P- Arylation

When aiomatics aie present, they can capture the intermediate vinyl cation to give P-aryl-a,P-unsatutated ketones (182). Thus acylation of alkyl or aryl acetylenes with acyhum salts in the presence of aromatics gives a,P-unsaturated ketones with a trisubstituted double bond. The mild reaction conditions employed do not cause direct acylation of aromatics. 

A technique based on ozonation, in contrast, provides information on the stmcture of the lignin side chain by degrading the aromatic rings (33). Thus the side chain of the dominant stmcture ia all native lignins, the arylglycerol—P-aryl ether moiety, can be obtained ia the form of erythronic and threonic acids. Ozonation proves to be an elegant method for determination of the stereospecificity ia lignin. 

In the presence of sulfide or sulfhydryl anions, the quinonemethide is attacked and a benzyl thiol formed. The P-aryl ether linkage to the next phenylpropane unit is broken down as a result of neighboring-group attack by the sulfur, eliminating the aryloxy group which becomes reactive phenolate ion (eq. 2). If sulfide is not present, a principal reaction is the formation of the stable aryl enol ether, ArCH=CHOAr. A smaller amount of this product also forms in the presence of sulfhydryl anion. 

Other authors have used dipole moments as an auxiliary technique to other physicochemical methods. Thus, Lumbroso has studied the tautomerism of 5-(p-aryl)tetrazoles in function of the substituent at the para position and compared the results with those obtained by NMR spectroscopy (Section VT,C) (80JHC1373). For a detailed description of Lum-broso s technique see [81JST(77)239]. 

As to arylisoxazoles, it was only in 1961 that Woodward et investigated the sulfonation of 5-phenylisoxazole. In contrast to nitration, only the phenyl nucleus is sulfonated to yield a mixture of m- and p-aryl sulfonic acid chlorides (62) in a 2 1 ratio. 

Tautomeric equilibrium in the symmetrical phenoxy-substituted derivative 136 (R = Ph, r = R = OPh) is fast at ambient temperature on the NMR time scale however, at —84°C the proton exchange becomes frozen and both annular tautomers 136a and 136b can be observed (Scheme 40). The similar exchange was also found for P-aryl-substituted 136 (R = Me, Ft, Ph R = R = Ph). In these cases, the equilibrium is very slow, even at ambient temperature, which was attributed to increased steric demands of four phenyl substituents. Unsymmetrically substituted azaphosphorinanes (R R ) provide even more interesting examples. These compounds (R = Ph R = Me, -Pr R = MeO, -PrO) were found to... 

It is thus clear that P-aryl groups can function as neighboring groups. Much less work has been done on aryl groups located in positions farther away from the leaving group, but there is evidence that these too can lend anchimeric assistance. ... 

The FeCls-catalyzed Friedel-Crafts reactions of electron-rich arenes with imines or aziridines provide a facile and convenient route for the synthesis of p-aryl... 

Hammel KE, MD Mozuch, KA Jensen, PJ Kersten (1994) HjOj recycling during oxidation of the arylglycerol P-aryl ether lignin structure by lignin peroxidase and glyoxal oxidase. Biochemistry 33 13349-13354. 

Masai E, A Ichimura, Y Sato, K Miyauchi, Y Katayama, M Fukuda (2003) Roles of enantioselective glutathione 5-transferases in cleavage of p-aryl ether. J Bacteriol 185 1768-1775. 

Bode and co-workers have extended the synthetic ntility of homoenolates to the formation of enantiomerically enriched IV-protected y-butyrolactams 169 from saccharin-derived cyclic sulfonylimines 167. While racemic products have been prepared from a range of P-alkyl and P-aryl substitnted enals and substitnted imi-nes, only a single example of an asymmetric variant has been shown, affording the lactam prodnct 169 with good levels of enantioselectivity and diastereoselectivity (Scheme 12.36) [71], As noted in the racemic series (see Section 12.2.2), two mechanisms have been proposed for this type of transformation, either by addition of a homoenolate to the imine or via an ene-type mechanism. 

Akiyama, T. Magara, K. Matsumoto, Y. Meshitsuka, G. Ishizu, A. Lundquist, K. Proof of the presence of racemic forms of arylglycerol-p-aryl ether structure in lignin studies on the stereo structure of lignin by ozonation. J. Wood Sci. 2000, 46, 414-4-15. 

