Elimination from allylic acetates

Trost and coworkers have devised a stereocontrolled 1,3-diene synthesis employing a palladium-catalysed decarboxylative elimination procedure from allylic acetates carrying carboxylic acid functionality ji- to the acetate group (equation 18)48. This decarboxylative elimination strategy has been applied to the synthesis of an insect pheromone, codlemone48a and the ethyl ester of vitamin A carboxylic acid (Table 5)48b. 

The total syntheses of these pepper alkaloids are not those of pyrrolidines but rather syntheses of their acid parts. Thus dihydrowisanidine (137) has been prepared by a series of reactions, the key step of which is the formation of the carbon-carbon double bond by a Wittig-Homer reaction (217, 218). Schemes 41 and 42 summarize two syntheses of okolasine from sesamolmethyl ether (279) of course, routes to okolasine also yield the corresponding piperidine alkaloid wisanine. Molybdenum-catalyzed elimination of allylic acetate (149) yielded (E,E)-diene ester 150 en route to trichonine (220) worthy of note is the use of an aluminum amide in the preparation of amide 143 from ester 150 (Scheme 43). 

Industrial (BASF) syntheses of vitamin A and vitamin A aldehyde have been accomplished utilizing the aldehydes obtained from allyl acetate hydroformylation.22 Either aldehyde (10) or (11) reacts with the same phosphorus ylide to give vitamin A or retinal (Scheme 4). Hydroformylation of 3-methyl-2-butenyl acetate gives a high yield of 2-formyl-3-methylbutyl acetate. Elimination of acetic acid followed by isomerization provides trimethylacrylaldehyde, which is an intermediate in the synthesis of irones (Scheme 5). 

Alkenes (e.g. camphene) are readily prepared by the BF3,Et20-catalysed elimination of secondary borate esters.Terminal conjugated dienes may be prepared by Pd(OAc)2-PPh3-catalysed elimination from allyl phenyl ethers or allylic acetates [e.g. geranyl, neryl, and linalyl acetates to form similar mixtures of myrcene (60—74%), trans-ocimene (8—20%), and c -ocimene (14—20%)], and the complex [(i7-CsH5)Cr(NO)2]2 dehalogenates n/c-dihalides (e.g. limonene tetrabromide) without affecting other halides (except for benzyl halides). 

H elimination from allylic complexes leads to 1,3-dienes and this is the final step of some synthetically useful reactions such as the Pd-catalyzed elimination of acetic acid from allylic acetates to give l,3.dienes. The fi-U elimination is believed to be analogous to that in the alkyl complexes, by previous isomerization of the allyl moiety from to a. However, recently some studies suggest that alternative mechanisms can be operating, sometimes simultaneously, such as direct deprotonation of the H in /i position to the allyl group [90-92], or even, in some special cases, a cyclic mechanism outside the metal coordination sphere... 

Several 1,3-diene syntheses involving elimination reactions that are catalyzed by Pd(Ph3P)4 have been reported. The first involves the Et3N mediated elimination of HOAc from allylic acetates in refluxing THF. A complementary procedure involves the Pd(Ph3P)4 catalyzed decarboxylative elimination of /3-acetoxy-carboxylic acids (eq 46). The substrates are easily prepared by the condensation of enals and carboxylate enolates irrespective of the diastereomeric mixture, ( )-alkenes are formed in a highly stereocontrolled manner. The geometry of the double bond present in the enal precursor remains unaffected in the elimination and the reaction is applicable to the formation of 1,3-cyclohexadienes. 

In 1967 elimination of phenol from allyl phenyl ethers to form 1,3-diene in the presence of a palladium catalyst was reported briefly by Smutny. Later, Tsuji applied the Pd-catalyzed elimination reaction of terminal allylic compounds for the synthesis of terminal 1,3-dienes.Thus, elimination of acetic acid and phenol from allylic acetates and allyl phenyl ethers was carried out by refluxing the allylic compounds in dioxane or toluene in the presence of catalytic amounts of palladium acetate and PPha as a ligand for the palladium catalyst (Table 1). The allylic isomers were converted to the same products. No reaction takes place with allylic methyl ether, an allylic alcohol, or an allylic amine, which cannot easily form 7r-allylpalladium complexes by oxidative addition. 

A new site-selective dehydration can convert allylic alcohols (64) and (66) into the dienes (65) and (67) respectively, using 2,4-dinitrobenzenesulphenyl chloride in triethylamine. The intermediate selenenate ester presumably undergoes [2,3] sigmatropic rearrangement to the allyl selenoxide, which then fragments to the diene. Palladium diacetate-triphenylphosphine appears to be an effective catalyst for the elimination of acetic acid or phenol from allylic acetates or phenyl ethers respectively, leading to 1,3-dienes in high yield. ... 

Based on the above-mentioned stereochemistry of the allylation reactions, nucleophiles have been classified into Nu (overall retention group) and Nu (overall inversion group) by the following experiments with the cyclic exo- and ent/n-acetales 12 and 13[25], No Pd-catalyzed reaction takes place with the exo-allylic acetate 12, because attack of Pd(0) from the rear side to form Tr-allyl-palladium is sterically difficult. On the other hand, smooth 7r-allylpalladium complex formation should take place with the endo-sWyWc acetate 13. The Nu -type nucleophiles must attack the 7r-allylic ligand from the endo side 14, namely tram to the exo-oriented Pd, but this is difficult. On the other hand, the attack of the Nu -type nucleophiles is directed to the Pd. and subsequent reductive elimination affords the exo products 15. Thus the allylation reaction of 13 takes place with the Nu nucleophiles (PhZnCl, formate, indenide anion) and no reaction with Nu nucleophiles (malonate. secondary amines, LiP(S)Ph2, cyclopentadienide anion). 

