Enantioselective hydrogenation of ethyl pyruvate catalyzed by - and -isocinchonine-modified Pt/AlO in toluene: inversion of enantioselectivity

Novel Evidence on the Role of the Nucleophilic Intermediate Complex in the Orito-Reaction: Unexpected Inversion in the Enantioselective Hydrogenation of 2,2,2-Trifluoroacetophenone on Pt-Cinchona Chiral Catalyst Using Continuous-Flow Fixed-Bed Reactor

“…According to the well-known empirical rule, the presence of (8S,9R) cinchonas (CD, QN) promote the formation of (R)-hydroxy compounds in excess, whereas the use of (8R,9S) cinchonas (CN, QD) lead to the excess of (S)-hydroxy compounds in the Orito reaction [8][9][10][11]. In the course of further studies, however, it was found that some derivatives of the parent cinchonas do not follow this rule [54][55][56][57][58][59][60][61]. Inversions of this type are usually designated ''unexpected inversions'' in the literature [62].…”

“…Since no inversion occurred in the hydrogenation of TFAP using AcOH, which would suggest a change in reaction mechanism, we interpreted the unexpected inversion on the basis of postulating a nucleophilic IC [54][55][56][57]62], also proposed by other authors [63][64][65][66]. The proposed nucleophilic IC is supported by earlier studies: (1) under the conditions of the Orito reaction NMR investigations support multipoint interaction between the substrate and chiral modifier; (2) the nucleophilic IC is identifiable in liquid phase by NMR and can also be quantified; (3) IC concentration decreases with increasing acid concentration; (4) there is a correlation between the concentration of this complex and the enantioselectivity of the hydrogenation [67][68][69].…”

Anomalous behavior of rigid cinchona alkaloids in the enantioselective hydrogenation of ethyl pyruvate in an aprotic solvent

“…Recently, it has been shown that rigid derivatives of cinchona alkaloids, such as a-isocinchonine (a-ICN) and b-isocinchonine (b-ICN) with exclusive open conformation can also induce ED in the hydrogenation of a-keto esters [24][25][26][27][28][29], although the ee values obtained in aprotic solvents were relatively low (ee < 30-40%). The structure of cinchona alkaloids discussed (CD, CN, a-ICN and b-ICN) is given in Fig.…”

New Data of Nonlinear Phenomenon in the Heterogeneous Enantioselective Hydrogenation of Activated Ketones

“…The results of studies carried out to date (using modifier mixtures, transient method, continuous flow measurements) can be summarized as follows. Studies on NLP have mainly been performed in enantioselective hydrogenations on Pt [10][11][12][13][14][15][16][17][18][19][20][21] and Pd [22][23][24][25] catalysts. A study using Rh catalyst has also been published [26].…”

“…The substrates hydrogenated over Pt catalysts were MP [10], but most of all EP [11, 14, 16-18, 21, 24, 27] and KPL [12,13,15,19,26,27]; hydrogenations over Pd were performed on 4-methoxy-6-methyl-2-pyrone [25], a-phenylcinnamic acid [23] and isoforon [22], and those over Rh on KPL [26] as substrate. One component of the chiral modifiers used was a parent cinchona alkaloid (CD, CN, QN, QD), whereas the other component was the opposite enantiomer of CD, CN, QN, QD or their C9-O-R derivatives [12,13,16,18,19,24,[26][27][28]. In addition to cinchona alkaloids and their derivatives, other chiral modifiers including synthetic chiral compounds and achiral modifiers were also investigated [11,15,20,22].…”