Phosphine-catalyzed [3+2] and [4+3] annulation reactions of C,N-cyclic azomethine imines with allenoates

Article abstract of DOI:10.1002/adsc.201100831

Phosphine-catalyzed [3+2] and [4+3] annulation reactions of C,N-cyclic azomethine imines with allenoates have been developed to give a variety of pharmaceutically attractive tetrahydroisoquinoline derivatives in moderate to excellent yields. The two disti

Full text of DOI:10.1002/adsc.201100831

FULL PAPERS
DOI: 10.1002/adsc.201100831
Phosphine-Catalyzed [3+2] and [4+3]Annulation Reactions of
C,N-Cyclic Azomethine Imines with Allenoates
Chengfeng Jing,a Risong Na,a Bo Wang,a Honglei Liu,a Lei Zhang,a Jun Liu,a,b
Min Wang,a Jiangchun Zhong,a,* Ohyun Kwon,c and Hongchao Guoa,*
a
Department of Applied Chemistry, China Agricultural University, Beijing 100193, Peopleꢀs Republic of China
Fax : (+86)-10-6282-0325; phone: (+86)-10-62731356; e-mail: dr_zhongjiangchun@yahoo.com.cn or hchguo@cau.edu.cn
Chemical Industry Press, 13 Qingnianhu South St., Beijing 100011, Peopleꢀs Republic of China
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, USA
b
c
Received: October 24, 2011; Published online: March 27, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100831.
Abstract: Phosphine-catalyzed [3+2] and [4+3]an-
nulation reactions of C,N-cyclic azomethine imines
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
with allenoates have been developed to give a variety phine was used; for a-ArCH2-substituted allenoates,
of pharmaceutically attractive tetrahydroisoquinoline the reaction pathway was controlled by the phos-
derivatives in moderate to excellent yields. The two phine catalyst used.
distinct reaction pathways, [3+2] and [4+3]cycliza-
tion, depend on the nature of the nucleophilic phos- Keywords: allenoates; annulation; azomethine
phine and the allenoate. Generally, for a-alkylallen- imines; catalysis; phosphines
Introduction
coupling partners. Consequently, searching for a new
electrophilic substrate with a proper reactivity that
Tetrahydroisoquinoline derivatives are structural can effectively be utilized in the synthesis of heterocy-
motifs often occurring in natural products and phar- cles with new skeletons or structural features consti-
macologically important agents exhibiting a wide tutes a major challenge for the formation of diverse
range of biological activities such as antitumor, antibi- cycloaddition products from the nucleophilic phos-
otic, antivirus, anti-inflammatory, anticoagulation, and phine catalysis of allenes. Recently, a new type of
bronchodilation.[1] Therefore, the synthesis of tetrahy- electrophilic coupling reagent, N,N’-cyclic azomethine
À À
droisoquinoline derivatives has attracted much atten- imines (1), has been used as an N N C trio-of-atoms
tion.[2] Although some synthetic methods have been synthon in the phosphine-catalyzed [3+2]annulation
developed,[2] novel procedures applicable for their with a-substituted allenoates to produce biologically
synthesis would still be highly desirable.
active tetrahydropyrazolopyrazolones (Scheme 1).[12]
The nucleophilic phosphine-catalyzed intermolecu- This work prompted us to investigate whether the cat-
lar cycloaddition reaction has been developed as one alytic process can be used in the reactions of another
of the most powerful tools for the convergent synthe- noteworthy class of azomethine imines, C,N-cyclic
sis of a variety of carbo- and heterocycles from sim- imines, to synthesize pharmaceutically attractive tet-
pler precursors.[3] In these cycloaddition reactions, ac- rahydroisoquinoline derivatives. In addition, while the
tivated allenes have been used as a versatile reaction [4+2] and [3+2]cycloadditions are widely explored
substrate and exhibited super diverse reactivity to- in phosphine-catalyzed annulation reactions of alle-
wards electrophilic reagents. These allenes act as one- noates, only two examples of the phosphine-catalyzed
, two-, three- or four-carbon synthons to react with [4+3]annulation reactions of allenes were reported
various electrophilic coupling partners including alde- so far.[8,12] Thus, we conceived to use an a-substituted
hydes, activated alkenes, imines or aziridines to allenoate as a 1,4-dipole to develop a novel [4+3]cy-
render all kinds of annulation reactions.[4–11] Such a di- cloaddition.
verse pattern of reactivity of the allene as one of the
N,N’-Cyclic azomethine imines 1 have recently
reaction substrates is often induced by its electrophilic been employed as efficient 1,3-dipoles in various
Adv. Synth. Catal. 2012, 354, 1023 – 1034
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Chengfeng Jing et al.
FULL PAPERS
Table 1. Screening of phosphine catalysts for annulations of
azomethine imines with allenoates.[a]
Entry
PR3
4af, Yield [%][b]
5af, Yield [%][b]
1
2
3
4
5
6
–
0[c]
66
<5
23
18
20
0[c]
<5
90
15
33
Scheme 1. Phosphine-catalyzed annulations of azomethine
imines with allenoates.
PMe3
PBu3
Me2PPh
EtPPh2
PPh3
metal-catalyzed or organocatalytic cycloadditions.[13]
However, catalytic cycloaddition reactions of C,N-
cyclic azomethine imines have rarely been studied.
Only three examples involving C,N-cyclic substrates
have been reported so far.[14] In 2008, Charette and
<5
[a]
1.2 equiv. of allenoate was used.
Isolated yields, unless otherwise indicated.
Without phosphine catalyst.
[b]
[c]
co-workers reported an Ni
ACHTUNGTREN(NNUG ClO4)2-catalyzed [3+3] cy-
cloaddition of C,N-cyclic aromatic azomethine imines
with 1,1-cyclopropane diesters, giving access to allenoates often occur,[15] the reaction of 2a with 3f
unique tricyclic dihydroquinoline derivatives.[14a] In was first carried out in dichloromethane at room tem-
2010, Maruoka and co-workers developed the perature in the absence of phosphines, no new spot
BINOL-Ti-catalyzed enantioselective [3+2]cycload- was observed on the TLC (entry 1), therefore, the
dition of C,N-cyclic azomethine imines with a,b-unsa- background reaction resulting from possible direct
turated
aldehydes,
providing
derivatives
of [3+2]cycloaddition of azomethine imine and alle-
1,2,3,5,6,10b-hexahydropyrazoloAHCUTNGTRENNUNG
[5,1-a]isoquinoline;[14b] noate in dichloromethane at room temperature could
in 2011, Maruoka’s group further developed an axially be excluded. However, once the temperature is above
chiral dicarboxylic acid-catalyzed asymmetric inverse- 308C, the thermal cycloaddition product would be ob-
electron-demand 1,3-dipolar cycloaddition of the served. In order to avoid the background reaction,
above azomethine imines with vinyl ether or vinylo- when the following reactions were performed, the re-
gous
aza-enamines,
affording
1,2,3,5,6,10b- action temperature was strictly controlled at room
hexahydropyrazoloAHCTUNGTRENNUNG
[5,1-a]isoquinoline derivatives.[14c] temperature (258C). Since the efficiency of nucleo-
Herein, we report the first example of phosphine-cat- philic phosphine catalysis often depends on the
alyzed cycloaddition of C,N-cyclic azomethine imines nature of the tertiary phosphine catalyst, several
with allenoates. The novel [3+2] and [4+3]annula- phosphines with different nucleophilicity have been
tion reactions were achieved depending on the screened (entries 2–6). When PMe3 was used, a 66%
number of carbon atoms that the allenoates contrib- yield of [3+2]cyclization product and <5%yield of
ute to the final cyclic products, furnishing [4+3]cyclization product were achieved (entry 2). In
1,2,3,5,6,10b-hexahydropyrazolo
ACHTUNGTRENN[UGN 5,1-a]isoquinoline de- contrast, with PBu3 as the catalyst, <5%yield of [3+
rivatives and 1,4,5,7,8,12b-hexahydro-[1,2]diazepino- 2]cyclization product and 90%yield of [4+3]product
A
derivatives,
respectively were obtained (entry 3). The structures of the new
[3+2]annulation product (4) and [4+3]product (5)
were confirmed by NMR spectra and subsequently by
the X-ray crystallography of 4ef and 5df (see Table 3
below). Notably, a single diastereomer (5af) of [4+
3]cyclization product was obtained, and other diaste-
Results and Discussion
We initiated our study and screened the reaction con- reomer was not observed. When phosphines Me2PPh,
ditions by evaluating the reactions of azomethine EtPPh2 and PPh3 were utilized as catalysts, the reac-
imine 2a and allenoate 3f (Table 1). Considering that tions were somewhat sluggish and both overall yield
the direct cycloadditions of azomethine imines with and chemoselectivity were unsatisfactory (entries 4–
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Phosphine-Catalyzed [3+2] and [4+3]Annulation Reactions of C,N-Cyclic Azomethine Imines
Table 2. Phosphine-catalyzed cycloaddition of azomethine
imine (2a) with allenoates.[a]
18). Those reactions demonstrated excellent chemose-
lectivity towards the [3+2]products in most cases,
giving only very small amounts (<1%) of the [4+
3]products (entries 2–5, 14–18), except that the reac-
tion of a-methylallenoate (3a) exhibited a moderate
chemoselectivity to deliver [3+2] and [4+3]products
in 62% and 7% yields, respectively (entry 1).
