Dienes reactions with carboxylic acids

The reaction of alkenyl mercurials with alkenes forms 7r-allylpalladium intermediates by the rearrangement of Pd via the elimination of H—Pd—Cl and its reverse readdition. Further transformations such as trapping with nucleophiles or elimination form conjugated dienes[379]. The 7r-allylpalladium intermediate 418 formed from 3-butenoic acid reacts intramolecularly with carboxylic acid to yield the 7-vinyl-7-laCtone 4I9[380], The /i,7-titisaturated amide 421 is obtained by the reaction of 4-vinyl-2-azetidinone (420) with an organomercur-ial. Similarly homoallylic alcohols are obtained from vinylic oxetanes[381]. 

Adipic acid, 219.2 g (1.5 mol), and 77.6 g (1.25 mol) of 1,2-ethanediol are weighed into a 500-mL glass reactor equipped with a mechanical stirrer, a nitrogen inlet, and a distillation head connected to a condenser and a receiver fiask. The reactor is placed in a salt bath preheated at 180°C and the temperature is dien raised gradually to 220°C (see note at end of procedure) until the greater part of water has been removed (3 h). The reactor is cooled down to 160°C and vacuum is applied slowly to ca. 0.07 mbar (30 min). Temperature is ramped to 220°C (see note below) at a rate of l°C/min and reaction is continued for an additional 90 min. At the end of reaction, the carboxylic acid endgroup content is close to 1.90 mol/kg. No purification of final polyester is carried out. 

The Pechmann and Knoevenagel reactions have been widely used to synthesise coumarins and developments in both have been reported. Activated phenols react rapidly with ethyl acetoacetate, propenoic acid and propynoic acid under microwave irradiation using cation-exchange resins as catalyst <99SL608>. Similarly, salicylaldehydes are converted into coumarin-3-carboxylic acids when the reaction with malonic acid is catalysed by the montmorillonite KSF <99JOC1033>. In both cases the use of a solid catalyst has environmentally friendly benefits. Methyl 3-(3-coumarinyl)propenoate 44, prepared from dimethyl glutaconate and salicylaldehyde, is a stable electron deficient diene which reacts with enamines to form benzo[c]coumarins. An inverse electron demand Diels-Alder reaction is followed by elimination of a secondary amine and aromatisation (Scheme 26) <99SL477>. 

Dienes (allenes) are also used for heteroannulation with 68 and 69. The eight-membered nitrogen heterocycle 78 is constructed by the reaction of 1,2-undecadiene (77) with o-(3-aminopropyl)iodobenzene (76) [34]. The lactones are prepared by trapping the 7i-allyl intermediates with carboxylic acids as an oxygen nucleophile. The unsaturted lactone 81 is prepared by the reaction of /1-bromo-v,/ -unsaturated carboxylic acid 79 with the allene 80 [35]. In the carboannulation of 82 with 1,4-cyclohexadiene (83), the 1,3-diene 85 is generated by / -elimination of 84, and the addition of H-PdX forms the 7i-allylpalladium 86, which attacks the malonate to give 87 [36],... 

A unique variant of catalyst preformation in the absence of dienes was described by Enichem in an early patent on Nd-BR. The active Nd catalyst was prepared by the reaction of neodymium oxide with carboxylic acid and (BuCl in vaseline at 80 °C. Subsequently, aqueous HC1 was added at 80 °C. Finally, the addition of the aluminum alkyl co catalyst yielded the active Nd catalyst [389,390]. 

Diels-Alder reactions. The laboratories of Breslow and of Grieco have reported that water can enhance the rate of Diels-Alder reactions of dienes that possess carboxylic acid or similar hydrophilic groups (12, 314). Liotta et al. have examined solvent effects on cycloaddition reactions of benzoquinones with dienes substituted with a relatively hydrophobic group, and report significant rate enhancement in ethylene glycol relative to benzene (26 1) or even to reactions in the absence of a solvent. They attribute the solvent effect to aggregation of the diene and the quinone. 

The rapid reaction between carboxylic acids and borane is related to the electrophilicity of the latter. The carbonyl group of the initially formed acyloxyborane intermediate, which is essentially a mixed anhydride, is activated by the Lewis acidity of the trivalent boron atom. Addition of 1/3 equiv of the Borane-Tetrahydrofuran complex to acrylic acid in dichloromethane followed by addition of a diene at low temperature results in the formation of Diels-Alder adducts in good yield (eq 1). Further, the reaction is successful even with a catalytic amount of borane. 

The precatalyst 17 was reported to promote a coupling reaction of two molecules of phenylacetylene or its derivatives 65 with carboxylic acids, leading to (l ,3i )-l,4-diaryl-l-acyloxybuta-1,3-dienes 66 in various yields (Scheme 4.24) [57]. Amino acids, as well as diacids, can also be employed as carboxylic acid components. A mechanism involving the addition of a carboxylic acid to the ruthenacydopentatriene intermediate 67 was proposed for this stereoselective coupling. 

