Cinnamyl allylic substitution

Scheme 1.64 Cu-catalysed allylic substitution of cinnamyl phosphate with ZnEt2 in the presence of P-aminosulfonamide ligands.

The first enantioselective, iridium-catalyzed allylic substitution was reported by Helmchen and coworkers soon after the initial report by Takeuchi. Helmchen studied catalysts generated from phosphinooxazoline (PHOX) ligands and [Ir(COD)Cl]2 for the reactions of sodium dimethylmalonate with cinnamyl acetates (Scheme 2) [50]. The alkylation products were isolated in nearly quantitative yield and were formed with ratios of branched-to-Unear products up to 99 1 and with enantioselectivities up to 95% ee. In this and subsequent studies with PHOX ligands [51,52], Helmchen et al. demonstrated that the highest yields and selectivities were obtained with a PHOX ligand containing electron-withdrawing substituents and... 

Markovic and Hartwig isolated and characterized the first intermediate in iridium-catalyzed allylic substitution [100]. They isolated the metalacyclic iridium-phosphor-amidite fragment containing COD and the olefinic portion ofN- l -phenylallyl)aniline, the product of the allylic substitution reaction between cinnamyl carbonate and aniline (5 in Scheme 22). This complex containing the product of allylic substitution was first detected by NMR spectroscopy during catalytic reactions. It was then isolated, prepared independently, and shown to be chemically and kinetically competent to be an intermediate in allylic substitutions. 

An interesting allylic substitution reaction of ( )-cinnamyl methyl carbonate 143 has been examined by Pfaltz s group. The use of a molybdenum complex of ligand 144 resulted in 145 in 88% yield with an ee of 99% [for the (R) isomer] (Fig. 9.45). 

The scope of the method turned out to be particularly broad (Table 12). The allylic substitution of cinnamyl bromide could also be performed with other linear alkyl Grignard... 

Allylic substitution Pd dendrimer (Ph2PCH2)2N cinnamyl carbonate 95 (Pd) 262 n.a. Brinkmann, 1996... 

Abnormal olefin arylation reactions which are of interest mechanistically and preparatively occur with some allylically substituted compounds. The ailylic esters and ethers appear normal and produce cinnamyl derivatives exclusively while ailylic alcohols and chlorides are abnormal. Ailylic alcohols and "arylpalladium acetates form 3-arylaldehydes from primary ailylic alcohols and 3-arylketones from secondary alcohols 3°). The mechanism of reaction apparently involves anti-Markovnikov addition of the palladium compound to the double bond followed by elimination of the hydrogen atom on the hydroxyl-bearing carbon rather than the benzylic hydrogen. This again would be elimination of the more electronegative hydrogen atom. 

Fig. 8.4. Ligands 38 employed in allylic substitution reactions between cinnamyl chloride and...

A different palladium-catalyzed reaction is allylic substitution. In this case, (E)-cinnamyl ethyl carbonate (3) and either ethyl acetoacetate (4) or morpholine... 

A supported aqueous phase system (SAPC see Section 2.6) has also been developed for allylic substitution. Alkylation of (Ej-cinnamyl ethyl carbonate by ethyl acetoacetate or morpholine occurs in acetonitrile or benzonitrile using Pd(OAc)2-TPPTS supported on mesoporous or nonporous silica no leaching of the catalyst has been observed, allowing proper recycling of the catalyst [22-26]. Polyhydroxylated supports such as cellulose and chitosan have also been used successfully in this approach [27-29]. 

The first application of dendrimers in a thermomorphic system was described by Kaneda and co-workers. Poly(propylene imine) dendrimer-bound Pd(0) complexes were synthesized by reduction of dendritic Pd(II) systems with hydrazine and used for the allylic substitution of trans-cinnamyl acetate with dibutylamine [Eq. (5)] [14]. 

The 5 2 allylic substitution of cinnamyl chloride by water in the presence of an (5)-Cp Ru catalyst and NaHC03 in aqueous THF at room temperature occurs with complete regiospeciflcity, giving a 93-99% yield of the branched allylic alcohol, with between 89 and 94% eeP A r-allyl-ruthenium complex is believed to form during the reaction. A tracer study using H2 0 showed that water is the nucleophile in the hydrolysis reaction. 

Allylic substitution of cinnamyl methylcarbonate with nucleophiles such as ethyl acetoacetate, diethylmalonate and morpholine was catalyzed by a Pd-complex prepared in situ from [Pd(dba)2] and P(C6H4-4-C2H4-C6Fi3)3 (Scheme 51). The substitution products were formed with high rates and good yields at 50°C in a perfluoromethylcyclohexane-THF solvent mixture, and the catalyst could be recycled several times without deterioration (259). 

