Tertiary allylic alcohols, oxidative rearrangement

Collins reagent can transform tertiary allylic alcohols into rearranged enones,101 similar to PCC, which is routinely used for this purpose (see page 55). As this reaction is normally slower than the oxidation of primary and secondary alcohols, these can be oxidized with Collins reagent with no interference from tertiary allylic alcohols present in the same molecule.102... 

We had two possible routes in which alcohol 72 could be used (Scheme 8.19). Route A would involve rearrangement of tertiary alcohol 72 to enone 76. Deprotonation at C5 and generation of the enolate followed by exposure to an oxaziridine or other oxygen electrophile equivalents might directly afford the hydrated furan C-ring of phomactin A (see 82) via hydroxy enone 81. We had also hoped to make use of a chromium-mediated oxidative rearrangement of tertiary allylic alcohols. Unfortunately, treatment of 72 to PCC produced only unidentified baseline materials, thereby quickly eliminating this route. 

Tertiary allylic alcohols form a chromate ester that, as it lacks a hydrogen on a to the alcohol, instead of suffering a normal oxidation to ketone rearranges to an enone. This transformation, which can be brought about by other chromium-based reagents, is normally carried out with PCC when it is purposefully sought at (see page 55). 

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. 

In a similar fiashion to the Collins reagent, PCC will also induce oxidative rearrangement of tertiary allylic alcohols (Table S). PCC, and several other chromium oxidants, will also cause tertiary cyclopropyl alcohols to rearrange to give 3,y-unsaturated carbonyl compounds (equation 8). ... 

However, the conversion to the transposed a,p-unsaturated carbtxiyl compound is by far the more useful reaction. The fiill sequence serves both to form carbon-carbon bonds as well as to adjust the functional group array in tlw synthetic intermediate. Thus, starting with the enone (15), organometallic addition generates a tertiary allylic alcohol (16) and oxidative rearrangement yields a P-a]kyl-a,p-enone... 

The allyl alcohol in the seven-membered ring is oxidized to the corresponding a,P-unsaturated ketone as expected, whereas the allyl alcohol in the five-membered ring is oxidized to afford the transposed a,P-unsaturated ketone after [3,3]-sigmatropic rearrangement. This behavior is only observed with cyclic, tertiary allyl alcohols upon treatment with one equivalent of pyridinium chlorochromate. The desired oxidation product 34 is obtained in 90 % over two steps. 

Ohler, E.. and Zbiral. Ei.. Oxidative rearrangement of phosphorus containing tertiary allylic alcohols. Synthesis of (3-oxo-l-cycloalkenyl)phosphonates, -methylphosphonates, -methyldiphenylphosphine oxides and their epoxy derivatives. Synthesis, 357, 1991. 

Recent Developments in the Pauson-Khand Reaction Oxidative Rearrangement of Tertiary Allylic Alcohols Other Methods... 

Addition of isopropyl lithium to the surviving ketone followed by oxidative rearrangement of the resulting tertiary allylic alcohol and concomitant oxidation of the secondary allylic alcohol gave the diketone 10. Selective addition of methyl lithium to the less hindered of the two ketones, again from the more open face, then gave 3. 

Ishihara and coworkers have developed an oxidative rearrangement of tertiary allylic alcohols 97 to enones 98 with Oxone promoted by catalytic quantities of sodium 2-iodobenzenesulfonate (Scheme 4.50)... 

The oxidative rearrangement of tertiary cyclopropylcarbinols to 3,4-unsaturated carbonyl conqrounds is analogous (or homologous) to the reaction of allylic alcohols, and is shown in the example in equation... 

The oxidative rearrangement of tertiary cyclopropylcarbinols to 3,4-unsaturated carbonyl compounds is analogous (or homologous) to the reaction of allylic alcohols, and is shown in the example in equation (29). This reaction has been shown to proceed stereospecifically in the conversion of the cis-substituted cyclopropylcarbinol (29) to the (Z)-enynone (30) shown in equation (30). The substrates with R = H, Me and TMS all gave comparable yields. 

Chiral tertiary allylic amines 191 with /ra r-2-phenylsulfonyl-3-phenyloxaziridine 33 also gave rise to amine A -oxides 192, which underwent the [2,3]-Meisenheimer rearrangement to hydroxylamines 193 with a high level of stereoselectivity (Table 14) <1999J(P1)2327>. Reduction of 193 gave the corresponding allylic alcohols 194. 

No other derivatives of the tertiary cation, such as the aUylic alcohol in the last part, can r formed this way because the rearrangement is too fast. The reaction with PhSe-SePh and NaBH a trick to get this allylic alcohol. The true reagent is PhSe , formed by reduction of the Se-Se bcr. It is very nucleophilic and will attack even the tertiary epoxide to give a selenide. Oxidation to rh selenoxide leads to a fast concerted cis elimination. The intermediate selenide is unstable as wel m very smelly and must be oxidized immediately before it decomposes. 

The rearrangement can be catalytically brought about with silver and copper salts or mote recently with Pd compounds. a, -Unsaturated carbonyl compounds are also often formed under rearrangement on oxidation of allylic alcohols, especially when they are tertiary. This process can serve to perform a 1,3-transposition of carbonyl groups in a, -unsaturated ketones (Scheme 9). ... 

The olefin 157 was epoxidized to an equimolar mixture (158a,b). Both epoxides opened with lithium di-/t-propy]amide to the desired allylic alcohols (159). Expoxide 158a also yielded unwanted tertiary alcohol 160 (40%). Reaction of the crude epoxide mixture with lithium di-/i-propylamide followed by oxidation (Ct03-py2) and purification resulted in a 71 29 mixture of enones 152 and 161, with an overall yield of 152 from 155 of 16%. The oxidation of 160 to 161 occurs by allylic rearrangement of the intermediate chromate ester. The reduction product from 154 was resolved into its enantiomers via the brucine salt of the hydrogen phthalate 162. The levorotatory enantiomer was found to have the absolute configuration corresponding to that of the pentacyclic triteipenes. 

A useful application of chromium-based oxidants, especially pyridinium chlorochromate, is in the conversion of allylic tertiary alcohols to their transposed a,(3-unsaturated ketones. For example, treatment of the allylic alcohol 24 with PCC gave the a,p-unsaturated ketone 25 (6.23). The reaction is thought to proceed by rearrangement of the chromate ester of the allylic alcohol to give a new allyl chromate ester that is oxidized to the ketone. 

Carbon-Oxygen Bond Formation. CAN is an efficient reagent for the conversion of epoxides into /3-nitrato alcohols. 1,2-cA-Diols can be prepared from alkenes by reaction with CAN/I2 followed by hydrolysis with KOH. Of particular interest is the high-yield synthesis of various a-hydroxy ketones and a-amino ketones from oxiranes and aziridines, respectively. The reactions are operated under mild conditions with the use of NBS and a catalytic amount of CAN as the reagents (eq 25). In another case, N-(silylmethyl)amides can be converted to A-(methoxymethyl)amides by CAN in methanol (eq 26). This chemistry has found application in the removal of electroauxiliaries from peptide substrates. Other CAN-mediated C-0 bondforming reactions include the oxidative rearrangement of aryl cyclobutanes and oxetanes, the conversion of allylic and tertiary benzylic alcohols into their corresponding ethers, and the alkoxylation of cephem sulfoxides at the position a to the ester moiety. 

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