Carbon compound protonation approaches

Acid-Catalyzed Hydrolysis. In acid-catalyzed ester hydrolysis the species that undergoes the rate-determining step is the protonated ester (Fig. 13.10). When the molecule is in this protonated form, the enhanced depletion of electrons near the central carbon promotes the approach of an electron-rich oxygen of a water molecule. Hence, the hydrolysis rate depends on the fraction of compound molecules that are protonated. This fraction, in turn, depends on how strong a base the ester function is. If we define an acidity constant (see Chapter 8) for the protonated species... 

How do you approach determining a structure of an unknown compound utilizing carbon and proton NMR spectra Let s look at the proton NMR spectrum shown in Figure 6.25. The spectrum is for a compound with formula C6H10O2. The index of hydrogen deficiency for this compound is calculated to be 2. 

Bates and his associates have found that cyclohexadienyl carbanion itself protonates at the central carbon atom from three to eight times as rapidly as at a terminal one, but the conditions involved were different from those encountered in a Birch reduction. Since the Birch reduction of many 3-meth-oxyestra-l,3,5(10)-triene derivatives affords 1,4-dihydro compounds in yields approaching 90%, the cyclohexadienyl carbanions involved in these reductions must protonate about eighteen times faster at the central carbon atom than at a terminal one. 

Both these methods require equilibrium constants for the microscopic rate determining step, and a detailed mechanism for the reaction. The approaches can be illustrated by base and acid-catalyzed carbonyl hydration. For the base-catalyzed process, the most general mechanism is written as general base catalysis by hydroxide in the case of a relatively unreactive carbonyl compound, the proton transfer is probably complete at the transition state so that the reaction is in effect a simple addition of hydroxide. By MMT this is treated as a two-dimensional reaction proton transfer and C-0 bond formation, and requires two intrinsic barriers, for proton transfer and for C-0 bond formation. By NBT this is a three-dimensional reaction proton transfer, C-0 bond formation, and geometry change at carbon, and all three are taken as having no barrier. 

The a-cyanoacetates 12 are optimal substrates for the approach outlined in Scheme 2.26 due to the low pKa of the a-proton. It has been reported that the quinidine-derived alkaloid /fisocupridine (/ -ICD) can catalyze the direct a-amination of a-cyanoacetates 12 (Eq. 4) and /fdicarbonyl compounds [10], probably by an enolate having a chiral /MCD-H+ counterion as the intermediate. The a-amination of a-cyanoacetates 12 with di-tert-butyl azodicarboxylate 2c is an efficient process that proceeds with only 0.5 mol% of /MCD. The expected products 13, having a stereogenic quaternary carbon center, were isolated in excellent yields and with excellent levels of enantioselectivity independently by the nature of the aryl-substituent in the a-cyanoacetates, while the / -dicarbonyl compounds give slightly lower enantioselectivty (83-90% ee). 

In both series [reactions 49 (R2 = Ph) and 51] the enamines are the most reactive of the neutral compounds included in the correlations. Enolate anions are protonated on carbon even faster, but these data points fall below the least-squares lines, in all likelihood because the rates are approaching the diffusion limit. 

When HX is a carbon acid the value of the rate coefficient, ) for a thermodynamically favourable proton transfer rarely approaches the diffusion limit. Table 1 shows the results obtained for a few selected carbon acids which are fairly representative of the different classes of carbon acids which will be discussed in detail in Sect. 4. For compounds 1—10, the value of k i is calculated from the measured value of k, and the measured acid dissociation constant and, for 13, k, is the measured rate coefficient and k1 is calculated from the dissociation constant. For 11 and 12, both rate coefficients contribute to the observed rate of reaction since an approach to equilibrium is observed. Individual values are obtained using the measured equilibrium constant. In Table 1, for compounds 1—10 the reverse reaction is between hydronium ion and a carbanion whereas for 11, 12 and 13 protonation of unsaturated carbon to give a carbonium ion is involved. For compounds 1—12 the reverse reaction is thermodynamically favourable and for 13 the forward reaction is the favourable direction. The rate coefficients for these thermodynamically favourable proton transfers vary over a wide range for the different acids. In the ionization of ketones and esters, for which a large number of measurements have been made [38], the observed values of fe, fall mostly within the range 10s—101 0 1 mole-1 sec-1. The rate coefficients observed for recombination of the anions derived from nitroparaffins with hydronium ion are several orders of magnitude below the diffusion limit [38], as are the rates of protonation and deprotonation of substituted azulenes [14]. For disulphones [65], however, the recombination rates of the carbanions with hydronium ion are close to 1010 1 mole-1 sec-1. Thermodynamically favourable deprotonation by water of substituted benzenonium ions with pK values in the range —5 to —9 are slow reactions [27(c)], with rate coefficients between 15 and 150 1 mole-1 sec-1 (see Sect. 4.7). 

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