When b’-arylallenoate was used as substrate, PBu3
and Me3P displayed quite different catalytic behav-
iors. Using PBu3 as the catalyst, contrary to chemose-
lectivity of a-alkylallenoates (3a–3e), all b’-arylallen-
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
Entry R1
PR3 4, Yield [%][b] 5, Yield [%][b]
AHCTUNGTRENNUNG
1
2
3
4
5
6
7
8
H (3a)
Me (3b)
Et (3c)
i-Pr (3d)
t-Bu (3e)
Ph (3f)
2-MeC6H4 (3g) PBu3 4ag, <2
3-MeC6H4 (3h) PBu3 4ah, <5
4-MeC6H4 (3i) PBu3 4ai, 16
PBu3 4aa, 62
PBu3 4ab, 89
PBu3 4ac, 87
PBu3 4ad, 79
PBu3 4ae, 74
PBu3 4af, <5
5aa, 7
excellent yields, together with small amounts of [3+
2]product (entries 6–13). A broad range of aryl
groups with electron-donating or electron-withdraw-
ing substituents on the benzene ring could be tolerat-
ed in the process. In general, allenoates bearing elec-
tron-withdrawing groups on the benzene ring provid-
ed somewhat higher yields of the [4+3]cyclization
products than did those bearing electron-donating
groups (entries 10–13 and 7–9). Particularly, with b’-
(4-BrC6H4)-substituted allenoate (3m) as substrate,
the desired [4+3]product was produced in up to 93%
yield (entry 13). With PMe3 as the catalyst, however,
the [4+3]products were obtained as the major prod-
uct in only three cases (entries 23, 24, 26). In another
five cases (entries 19—22, 25), the [3+2]products
were produced as the major products.
The generality of this reaction was explored with
several azomethine imines bearing different substitu-
ents on the benzene rings. a-Benzylallenoate (3f) and
a-ethylallenoate (3b) were used as the standard alle-
noates. The reaction is tolerant of a wide range of
azomethine imines (2b–2f), providing a series of the
corresponding products in moderate to excellent
yields with moderate to excellent chemoselectivity
(Table 3). In the presence of 20 mol% of PBu3, the re-
actions of azomethine imines (2b–2f) with a-benzylal-
lenoate (3f) afforded the [4+3]products as the major
products in 61–73% yield, and the [3+2]products as
the minor products in 23–34% yield (entries 1–5). In
5ab, <1
5ac, <1
5ad, <1
5ae, <1
5af, 90
5ag, 42
5ah, 55
5ai, 71
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
4-FC6H4 (3j)
PBu3 4aj, <5
5aj, 92
5ak, 75
5al, 84
3-ClC6H4 (3k) PBu3 4ak, <5
4-ClC6H4 (3l) PBu3 4al, <5
4-BrC6H4 (3m) PBu3 4am, <5
H (3a)
Me (3b)
Et (3c)
i-Pr (3d)
t-Bu (3e)
Ph (3f)
2-MeC6H4 (3g) PMe3 4ag, 18
3-MeC6H4 (3h) PMe3 4ah, 55
4-MeC6H4 (3i) PMe3 4ai, 92
5am, 93
5aa, <1
5ab, <1
5ac, <1
5ad, <1
5ae, <1
5af, <1
5ag, <5
5ah, 11
5ai, <5
5aj, 27
PMe3 4aa, 79
PMe3 4ab, 91
PMe3 4ac, 93
PMe3 4ad, 92
PMe3 4ae, 60
PMe3 4af, 66
4-FC6H4 (3j)
PMe3 4aj, 18
3-ClC6H4 (3k) PMe3 4ak, 28
4-ClC6H4 (3l) PMe3 4al, 40
4-BrC6H4 (3m) PMe3 4am, 30
5ak, 36
5al, <5
5am, 35
[a]
[b]
1.2 equiv. of allenoate was used.
Isolated yields, unless otherwise indicated.
6). On the basis of these results, PBu3 and PMe3 were contrast, using 20 mol% of PMe3 as the catalyst, the
established as the optimal catalysts in terms of both reactions of azomethine imines with a-benzylalle-
yield and chemoselectivity.
noate (3f) demonstrated excellent chemoselectivity,
With 20 mol% of PBu3 or PMe3 as catalyst, the an- giving the [3+2]products as major product in 40–
nulation reactions of C,N-cyclic azomethine imine 2a 92% yield and [4+3]product in <1% yield (en-
with various allenoates were performed in dichloro- tries 6–10). In these cases, a significant electronic
methane at room temperature for 24 h to provide the effect was observed. Electron-donating alkyl-substi-
corresponding products in moderate to excellent tuted azomethine imines provided lower yields than
yields (Table 2).[16] Especially, with either PBu3 or those with electron-withdrawing groups (entries 6, 7
PMe3 as the catalyst, a-alkylallenoates (3a–3e) under- vs. entries 8–10). When a-ethylallenoate (3b) was em-
went the reactions to afford the [3+2]products, ployed as the substrate, under the catalysis of
1,2,3,5,6,10b-hexahydropyrazolo-[5,1-a]isoquinoline
20 mol% PBu3, the [3+2]cycloaddition products were
derivatives, as the major products (entries 1–5, 14– acquired in uniformly high yields with excellent che-
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FULL PAPERS
Table 3. Phosphine-catalyzed cycloaddition of azomethine imines (2) with allenoates.[a]
Entry
R1
R2
PR3
4, Yield [%][b]
5, Yield [%][b]
1
2
3
4
5
6
7
8
5-Me (2b)
7-Me (2c)
6-Br (2d)
7-Br (2e)
7-Cl (2f)
5-Me (2b)
7-Me (2c)
6-Br (2d)
7-Br (2e)
7-Cl (2f)
5-Me (2b)
7-Me (2c)
6-Br (2d)
7-Br (2e)
7-Cl (2f)
Ph (3f)
Ph (3f)
Ph (3f)
Ph (3f)
Ph (3f)
Ph (3f)
Ph (3f)
Ph (3f)
Ph (3f)
Ph (3f)
Et (3c)
Et (3c)
Et (3c)
Et (3c)
Et (3c)
PBu3
PBu3
PBu3
PBu3
PBu3
PMe3
PMe3
PMe3
PMe3
PMe3
PBu3
PBu3
PBu3
PBu3
PBu3
4bf, 24
4cf, 23
4df, 34
4ef, 23
4ff, 27
4bf, 40
4cf, 46
4df, 73
4ef, 92
4ff, 80
4bc, 95
4cc, 97
4dc, 87
4ec, 96
4fc, 95
5bf, 73
5cf, 68
5df, 61
5ef, 62
5ff, 62
5bf, <1
5cf, <1
5df, <1
5ef, <1
5ff, <1
5bc, <1
5cc, <1
5dc, <1
5ec, <1
5fc, <1
9
10
11
12
13
14
15
[a]
1.2 equiv. of allenoate was used.
