Metal-Free Access to (Spirocyclic)Tetrahydro-β-carbolines in Water Using an Ion-Pair as a Superacidic Precatalyst

Zhenguo Zhang; Xiaoxiao Liu; Liang Ji; Ting Zhang; Zhenhua Jia; Teck Peng Loh

doi:10.1021/acscatal.1c05546

Metal-Free Access to (Spirocyclic)Tetrahydro-β-carbolines in Water Using an Ion-Pair as a Superacidic Precatalyst

Zhenguo Zhang, Xiaoxiao Liu, Liang Ji, Ting Zhang, Zhenhua Jia^*, Teck Peng Loh^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

The unprecedented triarylcarbonium ion-pair-catalyzed Pictet-Spengler reaction of tryptamines with aromatic aldehydes and cyclic ketones in water was disclosed. Under metal-free conditions, diverse tetrahydro-β-carbolines and spirocyclic tetrahydro-β-carbolines were obtained in good yields with excellent functional group tolerance, including late-stage modification of natural products and small molecular drugs. The practicability of this protocol is also characterized in the gram-scale synthesis of Komavine and several other functional compounds. Preliminary mechanistic studies indicated that in aqueous media the in situ-generated superacidic species from the carbonium ion pair with water was crucial to promote the Pictet-Spengler reaction.

Original language	English
Pages (from-to)	2052-2057
Number of pages	6
Journal	ACS Catalysis
Volume	12
Issue number	3
DOIs	https://doi.org/10.1021/acscatal.1c05546
Publication status	Published - Feb 4 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
©

ASJC Scopus Subject Areas

Catalysis
General Chemistry

Keywords

(spirocyclic)tetrahydro-β-carboline
biocompatible
ion-pair
metal-free
superacidic species

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10.1021/acscatal.1c05546

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title = "Metal-Free Access to (Spirocyclic)Tetrahydro-β-carbolines in Water Using an Ion-Pair as a Superacidic Precatalyst",

abstract = "The unprecedented triarylcarbonium ion-pair-catalyzed Pictet-Spengler reaction of tryptamines with aromatic aldehydes and cyclic ketones in water was disclosed. Under metal-free conditions, diverse tetrahydro-β-carbolines and spirocyclic tetrahydro-β-carbolines were obtained in good yields with excellent functional group tolerance, including late-stage modification of natural products and small molecular drugs. The practicability of this protocol is also characterized in the gram-scale synthesis of Komavine and several other functional compounds. Preliminary mechanistic studies indicated that in aqueous media the in situ-generated superacidic species from the carbonium ion pair with water was crucial to promote the Pictet-Spengler reaction.",

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author = "Zhenguo Zhang and Xiaoxiao Liu and Liang Ji and Ting Zhang and Zhenhua Jia and Loh, {Teck Peng}",

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doi = "10.1021/acscatal.1c05546",

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AU - Zhang, Zhenguo

AU - Liu, Xiaoxiao

AU - Ji, Liang

AU - Zhang, Ting

AU - Jia, Zhenhua

AU - Loh, Teck Peng

N1 - Publisher Copyright: ©

PY - 2022/2/4

Y1 - 2022/2/4

N2 - The unprecedented triarylcarbonium ion-pair-catalyzed Pictet-Spengler reaction of tryptamines with aromatic aldehydes and cyclic ketones in water was disclosed. Under metal-free conditions, diverse tetrahydro-β-carbolines and spirocyclic tetrahydro-β-carbolines were obtained in good yields with excellent functional group tolerance, including late-stage modification of natural products and small molecular drugs. The practicability of this protocol is also characterized in the gram-scale synthesis of Komavine and several other functional compounds. Preliminary mechanistic studies indicated that in aqueous media the in situ-generated superacidic species from the carbonium ion pair with water was crucial to promote the Pictet-Spengler reaction.

AB - The unprecedented triarylcarbonium ion-pair-catalyzed Pictet-Spengler reaction of tryptamines with aromatic aldehydes and cyclic ketones in water was disclosed. Under metal-free conditions, diverse tetrahydro-β-carbolines and spirocyclic tetrahydro-β-carbolines were obtained in good yields with excellent functional group tolerance, including late-stage modification of natural products and small molecular drugs. The practicability of this protocol is also characterized in the gram-scale synthesis of Komavine and several other functional compounds. Preliminary mechanistic studies indicated that in aqueous media the in situ-generated superacidic species from the carbonium ion pair with water was crucial to promote the Pictet-Spengler reaction.

KW - (spirocyclic)tetrahydro-β-carboline

KW - biocompatible

KW - ion-pair

KW - metal-free

KW - superacidic species

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DO - 10.1021/acscatal.1c05546

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ER -

Metal-Free Access to (Spirocyclic)Tetrahydro-β-carbolines in Water Using an Ion-Pair as a Superacidic Precatalyst

Abstract

Bibliographical note

ASJC Scopus Subject Areas

Keywords

Access to Document

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