Palladium-catalyzed C-C coupling of aryl halides with isocyanides: An alternative method for the stereoselective synthesis of (3E)-(Imino)isoindolin- 1-ones and (3E)-(imino)thiaisoindoline 1,1-dioxides

Article abstract of DOI:10.1002/adsc.201200212

A palladium-catalyzed, one-pot cyclization reaction to construct (3E)-(imino)isoindolin-1-ones and (3E)-(imino)thiaisoindoline 1,1-dioxides by introducing ortho-reactive functional groups on aryl halides is reported. Under optimal conditions, the cyclization reaction afforded the corresponding products in good to excellent yields (up to 93%) with high stereoselectivity. Notably, this transformation successfully extends its application for the synthesis of phenanthridines and dibenzooxazepines. This new synthetic protocol not only extends the application platform for palladium-catalyzed C-C coupling of aryl halides with isocyanides, but also opens atom-economic and step-economic synthetic routes for nitrogen-containing heterocyclic compounds with wide functional group compatibility. Copyright

Full text of DOI:10.1002/adsc.201200212

FULL PAPERS
DOI: 10.1002/adsc.201200212
À
Palladium-Catalyzed C C Coupling of Aryl Halides with
Isocyanides: An Alternative Method for the Stereoselective
Synthesis of (3E)-(Imino)isoindolin-1-ones and
(3E)-(Imino)thiaisoindoline 1,1-Dioxides
Bifu Liu,a Yibiao Li,a Huanfeng Jiang,a,* Meizhou Yin,a and Huawen Huanga
a
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, Peopleꢀs
Republic of China
Fax : (+86)-20-8711-2906; e-mail: jianghf@scut.edu.cn
Received: March 14, 2012; Revised: May 15, 2012; Published online: August 6, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200212.
Abstract: A palladium-catalyzed, one-pot cyclization synthetic protocol not only extends the application
À
reaction to construct (3E)-(imino)isoindolin-1-ones platform for palladium-catalyzed C C coupling of
and (3E)-(imino)thiaisoindoline 1,1-dioxides by in- aryl halides with isocyanides, but also opens atom-
troducing ortho-reactive functional groups on aryl economic and step-economic synthetic routes for ni-
halides is reported. Under optimal conditions, the trogen-containing heterocyclic compounds with wide
cyclization reaction afforded the corresponding prod- functional group compatibility.
ucts in good to excellent yields (up to 93%) with
À
high stereoselectivity. Notably, this transformation Keywords: C C coupling; isocyanides; nitrogen-con-
successfully extends its application for the synthesis taining heterocycles; one-pot cyclization; palladium-
of phenanthridines and dibenzooxazepines. This new catalyzed reaction
Introduction
roles and oxazolines. In addition, the transition metal-
catalyzed functionalization of C H bonds to construct
À
Since the pioneering work of Ugi[1] and Passerini,[2] useful N-containing heterocyclics has been reported.[8]
isocyanides have been widely applied to the creation More recently, palladium-catalyzed one-pot cycliza-
of molecular diversity, particularly in producing struc- tion reactions involving isocyanides have also been
turally appealing nitrogen-containing heterocycles, applied to the preparation of nitrogen heterocycles.[9]
which are low-molecular drug-like compounds and Very recently, our group developed a facile method
have potential utilization in the pharmaceutical indus- for the synthesis of 5-iminopyrrolones via palladium-
try.[3] Transition metal-catalyzed reactions have catalyzed annulation reaction of bromoalkynes and
emerged as a powerful tool for the synthesis of N- isocyanides.[10a] Therefore, from the view point of syn-
containing heterocycles via the formation of carbon- thetic chemistry, isocyanides are efficient building
carbon and carbon-heteroatom bonds and, hence, blocks for the synthesis of biologically active N-con-
have become the most attractive methodologies in taining molecules and for total synthesis.
modern organic synthesis.[4] Among a variety of tran-
Recently, our group utilized isocyanides as a source
sition metal-catalyzed transformations, great progress of both carboxy and amino group to construct syn-
has been made in using isocyanides as precursors for thetically useful amide compounds.[10b] In this palladi-
À
the synthesis of N-containing heterocycles. For exam- um-catalyzed C C coupling of aryl halides with iso-
ple, Odom and co-workers[5] have reported titanium- cyanides, the organopalladium intermediate is pro-
catalyzed one-pot multicomponent coupling reactions duced by the migratory insertion of isocyanide into
for direct access to different kinds of nitrogen hetero- the aryl palladium intermediate, which implied the
À
cycles, such as pyrazoles, pyrroles, and pyrimidines, potential possibilities of further formation of C C
À
À
quinolines and isoxazoles. Besides titanium catalysts, and C N bonds. Besides, the N H bond at an amide
copper[6] and silver[7] have also been employed in cat- group is generally reactive, and can be further func-
alytic cyclization reactions to prepare imidazoles, pyr- tionalized.[11] On the basis of the above facts, it may
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Palladium-Catalyzed C C Coupling of Aryl Halides with Isocyanides
Thus, it is still necessary to develop efficient and
simple protocols to synthesize iminoisoindolinones
and their structural analogues. Herein we disclose
a simple and highly efficient method for the stereose-
lective synthesis of (3E)-(imino)isoindolin-1-ones and
(3E)-(imino)thiaisoindoline 1,1-dioxides via Pd-cata-
À
lyzed C C coupling of aryl halides with isocyanides.
And further exploration revealed that this catalytic
system was also applicable for the synthesis of phe-
nanthridines and dibenzooxazepines.
Scheme 1. The reaction hypothesis.
Results and Discussion
be possible to develop more convenient routes for the
preparation of N-containing heterocycles via introduc- Palladium-Catalyzed One-Pot Cyclization Reaction of
ing reactive functional groups on suitable positions Isocyanides with ortho-Halobenzamides
(Scheme 1).
As we know, various heterocyclic compounds con- In a typical procedure, 2-bromobenzoyl chloride (1a)
taining the iminoisoindolinone or iminothiaisoindo- (0.5 mmol), aniline (2a) (0.5 mmol) and Et3N
line 1,1-dioxide skeleton exhibit important pharmaco- (1.0 mmol) in CH2Cl2 (2 mL) were stirred for two
logical activities.[12] Moreover, iminoisoindolinones hours at room temperature.[15] Then the solution was
are commonly used as precursors for the synthesis of evaporated to dryness under reduced pressure. Subse-
other heterocycles.[13] However, previously reported quently, solvent, tert-butyl isocyanide (3a) (0.6 mmol)
pathways are rare and have some drawbacks, such as and various palladium catalysts were added to screen
using inaccessible starting materials,[9d] low functional for the optimal reaction conditions (Table 1). Initially,
group compatibility[14,9d] or poor stereoselectivity.[8a] we preformed this palladium-catalyzed one-pot cycli-
Table 1. Optimization of reaction conditions.[a]
Entry
Pd source/Ligand
Base
Solvent
Yield [%][b]
1[c]
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16[d]
PdCl2/PPh3
PdCl2/PPh3
CsF
CsF
CsF
CsF
CsF
CsF
–
t-BuOK
Et3N
K2CO3
Cs2CO3
CsF
CsF
CsF
CsF
CsF
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
32
75
57
61
93(89)
50
trace
54
47
69
86
70
30
65
76
47
Pd
N
PdBr2/PPh3
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
N
toluene
CH3CN
1,4-dioxane
DMSO
PdCl2/PPh3
Pd(PPh3)2Cl2/PPh3
A
[a]
Reactions conditions: All reactions were performed with 1a (0.5 mmol), 2a (0.5 mmol), 3a (0.6 mmol), PdX2 (5 mol%),
PPh3 (10 mol%), base (2.0 equiv.), and 2.0 mL extra-dried solvent at 908C for 8 h unless otherwise noted.
Yields and conversions analysised by GC/MS are based on 1a. Number in parentheses is isolated yield.
0.2 mL of H2O was added to the extra-dried DMSO and 1.0 equiv. of CsF was used.
At 708C for 10 h.
[b]
[c]
[d]
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Table 2. Synthesis of (3E)-(imino)isoindolin-1-ones via palladium-cata-
lyzed one-pot cyclization reaction.[a,b]
[a]
All reactions were carried out using 1a (1.0 mmol), amines
(1.0 mmol) and isocyanides (1.2 mmol), PdACTHNUGTRNEG(UN PPh3)2Cl2 (5 mol%),
PPh3 (10 mol%), CsF (2.0 equiv.) in 2.0 mL extra-dried DMSO at
908C for 8 h unless otherwise noted.
Isolated yield.
93% isolated yield was obtained at 708C for 8 h when 1a was re-
placed by 2-iodobenzoyl chloride.
The isocyanide 4q is (isocyanomethyl)trimethylsilane.
