Phenyl-substituted alcohols

Various racemic secondary alcohols with different substituents, eg, a-hydroxyester (60), are resolved by PFL neatly quantitatively (75). The effect of adjacent unsatuiation on enzyme-catalyzed kinetic resolutions was thoroughly studied for a series of aHyUc (61), propargyUc (62), and phenyl-substituted 2-aIkanols (76,77). Excellent selectivity was observed for (E)-aHyhc alcohols whereas (Z)-isomers showed poor selectivity (76). 

FIGURE 2.13 Schematic presentation of the self-associated chain-like w-mer of the phenyl-substituted alcohol. 

FIGURE 2.14 A possibility to self-associate involving both the hydroxyl functionalities and the aromatic jr-electrons in the case of phenyl-substituted alcohols. 

The manner in which alcohols self-associate is different. Unlike carboxyhc acids, alcohols form the long chain-like structures of the self-associated -mers. Schematic presentation of the self-associated chain of the phenyl-substituted alcohol molecules is given in Figure 2.13. Moreover, an alternative possibility of the self-association with the aforementioned alcohols is shown in Figure 2.14. 

Wan s group investigated a number of phenyl-substituted hydroxybiphenylbenzyl alcohols in the hope that the a-phenyl quinone methides photogenerated from them might show enhanced absorption and lifetimes, and thus be easier to characterize by LFP.37,38 They were successfully able to photogenerate and characterize quinone... 

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. 

Kinetics of the reaction of diazodiphenylmethane (92) in a wide range of alcohols with pyridine and pyridine-A -oxide 3- and 4-carboxylic acids (84)-(87), 4-substituted benzoic acids (88)," cw -substituted cinnamic acids (89), 2-(4-phenyl-substituted)cyclohex-l-enyl carboxylic acids (90), and 4 -substituted-biphenyl-2-carboxylic acids (91)" have been reported. Comparison of the new results for 4-substituted benzoic acids with the published results of data for 3-substituted benzoic acids was made, " and it was concluded that the most important solvent property influencing the rate of reaction appears to be the polarity of the alkyl group expressed as Taft s polar constant a. Transmission coefficients in the cinnamic acids (89) were compared with those in the bicyclic acids (90) and... 

Verevkin, S.P. Strain effects in phenyl-substituted methanes, geminal interaction between phenyl and the electron-releasing substituent in benzylamines and benzyl alcohols, J. Chem. Eng. Data, 44(6) 1245-1251, 1999. 

Table 17) with two substituents in position C3 the oxygen transfer by the chiral hydroperoxides occurred from the same enantioface of the double bond, while epoxidation of the (ii)-phenyl-substituted substrates 142c,g,i resulted in the formation of the opposite epoxide enantiomer in excess. In 2000 Hamann and coworkers reported a new saturated protected carbohydrate hydroperoxide 69b , which showed high asymmetric induction in the vanadium-catalyzed epoxidation reaction of 3-methyl-2-buten-l-ol. The ee of 90% obtained was a milestone in the field of stereoselective oxygen transfer with optically active hydroperoxides. Unfortunately, the tertiary allylic alcohol 2-methyl-3-buten-2-ol was epoxidized with low enantioselectivity (ee 18%) with the same catalytic system . 

The technique of chiral auxiliaries was exploited in a synthesis of cholesterol absorption inhibitors, based on an imino-Reformatsky reaction between bromoacetates of chiral alcohols (e.g. 69a and 69b) and imine 70. Virtual complete asymmetric induction was found with (-)-trans-2-phenylcyclohexanol and (—)-phenyl substituted menthol derived chiral auxiliaries (equation 43)126. 

The reaction of phenyl-substituted alkenes (2-phenylprop-l-ene, ( )-l-phenylprop-l-ene, 1,1-diphenylethene, 1,1-diphenylprop-l-ene) with F-Teda BF4 (6) in the presence of various alcohols results in the formation of vicinal fluoro alkoxy adducts with Markovnikov-type regioselec-tivity.89,94 The stereochemistry of the fluorination-methoxylation addition reaction is slightly syn predominant in the case of (Z)-stilbene, indene, and dibenzosuberenone, while equal amounts of both diastereoisomers are formed in the case of ( )-l-phenylprop-l-ene and acenaphthylene. 

Asymmetric hydroboration.1 Hydroboration of phenyl-substituted trisubstituted alkenes, cyclic or acyclic, followed by oxidation results in alcohols with an optical purity of 80 100%, with the (S)-configuration at the hydroxylaled carbon predominating with reagent prepared from (+)-oc-pinene. 

