Β-aryl Group Research Articles

Calculated pKEnol Values for β,β-Diarylacetic Acids and β,β-Diarylacetaldehydes. Effect of Steric Bulk of Substituents on the Relative Stability of Enols of Carboxylic Acids and Aldehydes

The energies, pKEnol values, structures, and conformations of vinyl alcohol (3a), acetaldehyde (4a), 1,1-ethenediol (5a), acetic acid (6a), and six derivatives of each (3b−g, 4b−g, 5b−h, and 6b−h) substituted by two β-aryl groups of increasing bulk from Ph to Tip (2,4,6-tri-i-PrC6H2) were calculated by the B3LYP method in order to evaluate quantitatively the pKEnol reducing effect of bulky aryl groups. Also calculated were the same parameters for the ArCHXCO2H/ArC(X)C(OH)2 pairs for Ar = Ph, X = CN (9a/9b), OH (10a/10b), for which pKEnol is known, and for Ar = Mes (mesityl), X = CN. All the substituents significantly decrease the pKEnol values from 22.4 (6a/5a) and 9.1 (4a/3a). For example, pKEnol = 0.2, −2.7, −2.0, and −2.7 for ArAr‘CHCHO/ArAr‘CCHOH and 13.3, 11.5, 9.2, and 9.3 for ArAr‘CHCO2H/ArAr‘CC(OH)2 when Ar,Ar‘ = Ph,Ph, Ph,Mes, Mes,Mes, and Tip,Tip, respectively. For 9a/9b and 10a/10b, the calculated pKEnol values resemble the observed ones. The enols and enediols (except 3b and 5b, when Ar2C = fl...

The γ-Silicon Effect. I. Solvent Effects on the Solvolyses of 2,2-Dimethyl-3-(trimethylsilyl)propyl and 3-(Aryldimethylsilyl)-2,2-dimethylpropyl p-Toluenesulfonates

Abstract The solvolysis rates of 2,2-dimethyl-3-(trimethylsilyl)propyl and 3-(aryldimethylsilyl)-2,2-dimethylpropyl p-toluenesulfonates were measured in a wide variety of solvents at 45 °C. The solvent effects were analyzed by using the Winstein–Grunwald equation. The solvent effects observed did not give simple linear correlations with the 2-adamantyl YOTs parameter, but showed dispersion behavior in a series of binary solvents. The m values of 0.59—0.67 were remarkably lower than unity for the limiting kc solvolysis of 2-adamantyl p-toluenesulfonate. The deviation patterns could not be interpreted in terms of nucleophilic assistance by the solvent. The dispersion behavior with reduced m values was found to be more significant for the 3-(aryldimethylsilyl) than for the 3-(trimethylsilyl) derivatives and was compatible with the delocalization of the incipient cationic charge by participation of the Si–Cγ bond in the rate-determining step. An extended dual-parameter treatment, log (k/k80E) = mcYOTs + mΔYΔ, successfully correlated such γ-silyl assisted solvolyses. The MΔ values of 0.24—0.49 so obtained, where MΔ = 0.51mΔ/(mc + 0.51mΔ), are a measure of the extent of charge delocalization, suggesting that the γ-silyl group in the percaudal interaction is more effective in delocalizing the cationic charge than the alkyl group in C–C σ-participation, but less so than π-assisted interaction by the β-aryl group.

Elimination Reactions of (Z)-Thiophene- and (Z)-Furan-2-carbaldehydeO-Benzoyloximes. Effect of β-Aryl Group upon the Nitrile-Forming Anti Transition State

Elimination reactions of (Z)-thiophene- and (Z)-furan-2-carbaldehyde O-benzoyloximes 1 and 2 with DBU in MeCN have been investigated kinetically. The reactions are second order and exhibit substantial values of Hammett ρ and kH/kD values, and an E2 mechanism is evident. The relative rates of elimination from (Z)-ArCHNOC(O)C6H4Y are 1/1.1/0.6 for Ar = phenyl/thienyl/furyl, respectively. For reactions of 1 with DBU in MeCN, kH/kD = 8.2 ± 0.1, Hammett ρ = 1.22 ± 0.19, β1g = −0.43 ± 0.01, ΔH⧧ = 5.9 ± 0.1 kcal/mol, and ΔS⧧ = −28.5 ± 0.3 eu have been determined. The corresponding values for 2 are kH/kD = 8.8 ± 0.2, ρ = 1.87 ± 0.05, β1g = −0.55 ± 0.10, ΔH⧧ = 6.5 ± 0.1 kcal/mol, and ΔS⧧ = −29.0 ± 1.5 eu. The kH/kD, Hammett ρ, and |β1g| values increase as the β-aryl group is changed in the order phenyl < thienyl < furyl. The results indicate that the transition state structure for the nitrile-forming elimination changes slightly toward product-like with the change of the β-aryl group.

