Side proton abstraction

Filter/dry OH-functionality of polyol depends on structure of R Difficult to "cap all 2° OH groups with EO Side reactions (esp. proton abstraction) limit functionality of Urethane-grade polyol product and create unwanted functional groups... 

This method does not allow the formylation of aliphatic Grignard or organolithium reagents since in these cases the enhancement in base strength in the presence of hexamethylphosphoramide produces side reactions due to proton abstraction. 

How the dead species PnQ+ loses its charge will of course depend on the nature of Q and on the method of isolating the polymer. An analysis of the polymer for Q will give the concentration of growing centres at the instant at which the reaction was killed, and if the rate at that instant is known, kp can be calculated. One pre-requisite for the success of the method is that there should be no side-reactions, such as proton-abstraction from the growing centre ... 

Mandelate racemase, another pertinent example, catalyzes the kinetically and thermodynamically unfavorable a-carbon proton abstraction. Bearne and Wolfenden measured deuterium incorporation rates into the a-posi-tion of mandelate and the rate of (i )-mandelate racemi-zation upon incubation at elevated temperatures. From an Arrhenius plot, they obtained a for racemization and deuterium exchange rate was estimated to be around 35 kcal/mol at 25°C under neutral conditions. The magnitude of the latter indicated mandelate racemase achieves the remarkable rate enhancement of 1.7 X 10, and a level of transition state affinity (K x = 2 X 10 M). These investigators also estimated the effective concentrations of the catalytic side chains in the native protein for Lys-166, the effective concentration was 622 M for His-297, they obtained a value 3 X 10 M and for Glu-317, the value was 3 X 10 M. The authors state that their observations are consistent with the idea that general acid-general base catalysis is efficient mode of catalysis when enzyme s structure is optimally complementary with their substrates in the transition-state. See Reference Reaction Catalytic Enhancement... 

The presence of organolithium compounds in etheric solvents at temperatures above 0°C may lead to extensive decomposition of the solvent and solute a slow electron transfer side reaction of lithium naphthalene or sodium naphthalene with the THE solvent (equation 5) has been reported . The three isomeric forms of BuLi were shown to induce extensive decomposition of THE. The main path for this process is metallation at position 2 of THE, leading to ring opening and elimination of ethylene. An alternative path is proton abstraction at position 3, followed by ring opening. The presence of additives such as (—)-sparteine (24), DMPU (25), TMEDA and especially HMPA does not prevent decomposition but strongly affects the reaction path. ... 

In most cases, either R1 or R2 in amide 1 is a hydrogen. For configurational characterization the terms syn and anti for enolates having the non-hydrogen substituent in the position cis or trans to the oxygen, respectively, will be employed (see also Section A.I.). The ratio of syn- to anh-enolale formed in the proton abstraction process sets the upper limit for the stereoselectivity that can be achieved in a subsequent alkylation reaction, since it is generally assumed that attack of the electrophile occurs from the same side on both the syn- and anti-tnolate if the other side is blocked by a bulky substituent. 

Angular methylation at positions 8a, 9a and 14a has been carried out with the unsaturated keto steroids (16),158,159 (18), (20)160 and (21).161,162 The observed result is due to the presence of the double bond which controls the direction of enolization. Proton abstraction results in the formation of a conjugated dienolate anion which is alkylated from the less hindered side at the most electronegative carbon atom. 

Under conditions of kinetic control, the mixed Aldol Addition can be used to prepare adducts that are otherwise difficult to obtain selectively. This process begins with the irreversible generation of the kinetic enolate, e.g. by employing a sterically hindered lithium amide base such as LDA (lithium diisopropylamide). With an unsymmetrically substituted ketone, such a non-nucleophilic, sterically-demanding, strong base will abstract a proton from the least hindered side. Proton transfer is avoided with lithium enolates at low temperatures in ethereal solvents, so that addition of a second carbonyl partner (ketone or aldehyde) will produce the desired aldol... 

The alanine racemization catalyzed by alanine racemase is considered to be initiated by the transaldimination (Fig. 8.5).26) In this step, PLP bound to the active-site lysine residue forms the external Schiff base with a substrate alanine (Fig. 8.5, 1). The following a-proton abstraction produces the resonance-stabilized carbanion intermediates (Fig. 8.5, 2). If the reprotonation occurs on the opposite face of the substrate-PLP complex on which the proton-abstraction proceeds, the antipodal aldimine is formed (Fig. 8.5,3). The subsequent hydrolysis of the aldimine complex gives the isomerized alanine and PLP-form racemase. The random return of hydrogen to the carbanion intermediate is the distinguishing feature that differentiates racemization from reactions catalyzed by other pyridoxal enzymes such as transaminases. Transaminases catalyze the transfer of amino group between amino acid and keto acid, and the reaction is initiated by the transaldimination, followed by the a-proton abstraction from the substrate-PLP aldimine to form a resonance-stabilized carbanion. This step is common to racemases and transaminases. However, in the transamination the abstracted proton is then tranferred to C4 carbon of PLP in a highly stereospecific manner The re-protonation occurs on the same face of the PLP-substrate aldimine on which the a-proton is abstracted. With only a few exceptions,27,28) each step of pyridoxal enzymes-catalyzed reaction proceeds on only one side of the planar PLP-substrate complex. However, in the amino acid racemase... 

Monger et al. (100) reported the synthesis and screening of a 1344-member discrete polymer library L15 as a source of catalysts for the dehydration of the p-hydroxy ketone 11.33 to the enone 11.34 (equation 1, Fig. 11.21). The main feamres of L15, obtained from poly(acrylic anhydride) 11.32 (101) as a scaffold and the amine monomer set Mi (11 representatives) are reported in Fig. 11.21. The protocols for library preparation followed the same principles seen for L14 in the previous section. The presence of both acidic (the COOH backbone, to protonate the OH in 11.33 and promote its departure) and basic groups (side chains in some Mi representatives, to promote proton abstraction) should fulfill the core functional requirements to exert the overall catalytic activity. 

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