Iridium-catalyzed asymmetric -selective hydrogenation of 1,3-disubstituted isoquinolines

Iridium-catalyzed asymmetric -selective hydrogenation of 1,3-disubstituted isoquinolines

The development of the first asymmetric trans -selective hydrogenation of 1,3-disubstituted isoquinolines is reported. Utilizing [Ir(cod)Cl] 2 and a commercially available chiral Josiphos ligand, a variety of differentially substituted isoquinolines are hydrogenated to produce enantioenriched trans...

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Published in:Chemical science (Cambridge) Vol. 13; no. 11; pp. 3227 - 3232
Main Authors: Kim, Alexia N, Ngamnithiporn, Aurapat, Bartberger, Michael D, Stoltz, Brian M
Format: Journal Article
Published: 16-03-2022
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Abstract The development of the first asymmetric trans -selective hydrogenation of 1,3-disubstituted isoquinolines is reported. Utilizing [Ir(cod)Cl] 2 and a commercially available chiral Josiphos ligand, a variety of differentially substituted isoquinolines are hydrogenated to produce enantioenriched trans -tetrahydroisoquinolines in good yield with high levels of enantioselectivity. Directing group studies demonstrate that the hydroxymethyl functionality at the C1 position is critical for hydrogenation to favor the trans -diastereomer. Preliminary mechanistic studies reveal that non-coordinating chlorinated solvents and halide additives are crucial to enable trans -selectivity. trans -Selective asymmetric hydrogenation of 1,3-disubstituted isoquinolines.
AbstractList The development of the first asymmetric trans -selective hydrogenation of 1,3-disubstituted isoquinolines is reported. Utilizing [Ir(cod)Cl] 2 and a commercially available chiral Josiphos ligand, a variety of differentially substituted isoquinolines are hydrogenated to produce enantioenriched trans -tetrahydroisoquinolines in good yield with high levels of enantioselectivity. Directing group studies demonstrate that the hydroxymethyl functionality at the C1 position is critical for hydrogenation to favor the trans -diastereomer. Preliminary mechanistic studies reveal that non-coordinating chlorinated solvents and halide additives are crucial to enable trans -selectivity. trans -Selective asymmetric hydrogenation of 1,3-disubstituted isoquinolines.
Author Ngamnithiporn, Aurapat
Bartberger, Michael D
Kim, Alexia N
Stoltz, Brian M
AuthorAffiliation California Institute of Technology
Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering
1200 Pharma LLC
Laboratory of Medicinal Chemistry
Division of Chemistry and Chemical Engineering
Chulabhorn Research Institute
AuthorAffiliation_xml – name: 1200 Pharma LLC
– name: Division of Chemistry and Chemical Engineering
– name: Laboratory of Medicinal Chemistry
– name: Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering
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– name: Chulabhorn Research Institute
Author_xml – sequence: 1
  givenname: Alexia N
  surname: Kim
  fullname: Kim, Alexia N
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  givenname: Aurapat
  surname: Ngamnithiporn
  fullname: Ngamnithiporn, Aurapat
– sequence: 3
  givenname: Michael D
  surname: Bartberger
  fullname: Bartberger, Michael D
– sequence: 4
  givenname: Brian M
  surname: Stoltz
  fullname: Stoltz, Brian M
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Notes Electronic supplementary information (ESI) available. CCDC
10.1039/d1sc06729j
For ESI and crystallographic data in CIF or other electronic format see DOI
2120281
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Snippet The development of the first asymmetric trans -selective hydrogenation of 1,3-disubstituted isoquinolines is reported. Utilizing [Ir(cod)Cl] 2 and a...
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Title Iridium-catalyzed asymmetric -selective hydrogenation of 1,3-disubstituted isoquinolines
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