Allene, oxide, reaction

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 ... 

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. 

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. 

The first cyclopropanone to be isolated under Favorskii conditions was obtained from the reaction of the sterically hindered a-bromodineo-pentyl ketone (57) with potassium >-chlorophenyl-dimethylcarbinolate.13> The product, 7f MS-2,3-di-f-butylcyclopropanone (52) (20—40%) was later prepared independently by the valence isomerism of l,3-di-7-butyl-allene oxide 51> (see Section 2.6). 

In connection with the above discussion, formation of 3,3-disubsti-tuted 2 (3 H)-oxepinones (73) in the dye-sensitized photooxygenation of 6,6-disubstituted fulvenes is of special interest. 57>58> The reaction may be pictured in terms of an allene oxide intermediate which, as shown in Scheme 11, isomerizes to a cyclopropanone, followed by intramolecular rearrangement. 

Warren and coworkers have reported an interesting synthesis of nonracemic allenes by reaction of vinylphosphine oxides with aldehydes in the presence of chiral lithium [(R)-l-phenylethyl](benzyl)amide to give hydroxyvinylphosphine oxides in 33-87% yields (0-51% ee) [38]. These products underwent a Horner-Wittig elimination reaction to produce nonracemic allenes. A mechanism similar to the Baylis-Hillman reaction was suggested. 

PospKil J (1981) Photo-oxidation reactions of phenolic antioxidants, In Developments in polymer photochemistry-2, Allen N S (Ed), Applied Science Publishers London, pp 53-133. 

If a suitable (1,3-di-f-butyl) allene is epoxidized with m-CPBA the unstable allene oxide can actually be isolated. On heating, this epoxide gives a stable fra s-di-f-butylcycl6propanone. It is very difficult to see how this reaction could happen except via the oxyallyl cation intermediate. 

The same cyclopropanone gives a cycloadduct with furans—this must surely be a reaction of the oxyallyl cation and we can conclude that the three isomeric reactive intermediates (allene oxide, cyclopropanone, and oxyallyl cation) are all in equilibrium and give whichever product is appropriate for the conditions. 

Allenamides have been used as precursors for oxidation reactions <2002JOC1339>. The allene oxide products that are produced are useful oxyallyl cation equivalents for cycloaddition chemistry (Scheme 30) <2001JA7174, 2003JA12694>. 

The Woodward-Hoffman rules also predict that in a given cyclization mode a permutation of alkene geometry must be reflected in the configuration of the products. This test is precluded under the normal reaction conditions (acid, light) which would isomerize the dienone double bonds. However, Corey recently reported the formation of a c -disubstituted cyclopentenone from a (Z, )-precursor, derived fiom an allene oxide, which cyclizes via the 2-oxido pentadienylic cation (Section 6.3.8). ... 

Since epoxidation at the vinyl double bond is unproductive, it is desirable to direct reaction on the al-lene moiety. This can be accomplished by taking advantage of the hydroxy-directed epoxidation of allylic alcohols using the t-butyl hydroperoxide/vanadium(V) system.The directing effects of both allylic and homoallylic type hydroxy groups have been examined at both positions of the vinylallene unit. " At the 1-position (64), primary, secondary and tertiary allylic tdcohols are effective, while only primary homoallylic alcohols have bran examined (equation 35). Presumably the directing effect of the hydroxy groups favors formation of the intermediate allene oxide (65). A sample of the compounds prepared by this route is shown in Scheme 32. ... 

Homoallylic type alcohols (67), on the other hand, give predominantly cyclopentenones independent of substitution (equation 37). In Ae 3-hydroxyalkyl-substituted systems, presumably allene oxide (68) is the intermediate. Thus it would appear Aat the initial site of allene oxidation is not critical to the success of the reaction. Either precursor (58) or (59) is expected to give the observed stereochemical relationships of the newly formed stereocenters by the concerted mechanism. Finally, Cha has noted that the two intermediates may lead to different stereochemical relationships by the zwitterionic mechanism. This assumes a specific pathway for breakdown of (58) or (59). That stereochemical information is preserved in the reaction is shown by the selective transformations in equation (38). 

Finally, there has been speculation and recent experimental support for the involvement of a Nazarov-type cyclization in the biosynthesis of c/ s-jasmonic acid ° and marine-derived prostanoids. Radiolabel tracer studies have demonstrated Ae intermediacy of 8-HPETE (104) in the biosynthesis of prostanoid intermediate preclavulone A (lO ). This remarkable conversion was proposed to proceed by formation of allene oxide (105) followed by isomerization to (107) via the 2-oxidocyclopentadienyl cation (106 Scheme 41). To demonstrate the chemical feasibility of this proposal, Corey reported the transformation of epoxysilane (108) to, inter alia, the cyclopentenone (111 Scheme 42). The reaction is presumed to involve formation of the allene oxide (109) followed by isomerization to the 2-oxi-dopentadienylic cation (110). Conrotatory closure of (110) is expected to produce the cis isomer of (111) as observed. 

An interesting route to the cyclopropanone system involves the rearrangement of allene oxides, usually generated by the epoxidation of allenes. Thus, 1,3-di-t-butylallene oxide (11) may be prepared by the reaction of 1,3-di-t-butylallene with m-chloroperbenzoic acid. Heating 11 to 100 °C leads to isomerization, forming truns-2,3-di-t-butylcyclopropanone (10) (Scheme 4) Similarly, 1,1-di-t-butylallene (15) yields 2,2-di-t-butylcyclopropanone with peracetic acid (equation 7) ... 

Schuda and Heimann reported that activated vinyl bromides 168 afforded acetylenes 170 on the reaction of DBU in refluxing benzene for 1-9 days, probably via allene oxide intermediates 169 (82JOC2484). (THP, Tetra-hydropyranyl.)... 

The most well known and well investigated degradation reaction of 13S-HPOTE is the generation of jasmonic acid. 13S-HPOTE is converted by allene oxide hydroperoxydehydrase by an intramolecular elimination of water to an allene oxide [160]. The latter is cyclized by allene oxide cyclase to 9S,13S,12-oxo-10,15-phytodienoic acid [160] followed by a trifold P-oxidation and a hydrogenation step (Scheme 7) [108]. 

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