Johnson Group Research Summary (updated November 2013)
Work in the Johnson lab focuses on the mechanistic studies of known reactions, and the development of
new reaction methodology. These two areas feed one another, with the results of mechanistic studies
informing the development of new reactions, and new reactions providing a subject for mechanistic
investigations.
O
N R'
O
O
+ R2Zn
[Ni]
N
H
R'
N R'
R
O
O
+ R2Zn
[Ni]
Decarbonylative
Alkylation
N R'
HO R
O
Alkylative
Desymmetrization
Mechanistic
Studies
O
OH
[Pd]
Ar-Br
N
+
Ar-Ph
β-aryl Elimination and Coupling
N
[Rh]
O
O
O
O
Alkene Carboacylation
Projects Involving Carbon-Carbon Single Bond Activation
Many of the major products in the Johnson lab focus on the understanding and development of
methodologies utilizing carbon-carbon single bond activation. Although still in relatively early stages of
development, the process of C-C bond activation is slowly expanding beyond esoteric reactions limited to
strained rings and highly specialized substrates. Through mechanistic studies, efforts are underway to
better understand this transformation and to focus on the functionalization of organometallic
intermediates. In time this transformation has the promise to become a common synthetic tool such as its
related reaction, C-H bond activation.
For our previous work in this area, see (undergraduate coauthors are underlined):
Rathbun, C. M.; Johnson, J. B. J. Am. Chem. Soc. 2011, 133, 2031.
Lutz, J. P.; Rathbun, C. M.; Stevenson, S. M.; Powell, B. M.; Boman, T. S.; Baxter, C. E.; Zona, J. M.; Johnson, J. B.
J. Am. Chem. Soc. 2012, 134, 715.
Bour, J. R.; Green, J. C.; Winton, V. J.; Johnson, J. B. J. Org. Chem. 2013, 78, 1665.
Johnson Research Summary – Page 2
New Methodology
Using information gathered from previous mechanistic studies, our group is currently developing
new methodology that utilizes transition metal-catalyzed carbon-carbon single bond activation to generate
nucleophiles for cross-coupling reactions.
F
O
[Rh(C2H4)2Cl]2
(5 mol%)
O
+
OMe
N
F
O
OMe
130 oC, 16h
excess
H
N
N
O
O
O
(cat)
[Rh(C2H4)2Cl]2 (cat)
N
O
[Rh(C2H4)2Cl]2
(cat)
O
O
OMe
N
-CO
OMe
O
Investigation of Directing Groups
To achieve C-C bond activation, a directing group is necessary to promote the desired reactivity.
Our group is currently exploring potential directing groups and evaluating their relative abilities to promote
C-C bond activation in aryl ketones.
N
O
[Rh]
N
N
=
N
N
N
-CO
O
N
N
O
NH2
Mechanism of Ketone Decarbonylation
Aryl ketones containing benzoquinoline or 2-pyridyl directing groups have been demonstrated to
undergo rhodium-catalyzed decarbonylation. There are two probable metalacyclic intermediates for this
process, shown below. Mechanistic investigations are underway to determine the relatively likelihood of
each pathway.
N
O
[Rh]
N
O
[Rh]
N
- [Rh]
[Rh]
CO
N
[Rh]
O
- CO
N
Johnson Research Summary – Page 3
Projects Involving Nickel-Catalyzed Alkylation Methodology
For our previous work in this area, see (undergraduate coauthors are underlined):
Dennis, J. M.; Calyore, C. M.; Sjoholm, J. M.; Lutz, J. P.; Gair, J. J.; Johnson, J. B. Synlett eFirst (October,
2013).
Havlik, S. E.; Simmons, J. M.; Winton, V. J.; Johnson, J. B. J. Org. Chem. 2011, 76, 3588.
Mechanism of Decarbonylative Coupling
Our initial work achieved the nickel-mediated decarbonylative cross-coupling of imides with
diorganozinc reagents. Efforts are ongoing to understand the mechanism of this process. Investigations
include kinetic work, intermediate analysis with in situ IR and NMR spectroscopy, and the analysis of
product mixtures.
O
+ Et2Zn
(3 equiv)
N R
O
100 mol% Ni(acac)2
110 mol% bipy
N
H
dioxane, 95 oC
Et
O
13
C NMR
R
in situ IR
Development of Catalytic Decarbonylative Coupling
Although it uses inexpensive nickel species, our early methodology is limited by the requirement
of stoichiometric metal. Several approaches are being explored to develop methods that are catalytic in
the transition metal necessary for reactivity. These include changing variables such as the solvent, the
ligand, and the temperature, but also exploring substrate-based attributes such as the electronics of the
N-substitution.
O
N R
+ Et2Zn
(1.1 equiv)
O
10 mol% Ni(COD)2
11 mol% ligand
N
H
R
Et
O
Exploration of Regioselectivity
We continue to explore our earlier methodology through the investigation of the regioselectivity of
decarbonylative alkylation using unsymmetrically substituted phthalimide substrates.
O
R'
N R
O
+ Et2Zn
(3 equiv)
100 mol% Ni(acac)2
110 mol% bipy
O
R'
R'
N
H
dioxane, 95 oC
Et
Et
R
H
N
and/or
O
R
Johnson Research Summary – Page 4
Use of Saturated Backbones
Efforts are ongoing to expand the substrate scope to include non-aromatic backbones. With the
decarbonylative methodology, this could lead to the construction of new Csp3-Csp3 bonds as well the
formation of β-substituted chiral amides with contiguous stereocenters from achiral precursors.
O
N R
O
+ Et2Zn
(1.1 equiv)
10 mol% Ni(COD)2
11 mol% ligand
-CO
O
Et
N
H
R