Nickel-mediated decarbonylative cross-coupling of phthalimides with in situ generated diorganozinc reagents

Article abstract of DOI:10.1021/jo200347j

The nickel-mediated cross-coupling of phthalimides with diorganozinc reagents proceeds via a decarbonylative process to produce ortho-substituted benzamides in high yields. In addition to tolerating diverse phthalimide functionality, including alkyl, aryl

Full text of DOI:10.1021/jo200347j

NOTE
pubs.acs.org/joc
Nickel-Mediated Decarbonylative Cross-Coupling of Phthalimides
with in Situ Generated Diorganozinc Reagents
Sarah E. Havlik, Jessica M. Simmons, Valerie J. Winton, and Jeffrey B. Johnson*
Department of Chemistry, Hope College, Holland, Michigan 49423, United States
S Supporting Information
b
ABSTRACT: The nickel-mediated cross-coupling of phthalimides with
diorganozinc reagents proceeds via a decarbonylative process to produce
ortho-substituted benzamides in high yields. In addition to tolerating
diverse phthalimide functionality, including alkyl, aryl, and heteroatom
containing substituents, this methodology proceeds smoothly with di-
organozinc reagents prepared from aryl bromides and utilized without
purification.
ew cross-coupling methodologies for the construction of
We were led to the decarbonylative coupling of imides with
N
carbonꢀcarbon bonds continually transform organic synthe-
carbon nucleophiles through efforts to directly couple imides
with diorganozinc reagents, where initial efforts began with
conditions that were successful in related reactions of cyclic
anhydrides.23,24 In the presence of substoichiometric Ni(acac)2
(acac = acetylacetonate) and bipyridine, N-phenylphthalimide
was combined with an excess of diethylzinc in THF (Table 1,
entry 2). Spectroscopic characterization of the isolated product
indicated that instead of the ketamide product (3) anticipated
from direct coupling of the imide and diethylzinc, decarbony-
lated product 2 was the sole product recovered, with unreacted
imide making up the remainder of the mass balance.25 More
significantly, yields of the putative catalytic reaction closely
matched the catalyst loading, suggesting a failure of nickel
turnover. As efforts to induce catalysis were unsuccessful, we
opted for the development of the metal-mediated process and
turned our attention to the optimization of the nickel-mediated
decarbonylative process. These efforts are summarized in
Table 1.26 Several solvents were screened, as well as a number
of ligands. Bipyridine provides a significant increase in yield
compared to PPh3, pyridine, and pyphos [2-(2-(diphenyl-
phosphino)ethyl)pyridine] (entries 4ꢀ8). No product was ob-
served when the reaction is performed in the absence of nickel
(entry 9), demonstrating that the reaction is nickel mediated.
Ultimately, the coupling of phthalimide with Et2Zn was achieved
in 96% yield with the use of stoichiometric Ni(acac)2 and bipy in
dioxane at 95 °C (Table 1, entry 1). Ni(COD)2 (COD = 1,5-
cyclooctadiene) also proved to be a viable metal source, and with
the use of only 1.1 equiv of Et2Zn provided the desired product in
92% yield (entry 10). The use of other organometallic reagents,
including EtZnBr, was unsuccessful.
sis.1 Through the gradual expansion of available nucleophilic and
electrophilic coupling partners, innumerable previously unknown
synthetic disconnects are now possible. The currently available
battery of cross-coupling reactions includes diverse methods for
the coupling of wide varieties of functional groups, often
enhanced by the control of regiochemistry or stereochemistry
and significant increases in molecular complexity. The utility of a
given functional group, and cross-coupling methodologies as a
whole, can be further increased by its controlled modification
during the coupling process. For example, well-known decarbox-
ylative coupling procedures utilize carboxylic acids2ꢀ6 and
esters7,8 as the source of alkyl nucleophiles. Likewise, decarbo-
nylation provides a means of controlled functional group modi-
fication. Since being first reported in 1965,9 decarbonylative
coupling has been achieved with functional groups including
aldehydes,10ꢀ14 carboxylic acids,15 isopropenyl esters,16 car-
boxylic anhydrides,17ꢀ19 and only recently imides.20,21
The addition of carbon-based nucleophiles such as Grignard
or alkyl lithium reagents to imines has long been known. The use
of imides in transition metal-controlled cross-coupling meth-
odologies has only recently been demonstrated in a decarbony-
lative fashion for reaction with alkynes and dienes.19,20 Our
efforts focused on the use of imides as electrophilic coupling
partners in cross-coupling methodology with carbon nucleo-
philes. Herein we present the nickel-mediated decarbonylative
coupling of diorganozinc reagents to phthalimides, a process that
results in the creation of an unfunctionalized carbonꢀcarbon
bond. This decarbonylative methodology demonstrates signifi-
cant functional group compatibility and is applicable to a broad
range of diorganozinc reagents prepared from aryl bromides and
utilized without purification. This cross-coupling of phthalimides
with organozinc nucleophiles provides a highly efficient con-
struction of ortho-substituted benzamides, which have been the
focus of a number of studies of biologically active agents and
pharmaceuticals.22
These optimized conditions were in turn utilized to examine
the substrate scope of the decarbonylative coupling of diethylzinc
to a range of phthalimides (Table 2). A variety of imide-nitrogen
Received: February 16, 2011
Published: March 25, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo200347j J. Org. Chem. 2011, 76, 3588–3593
|

The Journal of Organic Chemistry
NOTE
Table 1. Optimization of Reaction Conditions for Decarbo-
nylative Coupling of Phthalimides with Diethylzinc
Scheme 1. Unsuccessful Substrates
Table 3. Scope of Organozinc Nucleophiles Compatible with
Phthalimide Cross-Coupling
entry
change from “standard” conditionsa
yield (%)
1
2
3
4
5
6
7
8
9
none
96
19
18
<5
60
76
6
20 mol % Ni(acac)2/bipy in THF at 50 °C
20 mol % Ni(acac)2/bipy
10 mol % Ni(COD)2/40 mol % PMe3, 1.1 equiv of Et2Znb
THF, 50 °C
pyphos instead of bipy
entrya
R
product
yield (%)
1
2
Phb
Phc
15
15
16
17
18
19
20
21
22
23
24
25
26
27
28
81
77
78
69
72
93
71
87
96
96
75
77
57d
83
69
2 equiv of PPh3 instead of bipy
2 equiv of pyridine instead of bipy
no bipyridine
13
0
3
4-MeO-C6H4
3-MeO-C6H4
2-MeO-C6H4
4-MeS-C6H4
4-F3C-C6H4
4-F-C6H4
4
10 no Ni source
0
5
11 Ni(COD)2 instead of Ni(acac)2
12 Ni(COD)2, 1.1 equiv of Et2Zn
13 EtZnBr instead of Et2Znc
93
92
<5
6
7
a “Standard” conditions: N-phenylphthalimide (0.9 mmol, 1.0 equiv),
Ni(acac)2 (1.0 equiv), bipyridine (1.1 equiv), Et2Zn (3.0 equiv), in
dioxane (2.5 mL) at 95 °C under an Ar atmosphere. b See ref 21.
c Prepared from EtMgBr (1.0 equiv) and ZnBr2 (1.0 equiv) in THF and
used without purification.
