Brønsted Acid Catalysis: Organocatalytic Hydrogenation of Imines

Rueping, Magnus; Azap, Cengiz; Sugiono, Erli; Theissmann, Thomas

doi:10.1055/s-2005-872251

Cited by 109 publications

(53 citation statements)

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“…However, the yields were considerable lower as compared to other solvents. The best results with regard to both selectivity and reactivity were obtained in aromatic solvents ( Table 2, entries [3][4][5]. This tendency is in agreement with our earlier observations on Brønst-ed acid-catalyzed reactions where halogenated and aromatic solvents gave often superior selectivities.…”

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confidence: 91%

“…In further experiments aiming to improve the enantioselectivities we decided to prepare different dihydropyridines 2a-e and tested them in our Brønsted acid-catalyzed reduction reaction (Table 4, entries [1][2][3][4][5]. Pleasingly, we found that the reaction proceeded with better enantiocontrol in all cases and the best selectivities of 8a (81% ee) were obtained if the allyl ester 2e was employed.…”

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confidence: 95%

“…In the first step of this enantioselective cascade a protonation of the quinoline 3 by a chiral phosphate catalyst 1 provides an intermediary chiral ion pair A. [4][5][6][7][8][9] This is now activated for the first hydride transfer from Hantzsch dihydropyridine 2 to the 4-position of the quinoline resulting in the formation of an enamine B. Subsequent Brønsted acid-catalyzed isomerization yields the iminium C, which is now susceptible for a second 1,2-hydride transfer to give the desired enantioenriched tetrahydroquinoline and the regenerated catalyst 1.…”

mentioning

confidence: 99%

“…[3] Within this context, and based on our previous work on organocatalytic transfer hydrogenations [4] we recently developed new highly enantioselective partial reductions of pyridines [5] and quinolines.…”

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Asymmetric Counterion Pair Catalysis: An Enantioselective Brønsted Acid‐Catalyzed Protonation

et al. 2008

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A new asymmetric Brønsted acid-catalyzed cascade reaction involving a 1,4-addition, enantioselective protonation and 1,2-addition has been developed. This organocatalytic cascade not only provides for the first time 3-and 2,3-substituted tetrahydroquinolines and octahydroacridines in good yields with high dia-and enantioselectivities under mild reaction conditions but additionally represents the first example of a chiral Brønsted acidcatalyzed protonation reaction in an organocatalytic domino reaction. Furthermore, the new Brønsted acid-catalyzed hydride-proton-hydride transfer cascade can be applied to prepare new molecular scaffolds with up to three new stereocenters in an efficient one-pot reaction sequence.Keywords: BINOL phosphate; enantioselective isomerization; Hantzsch dihydropyridine; organocatalytic cascade reaction; transfer hydrogenationThe hydrogenation of unsaturated organic compounds, such as olefins, carbonyls, imines as well as aromatic and heteroaromatic compounds is one of the most important and utilized transformations in both academia and chemical industry.[1] Due to the constantly increasing number of optically and biologically active substances asymmetric reductions have become a central research area in enantioselective catalysis. So far, most of these enantioselective reductions rely on chiral transition metal catalysts and highly enantioselective hydrogenations of ketones, ketimines and alkenes are known.[2] However, most of these metal catalysts failed to give satisfactory results for the asymmetric hydrogenation of aromatic and heteroaromatic compounds and examples of efficient and highly selective transformations are rare. [3] Within this context, and based on our previous work on organocatalytic transfer hydrogenations [4] we recently developed new highly enantioselective partial reductions of pyridines [5] and quinolines.[6] The corresponding products are not only of great synthetic importance in the preparation of pharmaceuticals, agrochemicals, and in materials science, but additionally many interesting alkaloid natural products contain these structural key elements.With the newly developed enantioselective Brønst-ed acid-catalyzed transfer hydrogenation we were, for instance, able to reduce quinolines to the corresponding 2-or 4-substituted tetrahydroquinolines,[6] which we isolated in good yields and with excellent enantioselectivities [Scheme 1, Eq. (1)].In this first organocatalytic transfer hydrogenation, the activation of the quinolines is achieved by a catalytic protonation through a chiral Brønsted acid which subsequently allows a cascade hydrogenation involving a 1,4-hydride addition, proton transfer and Scheme 1. Brønsted acid-catalyzed enantioselective transfer hydrogenation of quinolines using Hantzsch dihydropyridine as the hydride source.