[b]
[c]
[d]
zation reaction under the optimized conditions of our yield (entry 5), while the procedure was unfavorable
previous work.[10b] However, only a 32% yield of 4a in the absence of PPh3 (entry 6). Screening of various
was obtained (entry 1). Surprisingly, the yield of 4a bases revealed that the identity of the base was criti-
was increased to 75% when the reaction was carried cal to the success of the cyclization reaction (en-
out in extra-dried DMSO (entry 2). Testing different tries 7–11). Only a trace amount of 4a was detected in
palladium catalysts (entries 3–6) found that the yield the absence of base (entry 7), and we found Cs2CO3
of the desired product 4a decreased when PdCl2 was was also effective for this reaction system (entry 11),
replaced by Pd
best result was obtained when Pd
lized as the catalyst, affording 4a in 89% isolated zation reaction in different solvents (entries 12–15).
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
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Palladium-Catalyzed C C Coupling of Aryl Halides with Isocyanides
Comparing with DMSO, the yields of 4a were much lectivity and in good yields (4v, 4w). We also extended
lower when DMF, CH3CN, or 1,4-dioxane were used this transformation to 2-iodobenzoyl chloride (1a’)
as the solvents (entries 12, 14, and 15). Notably, the and found that the cyclization reaction gave an even
reaction was sluggish when toluene was employed better yield than with 1a at a lower reaction tempera-
(entry 13). Lower temperature disfavored the reaction ture (4a). In order to confirm the structure of the
and only gave a 47% yield of 4a after 10 h (entry 16). products obtained, the molecular structure of com-
With the optimized reaction conditions in hand, pound 4e was established by X-ray crystallography
various amines and isocyanides were employed in this (Figure 1).[17]
transformation to investigate the reaction’s scope and
limitations (Table 2). In all of the examples investigat-
ed, good to excellent yields of the corresponding Palladium-Catalyzed One-Pot Cyclization Reaction of
products were obtained, which indicates the excep- Isocyanides with ortho-Halobenzenesulfonamides
tional generality of this novel methodology. As
a matter of fact, both aromatic (4a–4i) and alkyl (4j– To further demonstrate the synthetic potential of our
4n) amines[16] exclusively gave the (3E)-(imino)isoin- methodology, we used 2-bromobenzene-1-sulfonyl
dolin-1-ones in good to excellent yields. Generally, (1b), amines (2) and isocyanides as substrates under
the aromatic rings with electron-donating groups (4b– the same reaction conditions to gain the correspond-
4d) afforded higher yields of the products than that ing (3E)-(imino)-thiaisoindoline 1,1-dioxides (5). To
with electron-withdrawing groups (4e–4i). It was explore the scope and limitations of this reaction, we
found that steric hindrance has a slight effect on the extended the procedure to various amines and isocya-
reaction (4e–4g). Meanwhile, good yields were nides (Table 3). To our delight, both aromatic (5a–5d)
achieved when alkyl- (4j–4l), cyclohexyl- (4m) and and aliphatic (5e–5h) amines have been successfully
benzyl- (4n) amines were used, although the yields of converted to the desired products in good to excellent
the desired product were slightly lower than with cor- yields (70–87%) under the optimized conditions. To
responding aromatic amines. Various alkyl, cycloalkyl, study the effects of the electronic properties of sub-
and aryl isocyanides (4o–4u) were also employed to stituents on aromatic amines, both electron-donating
probe the scope of the reaction substrates. Almost all (5b) and electron-withdrawing groups (5c, 5d) on the
the isocyanides were found suitable for this transfor- aromatic ring were screened. These results showed
mation, affording the corresponding (3E)-(imino)- that the electronic properties of the aromatic amines
ACHTUNGTRENNUNGisoindolin-1-ones in good yields. Even if sterically had no obvious effect on the yield of the desired
bulky isocyanides such as 1,1,3,3-tetramethylbutyl iso- products. Besides, the result of the experiment
cyanide and 2,6-dimethylphenyl isocyanide were used, showed that when methanamine and tert-butylamine
the reaction afforded the corresponding 4o and 4t in were used, the corresponding products were obtained
92% and 81% yield, respectively. Interestingly, 4q was in 78% (5e) and 70% (5f) yields respectively, which
obtained in 78% yield when (isocyanomethyl)trime- were much lower than those of propylamine (5g) and
thylsilane was used, caused by the cleavage of the tri- isopropylamine (5h). In addition, cyclohexanamine
methylsilyl group. In addition to the secondary, terti- and phenylmethanamine also reacted to form the
ary, and aromatic isocyanides, primary isocyanides products 5i and 5j in high yields.
were also effective in affording the corresponding
Finally, the scope of the process with respect to
(3E)-(imino)isoindolin-1-ones with excellent stereose- a variety of isocyanides was examined (5k–5q). Reac-
tion of isopropyl isocyanide (5k) was more efficient
than those of tert-butylisonitrile as reflected by the
fact that the corresponding (3E)-(imino)-thiaisoindo-
line 1,1-dioxide was formed in a much higher yield
(88%). It was worthy to note that the steric hindrance
on isocyanides had a great influenence on the one-pot
cyclization reaction. As shown in Table 3, when
1,1,3,3-tetramethylbutyl isocyanide (5l) was used in
this process, no desired product was detected. A simi-
lar phenomenon occurred when sterically hindered
aryl isocyanides were used, such as 2,6-dimethylphen-
yl isocyanide when only 47% yield of the correspond-
ing product (5p) obtained. However, the less hindered
p-methoxyphenyl isonitrile (5q) successfully partici-
pated in this process, giving the desired product in ex-
cellent yield (85%). Moreover, primary isocyanides
Figure 1. X-ray structure of compound 4e.
(5m, 5n) and cyclohexyl isocyanide (5o) were also ef-
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Table 3. Synthesis of (3E)-(imino)thiaisoindoline 1,1-dioxides via palladium-cata-
lyzed one-pot cyclization reaction.[a,b]
[a]
All reactions were carried out using 1b (1.0 mmol), amines (1.0 mmol) and 3a
(1.2 mmol), PdACTHUNTRGNE(UNG PPh3)2Cl2 (5 mol%), PPh3 (10 mol%), CsF (2.0 equiv.) in
2.0 mL extra-dried DMSO at 908C for 8 h unless otherwise noted.
Isolated yield.
90% isolated yield was obtained at 708C for 8 h when 1b was replaced by 2-io-
dobenzene-1-sulfonyl chloride.
[b]
[c]
fective to afford the corresponding (3E)-(imino)thia- (8a) and (E)-[6-(tert-butylimino)phenanthridin-5(6H)-
isoindoline 1,1-dioxides in good yields. yl](phenyl)methanone (8b) were obtained corre-
A
ACHTUNGTRENNUNG
spondingly when the free amino group of the 2’-bro-
mobiaryl-2-amines was protected by an acetyl or ben-
zoyl group. To our surprise, N-(tert-butyl)phenanthri-
Synthesis of Phenanthridines and Dibenzooxazepines
din-6-amine (9a) and N-(tert-butyl)dibenzo
ACHTUNGTREN[NGNU 1,4]oxazepin-11-amine (10a) were obtained in excel-
ACHTUNGTRENNUNG[b,f]-
With these results in hand, we envisioned that the 2’-
bromobiaryl-2-amines can also be applied to this lent yields when 2’-bromo-[1,1’-biphenyl]-2-amine
transformation (Scheme 2). Not surprisingly, (E)-1-[6- (6a) and 2-(2-bromophenoxy)aniline (6b) were used
(tert-butylimino)phenanthridin-5(6H)-yl]ethanone
as substrates under the standard reaction conditions.
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Palladium-Catalyzed C C Coupling of Aryl Halides with Isocyanides
Scheme 2. Palladium-catalyzed synthesis of phenanthridines and dibenzooxazepines.
