Synthesis of dibenzo[ b, f ][1,4]oxazepin-11(10 H)-ones via intramolecular cyclocarbonylation reactions using PdI2/Cytop 292 as the catalytic system

Article abstract of DOI:10.1021/jo101312z

Figure presented. The intramolecular cyclocarbonylation of substituted 2-(2-iodophenoxy)anilines was catalyzed by PdI₂ and 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phospha-adamantane (Cytop 292) in an efficient manner. A series of substituted dibenzo[b,f][1,4]oxazepin-11(10H)- ones were prepared in good yields under mild reaction conditions.

Full text of DOI:10.1021/jo101312z

pubs.acs.org/joc
conventional methods via multistep syntheses, the reactions
Synthesis of Dibenzo[b, f ][1,4]oxazepin-11(10H)-ones
via Intramolecular Cyclocarbonylation Reactions
Using PdI2/Cytop 292 as the Catalytic System
often require rather stringent reaction conditions, and low yields
of the products were obtained in some cases.3 Therefore, it
seems desirable to develop a general and effective route to
synthesize medium-sized ring heterocycles.
Qian Yang,† Hong Cao,† Al Robertson,‡ and
Howard Alper*,†
The transition-metal-catalyzed carbonylation reaction is
an effective tool for organic synthesis. It provides convenient
and direct access to a large number of heterocycles.4 Cata-
lysts with added bulky, electron-rich phosphine ligands are
useful for some of these applications.5 During the past
several years, a novel class of tertiary phosphine ligands
based on a phospha-adamantane framework were success-
fully utilized for various palladium-catalyzed reactions6 and
for the rhodium-catalyzed hydroformylation of unsaturated
esters.7 They are readily made, stable to air, and inert to
decomposition and have stereoelectronic properties similar
to those of bulky phosphines. Furthermore, the ability to
alter the aryl moiety of the phospha-adamantane ligand
affords the opportunity to sterically and electronically fine-
tune the phosphonite and hence generates transition-metal
complexes with different catalytic potentials.
†Centre for Catalysis Research and Innovation,
Department of Chemistry, University of Ottawa, 10 Marie
Curie, Ottawa, Ontario K1N 6N5, Canada, and
‡Cytec Canada, Inc., 9061 Garner Road, Niagara Falls,
Ontario L2E 6S5, Canada
howard.alper@uottawa.ca
Received July 4, 2010
In 2005, a publication from our group demonstrated that
palladium-complexed dendrimers supported on silica are
efficient catalysts for the synthesis of medium-sized oxygen-,
nitrogen-, or sulfur-containing heterocycles (Scheme 1).8 In
light of this research, we investigated the intramolecular
cyclocarbonylation reactions of substituted 2-(2-iodophenoxy)-
anilines to evaluate and compare the in situ generated palla-
dium(II)-1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phospha-
adamantane (Cytop 292, Figure 1) catalytic system with the
The intramolecular cyclocarbonylation of substituted 2-(2-
iodophenoxy)anilines was catalyzed by PdI2 and 1,3,5,7-
tetramethyl-6-phenyl-2,4,8-trioxa-6-phospha-adamantane
(Cytop 292) in an efficient manner. A series of substituted
dibenzo[b,f][1,4]oxazepin-11(10H)-ones were prepared in
good yields under mild reaction conditions.
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Medium-sized heterocycles, especially seven- and eight-
membered ring compounds, are receiving significant atten-
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[b,e][1,4]diazepin-11-one and dibenzo[b,e][1,4]diazepine deriva-
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DOI: 10.1021/jo101312z
r
Published on Web 08/26/2010
J. Org. Chem. 2010, 75, 6297–6299 6297
2010 American Chemical Society