Isolated yields, unless otherwise indicated.
[b]
moselectivity (entries 11–15). The X-ray crystallo-
graphic structures of 4ef and 5df are shown in the
Figure 1 and Figure 2.[17]
Figure 2. ORTEP view of compound 5df. The hydrogen
atoms have been omitted for clarity.
Asymmetric variants of these cyclizations had been
investigated too. Unfortunately, a variety of commer-
cial available chiral phosphines such as DiPAMP,
BINAP, Me-DuPhos, TangPhos, Et-BINEPINE, t-Bu-
BINEPINE, FerroPHANE, SITCP and Et-BPE were
not active in the reactions and afforded very small
amounts of [3+2]cyclization products (<10% yield
and <10% ee) and no [4+3]cyclization product.
Figure 1. ORTEP view of compound 4ef. The hydrogen
atoms have been omitted for clarity.
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Phosphine-Catalyzed [3+2] and [4+3]Annulation Reactions of C,N-Cyclic Azomethine Imines
Scheme 2. A plausible reaction mechanism for the phosphine-catalyzed cycloaddtion of azomethine imines with allenoates.
The transformations of [3+2] and [4+3]cyclization Conclusions
products have been demonstrated in several reports
for the synthesis of tetrahydroisoquinoline derivatives In summary, phosphine-catalyzed [3+2] and [4+
and other useful compounds. For example, the 3]cycloaddition reactions of C,N-cyclic azomethine
1,2,3,5,6,10b-hexahydropyrazoloACTHNUTRGNEU[GN 5,1-a]isoquinoline de- imines with allenoates have successfully been devel-
rivatives 4 could further be transformed to 1,3-di- oped, providing the 1,2,3,5,6,10b-hexahydropyrazolo-
À
G
ACHTUNGTRENNUNG
rium iodide (SmI2),[14b,18] reduced with SmI2 and ox- hexahydro
G
ACHTUNGTRENNUNG
[12]
idation[12] to give biologically important compounds tives, respectively, in high yields. Particularly, the
or building blocks for bioactive compounds. novel [4+3]cycloaddition represents one of the few
On the basis of the reported mechanistic studies of examples of phosphine-catalyzed [4+3]cycloaddition
nucleophilic phosphine-catalyzed reactions,[3] as of the allenoates.
shown in Scheme 2, a plausible mechanism has been
outlined. The zwitterionic intermediate A, which was
formed from the addition of PBu3 to the b-carbon of
allenoate, attacks the azomethine imine 2a via g-
carbon atom of A to provide the intermediate B. The
Experimental Section
intramolecular conjugate addition of B accomplishes
the [3+2]cyclization to form b-phosphonium enoate
C, which undergoes facile b-elimination to regenerate
the catalyst, affording the final [3+2]product 4.
When R is a hydrogen atom or aryl, the intermediate
B isomerizes into another amide species F due to the
more acidic nature of the g-proton. The ylide G
formed from the 7-endo cyclization of F, expels the
General Procedures
All reactions were performed under an argon atmosphere in
oven-dried glassware with magnetic stirring. Unless other-
wise stated, all reagents were purchased from commercial
suppliers and used without further purification. Dichlorome-
thane employed in the reactions was freshly distilled from
CaH2. Organic solutions were concentrated under reduced
pressure using a rotary evaporator or oil pump. Reactions
were monitored through thin-layer chromatography (TLC)
catalyst PBu3 through the ylide-to-enoate conversion
to furnish the [4+3]product 5. Compared with PBu3, on silica gel-precoated glass plates. Chromatograms were vi-
sualized by fluorescence quenching under UV light at
254 nm. Flash column chromatography was performed using
Qingdao Haiyang flash silica gel (200–300 mesh). Infrared
spectra were recorded using a Bruker Optics TENSOR 27
instrument. 1H and 13C NMR spectra were recorded in
CDCl3 using a Bruker 300M spectrometer, as indicated. Ac-
curate mass measurements were performed using an Agilent
instrument with the ESI-MS technique. X-ray crystallo-
graphic data were collected using a Bruker SMART CCD-
based diffractometer equipped with a low-temperature ap-
paratus operated at 100 K.
when PMe3 is used as the catalyst, conjugate addition
of the amide to the b-phosphonium enoates in B is
the major reaction pathway in most cases, resulting in
the [3+2]product due to decreased steric congestion
at the b-carbon atom.
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Chengfeng Jing et al.
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(E)-Ethyl 2-[3-benzoyl-1,5,6,10b-tetrahydropyrazolo
a]isoquinolin-2(3H)-ylidene]-4-methylpentanoate (4ad):
ACHTUNGTRENNUNG[5,1-
Preparation of C,N-Cyclic Azomethine Imines (2)
All C,N-cyclic azomethine imines (2) were prepared by the
Yield: 92% (Table 2, entry 17); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.58; IR (film): nmax =2957, 2867,
1704, 1644, 1600, 1581, 1493, 1456, 1367, 1297, 1217, 1115,
reported procedure.[14b,19]
1063, 1028, 973, 910, 863, 790, 763, 730, 696, 677, 647 cmÀ1
;
General Procedure for the [3+2] and [4+3]Cyclo-
addition Reactions of Azomethine Imines and
Allenoate
1H NMR (300 MHz, CDCl3): d=0.85 (d, J=6.5 Hz, 3H),
0.93 (d, J=6.6 Hz, 3H), 1.30 (t, J=7.1 Hz, 3H), 1.83–1.96
(m, 1H), 2.04 (dd, J=13.9, 9.5 Hz, 1H), 2.51–2.57 (m, 1H),
2.71–2.82 (m, 1H), 2.97–3.09 (m, 2H), 3.23–3.41 (m, 2H),
3.60 (ddd, J=18.7, 8.3, 1.4 Hz, 1H), 4.12–4.29 (m, 3H),
6.99–7.16 (m, 4H), 7.36–7.49 (m, 3H), 7.69–7.73 (m, 2H);
13C NMR (75 MHz, CDCl3): d=14.2, 22.0, 23.4, 27.6, 29.2,
39.3, 40.0, 47.7, 60.2, 61.3, 122.1, 126.3, 126.7, 127.1, 127.6,
128.2, 128.4, 131.1, 132.3, 135.3, 135.4, 147.9, 167.7, 171.3;
An oven-dried, 15-mL Schlenk tube was charged with azo-
methine imine (0.125 mmol), 5 mL of CH2Cl2 and allenoate
(0.15 mmol) at room temperature. Then, phosphine
(0.025 mmol) was added to the above solution and the mix-
ture was stirred at room temperature for 24 h. The reaction
mixture was concentrated and the residue was purified by
flash column (ethyl acetate/petroleum ether) to afford the
corresponding cycloaddition product.