It is noteworthy that phenanthridines and dibenzoox- palladium intermediate B. Subsequent insertion of
azepins are important units in numerous biologically isocyanide into the palladium-carbon bond results in
active natural products and medicinally significant the intermediate C. With the aid of the base, hydro-
compounds.[18] We presume that the intermediates (9’ gen halide was extruded out of C to generate the six-
and 10’) were unstable and easily tautomerized[8c,18c] membered ring azapalladacyclic intermediate D. Fi-
to the corresponding 6-aminophenanthridines (9) and nally, reductive elimination affords E, regenerating
11-aminodibenzooxazepines (10). Next, we examined the palladium(0) catalyst.
other isocyanides under the standard reaction condi-
tions. Specifically, alkyl, cycloalkyl, and aryl isocya-
nides were employed to probe the scope of the sub- Conclusions
strates. As shown in Scheme 2, almost all the isocya-
nides were found suitable for this transformation, af- In summary, we have demonstrated a most efficient,
fording the corresponding 6-aminophenanthridines mild, concise and facile protocol for the synthesis of
(9b–9d) and 11-aminodibenzooxazepines (10b and substituted (3E)-(imino)isoindolin-1-ones and (3E)-
10c) in high yield. These examples demonstrate the (imino)thiaisoindoline 1,1-dioxides via a palladium-
great potential of our new method for the construc- catalyzed one-pot cyclization reaction. Good to excel-
tion pharmacologically interesting nitrogen heterocy- lent yields and high stereoselectivity of the target
cles.
products were generally obtained from a broad range
of substrates. More importantly, this transformation
was successfully applied to the synthesis of phenan-
thridines and dibenzooxazepines. In addition, all of
the starting materials for the palladium-catalyzed
Plausible Reaction Mechanism
À
Based on the previous palladium-catalyzed C C cou- one-pot cyclization reaction were commercially avail-
pling of aryl halides with isocyanides,[10] a plausible able and the reactions were easy to handle, which of-
mechanism of this one-pot cyclization reaction was fered a simple way to increase the product diversity
proposed (Scheme 3). Initial oxidative addition of and structural complexity. Further research on the
ortho-halobenzamides or ortho-halobenzenesulfon- preparation of other useful nitrogen heterocycles by
ACHTUNGTRENNUNGamides (A) to a zerovalent Pd species affords aryl this catalytic system is underway in our laboratory.
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Scheme 3. Proposed mechanism for the one-pot cyclization reaction.
isocyanide (1.2 mmol) was added, and the mixture was
stirred at 908C for 12 h in 10-mL sealed tubes. Monitoring
with TLC was used to show when the reaction was com-
plete. Upon completion, the reaction mixture was extracted
with ethyl acetate (3ꢃ10 mL), and the combined organic
phase was dried with anhydrous MgSO4 and concentrated
under vacuum. The residue was loaded on a silica column
and purified by column chromatography (petroleum ether/
ethyl acetate, 10:1) to give the final product. The stereo-
chemistry was confirmed by the X-ray diffraction, see Sup-
porting Information.
Experimental Section
General Methods
All reactions were carried out in 10-mL tubes. TLC was per-
formed by using commercially prepared 100–400 mesh silica
gel plates (GF254) and visualization was effected at 254 nm.
The starting materials 6a and 6b were prepared according to
the literature.[19] Other reagents were purchased as reagent
grade and used without further purification. Extra-dried
DMSO was purchased as reagent grade and used without
further dehydration. Melting points were measured with
a Bꢂchi B-545 melting point instrument and are uncorrect-
1
ed. H and 13C NMR spectra were recorded on a 400 MHz
General Procedure for the Synthesis of Phenan-
thridines and Dibenzooxazepines
spectrometer using CDCl3 as solvent and TMS as an internal
standard. The chemical shifts were referenced to signals at
7.24 and 77.0 ppm, respectively.
To the mixture of 6a or 6b (1.0 mmol), PdACHTUNGTRNEG(UN PPh3)2Cl2
(5 mol%), PPh3 (10 mol%) in extra-dried DMSO (2 mL),
CsF (2.0 equiv.) were added successively and stirred for five
minutes at the room temperature. Then the isocyanide
(1.2 mmol) was added and the mixture was stirred at 908C
for 12 h in 10-mL sealed tubes. Monitoring with TLC was
used to show when the reaction was complete. Upon com-
pletion, the reaction mixture was extracted with ethyl ace-
tate (3ꢃ10 mL), and the combined organic phase was dried
with anhydrous MgSO4 and concentrated under vacuum.
The residue was loaded on silica column and purified by
column chromatography (petroleum ether/ethyl acetate,
10:1) to give the final product.
General Procedure for the Synthesis of (3E)-(Imino)-
isoindolin-1-ones and (3E)-(Imino)thiaisoindoline
1,1-Dioxides
2-Bromobenzoyl chloride (1a) (1.0 mmol) or 2-bromobenze-
nesulfonyl chloride (1b) (1.0 mmol), aniline (2a) (1.0 mmol)
and Et3N (2.0 mmol) in CH2Cl2 (2 mL) were stirred for two
hours at room temperature. Then the solution was evaporat-
ed to dryness under reduced pressure. Subsequently,
PdACHTUNGTRENNUNG(PPh3)2Cl2 (5 mol%), PPh3 (10 mol%), CsF (2.0 equiv.)
and extra-dried DMSO (2 mL) were added and the mixture
was stirred for five minutes at room temperature, then the
(E)-3-(tert-Butylimino)-2-phenylisoindolin-1-one
Light yellow solid; mp 120–1228C; IR (KBr): n=2969, 2362,
(4a):
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Palladium-Catalyzed C C Coupling of Aryl Halides with Isocyanides
1729, 1660, 1371, 1140, 698 cmÀ1 1H NMR (400 MHz,
;
7.39–7.32 (m, 4H), 1.48 (s, 9H); 13C NMR (100 MHz,
CDCl3): d=166.4, 146.4, 133.4, 132.8, 132.5, 132.3, 131.3,
129.7, 128.4, 128.1, 127.3, 123.6, 53.9, 30.5; ESI-HR-MS:
m/z=313.1098, calcd. for C18H17ClN2O (M+H)+: 313.1102.
(E)-3-(tert-Butylimino)-2-(3,4-dichlorophenyl)isoindolin-
1-one (4h): White solid; mp 132–1348C; mp 134–1368C; IR
(KBr): n=2970, 2361, 1731, 1665, 1475, 1369, 1135,
CDCl3): d=8.07 (d, J=7.6 Hz, 1H), 7.98 (d, J=7.2 Hz, 1H),
7.71–7.61 (m, 2H), 7.45–7.38 (m, 4H), 7.33–7.29 (m, 1H),
1.49 (s, 9H); 13C NMR (100 MHz, CDCl3): d=166.6, 146.7,
134.3, 133.6, 132.3, 131.2, 128.5, 128.5, 128.0, 127.2, 126.8,
123.5, 53.8, 30.5; ESI-HR-MS: m/z=279.1489, calcd. for
C18H18N2O (M+H)+: 279.1492.
701 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=8.06 (d, J=
(E)-3-(tert-Butylimino)-2-(4-methoxyphenyl)isoindolin-1-
one (4b): Light yellow solid; mp 136–1388C; IR (KBr): n=
2967, 2360, 1725, 1659, 1512, 1377, 1246, 1143, 1030,
8.0 Hz, 1H), 7.94 (d, J=7.2 Hz, 1H), 7.72–7.68 (m, 1H),
7.64–7.61 (m, 1H), 7.55(d, J=2.4 Hz, 1H), 7.45 (d, J=
8.4 Hz, 1H), 7.28 (dd, J1 =J2 =2.4 Hz, 1H), 1.48 (s, 9H);
13C NMR (100 MHz, CDCl3): d=166.1, 146.0, 133.6, 133.1,
132.7, 131.6, 131.5, 130.5, 130.3, 129.5, 128.3, 127.7, 127.4,
123.7, 54.0, 30.4; ESI-HR-MS: m/z=347.0705, calcd. for
C18H16Cl2N2O (M+H)+: 347.0712.
703 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=8.04 (d, J=
7.6 Hz, 1H), 7.95 (d, J=7.2 Hz, 1H), 7.68–7.58 (m, 2H),
7.30–7.26 (m, 2H), 6.97–6.93 (m, 2H), 3.80 (s, 3H), 1.47 (s,
9H); 13C NMR (100 MHz, CDCl3); d=166.8, 158.1, 146.9,
133.6, 132.2, 131.1, 129.5, 128.6, 127.1, 127.0, 123.4, 113.4,
55.2, 53.8, 30.5; ESI-HR-MS: m/z=309.1593, calcd. for
C19H20N2O2 (M+H)+: 309.1598.
(E)-3-(tert-Butylimino)-2-(4-fluorophenyl)isoindolin-1-one
(4i): Light yellow solid; mp 131–1338C; IR (KBr): n=2969,
1
2360, 1722, 1656, 1508, 1368, 1224, 1143, 701 cmÀ1; H NMR
(E)-3-(tert-Butylimino)-2-(3,4-dimethylphenyl)isoindolin-
1-one (4c): Light yellow solid; mp 124–1268C; IR (KBr):
(400 MHz, CDCl3): d=8.06 (d, J=7.6 Hz, 1H), 7.96 (d, J=
7.6 Hz, 1H), 7.71–7.61 (m, 2H), 7.37–7.31 (m, 2H), 7.13–
7.07 (m, 2H), 1.48 (s, 9H); 13C NMR (100 MHz, CDCl3):
d=166.7, 162.4, 160.0, 146.7, 133.5, 132.4, 131.3, 130.1 (d, J=
8.5 Hz), 128.5, 127.3, 123.6, 114.9 (d, J=22.5 Hz), 53.9, 30.5;
ESI-HR-MS: m/z=297.1392, calcd. for C18H17FN2O (M+
H)+: 297.1398.
n=2966, 2359, 1727, 1660, 1505, 1371, 1140, 702 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=8.06 (d, J=7.6 Hz, 1H),
7.98 (d, J=7.2 Hz, 1H), 7.70–7.60 (m, 2H), 7.20–7.09 (m,
3H), 2.28 (s, 6H), 1.49 (s, 9H); 13C NMR (100 MHz,
CDCl3): d=166.9, 146.9, 136.3, 135.3, 133.7, 132.2, 131.9,
131.1, 129.4, 129.3, 128.7, 127.2, 125.8, 123.5, 53.9, 30.6, 19.8,
19.4; ESI-HR-MS: m/z=307.1801, calcd. for C20H22N2O
(M+H)+: 307.1805.