Yang et al.
JOCNote
TABLE 2. Pd-Catalyzed Intramolecular Cyclocarbonylation of Substi-
tuted 2-(2-Iodophenoxy)anilines Using PdI2/Cytop 292 as Catalytic Systema
FIGURE 1. Structure of 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-
phospha-adamantane (Cytop 292).
SCHEME 1. Palladium-Complexed Dendrimers on Silica-
Catalyzed Intramolecular Carbonylation Reactions
TABLE 1. Pd-Catalyzed Intramolecular Cyclocarbonylation of 2-(2-
Iodophenoxy)aniline Using Different Catalytic Systemsa
aReaction conditions: substrate (1 mmol), PdI2 (2 mol %), Cytop
292 (4.5 mol %), iPr2NEt (1.5 mmol), toluene (5 mL), CO (15 psi), 80 °C,
20 h. bIsolated yield.
model substrate to perform the intramolecular cyclocarbo-
nylation reaction under different reaction conditions. The
results are shown in Table 1.
catalyst
loading
(mol %) CO (psi)
entry
catalyst
base
yield (%)b
1
Pd(OAc)2/Cytop 292
PdCl2/Cytop 292
Pd(PPh3)2Cl2/Cytop 292
Pd2(dba)3/Cytop 292
PdI2/Cytop 292
5
5
5
5
5
5
5
5
5
5
5
1
2
100
100
100
100
100
100
100
100
100
100
15
iPr2NEt
iPr2NEt
iPr2NEt
iPr2NEt
iPr2NEt
iPr2NEt
iPr2NEt
iPr2NEt
DBU
iPr2NEt
iPr2NEt
iPr2NEt
iPr2NEt
86
96
87
87
99
tr
2
3
4c
5
The results in Table 1 show that the intramolecular
cyclocarbonylation reaction of 2-(2-iodophenoxy)aniline
can be performed with different catalytic systems. With
Pd(OAc)2 or PdCl2 as the catalyst and Cytop 292 as the
ligand, the desired product was obtained in 86% and 96%
isolated yields, respectively (Table 1, entries 1 and 2). When
the reaction was catalyzed by Pd(PPh3)2Cl2/Cytop 292 or
Pd2(dba)3/Cytop 292, the product was isolated in 87% yield
in both cases, but in the case of Pd2(dba)3/Cytop 292, 2-(2-
iodophenoxy)aniline was not fully consumed (Table 1, en-
tries 3 and 4). We were pleased to observe that the yield of the
product was increased to 99% when PdI2 /Cytop 292 was
6
7d
Pd(PCy3)2Cl2/Cytop 292
PdI2/PPh3
PdI2/dppb
75
tr
8
9
PdI2/Cytop 292
78
84
99
82
99
i
10e PdI2/Cytop 292
11
12c PdI2/Cytop 292
13 PdI2/Cytop 292
aReaction conditions: 2-(2-iodophenoxy)aniline (1 mmol), Pr2NEt
or DBU (1.5 mmol), toluene or THF (5 mL), 80 °C, 20 h. bIsolated yield.
cSubstrate was not completely consumed. d20% substrate was recov-
ered. eTHF was used as solvent.
PdI2/Cytop 292
15
15
i
dendrimer-palladium catalytic system for the intramolecular
cyclocarbonylation reaction.
2-(2-Iodophenoxy)aniline was prepared from 1-fluoro-2-
nitrobenzene according to the literature (eq 1)8 and used as a
used as the catalytic system and Pr2NEt as the base under
100 psi CO pressure and 80 °C in toluene (Table 1, entry 5). In
contrast, when Pd(PCy3)2Cl2/Cytop 292 was used as the
catalyst, only trace quantities of the product was formed
6298 J. Org. Chem. Vol. 75, No. 18, 2010

