

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