+
HR-MS (ESI): m/z=419.2319, calcd. for C26H31N2O3 [M+
H]+: 419.2329.
(E)-Ethyl 2-[3-benzoyl-1,5,6,10b-tetrahydropyrazoloACTHNUTRGNEU[GN 5,1-
(E)-Ethyl 2-[3-benzoyl-1,5,6,10b-tetrahydropyrazoloACHTUNGTRENNUNG[5,1-
a]isoquinolin-2(3H)-ylidene]-propanoate (4aa): Yield: 79%
(Table 2, entry 14); a yellow solid. TLC (EtOAc/petroleum
ether 1/5): Rf =0.52; IR (film): nmax =2965, 2929, 2849, 1703,
1644, 1600, 1580, 1493, 1446, 1368, 1281, 1222, 1104, 1041,
a]isoquinolin-2(3H)-ylidene]-4,4-dimethylpentanoate (4ae):
Yield: 74% (Table 2, entry 5); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.60; IR (film): nmax =2953, 1705,
1682, 1541, 1508, 1456, 1364, 1294, 1165, 1094, 1067, 1026,
1
911, 866, 789, 762, 730, 677, 647 cmÀ1; H NMR (300 MHz,
789, 762, 695, 677 cmÀ1 1H NMR (300 MHz, CDCl3): d=
;
CDCl3): d=1.31 (t, J=7.1 Hz, 3H), 1.94 (t, J=1.9 Hz, 3H),
2.77 (dd, J=15.5, 2.4 Hz, 1H), 2.94–3.10 (m, 2H), 3.14–3.23
(m, 1H), 3.37–3.41 (m, 1H), 3.71 (ddd, J=18.7, 8.4, 1.9 Hz,
1H), 4.21 (q, J=7.1 Hz, 2H), 4.31 (apparent t, 1H), 7.02–
7.17 (m, 4H), 7.37–7.49 (m, 3H), 7.71–7.74 (m, 2H);
13C NMR (75 MHz, CDCl3): d=14.4, 16.7, 29.1, 40.2, 47.8,
60.5, 61.6, 117.9, 118.1, 126.4, 126.8, 127.1, 127.7, 128.3,
128.5, 131.1, 132.3, 135.22, 135.24, 148.5, 167.6, 170.7; HR-
0.92 (s, 9H), 1.31 (t, J=7.1 Hz, 3H), 2.27 (d, J=14.1 Hz,
1H), 2.64 (d, J=14.1 Hz, 1H), 2.77 (d, J=15.5 Hz, 1H),
3.06 (dtd, J=17.0, 12.4, 4.0 Hz, 2H), 3.38–3.45 (m, 3H),
4.16–4.23 (m, 3H), 6.98–7.14 (m, 4H), 7.36–7.49 (m, 3H),
7.67–7.70 (m, 2H); 13C NMR (75 MHz, CDCl3): d=14.2,
29.3, 29.9, 32.9, 40.3, 42.3, 47.6, 60.3, 61.4, 120.9, 126.3, 126.8,
127.1, 127.7, 128.25, 128.32, 131.1, 132.4, 135.3, 135.7, 147.6,
168.9, 171.7; HR-MS (ESI): m/z=433.2495, calcd. for
+
MS (ESI): m/z=377.1858, calcd. for C23H25N2O3 [M+H]+:
+
C27H33N2O3 [M+H]+: 433.2486.
377.1860.
(E)-Ethyl 2-[3-benzoyl-1,5,6,10b-tetrahydropyrazolo
a]isoquinolin-2(3H)-ylidene]-3-phenylpropanoate (4af):
ACHTUNGTRENNUNG[5,1-
(E)-Ethyl 2-[3-benzoyl-1,5,6,10b-tetrahydropyrazoloACTHNUTRGNEU[GN 5,1-
a]isoquinolin-2(3H)-ylidene]-butanoate (4ab): Yield: 91%
(Table 2, entry 15); yellow solid. TLC (EtOAc/petroleum
ether 1/5): Rf =0.56; IR (film): nmax =2926, 2853, 1704, 1638,
1581, 1493, 1455, 1368, 1299, 1240, 1220, 1142, 1106, 1062,
Yield: 66% (Table 2, entry 19); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.51; IR (film): nmax =2929, 1703,
1541, 1508, 1493, 1455, 1368, 1298, 1219, 1095, 1030. 770,
1
699, 677 cmÀ1; H NMR (300 MHz, CDCl3): d=1.20 (t, J=
1
1028, 973, 909, 865, 786, 736, 695, 678, 648 cmÀ1; H NMR
7.1 Hz, 3H), 2.62–2.78 (m, 2H), 2.84–2.97 (m, 2H), 3.25 (dd,
J=18.9, 10.1 Hz, 1H), 3.58–3.76 (m, 2H), 3.98 (d, J=
15.8 Hz, 1H), 4.08–4.27 (m, 3H), 6.99–7.04 (m, 2H), 7.07–
7.13 (m, 2H), 7.16–7.23 (m, 5H), 7.27–7.39 (m, 2H), 7.41–
7.47 (m, 1H), 7.51–7.56 (m, 2H); 13C NMR (75 MHz,
CDCl3): d=14.1, 29.1, 35.4, 40.5, 47.4, 60.6, 61.0, 122.0,
125.8, 126.3, 126.8, 127.1, 127.6, 128.1, 128.2, 128.4, 128.6,
131.0, 132.3, 135.1, 135.2, 140.7, 149.3, 167.4, 170.8; HRMS
(300 MHz, CDCl3): d=1.12 (t, J=7.4 Hz, 3H), 1.30 (t, J=
7.1 Hz, 3H), 2.34–2.47 (m, 2H), 2.73–2.79 (m, 1H), 2.91–
3.16 (m, 3H), 3.35–3.40 (m, 1H), 3.68 (dd, J=18.6, 8.5 Hz,
1H), 4.18–4.28 (m, 3H), 7.00–7.16 (m, 4H), 7.35–7.48 (m,
3H), 7.70–7.74 (m, 2H); 13C NMR (75 MHz, CDCl3): d=
12.7, 14.3, 23.8, 29.1, 40.0, 47.6, 60.3, 61.2, 124.6, 126.3, 126.7,
127.1, 127.6, 128.2, 128.5, 131.0, 132.3, 135.25, 135.31, 147.1,
167.4, 171.5; HR-MS (ESI): m/z=391.2016, calcd. for
+
(ESI): m/z=453.2165, calcd. for C29H29N2O3 [M+H]+:
+
C24H27N2O3 [M+H]+: 391.2016.
453.2173.
