Intramolecular hydride transfer, rate

In the aldol-Tishchenko reaction, a lithium enolate reacts with 2 mol of aldehyde, ultimately giving, via an intramolecular hydride transfer, a hydroxy ester (51) with up to three chiral centres (R, derived from rYhIO). The kinetics of the reaction of the lithium enolate of p-(phenylsulfonyl)isobutyrophenone with benzaldehyde have been measured in THF. ° A kinetic isotope effect of fee/ o = 2.0 was found, using benzaldehyde-fil. The results and proposed mechanism, with hydride transfer rate limiting, are supported by ab initio MO calculations. 

The mechanism of the aldol-Tishchenko reaction has been probed by determination of kinetics and isotope effects for formation of diol-monoester on reaction between the lithium enolate of p-(phenylsulfonyl)isobutyrophenone (LiSIBP) and two molecules of benzaldehyde. ". The results are consistent with the formation of an initial lithium aldolate (25) followed by reaction with a second aldehyde to form an acetal (26), and finally a rate-limiting intramolecular hydride transfer (Tishchenko... 

An effective concentration for the second aldehyde group of 13 has been quoted, obtained by taking the value of (kobs/[NaOH]) at low [NaOH] and comparing it with the third-order rate coefficient for the intermolecular Cannizzaro reaction of benazaldehyde under the same conditions. This does not compare inter- and intramolecular hydride transfer steps. 

Intramolecular hydride transfer in equation 4 proceeds with an enzymelike EM of 6.5 X 106 M. In other words, the intramolecular reaction is 6.5 X 106 times faster than the intermolecular counterpart at 1 M concentration (11). Davis et al. (II) argued that relief of strain cannot explain the fast rate because (a) the equilibrium constant in equation 4 is close to unity and (b) force-field calculations show that hydroxy ketone is only 1.7 kcal/mol more strained than the corresponding diketone, which lacks nonbonded H/C=0 interactions. The extremely fast nucleophilic attack on the carbonyl is, however, expected from our spatiotemporal hypothesis. Because the mobile hydrogen is held rigidly only 2.35 A away from the carbonyl carbon, well under the suspected critical distance of 2.8 A (6), the conditions for an enzyme-like acceleration are met. 

The reaction is not chelation-controlled and does not involve hydride transfer to the Lewis acid since BF3 OEt2, which can only be four-coordinate, also gives excellent anti stereoselectivity. Tethering the reagent and intramolecularizing the process is also important for the rate of reaction - the analogous intermolecular process was found to be sluggish, even at 0 °C. Rhodium(I) complexes also catalyze the reduction reaction. Burk... 

For example, a 6-rlng TS is favored for proton transfer to the carboxylate center in CH3CHN02CH2CH2C02 to form the nitrocarbanion. Hydride transfer is Intramolecularly base-catalyzed in the bromine oxidation of o-for-myl benzoate ion to produce a 70x acceleration (other substituents affect the benzaldehyde rate only within 3x). Nucleophilic addition of -OO2 to the formyl group Is excluded because phthallc anhydride hydrolyzes too... 

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