Construction of C-N Atropisomers by Aminocatalytic Enantioselective Addition of Indole-2-carboxaldehydes to o-Quinone Derivatives

Vasco Corti; Mathias Kirk Thøgersen; Valdemar Juel Enemærke; Nomaan M. Rezayee; Casper L. Barløse; Karl Anker Jørgensen

doi:10.1002/chem.202202395

Construction of C-N Atropisomers by Aminocatalytic Enantioselective Addition of Indole-2-carboxaldehydes to o-Quinone Derivatives

Vasco Corti, Mathias Kirk Thøgersen, Valdemar Juel Enemærke, Nomaan M. Rezayee, Casper L. Barløse, Karl Anker Jørgensen^*

^*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

1 Citation (Scopus)

Abstract

The first atroposelective aminocatalytic methodology for the construction of C−N atropisomers is presented. The synthesis of this class of axially chiral molecules typically encompasses substrates in which the C−N bond is pre-formed. In contrast, this work presents the direct coupling of indole-2-carboxaldehydes to ortho-quinones, to form the stereogenic C−N axis in an atroposelective way. Application of typical secondary amine catalysts furnished the desired product, however, in low yields and as a complex mixture arising from poor regiocontrol among the C₃- and N₁-sites of the indole core. A new aminocatalyst was designed and synthesized with increased outer-sphere steric bulk to address these challenges thereby providing good levels of regio- and enantioselectivity. A novel library of functionalized and enantioenriched C−N atropisomers was obtained and their synthetic utility was demonstrated by various transformations.

Original language	English
Article number	e202202395
Journal	Chemistry - A European Journal
Volume	28
Issue	60
Number of pages	5
ISSN	0947-6539
DOIs	https://doi.org/10.1002/chem.202202395
Publication status	Published - Oct 2022

Keywords

asymmetric catalysis
atropisomerism
heterocycles
organocatalysis
quinones

Access to Document

10.1002/chem.202202395

Cite this

@article{e7d66e981a1a4b9899751cdefb1d2fdb,

title = "Construction of C-N Atropisomers by Aminocatalytic Enantioselective Addition of Indole-2-carboxaldehydes to o-Quinone Derivatives",

abstract = "The first atroposelective aminocatalytic methodology for the construction of C−N atropisomers is presented. The synthesis of this class of axially chiral molecules typically encompasses substrates in which the C−N bond is pre-formed. In contrast, this work presents the direct coupling of indole-2-carboxaldehydes to ortho-quinones, to form the stereogenic C−N axis in an atroposelective way. Application of typical secondary amine catalysts furnished the desired product, however, in low yields and as a complex mixture arising from poor regiocontrol among the C3- and N1-sites of the indole core. A new aminocatalyst was designed and synthesized with increased outer-sphere steric bulk to address these challenges thereby providing good levels of regio- and enantioselectivity. A novel library of functionalized and enantioenriched C−N atropisomers was obtained and their synthetic utility was demonstrated by various transformations.",

keywords = "asymmetric catalysis, atropisomerism, heterocycles, organocatalysis, quinones",

author = "Vasco Corti and Th{\o}gersen, {Mathias Kirk} and Enem{\ae}rke, {Valdemar Juel} and Rezayee, {Nomaan M.} and Barl{\o}se, {Casper L.} and {Anker J{\o}rgensen}, Karl",

year = "2022",

month = oct,

doi = "10.1002/chem.202202395",

language = "English",

volume = "28",

journal = "Chemistry - A European Journal",

issn = "0947-6539",

publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",

number = "60",

}

Construction of C-N Atropisomers by Aminocatalytic Enantioselective Addition of Indole-2-carboxaldehydes to o-Quinone Derivatives. / Corti, Vasco; Thøgersen, Mathias Kirk; Enemærke, Valdemar Juel et al.
In: Chemistry - A European Journal, Vol. 28, No. 60, e202202395, 10.2022.

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

TY - JOUR

T1 - Construction of C-N Atropisomers by Aminocatalytic Enantioselective Addition of Indole-2-carboxaldehydes to o-Quinone Derivatives

AU - Corti, Vasco

AU - Thøgersen, Mathias Kirk

AU - Enemærke, Valdemar Juel

AU - Rezayee, Nomaan M.

AU - Barløse, Casper L.

AU - Anker Jørgensen, Karl

PY - 2022/10

Y1 - 2022/10

N2 - The first atroposelective aminocatalytic methodology for the construction of C−N atropisomers is presented. The synthesis of this class of axially chiral molecules typically encompasses substrates in which the C−N bond is pre-formed. In contrast, this work presents the direct coupling of indole-2-carboxaldehydes to ortho-quinones, to form the stereogenic C−N axis in an atroposelective way. Application of typical secondary amine catalysts furnished the desired product, however, in low yields and as a complex mixture arising from poor regiocontrol among the C3- and N1-sites of the indole core. A new aminocatalyst was designed and synthesized with increased outer-sphere steric bulk to address these challenges thereby providing good levels of regio- and enantioselectivity. A novel library of functionalized and enantioenriched C−N atropisomers was obtained and their synthetic utility was demonstrated by various transformations.

AB - The first atroposelective aminocatalytic methodology for the construction of C−N atropisomers is presented. The synthesis of this class of axially chiral molecules typically encompasses substrates in which the C−N bond is pre-formed. In contrast, this work presents the direct coupling of indole-2-carboxaldehydes to ortho-quinones, to form the stereogenic C−N axis in an atroposelective way. Application of typical secondary amine catalysts furnished the desired product, however, in low yields and as a complex mixture arising from poor regiocontrol among the C3- and N1-sites of the indole core. A new aminocatalyst was designed and synthesized with increased outer-sphere steric bulk to address these challenges thereby providing good levels of regio- and enantioselectivity. A novel library of functionalized and enantioenriched C−N atropisomers was obtained and their synthetic utility was demonstrated by various transformations.

KW - asymmetric catalysis

KW - atropisomerism

KW - heterocycles

KW - organocatalysis

KW - quinones

UR - http://www.scopus.com/inward/record.url?scp=85136584407&partnerID=8YFLogxK

U2 - 10.1002/chem.202202395

DO - 10.1002/chem.202202395

M3 - Journal article

C2 - 35921208

AN - SCOPUS:85136584407

SN - 0947-6539

VL - 28

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 60

M1 - e202202395

ER -

Construction of C-N Atropisomers by Aminocatalytic Enantioselective Addition of Indole-2-carboxaldehydes to o-Quinone Derivatives

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this