Brønsted-Acid-Promoted Rh-Catalyzed Asymmetric Hydrogenation of N-Unprotected Indoles: A Cocatalysis of Transition Metal and Anion Binding

Wen, Jialin; Fan, Xiangru; Tan, Renchang; Chien, Hui-Chun; Zhou, Qinghai; Chung, Lung Wa; Zhang, Xumu

doi:10.1021/acs.orglett.8b00312

Cited by 68 publications

(36 citation statements)

References 52 publications

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“…We recently developed ab ifunctional ligand, ZhaoPhos, [11] aiming to incorporate athiourea moiety on ab isphosphine ligand to render as econdary interaction with as ubstrate.A nion binding by thiourea with substrates assists to achieve high efficiencies and high enantioselectivities in homogeneous hydrogenation of cationic C=Nb onds present in iminium, [12] (iso)quinolinium, [13] and indolinium ions. [14] We envisioned that this type of highly reactive intermediate could be captured by thiourea [15] and be reduced by metal hydride complexes in an ionic hydrogenation manner. [16] Herein, we report an iridium-catalyzed hydrogenation of oxocarbenium ions to afford chiral isochromans smoothly with high enantioselectivities.…”

Section: Introductionmentioning

confidence: 99%

Iridium‐Catalyzed Enantioselective Hydrogenation of Oxocarbenium Ions: A Case of Ionic Hydrogenation

et al. 2020

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Ionic hydrogenation has not been extensively explored, but is advantageous for challenging substrates such as unsaturated intermediates. Reported here is an iridium‐catalyzed hydrogenation of oxocarbenium ions to afford chiral isochromans with high enantioselectivities. A variety of functionalities are compatible with this catalytic system. In the presence of a catalytic amount of the Brønsted acid HCl, an α‐chloroether is generated in situ and subsequentially reduced. Kinetic studies suggest first‐order kinetics in the substrate and half‐order kinetics in the catalyst. A positive nonlinear effect, together with the half kinetic order, revealed a dimerization of the catalyst. Possible reaction pathways based on the monomeric iridium catalyst were proposed and DFT computational studies revealed an ionic hydrogenation pathway. Chloride abstraction and the cleavage of dihydrogen occur in the same step.

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Section: Introductionmentioning

confidence: 99%

Iridium‐Catalyzed Enantioselective Hydrogenation of Oxocarbenium Ions: A Case of Ionic Hydrogenation

et al. 2020

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“…Notably, a variety of excellent methods for direct asymmetric reduction of N‐unprotected indoles, which is a more step‐economical and powerful strategy to access enantioenriched indolines, has been developed with various catalytic reductive systems (Figure a) . However, all these catalytic systems have similar limitations on the substrates: 1) C2‐aryl‐substituted N‐unprotected indoles failed in these asymmetric reductions;– 2) lack of broad functional‐group compatibility.…”

Section: Introductionmentioning

confidence: 99%

Chiral Brønsted Acid from Chiral Phosphoric Acid Boron Complex and Water: Asymmetric Reduction of Indoles

et al. 2020

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A new chiral Brønsted acid, generated in situ from a chiral phosphoric acid boron (CPAB) complex and water, was successfully applied to asymmetric indole reduction. This “designer acid catalyst”, which is more acidic than TsOH as suggested by DFT calculations, allows the unprecedented direct asymmetric reduction of C2‐aryl‐substituted N‐unprotected indoles and features good to excellent enantioselectivities with broad functional group tolerance. DFT calculations and mechanistic experiments indicates that this reaction undergoes C3‐protonation and hydride‐transfer processes. Besides, bulky C2‐alkyl‐substituted N‐unprotected indoles are also suitable for this system.

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“…[8a] If ac arbocation could be stabilized by either adjacent heteroatoms or substituents and therefore exist in considerable concentration,t he feasibility of being captured and subsequently reduced by am etal hydride would create an opportunity to form as tereogenic center.T his strategy offersa na lternative approacht op reparing chiral acetals by asymmetric hydrogenation.F ortunately,o ur group hasr ecently developed at hiourea-containing bis-phosphine ligand, ZhaoPhos, [9] which has the potential to bind with ionic substrates throughh ydrogen bonding. This catalytic system tolerates acidic conditions, [10] and has been successfully applied in the asymmetrich ydrogenation of imines, [11] quinolines/isoquinolines, [12] indoles, [10] and conjugated olefins. [13] Guided by these rationales, we envisioned that this catalytic system has the potential to achieve the asymmetric hydrogenation of cationic sp 2 carbon atoms to generate chiral acetal compounds.…”

Section: Introductionmentioning

confidence: 99%

Asymmetric Hydrogenation of Cationic Intermediates for the Synthesis of Chiral N,O‐Acetals

Sun

Zhao

Wang

et al. 2020

Chemistry A European J

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For over half a century, transition‐metal‐catalyzed homogeneous hydrogenation has been mainly focused on neutral and readily prepared unsaturated substrates. Although the addition of molecular hydrogen to C=C, C=N, and C=O bonds represents a well‐studied paradigm, the asymmetric hydrogenation of cationic species remains an underdeveloped area. In this study, we were seeking a breakthrough in asymmetric hydrogenation, with cationic intermediates as targets, and thereby anticipating applying this powerful tool to the construction of challenging chiral molecules. Under acidic conditions, both N‐ or O‐acetylsalicylamides underwent cyclization to generate cationic intermediates, which were subsequently reduced by an iridium or rhodium hydride complex. The resulting N,O‐acetals were synthesized with remarkably high enantioselectivity. This catalytic strategy exhibited high efficiency (turnover number of up to 4400) and high chemoselectivity. Mechanistic studies supported the hypothesis that a cationic intermediate was formed in situ and hydrogenated afterwards. A catalytic cycle has been proposed with hydride transfer from the iridium complex to the cationic sp2 carbon atom being the rate‐determining step. A steric map of the catalyst has been created to illustrate the chiral environment, and a quantitative structure–selectivity relationship analysis showed how enantiomeric induction was achieved in this chemical transformation.

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Brønsted-Acid-Promoted Rh-Catalyzed Asymmetric Hydrogenation of N-Unprotected Indoles: A Cocatalysis of Transition Metal and Anion Binding

Cited by 68 publications

References 52 publications

Iridium‐Catalyzed Enantioselective Hydrogenation of Oxocarbenium Ions: A Case of Ionic Hydrogenation

Iridium‐Catalyzed Enantioselective Hydrogenation of Oxocarbenium Ions: A Case of Ionic Hydrogenation

Chiral Brønsted Acid from Chiral Phosphoric Acid Boron Complex and Water: Asymmetric Reduction of Indoles

Asymmetric Hydrogenation of Cationic Intermediates for the Synthesis of Chiral N,O‐Acetals

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