8
9
4-Me-C6H4
10
11
12
13
14e
15
4-Me2N-C6H4
3-Me-C6H4
3,5-(F3C)2-C6H3
3,4,5-(MeO)3-C6H2
CH2CH2CO2Et
Bu
Table 2. Scope of Phthalimides Amenable to
Decarbonylative Cross-Coupling with Et2Zn
a Conditions: phthalimide (0.9 mmol, 1.0 equiv), Ni(COD)2 (1.0
equiv), bipyridine (1.1 equiv), R2Zn (1.3 equiv, used without purifica-
tion from RBr, nBuLi, and ZnCl2 in 2 mL of THF), 1,4-dioxane (2.5 mL)
at 95 °C under an Ar atmosphere. b Ph2Zn from commercial source.
c Ph2Zn prepared from PhBr. d Obtained as an inseparable mixture with
the biaryl homocoupling product. e Prepared from ZnCl2 and (1-
ethoxycyclopropoxy)trimethylsilane.
entrya
R
product
yield (%)
1
2
Ph
2
96
89
92
97
91
93
84
65
85
81
halides, and amines, and proceeds with yields generally exceeding
75%. The decarbonylative coupling also proceeds with substi-
tuted phthalimides, as illustrated by the reaction of N-phenyl-4-
methylphthalimide with Et2Zn, but generates an inseparable
mixture of two isomeric products.27 The imide substrates are
limited to phthalimide derivatives, as efforts using cyclic imides
with saturated backbones, including cyclohexane-containing
succinimide 13 and 3,4-dimethylsuccinimide 14, have resulted
in less than 10% of the desired product, with mass balance consisting
of unreacted or hydrolyzed starting material (Scheme 1).
4-Et-C6H4
4
3
4-iPr-C6H4
3,5-(CF3)2-C6H3
2,5-(OMe)2-C6H3
4-CO2Et-C6H4
Bn
5
4
6
5
7
6
8
7
9
8
Me
10
11
12
9
CH2CH2Ph
(CH2)3NMe2
10
Of greater synthetic interest is the range of diorganozinc
nucleophiles compatible with this reactivity. Commercially avail-
able diphenylzinc works smoothly in this reaction, providing
benzanilide 15 in 81% yield (Table 3, entry 1). Unfortunately, the
commercial availability of similar diorganozinc reagents is quite
limited, and thus there is great importance in the ability to use
nucleophiles prepared from corresponding aryl halides, prefer-
ably with minimum required purification. To this end, diphe-
nylzinc was prepared via lithiumꢀhalogen exchange with
bromobenzene by using nBuLi followed by reaction of the
a Conditions: phthalimide (0.9 mmol, 1.0 equiv), Ni(acac)2 (1.0 equiv),
bipyridine (1.1 equiv), Et2Zn (3.0 equiv), in dioxane (2.5 mL) at 95 °C
under an Ar atmosphere.
substitution was utilized in these reactions, including aromatic
substituents with both electron-rich and electron-deficient sub-
stituents (entries 2ꢀ6), alkyl groups (entries 7ꢀ9), and aliphatic
amines (entry 10). The reaction demonstrates significant func-
tional group tolerance on the imide, including esters, ethers,
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dx.doi.org/10.1021/jo200347j |J. Org. Chem. 2011, 76, 3588–3593

The Journal of Organic Chemistry
NOTE
Scheme 2. Proposed Mechanism
Scheme 3. Alternative Transmetalation/Migration
Mechanism
been deemed unlikely, however, as reductive elimination from
intermediate E to generate the ketoamide product would pre-
sumably be competitive with decarbonylation, providing at least
small amounts of the direct coupling product. No evidence
for this direct product has been observed under any tested
conditions.
In summary, the cross-coupling of diorganozinc nucleophiles
with electrophilic phthalimides proceeds via a decarbonylative
process to generate ortho-substituted benzamides and biaryls in
excellent yields. This method, with its compatibility with in situ
generated nucleophiles, provides a means of ready access to a
wide variety of synthetically useful species.
aryllithium reagent with zinc chloride. This THF solution of
diphenylzinc was then utilized directly in the decarbonylation
methodology, using Ni(COD)2 rather than the bench stable
Ni(acac)2 in order to minimize the amount of nucleophile
required to produce the active Ni0 species. Much to our
delight, the use of the unpurified diorganozinc reagent pro-
vided decarbonylated product 15 in a very similar yield (77%)
to that obtained with use of the commercial diorganozinc
reagent (81%).
Using this same nucleophile preparation, a series of diorga-
nozinc reagents were tested under similar conditions. The
reaction has proven to be remarkably resilient to changes in
nucleophile substitution and electronics. Ortho, meta, and para
substitution is tolerated, with relatively little influence upon the
reaction yield (Table 3, entries 3ꢀ8). A number of heteroatom
containing functionalities are tolerated, including ethers, thio-
ethers, halides and amines. When prepared directly from the
reaction of ZnCl2 with (1-ethoxycyclopropoxy)trimethylsilane,
esters are also competent nucleophiles (entry 13). To date, the
reaction proceeds with all arylbromides for which the diorgano-
zinc reagent can be successful generated. It is of note that
common byproducts of low yielding reactions include biaryl
species from Negishi-type coupling of the aryl nucleophile,
presumably with unreacted aryl halide, and hydrolyzed starting
material. In addition, efforts to utilize organozinc halide nucleo-
philes prepared in an analogous fashion have been unsuccessful.
