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

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

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Bibliographic Details
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
Language:	English
Published:	England Royal Society of Chemistry 16-03-2022 The Royal Society of Chemistry
Subjects:	Additives Asymmetry Chemistry Enantiomers Hydrogenation Iridium Selectivity
Online Access:	Get full text
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Summary:	The development of the first asymmetric -selective hydrogenation of 1,3-disubstituted isoquinolines is reported. Utilizing [Ir(cod)Cl] and a commercially available chiral Josiphos ligand, a variety of differentially substituted isoquinolines are hydrogenated to produce enantioenriched -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 -diastereomer. Preliminary mechanistic studies reveal that non-coordinating chlorinated solvents and halide additives are crucial to enable -selectivity.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-6520 2041-6539
DOI:	10.1039/d1sc06729j