Allenes oxidation

Methylideneoxiranes (allene oxides) (80T2269), e.g. (9) and (23), are also highly reactive, and undergo facile thermal isomerization to cyclopropanones, possibly via an oxyallyl intermediate (24 Scheme 20). 

Methylideneoxiranes (allene oxides Section 5.05.3.2.1) react with nucleophiles as if ring opening occurs to give a zwitterion (e.g. 51 or 52), which may be captured by the nucleophile before (Scheme 42) or after (Scheme 43) isomerization to a cyclopropanone. 

Extracts from Clavularia viridis and also many other coral species convert arachidonic acid to the prostanoidpreclavulone-A via 8-( f )-hydroperoxy-5,ll,14( Z), QfEj-eicosatetraenoic acid. The carbocyclization is considered to occur from allene oxide and oxidopentadienyl cation intermediates. An enantioselective total synthesis of preclavulone-A was developed to assist the biosynthetic research. 

As with i -substituted allyl alcohols, 2,i -substituted allyl alcohols are epoxidized in excellent enantioselectivity. Examples of AE reactions of this class of substrate are shown below. Epoxide 23 was utilized to prepare chiral allene oxides, which were ring opened with TBAF to provide chiral a-fluoroketones. Epoxide 24 was used to prepare 5,8-disubstituted indolizidines and epoxide 25 was utilized in the formal synthesis of macrosphelide A. Epoxide 26 represents an AE reaction on the very electron deficient 2-cyanoallylic alcohols and epoxide 27 was an intermediate in the total synthesis of (+)-varantmycin. 

Allenes 6 also react with peracids allene oxides 7 are formed, or even a spiro dioxide 8 can be obtained by reaction with a second equivalent of peracid ... 

Macomber has described the oxidation of 3-methyl-l,2-butadienephosphonic acid with 3-chloroperbenzoic acid to the corresponding cyclic allenic oxide, which undergoes rearrangement to produce the corresponding unstable 2,5-dihydro-1,2-oxaphosphole-2-oxide derivative (Scheme 25) [66],... 

Scheme 5. Proposed biosynthesis of allene oxide 64 from 8i -lipoxygenase initiated metabolism of arachidonic acid and subsequent non-enzymatic transformations to racemic cyclopenteone 30 [86]...

A reasonable route for the formation of this racemic cyclopentenone (30) was proposed from 8.R-HPETE (29), which involves the non-enzymatic hydrolysis of an allene oxide (64) intermediate (Scheme 5 ) [86]. Biochemical precedence for these transformations was provided by earlier work with plants [90] and C. 

An acetone powder of P. homomalla was subsequently used to generate allene oxide 64 from exogenous 8P-HPETE [91]. This highly unstable compound (t1/2 = ca. 15 s at 0 °C, pH 7.4) was obtained by performing the biosynthesis at low temperature (0 °C) for 2 min in a vortexed emulsion of pH 6 buffer and pentane. Under these conditions, the allene oxide partitioned into the pentane where it was relatively protected from hydrolysis. HPLC analysis of the... 

Additional hypotheses concerning prostaglandin biosynthesis in P. homomalla resulted from isolation of 11R-HETE (76) from the polar lipid fraction [95]. Apparently, 11R-HETE (76) is also a minor product of incubations of arachidonic acid with acetone powder preparations of P. homomalla [95], In this alternate hypothesis (Scheme 8), an 11-hydroxy or 11-hydroperoxy-8,9-allene oxide intermediate is formed from a sequence of oxidations at C8 and Cll. Opening of the allene oxide to a transient C8 earboeation induces eycli-zation with a consequent addition of water to C15. This proposed pathway leads initially to formation of PGE2 (16 or 38), which following acetylation, elimination of acetic acid from Cl 1-12, and esterification, forms the observed major natural product in the coral, 15-acetoxy methyl PGA2 (36 or 54). Notably, if... 

R-HETE is a very potent and selective inducer of oocyte maturation [196, 199]. 8S-HETE does not show this activity. The allene oxide hydrolysis products and the hydroperoxide lyase products were not active in promoting oocyte maturation [200]. 

Brash AR, Baertschi SW, Harris TM (1990) Non-cyclooxygenase prostaglandin biosynthesis formation of PGA3 isomers via an allene oxide. In Reddy CC, Hamilton GA, Madyastha KM (eds) Biological oxidation systems, vol 2. Academic, San Diego, p 683... 

Figure 8.6 A diagram of the oxylipin pathway. LOX lipoxygenase AOS allene oxide synthase HPL hydroperoxide lyase AOC allene oxide cyclase OPDA Reductase 12-oxo-phytodienoic acid-10,11-reductase.

LAU, S.M., HARDER, P.A., O KEEFE, D.P., Low carbon monoxide affinity allene oxide synthase is the predominant cytochrome P450 in many plant tissues, Biochemistry, 1993,32,1945-1950. 

