Selenium dioxide reaction with allylic alkenes

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. 

The allylic alcohol was subjected to an Eschenmoser-Claisen rearrangement with dimethylacetamide dimethylacetal to introduce the C14 substituent in a stereoselective manner. Reduction of the amide to the corresponding aldehyde with phenyl silane in the presence of Ti(0/Pr)4 was followed by an acid-promoted closure of the C-ring of codeine. In order to prevent N-oxidation, the amine was converted to the corresponding tosylamide, via debenzylation and treatment with tosyl chloride, before the allylic alcohol was introduced by the reaction of the alkene with selenium dioxide (65). The stereochemistry of the C6 hydroxy functionality was corrected by applying the well-known oxidation/reduction protocol [46, 60] before the benzylic double bond was reductively removed under Birch conditions. Codeine (2) was obtained in 17 steps with an overall yield of approximately 0.6%. 

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... 

Selenium dioxide is also an oxygen donor to alkenes. In this case, however, the initial reaction of the double bond is with the selenium center followed by two pericyclic steps. After hydrolysis of the organo-selenium intermediate, the result is a hydroxylation at the allylic carbon position65. Thus, limonene (2) yields racemic p-mentha-l,8(9)-dien-4-ol66. The high toxicity of selenium intermediates and prevalence of many rearrangements has limited the widespread use of the reagent in synthesis. 

Selenium dioxide exhibits a useful stereoselectivity in reactions with trisubstituted gem-dimethyl alkenes. The products are always predominantly the /f-allylic alcohol or unsaturated aldehyde221 ... 

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... 

The selenium-dioxide mediated allylic oxidation of alkenes was explored by means of 2H and 13C KIEs to clarify the mechanism of ene step.85 Changes of isotopic composition were determined for unreacted 2-methyl-2-butene 33 in reaction with Se02 at 25°C in ferf-butyl alcohol (Equation (49)). 

Oxidation of an alkene may take place at the double bond or at the adjacent allylic positions, and important synthetic reactions of each type are known. Reactions at the double bond, such as epoxidation and dihydroxylation, are described in Chapter 5. Allylic oxidation is of value in synthesis and provides a method to access allylic alcohols, a,p-unsaturated aldehydes or a,p-unsaturated ketones. A common reagent for such transformations is selenium dioxide. For example, with... 

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