Dimers enantioselective protonation

A preliminary approach to understand the mechanism of the enantioselective protonation and the role of lithium bromide, based on TSs containing one hthium atom, failed to explain the selectivity enhancement by hthium bromide, and the calculated energies of the TSs did not account for the experimentally observed selectivity. Asensio, Domingo and coworkers studied the molecular process associated with the proton transfer at the semiempirical PM3 level . Based on hterature data , they defined the structure of a mixed dimer enolate 234 consisting of a four-membered ring where the bromide anion and the oxygen atom of the enolate were connected by two hthium cations. These bridging... 

MeO X = -CH2-, -OCH2- and -CH2CH2-) undergo enantioselective protonation, using methanol as proton source and a chiral binaphthyl tin bromide methoxide as chiral catalyst, to give chiral ketones (121). ° Pronounced nonlinear effects are observed in 0 the ee and are rationalized in terms of monomer-dimer equilibria involving the catalyst. 

Since Corey s group first reported 0(9)-allyl-N-(9-anthracenylmethyl) cinchonidi-nium bromide as a new phase-transfer catalyst [13], its application to various asymmetric reactions has been investigated. In particular, this catalyst represents a powerful tool in various conjugated additions using chalcone derivatives (Scheme 3.2). For example, nitromethane [14], acetophenone [15], and silyl eno-lates [16] produce the corresponding adducts in high enantioselectivity. When p-alkyl substrates are used under PTC conditions, asymmetric dimerization triggered by the abstraction of a y-proton proceeds smoothly, with up to 98% ee [17]. 

C.ii.b. Enantioselective Catalysis. Hidai et al. reported enantiomeric excesses of up to 35% in a widely cited study on the influence of certain chiral phosphines in the linear dimerization of isoprene with methanol. The tail-to-head product 54 (Scheme 18) predominates (2-5 1) over the tail-to-tail isomer 55. According to the model presented above, in this case the enantiomer ratio is set in the protonation step of the catalytic cycle... 

Some systems of different structure have shown their ability to catalyze the formation of a new carbon-carbon bond by reaction of two ketones. The enantioselective aldol reaction between 1,3-cyclohexanedione (173) and different a-bromoketo esters 174 followed by final cyclization gave as the main compound cw-configured 176. Several Cinchona alkaloid derivatives were tested in this transformation, with the dimeric catalyst system 175 in the presence of a proton sponge and an ammonium salt affording the best results (Scheme 4.37) [256], Also dimeric cinchona... 

Considering that the a-proton-exchange of racemic azlactones occurred rapidly in the presence of a tertiary amine base. Song and coworkers demonstrated enan-tioselective synthesis of a-deuterated a-amino acids via dynamic kinetic resolution (DKR) of azlactones with EtOD using cinchona-derived dimeric squaramide catalyst 33 (Scheme 10.34) [112]. The authors noted that by increasing the amount of EtOD, the level of deuterium incorporation increased, whereas the enantioselectivity decreased. By using 50 equivalents of EtOD, the products were obtained with... 

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