Allylic ester isomerization

The maximum allylic ester isomerization possible can be measured when hexene is used in the reaction. Both hexene-l-yl acetates and hexen-2-yl acetates will give hexen-3-yl acetates upon allylic ester isomerization (Reactions 8a, 8b, and 8c). Therefore, the hexanol-3-acetate found after hydrogenating the hexenyl acetate product will be representative of the sum of both allylic attack on hexene during vinylation and allylic ester isomerization after vinylation and olefinic isomerization. If hexanol-3-acetate is found in only low levels in the reaction product, then both allylic attack during vinylation and allylic ester isomerization can be discounted in considering the major reaction pathways. 

Also, the low levels of hexanol-3-acetate found in all these experiments indicate that neither attack on the allylic position of hexene nor allylic ester isomerization is important under these reaction conditions. When the procedure of Kitching et al. (29) was repeated, a high level... 

The reactions and product distributions thus far reported have been exclusively concerned with hexene. It was of interest to see whether the high specificity of positional substitution could be maintained with the other hexene isomers. By positional substitution specificity is meant ester attachment on ether of the carbons involved in the original carbon-carbon double bond. Table VII shows the results of these studies. The internal olefins reacted more slowly than the a-olefin, and with both palladium chloride-cupric chloride and 7r-hexenylpalladium chloride-cupric chloride systems high substitutional specificity (> 95% ) was also maintained with 2-hexene (Table VII). However, with 3-hexene the specificity is considerably lower (80%). Whether this is caused by 3-hexene isomerization prior to vinylation or by allylic ester isomerization is not known. A surprisingly high ratio of 2-substitution to 3-substitution is found ( 7 1) in the products from 2-hexene. An effect this large... 

Meisenheimer et were the first to study the kinetics of allylic ester isomerizations. They followed the isomerization of a-phenylallyl p-nitroben-zoate and a-phenylallyl 3,4,5-tribromobenzoate to the corresponding cinnamyl benzoates by a tedious analytical procedure involving use of melting point-composition diagrams. They observed that isomerization of the molten esters at 137°C is autocatalytic due to partial slow decomposition of the esters to substituted benzoic acids and unidentified products, and demonstrated that the reaction is catalyzed by added benzoic acids. The rate law for these reactions is... 

Braude " later pointed out that mechanistic conclusions based on these early studies of allylic ester isomerization are of doubtful validity, since they do not account for the sensitivity of these reactions to adventitious acidic impurities. Braude et ti/, and Pocker " " " studied the kinetics of isomerization of a-phenylallyl esters [(3), R = = YCgH, R == H] in the weakly... 

In aqueous 90% acetone at 99.6°C, At for /r Ai.s-a,y-dimethylallyl p-nitro-benzoate is 2.6x10-6 ec" [(II), R = R = CH3 Y = p-O-.NQH.CO., SOH = HoO]. The rate is not affected by addition of small amounts of lithium p-nitrobenzoate or p-nitrobenzoic acid. In aqueous 60% acetone at 60 C, At = 1.5 X lO secBy using carbonyl- o-labeled ester, it was shown that 60 scrambling is about twice as fast as allylic rearrangement, which implies that the carboxyl group of the p-nitrobenzoate ion in the tight ion pair rotates relative to the allylic carbonium ion in some instances before the ions recombine to form enantiomeric esters . This and similar observations on other allylic esters (see below) rules out the concerted Sf i mechanism as the only mechanism for allylic ester isomerization under solvolytic conditions. 

The Noc group, developed for amino acid protection, is introduced with the acid chloride (Et3N, H2O, dioxane, 2 h, 20°, 61-95% yield). It is cleaved with Pd(Ph3P)4 (THF, A, A -dimethyibarbituric acid, 8 h, 20°, 80% yield). It is not isomerized by Wilkinson s catalyst, thus allowing selective removal of the allyl ester group. 

Intramolecular cycloadditions of substrates with a cleavable tether have also been realized. Thus esters (37a-37d) provided the structurally interesting tricyclic lactones (38-43). It is interesting to note that the cyclododecenyl system (w = 7) proceeded at room temperature whereas all others required refluxing dioxane. In each case, the stereoselectivity with respect to the tether was excellent. As expected, the cyclohexenyl (n=l) and cycloheptenyl (n = 2) gave the syn adducts (38) and (39) almost exclusively. On the other hand, the cyclooctenyl (n = 3) and cyclododecenyl (n = 7) systems favored the anti adducts (41) and (42) instead. The formation of the endocyclic isomer (39, n=l) in the cyclohexenyl case can be explained by the isomerization of the initial adduct (44), which can not cyclize due to ring-strain, to the other 7t-allyl-Pd intermediate (45) which then ring-closes to (39) (Scheme 2.13) [20]. While the yields may not be spectacular, it is still remarkable that these reactions proceeded as well as they did since the substrates do contain another allylic ester moiety which is known to undergo ionization in the presence of the same palladium catalyst. 

Synthesis of isomeric chiral protected (63 )-6-amino-hexahydro-2,7-dioxopyrazolo[l,2- ]pyrazole-l-carboxylic acid 280 is shown in Scheme 36. Crude vinyl phosphonate 275, obtained by treatment of diethyl allyloxycarbonylmethyl-phosphonate with acetic anhydride and tetramethyl diaminomethane as a formaldehyde equivalent, was used in the Michael addition to chiral 4-(f-butoxycarbonylamino)pyrazolidin-3-one 272. The Michael addition is run in dichloro-methane followed by addition of f-butyl oxalyl chloride and 2 equiv of Huning s base in the same pot to provide 276 in 58% yield. The allyl ester is deprotected using palladium catalysis to give the corresponding acid 277, which is... 