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confidence: 91%

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confidence: 95%

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confidence: 99%

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Asymmetric Counterion Pair Catalysis: An Enantioselective Brønsted Acid‐Catalyzed Protonation

et al. 2008

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“…Figure 2b shows metal-free organocatalysts. These depend on strong imine activation by protonation, which allows use of weaker nucleophiles such as the Hantzsch ester [30][31][32][33] . Recently, strong Brønsted-acid activation and organometallic hydride catalysis have been combined 34,35 .…”

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Imine hydrogenation with simple alkaline earth metal catalysts

et al. 2018

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W ith molecular hydrogen being one of the cleanest reducing agents, catalytic hydrogenation using the more noble transition metals is among the most studied of all chemical processes 1 . Increasing social pressure towards a sustainable society, however, dictates replacement of costly, and often harmful, precious metals by more abundant first-row transition metals or even biocompatible redox inactive main group metals [2][3][4][5][6] . The alkaline earth metal calcium does not possess partially filled d orbitals for substrate activation, but has recently shown catalytic activities in the hydrogenation of C= C double bonds with molecular H 2 (ref. 7 ). Although restricted to conjugated C= C bonds, this example strikingly broke the dogma that transition metals are needed for alkene hydrogenation. This was followed by the development of metal-free frustrated Lewis pair (FLP) catalysts [8][9][10][11] and, most recently, cationic calcium hydride catalysts that are also able to hydrogenate unactivated alkenes 12 . Figure 1a shows a working hypothesis for styrene hydrogenation with a dibenzylcalcium catalyst (CaBn 2 ) 7 . The first step is the generation of a calcium hydride species, for which ample precedence exists [13][14][15][16][17] . Further reaction with H 2 may cause precipitation of insoluble (CaH 2 ) n , but catalyst loss is partly prevented by aggregation to soluble but undefined Ca x Bn y H z species. Despite a lack of d orbitals, alkene activation proceeds through a weak electrostatic calciumalkene interaction, recently shown to be of importance in calcium catalysis 18 . The benzylic calcium intermediate formed after insertion may, after successive styrene insertions, form polystyrene 19 , but high H 2 pressure (20-100 bar) can prevent this side reaction by promoting σ-bond metathesis. The latter step in the cycle is, like the initiation reaction, formally a deprotonation of H 2 by a resonance-stabilized benzylic carbanion. Considering the high pK a of H 2 (≈ 49) 20 , this reaction seemed questionable. Stoichiometric conversions of model systems, however, underscored the feasibility of this pathway 7 . Independent theoretical calculations illustrate that the final σ-bond metathesis step is indeed highly endergonic: Gibbs free energy of activation Δ G ‡ (60 °C, 20 bar) = 25.7 kcal mol −1 (ref. 21 ).As the highly atom-efficient catalytic reduction of imines by H 2 received much less attention than alkene or ketone hydrogenation [22][23][24] , it remained an important question whether calcium-catalysed hydrogenation can be extended to imine reduction. Current stateof-the-art imine hydrogenation catalysts can be divided into four categories that vary in terms of substrate activation and nucleophilic power ( Fig. 2a-d). Figure 2a shows organometallic metal hydrides that rely on hydride nucleophilicity. Apart from few early transition metal catalysts (Ti 25 , lanthanides 26 ), these are generally based on late transition metals (Rh, Ir) 22 . The aluminium hydride compound (iso-butyl) 2 AlH is an odd example of a ...

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Diphenylphosphoric Acid

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2014

Encyclopedia of Reagents for Organic Synthesis

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Brønsted Acid Catalysis: Organocatalytic Hydrogenation of Imines

Cited by 109 publications

References 3 publications

Asymmetric Counterion Pair Catalysis: An Enantioselective Brønsted Acid‐Catalyzed Protonation

Asymmetric Counterion Pair Catalysis: An Enantioselective Brønsted Acid‐Catalyzed Protonation

Imine hydrogenation with simple alkaline earth metal catalysts

Diphenylphosphoric Acid

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