Kagan studies

Kagan studied the base-catalyzed cycloaddition reaction of anthrone and N-methylmaleimide (15) [16]. In contrast to the above reactions,2 and 3 gave (S,R)-16, while 1 and 4 gave (P,S)-16. The oxygen functionality at C(6) of the catalysts might be participating in the asymmetric induction. Besides the alkaloids, (S)-prolinol also gave R,S)-16 in 47% ee. 

Kagan and coworkers determined and studied in detail the crystal structure of a 1 1 molecular complex between (i )-methyl p-tolyl sulfoxide (10) and S)-N-(3,5-dinitrobenzoyl)-l-phenylethylamine (11). They suggested that amide 11, which had been used as a chiral solvating agent for sulfoxides, might find use as a resolving agent for these compounds. ... 

Shvedova, A.A. and Kagan, V.E. (2010) The role of nanotoxicology in realizing the helping without harm paradigm of nanomedicine lessons from studies of pulmonary effects of single-walled carbon nanotubes. Journal of Internal Medicine, 267 (1), 106—118. 

Kagan and coworkers studied the reaction between cyclopentadiene and 310 in the presence of aluminum alcoholates of chiral diols and their chiral mono ethers208. Among the various diols studied, only 1,1-diphenyl-1,2-propanediol (325) gave satisfactory results. Optimization by variation of the dienophile/catalyst ratio, aging of the catalyst and variation of the temperature ultimately resulted in a maximum of 86% ee at —100 °C. 

Rosenbaum JF, Biederman J, Hirshfeld DR, Bolduc EA, Faraone SV, Kagan J, Snidman N, Reznick JS (1991) Further evidence of an association between behavioral inhibition and anxiety disorders results from a family study of children from a non-clinical sample. J Psychiatr Res 25 49-65... 

Much attention has been paid to asymmetric amplification where the enantiomeric excess ( ) of the product is higher than that of the chiral catalyst (equation 35)136. The first experiment on asymmetric amplification was reported by Kagan and coworkers in the Katsuki-Sharpless asymmetric epoxidation of allyl alcohols137. Asymmetric amplification has also been studied in the asymmetric addition of dialkylzincs to carbonyl compounds. 

Maddison, S.E., Slemenda, S.B., Chandler, F.W. and Kagan, I.G. (1978) Studies on putative adult worm-derived vaccines and adjuvants for protection against Schistosoma mansoni infection in mice. Journal of Parasitology 64, 986-993. 

The pioneering studies of Kagan and Landis pave the way to the use of remote Lewis acids, but strong evidence for substrate anchoring under catalytic conditions is still missing. Further developments in this area would probably be possible by finely tuning the position and electron-deficiency of the pendant Lewis acid. 

Zhang, M. Y., Pace, N., Kerns, E. H., Kleintop, T., Kagan, N., and Sakuma, T. (2005). Hybrid triple quadrupole-linear ion trap mass spectrometry in fragmentation mechanism studies Application to structure elucidation of buspirone and one of its metabolites. J. Mass. Spectrom. 40 1017-1029. 

Whilst the use of Taddol as an asymmetric phase-transfer catalyst for asymmetric Michael reactions was only moderately successful, it was much more enantioselec-tive in catalyzing alkylation reactions. For this study, Belokon and Kagan employed alanine derivatives lib and 16a-c as substrates, and investigated their alkylation with benzyl bromide under solid-liquid phase-transfer conditions in the presence of 10 mol % of Taddol to form a-methyl phenylalanine, as shown in Scheme 8.8. The best results were obtained using the isopropyl ester of N-benzylidene alanine 16b as substrate and sodium hydroxide as the base. Under these conditions, (R)-a-methyl phenylalanine 17 could be obtained in 81% yield and with 82% ee [19]. Under the same reaction conditions, substrate 16b reacted with allyl bromide to give (R)-Dimethyl allylglycine in 89% yield and with 69% ee, and with (l-naphthyl)methyl chloride to give (R)-a-methyl (l-naphthyl)alanine in 86% yield and with 71% ee [20]. 

A detailed study of the effect of several reaction conditions was also conducted by the Kagan group [3], The nature of the solvent had a substantial effect on enantioselectivity. Compared with chloroform, much lower ee values were obtained with... 

THF, ethyl acetate, and methanol. In contrast, use of other chlorinated solvents, e.g. CCI4, and cyclohexane resulted in higher enantioselectivity, comparable with that for chloroform. The range of dienophile substrates was also studied. Replacing N-methylmaleimide by N-phenylmaleimide, in the presence of quinidine as a catalyst, also led to a good yield, although enantioselectivity was lower (20% ee compared with 61% ee). Much slower reaction rates were observed when methyl acrylate and methyl fumarate were used and enantioselectivity was low (0% ee for methyl acrylate and 30% ee for methyl fumarate). With methyl maleate as a dienophile no reaction was observed. Mechanistic studies were also conducted by Kagan et al. results were in accordance with a concerted [4+2]-cycloaddition process. 

Kagan and Schiffers carefully studied the effect of the lithium salts of BINOL (17) and related axially chiral binaphthols on the reduction of a variety of ketones with trialkoxysilanes [24]. They found that diethyl ether, with TMEDA as an additive, was the best solvent for asymmetric reduction of ketones. In the presence of 5 mol% of the monolithium salt of BINOL (17), acetophenone (1) could be reduced with trimethoxysilane in 80% yield and with 61% ee. Enantiomeric excesses > 90% were achieved under the same conditions with 2, 4, 6 -trimethyl-acetophenone (18) or a-tetralone (19) as substrates. Aliphatic ketones such as... 

Kreps, E.M., Tyurin, V.A., Chelomin, V.P., Gorbunov, N.V., Nalivaeva, N.N., iyurina, Yu.Yu, Avrova, N.F. and Kagan, V.E. (1987). The study of mechanisms of inactivation of peroxidative oxidation of lipids in synaptosomes of marine teleosts (In Russian). Zhumal Evolutsionnoy Biokhimii i Physiologii 23,461-467. 

Kagan et al. [145] quantified the results of these non-linear effects by applying theoretical models and providing several additional experimental systems. Furthermore, the origin of the non-linear effects has been also supported by theoretical and calorimetric kinetic studies [146-149]. 

The only paper concerning catalysis by Lewis acids of the Diels-Alder reactions of these simple sulfinyl ethylenes was due to Ronan and Kagan [20], who studied the influence of TMSOTf in the reaction of compound (S)-l with cyclo-pentadiene and furane. In the first case, the reaction occurs at 0°C in 3 h, giving an 89 11 mixture of endo and exo adducts (overall yield 60%) with very high n-facial selectivity (de> 92%). The high efficiency of the catalyst increasing the reactivity of 1 also made possible its reaction with furan, which evolved with low endo/exo selectivity (55 45) and lower 7r-facial selectivity (de 70%) than that observed with cyclopentadiene. These excellent results were nevertheless, eclipsed by those reported in the same paper [20] concerning the activation of... 

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