Various S-nucleophiles are allylated. Allylic acetates or carbonates react with thiols or trimethylsilyl sulfide (353) to give the allylic sulfide 354[222], Allyl sulfides are prepared by Pd-catalyzed allylic rearrangement of the dithio-carbonate 355 with elimination of COS under mild conditions. The benzyl alkyl sulfide 357 can be prepared from the dithiocarbonate 356 at 65 C[223,224], The allyl aryl sufide 359 is prepared by the reaction of an allylic carbonate with the aromatic thiol 358 by use of dppb under neutral condi-tions[225]. The O-allyl phosphoro- or phosphonothionate 360 undergoes the thiono thiolo allylic rearrangement (from 0-allyl to S -allyl rearrangement) to afford 361 and 362 at 130 C[226],... 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

When allylic compounds are treated with Pd(0) catalyst in the absence of any nucleophile, 1,4-elimination is a sole reaction path, as shown by 492, and conjugated dienes are formed as a mixture of E and Z isomers[329]. From terminal allylic compounds, terminal conjugated dienes are formed. The reaction has been applied to the syntheses of a pheromone, 12-acetoxy-1,3-dode-cadiene (493)[330], ambergris fragrance[331], and aklavinone[332]. Selective elimination of the acetate of the cyanohydrin 494 derived from 2-nonenal is a key reaction for the formation of the 1,3-diene unit in pellitorine (495)[333], Facile aromatization occurs by bis-elimination of the l,4-diacetoxy-2-cyclohex-ene 496[334],... 

The decarboxylation of ally / -keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl ji-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-elimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

The simplest monomer, ethylenesulfonic acid, is made by elimination from sodium hydroxyethyl sulfonate and polyphosphoric acid. Ethylenesulfonic acid is readily polymerized alone or can be incorporated as a copolymer using such monomers as acrylamide, allyl acrylamide, sodium acrylate, acrylonitrile, methylacrylic acid, and vinyl acetate (222). Styrene and isobutene fail to copolymerize with ethylene sulfonic acid. 

Although simple ketones and esters can not be allylated by Pd catalysts, they are allylated with allyl carbonates via their enol ethers of Si and Sn. In the allylation of the silyl enol ether 202 with allyl carbonate 200, transmetallation of 202 with the n-allylpalladium methoxide 201, generated from allyl methyl carbonate (200), takes place to generate the Pd enolates 203 and 204. Depending on the reaction conditions, allyl ketone 205 is formed by the reductive elimination of 203 [100]. When the ratio of Pd Ph3P is small, the a,/i-unsaturated ketone 206 is obtained by -elimination [101]. For example, the silyl enol ether 208 of aldehyde 207 is allylated with allyl carbonate (200) to give a-allylaldehyde 210 via 209. The a-allyl carboxylate 213 is obtained by allylation of ester 211 with allyl carbonate (200), after conversion of ester 211 to the ketene silyl acetal 212 [102], As the silyl group is trapped in these... 

The stereochemical outcome in the elimination reaction of acyclic ( >allylic acetates (7) to the corresponding dienes by the use of [Pd(dppe)2] as a catalyst in the presence of DBU has been elucidated by 2-dimina-tioi1 -30 The unprecedented Z-preference has been rationalized by the syn -effect in the transition state of deprotonation, which arose from a a n interaction. 

NBS was used for the allylic bromination and protection was needed for the thiol nucleophile to avoid over-reaction (chapter 5). The reactive nitroalkene 24 was introduced by elimination from 2-nitroethyl acetate. 

The reaction of 153 with the stannylated acetate 162 (Scheme 36) shows the directing effect of the Bu3Sn group. Both direct allylation and rearrangement of 164 give 163. Tin elimination from 163b (step c) results in the incorporation of a branched 2-butenyl chain in 165 (92ACS1215). 

Other known methods for preparing O-alkyl enol ethers include, most notably, alcohol elimination from acetals, double bond isomeri2ation in allylic ethers, reduction of alkoxy enol phosphates, and phosphorane-based condensation approaches.5 These methods, however, suffer from poor stereoselectivity, low yields, or lack of generality, if not a combination of these drawbacks. 

Rearrangement of acyclic allylic acetates 1 with a disubstituted double bond of either E or Z configuration gave only (ZO-allylic acetates 3a or 3c. The intermediate 2 a, with the substituent R1 at C-l in a quasiequatorial position, is favored over 2b with R1 in an axial position, thus syn elimination of palladium and oxygen from the cationic intermediate 2a with R1 in the equatorial position leads to the (Zfpallylic ester 3a. 

Another isohypsic transformation of special significance involves elimination of H-X elements from allylic derivatives to form 1,3-dienes. Besides being extremely important compounds as monomers, 1,3-dienes occupy a unique position in synthetic practice as components in the Diels-Alder reaction. One of the common routes of synthesis of 1,3-dienes also employs a vinyl Grignard addition to carbonyl compounds as the initial step (Scheme 2.55). Allylic alcohols thus formed can easily undergo 1,2-elimination (in some cases it is preferable first to transform the alcohols into their respective acetates). 

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