Epoxy Aldehyde

Unsaturated aUphatic endoperoxides form bis(epoxides) and/or epoxy aldehydes upon thermolysis (80,81). Thus 3,5-epidioxycyclopentene [6573-26-8] reacts as follows. 

A synthetically useful diastereoselectivity (90% dc) was observed with the addition of methyl-magnesium bromide to a-epoxy aldehyde 25 in the presence of titanium(IV) chloride60. After treatment of the crude product with sodium hydride, the yy -epoxy alcohol 26 was obtained in 40% yield. The yyn-product corresponds to a chelation-controlled attack of 25 by the nucleophile. Isolation of compound 28, however, reveals that the addition reaction proceeds via a regioselective ring-opening of the epoxide, which affords the titanium-complexed chloro-hydrin 27. Chelation-controlled attack of 27 by the nucleophile leads to the -syn-diastereomer 28, which is converted to the epoxy alcohol 26 by treatment with sodium hydride. 

Besides the addition of vinylation reagents, methyllithium and methyl Grignard reagents can react with a,/1-epoxy aldehydes in a nonchelation-controlled mode79. However, the level of diastereoselectivity is moderate. 

For example, the parent bicyclo[2.2.1] system 9 affords the epoxy-aldehyde 64 in high yield (97 %) in nonpolar solvents (cyclohexane)62). The mechanism is rationalized in equation 52. Small amounts (ca. 1 %) of the bicyclic ether 65 are also formed, but it is known that 64 rearranges into 65 on heating 62). 

Another approach to cyclic nitronates has been developed by Rosini et al. in which nitro-aldol and subsequent cyclization is used as a key step. For example, 2,3-epoxy aldehydes react with ethyl nitroacetate on alumina surface in the absence of solvent to give 4-hydroxyisoxazoline 2-oxides in good yields (Eq. 8.80).130... 

The catalytic asymmetric epoxidation of a,p-unsaturated aldehydes has also been an important challenge in iminium catalysis and for chemical synthesis in general. More recently, Jprgensen and coworkers have developed an asymmetric organocatalytic approach to ot, (3-epoxy aldehydes using pyrrolidine catalyst 20 and H2O2 as the stoichiometric oxidant. The reaction appears to be extremely general and will likely receive wide attention from the chemical synthesis community (Scheme 11.6b). 

In 2004, Bode and Rovis independently and concurrently reported the catalytic coupling of reducible aldehydes and alcohols. This mode of reactivity is most closely related to the work published by Wallach, who generated dichloroacetic acid from chloral under cyanide catalysis in aqueous media [108]. Bode and coworkers reported the catalytic, diastereoselective synthesis of P-hydroxy esters from a,P-epoxy aldehydes using thiazolium pre-catalyst 173 Eq. 16a [109]. MeOH, EtOH, and BnOH are effective nucleophiles providing upwards of >10 1 diastere-oselectivity. Aziridinylaldehyde 174 has also been shown to provide the desired iV-tosyl-P-aminoester 175 in 53% yield Eq. 16b. 

As previously explored by Bode, other a-reducible substrates, such as a,P-epoxy aldehyde and aziridinylaldehyde, are competent partners for redox reactions. (Scheme 33) [109], Various amines are compatible nucleophiles in this methodology in which P-hydroxy amides are furnished in good yield and excellent diastereose-lectivity. A similar reaction manifold was discovered concurrently by Bode and co-workers using imidazole as co-catalyst [117],... 

Cordova has also shown hydrogen peroxide to be an effective oxidant in the epoxidation of a,P-unsatnrated aldehydes using diarylprolinol ether 30 as the catalyst (Fig. 9) [146, 147], Within these reports it was also shown that the resulting epoxy aldehydes could be used directly in either Wittig or Mannich reactions, providing synthetically useful one-pot protocols to prepare densely functionalised building blocks for further elaboration. 

Aldol products do not have to come from an aldol condensation. In another example of catalysis by a small organic molecule, Jeffrey Bode of UC Santa Barbara reports (J- Am. Chem. Soc. 2004,126, 8126) that the thioazolium salt 7 effects the rearrangement of an epoxy aldehyde such as 6 to the aldol product 8. This is a net oxidation of the aldehyde, and reduction of the epoxide. As epoxy aldehydes such as 6 are readily available by Sharpless asymmetric epoxidation, this should be a general route to enantiomerically-aldol products. The rearrangement also works with an aziridine aldehyde such as 9, to give the ff-amino ester 10. 

A modification of this asymmetric bromolactonization affords optically active a,/J-epoxy aldehydes (equation I).2 Thus treatment of the bromolactone 1 with... 

Khalique20 synthesized D-apiose by treating /ceto-D-fructose pen-taacetate (18) with diazomethane, and deacetylating the product (19) with barium methoxide to give epoxide (20), which, by oxidation with 2 equivalents of sodium metaperiodate, was converted into a syrupy epoxy-aldehyde (21), characterized as its crystalline phenylos-azone. Hydrolysis of compound 21 with aqueous acid produced... 

