Premium
Palladium‐Catalyzed C(sp 3 )H Arylation of N ‐Boc Benzylalkylamines via a Deprotonative Cross‐Coupling Process
Author(s) -
Hussain Nusrah,
Kim ByeongSeon,
Walsh Patrick J.
Publication year - 2015
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.201502017
Subject(s) - palladium , deprotonation , yield (engineering) , catalysis , chemistry , combinatorial chemistry , coupling (piping) , surface modification , coupling reaction , medicinal chemistry , organic chemistry , materials science , metallurgy , ion
Abstract Diarylmethylamines are key intermediates and products in the pharmaceutical industry. Herein we disclose a novel method toward the synthesis of these important compounds via CH functionalization. Presented is a reversible deprotonation of N ‐Boc benzylalkylamines at the benzylic CH with in situ arylation by a NiXantPhos‐based palladium catalyst (50–93 % yield, 29 examples). The method is also successful with N ‐Boc‐tetrahydroisoquinolines. The advantages of this method are it avoids strong bases, low temperatures, and the need to transmetallate to main group metals for the coupling.