Yang et al.
JOCNote
(Table 1, entry 6). Thus PdI2 was chosen as the metal catalyst
for further investigations. When PdI2 was used as the catalyst
and PPh3 was used as the ligand instead of Cytop 292, the
yield decreased from 99% to 75% (Table 1, entry 7). Using
dppb as the ligand afforded only trace amounts of the
product (Table 1, entry 8). Running the reaction using
that previously reported,8 as it uses a simple catalytic system,
and mild reaction conditions.
The bulky Cytop 292 ligand shows distinct advantages
over some other commonly applied phosphanes for the
intramolecular cyclocarbonylation of substituted 2-(2-iodo-
phenoxy)anilines in terms of the reaction efficiency. With
simple PdI2/Cytop 292 as the catalytic system, a series of
substituted dibenzo[b, f ][1,4]oxazepin-11(10H)-ones were pre-
pared in good yields.
i
DBU as the base instead of Pr2NEt afforded the product
in 78% isolated yield (Table 1, entry 9). When the reaction
was carried out in THF with other reaction conditions
unchanged, the isolated yield decreased from 99% to 84%
(Table 1, entry 10). If the CO pressure was reduced from 100
psi to 15 psi keeping other reaction conditions unchanged,
there was no impact on the isolated yield of the product
(Table 1, entry 11). Reducing the catalyst loading from 5 to
1 mol % resulted in much lower yield, and some of the
substrate still remained after the reaction (Table 1, entry 12).
The efficiency of the reaction was improved when the
catalyst loading was increased to 2 mol % and the product
was obtained in 99% isolated yield.
The intramolecular carbonylation of several other sub-
stituted 2-(2-iodophenoxy)anilines was effected to form
substituted dibenzo[b,f][1,4]oxazepin-11(10H)-ones under
the optimized conditions, and the results are presented in
Table 2.
Experimental Section
General Procedure for the Intramolecular Cyclocarbonylation
Reaction of Substituted 2-(2-Iodophenoxy)anilines. A mixture of
substituted 2-(2-iodophenoxy)aniline (1.0 mmol), PdI2 (0.02
i
mmol), Cytop 292 (0.045 mmol), Pr2NEt (1.5 mmol), and
toluene (5 mL) was placed in a 45 mL autoclave with a magnetic
stirring bar. The autoclave was flushed three times with CO
and pressurized with CO to 15 psi at room temperature. The
autoclave was then immersed in an oil bath preheated at 80 °C
for 20 h. Excess CO was discharged at room temperature.
The reaction mixture was purified by flash chromatography
on silica gel with hexane/EtOAc (v/v, 10:1 to 8:1) as the eluant to
give the corresponding dibenzo[b, f ][1,4]oxazepin-11(10H)-ones
in 90-99% yields.
2-tert-Butyl-dibenzo[b,f][1,4]oxazepin-11(10H)-one (14). 1H
NMR (300 MHz, CDCl3): δ 10.26 (s, 1H), 7.98 (d, 1H, J =
2.4 Hz), 7.54 (dd, 1H, J = 8.4 and 2.4 Hz), 7.29 -7.25 (m, 2H),
The results in Table 2 show that by the use of PdI2 as the
i
catalyst and bulky Cytop 292 as the ligand, Pr2NEt as the
7.20 (d, 1H, J = 8.4 Hz), 7.17-7.07 (m, 2H), 1.31 (s, 9H). 13
C
base, and toluene as the solvent, the intramolecular cyclo-
carbonylation of substituted 2-(2-iodophenoxy)anilines pro-
ceeded very smoothly irrespective of the electronic nature of
the substituents on the aromatic rings, affording the desired
products in good yields comparable to our previous results.8
Thus, the iodinated arylamines containing either electron-
withdrawing or electron-donating substituents could effi-
ciently be converted to the corresponding dibenzoxazepi-
nones in 90-99% yields. Three new substrates were prepared
and subjected to the optimized reaction conditions, giving
products in 90-97% isolated yields (Table 2, entries 5, 6, and
7). This method can be considered as a valuable alternative to
NMR (75 MHz, CDCl3): δ 168.7, 157.5, 151.1, 148.0, 131.6,
130.9, 128.3, 125.7, 125.5, 124.4, 121.6, 121.3, 120.2, 34.4, 31.2.;
HRMS (EI) m/z: calcd for C17H17NO2 (Mþ) 267.1259, found
267.1262.
Acknowledgment. We are grateful to Cytec Canada, Inc.
and to the Natural Sciences and Engineering Research
Council for support of this work.
Supporting Information Available: Detailed experimental
procedures and spectral data for all compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 75, No. 18, 2010 6299