(E)-Ethyl 2-[3-benzoyl-1,5,6,10b-tetrahydropyrazolo-[5,1-
a]isoquinolin-2(3H)-ylidene]-pentanoate (4ac): Yield: 93%
(Table 2, entry 16); yellow solid. TLC (EtOAc/petroleum
ether 1/5): Rf =0.58; IR (film): nmax =2925, 2853, 1704, 1637,
1541, 1491, 1456, 1291, 1141, 1110, 1033, 910, 863, 789, 747,
(E)-Ethyl 2-[3-benzoyl-1,5,6,10b-tetrahydropyrazolo
ACHTUNGTRENNUNG[5,1-
a]isoquinolin-2(3H)-ylidene]-3-(o-tolyl)propanoate (4ag):
Yield: 18% (Table 2, entry 20); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.50; IR (film): nmax =3062, 3023,
2976, 2932, 2848, 1706, 1682, 1601, 1581, 1493, 1447, 1368,
1299,1272, 1219, 1095, 968, 909, 788, 761, 740, 716, 699, 678,
1
695, 677 cmÀ1; H NMR (300 MHz, CDCl3): d=0.91 (t, J=
7.4 Hz, 3H) 1.30 (t, J=7.1 Hz, 3H), 1.39–1.73 (m, 2H),
2.23–2.33 (m, 1H), 2.45 (ddd, J=14.0, 9.2, 5.0 Hz, 1H),
2.69–2.81 (m, 1H), 2.93–3.22 (m, 3H), 3.33–3.44 (m, 1H),
3.65 (dd, J=18.7, 8.5 Hz, 1H), 4.16–4.28 (m, 3H), 6.99–7.15
(m, 4H), 7.36–7.49 (m, 3H), 7.70–7.73 (m, 2H); 13C NMR
(75 MHz, CDCl3): d=14.2, 21.4, 29.1, 29.6, 32.4, 40.0, 47.6,
60.3, 61.2, 123.1, 126.3, 126.7, 127.1, 127.6, 128.2, 128.4,
131.0, 132.3, 135.3, 147.5, 167.6, 171.4; HR-MS (ESI):
648 cmÀ1
;
1H NMR (300 MHz, CDCl3): d=1.17 (t, J=
7.1 Hz, 3H), 2.27 (s, 3H), 2.66–2.98 (m, 4H), 3.34 (dd, J=
18.8, 10.0 Hz, 1H), 3.61–3.74 (m, 2H), 3.99 (d, J=16.3 Hz,
1H), 4.08–4.18 (m, 2H), 4.22–4.28 (m, 1H), 7.00–7.17 (m,
8H), 7.33–7.38 (m, 2H), 7.42–7.47 (m, 1H), 7.53–7.56 (m,
2H); 13C NMR (75 MHz, CDCl3): d=14.1, 19.8, 29.1, 33.4,
40.3, 47.4, 60.5, 61.1, 121.3, 125.5, 125.9, 126.3, 126.8, 127.1,
127.6, 128.2, 128.4, 128.9, 130.0, 131.0, 132.4, 135.1, 136.2,
+
m/z=405.2177, calcd. for C25H29N2O3 [M+H]+: 405.2173.
1028
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1023 – 1034

Phosphine-Catalyzed [3+2] and [4+3]Annulation Reactions of C,N-Cyclic Azomethine Imines
138.6, 148.9, 162.3, 167.3, 171.1; HR-MS (ESI): m/z=
467.2335, calcd. for C30H31N2O3 [M+H]+: 467.2329.
(E)-Ethyl 2-[3-benzoyl-1,5,6,10b-tetrahydropyrazoloACTHNUTRGNEU[GN 5,1-
(E)-Ethyl 2-[3-benzoyl-1,5,6,10b-tetrahydropyrazoloACHTUNGTRENNUNG[5,1-
a]isoquinolin-2(3H)-ylidene]-3-(4-chlorophenyl)propanoate
(4al): Yield: 40% (Table 2, entry 25); yellow solid. TLC
(EtOAc/petroleum ether 1/5): Rf =0.50; IR (film) nmax
=
a]isoquinolin-2(3H)-ylidene]-3-(m-tolyl)propanoate (4ah):
Yield: 55% (Table 2, entry 21); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.48; IR (film): nmax =2927, 2851,
1697, 1493, 1447, 1369, 1298, 1199, 1097, 1031, 969, 866, 766,
2927, 2853, 1697, 1600, 1541, 1490, 1455, 1368, 1276, 1199,
1
1095, 1015, 910, 866, 804, 763, 740, 696, 678 cmÀ1; H NMR
(300 MHz, CDCl3): d=1.21 (t, J=7.1 Hz, 3H), 2.67–2.84
(m, 2H), 2.91–3.00 (m, 2H), 3.25 (dd, J=18.8, 10.1 Hz, 1H),
3.48–3.78 (m, 2H), 3.93 (d, J=15.8 Hz, 1H), 4.11–4.34 (m,
3H), 7.00–7.25 (m, 8H), 7.32–7.58 (m, 5H); 13C NMR
(75 MHz, CDCl3): d=14.1, 29.1, 35.0, 40.5, 47.5, 60.7, 61.1,
67.1, 119.5, 121.4, 126.4, 126.9, 127.1, 127.4, 127.7, 127.8,
128.3, 128.4, 130.3, 131.1, 131.2, 131.5, 132.3, 132.7, 135.0,
139.7, 149.7, 167.2, 171.0; HR-MS (ESI): m/z=487.1776,
calcd. for C29H28ClN2O3+ [M+H]+: 487.1783.
1
703, 678 cmÀ1; H NMR (300 MHz, CDCl3): d=1.22 (t, J=
7.1 Hz, 3H), 2.25 (s, 3H), 2.62–2.93 (m, 4H), 3.24 (dd, J=
18.8, 10.1 Hz, 1H), 3.60–3.76 (m, 2H), 3.97 (d, J=15.9 Hz,
1H), 4.12–4.27ACHTUNGTRENNUNG(m, 3H), 6.94–7.04 (m, 5H), 7.07–7.14 (m,
3H), 7.31–7.37 (m, 2H), 7.40–7.46 (m, 1H), d 7.47–7.51 (m,
2H); 13C NMR (75 MHz, CDCl3): d=14.2, 21.3, 29.1, 35.2,
40.5, 47.4, 60.6, 61.0, 77.2, 122.1, 125.6, 126.3, 126.5, 126.8,
127.1, 127.6, 128.0, 128.2, 128.4, 129.6, 131.0, 132.4, 135.1,
135.2, 137.5, 140.6, 149.2, 167.5, 170.7; HR-MS (ESI): m/z=
(E)-Ethyl 2-[3-benzoyl-1,5,6,10b-tetrahydropyrazoloACHTUNGTRENNUNG[5,1-
a]isoquinolin-2(3H)-ylidene]-3-(4-bromophenyl)propanoate
(4am): Yield: 30% (Table 2, entry 26); yellow solid. TLC
+
467.2328, calcd. for C30H31N2O3 [M+H]+: 467.2329.
(E)-Ethyl 2-[3-benzoyl-1,5,6,10b-tetrahydropyrazolo
ACHTUNGTNER[NUNG 5,1-
(EtOAc/petroleum ether 1/5): Rf =0.48; IR (film): nmax
=
a]isoquinolin-2(3H)-ylidene]-3-(p-tolyl)propanoate (4ai):
2926, 2850, 1704, 1541, 1487, 1446, 1301, 1241, 1200, 1099,
Yield: 92% (Table 2, entry 22); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.48; IR (film): nmax =2924, 2853,
1704, 1580, 1514, 1494, 1455, 1369, 1293, 1198, 1095, 1030,
1
1011, 909, 788, 762, 736, 696, 677 cmÀ1; H NMR (300 MHz,
CDCl3): d=1.20 (t, J=7.1 Hz, 3H), 2.53–3.00 (m, 4H),
3.13–3.29 (m, 1H), 3.57–3.77 (m, 2H), 3.90 (d, J=15.8 Hz,
1H), 4.00–4.33 (m, 3H), 7.00–7.24 (m, 6H), 7.30–7.56 (m,
7H); 13C NMR (75 MHz, CDCl3): d=14.1, 29.1, 35.0, 40.5,
47.5, 60.7, 61.1, 119.5, 121.4, 126.4, 126.9, 127.1, 127.4, 127.7,
127.8, 128.3, 128.4, 130.3, 131.1, 131.2, 131.5, 132.3, 132.7,
135.0, 139.7, 149.7, 167.2, 171.0; HR-MS (ESI): m/z=
1
968, 909, 866, 787, 763, 677, 647 cmÀ1; H NMR (300 MHz,
CDCl3): d=1.21 (t, J=7.1 Hz, 3H), 2.33 (s, 3H), 2.66–3.00
(m, 4H), 3.26 (dd, J=18.8, 10.0 Hz, 1H), 3.62–3.76 (m, 2H),
3.91 (d, J=15.8 Hz, 1H), 4.08–4.34 (m, 3H), 7.00–7.15 (m,
8H), 7.34–7.59 (m, 5H); 13C NMR (75 MHz, CDCl3): d=
14.1, 21.0, 29.1, 35.1, 40.4, 47.4, 60.5, 61.1, 122.1, 126.3, 126.8,
127.1, 127.6, 128.2, 128.4, 128.5, 128.7, 131.1, 132.4, 135.20,
135.21, 137.5, 148.9, 167.4, 170.9; HR-MS (ESI): m/z=
+
531.1254, calcd. for C29H28BrN2O3 [M+H]+: 531.1278.