Mark and Rechnitz [3] systematized a vast amount of experimental material that can be used directly in KGCM. Some data are presented here that show the wide differences in organic compounds with regard to their kinetic characteristics. Table 2.1 [14] gives the relative rates of reaction of olefins with perbenzoic acid and Table 2.2 summarizes the rates of the etherification reaction of carboxylic acids with diphenyldiazomethane [15]. The tabulated data are indicative of large differences in organic compounds as far as their reactivity is concerned. The rates of reaction of some isomers differ so widely that one can, for example, analyse secondary and tertiary alkyl bromides in the presence of primary alkyl bromides in a reaction with silver nitrate [16]. It is possible to differentiate between CIS and trans isomers of 1,3-dienes by their reaction with dienophils (e.g., chloromethylene anhydride) because the cis isomer reacts much more slowly than the trans isomer [17]. 

By the reaction of theenolatc of camphor with carboxylic acid esters or chlorides, 1,3-diketones [better formulated as enols. such as (hydroxymethylene)camphor] are obtained. When trifluo-roacetic acid or heptafluorobutanoic acid are used, the corresponding diketones (abbreviated as tfc or hfc, respectively) have been successfully used as ligands for lanthanides and these are used as chiral shift reagents in NMR spectroscopy12. The complex Eu(hfc)3 [derived from ( + )-camphor)] 3 was used as a chiral catalyst for enantioselective Diels-Alder-type cycloadditions of aldehydes to dienes (Section D.l.6.1.1.1.2.4.). 

Menthol [(—)-l] has been used as a chiral ligand for aluminum in Lewis acid catalyzed Diels-Alder reactions with surprising success2 (Section D.l.6.1.1.1.2.2.1). The major part of its application is as a chiral auxiliary, by the formation of esters or ethers. Esters with carboxylic acids may be formed by any convenient esterification technique. Esters with saturated carboxylic acids have been used for the formation of enolates by deprotonation and subsequent addition or alkylation reactions (Sections D.l.1.1.3.1. and D.l.5.2.3.), and with unsaturated acids as chiral dienes or dienophiles in Diels-Alder reactions (Section D. 1.6.1.1.1.), as chiral dipolarophiles in 1,3-dipolar cycloadditions (Section D.l.6.1.2.1.), as chiral partners in /(-lactam formation by [2 + 2] cycloaddition with chlorosulfonyl isocyanate (SectionD.l.6.1.3.), as sources for chiral alkenes in cyclopropanations (Section D.l.6.1.5.). and in the synthesis of chiral allenes (Section B.I.). Several esters have also been prepared by indirect techniques, e.g.,... 

The chiral alcohols are mainly employed as esters or enol ethers. Esters with carboxylic acids can be obtained by any convenient esterification technique. Dienol ethers were obtained by transetherification with the ethyl enol ether of a 1,3-diketone, followed by Wittig reaction8 silyldienol ethers were obtained by the method of Danishefsky11-12 and simple enol ethers by mercury-catalyzed transetherification13. Esters and enol ethers have been used as chiral dienophiles or dienes in diastereoselective Diels-Alder reactions (Section D. 1.6.1.1.1.1.). (R)-l-Phenylethanol [(R)-4] has been used for enantioselective protonation (Section C.) and the (S)-enantiomer as chiral leaving group in phenol ethers for the synthesis of binaphthols (Section B.2.) the phenol ethers are prepared as described for menthol in the preceding section. (S)-2-Octanol [(S)-2] has found applications in the synthesis of chiral allenes (Section B.I.). 

A number of cycloaddition reactions involving allene derivatives as dienophiles have been recorded. Allene itself reacts only with electron-deficient dienes but allene carboxylic acid or esters, in which a double bond is activated by conjugation with the carboxylic group, react readily with cyclopentadiene to give 1 1 adducts in excellent yield. For example, the allene 12 gave, with very high yield and selectivity, the cycloadduct 13, used in a synthesis of (-)-P-santalene (3.19). An allene equivalent is vinyl triphenylphosphonium bromide, which is reported to react with a number of dienes to form cyclic phosphonium salts. These can be converted into methylene compounds by the usual Wittig reaction procedure (3.20). 

The oxidations of olefins with many oxygen nucleophiles other than water have also been reported. These reactions include the s5mthesis of vinylic and allylic ethers from reactions of olefins with alcohols and phenols, and vinylic and allylic esters from reactions of olefins with carboxylic acids. These reactions have been conducted with both monoenes and 1,3-dienes. Both intermolecular and intramolecular versions of each of these processes have been developed. Some discussion of these reactions was included in Chapter 11 because of their connection to the nucleophilic attack of oxygen nucleophiles on coordinated olefins and dienes. 

