Development of TfOH‐Catalyzed Spirocyclization by Intramolecular Friedel‐Crafts‐type 1,4‐Addition: Application to the Total Synthesis of the Unusual Proaporphine Alkaloid (±)‐Misrametine

Yoshida, Keisuke; Hidaka, Arisa; Fukami, Yuri; Fujino, Yuta; Imaizumi, Yuri; Takao, Ken Ichi; Kitagaki, Shinji

doi:10.1002/chem.202202188

Cited by 2 publications

(1 citation statement)

References 47 publications

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“…As such, contemporary organic synthesis evolves to synthesize this type of architecturally fascinating and valuable molecular motifs via transition‐metal catalysis and organocatalysis [2] . Modern spiroannelations typically involve semi‐pinacol rearrangement, [5] Friedel‐Craft type conjugate addition, [6,8a] Diels–Alder reactions, and organocatalytic conjugate addition/condensation sequence [7] . For instance, developing enantioselective all‐carbon spiroannelations is often imperative due to their presence in natural products and bioactive molecules.…”

Section: Introductionmentioning

confidence: 99%

Organocatalytic Enantioselective Intramolecular Michael Addition by In Situ Generated Aminoisobenzofulvenes: Construction of Spiro Quaternary Carbon Stereocenters

Midya,

Khalse,

Ghorai

2023

Chemistry A European J

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An unprecedented enantioselective organocatalytic spirocyclization strategy is presented via in situ generation of aminoisobezofulvenes. The reaction sequence involves a reductive Michael/aldol‐condensation/Michael addition cascade via iminium‐enamine catalysis. The key success of this spirocyclization was the formation of intermediatory nucleophilic aminoisobenzofuvenes accountable for intramolecular Michael addition. Benzospirononanes featuring an all carbon qauternary spirocenter were obtained using proline‐derived amino‐organocatalyst in moderate to good yields and excellent diastereo‐ and enantioselectivities (up to >20:1 dr, and 99% ee). Post‐methodological manipulation of benzospirononanes was also demonstrated.

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Section: Introductionmentioning

confidence: 99%

Organocatalytic Enantioselective Intramolecular Michael Addition by In Situ Generated Aminoisobenzofulvenes: Construction of Spiro Quaternary Carbon Stereocenters

Midya,

Khalse,

Ghorai

2023

Chemistry A European J

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Development of Organocatalytic Reactions for the Synthesis of Natural Products and Pharmaceuticals

Yoshida

2024

YAKUGAKU ZASSHI

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This review describes novel organocatalytic methods for the enantioselective construction of spiroindans and spirochromans and the application of the methods to the total synthesis of natural products. We developed an intramolecular Friedel-Craftstype 1,4-addition in which the substrates were a resorcinol derivative and 2-cyclohexenone linked by an alkyl chain. The reaction proceeded smoothly in the presence of a cinchonidine-based primary amine (30 mol%) with water and p-bromophenol as additives. A variety of spiroindanes were obtained with high enantioselectivity under these conditions. The reaction was applied in the first total synthesis of the unusual proaporphine alkaloid (−)-misramine, which included the key steps of enantioselective spirocyclization and double reductive amination of the keto-aldehyde to form a piperidine ring toward the end of the synthesis. The total synthesis of misrametine was achieved by selective demethylation of the methoxy group from the precursor to misramine. Next, a method for highly enantioselective organocatalytic construction of spirochromans containing a tetrasubstituted stereocenter was developed. An intramolecular oxy-Michael addition was catalyzed by a bifunctional cinchona alkaloid thiourea catalyst. A variety of spirochroman compounds containing a tetrasubstituted stereocenter were obtained with excellent enantioselectivity of up to 99% enantiomeric excess. The reaction was applied to the asymmetric formal synthesis of (−)-(R)-cordiachromene.

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Development of TfOH‐Catalyzed Spirocyclization by Intramolecular Friedel‐Crafts‐type 1,4‐Addition: Application to the Total Synthesis of the Unusual Proaporphine Alkaloid (±)‐Misrametine

Cited by 2 publications

References 47 publications

Organocatalytic Enantioselective Intramolecular Michael Addition by In Situ Generated Aminoisobenzofulvenes: Construction of Spiro Quaternary Carbon Stereocenters

Organocatalytic Enantioselective Intramolecular Michael Addition by In Situ Generated Aminoisobenzofulvenes: Construction of Spiro Quaternary Carbon Stereocenters

Development of Organocatalytic Reactions for the Synthesis of Natural Products and Pharmaceuticals

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