Exploiting the Imidazolium Effect in Base‐free Ammonium Enolate Generation: Synthetic and Mechanistic Studies

Young, Claire M.; Stark, Daniel G.; West, Thomas H.; Taylor, James E.; Smith, Andrew D.

doi:10.1002/ange.201608046

Cited by 16 publications

(1 citation statement)

References 42 publications

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“…N-Protonation of the acyl imidazole (acting as aBrønsted base) both activated the substrate to nucleophilic attack and generated free isothiourea for Lewis base catalysis. [26] Taking inspiration from this work, in this manuscript isothiourea hydrochloride salts are used to enable the catalytic enantioselective synthesis of aaryl-b 2 -amino esters.…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Synthesis of α‐Aryl‐β²‐Amino‐Esters by Cooperative Isothiourea and Brønsted Acid Catalysis

et al. 2021

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The synthesis of α‐aryl‐β2‐amino esters through enantioselective aminomethylation of an arylacetic acid ester in high yields and enantioselectivity via cooperative isothiourea and Brønsted acid catalysis is demonstrated. The scope and limitations of this process are explored (25 examples, up to 94 % yield and 96:4 er), with applications to the synthesis of (S)‐Venlafaxine⋅HCl and (S)‐Nakinadine B. Mechanistic studies are consistent with a C(1)‐ammonium enolate pathway being followed rather than an alternative dynamic kinetic resolution process. Control studies indicate that (i) a linear effect between catalyst and product er is observed; (ii) an acyl ammonium ion can be used as a precatalyst; (iii) reversible isothiourea addition to an in situ generated iminium ion leads to an off‐cycle intermediate that can be used as a productive precatalyst.

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Section: Introductionmentioning

confidence: 99%

Enantioselective Synthesis of α‐Aryl‐β²‐Amino‐Esters by Cooperative Isothiourea and Brønsted Acid Catalysis

et al. 2021

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Isothiourea‐Catalyzed Functionalization of Pyrrolyl‐ and Indolylacetic Acid: Enantioselective Synthesis of Dihydropyridinones and One‐pot Synthesis of Pyridinones

et al. 2020

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A protocol for the isothiourea-catalyzed enantioselective functionalization of pyrrolyl-and indolylacetic acids has been developed. Stereodefined dihydropyridinones are accessed through formal [4 + 2] cycloaddition of an in situ generated isothiouronium enolate with α,βunsaturated ketimines. The dihydropyridinones are obtained in moderate to excellent yield (26-97%), excellent diastereocontrol (all > 95 : 5 dr) and moderate to excellent enantiocontrol (75 : 25-99 : 1 er). An unusual elimination of pyrrole or indole from the dihydropyridinone to access achiral pyridinones was observed and could be selectively promoted. A further one-pot synthesis using an acyl imidazole was developed to give pyridinones in good to excellent yields (67-91%).

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Asymmetric Friedel−Crafts Alkylation of Indoles with α,β‐unsaturated Trifluoromethyl Ketones Using a Squaramide Organocatalyst

et al. 2022

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This study explores the asymmetric FriedelÀ Crafts alkylation of indoles with α,β-unsaturated trifluoromethyl ketones using a squaramide organocatalyst. The squaramide organocatalyst efficiently promoted the asymmetric FriedelÀ Crafts alkylation of indoles with α,β-unsaturated trifluoromethyl ketones, affording the corresponding products bearing both indole motif and trifluoromethyl group in high yields with excellent enantioselectivities (up to 99% ee). The transformation of the obtained adduct to chiral spiro indoline 3-one was also demonstrated.[a] K.

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Exploiting the Imidazolium Effect in Base‐free Ammonium Enolate Generation: Synthetic and Mechanistic Studies

Cited by 16 publications

References 42 publications

Enantioselective Synthesis of α‐Aryl‐β²‐Amino‐Esters by Cooperative Isothiourea and Brønsted Acid Catalysis

Enantioselective Synthesis of α‐Aryl‐β²‐Amino‐Esters by Cooperative Isothiourea and Brønsted Acid Catalysis

Isothiourea‐Catalyzed Functionalization of Pyrrolyl‐ and Indolylacetic Acid: Enantioselective Synthesis of Dihydropyridinones and One‐pot Synthesis of Pyridinones

Asymmetric Friedel−Crafts Alkylation of Indoles with α,β‐unsaturated Trifluoromethyl Ketones Using a Squaramide Organocatalyst

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Exploiting the Imidazolium Effect in Base‐free Ammonium Enolate Generation: Synthetic and Mechanistic Studies

Cited by 16 publications

References 42 publications

Enantioselective Synthesis of α‐Aryl‐β2‐Amino‐Esters by Cooperative Isothiourea and Brønsted Acid Catalysis

Enantioselective Synthesis of α‐Aryl‐β2‐Amino‐Esters by Cooperative Isothiourea and Brønsted Acid Catalysis

Isothiourea‐Catalyzed Functionalization of Pyrrolyl‐ and Indolylacetic Acid: Enantioselective Synthesis of Dihydropyridinones and One‐pot Synthesis of Pyridinones

Asymmetric Friedel−Crafts Alkylation of Indoles with α,β‐unsaturated Trifluoromethyl Ketones Using a Squaramide Organocatalyst

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Enantioselective Synthesis of α‐Aryl‐β²‐Amino‐Esters by Cooperative Isothiourea and Brønsted Acid Catalysis

Enantioselective Synthesis of α‐Aryl‐β²‐Amino‐Esters by Cooperative Isothiourea and Brønsted Acid Catalysis