In contemplating the reaction pathway, it is presumed that the
reaction proceeds via oxidative addition of a Ni0 species into the
nitrogenꢀcarbonyl bond of the cyclic imide to produce inter-
mediate A28 in analogy to more well studied anhydride reactions
(Scheme 2).29,30 Decarbonylation is anticipated to occur from
this intermediate, producing metalacycle B,31ꢀ33 which then
undergoes subsequent transmetalation with the diorganozinc
reagent. Reductive elimination from intermediate C releases the
product as well as regenerating a Ni0 species, now complexed to
CO. Unfortunately, no turnover is observed, suggesting that the
strong NiꢀCO bond of the proposed intermediate precludes
dissociation to regenerate the initial active species.34,35 These
observations also suggest that NiꢀCO complex D is of insufficient
nucleophilicity to undergo oxidative addition to another equiva-
lent of the starting material.
’ EXPERIMENTAL SECTION
General Methods. All reactions were carried out under an atmo-
sphere of nitrogen or argon in oven-dried glassware with magnetic
stirring. Solvents, including toluene, tetrahydrofuran, and diethyl ether,
were purged with argon and passed through two columns of neutral
alumina or molecular sieves. All starting materials are commercially
available and used without purification or prepared according to
procedures provided.
Unless otherwise noted, all reactions were performed in oven-dried
glassware under an inert atmosphere of N2 or Ar. H and 13C NMR
1
spectra were obtained using standard acquisition parameters and are
referenced to TMS.
All phthalimides were obtained commercially or prepared via the
condensation of phthalic acid with the appropriate amine in either
refluxing toluene (DeanꢀStark conditions) or refluxing acetic acid.36
Products 4 and 15 match literature precedent (melting point only).37,38
Full characterization data are provided for these compounds.
General Method for Decarbonylative Coupling with
Et2Zn. The general method will be illustrated with a specific example.
Ni(acac)2 (116 mg, 0.45 mmol), bipyridine (84 mg, 0.54 mmol), and N-
p-isopropylphenylphthalimide (119 mg, 0.45 mmol) were combined in
an oven-dried 25-mL round-bottomed flask and sealed with a septum.
The flask was evacuated and refilled (3ꢁ) and placed under N2. 1,4-
Dioxane (2.5 mL) was added via syringe, followed by Et2Zn (140 μL,
1.35 mmol) also via syringe. The dark solution was then suspended in a
95 °C oil bath and allowed to stir for 16 h. Following reaction, the
reaction mixture was cooled to room temperature, the septum was
removed, and the reaction mixture was diluted with Et2O (15 mL). The
addition of 2 M aq HCl (15 mL) quenched the reaction, which was then
extracted with Et2O (3 ꢁ 15 mL). The combined organic layers were
washed with brine (15 mL), dried over MgSO4, and concentrated under
reduced pressure. The resulting yellow oil was purified by column
chromatography (10:1 hexane:ethyl acetate) to provide 5 in 92% yield.
A similar mechanism can be drawn with transmetalation
preceding decarbonylation (Scheme 3). This mechanism has
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The Journal of Organic Chemistry
NOTE
General Method for Decarbonylative Coupling with in
Situ Generated Diorganozinc Reagents. The general method
will be illustrated with a specific example. p-Bromothioanisole (272 mg,
1.34 mmol) was added to an oven-dried 10-mL round-bottomed flask,
sealed with a septum, evacuated and refilled with Ar (3ꢁ) and dissolved
in THF (2 mL). The reaction mixture was cooled to ꢀ78 °C and nBuLi
(2.5 M, 536 μL, 1.34 mmol) was added dropwise with stirring at ꢀ78 °C
for 30 min. In a separate flask, ZnCl2 (91.3 mg, 0.67 mmol) was flame-
dried under vacuum, then dissolved in THF (1 mL). This solution was
then added to the solution of ArLi, still at ꢀ78 °C. The reaction was
removed from the cold bath and allowed to warm to room temperature
while stirring for 30 min.
In a separate 50-mL round-bottomed flask, N-phenylphthalimide
(115 mg, 0.51 mmol) and bipyridine (84 mg, 0.54 mmol) were
combined and transferred into an inert atmosphere glovebox, where
Ni(COD)2 (140 mg, 0.51 mmol) was added. This flask was sealed with a
septum and removed from the glovebox, whereupon 1,4-dioxane
(2.5 mL) was added, followed by the Ar2Zn solution. The flask was
then suspended in a 95 °C oil bath and allowed to stir for 16 h. Following
reaction, the mixture was cooled to room temperature, the septum was
removed, and the reaction mixture was diluted with Et2O (15 mL). The
addition of 2 M aq HCl (15 mL) quenched the reaction, which was then
extracted with Et2O (3 ꢁ 15 mL). The combined organic layers were
washed with brine (15 mL), dried over MgSO4, and concentrated under
reduced pressure. The resulting residue was purified by column chro-
matography (9:1 hexane:ethyl acetate) to provide 19 as a white solid in
93% yield.
2H), 1.25 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 168.5,
142.9, 139.4, 134.8, 132.4 (qrt, JCꢀF = 33 Hz), 131.0, 129.9, 126.5, 126.0,
123.1 (qrt, J = 273 Hz), 119.5 (qrt, JCꢀF = 3.1 Hz), 117.7 (pent, JCꢀF
=
3.6 Hz), 26.3, 15.8. IR (NaCl) 3429, 2975, 1659, 1557, 1470, 1438, 1380,
1278 cmꢀ1. HRMS (ESIþ) calcd for [C17H14F6NO]þ 362.0974, found
362.0970.
N-(2,5-Dimethoxyphenyl)-2-ethylbenzamide (7): The title
compound was prepared according to the general procedure for
decarbonylation with diethylzinc. Column chromatography with 4:1
hexane:EtOAc yielded 7 as a white solid (117 mg, 0.41 mmol, 91%
yield). Rf 0.23. Mp 119ꢀ120 °C. 1H NMR (400 MHz, CDCl3) δ 8.28
(d, J = 2.9 Hz, 1H), 8.11 (br s, 1H), 7.49 (d, J = 7.5 Hz, 1H), 7.41 (dt, J =
7.3, 1.6 Hz), 7.35ꢀ7.24 (mult, 2H), 6.82 (d, J = 8.9 Hz, 1H), 6.62 (dd,
J = 8.9, 3.0 Hz, 1H), 3.83 (s, 3H), 3.82 (s, 3H), 2.88 (qrt, J = 7.5 Hz, 2H),
1.28 (t, J = 7.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 168.0, 153.8,
142.5, 142.2, 136.5, 130.3, 129.6, 128.2, 126.9, 125.9, 110.7, 108.8, 106.0,
56.1, 55.9, 26.3, 15.9. IR (NaCl) 3419, 2963, 2942, 1676, 1526, 1468 cmꢀ1
.
