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

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.

SUBMITTER: Kim AN

PROVIDER: S-EPMC8926345 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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

Kim Alexia N AN Ngamnithiporn Aurapat A Bartberger Michael D MD Stoltz Brian M BM

Chemical science 20220218 11

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 crit ...[more]

PMID: 35414874

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