A supported aqueous phase system has been developed for ally lie substitution. Coabsorption of Pd(OAc)2 and TPPTS onto both mesoporous and nonporous silicas gave catalysts active for the reaction of cinnamyl ethyl carbonate with ethyl acetoacetate. The activity of supported catalyst depends on the amount of water used to form a layer on the surface of silica. In the absence of water the catalyst is inactive. The supported catalyst possesses activity close to the activity of Pd(OAc)2-TPPTS catalyst in a biphasic systan, though it is more stable, as even on prolonged reaction times no tokens of catalyst decomposition leading to the formation of Pd-black was noted for the former. Still, the recycled SAPC catalyst possesses lower activity than the one freshly prepared. Another report on glass bead technology applied to allylic substitution has been published. " ... 

The versatile triazene T1 linker has been applied to create a template for an allylic substitution with dibenzylamine on an immobiUzed cinnamyl acetate. Traceless cleavage furnished the tertiary amine in good yield and purity (Scheme 23). ... 

Studies reporting substituent effects on the palladium- and copper-catalysed Sonogashira coupling reaction between an aryl iodide and an alkyne the 5 2 allylic substitution reactions between benzyl amine and racemic allyl carbonates substituted with a j -X-Ph- group on C(l) in the presence of a Rh(15,15, 2/ ,2/ -tangphos)(COD)Bp4 catalyst the stereoselective 5 2 reactions between a-substituted linear 0-ketoesters and meta- and /Jura-substituted cinnamyl carbonates generating vicinal quaternary and tertiary stereocenters in the presence of an Ir-V-arylphosphoramidite catalyst, TBD, and LiOBu-t identity vinyl halide reactions the S N... 

These were converted to y-allyl-substituted y-butyrolactones in a one-pot reaction (Kunz and Reissig, 1989). Both p- and y-ketoesters underwent the same reaction. The i yn/anti-diastereoselectivity was only moderate, except in the reaction between benzoyl acid esters with cinnamyl chloride (Ahonen and Sjoholm, 1995). 

In order to complement earlier studies showing that IV-alkyl-substituted ben-zimidazolylidene-ruthenium complexes were efficient catalysts for the regiose-lective alkylation of cinnamyl carbonate by dimethyl malonate or 1,3-diketones, as well as etherification of allylic halides by phenols, Bruneau and co-workers prepared a wide range of imidazolinium 38, tetrahydropyrimidinium 39, and benzimidazolium salts 40 that were screened as NHC ligand precursors in various allylic substitution reactions (Equation (7.9)). Unfortunately, linear versus branched selectivities were only modest, and no characterisation of the [(NHC)Ru(Cp )] complexes assumed to take part in the reaction could be achieved, thereby preventing any further rational ligand modification that would have helped refine the catalytic system. 

Aryl alcohol oxidase from the ligninolytic fungus Pleurotus eryngii had a strong preference for benzylic and allylic alcohols, showing activity on phenyl-substituted benzyl, cinnamyl, naphthyl and 2,4-hexadien-l-ol [103,104]. Another aryl alcohol oxidase, vanillyl alcohol oxidase (VAO) from the ascomycete Penicillium simplicissimum catalyzed the oxidation of vanillyl alcohol and the demethylation of 4-(methoxymethyl)phenol to vanillin and 4-hydro-xybenzaldehyde. In addition, VAO also catalyzed deamination of vanillyl amine to vanillin, and hydroxylation and dehydrogenation of 4-alkylphenols. For the oxidation of 4-alkylphenol, the ratio between the alcohol and alkene product depended on the length and bulkiness of the alkyl side-chain [105,106]. 4-Ethylphenol and 4-propylphenol, were mainly converted to (R)-l-(4 -hydroxyphenyl) alcohols, whereas medium-chain 4-alkylphenols such as 4-butylphenol were converted to l-(4 -hydroxyphenyl)alkenes. 

The intramolecular cycloaddition of nitrones derived from iV-allyl-2-indolecarbaldehyde was used to an entry to pyrrolo- and pyrido[ 1,2-a]indole skeletons . For instance, the cinnamyl-substituted aldehyde 157 upon treatment with benzylhydroxylamine affords to the nitrone 158, which upon heating in refluxing toluene leads to mainly the cycloadduct 159. 

---