Conformational Preference in β-Aryldehydroalanine. Synthesis and Conformational Study of Tripeptides Containing β-Aryldehydroalanine Residues

Abstract In order to investigate the effect of bulky β-substituents on the conformational preference in α, β-dehydroamino acid residues, three kinds of tripeptides containing (Z)-β-phenyldehydroalanine, (Z)-β-(1-naphthyl)dehydroalanine, or (Z)-β-(1-pyrenyl)dehydroalanine residue were synthesized: Boc–Ala–ΔZAA–Val–OMe (Boc, t-butoxycarbonyl; Ala, L-alanine; ΔZAA, (Z)-β-aryldehydroalanine; Val, L-valine; OMe, methoxy). Their conformations in solution were investigated using 1H NMR spectroscopy. The solvent accessibility of the NH resonances and the nuclear Overhauser effect (NOE) indicated that the three peptides in CDCl3 form a type II β-turn conformation supported by hydrogen bonding between CO (Boc) and NH (Val). From a conformational energy calculation, the three kinds of ΔZAA residues were also shown to favor a type II β-turn conformation. In each β-turn, the orientation of the aryl plane was found to be non planar relative to the Cα=Cβ–Cγ plane, suggesting that a steric interaction between the β-aryl group and the peptide backbone leads to the internal rotation angles preferred for the β-turn backbone.

Substituent Effect Studies of Aryl-Assisted Solvolyses. I. The Acetolysis of 2,2-Bis(substituted phenyl)ethyl p-Toluenesulfonates

Abstract The substituent effect on the acetolysis of 2,2-bis(substituted phenyl)ethyl p-toluenesulfonates at 90.10 °C can be described accurately in terms of the Yukawa–Tsuno (LArSR) relationship, giving a ρ value of −4.44 and an r value of 0.53. The substituent effect correlation of this system carrying two aryls is quite comparable to that of the 2-methyl-2-phenylpropyl system carrying a single aryl group, suggesting the close similarity in the structure of the transition states between the systems. The results can be reasonably accounted for on the basis of the accepted mechanism of this reaction, involving a rate-determining aryl-assisted transition state where only one aryl group of the two β-aryl groups participates.

Additive Pummerer reactions of vinylic sulfoxides. Synthesis of γ-hydroxy-α,β-unsaturated esters, α-hydroxyketones, and 2-phenylsulfenyl aldehydes and primary alcohols

Treatment of β-monosubstituted vinylic sulfoxides 1 with trifluoroacetic anhydride in dichloromethane gave excellent yields of 1,2-bis(trifluoroacetoxy)thioethers 6. Mildly basic methanolysis of 2-alkyl-substituted 6 gave α-hydroxyaldehydes 11 as monomer-dimer mixtures; similar treatment of the 2-aryl analogues afforded aryl (hydroxymethyl) ketones 12. Compounds 11 underwent Wittig reactions with methoxycarbonylmethylenetriphenylphosphorane to give high yields of γ-hydroxy-α,β-unsaturated esters 13, predominantly as the E-isomers. β-Monosubstituted vinylic sulfoxides 1 possessing a β-aryl group, and β-disubstituted vinylic sulfoxides 3 reacted with trifluoromethanesulfonic anhydride-sodium acetate in acetic anhydride to give 2-(phenylsulfenyl)acylals 14. These gave 2-phenylsulfenyl aldehydes 15 upon basic methanolysis, and the corresponding primary alcohols 16 on reduction with sodium borohydride. Reaction of both geometric isomers of enantiomerically pure vinylic sulfoxide 1o with TFAA gave racemic 6o as a mixture of diastereomers. Reaction of optically pure ( E)- and ( Z)- 1p with trifluoromethanesulfonic anhydride-sodium acetate in acetic anhydride gave acylal 19 in 10.5 and 23% e.e., respectively.