HRMS (ESIþ) calcd for [C17H20NO3]þ 286.1438, found 286.1434.
Ethyl 4-(2-ethylbenzamido)benzoate (8): The title com-
pound was prepared according to the general procedure for decarbo-
nylation with diethylzinc. Column chromatography with 10:1 hexane:
EtOAc yielded 8 as a yellowish solid (124 mg, 0.42 mmol, 93% yield). Rf
0.41 (in 2:1 hex:EtOAc). Mp 109ꢀ110 °C. 1H NMR (400 MHz,
CDCl3) δ 8.00 (br s, 1H), 7.90 (d, J = 8.0 Hz, 2H), 7.61 (d, J = 8.0 Hz,
2H), 7.34ꢀ7.09 (mult, 4H), 4.23 (qrt, J = 7.2 Hz, 2H), 2.73 (qrt, J = 7.4
Hz, 2H), 1.29 (t, J = 7.2 Hz, 3H), 1.15 (t, J = 7.4 Hz, 3H). 13C NMR (100
MHz, CDCl3) δ 168.4, 166.1, 142.6, 142.2, 135.7, 130.7, 130.5, 129.6,
126.6, 126.0, 125.8, 118.9, 60.8, 26.3, 15.7, 14.3. IR (NaCl) 3303, 2972,
1713, 1682, 1651, 1595, 1536, 1309, 1272 1175, 1108 cmꢀ1 . HRMS
(ESIþ) calcd for [C18H20NO3]þ 298.1438, found 298.1443.
2-Ethyl-N-phenylbenzamide (2): The title compound was pre-
pared according to the general procedure for decarbonylation with
diethylzinc. Column chromatography with 4:1 hex:EtOAc yielded 2
1
(97 mg, 0.43 mmol, 96% yield) as a yellowish oil. Rf 0.27. H NMR
N-Benzyl-2-ethylbenzamide (9): The title compound was pre-
pared according to the general procedure for decarbonylation with
diethylzinc. Column chromatography with 10:1 hex:EtOAc yielded 9
(91 mg, 0.38 mmol, 84% yield) as a yellowish oil. Rf 0.13. 1H NMR (400
MHz, CDCl3) δ 7.39ꢀ7.24 (mult, 8H), 7.18 (dt, J = 7.5, 1.2 Hz, 1H),
4.62 (d, J = 5.7 Hz, 1H), 2.82 (qrt, J = 7.5 Hz, 2H), 1.23 (t, J = 7.5 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ 170.0, 142.4, 138.1, 136.0, 130.0,
129.5, 128.8, 127.8, 127.6, 126.6, 125.7, 43.9, 26.3, 15.9. IR (NaCl) 3328,
3281, 2962, 2931, 1633, 1531, 1310 cmꢀ1. HRMS (ESIþ) calcd for
[C16H18NO]þ 240.1383, found 240.1385.
N-Methyl-2-ethylbenzamide (10): The title compound was
prepared according to the general procedure for decarbonylation with
diethylzinc. Column chromatography with 10:1 hexane:EtOAc yielded
10 as a yellow oil (117 mg, 0.41 mmol, 65% yield). Rf 0.09 (in 2:1 hex:
EtOAc). 1H NMR (400 MHz, CDCl3) δ 7.36ꢀ7.28 (mult, 2H),
7.27ꢀ7.24 (mult, 1H), 7.18 (dt, J = 7.4, 1.5 Hz, 1H), 2.99 (d, J = 5.1
Hz, 3H), 2.79 (qrt, J = 7.3, 2H), 1.23 (t, J = 7.3, 3H). 13C NMR (100
MHz, CDCl3) δ 171.0, 142.3, 136.3, 129.9, 129.4, 126.7, 125.7, 26.7,
26.4, 15.8. IR (NaCl) 3378, 2963, 1717, 1652, 1599, 1557, 1260,
1013 cmꢀ1. HRMS (ESIþ) calcd for [C10H14NO]þ 164.1070, found
164.1037.
2-Ethyl-N-phenethylbenzamide (11): The title compound was
prepared according to the general procedure for decarbonylation with
diethylzinc. Column chromatography with 10:1 hex:EtOAc yielded 11
(97 mg, 0.38 mmol, 85% yield) as a colorless oil. Rf 0.13. 1H NMR (400
MHz, CDCl3) δ 7.34ꢀ7.12 (mult, 9H), 5.79 (br s, 1H), 3.71 (qrt, J = 7.6
Hz, 2H), 2.93, (t, J = 7.6 Hz, 2H), 2.73 (qrt, J = 7.6 Hz, 2H), 1.19 (t, J =
7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.2, 142.2, 138.7, 136.2,
129.8, 129.3, 128.7, 128.6, 126.6, 126.5, 125.6, 40.7, 35.6, 26.2, 15.8. IR
(NaCl) 3328, 3281, 2962, 2931, 1633, 1531, 1310 cmꢀ1. HRMS (ESIþ)
calcd for [C17H20NO]þ 254.1539, found 254.1531.
(400 MHz, CDCl3) δ 7.62 (d, J = 7.8 Hz, 2H), 7.52ꢀ7.22 (mult, 6H),
7.15 (t, J = 7.3 Hz, 2H), 2.86 (qrt, J = 7.2 Hz, 2H), 1.27 (t, J = 7.2 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ 168.2, 142.6, 138.0, 136.2, 130.3,
129.6, 129.1, 126.6, 125.9, 124.5, 119.8, 26.3, 15.9. IR (NaCl) 3259,
3234, 1640, 1595, 1539, 1324 cmꢀ1. HRMS (ESIþ) calcd for
[C15H16NO]þ 226.1226, found 226.1232.
2-Ethyl-N-(4-ethylphenyl)benzamide (4): The title com-
pound was prepared according to general procedure for decarbonylation
with diethylzinc. Column chromatography with 9:1 hex:EtOAc yielded
4 (101 mg, 0.40 mmol, 89%) as a white solid. Rf 0.52 (in 2:1 hex:EtOAc).
Mp 110ꢀ111 °C. 1H NMR (400 MHz, CDCl3) δ 7.54 (br s, 1H), 7.41
(d, J = 7.8 Hz, 2H), 7.33ꢀ7.04 (mult, 6H), 2.73 (qrt, J = 7.8 Hz, 2H),
2.54 (qrt, J = 7.8 Hz, 2H), 1.14 (t, J = 7.8 Hz, 6H). 13C NMR (100 MHz,
CDCl3) δ 168.1, 142.4, 140.5, 136.3, 135.6, 130.1, 129.5, 128.3, 126.5,
125.7, 120.0, 28.3, 26.3, 15.8, 15.6. IR (NaCl) 3279, 2922, 2866, 1650,
1599, 1536, 1503, 1409, 1323, 1274 cmꢀ1. HRMS (ESIþ) calcd for
[C17H20NO]þ 254.1539, found 254.1533.