(E)-3-(tert-Butylimino)-2-methylisoindolin-1-one
Light yellow solid; mp 132–1358C; IR (KBr): n=2925, 2360,
1724, 1645, 1515, 1463, 1423, 1364, 694 cmÀ1 1H NMR
(4j):
(E)-3-(tert-Butylimino)-2-(4-phenoxyphenyl)isoindolin-1-
one (4d): Light yellow solid; mp 140–1428C; IR (KBr): n=
;
(400 MHz, CDCl3): d=7.94 (d, J=7.6 Hz, 1H), 7.84 (d, J=
7.6 Hz, 1H), 7.60–7.51 (m, 2H), 3.13 (s, 3H), 1.50 (s, 9H);
13C NMR (100 MHz, CDCl3): d=167.4, 147.3, 134.3, 131.7,
130.8, 129.0, 127.0, 123.0, 53.6, 30.7, 25.1; ESI-HR-MS:
m/z=217.1329, calcd. for C13H16N2O (M+H)+: 217.1335.
2967, 2359, 1726, 1658, 1500, 1370, 1234, 1140, 698 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=8.07 (d, J=7.6 Hz, 1H),
7.98 (d, J=7.6 Hz, 1H), 7.71–7.62 (m, 2H), 7.36–7.32 (m,
4H), 7.12–7.04 (m, 5H), 1.50 (s, 9H); 13C NMR (100 MHz,
CDCl3): d=166.8, 156.8, 155.9, 146.8, 133.6, 132.3, 131.2,
129.8, 129.7, 129.3, 128.6, 127.2, 123.6, 123.4, 119.2, 118.0,
53.9, 30.6; ESI-HR-MS: m/z=371.1747, calcd. for
C24H22N2O2 (M+H)+: 371.1754.
(E)-3-(tert-Butylimino)-2-hexylisoindolin-1-one
Yellow oil; IR (KBr): n=2928, 2359, 1721, 1651, 1512, 1394,
702 cmÀ1 1H NMR (400 MHz, CDCl3): d=7.94 (d, J=
(4k):
;
7.6 Hz, 1H), 7.84 (d, J=7.2 Hz, 1H), 7.60–7.51 (m, 2H),
3.71 (t, J=7.2 Hz, 2H), 1.61–1.55 (m, 2H), 1.50 (s, 9H),
1.34–1.21 (m, 6H), 0.83 (t, J=6.8 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=167.2, 146.4, 134.3, 131.6, 130.8,
128.8, 126.9, 123.0, 53.6, 38.3, 31.4, 30.7, 28.1, 26.6, 22.5,
14.0; ESI-HR-MS: m/z=287.2112, calcd. for C18H26N2O
(M+H)+: 287.2118.
(E)-3-(tert-Butylimino)-2-(2-chlorophenyl)isoindolin-1-
one (4e): White solid; mp 139–1418C; IR (KBr): n=2966,
2357, 1730, 1659, 1479, 1367, 1147, 701 cmÀ1 1H NMR
;
(400 MHz, CDCl3): d=8.06 (d, J=7.6 Hz, 1H), 7.98 (d, J=
7.6 Hz, 1H), 7.69 (t, J=7.4 Hz, 1H), 7.62 (t, J=7.4 Hz, 1H),
7.48–7.46 (m, 1H), 7.35–7.28 (m, 3H), 1.42 (s, 9H);
13C NMR (100 MHz, CDCl3): d=166.2, 145.8, 133.6, 133.5,
132.8, 132.4, 131.4, 131.1, 129.6, 129.2, 128.9, 127.1, 126.9,
123.7, 53.8, 30.4; ESI-HR-MS: m/z=313.1095, calcd. for
C18H17ClN2O (M+H)+: 313.1102.
(E)-2-Butyl-3-(tert-butylimino)isoindolin-1-one (4l): Light
yellow oil; IR (KBr): n=2927, 2356, 1694, 1649, 1517,
670 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=7.95 (d, J=
7.6 Hz, 1H), 7.86 (d, J=6.4 Hz, 1H), 7.61–7.53 (m, 2H),
3.74 (t, J=7.2 Hz, 2H), 1.63–1.55 (m, 2H), 1.52 (s, 9H),
1.36–1.29 (m, 2H), 0.91 (t, J=7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=167.3, 146.5, 134.4, 131.7, 130.8,
128.9, 127.0, 123.1, 53.6, 38.1, 30.8, 30.4, 20.1, 13.4; ESI-HR-
MS: m/z=259.1801, calcd. for C16H22N2O (M+H)+:
259.1805.
(E)-3-(tert-Butylimino)-2-(3-chlorophenyl)isoindolin-1-
one (4f): Light yellow solid; mp 158–1608C; IR (KBr): n=
2969, 2357, 1726, 1660, 1472, 1361, 684 cmÀ1 1H NMR
;
(400 MHz, CDCl3): d=8.06 (d, J=7.6 Hz, 1H), 7.98 (d, J=
7.6 Hz, 1H), 7.73–7.63 (m, 2H), 7.42 (t, J=1.8 Hz, 1H),
7.37–7.26 (m, 3H), 1.49 (s, 9H); 13C NMR (100 MHz,
CDCl3): d=166.4, 146.3, 135.4, 133.4, 132.6, 131.4, 129.0,
128.8, 128.5, 127.4, 127.0, 126.7, 123.8, 54.1, 30.5; ESI-HR-
MS: m/z=313.1093. calcd. for C18H17ClN2O (M+H)+:
313.1102.
(E)-3-(tert-Butylimino)-2-cyclohexylisoindolin-1-one
(4m): Light yellow solid; mp 67–698C; IR (KBr): n=2927,
1
2359, 1713, 1652, 1515, 1363, 704 cmÀ1; H NMR (400 MHz,
CDCl3): d=7.93 (d, J=7.6 Hz, 1H), 7.82 (d, J=6.4 Hz, 1H),
7.59–7.51 (m, 2H), 4.36–4.28 (m, 1H), 2.40–2.30 (m, 2H),
1.85–1.75 (m, 2H), 1.65–1.59 (m, 2H), 1.52 (s, 9H), 1.37–
1.16 (m, 4H); 13C NMR (100 MHz, CDCl3): d=167.3, 146.2,
134.5, 131.5, 130.7, 128.4, 126.9, 122.9, 53.7, 50.1, 30.8, 29.4,
(E)-3-(tert-Butylimino)-2-(4-chlorophenyl)isoindolin-1-
one (4g): White solid; mp 152–1548C; IR (KBr): n=2966,
1
2380, 1729, 1660, 1492, 1373, 1138, 1087, 701 cmÀ1; H NMR
(400 MHz, CDCl3): d=8.06 (d, J=7.6 Hz, 1H), 7.96 (d, J=
7.6 Hz, 1H), 7.69 (t, J=7.6 Hz, 1H), 7.62 (t, J=7.4 Hz, 1H),
Adv. Synth. Catal. 2012, 354, 2288 – 2300
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Bifu Liu et al.
FULL PAPERS
26.4, 25.5; ESI-HR-MS: m/z=285.1952, calcd. for
C18H24N2O (M+H)+: 285.1961.
(KBr): n=2920, 2359, 1741, 1671, 1493, 1379, 1087, 771,
701 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=7.93 (d, J=
(E)-2-Benzyl-3-(tert-butylimino)isoindolin-1-one
(4n):
7.6 Hz, 1H), 7.59 (t, J=7.6 Hz, 1H), 7.54–7.49 (m, 4H), 7.39
(t, J=7.6 Hz, 1H), 7.10–6.99 (m, 3H), 6.61 (d, J=7.6 Hz,
1H), 2.05 (s, 6H); 13C NMR (100 MHz, CDCl3): d=166.8,
150.8, 145.7, 133.9, 133.6, 132.5, 131.8, 131.3, 129.7, 129.2,
129.1, 128.2, 126.3, 124.3, 123.8, 123.7, 18.1; MS (EI): m/z=
77, 102, 130, 151, 179, 219, 234, 255, 281, 315, 345, 360.
