Borylation Directed Borylation of Indoles Using Pyrazabole Electrophiles: A One-Pot Route to C7-Borylated-Indolines

Jürgen Pahl; Emily Noone; Marina Uzelac; Kang Yuan; Michael J. Ingleson

doi:10.1002/anie.202206230

Borylation Directed Borylation of Indoles Using Pyrazabole Electrophiles: A One-Pot Route to C7-Borylated-Indolines

Jürgen Pahl, Emily Noone, Marina Uzelac, Kang Yuan, Michael J. Ingleson

Department of Chemistry

The University of Edinburgh

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

16 Citations (SciVal)

Abstract

Pyrazabole (1) is a readily accessible diboron compound that can be transformed into ditopic electrophiles. In 1 (and derivatives), the B⋅⋅⋅B separation is ca. 3 Å, appropriate for one boron centre bonding to N and one to the C7 of indoles and indolines. This suitable B⋅⋅⋅B separation enables double E−H (E=N/C) functionalisation of indoles and indolines. Specifically, the activation of 1 with HNTf₂ generates an electrophile that transforms N−H indoles and indolines into N/C7-diborylated indolines, with N−H borylation directing subsequent C7−H borylation. Indole reduction to indoline occurs before C−H borylation and our studies indicate this proceeds via hydroboration—C3-protodeboronation to produce an intermediate that then undergoes C7 borylation. The borylated products can be converted in situ into C7-BPin-N-H-indolines. Overall, this represents a transient directed C−H borylation to form useful C7-BPin-indolines.

Original language	English
Article number	e202206230
Journal	Angewandte Chemie - International Edition
Volume	61
Issue number	32
DOIs	https://doi.org/10.1002/anie.202206230
Publication status	Published - 8 Aug 2022

Bibliographical note

Funding Information:
This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 769599). We acknowledge SIRCAMS at University of Edinburgh for performing mass spectrometry and Dr. G. Nichol for collecting X‐ray diffraction data for . 2 [30]

Data Availability Statement
The data that support the findings of this study are available in the Supporting Information of this article

Funding

This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 769599). We acknowledge SIRCAMS at University of Edinburgh for performing mass spectrometry and Dr. G. Nichol for collecting X‐ray diffraction data for . 2 [30]

Keywords

Boranes
C−H Borylation
Electrophilic Substitution
Indoles
Transient Directing Group

ASJC Scopus subject areas

Catalysis
General Chemistry

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10.1002/anie.202206230Licence: CC BY

Cite this

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title = "Borylation Directed Borylation of Indoles Using Pyrazabole Electrophiles: A One-Pot Route to C7-Borylated-Indolines",

abstract = "Pyrazabole (1) is a readily accessible diboron compound that can be transformed into ditopic electrophiles. In 1 (and derivatives), the B⋅⋅⋅B separation is ca. 3 {\AA}, appropriate for one boron centre bonding to N and one to the C7 of indoles and indolines. This suitable B⋅⋅⋅B separation enables double E−H (E=N/C) functionalisation of indoles and indolines. Specifically, the activation of 1 with HNTf2 generates an electrophile that transforms N−H indoles and indolines into N/C7-diborylated indolines, with N−H borylation directing subsequent C7−H borylation. Indole reduction to indoline occurs before C−H borylation and our studies indicate this proceeds via hydroboration—C3-protodeboronation to produce an intermediate that then undergoes C7 borylation. The borylated products can be converted in situ into C7-BPin-N-H-indolines. Overall, this represents a transient directed C−H borylation to form useful C7-BPin-indolines.",

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author = "J{\"u}rgen Pahl and Emily Noone and Marina Uzelac and Kang Yuan and Ingleson, {Michael J.}",

note = "Funding Information: This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 769599). We acknowledge SIRCAMS at University of Edinburgh for performing mass spectrometry and Dr. G. Nichol for collecting X‐ray diffraction data for . 2 [30] Data Availability Statement The data that support the findings of this study are available in the Supporting Information of this article",

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AU - Noone, Emily

AU - Uzelac, Marina

AU - Yuan, Kang

AU - Ingleson, Michael J.

N1 - Funding Information: This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 769599). We acknowledge SIRCAMS at University of Edinburgh for performing mass spectrometry and Dr. G. Nichol for collecting X‐ray diffraction data for . 2 [30] Data Availability Statement The data that support the findings of this study are available in the Supporting Information of this article

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AB - Pyrazabole (1) is a readily accessible diboron compound that can be transformed into ditopic electrophiles. In 1 (and derivatives), the B⋅⋅⋅B separation is ca. 3 Å, appropriate for one boron centre bonding to N and one to the C7 of indoles and indolines. This suitable B⋅⋅⋅B separation enables double E−H (E=N/C) functionalisation of indoles and indolines. Specifically, the activation of 1 with HNTf2 generates an electrophile that transforms N−H indoles and indolines into N/C7-diborylated indolines, with N−H borylation directing subsequent C7−H borylation. Indole reduction to indoline occurs before C−H borylation and our studies indicate this proceeds via hydroboration—C3-protodeboronation to produce an intermediate that then undergoes C7 borylation. The borylated products can be converted in situ into C7-BPin-N-H-indolines. Overall, this represents a transient directed C−H borylation to form useful C7-BPin-indolines.

KW - Boranes

KW - C−H Borylation

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KW - Transient Directing Group

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Borylation Directed Borylation of Indoles Using Pyrazabole Electrophiles: A One-Pot Route to C7-Borylated-Indolines

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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