Why Does an Inert C4–H Bond in Indolyl Aldehyde Get Activated Unexpectedly by a Rh(III) Catalyst over a More Reactive C2–H Bond while the Opposite Is True for Acetophenone? Guidelines for Inverting Regioselectivity
Abstract:Rh(III)-catalyzed regioselective C−H activation/alkyne insertion/ cyclization of indolyl aldehyde and acetophenone with alkynes was investigated using density functional theoretical models. Previously, it was observed that acetophenone demonstrates activation of the more reactive C2−H bond, but indolyl aldehyde showed an unexpected reactivity of the inert C4−H bond under comparable conditions. To understand this substrate-dependent outcome and provide a set of much-awaited guiding principles to invert the regi… Show more
“…Thus, path b is unlikely. 33 However, as we observed the catalytic formation of imines in anaerobic conditions as well, we were interested in calculating the activation energy barrier for the release of H 2 from the intermediate V (Figures 5 and 6). All the possible pathways for the release of H 2 were explored (Figure S31); however, the lowest energy barrier for the release of H 2 was found to be 27.4 kcal/mol (TSD1, Path-b′: Figures 5 and 6) from reference point I where alcohol was found to mediate the release of H 2 .…”
Herein, a new pincer-like amino phosphine
donor ligand, H
2
L
1
,
and its phosphine-oxide analog, H
2
L
2
, were synthesized. Subsequently,
cobalt(II) complexes 1 and 2 were synthesized
by the reaction of anhydrous Co(II)Cl2 with ligands H
2
L
1
and H
2
L
2
, respectively. The ligands and
complexes were fully characterized by various physicochemical and
spectroscopic characterization techniques. Finally, the identity of
the complexes 1 and 2 was confirmed by single
crystal X-ray structure determination. The phosphine ligand containing
complex 1 was converted to the phosphine oxide ligand
containing complex 2 in air in acetonitrile solution.
Both complexes 1 and 2 were investigated
as precatalysts for alcohol dehydrogenation-triggered synthesis of
imines in air. The phosphine-oxide complex 2 was more
efficient than the phosphine complex 1. A wide array
of alcohols and amines were successfully reacted in a mild condition
to result in imines in good to excellent yields. Precatalyst 2 was also highly efficient for the synthesis of varieties
of quinolines in air. As H
2
L
2
in 2 has side arms
that can be deprotonated, we investigated complex 2 for
its base (KO
t
Bu) promoted deprotonation
events by various spectroscopic studies and DFT calculations. These
studies have shown that mono deprotonation of the amine side arm attached
to the pyridine is quite feasible, and deprotonation of complex 2 leads to a dearomatized pyridyl ring containing complex 2a. The mechanistic investigations of the catalytic reaction,
by a combination of experimental and computational studies, have suggested
that the dearomatized complex, 2a acted as an active
catalyst. The reaction proceeded through the hydride transfer pathway.
The activation barrier of this step was calculated to be 26.5 kcal/mol,
which is quite consistent with the experimental reaction temperature
under aerobic conditions. Although various pincer-like complexes are
explored for such reactions, phosphine oxide ligand-containing complexes
are still unexplored.
“…Thus, path b is unlikely. 33 However, as we observed the catalytic formation of imines in anaerobic conditions as well, we were interested in calculating the activation energy barrier for the release of H 2 from the intermediate V (Figures 5 and 6). All the possible pathways for the release of H 2 were explored (Figure S31); however, the lowest energy barrier for the release of H 2 was found to be 27.4 kcal/mol (TSD1, Path-b′: Figures 5 and 6) from reference point I where alcohol was found to mediate the release of H 2 .…”
Herein, a new pincer-like amino phosphine
donor ligand, H
2
L
1
,
and its phosphine-oxide analog, H
2
L
2
, were synthesized. Subsequently,
cobalt(II) complexes 1 and 2 were synthesized
by the reaction of anhydrous Co(II)Cl2 with ligands H
2
L
1
and H
2
L
2
, respectively. The ligands and
complexes were fully characterized by various physicochemical and
spectroscopic characterization techniques. Finally, the identity of
the complexes 1 and 2 was confirmed by single
crystal X-ray structure determination. The phosphine ligand containing
complex 1 was converted to the phosphine oxide ligand
containing complex 2 in air in acetonitrile solution.
Both complexes 1 and 2 were investigated
as precatalysts for alcohol dehydrogenation-triggered synthesis of
imines in air. The phosphine-oxide complex 2 was more
efficient than the phosphine complex 1. A wide array
of alcohols and amines were successfully reacted in a mild condition
to result in imines in good to excellent yields. Precatalyst 2 was also highly efficient for the synthesis of varieties
of quinolines in air. As H
2
L
2
in 2 has side arms
that can be deprotonated, we investigated complex 2 for
its base (KO
t
Bu) promoted deprotonation
events by various spectroscopic studies and DFT calculations. These
studies have shown that mono deprotonation of the amine side arm attached
to the pyridine is quite feasible, and deprotonation of complex 2 leads to a dearomatized pyridyl ring containing complex 2a. The mechanistic investigations of the catalytic reaction,
by a combination of experimental and computational studies, have suggested
that the dearomatized complex, 2a acted as an active
catalyst. The reaction proceeded through the hydride transfer pathway.
The activation barrier of this step was calculated to be 26.5 kcal/mol,
which is quite consistent with the experimental reaction temperature
under aerobic conditions. Although various pincer-like complexes are
explored for such reactions, phosphine oxide ligand-containing complexes
are still unexplored.
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