10.1021/jo202358p.s002
Bennett
J. Tardiff
Bennett
J.
Tardiff
Robert McDonald
Robert
McDonald
Michael J. Ferguson
Michael J.
Ferguson
Mark Stradiotto
Mark
Stradiotto
Rational and Predictable
Chemoselective Synthesis
of Oligoamines via Buchwald–Hartwig Amination of (Hetero)Aryl
Chlorides Employing Mor-DalPhos
American Chemical Society
2012
Preferential arylation
tri
aminophenyl
alkylamine position
Competition reactions
Pd
crystallographically
catalyst system
chemoselective synthesis
coordination chemistry studies
tetraamine
Predictable Chemoselective Synthesis
cyclic
Buchwald
aniline
amine moiety
reactivity trends
acyclic
2012-01-20 00:00:00
Journal contribution
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
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]<sub>2</sub>/<b>L1</b>; <b>L1</b> = <i>N</i>-(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, <i>N</i>,<i>N</i>-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 <i>N</i>-(4-(di(1-adamantyl)phosphino)phenyl)morpholine (<i>p</i>-Mor-DalPhos, <b>L2</b>) was prepared in 63% yield and was
crystallographically characterized; the [Pd(cinnamyl)Cl]<sub>2</sub>/<b>L2</b> catalyst system exhibited divergent reactivity.
Application of the reactivity trends established for [Pd(cinnamyl)Cl]<sub>2</sub>/<b>L1</b> 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]<sub>2</sub>/<b>L1</b> and 4-chlorotoluene
(affording <b>5a</b>); the alternative regioisomer (<b>5a′</b>) was obtained when using [Pd(cinnamyl)Cl]<sub>2</sub>/<b>L2</b>. These observations are in keeping with coordination chemistry studies,
whereby binding of 2-(4-aminophenyl)ethylamine to the in situ generated
[(<b>L1</b>)Pd(<i>p</i>-tolyl)]<sup>+</sup> fragment
occurred via the primary amine moiety, affording the crystallographically
characterized adduct [(<b>L1</b>)Pd(<i>p</i>-tolyl)(<i>N</i>H<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>(4-C<sub>6</sub>H<sub>4</sub>NH<sub>2</sub>)]<sup>+</sup>OTf<sup>–</sup> (<b>7</b>) in 72% yield.