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Experimental and Computational Study on the Anti‐Markovnikov Hydrofunctionalization of Olefins Using Glycine‐Extended AQ‐Auxiliaries
Author(s) -
Nnamdi Fred U.,
Diner Colin,
Champagne Pier Alexandre,
Organ Michael G.
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202004881
Subject(s) - markovnikov's rule , glycine , protonation , chemistry , substrate (aquarium) , reactivity (psychology) , catalysis , combinatorial chemistry , palladium , medicinal chemistry , computational chemistry , stereochemistry , organic chemistry , regioselectivity , amino acid , biochemistry , medicine , ion , oceanography , alternative medicine , pathology , geology
Abstract Two similar tridentate directing groups derived from glycine and 8‐aminoquinoline were shown to enable the palladium‐catalyzed anti‐Markovnikov hydrofunctionalization of 4‐pentenylamine with drastically different efficiencies. A computational investigation into the origin of the reactivity difference between these isomeric, carbonyl‐transposed auxiliaries suggests that protonation state, thus charge of the substrate‐metal complex prior to nucleopalladation is key. These investigations have culminated in a directing group design that can undergo Pd‐catalyzed hydrofunctionalization under relatively mild conditions, as low as room temperature.