Benzylic hydroxyl group, role

In simplifying the complex structure of (1) we are eliminating all features that do not play a direct role in binding (e.g. carbohydrate and benzylic hydroxyl groups). We are also, in our early models, focusing on the right hand portion of (1) which forms, in (2), five of the six hydrogen bonds... 

The oxidation by strains of Pseudomonas putida of the methyl group in arenes containing a hydroxyl group in the para position is, however, carried out by a different mechanism. The initial step is dehydrogenation to a quinone methide followed by hydration (hydroxylation) to the benzyl alcohol (Hopper 1976) (Figure 3.7). The reaction with 4-ethylphenol is partially stereospecific (Mclntire et al. 1984), and the enzymes that catalyze the first two steps are flavocytochromes (Mclntire et al. 1985). The role of formal hydroxylation in the degradation of azaarenes is discussed in the section on oxidoreductases (hydroxylases). 

The Delft synthesis makes use of an acid-catalyzed ring closure - in fact an intramolecular aromatic alkylation - of a l-(3,5-dihydroxy-4-methoxybenzyl) isoquinoline derivative that is prepared starting from (natural) gallic acid. One of the hydroxyl groups is removed via a Pd/ C hydrogenation of the benzyl ether. Other catalytic steps play an important role some steps were improved recently [27]. The crucial step in the Rice synthesis makes use of a l-(2-bromo-5-hydroxy-4-methoxybenzyl)isoquinoline derivative that is also cyclized in an acid-catalyzed ring closure to the morphinan skeleton, followed by catalytic removal of the bromo substituent (Scheme 5.8). 

Benzylic ethers (Ph CH2 OR), allylic ethers (R-CH=CH-CH2 OR) and vinylic ethers [R CH=CH(OR)] together with the most commonly encountered tetrahydropyranyl ethers [THP-ethers, (5)] and /J-methoxyethoxymethyl ethers [MEM-ethers, R0CH2 0(CH2)2 0CH3] play an important role in the protection of a hydroxyl group (p. 550). Macrocyclic ethers (the crown ethers) are important phase transfer catalysts [e.g. 18-Crown-6 (6)]. 

Reduction of, (t-epoxy alcohols. Reduction of 3-substituted-2,3-epoxy alcohols by SMEAH, particularly in THF, gives essentially only the 1,3-diol. However, a substituent at C2 reverses the selectivity and decreases the reaction rate. The hydroxyl group also plays a role the corresponding benzyl ethers show only a slight preference for reduction at C3.1... 

Role of the p-Hydroxyl Group. Preliminary nitrobenzene oxidation experiments were conducted on several benzylic hydroxyl compounds, both with and without a p-hydroxyl group (5). Contrary to what was expected from the literature, some compounds without a p-hydroxyl group formed benzaldehyde products. 

It must be noted that the phenol/aldehyde reaction can be catalyzed by Bronsted acids (protonation of the carbonyl oxygen) as well as by Lewis acids (coordination of the carbonyl oxygen). In the latter case one Lewis centre (e.g. Al ) can accommodate and activate both the phenol and the aldehyde (cq. the benzyl alcohol, in the consecutive reaction). As a consequence, ortho-substitution is favoured [14,15]. The high 2,2 -dihydroxydiphenylmethane selectivity we obtained with homogeneous Al " -catalysis and with 7-alumina is consistent with these data. Additionally, the finding that the H - US - Y catalyzed toluene/formaldehyde-condensation gives a low 2,2 -selectivity, 19% [16], compared to the 32% we obtained with phenol, also indicates the hydroxyl-group plays a role. However, transalkylation, reported to lead to ortho-substitution in condensations of phenol with methanol on both zeolite- and non-zeolite Bronsted acid catalysts [17], can t be ruled out. 

Among the various factors influencing enantioselection, hydrogen bonding between the residual hydroxyl group of tri-O-alkylated compounds and the Chiral-cel OD phase seems to play an important role. As a matter of fact, the separation factor of compound 10 (R = benzyl) (a = 3.45 under optimum conditions) dramatically drops to 1.24 when the OH group is replaced by a propoxy group [55]. 

The high stereopreference was rationalized by considering complex 388 in which an attractive n-n donor-acceptor interaction favors co-ordination of the dienophile to the face of the boron center which is cis to the 2-hydroxyphenyl substituent. Hydrogen bonding of the hydroxyl proton of the 2-hydroxyphenyl group to an oxygen of the adjacent B—O bond played an important role in the asymmetric induction. Protection of this hydroxy functionality with a benzyl group caused reversal of enantioselectivity in the cycloaddition of cyclopentadiene with methacrolein (model 389)244. 

The carbonyl group in 24 could be temporarily protected as the dioxolane,16 or somewhat more efficiently as the dimethyl acetal 25.17 Subsequent conventional hydroboration led stereoselectively to the P alcohol 26. Although our earliest considerations called for ultimate base-promoted elimination of the OR substituent in intermediates more advanced than 16, we later came to recognize that a methoxy derivative was not going to fulfill this role to our satisfaction. Alternatively, the tactic of forming the benzyl ether at this point ultimately proved well suited to the eventual return to an unmasked hydroxyl at this site.17,18... 

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