The noteworthy advantages of the allyl ester are (a) it is readily introduced into amino acids (b) after isomerization (to 1-propenyl) by a palladium(O) catalyst it may be removed under weakly acidic or basic and neural conditions (32), even if sulfur-containing amino acids are present (34) (c) it shows orthogonal stability to the tert-butyloxycarbonyl and 9-fluorenylmethoxy-carbonyl groups (10) and (d) it is not affected by the hydrogen fluoride-pyridine complex (35). 

Hartwig and coworkers reported an approach to address this limitation involving tandem catalytic reactions. In this tandem process, sequential palladium-catalyzed isomerization of the branched isomer to the linear isomer, followed by iridium-catalyzed allylic substitution leads to the branched product with high enantiomeric excess [105]. More specifically, treatment of branched allylic esters with catalytic amounts of the combination of Pd(dba)2 and PPhs led to rapid isomerization of the branched allylic ester to the linear isomer, and the linear isomer underwent allylic substitution after addition of the iridium catalyst and nucleophile (Scheme 31). 

The reactions of arylation of heterocyclic /3-ketoesters were employed in the synthesis of a number of isoflavanones and isoflavones.27,28 cr-Methylene cr-arylketones can be easily and selectively obtained by arylation of allyl /3-ketoesters which are eventually deprotected by the Tsuji s procedures. a Deallyloxycarbonylation was performed by treatment of the allyl cr-aryl-/3-ketoesters with catalytic amounts of palladium(n) acetate, triethylammo-nium formate and triphenylphosphane in THF at room temperature and afforded the a-arylketones in 75-97% yield.27 Deallyloxycarbonylation-dehydrogenation can be realized with the same allyl esters by treatment with catalytic amounts of palladium(n) acetate and l,2-bis(diphenylphosphino)ethane (DPPE) in acetonitrile under reflux and affords the ct-aryl cr,/3-unsaturated ketones in 60-90% yield (Scheme 4).28 In particular, this reaction was used in a direct convergent synthesis of 2 -hydroxyisoflavones involving arylation of an appropriate allyl /3-ketoester with the MOM-protected (2-methoxymethoxyphenyl)lead triacetate derivative (Scheme 4). The reaction of the isomeric... 

Enantiomerically pure carboxylic acids are routinely obtained from N-acylsultams by Hydrogen Peroxide assisted saponification with Lithium Hydroxide in aqueous THF. 4 Alternatively, transesterification can be effected under neutral conditions in allyl alcohol containing Titanium Tetraisopropoxide, giving the corresponding allyl esters which can be isomerized/hydrolyzed with Wilkinson s catalyst (Chlorotris(triphenylphosphine)rhodium(I)) in Et0H-H20. This provides a convenient route to carboxylic acids containing base-sensitive functionality. Primary alcohols are obtained by treatment with L-Selectride (Lithium Tri-s-butylborohydride) in THF at ambient temperature. ... 

Allyl esters rearrange to isomeric allyl esters. Reactions are concerted and undoubtedly involve 6-center polar transition states, viz. 

The a-substituted 1-methyl allyl vinyl ether was shown to isomerize with a strong preference for the irons product (i.e., 95 % irons, 5 % cfe) . This corresponds to a conformational preference for equatorial methyl (as opposed to axial) in the chair transition state of about 2.4 kcal.mole . The identical value was calculated from the irons product preference in the allyl ester Claisen rearrangements (see a-methyl allyl acetate and a-trifluoromethyl allyl trifluoroacetate). 

Certainly more work is required before a definite mechanism can be proposed and it is very likely that more than one mechanism is operative. Another new isomerization involves allylic esters 118, 125). 

When C2H5 is replaced with the more electron withdrawing CF3, the rate is slower, indicating that reaction does not proceed via allylic carbanions, the path for thermal isomerization of allylic esters. Oxygen-18-labeling experiments and the electronic effects are consistent with an internal ox3q>alladation mechanism ... 

As has already been detailed for the allyloxycarbonyl (Aloe) moiety, allyl esters also proved to be very versatile and useful carboxy-protecting groups. They can be easily constructed by azeotropic esterification or nucleophilic displacement on allylic halides. For the cleavage of these esters lithium di-methylcuprate can be used. However, a much milder method is found in the Rh -catalyzed isomerization of the allyl moiety to a propenyl ester which immediately hydrolyzes under the reaction conditions (Scheme 67). Even milder is the Pd°-catalyzed allyl transfer to morpholine as an accepting nucleophile. The removal of allyl ester protection has earlier been used in particular in -lactam anti-... 

With higher olefins the product distribution becomes more variable. Not only the expected enol acetates but also allylic acetates are formed. Thus, propene forms isopropenyl acetate along with some n-propenyl acetate and allyl acetate [6, 7]. Higher and cyclic olefins react to form mainly allylic esters [8-18] moreover pre-isomerization of the olefins give rise to an even broader spectrum of products. The results published differ from each other, probably because of different reaction conditions and composition of reaction mixtures. 

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