Atroposelective brominations to access chiral biaryl scaffolds using high-valent Pd-catalysis

Sif T. Linde; Vasco Corti; Vibeke H. Lauridsen; Johannes N. Lamhauge; Karl Anker Jørgensen; Nomaan M. Rezayee

doi:10.1039/d2sc06131g

Atroposelective brominations to access chiral biaryl scaffolds using high-valent Pd-catalysis

Sif T. Linde, Vasco Corti, Vibeke H. Lauridsen, Johannes N. Lamhauge, Karl Anker Jørgensen, Nomaan M. Rezayee^*

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Compounds featuring atropisomerism are ubiquitous in natural products, therapeutics, advanced materials, and asymmetric synthesis. However, stereoselective preparation of these compounds presents many synthetic challenges. This article introduces streamlined access to a versatile chiral biaryl template through C-H halogenation reactions employing high-valent Pd catalysis in combination with chiral transient directing groups. This methodology is highly scalable, insensitive to moisture and air, and proceeds, in select cases, with Pd-loadings as low as 1 mol%. Chiral mono-brominated, dibrominated, and bromochloro biaryls are prepared in high yield and excellent stereoselectivity. These serve as remarkable building blocks bearing orthogonal synthetic handles for a gamut of reactions. Empirical studies elucidated regioselective C-H activation to be predicated on the oxidation state of Pd and diverging site-halogenation to result from cooperative effects of Pd and oxidant.

Original language	English
Journal	Chemical Science
Volume	14
Issue	13
Pages (from-to)	3676-3681
Number of pages	6
ISSN	2041-6520
DOIs	https://doi.org/10.1039/d2sc06131g
Publication status	Published - Apr 2023

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10.1039/d2sc06131gLicence: CC BY-NC

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title = "Atroposelective brominations to access chiral biaryl scaffolds using high-valent Pd-catalysis",

abstract = "Compounds featuring atropisomerism are ubiquitous in natural products, therapeutics, advanced materials, and asymmetric synthesis. However, stereoselective preparation of these compounds presents many synthetic challenges. This article introduces streamlined access to a versatile chiral biaryl template through C-H halogenation reactions employing high-valent Pd catalysis in combination with chiral transient directing groups. This methodology is highly scalable, insensitive to moisture and air, and proceeds, in select cases, with Pd-loadings as low as 1 mol%. Chiral mono-brominated, dibrominated, and bromochloro biaryls are prepared in high yield and excellent stereoselectivity. These serve as remarkable building blocks bearing orthogonal synthetic handles for a gamut of reactions. Empirical studies elucidated regioselective C-H activation to be predicated on the oxidation state of Pd and diverging site-halogenation to result from cooperative effects of Pd and oxidant.",

author = "Linde, {Sif T.} and Vasco Corti and Lauridsen, {Vibeke H.} and Lamhauge, {Johannes N.} and J{\o}rgensen, {Karl Anker} and Rezayee, {Nomaan M.}",

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doi = "10.1039/d2sc06131g",

language = "English",

volume = "14",

pages = "3676--3681",

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T1 - Atroposelective brominations to access chiral biaryl scaffolds using high-valent Pd-catalysis

AU - Linde, Sif T.

AU - Corti, Vasco

AU - Lauridsen, Vibeke H.

AU - Lamhauge, Johannes N.

AU - Jørgensen, Karl Anker

AU - Rezayee, Nomaan M.

PY - 2023/4

Y1 - 2023/4

N2 - Compounds featuring atropisomerism are ubiquitous in natural products, therapeutics, advanced materials, and asymmetric synthesis. However, stereoselective preparation of these compounds presents many synthetic challenges. This article introduces streamlined access to a versatile chiral biaryl template through C-H halogenation reactions employing high-valent Pd catalysis in combination with chiral transient directing groups. This methodology is highly scalable, insensitive to moisture and air, and proceeds, in select cases, with Pd-loadings as low as 1 mol%. Chiral mono-brominated, dibrominated, and bromochloro biaryls are prepared in high yield and excellent stereoselectivity. These serve as remarkable building blocks bearing orthogonal synthetic handles for a gamut of reactions. Empirical studies elucidated regioselective C-H activation to be predicated on the oxidation state of Pd and diverging site-halogenation to result from cooperative effects of Pd and oxidant.

AB - Compounds featuring atropisomerism are ubiquitous in natural products, therapeutics, advanced materials, and asymmetric synthesis. However, stereoselective preparation of these compounds presents many synthetic challenges. This article introduces streamlined access to a versatile chiral biaryl template through C-H halogenation reactions employing high-valent Pd catalysis in combination with chiral transient directing groups. This methodology is highly scalable, insensitive to moisture and air, and proceeds, in select cases, with Pd-loadings as low as 1 mol%. Chiral mono-brominated, dibrominated, and bromochloro biaryls are prepared in high yield and excellent stereoselectivity. These serve as remarkable building blocks bearing orthogonal synthetic handles for a gamut of reactions. Empirical studies elucidated regioselective C-H activation to be predicated on the oxidation state of Pd and diverging site-halogenation to result from cooperative effects of Pd and oxidant.

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U2 - 10.1039/d2sc06131g

DO - 10.1039/d2sc06131g

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AN - SCOPUS:85151019064

SN - 2041-6520

VL - 14

SP - 3676

EP - 3681

JO - Chemical Science

JF - Chemical Science

IS - 13

ER -

Atroposelective brominations to access chiral biaryl scaffolds using high-valent Pd-catalysis

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