(E)-Ethyl
2-[3-benzoyl-7-methyl-1,5,6,10b-tetrahydro-
pyrazolo[5,1-a]isoquinolin-2(3H)-ylidene]butanoate (4bb):
AHCTUNGTRENNUNG
+
467.2323, calcd. for C30H31N2O3 [M+H]+: 467.2329.
Yield: 95% (Table 3, entry 11); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.52; IR (film): nmax =3059, 2974,
2934, 1941, 1704, 1639, 1599, 1447, 1369, 1299, 1252, 1234,
1211, 1175, 1143, 1110, 1046, 1027, 935, 921, 866, 785, 758,
(E)-Ethyl 2-[3-benzoyl-1,5,6,10b-tetrahydropyrazoloACTHNUTRGNEU[GN 5,1-
a]isoquinolin-2(3H)-ylidene]-3-(4-fluorophenyl)propanoate
(4aj): Yield: 18% (Table 2, entry 23); yellow solid. TLC
(EtOAc/petroleum ether 1/5): Rf =0.48; IR (film): nmax
=
1
713, 696, 678, 648, 617, 545, 517 cmÀ1; H NMR (300 MHz,
2930, 1714, 1650, 1602, 1507, 1455, 1369, 1310, 1240, 1158,
CDCl3): d=1.13 (t, J=7.4 Hz, 3H), 1.31 (t, J=7.1 Hz, 3H),
2.20 (s, 3H), 2.40–2.44 (m, 2H), 2.78–2.83 (m, 1H), 2.92–
3.01 (m, 2H), 3.15 (dd, J=18.7, 10.0 Hz, 1H), 3.41–3.45 (m,
1H), 3.69 (dd, J=18.6, 8.5 Hz, 1H), 4.19–4.26 (m, 3H), 6.86
(s, 1H), 6.90–7.09 (m, 2H), 7.39–7.46 (m, 3H), 7.71–7.74 (m,
2H); 13C NMR (75 MHz, CDCl3): d=12.7, 14.3, 19.2, 23.8,
26.6, 39.9, 47.4, 60.3, 61.3, 124.7, 124.9, 126.2, 127.6, 128.0,
128.4, 130.9, 131.0, 135.1, 135.3, 135.8, 147.0, 167.4, 171.5;
1
1097, 1059, 1026, 912, 958, 825, 733, 700, 672 cmÀ1; H NMR
(300 MHz, CDCl3): d=1.20 (t, J=7.1 Hz, 3H), 2.72 (ddd,
J=18.7, 13.2, 3.5 Hz, 2H), 2.89–3.00 (m, 2H), 3.23 (dd, J=
18.7, 10.2 Hz, 1H), 3.62–3.77 (m, 2H), 3.92 (d, J=15.8 Hz,
1H), 4.07–4.33 (m, 3H), 6.86–7.18 (m, 8H), 7.33–7.58 (m,
5H); 13C NMR (75 MHz, CDCl3): d=14.2, 29.1, 34.7, 40.5,
47.5, 60.6, 61.1, 114.9, 121.9, 126.4, 126.8, 127.1, 127.7, 128.3,
128.4, 129.9, 130.0, 131.1, 132.3, 135.0, 136.28, 136.32, 149.4,
+
HR-MS (ESI): m/z=405.2138, calcd. for C25H29N2O3 [M+
H]+: 405.2173.
159.7,
m/z=471.2068, calcd. for C29H28FN2O3 [M+H]+: 471.2078.
(E)-Ethyl 2-[3-benzoyl-1,5,6,10b-tetrahydropyrazolo[5,1-
162.9,
167.3,
170.9;
HR-MS
(ESI):
+
(E)-Ethyl
2-[3-benzoyl-9-methyl-1,5,6,10b-tetrahydro-
AHCTUNGTRENNUNG
pyrazolo[5,1-a]isoquinolin-2(3H)-ylidene]butanoate (4cb):
AHCTUNGTRENNUNG
a]isoquinolin-2(3H)-ylidene]-3-(3-chlorophenyl)propanoate
(4ak): Yield: 28% (Table 2, entry 24); yellow solid. TLC
Yield: 97% (Table 3, entry 12); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.53; IR (film): nmax =3055, 2975,
2933, 1895, 1765, 1679, 1638, 1600, 1581, 1505, 1463, 1446,
1429, 1365, 1299, 1276, 1239, 1214, 1195, 1175, 1142, 1107,
1063, 1028, 977, 921, 880, 866, 843, 785, 734, 711, 695, 677,
(EtOAc/petroleum ether 1/5): Rf =0.52; IR (film): nmax
=
2979, 1701, 1598, 1474, 1429, 1368, 1297, 1200, 1096, 1030,
1
865, 767, 697 cmÀ1; H NMR (300 MHz, CDCl3): d=1.21 (d,
641, 617, 550, 517, 460 cmÀ1 1H NMR (300 MHz, CDCl3):
;
J=7.1 Hz, 3H), 2.66–2.79 (m, 2H), 2.86–2.96 (m, 2H), 3.24
(dd, J=18.8, 10.1 Hz, 1H), 3.62–3.78 (m, 2H), 3.96 (d, J=
15.7 Hz, 1H), 4.10–4.33 (m, 3H), 7.01–7.08 (m, 3H), 7.10–
7.18 (m, 5H), 7.33–7.38 (m, 2H), 7.42–7.47 (m, 1H), 7.50–
7.53 (m, 2H); 13C NMR (75 MHz, CDCl3): d=14.2, 29.1,
35.1, 40,6, 47.5, 60.7, 61.0, 121.3, 126.0, 126.4, 126.8, 126.9,
127.1, 127.7, 128.2, 128.3, 128.7, 129.3, 131.1, 132.3, 133.9,
135.0, 142.8, 150.0, 167.2, 170.9; HR-MS (ESI): m/z=
d=1.13 (t, J=7.4 Hz, 3H), 1.32 (t, J=7.1 Hz, 3H), 2.25 (s,
3H), 2.37–2.47 (m, 2H), 2.66–2.77 (m, 1H), 2.89–3.01 (m,
2H), 3.11 (dd, J=18.6, 9.9 Hz, 1H), 3.35–3.38 (m, 1H), 3.67
(dd, J=18.6, 8.5 Hz, 1H), 4.18–4.26 (m, 3H), 6.83 (s, 1H),
6.91–6.97 (m, 2H), 7.36–7.46 (m, 3H), 7.70–7.73 (m, 2H);
13C NMR (75 MHz, CDCl3): d=12.7, 14.3, 20.9, 23.7, 28.6,
40.0, 47.7, 60.3, 61.1, 124.5, 127.51, 127.58, 127.60, 128.0,
128.4, 129.1, 131.0, 135.1, 135.3, 135.8, 147.2, 167.4, 171.5;
+
487.1772, calcd. for C29H28ClN2O3 [M+H]+: 487.1783.
