Syntheses from epoxides

DesilyltUive reactions. A new version of the Peterson olefination employs a combination of ethyl trimethylsilylacetate, an aldehyde, and CsF. Similarly, epoxide synthesis from carbonyl compounds avoids strongly basic conditions by using [Ph SCHjSiMej]" TfO as a source of the sulfonium methylide. ... 

The most important oxirane syntheses are by addition of an oxygen atom to a carbon-carbon double bond, i.e. by the epoxidation of alkenes, and these are considered in Section 5.05.4.2.2. The closing, by nucleophilic attack of oxygen on carbon, of an OCCX moiety is dealt with in Section 5.05.4.2.1 (this approach often uses alkenes as starting materials). Finally, oxirane synthesis from heterocycles is considered in Section 5.05.4.3 one of these methods, thermal rearrangement of 1,4-peroxides (Section 5.05.4.3.2), has assumed some importance in recent years. The synthesis of oxiranes is reviewed in (B-73MI50500) and (64HC(19-1U). 

The remarkable stereospecificity of TBHP-transition metal epoxidations of allylic alcohols has been exploited by Sharpless group for the synthesis of chiral oxiranes from prochiral allylic alcohols (Scheme 76) (81JA464) and for diastereoselective oxirane synthesis from chiral allylic alcohols (Scheme 77) (81JA6237). It has been suggested that this latter reaction may enable the preparation of chiral compounds of complete enantiomeric purity cf. Scheme 78) ... 

Thus, the key reason for the paucity of methods available by analogy with epox-idation methods is the comparative inertness of N-O and N-N bonds relative to the peroxide bond. This means that the synthetic methods that have been developed for preparation of aziridines are distinct from those that have evolved for epoxide synthesis. 

Synthesis of Allylic Alcohol Xa. A 3.84 g sample of olefin VII was treated with m-chloroperoxybenzoic acid (MCPBA) in dichloromethane for 1.5 hours at 0°C and 2.5 hours at 20°C. The NMR spectrum of the crude product indicated a mixture of approximately 75% epoxide VIII and 25% IX (structural assignments based upon assumed epoxidation preferentially from the less hindered side). Purification by column chromatography furnished 0.61 g of IX and 2.58 g of VIII. The separation was performed for characterization purposes the crude epoxidation mixture was suitable for subsequent transformations. 

Figure 11. Synthesis of the chrysene 1,2- and 3,4-dihydrodiols and the corresponding diol epoxide derivatives from chrysene by Method III (50. Reagents (i) H2,Pd (ii) H2,Pt (iii) DDQ (iv) AgOBZ,I25 (v) NBS A.

Historically, the asymmetric synthesis of epoxides derived from electron-poor alkenes, for example a, (3-unsaturated ketones, has not received as much attention as the equivalent reaction for electron-rich alkenes (vide supra). However, a recent flurry of research activity in this area has uncovered several... 

In spite of the potential interest of such enzymes for fine chemical synthesis, it was only recently that a detailed search for epoxide hydrolases from microbial... 

This procedure was extended to a method for asymmetric synthesis of optically active epoxides starting from optically active sulfoxides. As the oxiranyUithium 131 reacts with the acidic hydrogen of the n-butyl aryl sulfoxide, the introduction of electrophiles to the reaction mixture was problematic. Therefore, the reaction was performed by addition of 1 equivalent of f-C4H9Li at — 100°C to 130 and the sulfoxide-lithium exchange reaction was found to be extremely rapid (within a few seconds at this temperature). Moreover, as f-butyl aryl sulfoxide 138 has now no more acidic hydrogen, the addition of several electrophiles leads to functionalized epoxides 139 (equation 48). ... 

AUyl transfer reactions, 73, 1 Allylic alcohols, synthesis from epoxides, 29, 3 by Wittig rearrangement, 46, 2 Allylic and benzylic carbanions, heteroatom-substituted, 27, 1 Allylic hydroperoxides, in... 

Quan Z, Min J, Zhou Q, Xie D, Liu J, Wang X, Zhao X, Wang F (2003) Synthesis and properties of carbon dioxide-epoxides coplymers from rare earth metal catalyst. Macromol Symp 195 281-286... 

SCHEME 9. Durette, Hough, and Richardson s synthesis of methyl 3-bromo-3-deoxy-p-maltoside via opening of the 2,3-allo-epoxide derived from the l,2,2, 3, 4, 6,6 -heptaacetate of methyl p-maltopyranoside (1974). 

Scheme 7.2. Synthesis of epoxide 9 from (—)-quinic acid (15).

In recent years, dioxiranes have become workhorses for a variety of selective transformations in organic synthesis, from epoxidation of alkenes to the conversion of alcohols into fee corresponding ketones <99CJC308>. Dioxirane-mediated epoxidation continues to be the method of choice for complex substrates wife acid-sensitive functionality. Thus, fee dimethyl-dioxirane (DMD)-mediated epoxidation of the silylated stilbene lactam 159 has been reported as a key step in fee synthesis of protoberberines <99JOC877>. 

A stereoselective total synthesis of dendrobatide toxin 251 D was developed by Overman et al.237) involving an epoxidation of the (S)-proline derivative (237) to furnish the oxirane (238) as major product. In their approach towards the total synthesis of the same natural product Thomas et al.238) investigated the stereoselectivity of the epoxide formation from (S)-5-acetylpyrrolidin-2-one and dimethyloxosulfonium methylide. A diastereoselectivity of d.s. 50-60% was achieved 238. ... 

Reduction of the carbonyl in the r >[CO-CH2-NH] link 7 (R1 = H) results in the (hy-droxy)ethyleneamino or r >[CH(OH)-CH2-NH] link 8 (R1 = H), which has proved to be a very potent analogue of the tetrahedral hydrated intermediate of the scissile amide bond. It has been widely used for the design of various inhibitors of HIV protease 141,142 14 154 and ACE, 155-157 and to synthesize angiotensin II, III, and IV analogues. 158,159 Indeed, the chirality of the hydroxylated carbon is critical for HIV protease inhibition, but separation of the epimers may be difficult. Therefore, the stereoselective synthesis from epoxides has been actively investigated. An example of a C-methylated tp[CMe(OH)-CH2-NH] link, obtained from an epoxide with chromatographic separation of the epimers, has also been described. 157 Most of the [(hydroxy)ethyleneamino] peptides have been prepared by solution procedures, but two examples of solid-phase synthesis have been reported. A theoretical study of the (hydroxy)ethyleneamino replacement for the amide bond has been carried out on a HIV protease inhibitor. 160 ... 

Illustrative of the use of methylsulfonate caters for epoxide synthesis are several preparations drawn from the steroid litera-tnj-oMH-ww. i ot, ls 3 j nd depicted in Eqs. (23fi)-(24l). Although other... 

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