Epoxides, preparation from aldehydes

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>. 

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... 

Ng, J. S. Epoxide formation from aldehydes and ketones - a modified method for preparing the Corey-Chaykovsky reagents. Synth. Commun. 1990, 20,1193-1202. 

The addition of aldehydes to carb - rCHN, to form stilbene epoxides prepared from 10-mercaptoisobc Jes derived from 48 on aldehydes i - -nciple underlies a synthesis of chn... 

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). 

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). 

Dioxolanes haye been prepared from a carbonyl compound and an epoxide (e.g., ketone/SnC, CCI4, 20°, 4 h, 53% yield or aldehyde/ Et4N Br, 125-220°, 2-4 h, 20-85% yield ). Perhalo ketones can be protected by reaction with ethylene chlorohydrin under basic conditions (K2CO3, pentane, 25°, 2 h, 85% yield or NaOH, EtOH—H2O, 95% yield ). 

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

This review summarizes the best asymmetric methods for preparing epoxides and aziridines from aldehydes (or ketones) and imines. 

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. 

Finally, chiral epoxides can be prepared from a,p-unsaturated carbonyl compounds through an entirely different approach, in which the epoxide oxygen is derived from the carbonyl moiety. For example, trans-aryl-vinyl epoxides 52 can be synthesized from conjugated aldehydes 50 and chiral sulfonium salts 51, with excellent ee s. The protocol is especially effective for substrates which bear a p-mcthoxy group on the aryl substituent <00TL7309>. 

Aggarwal et al.108 reported excellent results with the catalytic asymmetric epoxidation of aldehydes. As shown in Scheme 4-52, a series of thioacetals 137 was prepared from hydroxy thiol 136 and the corresponding carbonyl compound. Among them, compound 138, derived from 136 and acetaldehyde, proved to be the best catalyst for asymmetric epoxidation of aldehydes. 

Lactol 128 has been converted into a variety of racemic C-nucleosides. The unstable aldehyde 130 was prepared from 128 by way of oxazolidine 129. Lactone 131 was also derived from 128 and used as starting material in the synthesis of racemic C-nucleosides. Adducts 77 + 77 were transformed into epoxide 132. Opening of the epoxide, followed by ozonolysis and reduction allowed one to... 

In contrast to the epoxides, preparative routes to the aziridines are fairly evenly split between the [C=N + C] and the [C=C + N] routes. Among contributions in the former category, aziridine carboxylate derivatives 110 can be prepared through the lanthanide-catalyzed reaction of imines with diazo compounds, such as ethyl diazoacetate (EDA). In this protocol, iV-benzyl aryl aldimines and imines derived from aromatic amines and hindered aliphatic aldehydes are appropriate substrates <99T12929>. An intramolecular variant of this reaction (e.g.. Ill —> 112) has also been reported <990L667>. 

Masakatsu Shibasaki of the University of Tokyo reports (J. Am. Chem. Soc. 2004,126, 7559) that use of a BINOL-derived catalyst with cumyl hydroperoxide enables the enantioselective epoxidation of unsaturated N-acyl pyrroles such as 7. The pyrroles 7, prepared from the precursor aldehydes such as 5 with the reagent 6, can be used directly, without further purification. 

Epoxides are reactive electrophiles, which enable the facile preparation of substituted alcohols by reaction with a broad range of nucleophiles. Epoxides can be prepared on insoluble supports either by epoxidation of alkenes or from aldehydes (Table 15.1). 

For example, polymers having hydroxyl end groups can be prepared by reaction of polymer lithium with epoxides, aldehydes, and ketones III-113). Carboxylated polymers result when living polymers are treated with carbon dioxide (///) or anhydrides (114). When sulfur (115, 116), cyclic sulfides (117), or disulfides (118) are added to lithium macromolecules, thiol-substituted polymers are produced. Chlorine-terminus polymers have reportedly been prepared from polymer lithium and chlorine (1/9). Although lithium polymers react with primary and secondary amines to produce unsubstituted polymers (120), tertiary amines can be introduced by use of p-(dimethylamino)benzaldehyde (121). 

In many of the syntheses, aza-/3-lactam aldehyde 151 has been used as a key synthon (Scheme 20). For example, aldehyde 151 gives epoxide 157 by treatment with NaH and Me3S+I in DMSO at low temperature. Similarly, alcohol 156 may be prepared from 151 by reduction with LiAlH4 in ether. When NaBH4 is used in methanol a cyclic product 159 was isolated along with alcohol 158 (Scheme 20) <1998J(P1)2597>. 

Epoxides can be synthesised by the action of aldehydes or ketones with sulphur-ylides. They can also be prepared from alkenes by reaction with m-chloroperoxybenzoic acid. 

The epoxide can be prepared from an alkene and the amide from a carboxylic acid. The new target. 2-ethyl-2-hexenoic acid, has a CC double bond in conjugation with the carbonyl group of the carboxylic acid. Whenever a compound with an ,/3-unsaturated carbonyl group is encountered, it is worthwhile to consider the possibility of using an aldol condensation (see Section 20.5) or a related reaction to prepare it. To examine this possibility, the aldehyde that will provide the carboxylic acid upon oxidation is disconnected at the double bond. Because both fragments produced by this disconnection are the same, it is apparent that an aldol condensation of butanal can be employed to prepare this compound. The synthesis was accomplished as shown in Figure 23.5. 

Trifluoroacetimidoyllithiums 75 have been prepared from imidoyl iodides by reaction with n-BuLi at — 78 °C and have been trapped with aldehydes, ketones, epoxides,... 

The lower mercapto side chains were mainly prepared by formation of epoxides starting from the corresponding ketones or aldehydes, respectively107. Treatment... 

Aldehyde 5, prepared from (17 ,2S)-norephedrine, was subjected to epoxidation with potassium hypochlorite in aqueous tetrahydrofuran to yield selectively (> 20 1 by 1H NMR) an epoxy aldehyde, which was oxidized to epoxy acid 6 by prolonged treatment with potassium hypochlorite at room temperature. ... 

Ahn efa/. examined a number of novel sterically hindered Mn(salen) complexes prepared from an aldehyde derived from BINOL. These complexes efficiently catalyzed the asymmetric epoxidation of several cycloalkenes (Table 4 Figure 9) <2001TL2485>. 

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