Rhodium-catalyzed intramolecular aminocarbonylation of aryl halides using aldehydes as a source of carbon monoxide

Article abstract of DOI:10.1246/cl.2003.154

The reaction of N-Ts-(2-bromophenyl)alkylamines with aldehydes in the presence of a catalytic amount of a rhodium complex results in the intramolecular aminocarbonylation of the aryl halides to give five-, six-, and seven-membered benzolactams.

Full text of DOI:10.1246/cl.2003.154

154
Chemistry Letters Vol.32, No.2 (2003)
Rhodium-Catalyzed Intramolecular Aminocarbonylation of Aryl Halides
Using Aldehydes as a Source of Carbon Monoxide
Tsumoru Morimoto,ꢀ Masahiko Fujioka, Koji Fuji, Ken Tsutsumi, and Kiyomi Kakiuchiꢀ
Graduate School of Materials Science, Nara Institute of Science and Technology (NAIST), Takayama, Ikoma, Nara 630-0192
(Received November 13, 2002; CL-020970)
The reaction of N-Ts-(2-bromophenyl)alkylamines with
but to the aminocarbonylation of aryl halides as well, which
involves the oxidative addition of an aryl halide to the rhodium
metal.11
aldehydes in the presence of a catalytic amount of a rhodium
complex results in the intramolecular aminocarbonylation of the
aryl halides to give five-, six-, and seven-membered benzolac-
tams.
Catalytic carbonylation reactions using carbon monoxide
have found widespread use in many areas of organic synthesis.1
The use of highly poisonous carbon monoxide, however, is
essential for the carbonylation reaction to proceed. Recently,
carbonylation processes, in which gaseous carbon monoxide is
not required, have been developed, to solve this drawback. It has
been reported that palladium-catalyzed carbonylative coupling
reactions of aryl halides with alcohols and amines can be carried
out using carbon monoxide generated in situ by the treatment of
formate2 or formamide3 with strong bases. Alper has also
reported on the palladium-catalyzed carbonylation of organic
halides using chloroform and aqueous alkali.4 A palladium
carbonyl complex formed from its noncarbonyl precursor and the
dichlorocarbene, generated in situ from the reaction of chloro-
form and aqueous alkali, plays a key role in this carbonylation.
Owing to the requirement of a strong base, these methods are
limited to applications of carbonylations which permit or require
the presence of a base.2{4 Larhed reported that the in situ
liberation of carbon monoxide from Mo(CO)6 under neutral
conditions could be applied to the catalytic aminocarbonylation
of aryl halides with amines, but the reaction required a
stoichiometric amount of Mo(CO)6.5 Simonato utilized carbon
monoxide, generated by the thermolysis of formic acid, which
requires a high temperature (190 ꢁC), to achieve the hydrocar-
boxylation of cyclohexene.6
When the reaction of 1 was carried out under the same
conditions using 1 atm of carbon monoxide instead of C6F5CHO,
87% of 2 was obtained, although a longer reaction time (18 h) was
required for the complete consumption of 1 (Eq 1). These results
show that the presence of excess carbon monoxide appears to
inhibit the catalysis.
Some other rhodium complexes, such as RhCl(CO)(PPh3)2
(86%), [RhCl(cod)]2/dppe (51%), and [RhCl(cod)]2/dppb (32%),
also showed catalytic activity. Among other aldehydes examined
as a source of carbon monoxide, the use of cinnamaldehyde (5
equiv.) and paraformaldehyde (10 equiv.) resulted in the forma-
tion of 2 in 93% and 69% yields, respectively, although only a
trace amount of 2 was obtained in the case of benzaldehyde, p-
anisaldehyde, p-trifluoromethylbenzaldehyde, and decanal.
When the substituent on the nitrogen atom was changed to Boc,
the corresponding benzolactam was obtained in 22% yield along
with 63% of unreacted substrate (54 h), while no lactams were
obtained from the reaction of the substrates having other
substituents, such as H, Ac, Bn, and p-MeOC6H4. A high
temperature is not essential for the reaction to proceed; 59% of 2
was obtained at 110 ꢁC for a 19 h reaction.
