Allylic hydroxylation selenium dioxide

Allylic oxidation. Selenium dioxide is the classical reagent for allylic hydroxylation (1,994-996), but it has the drawback that selenium compounds are about as toxic as arsenic compounds. However, SeOa need be used in only catalytic amounts if used in conjunction with H2O2 (507 ). Thus -pinene (1) can be converted into /runi-pinocarveol (2) in 49-55% yield by oxidation with Se02-H2O2 in /-butyl alcohol. This product has been prepared in somewhat higher yield... 

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. 

Allylic Hydroxylation and Acyloxylation. Selenium dioxide is a standard, commonly used stoichiometric oxidant to convert alkenes to allylic alcohols.668-671 In aqueous solution it reacts as seleniuos acid (84), whereas in other hydroxylated solvents (alcohols, carboxylic acids) the alkyl selenite (85) and the mixed anhydride (86), respectively, are the actual reagents ... 

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]. 

Hydroxylation of the allylic methylene group in a- and 5,6-epoxides 56 and 57 was very effectively realized by a combination of selenium dioxide and pyridine N-oxide in dioxane [22 a]. Starting from 56 the Ip-hj-droxy isomer of 58 was obtained as a single product (Eq. 8) while, under the same conditions, the acetate 57 was converted to a 78 22 mixture of the la- and 1 5-hydroxy isomers 59a and 59b, respectively (Eq. 9). In this context it is interesting to note that a similar hydroxylation procedure with... 

During the enantioselective total synthesis of miroestrol by E.J. Corey and co-workers, the introduction of a hydroxyl group was required at one of the bridgehead positions. This position was a to a ketone and was also the allylic position to a double bond. The oxidation was effected by selenium dioxide/fert-butyl hydroperoxide at 25 °C. 

Ra, C. S., Park, G. Ah initio studies of the allylic hydroxylation DFT calculation on the reaction of 2-methyl-2-butene with selenium dioxide. Tetrahedron Lett. 2003, 44, 1099-1102. 

Singleton, D. A., Hang, C. Isotope effects and the mechanism of allylic hydroxylation of alkenes with selenium dioxide. J. Org. Chem. 2000, 65, 7554-7560. 

Selenium dioxide (Se02) is commonly used to hydroxylate alkenes in the al-lylic position. The mechanism of this transformation involves two sequential peri-cyclic reactions. The first reaction is an ene reaction. It gives a selenenic acid. Then a [2,3] sigmatropic rearrangement occurs, and the intermediate loses SeO to give the observed product. Note how two allylic transpositions result in no al-lylic transposition at all ... 

AUyUc hydroxylation. From investigations of his own and analysis of the literature, Guillemonat" proposed the following rules regarding the allylic hydroxylation of olefins by selenium dioxide ... 

Diagnosis of unsaturation types. A -Cholestenyl acetate is oxidized by selenium dioxide in acetic acid-benzene to give 7a-acetoxy-A -cholestene (2), probably by allylic hydroxylation at C14, allylic rearrangement, and acetylation. Since oxidation occurs readily at room temperature whereas cholesterol is attacked only at 55-60°, the reaction can be used to detect small amounts of A -cholestenol... 

AUylic hydroxylation [1, 994-996, at end]. Oxidation of a-cyclodihydrocostun-olide (I) with selenium dioxide unexpectedly results in attack of the allylic methine group to give (II) as the major product (30% yield).1811... 

An Upjohn group181 found that steroid c/.v-unsaturated esters of type (6) undergo allylic hydroxylation at C16 when treated with selenium dioxide in THF in the presence of acetic acid. Both the a- and /3-alcohols are formed. The products (7) and (8) were used for preparation of 16-halocorticoids. 

A key step in the partial synthesis of the steroidal insect hormone ecdysone is introduction of a 14a-hydroxyl group. Three groups [Schering (Berlin)-Hoffmann La Roche (Basel)18d and Syntex18 ] achieved this end by allylic oxidation of A7-6-keto-stcroids, both 5a and 5/3, by selenium dioxide in dioxane. Yields are high. 

Oxidative cleavage of aUyl and propargyl ethers. Hydroxyl and phenolic groups have been protected as the allyl ethers. Hydrolytic cleavage of protective group involved isomerization to the propenyl ether by potassium r-butoxide in DMSO followed by hydrolysis (1, 300 2, 158). Japanese chemists4 now find that allyl ethers can be cleaved in one step by oxidation with a slight excess of selenium dioxide in acetic acid-dioxane (reflux, 1 hr.). Presumably a hemiacetal of acrolein... 

Allylic functionalization of 187 could not be effected under a variety of conditions (e.g., A-bromosuccinimide, lead tetraacetate, selenium dioxide), nor could an additional double bond be introduced under dehydrogenation conditions (e.g., chloranil). Osmium tetroxide was ineffective in hydroxylation of 187 however, potassium permanganate treatment gave the diol 189 although in only 5.5% yield [originally reported as 33% (67)]. Compound 189 could be converted into 190 again in low yield (4.5%). The latter was shown to be identical with yet another degradation product (68, Scheme 11) of securinine by comparison of IR spectra and GLC behavior. 

From a practical viewpoint, direct C-1 hydroxyktion of vitamin D3 is a highly desirable reaction. However, direct allylic oxidation of vitamin D3, for example, with selenium dioxide/t-butylhydroperoxide [scheme (31)] produces only small amounts (< 5%) of 1 -hydroxylated compounds. 

With the two methyl stereocenters successfully set, we next focused on installing the secondary C4-hydroxyl group. Using selenium dioxide, we were able to convert the allylic methyl ether in one step into an enal (174), which we then reduced with diisobutylaluminum hydride (175, Scheme 32). This allylic alcohol could be epoxidized with /m-CPBA, thus ensuring installation of the desired C4-hydroxyl group stereocenter under substrate-controlled conditions... 

Hydroxylation of oleic acid, 18 1(9Z), in the allylic positions with selenium dioxide//er/-butylhydroperoxide has been reported (27,28). 9,18- and 10,18-Dihy-droxy-18 0 were prepared by condensation of two a,co-difunctional synthons derived from suitable a,co-alkanediols (29). The synthesis of 7,10-dihydroxy-18 1 (8E) was achieved by Wittig olefination reaction of appropriate synthons (30). 

Thus, ergocalciferol is reacted with sulfur dioxide at -10 °C, and then the hydroxy-group is sUylated. The chelotropic extrusion of sulfur dioxide produces the (5 ,7 )-isomer. Allylic hydroxylation by Barton s method with selenium dioxide and JV-methylmorpholine JV-oxide gives a mixture of (IS)- and (lH)-isomers in the ratio of 7 1. SUylation of the hydroxy-group at the 1-position and crystallisation lead finally to the (lS,5 )-hydroxy-derivative in pure form. The yield over all the reaction stages is around 28-35 %. [102,103]... 

Despite selenium s toxicity, selenium reagents occupy an important niche in organic chemistry. Selenium dioxide, in particular, allows a number of oxidative transformations that are not as readily accomplished by other methods. One such reaction is allylic hydroxylation, where Se02 oxidizes an allylic C-H bond to C-OH without rearrangement of the double bond. Thus, the plant natural product (-)-/ -pinene is oxidized as follows ... 

---