Rapid injection NMR

Arnett and coworkers later examined the reaction of lithium pinacolone enoiate with substituted benzaldehydes in THE at 25 °C. The determination of the heat of reaction indicated that the Hammett p value for the process is 331. Although the aldol reaction was instantaneous in THF at 25 °C, the reaction with o- or p-methylbenzaldehyde could be followed using a rapid injection NMR method in methylcyclohexane solvent at —80 °C. Application of Eberson s criterion based on the Marcus equation, which relates the free energy of ET determined electrochemically and the free energy of activation determined by kinetics, revealed that the barriers for the ET mechanism should be unacceptably high. They concluded that the reaction proceeds via the polar mechanism . Consistent with the polar mechanism, cyclizable probe experiments were negative . The mechanistic discrepancy between the reactions of benzaldehyde and benzophenone was later solved by carbon kinetic isotope effect study vide infraf. ... 

LiC104 was shown to be a more compatible Lewis acid for chelation in an ethereal solvent—when TiCU, a typical chelation agent for a-alkoxyaldehydes, was used in EtaO for alkylation of 79, moderate diastereoselectivity (68 32) was obtained. Rapid injection NMR studies of the TiCU-promoted chelation-controlled Mukaiyama aldol reaction and the Sakurai reaction show that an acyclic transition state must be involved in which the silyl groups never reach the carbonyl oxygen atom. In LPDE-mediated enolsilane additions silylated products predominate. Obviously, the mechanism is different—it is a group-transfer aldol reaction [107]. 

Another mixed aggregate complex consisting of Bu°Li and r-butoxide was reported in 1990 as the tetramer (45). Hiis complex was first isolated by Lochmann and has been shown to be tetrameric and dimeric in benzene and THF, respectively, by cryoscopic measurements, and it has also been studied by rapid injection NMR techniques. Hiis species has received much attention because it is related to the synthetically useful superbasic or LiKOR reagents prepared by mixing alkali metal alkoxides with lithium alkyls or lithium amides. ... 

In concluding this review it must be noted that there are many other techniques that are being utilized to increase our understanding about the structure of synthetically important carbanions. A partial listing of these techniques would include the theoretical approaches taken by Schleyer, Streitweiser, Houk and others and classical spectroscopic techniques. There exist also a number of useful NMR techniques in addition to the 2D-HOESY method previously mentioned. These NMR techniques include analysis of C chemical shifts, Li- N spin-spin splitting, Li quadrupolar coupling and rapid injection NMR which has proven useful as a technique for structural investigations of aliphatic carba-nions. Last, but certainly not least, the excellent thermochemical measurements recently reported by Amett and coworkers serve to correlate the solid state structural studies with solution species. A... 

Reetz, M. T., Raguse, B., Marth, C. F., Huegel, H. M., Bach, T., Fox, D. N. A. A rapid injection NMR study of the chelation controlled Mukaiyama aldol addition TiCl4 versus LiCI04 as the Lewis acid. Tetrahedron 1992, 48, 5731-5742. 

This assumption was also verified by measurements of McGarrity and Ogle and their coworkers148 b). Introducing a rapid-injection nmr method to study fast reactions like the reaction of n-butyllithium with benzaldehyde they reached the following conclusions if n-butyllithium in toluene-D8 is mixed with THF and benzaldehyde ... 

These results are an elegant demonstration of the power of the new rapid-injection nmr technique. One can expect an increasing amount of new information especially about rearrangements and reactions of organometallic compounds by this method because reactions of this type are normally very fast . 

Using a home-built rapid injection NMR system (RINMR), our plan was to determine the order in each of the reactive compraients. RINMR is uniquely suited... 

Denmark SE, Pham SM (2000) Kinetic analysis of the divergence of reaction pathways in the chiral lewis base promoted aldol addition of trichlorosilyl enolates a rapid injection NMR study. Helv Chim Acta 83 1846-1853... 

Denmark SE, Williams BJ, Eklov BM, Pham SM, Beutner GL (2010) Design, validation, and implementation of a rapid-injection NMR system. J Am Chem Soc 75 5558-5572... 

Denmark SE, Eklov BM, Yao PJ, Eastgate MD (2009) On the mechanism of lewis base catalyzed aldol addition reactions kinetic and spectroscopic investigations using rapid-injection NMR. J Am Chem Soc 131 11770-11787... 

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