Preparation epoxides from aldehydes using

Epoxides from aldehydes, 46, 44 Equatorial alcohols, preparation by use of the lithium aluminum hydride-aluminum chloride reagent, 47, 19... 

The carbon fragment used in this approach can also be provided by sulfur yUdes. In this arena, Metzner and co-workers <99JCS(P1)731> developed a novel asymmetric variant employing (+)-(2/J,5/J)-2,5-dimethylthiolane (53) as the chiral auxiliary to prepare rrons-(S,S)-stilbene oxide (56). Chiral epoxides have also been prepared from aldehydes using sulfur ylides derived from the products of Baker s yeast reductions <99SL1328>. 

Corey-Chaykovsky epoxidation Preparation of epoxides from aldehydes and ketones using sulfur ylides. 102... 

Previous syntheses of terminal alkynes from aldehydes employed Wittig methodology with phosphonium ylides and phosphonates. 6 7 The DuPont procedure circumvents the use of phosphorus compounds by using lithiated dichloromethane as the source of the terminal carbon. The intermediate lithioalkyne 4 can be quenched with water to provide the terminal alkyne or with various electrophiles, as in the present case, to yield propargylic alcohols, alkynylsilanes, or internal alkynes. Enantioenriched terminal alkynylcarbinols can also be prepared from allylic alcohols by Sharpless epoxidation and subsequent basic elimination of the derived chloro- or bromomethyl epoxide (eq 5). A related method entails Sharpless asymmetric dihydroxylation of an allylic chloride and base treatment of the acetonide derivative.8 In these approaches the product and starting material contain the same number of carbons. 

The method of Kim et al.[89-93] starts from the synthesis of the three-carbon phosphonium salt according to the modified method of Corey et alJ94,95] The Wittig reaction of the phosphonium salt with a Z-protected a-amino aldehyde using potassium hexamethyldisilazanide provides the ds-alkene without racemization. Efficient hydrolysis of the orthoester without double bond migration is achieved by acidolytic hydrolysis with aqueous hydrochloric acid in tert-butyl alcohol under reflux conditions. Then, an a-amino acid methyl ester is coupled. The desired epoxide product is obtained by treatment with 3-chloroperoxybenzoic acid. The epoxidation reaction is stereoselective and predominantly provides one isomer (R,S S,R = 4-10 1). The trans-epoxide can also be prepared using a trans-alkene-containing peptide. A representative synthetic procedure to obtain the ds-epoxide isostere is detailed below. 

This is a general method of preparing hexaalkylphosphorous triamides from the corresponding dialkylamines. The procedure is simple, and the yields are high. Hexaalkylphosphorous triamides are powerful nucleophiles.8 This feature can be used in a rather unique way to synthesize epoxides directly from aldehydes.8, 6... 

Nitroperbenzoic acid has been used for the preparation of the epoxide (116 equation 42). In the aldehyde (115), the tetrasubstituted C(l)—C(2) double bond is not epoxidized since it is deactivated by conjugation with the aldehyde group, llie disubstituted double bond is not sufficiently reactive due to the inductive effect of the allyl ether moieties. The epoxidadon takes place from the a-face since the P-face is blocked by the allylic substituents. The epoxide (116) cannot be prepared in satisfactory yields using MCPBA. 

Preparation.—A historical account of the development of the synthesis of methylenephosphoranes has been given. Details have appeared - of the use of epoxides in the generation of ylides from phosphonium salts. Weakly acidic salts are deprotonated by the anions such as XCHaCH20 formed by attack of the phosphonium covmter-anion on epoxide, but strongly acidic phosphonium salts are deprotonated more rapidly than these species are produced. The base in these cases must be either epoxide or original anion. Side-reactions in olefin syntheses using epoxides as base include acetal formation from aldehyde and epoxide, cyclopropane formation from ylide and epoxide, and decomposition of quinquecovalent phosphoranes, e.g. (1), formed from phosphonium salt and... 

Other Methods.— The palladium-catalysed oxidation of terminal olefins to methyl ketones is very efficient using 30% hydrogen peroxide in acetic acid or t-butyl alcohol. The method offers advantages in that conversions are usually high, aldehyde production is very low, and the method requires only very low concentrations of palladium [20—40p.p.m, as palladium(li) acetate], fi-Hydroxy-o-nitrophenylselenides, or their O-acyl derivatives, on oxidation with hydrogen peroxide undergo elimination to form ketones or enol esters [equation (10)]. The starting materials can be prepared easily from alkenes via their epoxides. 

Aldehyde 73 was prepared from aldehyde 70 using a Brown Allylation to control absolute stereochemistry in the preparation of 72. Bromide 68 was prepared using a Sharpless epoxidation to control absolute stereochemistry. Conversion of 73 to the corresponding enolate, alkylation with 68, and addition of more LDA to generate a new enolate (74) gave a reasonable yield of 75 (see Histrionicotoxin-8/9). 

The compounds 96-99, shown in Scheme 3.26, are all metabolites of arachidonic acid (8) produced in a NADPH-dependent cytochrome P-450-meditated oxidative pathways. Falck and coworkers [77] prepared these from Corey s epoxide methyl ester 89a as shown in Scheme 3.26. Hydrolysis of the epoxide ester 89a using perchloric acid, followed by oxidative cleavage of the resulting diol 100, provided aldehyde 101. Next, a Wittig reaction with aldehyde 101 followed by Jones oxidation and/or saponification... 

In 2002, Shing et al. reported glucose-derived ketones 391 and 392. Ketone 391 epoxidizes tran -stilbene with up to 71% ee [277]. A series of L-arabinose-derived ketones 393-399 followed, and up to 90% ee was obtained for tran -stilbene epoxide with ketone 396 [278], In the same year, Zhao et al. reported three fructose-derived ketones and aldehydes 400-402 for the asymmetric epoxidation [279], Aldehyde 402 achieved 94% ee for tran -stilbene. hi 2009, Davis et al. presented a variety of conformationally restricted ketones 403, prepared from A-acetyl-D-glucosamine which show useful selectivities with terminal olefins (styrene 81% ee. Fig. 7.19) [280]. 

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). 

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