Selenium dioxide oxidative rearrangement

Scheme 2 shows Rapoport s synthesis [15]. The cinnamic acid derivative 3 prepared from m-methoxy benzaldehyde [20] was ethylated by diethyl sulfate to give ethyl cinnamate derivative 4, followed by Michael addition with ethyl cyanoacetate to afford compound 5. Compound 5 was converted to lactam 6 by the reduction of the cyano group and subsequent cyclization. Selective reduction of the lactam moiety of 6 was achieved by treatment with trimethy-loxonium fluorob orate followed by sodium borohydride reduction. Amine 8 was obtained by the reductive methylation of amine 7. Amine 8 was converted to compound 9 by methylene lactam rearrangement [21], followed by selenium dioxide oxidation to provide compound 10. Allylic rearrangement of compound 10 and subsequent hydrolysis gave compound 12. The construction of the decahydroisoquinoline structure began with compound 12,... 

Selenium dioxide oxidation of alkenes with a hydrogen in an a-position involves the formation of the allyl selenic ester (X = OH) by an ene reaction. [2,3] Sigmatropic rearrangement of the allyl selenic ester to the selenium(II) ester and its hydrolysis also resulted in the formation of allylic alcohols. The oxidation of alkenes with selenium dioxide is covered in Section D.4.10. 

Amax 263 mfjL. In accord with the assigned structure there was no resonance for a vinyl proton in the NMR spectrum. Selenium dioxide oxidation of 69 gave the conjugated ketone 74, v ax I , nd 1628 cm . The single vinyl proton in the NMR spectrum of this compound appeared at S 6.02. Catalytic reduction of 74 to 70 proved that rearrangement had not occurred in this series of reactions. 

Spiro(adamantane-2,2 -adamantane) (223) has been synthesized from diketone (224) by selenium dioxide oxidation and ring-contraction by a benzilic acid rearrangement and also from (225), which is obtained by rearrangement of (226). Also noted are C-labelling studies which show that Wolff... 

To meet the needs of the advanced students, preparations have now been included to illustrate, for example, reduction by lithium aluminium hydride and by the Meerwein-Ponndorf-Verley method, oxidation by selenium dioxide and by periodate, the Michael, Hoesch, Leuckart and Doebner-Miller Reactions, the Knorr pyrrole and the Hantzsch collidine syntheses, various Free Radical reactions, the Pinacol-Pinacolone, Beckmann and Arbusov Rearrangements, and the Bart and the Meyer Reactions, together with many others. 

Selenium dioxide is a useful reagent for allylic oxidation of alkenes. The products can include enones, allylic alcohols, or allylic esters, depending on the reaction conditions. The mechanism consists of three essential steps (a) an electrophilic ene reaction with Se02, (b) a [2,3]-sigmatropic rearrangement that restores the original location of the double bond, and (c) solvolysis of the resulting selenium ester.183... 

The cyclic enediynyl sulfide 93 is also prone to undergo prototropic rearrangement (Scheme 20.21) [57]. When the l,8-diazabicydo[5.4.0]undec-7-ene (DBU)-induced isomerization was conducted in carbon tetrachloride, three cycloaromatized products, 96 to 98, were isolated, indicating the formation of the biradical 95a as a transient intermediate. In a polar solvent, such as methanol or ethanol, the formation of 99 can best be accounted for by regarding the biradical 95a as the zwitterion ion 95b. A related process involving the oxidation of 93 with selenium dioxide has also been reported [58],... 

A double oxidation at the 5,6-carbon-carbon double bond and N-9 by 2equiv of OT-chloroperbenzoic acid (MCPBA) was postulated as the mechanism for the oxidative rearrangement of 8-dialkylaminoxanthines to novel l-oxo-2,4,7,9-tetraazaspiro[4,5]dec-2-ene-6,8,10-triones <1999EJ02419>. The presence of an electron-donating 8-amino substituent was essential for this reaction to occur. Further oxidation of the products gave 1,3-dimethylpara-benic acid 45, which was also produced directly when selenium dioxide or hydrogen peroxide were used (Scheme 11). 

Oxidation of the allylic carbon of alkenes may lead to allylic alcohols and derivatives or a, 3-unsaturated carbonyl compounds. Selenium dioxide is the reagent of choice to carry out the former transformation. In the latter process, which is more difficult to accomplish, Cr(VI) compounds are usually applied. In certain cases, mixture of products of both types of oxidation, as well as isomeric compounds resulting from allylic rearrangement, may be formed. Oxidation of 2-alkenes to the corresponding cc,p-unsaturated carboxylic acids, particularly the oxidation of propylene to acrolein and acrylic acid, as well as ammoxidation to acrylonitrile, has commercial importance (see Sections 9.5.2 and 9.5.3). 

It has been generally accepted (5, 6) that the oxidation of olefins with selenium dioxide proceeds through attack on the olefinic double bond by selenium dioxide followed by rearrangement and solvolysis of the intermediate selenium (II) ester formed. 

Synthetic methods for 2(5jF/)-furanones have been developed in the preparation of cardenolides (65MI31200). The ketone (171) when reacted with lithium ethoxyacetylide gives the carbinol (172) which undergoes acid catalyzed rearrangement to the a,/3-unsaturated ester (173). Allylic oxidation of (173) with selenium dioxide under mild conditions gives digitoxigenin acetate (174) (Scheme 38). 

Allylic oxidation is carried out by addition of one equivalent of selenium dioxide. First Se02 will react with the alkene in a [4 + 2] cycloaddition reminiscent of the ene reaction. The initial product is an allylic selenic acid 40, which undergoes - like an allylic sulfoxide -allylic rearrangement to give an unstable intermediate, which decomposes rapidly to the allylic alcohol 42.16... 

Oxidation reactions of this nature are common in the literature. For example, selenium dioxide in refluxing etiumolic solution brought about the allylic oxidative rearrangement geranyl acetate, which was further functionalized in a synthesis of the norsesquiterpenoid gytinidal (equation 46). This trans formation was also used in a total synthesis of phytol. Similarly, an a, -unsaturated aldehyde was obtained undm similar conditions in studies of a synthesis of pentalenic acid derivatives (equation 47). ... 

Evidence for the preferential formation of the rraRS-substituted product of selenium dioxide allylic oxidation is seen in the synthesis of part of (13Z)-retinoic acid (equation 48). Reaction took place exclusively at the exocyclic double bond without rearrangement. Allylic oxidation of this nature has also been used in the synthesis of 6-conjugated 2-pyrones (equation 49). This intermediate was employed in the total synthesis of natural pyrones such as yangonin. 

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