Adv. Synth. Catal. 2012, 354, 1023 – 1034
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1029

Chengfeng Jing et al.
FULL PAPERS
+
HR-MS (ESI): m/z=405.2164, calcd. for C25H29N2O3 [M+
(m, 2H), 3.99 (d, J=15.8 Hz, 1H), 4.12–4.25 (m, 3H), 6.85–
7.24 (m, 8H), 7.33–7.55 (m, 5H); 13C NMR (75 MHz,
CDCl3): d=14.1, 19.2, 26.6, 35.4, 40.4, 47.2, 60.6, 61.2, 122.1,
124.9, 125.8, 126.2, 127.6, 128.04, 128.08, 128.4, 128.6, 131.0,
134.9, 135.2, 135.9, 140.7, 149.3, 167.4, 170.8; HR-MS (ESI):
H]+: 405.2173.
(E)-Ethyl
2-[3-benzoyl-8-bromo-1,5,6,10b-tetrahydro-
pyrazolo[5,1-a]isoquinolin-2(3H)-ylidene]butanoate (4db):
ACHTUNGTRENNUNG
Yield: 87% (Table 3, entry 13); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.47; IR (film): nmax =3058, 2974,
2934, 1891, 1704, 1638, 1599, 1580, 1466, 1446, 1425, 1369,
1299, 1252, 1211, 1175, 1143, 1110, 1046, 1027, 935, 921, 866,
+
m/z=467.2322, calcd. for C30H31N2O3 [M+H]+: 467.2329.
(E)-Ethyl
pyrazolo[5,1-a]isoquinolin-2(3H)-ylidene]-3-phenylpropa-
noate (4cf): Yield: 46% (Table 3, entry 7); yellow solid. TLC
(EtOAc/petroleum ether 1/5): Rf =0.53; IR (film): nmax
2-[3-benzoyl-9-methyl-1,5,6,10b-tetrahydro-
AHCTUNGTRENNUNG
784, 758, 713, 696, 678, 649, 617, 522 cmÀ1
;
1H NMR
(300 MHz, CDCl3): d=1.12 (t, J=7.4 Hz, 3H), 1.31 (t, J=
7.1 Hz, 3H), 2.20 (s, 3H), 2.35–2.43 (m, 2H), 2.69–2.74 (m,
1H), 2.87–3.11 (m, 3H), 3.35–3.39 (m, 1H), 3.66 (dd, J=
18.6, 8.5 Hz, 1H), 4.15–4.25 (m, 3H), 6.87 (d, J=8.2 Hz,
1H), 7.21–7.26 (m, 2H), 7.37–7.47 (m, 3H),7.69–7.72 (m,
2H); 13C NMR (75 MHz, CDCl3): d=12.7, 14.2, 23.7, 28.8,
39.8, 47.2, 60.3, 60.8, 120.4, 124.8, 127.7, 128.4, 128.6, 129.4,
131.0, 131.1, 134.3, 134.6, 135.1, 146.6, 167.3, 171.4; HR-MS
=
3059, 3026, 2925, 2851, 1766, 1601, 1581, 1505, 1494, 1447,
1428, 1365, 1298, 1274, 1251, 1216, 1136, 1095, 1077, 1030,
975, 867, 814, 788, 734, 699, 678, 561, 465 cmÀ1 1H NMR
;
(300 MHz, CDCl3): d=1.21 (t, J=7.1 Hz, 3H), 2.26 (s, 3H),
2.59–2.88 (m, 4H), 4.13–4.24 (m, 3H), 3.26 (dd, J=18.9,
10.1 Hz, 1H), 3.67–3.77 (m, 2H), 3.99 (d, J=15.7 Hz, 1H),
6.82 (s, 1H), 6.93 (d, J=1.0 Hz, 2H), 7.16–7.25 (m, 5H),
7.33–7.56 (m, 5H); 13C NMR (75 MHz, CDCl3): d=14.1,
20.9, 28.6, 35.4, 40.5, 47.5, 60.5, 61.0, 121.9, 125.8, 127.51,
127.55, 127.64, 128.0, 128.3, 128.5, 128.6, 129.2, 130.9, 134.9,
135.2, 135.9, 140.7, 149.4, 167.4, 170.84; HR-MS (ESI): m/
(ESI): m/z=469.1113, calcd. for C24H26BrN2O3 [M+H]+:
+
469.1121.
(E)-Ethyl
2-[3-benzoyl-9-bromo-1,5,6,10b-tetrahydro-
pyrazolo[5,1-a]isoquinolin-2(3H)-ylidene]butanoate (4eb):
ACHTUNGTRENNUNG
+
Yield: 96% (Table 3, entry 14); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.50; IR (film): nmax =3057, 2975,
2934, 2850, 1891, 1704, 1680, 1597, 1579, 1486, 1464, 1446,
1427, 1412, 1365, 1330, 1299, 1268, 1254, 1240, 1217, 1189,
1177, 1142, 1107, 1077, 1063, 1027, 974, 924, 867, 800, 785,
z=467.2326, calcd. for C30H31N2O3 [M+H]+: 467.2329.
(E)-Ethyl
2-[3-benzoyl-8-bromo-1,5,6,10b-tetrahydro-
pyrazolo[5,1-a]isoquinolin-2(3H)-ylidene]-3-phenylpropa-
AHCTUNGTRENNUNG
noate (4df): Yield: 73% (Table 3, entry 8); yellow solid.
TLC (EtOAc/petroleum ether 1/5): Rf =0.46; IR (film):
nmax =3057, 3018, 2981, 2928, 2849, 1703, 1676, 1599, 1580,
1493, 1483, 1447, 1426, 1368, 1300, 1266, 1241, 1204, 1188,
1138, 1075, 1029, 998, 969, 908, 889, 866, 854, 839, 817, 781,
769, 725, 710, 696, 677, 656, 639, 611, 533 cmÀ1 1H NMR
;
(300 MHz, CDCl3): d=1.12 (t, J=7.4 Hz, 3H), 1.32 (t, J=
7.1 Hz, 3H), 2.35–2.44 (m, 2H), 2.68–2.73 (m, 1H), 2.90–
2.97 (m, 2H), 3.10 (dd, J=18.6, 9.9 Hz, 1H), 3.35–3.39 (m,
1H), 3.65 (dd, J=18.6, 8.6 Hz, 1H), 4.16–4.26 (m, 3H), 6.92
(d, J=8.2 Hz, 1H), 7.14–7.24 (m, 2H), 7.39–7.41 (m, 3H),
7.69–7.72 (m, 2H); 13C NMR (75 MHz, CDCl3): d=12.7,
14.3, 23.7, 28.6, 39.8, 47.4, 60.4, 60.7, 119.9, 124.8, 127.7,
128.4, 129.85, 129.88, 129.89, 131.1, 131.3, 135.1, 137.5, 146.5,
167.4, 171.4; HR-MS (ESI): m/z=469.1123, calcd. for
738, 702, 679, 650, 545 cmÀ1 1H NMR (300 MHz, CDCl3):
;
d=1.21 (t, J=7.1 Hz, 3H), 2.60–2.73 (m, 2H), 2.83–2.87 (m,
2H), 3.21 (dd, J=18.8, 10.1 Hz, 1H), 3.63–3.75 (m, 2H),
3.98 (d, J=15.7 Hz, 1H), 4.12–4.22 (m, 3H), 6.88 (d, J=
8.2 Hz, 1H), 7.14–7.23 (m, 7H), 7.33–7.52 (m, 5H);
13C NMR (75 MHz, CDCl3): d=14.1, 28.9, 35.4, 40.3, 46.9,
60.6, 60.7, 120.5, 122.2, 125.9, 127.7, 128.1, 128.4, 128.6,
128.7, 129.5, 131.08, 131.12, 134.15, 134.7, 135.0, 140.6, 148.9,
167.4, 170.7; HR-MS (ESI): m/z=531.1261, calcd. for
+
C24H26BrN2O3 [M+H]+: 469.1121.
