Allene epoxide

Since cumulenes and alkynes are often easily interconvertible, many syntheses discussed above have allenic counterparts, especially base-catalyzed cyclizations of allenic alcohols.77 And, of course, several of the alkyne-based syntheses may well have allenic intermediates. There are, however, a few syntheses based specifically upon allene chemistry. In an important one, due to Stirling and his collaborators,78 an allenic sulfonium salt reacts with an enolate anion. Scheme 12 sketches the main features yields as high as 86% are recorded. Methoxyallene is easily metallated by butyllithium and so converted into an allenic epoxide that can be isomerized by fe/T-butoxide into a furan (Scheme 13) or an exocyclic equivalent similar to 15 clearly this method is particularly suited to the preparation of 3-methoxyfuran... 

On the other hand, no epoxide has been reported to be immune to reaction with BF3, although an interesting example of inertness was noted by Crandall and Machleder. Allene epoxides are usually too sensitive to acids to be isolable from peroxy acid epoxidations, but the bulky r-butyl groups on (70 equation 30) make it exceptionally unreactive. Several hours of reflux with BF3 in ether were required to effect the conversion to (71). 

The thermal rearrangement of methyleneoxiranes (allene epoxides) and a related photochemical rearrangement lead to cyclopropanones. An example is the rearrangement of 1 to 2. ... 

The isomerization reaction of alkylidene oxiranes, i.e. allene epoxides, to cyclopropanones has stimulated many investigations. Several experimental and theoretical studies suggest that the reaction proceeds through an oxyallyl intermediate. 

The method was also used for epoxidation of the alkenylidenecyclopropane (1) the predominant product (64% yield) was the ketone (3). The minor product (27% yield) was identified as (4). Both are considered to be formed from an intermediate allene epoxide (2).3 1... 

Allene epoxides. Synthesis of allene epoxides is difficult because of the tendency to undergo further epoxidation and to isomerize to the corresponding cyclopropanone (2, 308-309). The first known one was obtained by Camp and Green (2, 309, ref. 3g) by oxidation of 1,3-di-f-butylallene with m-chloroper-benzoic acid. Crandall and Machlcdcr 1 have now reported successful mono-epoxidation of 1,1,3-tri-t-butvlallene (1), also using m-chloroperbenzoic acid. The epoxide (2) is the main product but is accompanied by an oxetanone (3), undoubtedly formed via an intermediate diepoxide. The epoxide (2) is extraordinarily stable and shows no tendency to isomerize to a cyclopropanone. 

Scheme 4.9 Cationic Au(I)-catalyzed allene-epoxide cascade to generate medium-sized...

Some allenic alcohols can be prepared in analogous waysfrom acetylenic epoxides or tetrahydropyrans ... 

To a mixture of 100 ml of THF and 0.10 mol of the epoxide (note 1) was added 0.5 g Of copper(I) bromide. A solution of phenylmagnesium bromide (prepared from 0.18 mol of bromobenzene, see Chapter II, Exp. 5) in 130 ml of THF was added drop-wise in 20 min at 20-30°C. After an additional 30 min the black reaction mixture was hydrolysed with a solution of 2 g of NaCN or KCN and 20 g of ammonium chloride in 150 ml of water. The aqueous layer was extracted three times with diethyl ether. The combined organic solutions were washed with water and dried over magnesium sulfate. The residue obtained after concentration of the solution in a water-pump vacuum was distilled through a short column, giving the allenic alcohol, b.p. 100°C/0.2 mmHg, n. 1.5705, in 75% yield. 

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. 

Epoxidations of chiral allenamides lead to chiral nitrogen-stabilized oxyallyl catioins that undergo highly stereoselective (4 + 3) cycloaddition reactions with electron-rich dienes.6 These are the first examples of epoxidations of allenes, and the first examples of chiral nitrogen-stabilized oxyallyl cations. Further elaboration of the cycloadducts leads to interesting chiral amino alcohols that can be useful as ligands in asymmetric catalysis (Scheme 2). 

Ensign SA, FJ Smakk, JR Allen, MK Sluis (1998) New roles for COj in the microbial metabolism of aliphatic epoxides and ketones. Arch Microbiol 169 179-187. 

Allen JR, DD Clark, JG Krumn, SA Ensign (1999) A role for coenzyme M (2-mercaptoethanesulfonic acid) in a bacterial pathway of aliphatic epoxide carboxylation. Proc Natl Acad Sci USA 96 8432-8437. 

Allen JR, SA Ensign (1997) Purification to homogeneity and reconstitution of the individual components of the epoxide carboxylase multiprotein enzyme complex from Xanthobacter strain Py2. J Biol Chem 272 32121-32128. 

C[bicarbonate] and NMR were used to demonstrate that the first product in the metabolism of propene epoxide is acetoacetate, which is then reduced to (3-hydroxybutyrate (Allen and Ensign 1996). 

Allen JR, SA Ensign (1996) Carboxylation of epoxides to 3-keto acids in cell extracts of Xanthobacter strain Py2. J Bacterial 178 1469-1472. 

Clark DD, JR Allen, SA Ensign (2000) Characterization of five catalytic activities associated with the NADPH 2-ketopropyl-coenzyme M [2-(2-ketopropylthio)ethanesulfonate] oxidoreductase/carboxylase of the Xanthobacter strain Py2 epoxide carboxylase system. Biochemistry 39 1294-1304. 

The Pd-catalysed carbonylation of alkynyl epoxides 60 and alkynyldioxolanones 61 leads to the allenes 62 which can then be converted to the same pyranones through a tandem conjugate addition-cyclisation (Scheme 40) <00JCS(P1)3188>. Carbonylation of allenyl alcohols is catalysed by Ru3(CO)i2 and yields 5,6-dihydropyran-2-ones . 

Photo-addition of allene to the enone (90) yield adduct (91) in 75 % yield, which was subjected to ketalization in 77% yield. Epoxidation of (92) with perbenzoic acid followed by chromatography on alumina afforded two expoxides (93) and (94). Both (93) and (94) could be converted separately through (95) and (96) respectively which was the common intermediate leading to isoishwarane (98) and ishwarane following a deketalization-retroaldol-aldol process to furnish the keto-alcohol (97) (99) 30>. 

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