Allylic reactions Selenium dioxide

Allylic oxidation. Selenium dioxide has been widely used for allylic oxidation of olefins, but this reaction is often troublesome because of formation of selenium-containing by-products and colloidal selenium, which are not easily eliminated. The combination of Se02 with H2O2 to reoxidize selenium species to Set) , has been used to convert olefins into diols and epoxides (2, 362), but this iiicIIuhI is not general for allylic oxidations. Umbreit and Sharpless have effected allylic oxidations with an excess of /-butyl hydroperoxide (90"i.) in combination... 

Treatment of double-bond compounds with selenium dioxide introduces an OH group into the allylic position (see also 19-14). This reaction also produces conjugated aldehydes in some cases.Allylic rearrangements are common. There is evidence that the mechanism does not involve free radicals but includes two pericyclic steps (a and... 

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 ... 

The isomerization of allyl ethers to 1-propenyl ethers, which is usually performed with potassium tert-butoxide in dimethyl sulfoxide, can also be carried out under milder conditions using tris(triphen-ylphosphine)rhodium chloride,208 and by an ene reaction with diethyl azodicarboxylate,209,210 which affords a vinyl ether adduct. Removal of an O-allyl group may be achieved by oxidation with selenium dioxide in acetic acid,211 and by treatment with N-bromosuccinimide, followed by an aqueous base.201,212... 

T he oxidation of olefins by selenium dioxide has received much atten-- tion because of the unique characteristics of the reaction that produces an allylic derivative of the olefin (ester, alcohol, or ether, depending upon the solvent) and elemental selenium as the final reduced state of the oxidant. 

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)). 

While most synthetic examples of selenium dioxide allylic oxidation now involve more sophisticated systems (see below), use of the simple stoichiometric reagent alone is still popular. One recent example which well illustrates the mildness and possible selectivity of the reaction is shown in equation... 

A useful modification of selenium dioxide allylic oxidation was introduced by Sharpless in 1977. An inevitable complication of the normal reaction is the production of odoriferous low-valent selenium species which may be difficult to remove from the product mixtures and which can give rise to organo-selenium by-products. Sharpless provided a solution to this problem by the introduction into tlw re-... 

Selenium-mediated allylic oxidations producing allylic alcohols have been discussed above however, in some cases oxidation proceeds further to give the a, -unsaturated carbonyl compounds directly, or mixtures of alcoholic and ketonic products. That the regioselectivity observed in these allylic oxidation reactions closely resembles that found in classical selenium dioxide oxidations is in accord with initial formation of the intermediate allylic alcohol before in situ oxidation to the carbonyl compound. This process was studied by Rapoport and was explained mechanistically as an elimination of the intermediate allylic selenite ester via a cyclic transition state, analogous to Ssi (rather than 5n20 solvolysis (Scheme 21). Of the two possible transition states (78) and (79), the cyclic alternative (78) was preferred tecause oxidation exclusively yields trans aldehydes. 

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. 

Among oxi tions producing allylic alcohols or their derivatives the modem variants of selenium dioxide oxidations are by far the most popular. Systems based on metal acetates, particularly palladium tri-fluoroacetate, can be very useful and are receiving increasing attention but the Kharasch-Sosnovsky reaction, once very common for allylic oxidation, is now rarely used. Sensitized photooxidation with singlet oxygen, a very well-known procedure, is still somewhat unpredictable and has periu K received less consideration than it deserves. 

SAFETY PROFILE Poison by ingestion and inhalation. A corrosive irritant to skin, eyes (at 2 ppm), and mucous membranes. Potentially explosive reaction with chlorobenzene + sodium, dimethyl sulfoxide, molten sodium, chromyl chloride, nitric acid, sodium peroxide, oxygen (above 100°C), tetravinyl lead. Reacts with carboxylic acids (e.g., acetic acid) to form violently unstable products. Violent reaction or ignition with Al, chromium pentafluoride, diallyl phosphite + allyl alcohol, F2, hexafluoroisopropylideneaminolithium, hydroxylamine, iodine chloride, PbOa, HNO2, organic matter, potassium, selenium dioxide, sulfur acids (e.g., sulfuric acid. 

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. 

Earlier synthetic applications of selenium dioxide for the introduction of the carbonyl functionality at activated positions, to dehydrogenation of highly activated saturated sites, to hydroxylation of activated carbon-bearing positions, particularly at allylic(propargylic) sites, and to oxidative bond cleavage are presented in a few books devoted to selenium chemistry [2] or oxidation reactions [14]. These procedures are also permanently included in the Fieser Fieser compendium of reagents [15]. 

Allylic oxidation of olefins is a reaction of considerable value in organic synthesis [18] and selenium dioxide itself or in combination with other cooxidants remains a highly predictable and reliable reagent to perform these reactions. Thus, selenium dioxide oxidation of (Z)-tributyltin 1-alkenylcarba-mates 46 constitutes the first successful example of such a conversion ever reported with an element other than hydrogen [19]. Namely, it was found that with the allylic stannanes 46a or 46b oxidation occurred smoothly within 15 min to deliver in good yields the expected corresponding allylic alcohols 47a and 47b, respectively (Eqs. 6 and 7). 

---