Enantioselective Synthesis of 1-Substituted 1,2,3,4-Tetrahydroisoquinolines through 1,3-Dipolar Cycloaddition by a Chiral Phosphoric Acid

Jin, Yuan; Honma, Yasushi; Morita, Hisashi; Miyagawa, Masamichi; Akiyama, Takahiko

doi:10.1055/s-0039-1690108

Cited by 11 publications

(2 citation statements)

References 3 publications

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“…Where additional comparison data is available, several other studies involving imine-type electrophiles (C=N-R) have shown the importance of including TCYP in a catalyst evaluation despite the structural similarities with TRIP. [32][33][34][35][36][37][38][39][40][41] By performing this type of analysis with similarly related electrophiles, azo compounds, [42][43][44][45][46] precedent shows TCYP to be a top performer. Continued expansion of this comparative analysis demonstrates TCYP to be effective in condensation, 47,48 halogenation [49][50][51][52] and organometallic reactions.…”

Section: Inverse Catalyst Designmentioning

confidence: 99%

A Statistical Modeling Approach to Catalyst Generality Assessment in Enantioselective Synthesis

Lai

Betinol

et al. 2022

Preprint

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Selecting the optimal catalyst to impart high levels of enantioselectivity in a new transformation is challenging because the ideal molecular requirements of the catalyst for one reaction do not always simply translate to another. In these reaction scenarios practitioners typically use the most general catalyst structure as a starting point for optimization. However, for many reaction systems and catalyst chemotypes the most general catalyst structure may be largely unknown presenting a significant limitation in catalyst application to new reaction space. Herein, we demonstrate that comprehensive statistical models can be applied to identify the most general catalyst for many chemical systems. These inclusive statistical models that encompass many reaction types can provide information about the relevant structural requirements necessary for high enantioselectivity across a broad reaction range. By validating this approach on diverse regions of organocatalyzed reaction space we discovered structurally distinct catalysts can in some cases provide similar levels of enantioselectivity. The second curious finding determined that the best and most popular catalyst systems may not be equivalent. Validation of this approach on a multi-catalytic dearomatization reaction resulted in the discovery that our general catalyst findings allowed for streamlined reaction development for highly complex transformations.

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Section: Inverse Catalyst Designmentioning

confidence: 99%

A Statistical Modeling Approach to Catalyst Generality Assessment in Enantioselective Synthesis

Lai

Betinol

et al. 2022

Preprint

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“…[30] In this context, Akiyama and co-workers developed the chiral phosphoric acid catalyzed enantioselective synthesis of 1-substituted 1,2,3,4-tetrahydroisoquinolines ( 8) by 1,3dipolar cycloaddition reaction (Scheme 2). [31] In the presence of CPA, only various nitrones (6) with electron-withdrawing groups at the 5-or 7-position of the isoquinoline readily gave the desired product, chiral 1-substituted 1,2,3,4-tetrahydroisoquinolines, in moderate yields (46-75 %), excellent exo selectivity (exo/endo ratios; up to 100 : 0) and moderate to good enantioselectivities (75-87 % ee), while nitrones with electrondonating groups and vinyl ethers (7) do not undergo this reaction under established reaction conditions. With the mediation of chiral phosphoric acid, 6 and 7 form the intermediate (In-1), which is then deprotonated by the phosphonate ion to give product 8.…”

Section: Stereoselective 13-dipolar Cycloadditionmentioning

confidence: 99%

Asymmetric Cycloaddition/Annulation Reactions by Chiral Phosphoric Acid Catalysis: Recent Advances

2022

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Asymmetric cycloaddition/annulation reactions have contributed greatly to the synthesis of a variety of novel cyclic compounds used in organic synthesis, natural product synthesis, material science, and chemical biology. Thus, chiral phosphoric acid‐catalyzed asymmetric cycloaddition reactions have received the attention of the synthetic community to design new vital asymmetric reactions and synthesize complex molecules for the past two decades. Although several review articles on organocatalyzed asymmetric cycloaddition reactions can be found in the literature, there has been no specific review on CPA‐catalyzed asymmetric cycloaddition/annulation reactions. Herein, the most recent research progress on chiral phosphoric acid catalyzed asymmetric [3+2], [4+2], [2+2], [3+3], [4+3], [4+1] annulation, and 1,3‐dipolar cycloadditions have been compiled and analyzed to demonstrate the importance of chiral phosphoric acid catalysis in asymmetric cycloaddition or annulation reactions.

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Regio‐ and Enantioselective (3+3) Cycloaddition of Nitrones with 2‐Indolylmethanols Enabled by Cooperative Organocatalysis

Liu

Sun

et al. 2020

Angewandte Chemie

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The regio‐ and enantioselective (3+3) cycloaddition of nitrones with 2‐indolylmethanols was accomplished by the cooperative catalysis of hexafluoroisopropanol (HFIP) and chiral phosphoric acid (CPA). Using this approach, a series of indole‐fused six‐membered heterocycles were synthesized in high yields (up to 98 %), with excellent enantioselectivities (up to 96 % ee) and exclusive regiospecificity. This approach enabled not only the first organocatalytic asymmetric (3+3) cycloaddition of nitrones but also the first C3‐nucleophilic asymmetric (3+3) cycloaddition of 2‐indolylmethanols. More importantly, theoretical calculations elucidated the role of the cocatalyst HFIP in helping CPA control the reactivity and enantioselectivity of the reaction, demonstrating a new mode of cooperative catalysis.

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Enantioselective Synthesis of 1-Substituted 1,2,3,4-Tetrahydroisoquinolines through 1,3-Dipolar Cycloaddition by a Chiral Phosphoric Acid

Cited by 11 publications

References 3 publications

A Statistical Modeling Approach to Catalyst Generality Assessment in Enantioselective Synthesis

A Statistical Modeling Approach to Catalyst Generality Assessment in Enantioselective Synthesis

Asymmetric Cycloaddition/Annulation Reactions by Chiral Phosphoric Acid Catalysis: Recent Advances

Regio‐ and Enantioselective (3+3) Cycloaddition of Nitrones with 2‐Indolylmethanols Enabled by Cooperative Organocatalysis

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