%0 Journal Article
%A Tardiff, Bennett
J.
%A McDonald, Robert
%A Ferguson, Michael J.
%A Stradiotto, Mark
%D 2012
%T Rational and Predictable
Chemoselective Synthesis
of Oligoamines via Buchwald–Hartwig Amination of (Hetero)Aryl
Chlorides Employing Mor-DalPhos
%U https://acs.figshare.com/articles/journal_contribution/Rational_and_Predictable_Chemoselective_Synthesis_of_Oligoamines_via_Buchwald_Hartwig_Amination_of_Hetero_Aryl_Chlorides_Employing_Mor_DalPhos/2557546
%R 10.1021/jo202358p.s002
%2 https://ndownloader.figshare.com/files/4200622
%K Preferential arylation
%K tri
%K aminophenyl
%K alkylamine position
%K Competition reactions
%K Pd
%K crystallographically
%K catalyst system
%K chemoselective synthesis
%K coordination chemistry studies
%K tetraamine
%K Predictable Chemoselective Synthesis
%K cyclic
%K Buchwald
%K aniline
%K amine moiety
%K reactivity trends
%K acyclic
%X We report a diverse demonstration of synthetically useful
chemoselectivity
in the synthesis of di-, tri-, and tetraamines (62 examples) by use
of Buchwald–Hartwig amination employing a single catalyst system
([Pd(cinnamyl)Cl]2/L1; L1 = N-(2-(di(1-adamantyl)phosphino)phenyl)morpholine, Mor-DalPhos).
Competition reactions established the following relative preference
of this catalyst system for amine coupling partners: linear primary
alkylamines and imines > unhindered electron-rich primary anilines,
primary hydrazones, N,N-dialkylhydrazines,
and cyclic primary alkylamines > unhindered electron-deficient
primary
anilines, α-branched acyclic primary alkylamines, hindered electron-rich
primary anilines ≫ cyclic and acyclic secondary dialkylamines,
secondary alkyl/aryl and diarylamines, α,α-branched primary
alkylamines, and primary amides. The new isomeric ligand N-(4-(di(1-adamantyl)phosphino)phenyl)morpholine (p-Mor-DalPhos, L2) was prepared in 63% yield and was
crystallographically characterized; the [Pd(cinnamyl)Cl]2/L2 catalyst system exhibited divergent reactivity.
Application of the reactivity trends established for [Pd(cinnamyl)Cl]2/L1 toward the chemoselective synthesis of di-,
tri-, and tetraamines was achieved. Preferential arylation was observed
at the primary alkylamine position within 2-(4-aminophenyl)ethylamine
with [Pd(cinnamyl)Cl]2/L1 and 4-chlorotoluene
(affording 5a); the alternative regioisomer (5a′) was obtained when using [Pd(cinnamyl)Cl]2/L2. These observations are in keeping with coordination chemistry studies,
whereby binding of 2-(4-aminophenyl)ethylamine to the in situ generated
[(L1)Pd(p-tolyl)]+ fragment
occurred via the primary amine moiety, affording the crystallographically
characterized adduct [(L1)Pd(p-tolyl)(NH2CH2CH2(4-C6H4NH2)]+OTf– (7) in 72% yield.
%I ACS Publications