Preparation of Newly Modified DIOP Bearing Bis(4-dimethylamino-3,5-dimethylphenyl)phosphino Groups and Its Application to Efficient Asymmetric Hydrogenation of Itaconic Acid Derivatives

We prepared a modified DIOP analogue bearing bis(4-dimethylamino-3,5-dimethylphenyl)phosphino groups. Its rhodium complex was found to be a useful catalysts for asymmetric hydrogenation of dimethyl itaconate and itaconic acid derivatives bearing β-aryl groups

ChemInform Abstract: Highly Efficient Asymmetric Hydrogenation of Itaconic Acid Derivatives Catalyzed by a Modified DIOP‐Rhodium Complex.

Abstract A modified DIOP analogue bearing 4-methoxy and 3,5-dimethyl groups on each phenyl group has been synthesized. The rhodium complex of the ligand has been found to give very high optical yields in the asymmetric hydrogenation of itaconic acid and its derivatives bearing β-aryl groups, the products of which are the key-intermediates for optically active lignan derivatives.

Highly efficient asymmetric hydrogenation of itaconic acid derivatives catalyzed by a modified DIOP-rhodium complex

A modified DIOP analogue bearing 4-methoxy and 3,5-dimethyl groups on each phenyl group has been synthesized. The rhodium complex of the ligand has been found to give very high optical yields in the asymmetric hydrogenation of itaconic acid and its derivatives bearing β-aryl groups, the products of which are the key-intermediates for optically active lignan derivatives.

Phosphorescence of lyophilized complexes between cyclodextrins and?-arylpropiophenones

β-Arylpropiophenones do not phosphoresce in homogeneous solution as a result of excited state quenching by the β-aryl group. In the presence of cyclodextrins the parent substrate, β-phenylpropiophenone, shows readily detectable phosphorescence. The complexes show strong phosphorescence after lyophilization to dryness. The phosphorescence intensity of ring-substituted derivatives is strongly dependent upon molecular size and cavity dimensions, suggesting that the β-arylpropiophenones can be used to probe these properties.

A novel C α-C β cleavage of a β- O-4 lignin model dimer with rearrangement of the β-aryl group by Phanerochaete chrysosporium

Incubation of aβ- O-4 lignin substructure model dimer, 4-ethoxy-3-methoxyphenylglycerol-β-guaiacyl ether (I), with a culture of Phanerochaete chrysosporium yielded 2-guaiacoxyethanol (II) as one of the main catabolites. It was demonstrated by isotopic investigation with β- 18O- and γ- 13C-labeled substrates that the guaiacyl group at the β-position of (I) was rearranged to the adjacent γ-position in the formation of (II) by C α-C β cleavage.

A NOVEL ORTHO-SUBSTITUENT EFFECT ON FORMATION OF VINYL CATIONS IN THE PHOTOLYSIS OF VINYL BROMIDES

Abstract Introduction of a substituent into ortho-position of β-aryl group in a vinyl bromide resulted in the preferential formation of a vinyl cation in the photolysis. It is considered that the steric repulsion of β-aryl groups makes a convenient conformation for an electron transfer from the aromatic ring to the halogen atom in the radical pair.

Vinylic cations from solvolysis. Part XI. Solvolysis of triarylvinyl arenesulphonates and bromides

Triarylvinyl arenesulphonates and bromides, Ar22CC(Ar1)X (X = Br or O·SO2Ar3), were solvolysed in 70% acetone, and tris-p-methoxyphenylvinyl tosylate (II–OTs) and brosylate were solvolysed in acetic acid. The products were 2,2-diarylacetophenones and tris-p-methoxyphenylvinyl acetate, respectively. The solvolysis of (II–OTs) shows common ion rate depression and the intermediate vinyl cation is captured by bromide and tosylate ions. For change in Ar3 of the leaving group, the Hammett ρ value is 1·91 at 50 and 1·67 at 75°. For 60–90% aqueous acetone a Winstein–Grunwald mY plot is linear with m= 0·42. The reaction rate is sensitive to the α-activating substituent with kα-p-MeO·C6H4/kα-Ph= 630, and much less sensitive to the nature of the β-aryl groups. Solvent isotope effects are small. It is suggested that the reaction has an SN1 mechanism with an intermediate ‘selective’ vinyl cation. The solvent effect and the kOBs : kOTs and the kOTs : kBr reactivity ratios are discussed and it is concluded that the solvolysis is anchimerically and nucleophilically unassisted.