2-Ethyl-N-(4-isopropylphenyl)benzamide (5): The title com-
pound was prepared according to the general procedure for decarbo-
nylation with diethylzinc. Column chromatography with 10:1 hex:
EtOAc yielded 5 (111 mg, 0.41 mmol, 92% yield) as a viscous yellow
oil. Rf 0.15. 1H NMR (400 MHz, CDCl3) δ 7.56ꢀ7.19 (mult, 9H), 2.90
(pent, J = 7.1 Hz, 1H), 2.84 (qrt, 7.6 Hz, 2H), 1.25 (t, J = 7.6 Hz, 3H),
1.25 (d, J = 7.1 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ 168.2, 145.3,
142.5, 136.3, 135.6, 130.2, 129.6, 126.9, 126.6, 125.8, 120.0, 33.6, 26.3,
24.0, 15.9. IR (NaCl) 3286, 2960, 1651, 1597, 1517, 1411, 1320 cmꢀ1
.
HRMS (ESIþ) calcd for [C18H22NO]þ 268.1696, found 268.1699.
N-(3,5-Bis(trifluoromethyl)phenyl)-2-ethylbenzamide (6):
The title compound was prepared according to the general procedure for
decarbonylation with diethylzinc. Column chromatography with 10:1
hex:EtOAc yielded 6 (158 mg, 0.43 mmol, 97% yield) as a white solid. Rf
N-(3-(Dimethylamino)propyl)-2-ethylbenzamide (12): The
title compound was prepared according to the general procedure for
decarbonylation with diethylzinc. Column chromatography with 10:1
1
0.19. Mp 123ꢀ124 °C. H NMR (400 MHz, CDCl3) δ 8.13 (s, 2H),
7.97 (br s, 1H), 7.64 (s, 1H), 7.44ꢀ7.20 (mult, 4H), 2.83 (qrt, J = 7.4 Hz,
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The Journal of Organic Chemistry
NOTE
hex:EtOAc yielded 12 (85 mg, 0.36 mmol, 81% yield) as a yellow solid.
Rf 0.04. Mp 136ꢀ138 °C. 1H NMR (400 MHz, CDCl3) δ 7.35ꢀ7.10
(mult, 5H), 3.50 (qrt, J = 6.3 Hz, 2H), 2.81 (qrt, J = 7.4 Hz, 2H), 2.44
(t, J = 6.3 Hz, 2H), 2.22 (s, 6H), 1.76 (pent, J = 6.5 Hz, 2H), 1.20 (t, J =
7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.1, 142.2, 136.5, 129.6,
129.3, 126.6, 125.5, 58.3, 45.2, 39.3, 26.3, 26.2, 15.8. IR (NaCl) 3428,
2965, 2869, 1638, 1535, 1543, 1459, 1311 cmꢀ1. HRMS (ESIþ) calcd
for [C14H23N2O]þ 235.1805, found 235.1801.
N-Phenylbiphenyl-2-carboxamide (15): The title compound
was prepared according to the general procedure for decarbonylation
with the in situ generated diarylzinc reagent. Column chromatography
with 9:1 hex:EtOAc yielded 15 (110 mg, 0.40 mmol, 81% yield) as a
white solid. Rf 0.40 (in 2:1 hex:EtOAc). Mp 119ꢀ120 °C. 1H NMR (400
MHz, CDCl3) δ 7.86 (d, J = 7 Hz, 1H), 7.58ꢀ7.31 (mult, 8H),
7.26ꢀ7.16 (mult, 2H), 7.10 (d, J = 7.7 Hz, 2H), 7.04 (t, J = 7.0 Hz,
1H), 6.97 (br s, 1H). 13C NMR (100 MHz, CDCl3) δ 167.1, 139.9,
139.5, 137.5, 135.2, 130.6, 130.3, 129.4, 128.9, 128.8, 128.7, 128.0, 127.8,
124.3, 119.9. IR (NaCl) 3329, 3059, 1660, 1651, 1600, 1537, 1441,
1323 cmꢀ1. HRMS (ESIþ) calcd for [C19H16NO]þ 274.1226, found
274.1220.
1H), 7.46 (t, J = 7.5 Hz, 1H), 7.39 (t, J = 7.3 Hz, 1H), 7.36ꢀ7.29 (mult,
3H), 7.27ꢀ7.05 (mult, 7H), 7.00 (t, J = 7.3 Hz, 1H), 6.88 (br s, 1H), 2.41
(s, 3H). 13C NMR (100 MHz, CDCl3) δ 167.3, 138.9, 137.5, 136.4,
135.3, 130.7, 130.3, 129.4, 129.2, 128.9, 127.8, 126.8, 124.5, 119.9, 15.7.
IR (NaCl) 3383, 2965, 2846, 1658, 1608, 1539, 1432, 1324, 1242 cmꢀ1
.
HRMS (ESIþ) calcd for [C20H18NOS]þ 320.1104, found 320.1093.
N-Phenyl-40-(trifluoromethyl)biphenyl-2-carboxamide
(20): The title compound was prepared according to the general
procedure for decarbonylation with in situ generated diarylzinc reagent.
Column chromatography with 10:1 hex:EtOAc yielded 20 (124 mg, 0.36
mmol, 71% yield) as a white solid. Rf 0.38 (in 2:1 hex:EtOAc). Mp
148 °C dec. 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 7.1 Hz, 1H),
7.63ꢀ7.43 (mult, 6H), 7.37 (d, J = 7.5 Hz, 1H), 7.21ꢀ7.08 (mult, 4H),
7.02 (t, J = 7.3 Hz, 1H), 6.86 (br s, 1H). 13C NMR (100 MHz, CDCl3)
δ 167.0, 143.6, 138.3, 137.3, 135.9, 130.8, 130.0, 129.1, 129.05, 129.0,
128.6, 125.7 (qrt, JCꢀF = 3.7 Hz), 124.8, 124.1 (qrt, JCꢀF = 271 Hz),
122.7, 119.9. IR (NaCl) 2920, 2849, 1650, 1443, 1324, 1119 cmꢀ1
.
HRMS (ESIþ) calcd for [C20H15F3NO]þ 342.1100, found 342.1092.
