Allylic oxidation of alkenes

Since 1-aikynes are relatively resistant to oxidation, strong oxidants are required to effect oxidative cleavage of terminal aikynes to carboxylic acids with loss of one carbon. lodosylbenzene in combination with Ru catalysts or potassium perman-ganate cleaves 1-aikynes to carboxylic acids. Phase transfer agents (quaternary ammonium salts ) are used in the KMn04 oxidations to overcome problems associated with the low solubility of permanganate in nonpolar solvents. 

Conversion of 1-aikynes into substituted acetic acids without the loss of one carbon is accomplished via hydroboration-oxidation, as exemplified below.  

Ruthenium- or permanganate-mediated oxidations of internal aikynes are highly dependent on solvent conditions and generally afford the corresponding a-diketones.  

Alkenes possessing allylic C-H bonds are oxidized by SeOj either to allylic alcohols or esters or to a,p-unsaturated aldehydes or ketones, depending on the experimental conditions.The reaction involves an ene-type reaction (A) followed by a sigmatrop-ic [2,3]-shift (B) to give the selenium ester (C), which is converted to the corresponding allylic alcohol (D) on solvolysis.  

If the alkene possesses a methyl substituent, oxidative cleavage of C (elimination of a selenium atom and water) furnishes the corresponding a,(3-unsaturated aldehyde. Lower yields of products were obtained when using stoichiometric amounts of Se02. t-Butyl hydroperoxide is used to reoxidize selenium. Besides giving the desired carbonyl compounds, the reaction may also produce allylic alcohols as side products. 

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Alkenes can be aminated in the allylic position by treatment with solutions of imido selenium compounds R—N—Se=N—R. The reaction, which is similar to the allylic oxidation of alkenes with Se02 (see 14-4), has been performed with R = t-Bu and R=Ts. The imido sulfur compound TsN=S=NTs has also been used... 

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 equivalent to allylic oxidation of alkenes, but with allylic transposition of the carbon-carbon double bond, can be carried out by an indirect oxidative process involving addition of an electrophilic arylselenenyl reagent, followed by oxidative elimination of selenium. In one procedure, addition of an arylselenenyl halide is followed by solvolysis and oxidative elimination. 

Scheme 8. General mechanism of the copper-catalyzed allylic oxidation of alkenes (Kharasch-Sosnovsky reaction).

Figure 13. Stereochemical model proposed by Andrus for the allylic oxidation of alkenes using 55c Cu complexes. [Adapted from (109).]...

Scheme 11. Results and stereochemical model proposed by Singh for the allylic oxidation of alkenes using 157-Cu complexes [Adaptedfrom (111).]...

Scheme 12. Proposed mechanism leading to the allylic imide observed as a side product in the allylic oxidation of alkenes in nitrile solvents. [Adapted from (120).]...

Scheme 48 Allylic oxidation of alkene with Ru(IV)-complexes.

A catalytic method for the allylic oxidation of alkenes was first reported by Umbreit and Sharpless in 1977, who utilized TBFIP as oxidant and Se02 as catalyst for selective aUylic oxidation. Yields were moderate providing aUylic alcohols or ketones with 54-86% yield. The reaction did not proceed under strictly anhydrous conditions but with one equivalent of water present the oxidation proceeds smoothly at room temperature. In... 

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]. 

SCHEME 126. Allylic oxidation of alkenes and alkynes with Se02/TBHP... 

Freshly prepared Mn02 is a useful reagent in organic chemistry and has been used in a large variety of oxidative transformations.311 These reactions involve the allylic oxidation of alkene to a,/3-unsaturated carbonyl compounds, the transformation of methylarenes to benzaldehyde and benzoic acid derivatives, the oxidation of secondary methylene groups to ketones, and the oxidation of alcohols to carbonyl compounds.311 The yields are generally fair to good. 

Selenium dioxide, Se02, is a widely used reagent for the allylic oxidation of alkenes and ketones. The subject has been extensively covered by recent review articles56,291 293 and only a short summary will be given in this chapter. 

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)). 

Sharpless has achieved the allylic oxidation of alkenes using arylselenenic acids, generated in situ from the diselenide and r-butyl hydroperoxide, a reaction claimed to occur with exclusive allylic rearrangement. ... 

Examples of the use of chromium(VI) reagents to effect the allylic oxidation of alkenes to give a,3-unsaturated carbonyl compounds are very common in the literature. The reaction was first reported by Treibs and Schmidt for the allylic oxidations of a-pinene to verbenone and verbenol, of dipentene to carvone and caiveol, and of cyclohexene to cyclohexenol and cyclohexenone, using a solution of chromium trioxide in a mixture of acetic anhydride and carbon tetrachloride. However, yields were low and no synthetic use of this observation was made. 

A combination of rtiodium(III) chloride with silver acetate, and treatment of rhodium(II) acetate in acetic acid solution with ozone, are two methods for generation of the (is-oxotrimetal-acetato complex of rhodium [Rhs0(0Ac)6 2O)3]0Ac. This RhsO complex was found to effect catalytic allylic oxidation of alkenes efficiently to give the corresponding a -unsaturated carbonyl compounds in the presence of a reoxidant such as r-butyl hydroperoxide, although in disappointing yield (equation 44). 

More recently Barton and Crich reported the use of 2-pyiidineseleninic anhydride in the allylic oxidation of alkenes. This reagent is prepared in situ by the oxidation of the corresponding diselenide by iodylbenzene. It effects oxidation to a -unsaturated ketones with retention of the double bond regio-chemistry (e.g. equation SO). 

The allylic oxidation of alkenes by O2 involves an ene reaction, and proceeds with rearrangement s as in Scheme 4. The intermediate allylic hydroperoxide (5) can be reduced to yield an allylic alcohol (6), or be treated with base to give an unsaturated carbonyl conqiound (7). The reaction works best on tri- or tetra-substituted alkenes, and the relative preference for attack is Me - CH2 CH. The O2 allylic oxidation has been used in the synthesis of a large number of natural products, including some naturally occurring allylic hydroperoxides. It is possible that O2 reactions of this type are involved in biosynAetic processes. 

Catalytic Allylic Oxidation of Alkenes Using Diselenides... 

A thoughtful reader would have noticed that, while plenty of methods are available for the reductive transformation of functionalized moieties into the parent saturated fragments, we have not referred to the reverse synthetic transformations, namely oxidative transformations of the C-H bond in hydrocarbons. This is not a fortuitous omission. The point is that the introduction of functional substituents in an alkane fragment (in a real sequence, not in the course of retrosynthetic analysis) is a problem of formidable complexity. The nature of the difficulty is not the lack of appropriate reactions - they do exist, like the classical homolytic processes, chlorination, nitration, or oxidation. However, as is typical for organic molecules, there are many C-H bonds capable of participating in these reactions in an indiscriminate fashion and the result is a problem of selective functionalization at a chosen site of the saturated hydrocarbon. At the same time, it is comparatively easy to introduce, selectively, an additional functionality at the saturated center, provided some function is already present in the molecule. Examples of this type of non-isohypsic (oxidative) transformation are given by the allylic oxidation of alkenes by Se02 into respective a,/3-unsaturated aldehydes, or a-bromination of ketones or carboxylic acids, as well as allylic bromination of alkenes with NBS (Scheme 2.64). 

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