(E)-2-(4-Chlorophenyl)-3-[(4-methoxyphenyl)imino]isoin-
dolin-1-one (4u): Yellow solid; mp 56–588C; IR (KBr): n=
White solid; mp 107–1098C; IR (KBr): n=2964, 2359, 1717,
1
1653, 1516, 1396, 701 cmÀ1; H NMR (400 MHz, CDCl3): d=
7.96 (d, J=7.6 Hz, 1H), 7.88 (d, J=7.2 Hz, 1H), 7.61–7.52
(m, 2H), 7.46 (d, J=7.6 Hz, 2H), 7.28–7.17 (m, 3H), 4.94 (s,
2H), 1.52 (s, 9H); 13C NMR (100 MHz, CDCl3): d=167.0,
146.0, 138.2, 134.1, 131.9, 130.9, 128.9, 128.8, 128.0, 127.0,
126.9, 123.2, 53.7, 41.8, 30.7; ESI-HR-MS: m/z=293.1646,
calcd. for C19H20N2O (M+H)+: 293.1648.
2929, 2362, 1736, 1658, 1498, 1382, 1239,1117, 697 cmÀ1
;
(E)-2-(4-Chlorophenyl)-3-[(2,4,4-trimethylpentan-2-yl)-
imino]isoindolin-1-one (4o): Yellow oil; IR (KBr): n=2950,
1H NMR (400 MHz, CDCl3): d=7.93 (d, J=7.6 Hz, 1H),
7.58 (t, J=7.6 Hz, 1H), 7.49–7.44 (m, 4H), 7.38 (t, J=
7.6 Hz, 1H), 6.93–6.86 (m, 4H), 6.79 (d, J=7.6 Hz, 1H),
3.83 (s, 3H); 13C NMR (100 MHz, CDCl3): d=166.9, 156.7,
151.4, 141.5, 133.6, 133.1, 132.2, 131.9, 131.8, 129.2, 129.2,
129.1, 125.8, 123.8, 120.6, 114.6, 55.5; ESI-HR-MS: m/z=
363.0908, calcd. for C21H16ClN2O2 (M+H)+: 363.0895.
2360, 1728, 1660, 1493, 1373, 1087, 701 cmÀ1 1H NMR
;
(400 MHz, CDCl3): d=8.08 (d, J=7.6 Hz, 1H), 7.95 (d, J=
7.2 Hz, 1H), 7.70–7.60 (m, 2H), 7.38–7.35 (m, 2H), 7.27–
7.24 (m, 2H), 1.79 (s, 2H), 1.50 (s, 6H), 0.81 (s, 9H);
13C NMR (100 MHz, CDCl3): d=166.5, 145.5, 133.7, 133.2,
132.8, 132.4, 131.2, 130.2, 128.7, 128.3, 127.1, 123.6, 57.9,
56.0, 31.7, 31.6, 30.1; ESI-HR-MS: m/z=369.1724, calcd. for
C22H25ClN2O (M+H)+: 369.1728.
(E)-3-(Butylimino)-2-(4-chlorophenyl)isoindolin-1-one
(4v): Pale yellow oily liquid; IR (KBr): n=2958, 2353, 1700,
1
1625, 1520, 593 cmÀ1; H NMR (400 MHz, CDCl3): d=7.82
(E)-2-(4-Chlorophenyl)-3-(isopropylimino)isoindolin-1-
one (4p): Light yellow solid; mp 91–938C; IR (KBr): n=
(d, J=7.2 Hz, 1H), 7.51 (t, J=7.4 Hz, 1H), 7.35–7.29 (m,
3H), 6.90–6.88 (m, 2H), 6.68 (d, J=7.6 Hz, 1H), 3.85 (t, J=
7.2 Hz, 2H), 1.76–1.68 (m, 2H), 1.44–1.35 (m, 2H), 0.95 (t,
J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=167.7,
151.3, 147.4, 132.7, 132.5, 132.0, 129.5, 129.4, 129.4, 125.2,
123.4, 121.3, 38.7, 30.4, 20.2, 13.8; ESI-HR-MS: m/z=
313.1108, calcd. for C18H18ClN2O (M+H)+: 313.1102.
1
2970, 2359, 1731, 1664, 1494, 1375, 1117, 699 cmÀ1; H NMR
(400 MHz, CDCl3): d=7.99–7.93 (m, 2H), 7.68–7.60 (m,
2H), 7.44–7.38 (m, 4H), 4.68–4.59 (m, 1H), 1.29 (s, 6H);
13C NMR (100 MHz, CDCl3): d=166.4, 148.3, 133.3, 132.5,
132.2, 132.2, 131.5, 129.3, 129.1, 128.4, 125.7, 123.7, 49.6,
24.1; ESI-HR-MS: m/z=299.0942, calcd. for C17H15ClN2O
(M+H)+: 299.0946.
(E)-2-(4-Chlorophenyl)-3-[(2-morpholinoethyl)imino]iso-
indolin-1-one (4w): Yellow solid; mp 65–678C; IR (KBr):
(E)-2-(4-Chlorophenyl)-3-(methylimino)isoindolin-1-one
(4q): Yellow solid; mp 139–1418C; IR (KBr): n=2925, 2360,
n=2935, 2345, 1736, 1658, 1479, 1412, 1232,1107, 721 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=7.83 (d, J=7.2 Hz, 1H),
7.53 (t, J=7.6 Hz, 1H), 7.35–7.31 (m, 3H), 6.88 (d, J=
8.0 Hz, 2H), 6.69 (d, J=7.6 Hz, 1H), 4.00 (t, J=6.4 Hz,
2H), 3.73–3.60 (m, 4H), 2.77–2.68 (m, 2H), 2.65–2.47 (m,
4H); 13C NMR (100 MHz, CDCl3): d=167.6, 164.7, 151.2,
147.3, 132.1, 132.0, 129.4, 128.5, 128.4, 125.2, 123.4, 121.2,
66.9, 56.1, 53.6, 53.4; ESI-HR-MS: m/z=370.1313, calcd. for
C20H21ClN3O2 (M+H)+: 370.1317.
1735, 1660, 1382, 1031, 695 cmÀ1
;
1H NMR (400 MHz,
CDCl3): d=7.82 (d, J=7.6 Hz, 1H), 7.53–7.49 (m, 1H),
7.32–7.29 (m, 3H), 6.91–6.89 (m, 2H), 6.68 (d, J=8.0 Hz,
1H), 3.31 (s, 3H); 13C NMR (100 MHz, CDCl3): d=167.6,
151.8, 147.3, 132.7, 132.5, 132.0, 129.5, 129.4, 125.2, 123.4,
121.3, 25.2; ESI-HR-MS: m/z=271.0626, calcd. for
C15H11ClN2O (M+H)+: 271.0633.
(E)-2-(4-Chlorophenyl)-3-(cyclohexylimino)isoindolin-1-
one (4r): Yellow solid; mp 149–1518C; IR (KBr): n=2929,
(E)-3-(tert-Butylimino)-2-phenyl-2,3-dihydrobenzo[d]iso-
thiazole 1,1-dioxide (5a): White solid; mp 164–1668C; IR
(KBr): n=2926, 2360, 1659, 1319, 1236, 1188, 1128, 973,
2362, 1732, 1662, 1494, 1378, 1090, 697 cmÀ1 1H NMR
;
(400 MHz, CDCl3): d=7.97 (d, J=7.2 Hz, 1H), 7.92 (d, J=
7.6 Hz, 1H), 7.72–7.63 (m, 2H), 7.41–7.36 (m, 4H), 4.31–
4.23 (m, 1H), 1.87–1.78 (m, 4H), 1.67–1.64 (m, 1H), 1.59–
1.49 (m, 2H), 1.47–1.37 (m, 2H), 1.33–1.24 (m, 1H);
13C NMR (100 MHz, CDCl3): d=166.6, 148.4, 133.4, 132.6,
132.4, 132.4, 131.6, 129.3, 128.5, 125.6, 123.9, 57.6, 34.1, 25.5,
24.4; ESI-HR-MS: m/z=339.1250, calcd. for C20H19ClN2O
(M+H)+: 339.1259.
772 cmÀ1 1H NMR (400 MHz, CDCl3): d=7.76 (d, J=
;
7.6 Hz, 1H), 7.53 (t, J=7.6 Hz, 1H), 7.34 (t, J=7.8 Hz, 2H),
7.24 (t, J=8.2 Hz, 1H), 7.12 (t, J=7.4 Hz, 1H), 6.83 (d, J=
7.2 Hz, 2H), 6.68 (d, J=8.0 Hz, 1H), 1.85 (s, 9H); 13C NMR
(100 MHz, CDCl3): d=148.3, 143.3, 137.3, 132.5, 132.1,
129.7, 126.8, 124.5, 123.4, 120.6, 118.9, 60.9, 27.8; ESI-HR-
MS: m/z=315.1169, calcd. for C17H18N2O2S (M+H)+:
315.1162.