Although the mechanism for the intramolecular amino-
carbonylation of an aryl halide is currently unclear, a possible
mechanism is shown in Scheme 1. This mechanism includes (a)
decarbonylation of the aldehyde by the rhodium(I) complex to
form the rhodium(I) carbonyl C, (b) oxidative addition of the aryl
halide to rhodium(I) to give arylrhodium(III) halide D,12 (c)
insertion of CO into the rhodium–carbon bond to give acylrho-
We previously reported on the first use of aldehydes as a
source of carbon monoxide in carbonylation reactions,7 in the
catalytic Pauson–Khand-type reaction of enynes, in which
aldehydes were used as a source of carbon monoxide.8 This
development of a CO gas-free carbonylation method under
neutral and mild conditions prompted us to explore its general
use. We wish to describe herein a novel carbonylation system, in
which aldehydes are used as a source of carbon monoxide, which
is applicable to the intramolecular animocarbonylation of aryl
halides leading to the production of benzolactams.9
The reaction of N-Ts-2-bromobenzylamine (1, 0.25 mmol)
with pentafluorobenzaldehyde (0.50 mmol) and K2CO3
(0.50 mmol) in xylene (2 cm3) at 130 ꢁC in the presence of
[RhCl(cod)]2 (0.00625 mmol) and 1,3-bis(diphenylphosphino)-
propane (dppp, 0.0125 mmol) afforded the benzolactam 2 in 92%
yield (Eq 1).10 This demonstrates that the carbonylation system,
which consists of the rhodium catalyst and an aldehyde, is
applicable, not only to the carbonylative cyclization of enynes,7
Scheme 1. Possible mechanism.
Copyright ꢀ 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.2 (2003)
155
dium(III) complex E, and (d) reductive cleavage of the acyl-
rhodium bond to produce benzolactam 2 and regeneration the
rhodium(I) complex. In the reaction using C6F5CHO, cinnamal-
dehyde, and paraformaldehyde, decarbonylation of the acylrho-
dium(III) A to R-rhodium(III) B would readily occur due to
thermodynamic stability of B (R = C6F5, Ph–CH=CH, and H),
and therefore, optimal carbonylation catalysis would result.
Replacement of the Br atom in 1 by a Cl atom also resulted in
the formation of 2 in high yields both with pentafluorobenzalde-
hyde and with cinnamaldehyde as the source of carbon monoxide
(Eq 2).
reaction affords a new protocol for the synthesis of benzolactams.
We thank Ms. Yoshiko Nishiura for assistance in obtaining
HRMS. T.M. thanks the Inoue Research Award for Young
Scientists from the Inoue Foundation for Science.
References and Notes
1
H. M. Colquhoun, D. J. Thompson, and M. V. Twigg, ‘‘Carbonylation,’’
Plenum Press, New York (1991).
2
J.-F. Carpentier, Y. Castanet, J. Brocard, A. Mortreux, and F. Petit,
Tetrahedron Lett., 32, 4705 (1991); J.-F. Carpentier, Y. Castanet, J.
Brocard, A. Mortreux, and F. Petit, Tetrahedron Lett., 33, 2001 (1992).
Y. Wan, M. Alterman, M. Larhed, and A. Hallberg, J. Org. Chem., 67,
6232 (2002).
3
4
5
V. V. Grushin and H. Alper, Organometallics, 12, 3846 (1993).
N.-F. K. Kaiser, A. Hallberg, and M. Larhed, J. Comb. Chem., 4, 109
(2002).
6
7
8
J.-P. Simonato, T. Walter, and P. Metivier, J. Mol. Catal. A: Chem., 171,
91 (2001).
T. Morimoto, K. Fuji, K. Tsutsumi, and K. Kakiuchi, J. Am. Chem. Soc.,
124, 3806 (2002).
Recently, Shibata et al. reported the rhodium-catalyzed Pauson-Khand-
type reaction of enynes with aldehyde as a source of carbon monoxide
without solvent. T. Shibata, N. Toshida, and K. Takagi, Org. Lett., 4,
1619 (2002); T. Shibata, N. Toshida, and K. Takagi, J. Org. Chem., 67,
7446 (2002).
For a representative report of the catalytic intramolecular aminocarbo-
nylation of aryl halides, see: M. Mori, K. Chiba, and Y. Ban, J. Org.
Chem., 43, 1684 (1978).
The carbonylation reaction described here could be applied to
the syntheses of six- and seven-membered benzolactams. Under
conditions similar to Eq 2, the reactions of N-Ts-2-(2-bromo-
phenyl)ethylamine (4) with pentafluorobenzaldehyde and cinna-
maldehyde gave the six-membered benzolactam 513 in 84% and
93% yields, respectively (Eq 3). In the case of N-Ts-3-(2-
bromophenyl)propylamine (6), pentafluorobenzaldehyde served
as a more efficient source of carbon monoxide than cinnam-
aldehyde, in contrast to the above reactions; the reaction of 6 with
pentafluorobenzaldehyde for 48 h afforded 66% of the seven-
membered benzolactam 714 along with 16% of recovered 6,
while, with cinnamaldehyde, 17% of 7 was obtained and 77% of 6
was recovered (Eq 4).
