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A Borrowing Hydrogen Strategy for Dehydrative Coupling of Aminoisoquinolines with Benzyl Alcohols in Water
Author(s) -
Hikawa Hidemasa,
Tan Rie,
Tazawa Aoi,
Kikkawa Shoko,
Azumaya Isao
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201901606
Subject(s) - chemistry , benzyl alcohol , nucleophile , kinetic isotope effect , amination , catalysis , solvent , alcohol , hydrogen , palladium , medicinal chemistry , organic chemistry , deuterium , physics , quantum mechanics
We report a borrowing hydrogen strategy for a palladium‐catalyzed dehydrative coupling of aminoisoquinolines with benzylic alcohols in water. This cascade reaction using the π‐benzylpalladium system can be achieved in an atom‐economic process without the need for base or other additives, furnishing the N ‐benzylated aminoisoquinolines in moderate to excellent yields along with water as the sole co‐product. The crossover experiment using [D 7 ]benzyl alcohol and 4‐methoxybenzyl alcohol afforded H/D scrambled products. KIE experiments showed that benzylic C–H bond cleavage of benzyl alcohol was involved in the turnover limiting step (KIE = 4.4). The coupling reaction was found to be first order in benzyl alcohol with a kinetic solvent isotope effect (KSIE) of 1.6. These experimental results are consistent with a borrowing hydrogen mechanism in water. Notably, the water‐soluble Pd 0 /TPPMS system can be applied to the more challenging catalytic benzylic amination with aminoisoquinoline nucleophiles despite the possible deactivation of Pd II species.