The synthesis of glytidaldehyde, as well as that of other simple c./J-epoxy aldehydes, had proved impossible until recently, when it was reported1 11-w that careful pH control at 8.0-8.5 during the cpoxidation of acrolein and a-methylacrolein allows the isolation of lilycidaldehytie and a-methylglycid ldehyde in good yield (Eq. 71). 

Titanium(IV) isopropoxide, 311 a,(3-Epoxy aldehydes and ketones Fluorine-Acetonitrile, 135 Oxodiperoxymolybdenum-(pyridine)(hexamethylphosphoric triamide), 227 a,(3-Epoxy silanes Allyltriisopropylsilane, 11 m-Chloroperbenzoic acid, 76 Esters (see also Dicarbonyl compounds, Unsaturated esters)... 

The initially formed chromate ester, from this very hindered secondary alcohol, suffers a transposition to an isomeric chromate ester. The isomeric chromate ester produces the transposed enal. Alternatively, the transposed chromate ester can produce the epoxidation of the alkene, giving an epoxy alcohol that is further oxidized to an epoxy aldehyde. 

Asymmetric bromolactonization (8, 421-423) ct,fi-epoxy aldehydes(2R.3S)-Epoxy aldehydes (2) can be prepared in high optical yield by an extension of the asymmetric bromolactonization of N-(a,/(-unsaturated) acylprolines (1), as shown in the example. 

Hayakawa, H. Miyashita, M. An efficient and stereoselective construction of the C(9)-C(17) dihydropyran segment of swinholides A-C via a novel reductive cleavage of an epoxy aldehyde. Tetrahedron Lett. 2000, 41, 707-711. 

The broad scope of the catalytic generation of activated carboxylates was demonstrated by Bode et al. in the diastereoselective synthesis of / -hydroxy esters 79 from a,/ -epoxy aldehydes 80 employing achiral thiazolium salts 81 as precatalysts (Scheme 9.24) [67]. The incorporation of a reducible functionality into the aldehyde substrate is the premise for a catalyst-induced intramolecular redox reaction generating the activated carboxylate 82. 

For the synthesis of pandoline (284) and 20-epi-pandoline (285), the epoxy-aldehyde (286) was condensed with the indolo-azepine (278) (Scheme 40) the result was an equimolecular mixture of the two alkaloids, in total yield of 64%, based on (278). In accordance with earlier observations, pandoline and 20-epi-pandoline can be reduced to the velbanamine derivatives (287) and (288), which can be isomerized to the C-16 epimers (289) and (290). These compounds contain, respectively, the complete structure and stereochemistry of the non-vindoline component of the oncolytic alkaloids leurosidine and vinblastine. 

Sartobind Sartorius, Goettingen, Germany Flat sheet (syringe, disk) cylindrical Regenerated cross-linked cellulose IEX AF epoxy aldehyde IMAC 31... 

The Passerini reaction is a useful method for the synthesis of substituted a-acyloxy carbocyclic acids. This is another reaction that one might assume an epoxide would not survive. Reaction of an epoxy aldehyde with benzoic and TosMIC provided the Passerini product in good yield as a mixture of diastereomers <07SL83>. 

Suggest a mechanism for the formation of the furan ring upon treatment of the epoxy-aldehyde derived from 7 with acid. 

Covalent, random Epoxy, aldehyde, carbodiimide groups React with primary amines of lysine and arginine High densihes are available and strong protein attachment/ random orientahon and surface interference... 

The chroniium(VI) oxide-dipyridine complex also has beoi found to cause oxidative rearrangement of tertiary allylic alcohols to a,3-epoxy aldehydes and small amounts of a,3-unsaturated aldehydes (equation 6 and Table 3). This is potentially useful as a homologation sequence since the starting materials are readily available from vinyl metal addition to ketones. Use of pyridinium chlorochromate (PCC) for this transformation gives mosdy a,3 unsaturated aldehydes. 

The lactol 3 has been converted into the protected epoxy aldehyde 4 and into the hydroxy epoxide 5, both with established configuration. These particular six-carbon units were required for synthesis of a natural product, rifamycin. A number of other Ininsformations arc also possible. 

Zou, Y, Lobera, M. and Snider, B.B. (2005) Synthesis of 2,3-dihydro-3-hydroxy-2-hydroxylalkylbenzofurans from epoxy aldehydes. One-step syntheses of brosima-cutin G, vaginidiol, vaginol, smyrmdiol, xanthoarnol, and avicenol A. Biomimetic syntheses of angelicin and psoralen.. Org. Chem., 70,1761-70. 

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. ... 

The bromolactones prepared from a,/l-unsaturated acids, via the acyl prolines, can be converted to optically active a,/(-epoxy aldehydes 9 in 84-98 % ee by treatment with sodium methoxide in methanol, followed by reductive cleavage5. ... 

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