40-Fluoro-N-phenylbiphenyl-2-carboxamide (21): The title
compound was prepared according to the general procedure for
decarbonylation with in situ generated diarylzinc reagent. Column
chromatography with 10:1 hex:EtOAc yielded 21 (129 mg, 0.44 mmol,
87% yield) as a white solid. Rf 0.34 (in 2:1 hex:EtOAc). Mp
40-Methoxy-N-phenylbiphenyl-2-carboxamide (16): The
title compound was prepared according to the general procedure for
decarbonylation with in situ generated diarylzinc reagent. Column
chromatography with 10:1 hex:EtOAc yielded 16 (121 mg, 0.40 mmol,
78% yield) as a white solid. Rf 0.22 (in 2:1 hex:EtOAc). Mp 143ꢀ144 °C.
1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 7.4 Hz, 1H), 7.51 (dt, J = 7.5,
1.8 Hz, 1H), 7.48ꢀ7.36 (mult, 4H), 7.23 (d, J = 7.9 Hz, 1H), 7.17 (d, J =
8.3 Hz, 2H), 7.05 (t, 7.0 Hz, 1H), 7.00ꢀ6.85 (mult, 4H), 3.82 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 167.3, 159.6, 139.2, 137.7, 135.2, 132.2, 130.6,
130.4, 130.1, 129.6, 128.8, 127.5, 124.4, 119.9, 114.5, 55.4. IR (NaCl) 3380,
2962, 2836, 1653, 1600, 1539, 1437, 1320, 1249 cmꢀ1. HRMS (ESIþ)
calcd for [C20H18NO2]þ 304.1332, found 304.1336.
1
137ꢀ139 °C. H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 7.4 Hz,
1H), 7.58ꢀ7.37 (mult, 5 H), 7.31ꢀ7.05 (mult, 7H), 6.92 (br s, 1H). 13C
NMR (100 MHz, CDCl3) δ 167.2, 162.6 (d, JCꢀF = 248 Hz), 138.45,
137.5, 135.9 (d, JCꢀF = 3.1 Hz), 130.6 (d, JCꢀF = 27 Hz), 130.5, 130.4,
129.3, 129.1, 129.0, 128.0, 124.6, 119.9, 115.9 (d, JCꢀF = 21 Hz). IR
(NaCl) 3282, 3131, 3063, 1658, 1650, 1537, 1514, 1440, 1323, 1224 cmꢀ1
.
HRMS (ESIþ) calcd for [C19H15FNO]þ 292.1132, found 292.1136.
40-Methyl-N-phenylbiphenyl-2-carboxamide (22): The title
compound was prepared according to the general procedure for
decarbonylation with in situ generated diarylzinc reagent. Column
chromatography with 9:1 hex:EtOAc yielded 22 (141 mg, 0.49 mmol,
96% yield) as a white solid. Rf 0.39 (in 2:1 hex:EtOAc). Mp
30-Methoxy-N-phenylbiphenyl-2-carboxamide (17): The
title compound was prepared according to the general procedure for
decarbonylation with in situ generated diarylzinc reagent. Column
chromatography with 10:1 hex:EtOAc yielded 17 (60 mg, 0.20 mmol,
39% yield) as an off white solid. Rf 0.15 (in 2:1 hex:EtOAc). Mp
104ꢀ105 °C. 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 7.7 Hz, 1H),
7.46 (dt, J = 7.3, 1.8 Hz, 1H), 7.40 (dt, J = 7.5, 1.8 Hz, 1H), 7.36 (d, J =
7.7 Hz, 1H), 7.28 (t, J = 8.2 Hz, 1H), 7.15 (d, J = 7.8 Hz, 2H), 7.07 (d, J =
8.1 Hz, 2H), 7.01ꢀ6.83 (mult, 5H), 3.68 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 167.1, 160.0, 141.4, 139.4, 137.6, 135.2, 130.6, 130.2, 130.0,
129.6, 128.8, 128.0, 124.4, 121.2, 120.0, 114.2, 114.1, 55.4. IR (NaCl)
3380, 3065, 2957, 2848, 1659, 1650, 1537, 1440, 1322 cmꢀ1. HRMS
(ESIþ) calcd for [C20H18NO2]þ 304.1332, found 304.1330.
1
148ꢀ149 °C. H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 7.0 Hz,
1H), 7.52, (dt, J = 7.5, 1.3 Hz, 1H), 7.45 (dt, J = 7.6, 1.3 Hz, 1H), 7.41
(d, J = 7.5 Hz, 1H), 7.37 (d, J = 8.0 Hz, 2H), 7.27ꢀ7.20 (mult, 4H), 7.13
(d, J = 7.7 Hz, 2H), 7.05 (t, J = 7.3 Hz, 1H), 6.95 (br s, 1H), 2.39 (s, 3H).
13C NMR (100 MHz, CDCl3) 167.2, 139.6, 137.9, 137.6, 137.0, 135.2,
130.6, 130.4, 129.7, 129.5, 128.8, 128.7, 127.7, 124.3, 119.9, 21.2. IR
(NaCl) 3282, 3053, 3020, 2921, 1656, 1599, 1536, 1438, 1322 cmꢀ1
.
HRMS (ESIþ) calcd for [C20H18NO]þ 288.1383, found 288.1382.
40-(Dimethylamino)-N-phenylbiphenyl-2-carboxamide
(23): The title compound was prepared according to the general
procedure for decarbonylation with in situ generated diarylzinc reagent.
Column chromatography with 10:1 hex:EtOAc yielded 23 (155 mg, 0.49
mmol, 96% yield) as a yellow solid. Rf 0.55 (in 2:1 hex:EtOAc). Mp
158 °C. 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 7.2 Hz, 1H), 7.42,
(t, J = 7.5 Hz, 1H), 7.33 (t, J = 7.2 Hz, 2H), 7.27 (d, J = 8.6 Hz, 2H),
7.20ꢀ7.04 (mult, 2H), 7.02 (br s, 1H), 6.97 (t, J = 7.2 Hz, 1H), 6.69
(d, J = 8.6 Hz, 2H), 2.90 (s, 6H). 13C NMR (100 MHz, CDCl3) δ 167.5,
150.3, 139.8, 137.8, 134.7, 130.6, 130.3, 129.76, 129.74, 128.7, 127.2,
126.9, 124.1, 120.1, 112.7, 40.4. IR (NaCl) 3299, 3059, 2889, 1659,
1611, 1529, 1440, 1320 cmꢀ1. HRMS (ESIþ) calcd for [C21H21N2O]þ
317.1648, found 317.1652.