In some cases, the effect of reactant structure may outweigh the influence of catalyst nature. This is seen by comparison with the dehydration of aliphatic secondary alcohols and substituted 2-phenylethanols on four different oxide catalysts (Table 4). With aliphatic alcohols, the slope of the Taft correlation depended on the nature of the catalyst (A1203 + NaOH 1.2, Zr02 0.3, Ti02—0.8, Si02—2.8 [55]) whereas for 2-phenyl-ethanols, the slope of the corresponding Hammett correlation had practically the same value (from —2.1 to —2.4) for all catalysts of this series [95]. The resonance stabilisation of an intermediate with a positive charge on Ca clearly predominates over other influences. 

Among the phenyl-substituted ethylenes that have been cleaved with alcohols are styrene oxide.144 -methylstyrene oxide,101 and stilbene oxide.143 Sodium methoxide is capable of adding to either nf... 

The 2-methyl, 2-cyclopropyl and 2-phenyl substituted 8,9-dehydro-2-adamantyl cations 25 were prepared from their respective alcohols using fluorosulfuric acid in sulfuryl chloride fluoride at low temperatures (equation 27). The relative extent of charge delocalization in these cations was estimated by comparing their NMR spectra. The ions are nonequilibrating static cations, as shown by their proton NMR spectra56. 

Arnett and Hofelich measured heats of reaction of a variety of alcohols with SbF5/FS03H in sulfuryl chloride fluoride to form their respective carbocations at constant temperature (-40 °C). In this superacid medium there were no ion-pair complications126 and hence reliable calorimetric data were obtained for various cyclopropyl and phenyl substituted cations. The heats of reaction for the formation of tricyclopropylcarbinyl cation (-59.2 kcalmol ), trityl cation (-49.0 kcalmol1) and ferr-butyl cation (-35.5 kcalmol1) show that the relative order of the stabilization of the cationic center is cyclopropyl >... 

Kinetic data for the reactions of diazodiphenylmethane in 10 different alcohols with 2-(4-phenyl substituted)cyclohex-l-enylcarboxylic acids (75) were correlated using the extended Hammett equation.68 Reaction of the species (76)-(78) with the light radioactive H isotope, the muonium atom, has been studied.69 The largest primary kinetic isotope effects ever reported (ca 850) are seen in this work for the addition of muonium to one of the C=0 groups. 

B. Generation of Phenyl-substituted Disilenes. Spectra and Kinetics of Addition of Alcohols... 

Generation of various phenyl-substituted disilenes by the photolysis of the masked disilenes, 7,8-disilabicyclo[2.2.2]octadiene derivatives, is quite useful, especially for unsymmetrically substituted disilenes. Investigation of the regiochemistry as well as the diastereochemistry of alcohol addition to phenyltrimethyldisilene was made possible for the first time by using this method27. 

The results in Table 3 were explained as shown in Scheme 4. From the fact that no kinetic isotope effect was observed in the reaction of phenyl-substituted disilenes with alcohols (Table 1), it is assumed that the addition reactions of alcohols to phenyltrimethyl-disilene proceed by an initial attack of the alcoholic oxygen on silicon (nucleophilic attack at silicon), followed by fast proton transfer via a four-membered transition state. As shown in Scheme 4, the regioselectivity is explained in terms of the four-membered intermediate, where stabilization of the incipient silyl anion by the phenyl group is the major factor favoring the formation of 26 over 27. It is well known that a silyl anion is stabilized by aryl group(s)443. Thus, the product 26 predominates over 27. However, it should be mentioned that steric effects also favor attack at the less hindered SiMe2 end of the disilene, thus leading to 26. 

It is not intended to extend this discussion of reactions of carbocations with water to consideration of the alcoholic solvents trifluoroethanol (TFE) and hexa-fluoroisopropanol (HFIP), which have been extensively studied and reviewed by McClelland and Steenken.3 However, an important point of interest of these solvents is that their reactivities toward carbocations are greatly reduced compared with water (by up to a factor of 104 in TFE and 108 in HFIP) and that differences in rate constants can be observed between cations which would react indiscriminately at the solvent relaxation limit in water. The following comparisons of rate constants for carbocations with similar pAR values reacting with hexafluoroiso-propanol241,242 reinforces the conclusion that structural variations in the cation lead to changes in intrinsic barrier and, for example, that phenyl substitution is probably associated with such an increase in going from benzyl to benzhydryl (although the benzyl cation itself is not shown). 

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