9
10 (2). White solid; mp 216–218 ꢁC; Rf 0.29 (hexane/AcOEt = 2/1); 1H
NMR (CDCl3) d 2.42 (s, 3H), 4.91 (s, 2H), 7.34 (d, J ¼ 8:0 Hz, 2H),
7.47 (t, J ¼ 8:0 Hz, 1H), 7.49 (d, J ¼ 8:0 Hz, 1H), 7.64 (t, J ¼ 8:0 Hz,
1H), 7.80 (d, J ¼ 8:0 Hz, 1H), 8.03 (d, J ¼ 8:0 Hz, 2H); 13CNMR
(CDCl3) d 21.62, 49.80, 123.30, 124.98, 128.09, 128.77, 129.71,
130.16, 133.82, 135.35, 140.97, 145.19, 166.06; IR (KBr, cmÀ1) 1724,
1363, 1174, 1088; MS m=z (relative intensity, %) 223 (Mþ–SO2, 100);
HRMS-FAB (m=z): [M+H]þ calcd for C15H14NO3S, 288.0694; found,
288.0693.
11 For rhodium-catalyzed carbonylation reactions of aryl halides using
carbon monoxide, see: T. Mizuno and H. Alper, J. Mol. Catal. A: Chem.,
123, 21 (1997); C. Buchan, N. Hamel, J. B. Woell, and H. Alper, J.
Chem. Soc., Chem. Commun., 1986, 167.
12 For rhodium-catalyzedreactionsinvolvingthe oxidativeadditionofaryl
halides to rhodium metal, see: Ref. 11; T. Ishiyama and J. Hartwig, J.
Am. Chem. Soc., 122, 12043 (2000); K. M. Hossain and K. Takagi,
Chem. Lett., 1999, 1241; S. Iyer, J. Organomet. Chem., 490, C27 (1995).
13 (5). White solid; mp 132–133 ꢁC; Rf 0.24 (hexane/AcOEt = 2/1); 1H
NMR (CDCl3) d 2.42 (s, 3H), 3.13 (t, J ¼ 6:0 Hz, 2H), 4.23 (t,
J ¼ 6:0 Hz, 2H), 7.22 (d, J ¼ 8:0 Hz, 1H), 7.31(t, J ¼ 8:0 Hz, 1H), 7.33
(d, J ¼ 8:5 Hz, 2H), 7.47 (t, J ¼ 8:0 Hz, 1H), 7.98 (d, J ¼ 8:5 Hz, 2H),
7.99 (d, J ¼ 8:0 Hz, 1H); 13C NMR (CDCl3) d 21.61, 28.89, 44.68,
127.33, 127.39, 128.14, 128.52, 129.12, 129.38, 133.45, 136.10, 139.21,
144.70, 163.39; IR (KBr, cmÀ1) 1686, 1598, 1351, 1243, 1088; MS m=z
(relative intensity, %) 237 (Mþ–SO2, 65), 118 (100); HRMS-FAB
(m=z): [M+H]þ calcd for C16H16NO3S, 302.0851; found, 302.0850.
14 (7). White solid; mp 117–118 ꢁC; Rf 0.28 (hexane/ether = 1/1); 1H
NMR (CDCl3) d 2.17 (quint, J ¼ 6:5 Hz, 2H), 2.43 (s, 3H), 2.84 (t,
J ¼ 6:5 Hz, 2H), 3.82 (t, J ¼ 6:5 Hz, 2H), 7.15 (d, J ¼ 7:5 Hz, 1H), 7.28
(t, J ¼ 7:5 Hz, 1H), 7.34 (d, J ¼ 8:0 Hz, 2H), 7.42 (t, J ¼ 7:5 Hz, 1H),
7.60 (d, J ¼ 7:5 Hz, 1H), 8.01 (d, J ¼ 8:0 Hz, 2H); 13C NMR (CDCl3) d
21.55, 29.19, 29.61, 44.77, 127.11, 128,64, 128.82, 129.32, 129.38,
132.57, 133.88, 136.04, 137.93, 144.67, 170.12; IR (KBr, cmÀ1) 1692,
1354, 1167, 1001; MS m=z (relative intensity, %) 251 (Mþ–SO2, 52),
144 (100); HRMS-FAB (m=z): [M+H]þ calcd for C17H18NO3S,
316.1007; found, 316.1000.
In conclusion, we describe here the first catalytic intramo-
lecular aminocarbonylation of an aryl halide using aldehydes as
the source of carbon monoxide. The CO gas-free carbonylation
system, consisting of the rhodium(I) complex and an aldehyde as
a source of carbon monoxide, has also proven to be effective for
carbonylation reactions under basic conditions. Thus, this
carbonylation system has a wider scope of application than other
CO gas-free carbonylations reported to date, and has the potential
to become a new, powerful tool for carbonylation. The present