(E)-2-(4-Chlorophenyl)-3-(cyclopentylimino)isoindolin-1-
one (4s): White solid; mp 128–1308C; IR (KBr): n=2954,
(E)-3-(tert-Butylimino)-2-(4-methoxyphenyl)-2,3-dihydro-
benzo[d]isothiazole 1,1-dioxide (5b): Yellow solid; mp 122–
1248C; IR (KBr): n=2928, 2358, 1661, 1489, 1315, 1237,
2360, 1731, 1662, 1493, 1377, 1089, 699 cmÀ1 1H NMR
;
(400 MHz, CDCl3): d=8. 02(d, J=7.6 Hz, 1H), 7.95 (d, J=
6.8 Hz, 1H), 7.69–7.60 (m, 2H), 7.42–7.34 (m, 4H), 4.80–
4.74 (m, 1H), 2.03–1.94 (m, 2H), 1.83–1.74 (m, 2H), 1.73–
1.61 (m, 4H); 13C NMR (100 MHz, CDCl3): d=166.4, 148.7,
133.2, 132.4, 132.3, 132.2, 131.5, 129.2, 129.1, 128.3, 125.6,
123.7, 59.9, 35.1, 24.2; ESI-HR-MS: m/z=325.1097, calcd.
for C19H17ClN2O (M+H)+: 325.1102.
1192, 979, 766 cmÀ1 1H NMR (400 MHz, CDCl3): d=7.77
;
(d, J=7.6 Hz, 1H), 7.54 (t, J=7.6 Hz, 1H), 7.28 (t, J=
7.8 Hz, 1H), 6.91 (d, J=8.0 Hz, 2H), 6.76 (d, J=7.6 Hz,
3H), 3.82 (s,3H), 1.85 (s, 9H); 13C NMR (100 MHz, CDCl3):
d=156.1, 144.0, 141.7, 137.4, 132.6, 132.1, 126.9, 124.5, 120.6,
119.9, 115.0, 60.9, 27.8; ESI-HR-MS: m/z=345.1273, calcd.
for C18H20N2O3S (M+H)+ 345.1267.
(E)-2-(4-Chlorophenyl)-3-[(2,6-dimethylphenyl)imino]-
(E)-3-(tert-Butylimino)-2-(4-chlorophenyl)-2,3-dihydro-
benzo[d]isothiazole 1,1-dioxide (5c): Light yellow solid; mp
isoindolin-1-one (4t):[9d] Yellow solid; mp 136–1388C; IR
2296
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Adv. Synth. Catal. 2012, 354, 2288 – 2300

À
Palladium-Catalyzed C C Coupling of Aryl Halides with Isocyanides
173–1758C; IR (KBr): n=2926, 2360, 1660, 1320, 1236,
4.17 (m, 1H), 2.16–2.02 (m, 4H), 1.90–1.83 (m, 2H), 1.67–
1186, 1129, 974, 834, 652 cmÀ1; H NMR (400 MHz, CDCl3);
1.63 (m, 1H), 1.50 (s, 9H), 1.37–1.20 (m, 3H) . 13C NMR
(100 MHz, CDCl3): d=138.3, 137.6, 132.2, 131.5, 128.2,
125.1, 121.0, 54.6, 53.3, 30.8, 29.6, 26.3, 25.4; ESI-HR-MS:
m/z=321.1642, calcd. for C17H24N2O2S (M+H)+: 321.1631.
(E)-2-Benzyl-3-(tert-butylimino)-2,3-dihydrobenzo[d]iso-
thiazole 1,1-dioxide (5j): White solid; mp 139–1418C; IR
(KBr): n=2970, 2356, 1669, 1311, 1236, 1178, 1059,
1
d=7.77 (d, J=7.6 Hz, 1H), 7.57 (t, J=7.6 Hz, 1H), 7.34–
7.29 (m, 3H), 6.79–6.77 (m, 3H), 1.83 (s, 9H); 13C NMR
(100 MHz, CDCl3): d=146.8, 143.7, 137.3, 132.6, 132.4,
129.6, 128.5, 126.6, 124.2, 120.7, 120.3, 61.0, 27.7; ESI-HR-
MS: m/z=371.0622, calcd. for C17H17ClN2O2S (M+Na)+:
371.0591.
(E)-3-(tert-Butylimino)-2-(4-fluorophenyl)-2,3-dihydro-
benzo[d]isothiazole 1,1-dioxide (5d): Yellow solid; mp 138–
1408C; IR (KBr): n=2977, 2360, 1660, 1501, 1319, 1193,
741 cmÀ1 1H NMR (400 MHz, CDCl3): d=8.05 (d, J=
;
7.2 Hz, 1H), 7.88 (d, J=6.8 Hz, 1H), 7.66–7.59 (m, 2H),
7.47 (d, J=7.6 Hz, 2H), 7.28–7.17 (m, 3H), 4.80 (s, 2H),
1.34 (s, 9H); 13C NMR (100 MHz, CDCl3): d=138.0, 137.8,
136.7, 132.5, 131.7, 128.5, 128.3, 127.8, 126.9, 125.3, 121.4,
53.4, 42.1, 30.6; ESI-HR-MS: m/z=329.1311, calcd. for
C18H20N2O2S (M+H)+: 329.1318.
1131, 976, 839 cmÀ1 1H NMR (400 MHz, CDCl3): d=7.76
;
(d, J=7.6 Hz, 1H), 7.56 (t, J=7.4 Hz, 1H), 7.30 (t, J=
7.8 Hz, 1H), 7.04 (t, J=8.0 Hz, 2H), 6.80–6.77 (m, 2H), 6.73
(d, J=8.0 Hz, 1H), 1.83 (s, 9H); 13C NMR (100 MHz,
CDCl3): d=160.4, 158.0, 144.3 (d, J=2.7 Hz), 144.0, 137.3,
132.4 (d, J=27.5 Hz), 126.6, 124.2, 120.6, 120.1 (d, J=
7.7 Hz), 116.3 (d, J=22.3 Hz), 60.9, 27.7; ESI-HR-MS:
m/z=333.1084, calcd. for C17H17FN2O2S (M+H)+: 333.1068.
(E)-3-(tert-Butylimino)-2-methyl-2,3-dihydrobenzo[d]iso-
thiazole 1,1-dioxide (5e): Light yellow solid; mp 100–1028C;
IR (KBr): n=2971, 2360, 1664, 1312, 1246, 1192, 980,
(E)-2-(4-Chlorophenyl)-3-(isopropylimino)-2,3-dihydro-
benzo[d]isothiazole 1,1-dioxide (5k): Light yellow oil; IR
(KBr): n=2979, 2358, 1636, 1315, 1235, 1203, 1146, 1015,
1
765, 578 cmÀ1; H NMR (400 MHz, CDCl3): d=7.82 (d, J=
7.6 Hz, 1H), 7.61 (t, J=7.6 Hz, 1H), 7.38–7.30 (m, 3H),
6.84–6.80 (m, 3H), 4.71–4.64 (m, 1H), 1.64 (d, J=7.2 Hz,
6H); 13C NMR (100 MHz, CDCl3): d=146.8, 142.9, 137.3,
132.9, 132.6, 129.7, 128.9, 126.7, 124.3, 121.1, 120.8, 47.7,
19.7; ESI-HR-MS: m/z=335.0621, calcd. for C16H16ClN2O2S
(M+H)+: 335.0616.
756 cmÀ1
7.6 Hz, 1H), 7.84 (d, J=8.0 Hz, 1H), 7.69–7.61 (m, 2H), 3.0-
(s, 3H), 1.43 (s, 9H); 13C NMR (100 MHz, CDCl3): d=
;
1H NMR (400 MHz, CDCl3): d=8.07 (d, J=
ACHTUNGTRENNUNG
138.7, 137.6, 132.5, 131.6, 128.1, 126.0, 121.3, 53.2, 30.8, 24.4;
ESI-HR-MS: m/z=253.1009, calcd. for C12H16N2O2S (M+
H)+: 253.1005.
(E)-3-(Butylimino)-2-(4-chlorophenyl)-2,3-dihydrobenzo-
[d]isothiazole 1,1-dioxide (5m): Light yellow oil; IR (KBr):
n=2968, 2354, 1638, 1315, 1231, 1186, 1145, 1017, 731,
(E)-2-(tert-Butyl)-3-(tert-butylimino)-2,3-dihydrobenzo-
[d]isothiazole 1,1-dioxide (5f): White solid; mp 101–1038C;
IR (KBr): n=2969, 2361, 1665, 1307, 1196, 1119, 990,
561 cmÀ1 1H NMR (400 MHz, CDCl3): d=7.86 (d, J=
;
7.6 Hz, 1H), 7.63 (t, J=7.6 Hz, 1H), 7.38 (t, J=7.6 Hz, 1H),
7.30 (d, J=8.4 Hz, 2H), 6.86–6.81 (m, 3H), 3.81 (t, J=
7.0 Hz, 2H), 1.88–1.85 (m, 2H), 1.46–1.40 (m, 2H), 0.95 (t,
J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=146.7,
143.2, 136.8, 133.0, 132.6, 130.0, 129.0, 126.7, 124.5, 121.4,
121.0, 39.7, 29.9, 20.0, 13.5; ESI-HR-MS: m/z=349.0765,
calcd. for C17H18ClN2O2S (M+H)+: 349.0772.
