Propargyl esters isomerization

The isomerization of propargylic alcohols to a, -unsaturated carbonyl compounds can also be effected by means of the rearrangement of derived propargylic esters (5) via allenic esters (6 equation 13). ... 

A fascinating approach to the synthesis of pyridine heterocycles has been discovered by using (arene)Fe(O) complexes to catalyze [2+2+2] cycloaddition reactions. The proposed method consists of a cross cyclization of alkynes and nitriles [45]. An example of such a reaction is depicted in Scheme 25. In the presence of (Ty -l,5-cyclooctadiene)(Ty -phosphinine)Fe(0) 85, butyronitrile 86 combines with two molecules of methyl propargyl ester 87 yielding a mixture of isomeric pyrroles 88 and 89. The reaction proceeds at ambient temperature, but relatively long reaction times are required to obtain good yields. The symmetric... 

In contrast to facile Pd(0)-catalyzed reactions of allyl esters with soft carbon nucleophiles via r-allylpalladium intermediate, propargyl esters such as acetate are less reactive toward soft carbon nucleophiles. However, /3-keto esters and malonates react under neutral conditions with propargyl carbonates using DPPE as a ligand [37], Acetoacetate reacts with meAyl propargyl carbonate (119) in THF at room temperature to afford 4-(methoxycarbonyl)-5-methyl-3-methylene-2,3-dihydrofuran (120) in 88 % yield. The furan 121 was obtained by isomerization of the methylenefuran 120 under slightly acidic conditions. 

Other indole syntheses of this type include the iridium-catalyzed hydrogen transfer of amine-substituted benzylic alcohols (130L3876), the intramolecular dehydrative coupling of tertiary amines with ketones (13OL6018), and the sequential alkylation/cyclization/isomerization of 3-(o-tri luoroacetamidoaryl)-l-propargylic esters (13T9494). 

In 2006, Toste and coworkers reported the bimolecular synthesis of benzonor-caradienes by building three carbon-carbon bonds as well as two cycles in a one-pot diastereoselective reaction. Indeed, in the presence of a cationic gold catalyst, a 1,2-propargylic ester shift/isomerization/cyclopropanation/hydroarylation sequence generated the desired tricyclic product as a single diastereomer (Scheme 7.20) [32]. 

Acyl shift isomerizations are generally observed when propargylic esters bearing an internal alkyne moiety are involved in the process. Zhang has reported that... 

Another route to cyclobutenes is [2+2] cyclization of 1,3-butadienes [440]. Normally the focus of this reaction goes back to the synthesis of 1,3-dienes, but in the case of bulky substituents, formation of cyclobutenes 4.987 are preferred. Such bulky substituents can be introduced by means of acetylene-allene isomerization of trivalent phosphorous propargyl esters, as shown in Scheme 4.11. 

The isomerization of the smallest alkynes 80 with halogens in a propargylic position has been described for chlorine [151, 152], bromine [153] and iodine [154] (Scheme 1.35), but often might proceed by an SN2 -type substitution rather than a prototropic rearrangement [155-159]. On the other hand, transformations such as 82 —> 83 [160] or 84 —> 85 [161] are clearly prototropic (Scheme 1.36). This is also true for propargylic halides such as 86 with its additional ester group assisting the prototropic isomerization [162,163] (Scheme 1.37). 

Other functional groups tolerated in these isomerizations are ethers [65], alcohols [38, 66-69], propargylic trifluoromethyl groups [70], conjugated enones such as 36 [71] and esters [72] (Scheme 1.14). 

Whereas the Markovnikov addition of carboxylic acids to propargylic alcohols produces P-ketoesters, resulting from intramolecular transesterification [30, 31], the addition to propargylic alcohols in the presence of Ru(methallyl)2(dppe) 1 at 65 °C leads to hydroxylated alk-l-en-l-yl esters via formation of a hydroxy vinylidene intermediate [32, 33]. The stereoselectivities are lo ver than those obtained from non-hydroxylated substrates. These esters, which are protected forms of aldehydes, can easily be cleaved under thermal or acidic conditions to give conjugated enals, corresponding to the formal isomerization products of the starting alcohols (Scheme 10.6). 

Isomerizations. A convenient method for the conversion of alkynes to conjugated dienes is by treatment with Ph P. The synthetic application is shown in the preparation of 2,4-alkadienols from 2-alkynoic acids involving esterification with pentafluorophenol, isomerization with PhjP (PhMe, 50°), and reduction with DIBAL-H. Even propargyl bromide can be isomerized to give 1-bromopropadiene, albeit in 29% yield. Conjugated alkadienoic esters and amides are obtained in one step from the pentafluorophenyl alkynoates on reaction with alcohols and amines, respectively, after treatment with catalytic amount of PhjP. 

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