20-Methoxy-N-phenylbiphenyl-2-carboxamide (18): The
title compound was prepared according to the general procedure for
decarbonylation with in situ generated diarylzinc reagent. Column
chromatography with 9:1 hex:EtOAc yielded 18 (111 mg, 0.37 mmol,
72% yield) as a white solid. Rf 0.18 (in 2:1 hex:EtOAc). Mp 128 °C. 1H
NMR (400 MHz, CDCl3) δ 7.85 (d, J = 7.5 Hz, 1H), 7.47 (dt, J = 7.5, 1.7
Hz, 1H), 7.40 (dt, J = 7.4, 1.5 Hz, 1H), 7.34ꢀ7.22 (mult, 4H),
7.18ꢀ7.06 (mult, 4H), 7.02 (t, J = 7.4, 1H), 6.95 (tt, J = 7.1, 1.2 Hz,
1H), 6.84 (d, J = 8.4 Hz, 1H), 3.59 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ 166.8, 156.4, 137.9, 136.0, 135.8, 131.0, 130.7, 130.1, 129.9,
129.0, 127.9, 127.0, 124.0, 121.3, 119.5, 111.1, 55.6. IR (NaCl) 3391,
2959, 2871, 1777, 1686, 1599, 1531, 1365, 1248 cmꢀ1. HRMS (ESIþ)
calcd for [C20H18NO2]þ 304.1332, found 304.1334.
30-Methyl-N-phenylbiphenyl-2-carboxamide (24): The title
compound was prepared according to the general procedure for
decarbonylation with in situ generated diarylzinc reagent. Column
chromatography with 10:1 hex:EtOAc yielded 24 (110 mg, 0.38 mmol,
75% yield) as a yellow oil. Rf 0.45 (in 2:1 hex:EtOAc). 1H NMR (400
MHz, CDCl3) δ 7.81 (d, J = 7.3 Hz, 1H), 7.49ꢀ7.09 (mult, 10H),
7.05ꢀ6.93 (mult, 3H), 2.26 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ 167.1, 139.9, 139.7, 138.7, 137.5, 135.1, 130.6, 130.3, 129.6, 129.5,
40-(Methylthio)-N-phenylbiphenyl-2-carboxamide (19):
The title compound was prepared according to the general procedure
for decarbonylation with in situ generated diarylzinc reagent. Column
chromatography with 9:1 hex:EtOAc yielded 19 (163 mg, 0.47 mmol,
93% yield) as a white solid. Rf 0.28 (in 2:1 hex:EtOAc). Mp
1
155ꢀ156 °C. H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.8 Hz,
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The Journal of Organic Chemistry
NOTE
128.84, 128.81, 128.76, 127.8, 125.9, 124.3, 120.0, 21.3. IR (NaCl) 3323,
3029, 1651, 1600, 1537, 1440, 1323 cmꢀ1. HRMS (ESIþ) calcd for
[C20H18NO]þ 288.1383, found 288.1385.
(2) For a review, see: Goossen, L. J.; Rodríguez, N.; Goossen, K.
Angew. Chem., Int. Ed. 2008, 47, 3100.
(3) Goossen, L. J.; Deng, G.; Levy, L. M. Science 2006, 313, 662.
(4) Baudoin, O. Angew. Chem., Int. Ed. 2007, 46, 1373 and references
cited therein.
(5) Zhang, F.; Greaney, M. F. Org. Lett. 2010, 12, 4745.
(6) Goossen, L. J.; Rodriguez, N.; Lange, P.; Linder, C. Angew.
Chem., Int. Ed. 2010, 49, 1111.
(7) Mohr, J. T.; Nishimata, T.; Behenna, D. C.; Stoltz, B. M. J. Am.
Chem. Soc. 2006, 128, 11348.
N-Phenyl-30,50-bis(trifluoromethyl)biphenyl-2-carboxa-
mide (25): The title compound was prepared according to the general
procedure for decarbonylation with in situ generated diarylzinc reagent.
Column chromatography with 10:1 hex:EtOAc yielded 25 (158 mg, 0.39
mmol, 77% yield) as an off-white solid. Rf 0.38 (in 2:1 hex:EtOAc). Mp
1
128ꢀ129 °C dec. H NMR (400 MHz, CDCl3) δ 7.86 (s, 2H), 7.77
(s, 1H), 7.64 (d, J = 7.1 Hz, 1H), 7.57ꢀ7.36 (mult, 4H), 7.28ꢀ7.15
(mult, 4H), 7.04 (br s, 1H). 13C NMR (100 MHz, CDCl3) δ 166.8,
142.0, 137.0, 136.2, 131.9 (qrt, JCꢀF = 36 Hz), 130.9, 130.4, 129.0, 128.8,
128.3, 125.0, 123.3 (qrt, JCꢀF = 273 Hz), 121.5 (mult), 120.1, 119.7. IR
(NaCl) 3473, 2924, 1651, 1602, 1541, 1379, 1278 cmꢀ1. HRMS (ESIþ)
calcd for [C21H14F6NO]þ 410.0974, found 410.0978.
(8) Trost, B. M.; Xu, J.; Schmidt, T. J. Am. Chem. Soc. 2009,
131, 18343.
(9) Tsuji, J.; Ohno, K. Tetrahedron Lett. 1965, 6, 3969.
(10) Kreis, M.; Palmelund, A.; Bunch, L.; Madsen, R. Adv. Synth.
Catal. 2006, 348, 2148.
(11) Iwai, T.; Fujihara, T.; Tsuji, Y. Chem. Commun. 2008, 6215.
(12) Guo, X.; Wang, J.; Li, C.-J. J. Am. Chem. Soc. 2009, 131, 15092.
(13) Varela, J. A.; Gonzꢀalez-Rodriguez, C.; Rubín, S. G.; Castedo, L.;
Saꢀa, C. J. Am. Chem. Soc. 2006, 128, 9576.
(14) Gonzꢀalez-Rodriguez, C.; Varela, J. A.; Castedo, L.; Saꢀa, C. J. Am.
Chem. Soc. 2007, 129, 12916.
(15) Goossen, L. J.; Rodríguez, N.; Chem. Commun. 2004, 724.
(16) Goossen, L. J.; Paetzold, J. Angew. Chem., Int. Ed. 2004, 43, 1095.