Palladium-catalyzed intermolecular oxidations of dienes with carboxylic acids and alcohols as donors give 1,4-addition products. This chemistry has been studied extensively by Backvall. Early studies involved 1,4-additions of two acetoxy or alkoxy groups across a diene,More recently, intermolecular additions of two different nucleophiles have been developed. The ability to control the stereochemistry of the additions across cyclic dienes makes this procedure particularly valuable. As shown in Scheme 16.25, conditions for either cis or trans additions have been developed. Reactions conducted in the absence of added chloride form products from trans 1,4-addition, while reactions conducted in the presence of added chloride form products from cis 1,4-addition. 

The most used reaction with respect to electrophilic substitution at (diene)iron complexes is the acylation. (Dienone)iron complexes are obtained by reaction of acyclic tricarbonyl(Ti -l,3-diene)iron complexes with carboxylic acid chlorides in the presence of aluminum trichloride in high yields (Scheme 4-11 i).P65-271]... 

Carboxylic acids react with butadiene as alkali metal carboxylates. A mixture of isomeric 1- and 3-acetoxyoctadienes (39 and 40) is formed by the reaction of acetic acid[13]. The reaction is very slow in acetic acid alone. It is accelerated by forming acetate by the addition of a base[40]. Addition of an equal amount of triethylamine achieved complete conversion at 80 C after 2 h. AcONa or AcOK also can be used as a base. Trimethylolpropane phosphite (TMPP) completely eliminates the formation of 1,3,7-octatriene, and the acetoxyocta-dienes 39 and 40 are obtained in 81% and 9% yields by using N.N.N M -tetramethyl-l,3-diaminobutane at 50 in a 2 h reaction. These two isomers undergo Pd-catalyzed allylic rearrangement with each other. 

Conjugated dienes give 1,4 addition. This reaction has also been performed with salts of carboxylic acids in what amounts to a method of alkylation of carboxylic acids (see also 10-96). ... 

Isomerization has been observed with many a,j3-unsaturated carboxylic acids such as w-cinnamic 10), angelic, maleic, and itaconic acids (94). The possibility of catalyzing the interconversion of, for example, 2-ethyl-butadiene and 3-methylpenta-l,3-diene has not apparently been explored. The cobalt cyanide hydride will also catalyze the isomerization of epoxides to ketones (even terminal epoxides give ketones, not aldehydes) as well as their reduction to alcohols. Since the yield of ketone increases with pH, it was suggested that reduction involved reaction with the hydride [Co" (CN)jH] and isomerization reaction with [Co (CN)j] 103). A related reaction is the decomposition of 2-bromoethanol to acetaldehyde... 

Many other examples of synthetic equivalent groups have been developed. For example, in Chapter 6 we discussed the use of diene and dienophiles with masked functionality in the Diels-Alder reaction. It should be recognized that there is no absolute difference between what is termed a reagent and a synthetic equivalent group. For example, we think of potassium cyanide as a reagent, but the cyanide ion is a nucleophilic equivalent of a carboxy group. This reactivity is evident in the classical preparation of carboxylic acids from alkyl halides via nitrile intermediates. 

The chloroacetoxylation is a quite general reaction and works well with a number of conjugated dienes. Some additional examples are given in Scheme 6 and in equations 15 and 16. The reaction is highly syn stereoselective for a number of cyclic dienes tried. Also, for acyclic dienes the reaction leads to a 1,4 syn addition and the reaction takes place with good stereospecificity (94 -96% syn). Thus (Zi,.E)-dienes give the R R isomer whereas (E,Z)-dienes produce the R S isomer (equations 15 and 16). The reaction has also been extended to include other carboxylic acids than acetic acid (chloroacyloxylation)33d. 

Diels-AIder reactions were utilized to prepare isoquinoline derivatives. Various tetrahydroisoquinoline-3-carboxylic acid derivatives were prepared by an enyne metathesis followed by a Diels-AIder reaction. For example the enyne 71 was treated with Grubb s catalyst to afford diene 72 in 65% yield. Subsequent Diels-AIder reaction and oxidation gave tetrahydroisoquinoline 73 in 93% yield <0OCC5O3>. Dihydrosoquinoline 75 was prepared... 

Carbon dioxide instead of aldehydes can be involved in Ni(0)-promoted reductive coupling reactions (Equations (76) and (77) Scheme 90).434,434a 434c A stoichiometric amount of Ni(COD)2/DBU reacts with C02 and dienes, alkynes, or allenes to afford a metallacycle intermediate. This metallacycle reacts with organozinc compounds or aldehydes in one-pot to give carboxylic acid derivatives. As shown in Scheme 90, double carboxylation occurs in the presence of dimethylzinc, where the stereochemical outcome is opposite to that of the reaction with diphenylzinc. 

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