Chiral Brønsted acids in enantioselective carbonyl activations – activation modes and applications

Rueping, Magnus; Kuenkel, Alexander; Atodiresei, Iuliana

doi:10.1039/c1cs15087a

Cited by 526 publications

(133 citation statements)

References 85 publications

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“…23 While phosphoric acid protonation of carbonyl groups is a well-established mode of activation toward nucleophilic addition, 24 enolization has rarely been considered. These observations suggest that it is possible to achieve the kinetic resolution of the ketone substrates with phosphoric acid catalysts, provided the rate of the electrophilic addition (amination) step is faster than that of the enolization process.…”

mentioning

confidence: 99%

Direct Asymmetric Amination of α-Branched Cyclic Ketones Catalyzed by a Chiral Phosphoric Acid

2015

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Here we report the direct asymmetric amination of α-substituted cyclic ketones catalyzed by a chiral phosphoric acid, yielding products with a N-containing quaternary stereocenter in high yields and excellent enantioselectivities. Kinetic resolution of the starting ketone was also found to occur on some of the substrates under milder conditions, providing enantio-enriched α-branched ketones, another important building block in organic synthesis. The utility of this methodology was demonstrated in the short synthesis of (S)-ketamine, the more active enantiomer of this versatile pharmaceutical.

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confidence: 99%

Direct Asymmetric Amination of α-Branched Cyclic Ketones Catalyzed by a Chiral Phosphoric Acid

2015

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“…In general, the activation of the substrate is enabled through hydrogen bonding or formation of ion pairs, depending on the acidic strength of the catalyst such as phosphoric acids, [188][189][190][191][192][193][194][195] ammonium salts, thioureas, 196 diols, 197 and squaramides. 198 Among the different chiral Brønsted acids (Figure 15), axial chiral phosphoric acid derivatives have shown astonishing versatility.…”

Section: Brønsted Acid and Hydrogen-bond Catalysismentioning

confidence: 99%

2.07 The Aldol Reaction: Organocatalysis Approach

Mase

Hayashi²

2014

Comprehensive Organic Synthesis II

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“…[9] Catalyst optimization is summarized in Table 1. The phenyl ester group in 3 strongly influenced the enantioselectivity of the reaction.…”

Section: Introductionmentioning

confidence: 99%

Catalytic Enantioselective Nazarov Cyclization: Construction of Vicinal All‐Carbon‐Atom Quaternary Stereocenters

et al. 2014

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Abstract:The diastereoselective asymmetric synthesis of vicinal all-carbon-atom quaternary stereocenters is a challenging problem in organic synthesis for which only few solutions have been described. A catalytic asymmetric Nazarov cyclization of fully substituted dienones that provides cyclopentenone derivatives with vicinal quaternary stereocenters in high optical purity and as single diastereoisomers is now reported.The catalytic asymmetric synthesis of vicinal, all-carbonatom quaternary stereocenters presents a difficult challenge for which only a small number of solutions, none of which are completely general, have been described to date.[1] The enantioselective version of the reaction that is shown in Equation (1) would constitute a new solution to this problem. None of the asymmetric Nazarov cyclizations that have been described thus far [2] form vicinal quaternary stereocenters. At best, vicinal quaternary and tertiary stereocenters could be generated. [3] Polarization of the acyclic dienone precursor [4] accelerates the Nazarov cyclization.[5] We have previously disclosed the highly diastereoselective triflimide-catalyzed cyclization that converts dienone 1 into cyclopentenone 2 in 80 % yield [Eq. (1)].[6] The stereochemistry of 2 reveals that a conrotatory process, which is required to conserve orbital symmetry, has occurred. The polarization of "push-pull" dienone 1 and the rapid termination process that is enabled through loss of the 2-(trimethylsilyl)ethoxymethyl (SEM) group contribute to the success of this cyclization, which results in the formation of vicinal all-carbon-atom quaternary stereocenters. Rapid termination is especially important in the case of Nazarov cyclizations that lead to sterically congested products as Wagner-Meerwein rearrangements of the intermediate cyclic cation, which would be driven by relief of steric compression, have to be suppressed.[7] Herein, we report the first catalytic asymmetric Nazarov cyclization of fully substituted dienones for the construction of vicinal all-carbon-atom stereocenters.We had confidence that an asymmetric version of the cyclization that is shown in Equation (1) could be developed through systematic variation of the enol ether and ester groups, which could serve as recognition elements for a catalyst. The process could be optimized through iterative changes in catalyst, solvent, and additive(s). As the enol ether moiety must depart as a stable cation following the cyclization, its choice does not restrict the structural types of cyclopentenones that might be accessed by this reaction.We chose the (R)-BINOL scaffold for our screen of chiral Brønsted acids.[8] The broad utility of this class of compounds for a variety of catalytic asymmetric reactions is related to the ease with which substituents at the C3 and C3' positions can be introduced to quickly assemble a library of catalysts. [9] Catalyst optimization is summarized in Table 1. The phenyl ester group in 3 strongly influenced the enantioselectivity of the reaction. The ethyl ester analo...

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Chiral Brønsted acids in enantioselective carbonyl activations – activation modes and applications

Cited by 526 publications

References 85 publications

Direct Asymmetric Amination of α-Branched Cyclic Ketones Catalyzed by a Chiral Phosphoric Acid

Direct Asymmetric Amination of α-Branched Cyclic Ketones Catalyzed by a Chiral Phosphoric Acid

2.07 The Aldol Reaction: Organocatalysis Approach

Catalytic Enantioselective Nazarov Cyclization: Construction of Vicinal All‐Carbon‐Atom Quaternary Stereocenters

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