Cinchonidine hydrogen bonds

Recently, Vayner and coworkers [239] have revisited the model proposed by Augustine et al. [34] which is based on the assumption that the QN can make a nucleophilic attack to an activated carbonyl. According to this model the two possible zwitterionic intermediates that can thus be formed have different energies, which leads to the selective formation of one of the two intermediates, and, therefore, to e.s. after hydrogenolysis by surface hydrogen. This model nevertheless does not explain the e.d. of nonbasic modifiers, such as the one reported by Marinas and coworkers [240], which have no quinuclidine moiety and no nitrogen atom, and thus no possibility to form zwitterionic intermediates. Furthermore, in situ spectroscopic evidence for hydrogen bond formation between the quinuclidine moiety of cinchonidine and the ketopantolactone has been provided recently [241], which supports the hypothesis of the role of weak bond formation rather than the formation of intermediates such as those proposed by Vayner and coworkers. 

Hydrogen-bonding between the 3-oxo group of 1,4,4-trisubstituted pyrrolidine-2,3,5-triones and catalytic amounts of cinchonidine controls the stereospecific hydrogenation of the system over Pt/Al203 to yield chiral 3-hydroxy compounds (-100% yield with ee >60) [21] the nature of the (V-substituent appears to be the controlling factor for the stereoselectivity with PhCH2> Et > n-Bu > cyclo-C6H . 

Scheme 6.112 Michael addition of thiophenol to an a,p-unsaturated imide catalyzed by cinchonidine-derived thiourea 116 and cinchonine-derived thiourea 117, the first representatives of this class of bifunctional hydrogen-bonding cinchona alkaloid-thioureas.

Fig. 34. Investigation of the molecular interaction between adsorbed chiral modifier and KPL by MES 41. The modifiers were the following (a) CD and (b) A-methyl cinchonidine chloride. The KPL concentration was modulated (modulation period T = 180 s) between 0 and 5 x 10 mol/L in ( ILClz. The modifier concentration was 5 x 10 mol/L. The proposed model for the CD-KPL interaction is shown at the bottom (a). This hydrogen bonding interaction is prohibited when A-methyl-cinchonidine (b) is used as a chiral modifier instead of CD.

Quinine (14a), cinchonine (14b), quinidine (15a), and cinchonidine (15b), which are so-called cinchona alkaloids, occur in cinchona barks. Although 14a and 15a are the diastereomers of each other, they have been used as alternatives of the corresponding enantiomers, respectively. Quininium and quinidinium ions (14a H+ and 15a H+) have two possible hydrogen-bond donors, a ternary ammonium ion and a hydroxy group. They also have two... 

In 2006, Ohkata and coworkers found that the natural cinchonidine (CD) functions as a Brans ted base catalyst (1 mol%) in the reaction between chloromethyl ketones 193 and (3-substituted methylidenemalononitriles 194 to furnish the corresponding tetrasubstituted trans-cyclopropanes 195 with enantioselectivities of up to 82% ee (Scheme 9.68) [62]. The 9-0H-protected derivatives provided almost no enantios-electivity, indicating that the hydrogen bonding is crucial for stereoinduction. 

The X-ray-determined structure of the complex of 16 and 19 with quaternary salt 15 revealed that the primary discriminative forces leading to an efficient resolution are the formation of directional hydrogen bonds of hydroxy groups of cinchonidine and BINOL with the halide anion as well as aryl-aryl interaction between the naphthyl and the quinoline rings [40]. 

The asymmetric hydrogenation site A is accessible to methyl pyruvate provided adsorption is in the configuration required to give R-(+)-lactate on hydrogenation. The spatial relationship of adsorbed methyl pyruvate to molecule x of cinchonidine is such as to permit the hydrogen bonding interaction that is proposed to occur when the reactant is converted to its half-hydrogenated state. 

Scheme 5.24. shows the proposed adsorbed state of the cinchonidine molecule which provides the templated surface for enantioselective hydrogenation. With the half-hydrogenated state of methyl pyruvate stabilized by hydrogen bonding, the geometrical requirements are achieved by rotation about the C8-C9 bond in the cinchonidine molecule. 

Quinine, quinidine and cinchonidine, which are amino alcohols with high chiral capability, have been used as selectors for the separation of enantiomers of acids containing a hydrogen bonding function [24]. These chiral selectors have high UV absorbance, providing indirect detection possibilities for solutes without inherent UV absorbance (Figure 6). 

In the early studies of the conjugate addition of aromatic thiols to a,p-unsaturated cyclohexenones, cinchonidine 2 gave the best enantioselectivity (Scheme 6.1), while somewhat lower ee s were obtained with quinine 1 or quinidine 4 [9j. The mechanistic model advanced in these studies involved activation of the thiol by proton transfer to the nitrogen atom of the quinucUdine moiety and hydrogen bonding between the hydroxyl group at the C9 and the carbonyl group of the unsaturated substrate (Scheme 6.1). 

In addition to the carbon-carbon bond formation, the carbon-hydrogen bond-forming reaction under biphasic conditions was also controlled by the cinchonidine-derived PTC 20 and the synthetic utility of this reaction was demonstrated through the formal total synthesis of a natural product, (/ )- O-methyl-6-undecanolide 128 (Scheme 4.30). The enantioselective protonation of a chiral ammonium enolate via nonbiomimetic hydrolysis of the vinylic ester 129 was successfully developed to... 

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