539 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=7.98 (d, J=
7.6 Hz, 1H), 7.71 (d, J=7.2 Hz, 1H), 7.62–7.53 (m, 2H),
1.70 (s, 9H), 1.43 (s, 9H); 13C NMR (100 MHz, CDCl3): d=
139.1, 138.3, 132.0, 131.3, 127.8, 124.9, 120.5, 59.4, 53.8, 30.6,
27.9; ESI-HR-MS: m/z=317.1281, calcd. for C15H22N2O2S
(M+Na)+: 317.1294.
(E)-3-(tert-Butylimino)-2-propyl-2,3-dihydrobenzo[d]iso-
thiazole 1,1-dioxide (5g): Light yellow oil; IR (KBr): n=
2969, 2357, 1665, 1515, 1461, 1312, 1236, 1181, 1007, 544;
1H NMR (400 MHz, CDCl3): d=8.08 (d, J=8.0 Hz, 1H),
7.87 (d, J=7.2 Hz, 1H), 7.70–7.62 (m, 2H), 3.56 (t, J=
(E)-2-(4-Chlorophenyl)-3-[(2-morpholinoethyl)imino]-2,3-
dihydrobenzo[d]isothiazole 1,1-dioxide (5n): Yellow oil; IR
(KBr): n=2983, 2368, 1663, 1321, 1214, 1197, 1145, 1026,
1
781, 532 cmÀ1; H NMR (400 MHz, CDCl3): d=7.85 (d, J=
7.6 Hz, 1H), 7.63 (t, J=7.6 Hz, 1H), 7.38 (t, J=7.6 Hz, 1H),
7.32–7.28 (m, 2H), 6.86–6.79 (m, 3H), 3.95 (t, J=6.8 Hz,
2H), 3.75–3.56 (m, 4H), 2.80 (t, J=6.8 Hz, 2H),2.64–2.43
(m, 4H); 13C NMR (100 MHz, CDCl3): d=146.5, 143.2,
136.7, 133.1, 132.7, 129.6, 129.1, 126.7, 124.4, 121.5, 120.9,
66.8, 60.2, 55.8, 53.5; ESI-HR-MS: m/z=406.0983, calcd. for
C19H21ClN3O3S (M+H)+: 406.0987.
7.4 Hz, 1H), 1.79–1.70 (m, 2H), 1.45ACTHNUTRGNE(NUG s, 9H), 0.92 (t, J=
7.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=138.3, 137.9,
132.4, 131.6, 128.3, 125.7, 121.4, 53.2, 40.7, 30.9, 21.3, 11.4;
ESI-HR-MS: m/z=281.1311, calcd. for C14H20N2O2S (M+
H)+: 281.1318.
(E)-3-(tert-Butylimino)-2-isopropyl-2,3-dihydrobenzo[d]-
isothiazole 1,1-dioxide (5h): Light yellow solid; mp 102–
1048C; IR (KBr): n=2972, 2360, 1658, 1301, 1225, 1196,
(E)-2-(4-Chlorophenyl)-3-(cyclohexylimino)-2,3-dihydro-
benzo[d]isothiazole 1,1-dioxide (5o): Yellow oil; IR (KBr):
n=2970, 2347, 1641, 1498, 1325, 1191, 1141, 986, 798,
1
1135, 1008, 751, 541 cmÀ1; H NMR (400 MHz, CDCl3): d=
721 cmÀ1 1H NMR (400 MHz, CDCl3): d=7.81 (d, J=
;
8.06 (d, J=7.6 Hz, 1H), 7.82 (d, J=6.8 Hz, 1H), 7.68–7.60
8.0 Hz, 1H), 7.60 (t, J=7.6 Hz, 1H), 7.37–7.29 (m, 3H),
6.83–6.80 (m, 3H), 4.40–4.26 (m, 1H), 2.27–2.12 (m, 4H),
1.93–1.79 (m, 2H), 1.74–1.56 (m, 1H), 1.42–1.18 (m, 3H);
13C NMR (100 MHz, CDCl3): d=146.9, 142.8, 137.2, 132.8,
132.5, 129.6, 128.8, 126.7, 124.2, 121.0, 120.8, 55.5, 29.7, 26.1,
25.1; ESI-HR-MS: m/z=375.0926, calcd. for C19H20ClN2O2S
(M+H)+: 375.0929.
(m, 2H), 4.59–4.49 (m, 1H), 1.53ACHTUNTGRENNUG(s, 6H), 1.47ACHUTNGTREN(NUGN s, 9H), 0.92 (t,
J=7.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=138.4,
137.9, 132.3, 131.5, 128.3, 125.2, 121.0, 53.4, 46.4, 30.9, 19.6;
ESI-HR-MS: m/z=281.1310, calcd. for C14H20N2O2S (M+
H)+: 281.1318.
(E)-3-(tert-Butylimino)-2-cyclohexyl-2,3-dihydrobenzo[d]-
isothiazole 1,1-dioxide (5i): White solid; mp 133–1358C; IR
(KBr): n=2932, 2360, 1663, 1310, 1223, 1177, 1066,
(E)-2-(4-Chlorophenyl)-3-((2,6-dimethylphenyl)imino)-
2,3-dihydrobenzo[d]isothiazole 1,1-dioxide (5p): Yellow
solid; mp 125–1288C; IR (KBr): n=2922, 2354, 1670, 1497,
757 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=8.08 (d, J=
1
6.8 Hz, 1H), 7.88–7.86 (m, 1H), 7.69–7.62 (m, 2H), 4.24–
1371, 1083, 760, 698 cmÀ1; H NMR (400 MHz, CDCl3): d=
Adv. Synth. Catal. 2012, 354, 2288 – 2300
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asc.wiley-vch.de
2297

Bifu Liu et al.
FULL PAPERS
7.96 (d, J=7.6 Hz, 1H), 7.63–7.39 (m, 6H), 7.12–7.01 (m,
3H), 6.63 (d, J=7.6 Hz, 1H), 2.07 (s, 6H); 13C NMR
(100 MHz, CDCl3): d=151.0, 145.9, 134.0, 133.8, 132.6,
132.0, 131.5, 129.8, 129.4, 129.3, 128.4, 126.4, 124.4, 123.9,
123.8, 18.3; ESI-HR-MS: m/z=397.0781, calcd. for
C21H18ClN2O2S (M+H)+: 397.0772.
2H), 7.33 (t, J=7.6 Hz, 1H), 5.26(br. s, 1H), 4.77–4.39 (m,
1H), 2.73–2.36 (m, 2H), 1.84–1.70 (m, 3H), 1.61–1.50 (m,
2H), 1.36–1.27 (m, 3H); 13C NMR (100 MHz, CDCl3): d=
152.2, 145.0, 133.9, 129.8, 128.7, 126.9, 126.7, 122.7, 122.1,
121.7, 120.4, 119.2, 49.2, 33.3, 25.9, 25.0; ESI-HR-MS: m/z=
277.1615, calcd. for C19H20N2 (M+H)+: 277.1699.
N-(2,6-Dimethylphenyl)phenanthridin-6-amine (9d): Light
yellow solid; mp 201–2038C; IR (KBr): n=3743, 3425, 2922,
(E)-2-(4-Chlorophenyl)-3-[(4-methoxyphenyl)imino]-2,3-
dihydrobenzo[d]isothiazole 1,1-dioxide (5q): Yellow solid;
mp 47–498C; IR (KBr): n=2930, 2357, 1658, 1489, 1412,
1
2360, 1509, 761, 723 cmÀ1; H NMR (400 MHz, DMSO-d6):
1242,1125, 671 cmÀ1 1H NMR (400 MHz, CDCl3): d=7.95
;
d=8.87 (br. s, 1H), 8.71–8.68 (m, 2H), 8.47 (d, J=8.0 Hz,
1H), 7.88 (t, J=7.4 Hz, 1H), 7.76 (t, J=7.4 Hz, 1H), 7.46–
(d, J=7.2 Hz, 1H), 7.60 (t, J=7.6 Hz, 1H), 7.48 (s, 4H),
7.40 (t, J=7.6 Hz, 1H), 6.95–6.88 (m, 4H), 6.81 (d, J=
7.6 Hz, 1H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3): d=
156.8, 151.4, 141.6, 133.6, 133.2, 132.3, 132.0, 131.9, 129.3,
129.1, 125.8, 123.9, 120.7, 114.7, 55.5; ESI-HR-MS: m/z=
399.0572, calcd. for C21H16ClSN2O3 (M+H)+: 399.0565.