Ralph, J. Ede, R. M. Robinson, N. P. Main, L. Reactions of P-aryl lignin model quinone methides with anthrahydroquinone and anthranol. J. Wood Chem. Technol. 1987, 7, 133-160. 

Transport of amino acids across a chloroform liquid membrane with these carriers also revealed a high specificity (Scheme 2). For efficient transport, an aromatic side chain must be present and the distance between the aryl and ammonium functions is optimal in the P-aryl systems. Neither oe-phenyl-glycine 42 nor y-phenyl-butyrine 43 are transported to significant extents 25a>. These results are shown in Table 2. The selectivity with 13 contrasts sharply for that observed with typical detergents wherein side chain hydrophobicity determines the relative transport rates. 

The P-aryl phosphanorbomenes (85 and 104) prepared by us served as excellent model compounds in photoinduced fragmentation-related phosphorylations. On the one hand, new //-phosphinates (105) were synthesized (Scheme 27), while on the other hand, our experiments indicating a high sensitivity towards the steric effects substantiated the AE mechanism involving a pentacoordinated pentavalent intermediate (106) (Scheme 28) [74, 75],... 

The enantioselectivity increases dramatically when the ligands contain electron-withdrawing P-aryl substituents. Electron-donating substituents on the substrate give the highest ee (91% for 6-methoxy-2-vinylnaphthalene in apolar solvents). Mechanistic studies at room temperature have shown that at low concentration of HCN nickel zero species are the resting states, but at higher concentrations of HCN q3-benzyl nickel cyanide species were also observed. 

Acyclic Enones as Substrates Compared to cyclic enones, acyclic enones are generally more challenging substrates for the copper-catalyzed asymmetric 1,4-addition reactions. Several ligands have been reported that can achieve high ee when p-aryl acyclic enones are used as substrates in the 1,4-addition of diethyl-zinc (Figure 3.5). ° ... 

However, very few catalyst systems reported to date are highly effective for both p- aryl and p-alkyl acyclic enone substrates in the copper-catalyzed asymmetric 1,4-addition. Ligand 27, developed by Hoveyda, shows high enantioselectivity in the 1,4-addition of dialkylzinc reagents to various acyclic enones (Figure 3.6). " ... 

Figure 3.5. Chiral hgands that exhibit >90% ee in the reaction between P-aryl acyclic enones and diethylzinc under copper catalysis.

Bode and co-workers rendered this transformation asymmetric allowing access to a>cyclopentenes 244 with high enantioselectivity (Table 19) [128], Optimized reaction conditions include the use of A-mesityl substituted aminoindanol derived triazo-lium catalyst 214. When chalcone and derivatives we re subjected to the reaction conditions, ax-cyclopentenes were formed selectively. Although the substrate scope is also limited to P-aryl substituted enals, cis. trans ratios of up to >20 1 are observed. 

The potential application of this catalytic system was illustrated by Takemoto in the application to a tandem conjugate addition towards the asymmetric synthesis of (-)-epibatidine, a biologically active natural product [100, 101], The authors designed an enantioselective double Michael addition of an unsaturated functionalized P-ketoester to a p-aryl nitro-olefm. The asymmetric synthesis of the 4-nitro-cyclohexanones was achieved in both high diastereoselectivity and enantioselectivity, with the natural product precursor synthesized in 90% yield and 87.5 12.5 er (Scheme 49). The target (-)-epibatidine was subsequently achieved in six steps. 

The best reactivity and selectivity was illustrated with the binaphthol derived thiourea amine catalyst 277. The substrate scope was explored primarily with P-aryl-nitro-olefms of both electron-donating and electron-withdrawing natures. Yields and selectivities were high for the majority of substrates (Scheme 78). 

An unexpected and potentially useful mode of reactivity was observed in the reaction of cinnamaldehyde and cyclopentadiene catalysed by diarylprolinol silyl ether 39 [73]. Rather than observing a Diels-Alder adduct, the products resulting from an ene reaction were isolated in excellent yield. The transformation was found to be general for a series of P-aryl acroleins (40) with routinely excellent levels of... 

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