Oxidation of Tertiary Allylic Alcohols

Oxidation of Tertiary Allylic Alcohols (The Babler Oxidation) 97... 

OXIDATION OF TERTIARY ALLYLIC ALCOHOLS (THE BABLER OXIDATION)... 

Oxidation of allylic and homoaUyic alcohols. A convenient route to 3-thioalkyl-2-cycloalkenones is based on the established pattern of transpositional oxidation of tertiary allylic alcohols. The substrates are readily prepared by reaction of the enones with phenylthiomethyllithium or l,3-dithian-2-yllithium reagents. 

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. 

As the Jones-mediated transformation of tertiary allylic alcohols into enones is normally slower than the oxidation of secondary alcohols into ketones it is possible to selectively oxidize a secondary alcohol to ketone, without affecting a tertiary allylic alcohol present in the same molecule. 

This oxidative transposition of tertiary allylic alcohols into enones or enals is carried out under mild conditions and has ample application in organic synthesis. Although, it can be carried out with other chromium-based reagents (see pages 16 and 35), PCC is the reagent of choice.272... 

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). ... 

J.-M. Bregeault, C. Lepetit, F. Ziani-Derdar, O. Mohammed i, L. Salles, A. Deloffre, Epoxidation of tertiary allylic alcohols and subsequent isomerization of tertiary epoxy-alcohols A comparison of some catalytic systems for demanding ketonization processes, in R. K. Grasselli, S. T. Oyama, A. M. Gaffney, J. E. Lyons (Eds.), 3rd World Congress on Oxidation Catalysis, Elsevier, Amsterdam, Stud. Surf. Sci. Catal. 110 (1997) 545. 

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

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)... 

As a further extension, the Kim group very recently developed the aerobic oxidation and [l,5]-hydride transfer/cyclization sequence starting from readily available ortho tertiary amine substituted cinnamyl alcohols 24 (Scheme 4.12). The tetrapropylammonium perruthenate (TPAP) was identified as the competent catalyst for the initial aerobic oxidation of the allylic alcohols. The synthetically useful tetrahydroquinoline derivatives 25 were prepared in moderate yields and high level of enantioselectivity. 

The relationship between 9 and its predecessor 10 is close. Oxidation of the allylic C-3 methylene group in 10 and elimination of the methoxy group could furnish enone 9. Retrosynthetic disassembly of ring E in 10 furnishes tertiary alcohol 11 as a viable precursor. That treatment of 11 with a catalytic amount of acid will induce the formation of a transient oxonium ion at C-12 which is then intercepted by the appropriately placed C-4 tertiary hydroxyl group is a very reasonable proposition. As we will see, the introduction of the requisite C-4 hydroxyl group is straightforward from intermediate 12. 

The reaction sequence Is based on the readiness with which a-pinene undergoes oxidation predominantly to the tertiary acetate with Pb(OAc)4.3 4 Dichromate oxidation of the derived alcohol proceeds by way of a second allylic rearrangement to give verbenone without affecting the neighboring stereogenic centers. 

In most cases the catalytically active metal complex moiety is attached to a polymer carrying tertiary phosphine units. Such phosphinated polymers can be prepared from well-known water soluble polymers such as poly(ethyleneimine), poly(acryhc acid) [90,91] or polyethers [92] (see also Chapter 2). The solubility of these catalysts is often pH-dependent [90,91,93] so they can be separated from the reaction mixture by proper manipulation of the pH. Some polymers, such as the poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymers, have inverse temperature dependent solubihty in water and retain this property after functionahzation with PPh2 and subsequent complexation with rhodium(I). The effect of temperature was demonstrated in the hydrogenation of aqueous allyl alcohol, which proceeded rapidly at 0 °C but stopped completely at 40 °C at which temperature the catalyst precipitated hydrogenation resumed by coohng the solution to 0 °C [92]. Such smart catalysts may have special value in regulating the rate of strongly exothermic catalytic reactions. 

Substituted allylic alcohols are carbonylated using the oxidizing system of PdCl2 and CuCU in the presence of HCI and oxygen at room temperature and l atm of CO to give the 7-lactone 16 in moderate yields[20], Carbonylation of secondary and tertiary allylic alcohols catalyzed by Pd2(dbah and dppb affords the 7-lactone 17 by selective attack of CO at the terminal carbon under fairly severe conditions[21]. 

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). 

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... 

Sometimes, tertiary allylic alcohols interfere with the oxidation of primary and secondary alcohols with PDC, causing low-yielding transformations into the desired aldehydes and ketones.161 Secondary allylic alcohols occasionally suffer oxidative transposition to enones rather than a direct oxidation.162... 

PCC reacts with tertiary allylic alcohols, forming an intermediate chromate ester that evolves giving a conjugated enone or enal. Sometimes, the isomeric chromate ester produces the epoxidation of the alkene, giving an epoxy alcohol that can be further oxidized to an epoxy ketone. 

Of course, using excess of PCC allows the operation of both, an oxidative transposition of a tertiary allylic alcohol and a normal oxidation of a primary or a secondary alcohol.276... 

The oxidation with PCC causes both, a normal oxidation of the primary alcohol and an oxidative transposition of the tertiary allylic alcohol. 

Although secondary allylic alcohols can suffer an oxidative transposition via the corresponding allylic chromate ester, in the same manner that the tertiary allylic alcohols normally, a direct oxidation to the corresponding enone with no transposition predominates.277 Nevertheless, minor amounts of enone, resulting from an oxidative transposition, can be formed.278 The formation of transposed enone may be minimized using the less transposing-prone PDC, instead of PCC.279... 

Although allyl-arenes are prone to olefin isomerization, several successful reactions have been performed, for example in the chemoselective oxygenation of 22 to aryl-acetone 23 (Table 2) [38]. Allyl alcohols sometimes react sluggishly, but examples with high ketone selectivity are known, for example the oxidation of tertiary alcohol 24 to a-hydroxyketone 25 [39]. 

That was a [3,31 -sigmatropic reaction involving two nitrogens. There follows one with two oxygens and a chromium atom. When tertiary allylic alcohols are oxidized with CrC>3 in acid solution, no direct oxidation can take place, but a kind of conjugate oxidation occurs. 

There are a variety of products, depending upon the alcohol. Allylic and benzylic alcohols are easily oxidized under mild conditions. Secondary alcohols are oxidized under rather stronger conditions. Simple primary alcohols (i.e., not activated benzylic alcohols) are not oxidized. The oxidation of tertiary alcohols is accomplished with C-C bond fission. 

---