Friedel–Crafts cyclisations. Part III. Synthesis of derivatives of 2(1H)-quinolone (carbostyril) by aluminium chloride-catalysed cycloeliminations of cinnamanilide and related compounds

For the conversion of cinnamanilide into 2(1H)-quinolone (carbostyril) the use of 3 mol. equiv. of the catalyst, aluminium chloride, is desirable; the low yield of 2(1 H)-quinolone obtained from 4-phenyl-3.4-dihydro-2(1H)-quinolone however, indicated that loss of the β-aryl group from cinnamanilide probably occurs virtually simultaneously with the cyclisation. Cyclisation was prevented by either a p-nitro- or a p-methoxy-group in the N-aryl nucleus, and also by an α-chloro-substituent in the cinnamoyl moiety. p-Chlorocinnamanilide was cyclised, however, to 4-phenyl-2(1H)-quinolone with loss of hydrogen chloride. The scope of the cycloelimination was indicated by the formation of 5,6,8-trichloro-2(1H)-quinolone from 2′,4′,5′-trichlorocinnamanilide. Although migration of a methyl group did not accompany the cyclisation of o′-methylcinnamanilide, cyclisation of 2′,6′-dimethylcin-namanilide was permitted by shift of an ortho-methyl group to the adjacent meta-position.

On the Active Site of α-Chymotrypsin: Absolute Configurations and Kinetics of Hydrolysis of Cyclized and Noncyclized Substrates

Abstract The absolute steric course, stereoselectivity, and kinetics of hydrolysis of cyclized and noncyclized ester substrates by α-chymotrypsin are compared. The cyclized substrates are of the form [see PDF for sequence] The noncyclized substrates are analogous α-substituted β-phenylpropionates, C6H5CH2CH(X)CO2R, II-A, X = —NHCOCH3; II-B, X = OCOCH3; II-C, X =—CH2CO2R; V-A, X = Cl; V-B, X = OH; V-C, X = CH3. The absolute configurations of I-C, I-F, and I-G are established in this work; absolute configurations of the other compounds were previously known or recently established. The active site of α-chymotrypsin is described in terms of loci complementary to a conformation of l(+)-II-A, in which the aryl and ester groups are transoid, the β-aryl and α-hydrogen are directed into the enzyme, and the α-acetamido and hydrolyzing ester groups are directed along the exterior of the enzyme. Conditions for hydrolysis of l and d enantiomers by α-chymotrypsin are described. Association is generally dominated by the β-aryl group at its locus, ar. Hydrolysis requires the ester group to be at the hydrolytic site n. Compounds II-A, II-B, and II-C hydrolyze in the l sense as the large α-substituents occupy the α-acetamido site, am, and may not fit into the α-hydrogen locus, h. Both enantiomers of V-A and V-B are hydrolyzed as the small polar substituents, Cl and HO, may be directed in the l sense toward am and in the d sense toward h. Only the l enantiomer of V-C is hydrolyzed, and the small hydrocarbon group, CH3, may not fit at h. All of the cyclized substrates, IA-IG, with five- and six-membered second rings, are hydrolyzed preferentially in the d sense, but with widely varying reactivity and stereoselectivity. In every case the more effective d sense orientation directs the -X-Y- grouping toward h-ar, leaving the remainder of the carbon chain in the same conformation and orientation as that of l-II-A during its enzymic hydrolysis. In d(-)-I-A, d(-)- I-B, S(-)-I-C, and d(-)-I-D, the groupings -X-Y- fit well into ar-h and very high reactivity and high stereoselectivity result. The α-heteroatoms of I-A and I-B and I-D, and the planar π-electron structure of I-C permit fit in ar-h, as do the α-heteroatom substituents in V-A and V-B. In I-F and I-G, the α-CH2, like the α-CH3 in V-C, does not permit the -X-Y- grouping to fit easily into h-ar, and low reactivity and low stereoselectivity result, still with d preference. During hydrolysis of these cyclized substrates in the d sense, the am site is unoccupied. When the second ring in a cyclized substrate is eight-membered, hydrolysis in the l sense may be preferred.