Epoxide To aldehyde

The development of new methods for carbon-caihon bond formation is at the heart of organic synthesis. The most desirable methods are those that are easily practiced at scale, operate near ambient temperature, and that do not require strong acid or base. David C. Forbes of the University of South Alabama and Michael C. Standen of Synthetech in Albany, OR report (Organic Lett. 5 2283,2003) that the crystalline salt 2, which can be stored, smoothly converts aldehydes to epoxides, without any additional added base. The reaction is apparently proceeding by the loss of CO, from 2 to give the intermediate sulfonium methylide. 

It should be noted that the nucleofugal group in component XII (Scheme 6.83) might also be a cationic sulfonium moiety. In this circumstance the nucleophile attacking the aldehyde is a sulfur ylide. Catalytic enantioselective versions of the transformation of aldehydes to epoxides involving sulfur ylides are covered in Section 6.8. 

Another FBC approach was developed by Knochel and co-workers to oxidize olefins, sulfides, and aldehydes to epoxides, sulfoxides, sulfones, and carboxylic acids (79). They used the Ru and Ni complexes of a perfluorinated 1,3-diketone, obtained in one step in 80 % yield by the condensation of a perfluoromethyl ester and a perfluoromethyl ketone, as catalysts for these oxidation reactions. More importantly, these Ru and Ni complexes were found to be highly soluble in perfluorocarbons (Figure 3). 

Solutions of RC triple-bond C—Ti(0-/-C2H2)2 can be prepared by treating acetylenic compounds, such as phenylacetylene, with butyl lithium and then Cl—Ti(0-/-C2H2)2. These materials can react with aldehydes and epoxides to give the expected addition products (215). 

Other modifications of the polyamines include limited addition of alkylene oxide to yield the corresponding hydroxyalkyl derivatives (225) and cyanoethylation of DETA or TETA, usuaHy by reaction with acrylonitrile [107-13-1/, to give derivatives providing longer pot Hfe and better wetting of glass (226). Also included are ketimines, made by the reaction of EDA with acetone for example. These derivatives can also be hydrogenated, as in the case of the equimolar adducts of DETA and methyl isobutyl ketone [108-10-1] or methyl isoamyl ketone [110-12-3] (221 or used as is to provide moisture cure performance. Mannich bases prepared from a phenol, formaldehyde and a polyamine are also used, such as the hardener prepared from cresol, DETA, and formaldehyde (228). Other modifications of polyamines for use as epoxy hardeners include reaction with aldehydes (229), epoxidized fatty nitriles (230), aromatic monoisocyanates (231), or propylene sulfide [1072-43-1] (232). 

Variations and Improvements on Alkylations of Chiral OxazoUnes Metalated chiral oxazolines can be trapped with a variety of different electrophiles including alkyl halides, aldehydes,and epoxides to afford useful products. For example, treatment of oxazoline 20 with -BuLi followed by addition of ethylene oxide and chlorotrimethylsilane yields silyl ether 21. A second metalation/alkylation followed by acidic hydrolysis provides chiral lactone 22 in 54% yield and 86% ee. A similar... 

The essential features of the Masamune-Sharpless hexose synthesis strategy are outlined in a general way in Scheme 4. The strategy is based on the reiterative- application of a two-carbon extension cycle. One cycle comprises the following four key transformations (I) homologation of an aldehyde to an allylic alcohol (II) Sharpless asymmetric epoxidation of the allylic alcohol ... 

Alternatively, epoxides can be formed with concomitant formation of a C-C bond. Reactions between aldehydes and various carbon nucleophiles are an efficient route to epoxides, although the cis. trans selectivity can be problematic (see Section 9.1.4). Kinetic resolution (see Section 9.1.5.2) or dihydroxylation with sequential ring-closure to epoxides (see Section 9.1.1.3) can be employed when asymmetric epoxidation methods are unsatisfactory. 

Chiral sulfonium salts derived from oxathianes have been developed for stoichiometric epoxidation reactions. The sulfonium salts were deprotonated and allowed to react with a, 3-unsaturated aldehydes to give trons-vinylepoxides with excellent ees and transxis ratios (Scheme 9.16b) [76]. The yields were generally high [75], and the best results were obtained with Ar = 4-OMePh. 

Aldehydes and ketones can be converted to epoxides in good yields with the sulfur ylids dimethyloxosulfonium methylid (60) and dimethylsulfonium methylid (61). For most purposes, 60 is the reagent of choice, because 61 is much less... 

Aldehydes and ketones can also be converted to epoxides by treatment with a diazoalkane,most commonly diazomethane, but an important side reaction is the formation of an aldehyde or ketone with one more carbon than the starting compound (Reaction 18-9). The reaction can be carried out with many aldehydes, ketones, and quinones. A mechanism that accounts for both products is... 

By 1990, most of the catalytic reactions of TS-1 had been discovered. The wide scope of these reactions is shown in Fig. 6.1.35 Conversions include olefins and diolefins to epoxides,6,7 12 16 19 21 24 34 36 38 13 aromatic compounds to phenols,7,9 19 25 27 36 ketones to oximes,11 20 34 46 primary alcohols to aldehydes and then to acids, secondary alcohols to ketones,34-36 42 47-30 and alkanes to secondary and tertiary alcohols and ketones.6 34 43 31 52... 

Sulfur ylides are a classic reagent for the conversion of carbonyl compounds to epoxides. Chiral camphor-derived sulfur ylides have been used in the enantioselective synthesis of epoxy-amides <06JA2105>. Reaction of sulfonium salt 12 with an aldehyde and base provides the epoxide 13 in generally excellent yields. While the yield of the reaction was quite good across a variety of R groups, the enantioselectivity was variable. For example benzaldehyde provides 13 (R = Ph) in 97% ee while isobutyraldehyde provides 13 (R = i-Pr) with only 10% ee. These epoxy amides could be converted to a number of epoxide-opened... 

The principal side reaction to epoxide coupling is hydrolysis. Particularly at acid pH values, the epoxide ring can hydrolyze to form adjacent hydroxyls. This diol can be oxidized with periodate to create a terminal aldehyde residue with loss of one molecule of formaldehyde (Chapter 1, Section 4.4). The aldehyde then can be used in reductive amination reactions. The reaction of an epoxide group with an ammonium ion generates a terminal primary amine group that also can be used for further derivatization. 

Treatment of benzaldehydes with ethyl diazoacetate and a catalytic quantity of the iron Lewis acid [ -CpFe(CO)2(THF)]+BF4 yields the expected homologated ketone (80). However, the major product in most cases is the aryl-shifted structure (81a), predominantly as its enol tautomer, 3-hydroxy-2-arylacrylic acid (81b). This novel reaction occurs via a 1,2-aryl shift. Although the mechanism has not been fully characterized, there is evidence for loss of THF to give a vacancy for the aldehyde to bind to the iron, followed by diazoacetate attachment. The product balance is then determined by the ratio of 1,2-aryl to -hydride shift, with the former favoured by electron-donating substituents on the aryl ring. An alternative mechanism involving epoxide intermediates was ruled out by a control experiment. 

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