(E)-1-[6-(tert-Butylimino)phenanthridin-5(6H)-yl]ethan-
one (8a): White solid; mp 193–1958C; IR (KBr): n=3744,
(m, 4H), 2.20 (s, 6H); 13C NMR
7.36ACTHNUTRGNENG(U m, 2H), 7.30–7.16AHCTUNGTRENNGUN
(100 MHz, DMSO-d6): d=152.2, 144.6, 137.6, 136.1, 133.5,
130.6, 128.6, 127.7, 127.4, 126.4, 125.9, 123.9, 122.7, 122.3,
122.2, 120.3, 118.8, 18.4; ESI-HR-MS: m/z=299.1529, calcd.
for C21H18N2 (M+H)+: 299.1543.
N-(tert-Butyl)dibenzo
Light yellow solid; mp 105–1078C; IR (KBr): n=3743, 3431,
2963, 2360, 1616, 1513, 1478, 1216, 756 cmÀ1 1H NMR
ACHUTGTNRENNUG[b,f]ACHTUNGTRENN[UGN 1,4]oxazepin-11-amine (10a):
2972, 2363, 1664, 1364, 1326, 1195, 766 cmÀ1 1H NMR
;
;
(400 MHz, CDCl3): d=7.42–7.37 (m, 2H), 7.24–7.05 (m,
5H), 6.94–6.90 (m, 1H), 4.57 (br. s, 1H), 1.59 (s, 9H);
13C NMR (100 MHz, CDCl3): d=161.0, 155.1, 151.8, 141.6,
132.3, 127.2, 127.0, 126.9, 125.4, 125.0, 123.0, 120.8, 120.2,
52.2, 29.0; ESI-HR-MS: m/z=267.1497, calcd. for
C17H18N2O (M+H)+: 267.1492.
(400 MHz, CDCl3): d=8.65 (d, J=8.4 Hz, 1H), 8.58 (d, J=
8.0 Hz, 1H), 8.23 (d, J=8.0 Hz, 1H), 8.14 (d, J=8.0 Hz,
1H), 7.88 (t, J=7.6 Hz, 1H), 7.78–7.69 (m, 3H), 1.63 (s,
3H), 1.49 (s, 9H); 13C NMR (100 MHz, CDCl3): d=170.7,
155.0, 143.1, 134.6, 131.3, 130.4, 129.1, 127.8, 126.0, 124.2,
122.5, 122.0, 59.5, 28.5, 25.4; ESI-HR-MS: m/z=315.1459,
calcd. for C19H20N2O (M+Na)+: 315.1468.
N-(2,4,4-Trimethylpentan-2-yl)dibenzoACTHNUGRTENNU[G b,f]ACHTUNTGERN[NUGN 1,4]oxazepin-
11-amine (10b): Yellow solid; mp 44–468C; IR (KBr): n=
(E)-[6-(tert-Butylimino)phenanthridin-5(6H)-yl]ACTHNUGRTNEUNG(phenyl)-
3855, 3743, 2953, 2361, 1620, 1514, 1384, 1224, 759, 680,
methanone (8b): White solid; mp 165–1678C; IR (KBr): n=
516 cmÀ1 1H NMR (400 MHz, CDCl3): d=7.40–7.34 (m,
;
1
2967, 2360, 1651, 1342, 1190, 762 cmÀ1; H NMR (400 MHz,
2H), 7.20–7.03 (m, 5H), 6.92–6.88 (m, 1H), 4.54 (br. s, 1H),
2.07 (s, 2H), 1.60 (s, 6H), 1.08 (s, 9H); 13C NMR (100 MHz,
CDCl3): d=161.1, 154.9, 151.8, 141.7, 132.2, 127.2, 127.0,
126.9, 125.4, 125.1, 122.8, 121.0, 120.2, 56.2, 50.6, 31.8, 31.6,
29.7; ESI-HR-MS: m/z=323.2104, calcd. for C21H26N2O
(M+H)+: 323.2118.
CDCl3): d=8.39–8.36 (m, 2H), 8.23–8.21 (m, 1H), 8.13–8.11
(m, 1H), 7.69–7.57 (m, 4H), 7.23–7.20 (m, 2H), 6.80–6.73
(m, 3H), 1.65ACHTUNGTRENNUNG
(s, 9H); 13C NMR (100 MHz, CDCl3): d=
171.2, 154.0, 142.4, 138.7, 134.0, 131.0, 129.9, 128.7, 128.2,
127.4, 127.3, 127.0, 126.8, 126.4, 126.2, 123.6, 121.9, 121.7,
60.1, 28.6; ESI-HR-MS: m/z=355.1810, calcd. for
C24H22N2O (M+H)+: 355.1805.
N-Cyclohexyldibenzo
G
G
(10c):
Light yellow solid; mp 149–1518C; IR (KBr): n=3450, 2361,
N-(tert-Butyl)phenanthridin-6-amine (9a):[18c] Light yellow
solid; mp 92–948C; IR (KBr): n=3741, 2960, 2359, 1583,
1
1646, 1513, 1110, 618 cmÀ1; H NMR (400 MHz, CDCl3): d=
7.43–7.37 (m, 2H), 7.21–7.13 (m, 3H), 7.10–7.02 (m, 2H),
6.93–6.89 (m, 1H), 4.63 (br. s, 1H), 4.20–4.00 (m, 1H), 2.20–
2.16 (m, 2H), 1.78–1.73 (m, 2H), 1.68–1.63 (m, 1H), 1.51–
1.41 (m, 2H), 1.31–1.20 (m, 3H); 13C NMR (100 MHz,
CDCl3): d=161.0, 155.7, 151.9, 141.5, 132.5, 127.0, 126.9,
126.5, 125.5, 125.1, 123.2, 120.9, 120.3, 49.4, 33.0, 25.9, 24.9;
ESI-HR-MS: m/z=293.1638, calcd. for C19H20N2O (M+
H)+: 293.1648.
1522, 1425, 1213, 757, 722 cmÀ1
;
1H NMR (400 MHz,
CDCl3): d=8.55 (d, J=8.4 Hz, 1H), 8.42 (d, J=8.0 Hz, 1H),
8.00 (d, J=8.0 Hz, 1H), 7.83 (d, J=8.4 Hz, 1H), 7.77–7.69
(m, 2H), 7.60 (t, J=7.6 Hz, 1H), 7.45 (t, J=7.4 Hz, 1H),
5.35(br. s, 1H), 1.85 (s, 9H); 13C NMR (100 MHz, CDCl3):
d=152.1, 144.7, 133.7, 129.5, 128.5, 127.3, 126.6, 122.6, 122.1,
121.7, 121.7, 120.1, 119.5, 51.8, 29.3; MS (EI): m/z=77, 110,
140, 151, 166, 178, 194, 235, 250.
N-(2,4,4-Trimethylpentan-2-yl)phenanthridin-6-amine
(9b): Light yellow oil; IR (KBr): n=3743, 2952, 2360, 1522,
1425, 1383, 1223, 757, 720 cmÀ1
;
1H NMR (400 MHz,
Acknowledgements
CDCl3): d=8.56 (d, J=8.0 Hz, 1H), 8.40 (d, J=8.0 Hz, 1H),
7.92 (d, J=8.0 Hz, 1H), 7.82 (d, J=8.0 Hz, 1H), 7.73 (t, J=
8.0 Hz, 1H), 7.67–7.59 (m, 2H), 7.40 (t, J=7.4 Hz, 1H), 5.36
(br. s, 1H), 2.27 (s, 2H), 1.84 (s, 6H), 1.16 (s, 9H); 13C NMR
(100 MHz, CDCl3): d=152.0, 144.8, 133.8, 129.5, 128.5,
127.3, 126.7, 122.8, 122.0, 121.7, 121.6, 120.1, 119.7, 55.8,
51.6, 31.8, 31.7, 29.8; ESI-HR-MS: m/z=307.2157, calcd. for
C21H26N2 (M+H)+: 307.2169.
We thank the National Natural Science Foundation of China
(20932002), National Basic Research Program of China (973
Program) (No. 2011CB808600), Guangdong Natural Science
Foundation (No. 10351064101000000) and the Fundamental
Research Funds for the Central Universities (2010ZP0003)
for financial support.
N-Cyclohexylphenanthridin-6-amine (9c): Light yellow
solid; mp 83–858C; IR (KBr): n=3743, 2927, 2851, 2360,
1582, 1523, 1427, 758, 722 cmÀ1
;
1H NMR (400 MHz,
CDCl3): d=8.50 (d, J=8.0 Hz, 1H), 8.33 (d, J=8.0 Hz, 1H),
7.84–7.81 (m, 2H), 7.12 (t, J=7.6 Hz, 1H), 7.59–7.54 (m,
2298
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Adv. Synth. Catal. 2012, 354, 2288 – 2300

À
Palladium-Catalyzed C C Coupling of Aryl Halides with Isocyanides
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