Enones allylic oxidation

Now that the allylic oxidation problem has been solved adequately, the next task includes the introduction of the epoxide at C-l and C-2. When a solution of 31 and pyridinium para-tolu-enesulfonate in chlorobenzene is heated to 135°C, the anomeric methoxy group at C-l 1 is eliminated to give intermediate 9 in 80% yield. After some careful experimentation, it was found that epoxy ketone 7 forms smoothly when enone 9 is treated with triphenyl-methyl hydroperoxide and benzyltrimethylammonium isopropoxide (see Scheme 4). In this reaction, the bulky oxidant adds across the more accessible convex face of the carbon framework defined by rings A, E, and F, and leads to the formation of 7 as the only stereoisomer in a yield of 72%. 

All that remains before the final destination is reached is the introduction of the C-l3 oxygen and attachment of the side chain. A simple oxidation of compound 4 with pyridinium chlorochro-mate (PCC) provides the desired A-ring enone in 75 % yield via a regioselective allylic oxidation. Sodium borohydride reduction of the latter compound then leads to the desired 13a-hydroxy compound 2 (83% yield). Sequential treatment of 2 with sodium bis(trimethylsilyl)amide and /(-lactam 3 according to the Ojima-Holton method36 provides taxol bis(triethylsilyl ether) (86 % yield, based on 89% conversion) from which taxol (1) can be liberated, in 80 % yield, by exposure to HF pyridine in THF at room temperature. Thus the total synthesis of (-)-taxol (1) was accomplished. 

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... 

The related dirhodium(II) a-caprolactamate (cap) complex [Rh2(p--cap)4] undergoes a one-electron oxidation process at quite a lower potential (11 mV) than the acetate complex (1170 mV). In agreement with the Kochi hypothesis, the a-caprolactamate complex has recently been found to be an exceptional catalyst for the allylic oxidation of alkenes under mild conditions. A wide range of cyclohexenes, cycloheptenes, and 2-cycloheptenone (Eq. 5) are rapidly converted to enones and enediones in 1 h with only 0.1 mol % of [Rh2( x-cap)4] and yields ranging from 60 to 90%, in the presence of potassium carbonate [34]. 

C>2 is known to react with olefins to form allylic hydroperoxides via the Schenck reaction. Even if cyclohexene has a rather low reactivity towards 02 [19], it is likely that at least part of the allylic oxidation products (enylOOH, enol, enone) arise from a 02 reaction, rather than from a free radical chain process. 

Allylic oxidation.2 t-Butyl hydroperoxide (0.5 equiv.) in acetic acid in the presence of catalytic amounts of this Rh30 complex (1) oxidizes cycloalkenes to a,/ -enones and the corresponding allylic acetates in the ratio of 6-7 1. Other rhodium complexes are less effective. Allylic alcohols (but not the acetates) are oxidized by this reaction to a,/ -enones. 

As shown in Scheme 3.19, two competing pathways are possible with regard to allylic oxidation. The alkene 1 can either undergo abstraction of an allylic hydrogen and subsequent formation of the allylic alcohol 2 and the enone 3 (path A), respectively, or alternatively epoxidation of the C=C double bond occurs to give derivative 4 (path B). In order to develop a suitable catalytic system for path A, it is of utmost importance to achieve high chemoselectivity in addition to high catalytic... 

Allylic oxidation. Reaction of alkenes with /-butyl hydroperoxide (90%) in the presence of catalytic amounts of Cr(CO)6 results in oxidation to a,p-enones in 25-100%... 

Chromic acid itself has been used in the oxidation of alkenes and in some cases allylic oxidation products were observed for example, cyclohexene was converted to cyclr xenone in 37% yield and l methylcyclohexene was oxidized to a mixture of enones (Scheme 16)." ... 

Overall, many transition metal complexes have been investigated. Among those not mentioned above which may carry out catalytic allylic oxidation to give enones under certain drcumstances are Co(PPh3)Cl/02, Mn(TPP)Cl/02, [Fe(PPh3)]20AJV, Ni(phthalocyanine)/02 and an unusual mercury(II) acetate example in which the enone is formed rather than the expected acetate. 

Observation of the reaction by TLC indicated initial formation of the allylic alcohols which were oxidized in situ to give the enone. The foUowing mechanism for allylic oxidation was proposed (Scheme 22). 

Clearly, regio- and chemo-selectivities of this reagent are highly dependent on the substrate structure. Allylic oxidation to give enones has also been reported at the 11-position of steroids upon treatment with nitrosyl fluoride solutions. °°... 

Deoxygenation. Greene has applied Kabalka s method for reduction of an enone (6, 98 7, 54) to the tosylhydrazone of a cross-conjugated ketone, 6-epi-a-santonin (2). Unexpectedly only one olefin (3) was obtained in 50% yield. This product was converted into the diene 4 by allylic oxidation, reduction to an allylic alcohol, and dehydration. The product was converted into (—)-dictyolene (5) by a method developed previously. ... 

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