SONG, W.C., FUNK, C.D., BRASH, A.R., Molecular cloning of an allene oxide synthase A cytochrome P450 specialized for the metabolism of fatty acid hydroperoxides, Proc. Natl. Acad. Sci. USA, 1993, 90, 8519-8523. 

LAUDERT, D., PFANNSCHMIDT, U., LOTTSPEICH, F HOLLANDER-CZYTKO, H., WEILER, E.W., Cloning, molecular and functional characterization of Arabidopsis thaliana allene oxide synthase (CYP74) the first enzyme for the octadecanoid pathway to jasmonates, Plant Mol. Biol., 1996,31,323-335. 

If epoxidation is accepted as [2 + l]-cydoaddition, then the rare transformation of an allenyl ketone to an isolable allene oxide should be mentioned [170]. The Pau-son-Khand reaction, probably the best known of the [2 + 2 + l]-cycloadditions, can also be performed using an alkyne and an allene, the latter replacing a simple alkene. These reactions were summerized recently by Brummond also induding acceptor-substituted allenes [361]. 

A hydroxyalkyl substituent on the internal carbon atom of the allene can also be used to direct the epoxidation reaction (Eq. 13.22) [26]. In the case of vinylallene 70, hydroxyl-directed epoxidation, followed by cyclization of the allene oxide, leads to cyclopentenone 71 in 60% yield, along with 20% of epoxide 72. The greater reactivity of the allene ensures that the epoxidation step will be selective however, in this case the selectivity is not complete. 

The oxidative cyclization of vinylallenes need not be directed by a pendant hydroxyl group in order to succeed. The higher reactivity of the allene compared with the exocyclic methylene group in 73 (Eq. 13.23) with monoperphthalic acid leads primarily to the allene oxide which rearranges to cydopentenone 74 [27]. Inevitably some epoxidation of the alkene also takes place during the reaction. When m-CPBA is used as the oxidant, another side reaction is associated with m-chlorobenzoic add-mediated decomposition of the intermediate epoxide. It is possible to overcome this problem by performing the epoxidation in dichloromethane in a two-phase system with aqueous bicarbonate so as to buffer the add [28]. 

Epoxidation of amidoallenes with dimethyldioxirane leads to allene oxides as reactive intermediates which can be trapped with dienes in a [4+ 3]-cycloaddition reaction. Exposure of a mixture of amidoallene 177 with cydopentadiene to a small excess of dimethyldioxirane at -45 °C produced endo-bicydooctanone 178 in 60% yield (Eq. 13.60) [69]. The allene oxide is electrophilic, since no reaction takes place with methyl acrylate. 

The reaction of allenes with peracids and other oxygen transfer reagents such as dimethyldioxirane (DM DO) or hydrogen peroxide proceeds via allene oxide intermediates (Scheme 17.17). The allene oxide moiety is a versatile functionality. It encompasses the structural features of an epoxide, an olefin and an enol ether. These reactive intermediates may then isomerize to cyclopropanones, react with nucleophiles to give functionalized ketones or participate in a second epoxidation reaction to give spirodioxides, which can react further with a nucleophile to give hydroxy ketones. 

Only a few isolated allene oxides have been synthesized from allenes and characterized. Most often peracids are used but the oxidative and acidic conditions usually result in a complex mixture of products. To overcome this problem, dimethyldioxirane (DMDO) can be used, which rapidly oxidizes allenes to spirodiepoxides. Several synthetically useful methods have been developed via in situ reaction of the intermediate allene oxide or spirodioxide with different nucleophiles. 

In situ epoxidation of allenyl alcohols [20], aldehydes [21], acids [22] and sulfonamides [23] followed by intramolecular ring opening of the intermediates was thoroughly investigated by Crandall and co-workers. They showed that products formed either from the allene oxide or the spirodioxide intermediate can be prepared selectively. Allenyl acids 56, for example, react first with DMDO on their more substituted double bond. When the concentration of the oxidant is low (DMDO is formed... 

The oxidation of allenylsulfonamides 75 is also possible by using DMDO [23], Unlike the corresponding reaction of allenyl acids, oxidation of allenyl sulfonamides usually cannot be stopped after the formation of the allene oxide 76 but proceeds further to the spirodiepoxide intermediate 77, finally giving hydroxypyrrolidinone 78 and hydroxypiperidone 79, respectively (Scheme 17.23). Similarly to y-allenyl alcohols, aldehydes and acids, five-membered heterocycles, e.g. 80, are also formed from y-allenylsulfonamides. In the latter case the reaction can be terminated after the first epoxidation by addition of p-toluenesulfonic acid. 

In a different study, a d-allenyl alcohol 81 containing a chiral substituent was oxidized by DMDO and then cyclized to afford the substituted tetrahydropyran 82 with good diastereoselectivity [19] (Scheme 17.24). Interestingly, when oxone was used instead of DMDO, the eight-membered cyclic ether 83 was formed via the allene oxide intermediate. 

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