(17) Stephan, M. S.; Teunissen, A. J. J. M.; Verzijl, G. K. M.; de Vries,
J. G. Angew. Chem., Int. Ed. 1998, 37, 662.
Ethyl 3-(2-(Phenylcarbamoyl)phenyl)propanoate (27):
The diorganozinc reagent, bis(3-ethoxy-3-oxopropyl)zinc, was prepared
according to literature precedent and used without further purification39
in the general procedure for decarbonylation with in situ generated
diarylzinc reagent. Column chromatography with 50:1 CH2Cl2:Et2O
yielded 27 (126 mg, 0.42 mmol, 83% yield) as a yellow oil. Rf 0.25. 1H
NMR (400 MHz, CDCl3) δ 8.72 (br s, 1H), 7.63 (d, J = 8.1 Hz, 2H),
7.47 (d, J = 7.6, 1H), 7.36ꢀ7.15 (mult, 5H), 7.07 (t, J = 7.3 Hz, 1 H),
4.03 (qrt, J = 7.3 Hz, 2H), 3.05 (t, J = 6.9 Hz, 2H), 2.76 (t, J = 6.9 Hz,
2H), 1.14 (t, J = 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 173.8,
168.0, 138.4, 137.7, 137.2, 130.3, 129.2, 129.0, 127.9, 126.6, 126.5, 124.3,
119.9, 60.8, 35.0, 27.2, 14.1. IR (NaCl) 3327, 3061, 2976, 2932, 1729,
1712, 1649, 1599, 1535, 1430 cmꢀ1. HRMS (ESIþ) calcd for
[C18H20NO3]þ 298.1438, found 298.1432.
(18) O’Brien, E. M.; Bercot, E. A.; Rovis, T. J. Am. Chem. Soc. 2003,
125, 10498.
(19) Kajita, Y.; Kurahashi, T.; Matsubara, S. J. Am. Chem. Soc. 2008,
130, 17226.
(20) Kajita, Y.; Matsubara, S.; Kurahashi, T. J. Am. Chem. Soc. 2008,
130, 6058.
2-Butyl-N-phenylbenzamide (28): The diorganozinc reagent
was prepared by addition of nBuLi (2 equiv) with ZnCl2 in THF at 0 °C
and was used in the general procedure for decarbonylation with in situ
generated diarylzinc reagent. Column chromatography with 9:1 hexane:
EtOAc yielded 28 (88 mg, 0.35 mmol, 69% yield) as a white solid. Rf 0.34 in
(21) Fujiwara, K.; Kurahashi, T.; Matsubara, S. Org. Lett. 2010,
12, 4548.
(22) For example, see: Tsunoda, T.; Yamazaki, A.; Iwamoto, H.;
Sakamoto, S. Org. Process Res. Dev. 2003, 7, 883.
(23) Bercot, E. A.; Rovis, T. J. Am. Chem. Soc. 2002, 124, 174.
(24) Bercot, E. A.; Rovis, T. J. Am. Chem. Soc. 2005, 127, 247.
(25) A similar transformation with carboxylic anhydrides, but with
limited diorganozinc scope, has been described. See ref 18.
(26) A more comprehensive list of optimization efforts is included in
the Supporting Information.
(27) The two isomeric products were obtained in a 1:1.2 ratio and
identified as decarbonylative alkylation products by mass spectrometry.
Conclusive identification of the structure of the isomers in the mixture
was unsuccessful.
1
4:1 hexane:EtOAc. Mp 107ꢀ108 °C. H NMR (400 MHz, CDCl3)
δ 7.59 (d, J = 7.9 Hz, 2H), 7.48ꢀ7.19 (mult, 6H), 7.14 (t, J = 7.2 Hz,
1H), 2.81 (t, J= 7.9 Hz, 2H), 1.64 (br s, 1H), 1.61 (mult, 2H), 1.35 (hex, J=
7.5 Hz, 2H), 0.88 (t, J = 7.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) 168.2,
141.3, 138.0, 136.5, 130.4, 130.2, 129.2, 126.7, 125.9, 124.6, 119.9, 33.9,
32.9, 22.6, 13.9. IR (NaCl) 3273, 2956, 2922, 2853, 1653, 1598, 1534, 1438,
1323. HRMS (ESIþ) calcd for [C17H20NO]þ 254.1539, found 254.1534.
’ ASSOCIATED CONTENT
(28) D€oring, M.; Kosemund, D.; Uhlig, E.; G€orls, H. Z. Anorg. Allg.
Chem. 1993, 619, 1512.
(29) Sano, K.; Yamamoto, T.; Yamamoto, A. Bull. Chem. Soc. Jpn.
1984, 57, 2741.
(30) Johnson, J. B.; Bercot, E. A.; Rowley, J. M.; Coates, G. W.;
Rovis, T. J. Am. Chem. Soc. 2007, 129, 2718.
S
Supporting Information. Experimental procedures and
b
characterization material for all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
(31) Hoberg, H.; Guhl, D. J. Organomet. Chem. 1989, 375, 245.
(32) For oxygen containing analogues, see: Castan~o, A. M.; Echa-
varren, A. M. Organometallics 1994, 13, 2262.
(33) Sch€onecker, B.; Walther, D.; Fischer, R.; Nestler, B.; Br€aunlich,
G.; Eibisch, H.; Droescher, P. Tetrahedron Lett. 1990, 31, 1257.
(34) NiꢀCO bond strengths have been estimated to be anywhere
from 28.3 to 47.1 kcal/mol; see: Sunderlin, L. S.; Wang, D.; Squires, R. R.
J. Am. Chem. Soc. 1992, 114, 2788.
(35) Li, J.; Schreckenbach, G.; Ziegler, T. J. Am. Chem. Soc. 1995,
117, 486.
(36) Bilyard, K. G.; Garratt, P. J.; Hunter, R.; Lete, E. J. Org. Chem.
1982, 47, 4731.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: jjohnson@hope.edu.
’ ACKNOWLEDGMENT
We thank the Camille and Henry Dreyfus Foundation and the
Research Corporation for support. J.B.J. also thanks the Towsley
Foundation for support. We also gratefully acknowledge NSF
funding for instrumentation (CHE-0922623).
(37) Kobs, U.; Neumann, W. P. Chem. Ber. 1990, 123, 2191.
(38) Smith, P. A. S. J. Am. Chem. Soc. 1954, 76, 431.
(39) Zhang, Y.; Rovis, T. J. Am. Chem. Soc. 2004, 126, 15964.
’ REFERENCES
(1) de Meijere, A.; Diederich, F. Metal-catalyzed Cross-Coupling
Reactions, 2nd ed.; Wiley-VCH: Weinheim, Germany, 2004.
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