(E)-Ethyl
2-[3-benzoyl-9-chloro-1,5,6,10b-tetrahydro-
pyrazolo[5,1-a]isoquinolin-2(3H)-ylidene]butanoate (4fd):
+
N
C29H28BrN2O3 [M+H]+: 531.1278.
Yield: 95% (Table 3, entry 15); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.51; IR (film): nmax =3057, 2975,
2934, 2850, 1891, 1704, 1681, 1640, 1600, 1579, 1489, 1464,
1446, 1427, 1365, 1299, 1268, 1254, 1239, 1216, 1192, 1176,
1142, 1107, 1063, 1027, 975, 867, 801, 785, 725, 711, 695, 677,
(E)-Ethyl
2-[3-benzoyl-9-bromo-1,5,6,10b-tetrahydro-
pyrazolo[5,1-a]isoquinolin-2(3H)-ylidene]-3-phenylpropa-
AHCTUNGTRENNUNG
noate (4ef): Yield: 92% (Table 3, entry 9); yellow solid.
TLC (EtOAc/petroleum ether 1/5): Rf =0.52; IR (film):
nmax =3059, 3026, 2977, 2930, 2849, 1705, 1677, 1599, 1578,
1485, 1446, 1426, 1365, 1298, 1270, 1240, 1201, 1131, 1096,
1077, 1030, 968, 917, 867, 810, 785, 736, 700, 678, 610,
1
630, 539 cmÀ1; H NMR (300 MHz, CDCl3): d=1.12 (t, J=
7.4 Hz, 3H), 1.32 (t, J=7.1 Hz, 3H), 2.35–2.44 (m, 2H),
2.70–2.75 (m, 1H), 2.92–3.15 (m, 3H), 3.37–3.39 (m, 1H),
3.66 (dd, J=18.6, 8.6 Hz, 1H), 4.16–4.26 (m, 3H), 6.97–7.10
(m, 3H), 7.39–7.47 (m, 3H),7.69–7.72 (m, 2H); 13C NMR
(75 MHz, CDCl3): d=12.7, 14.3, 23.7, 28.6, 39.8, 47.4, 60.4,
60.8, 124.9, 126.9, 127.0, 127.7, 128.4, 129.6, 130.8, 131.1,
132.0, 135.1, 137.1, 146.5, 167.4, 171.4; HR-MS (ESI): m/z=
558 cmÀ1
;
1H NMR (300 MHz, CDCl3): d=1.22 (t, J=
7.1 Hz, 3H), 2.58–2.88 (m, 4H), 3.24 (dd, J=18.8, 10.1 Hz,
1H), 3.64–3.74 (m, 2H), 3.99 (d, J=15.9 Hz, 1H), 4.13–4.23
(m, 3H), 6.90 (d, J=8.2 Hz, 1H), 7.14–7.25 (m, 7H), 7.33–
7.53 (m, 5H); 13C NMR (75 MHz, CDCl3): d=14.2, 28.6,
35.4, 40.3, 47.1, 60.58, 60.65, 119.9, 122.3, 125.9, 127.6, 128.1,
128.3, 128.6, 129.9, 131.1, 131.4, 135.0, 137.3, 140.6, 148.7,
167.4, 170.7; HR-MS (ESI): m/z=531.1253, calcd. for
+
425.1599, calcd. for C24H26ClN2O3 [M+H]+: 425.1626.
(E)-Ethyl
2-[3-benzoyl-7-methyl-1,5,6,10b-tetrahydro-
+
pyrazolo[5,1-a]isoquinolin-2(3H)-ylidene]-3-phenylpropa-
G
C29H28BrN2O3 [M+H]+: 531.1278.
noate (4bf): Yield: 40% (Table 3, entry 6); yellow solid.
TLC (EtOAc/petroleum ether 1/5): Rf =0.51; IR (film):
nmax =3060, 3026, 2926, 2852, 1705, 1674, 1600, 1494, 1469,
1446, 1369, 1299, 1236, 1210, 1140, 1093, 1052, 1029, 979,
(E)-Ethyl
2-[3-benzoyl-9-chloro-1,5,6,10b-tetrahydro-
pyrazolo[5,1-a]isoquinolin-2(3H)-ylidene]-3-phenylpropa-
AHCTUNGTRENNUNG
noate (4ff): Yield: 80% (Table 3, entry 10); yellow solid.
TLC (EtOAc/petroleum ether 1/5): Rf =0.52; IR (film):
nmax =3060, 3027, 2929, 2852, 1706, 1681, 1601, 1578, 1489,
1447, 1426, 1366, 1296, 1269, 1240, 1201, 1130, 1094, 1030,
921, 885, 866, 845, 812, 783, 699, 677, 552 cmÀ1 1H NMR
;
(300 MHz, CDCl3): d=1.21 (t, J=7.1 Hz, 3H), 2.17 (s, 3H),
2.66–2.89 (m, 4H), 3.28 (dd, J=18.9, 10.1 Hz, 1H), 3.66–3.77
969, 932, 868, 839, 813, 785, 699, 678, 630, 563 cmÀ1
;
1030
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1023 – 1034

Phosphine-Catalyzed [3+2] and [4+3]Annulation Reactions of C,N-Cyclic Azomethine Imines
1H NMR (300 MHz, CDCl3): d=1.21 (t, J=7.1 Hz, 3H),
2.60–2.72 (m, 2H), 2.80–2.88 (m, 2H), 3.23 (dd, J=18.8,
10.1 Hz, 1H), 3.63–3.75 (m, 2H), 3.98 (d, J=15.8 Hz, 1H),
4.13–4.22 (m, 3H), 6.94–7.23 (m, 8H), 7.33–7.52 (m, 5H);
13C NMR (75 MHz, CDCl3): d=14.1, 28.6, 35.4, 40.3, 47.2,
60.6, 60.7, 122.3, 125.9, 126.95, 127.03, 127.6, 128.1, 128.4,
128.6, 129.6, 130.9, 131.1, 132.0, 135.0, 136.9, 140.6, 148.7,
167.4, 170.7; HR-MS (ESI): m/z=487.1766, calcd. for
J=45.9 Hz, 1H), 5.07–5.26 (m, 1H), 5.97 (s, 1H), 7.05–7.20
(m, 8H), 7.31–7.39 (m, 2H), 7.48–7.53 (m, 3H); 13C NMR
(75 MHz, CDCl3): d=13.8, 21.1, 30.6, 38.1, 49.0, 59.5, 60.7,
64.9, 125.9, 126.0, 126.1, 128.4, 128.6, 128.7, 129.6, 134.1,
134.8, 135.0, 137.0, 137.3, 138.3, 141.1, 166.0, 170.7; HR-MS
+
(ESI): m/z=467.2320, calcd. for C30H31N2O3 [M+H]+:
467.2329.
Ethyl
5-benzoyl-4-(4-fluorophenyl)-1,4,5,7,8,12b-hexa-
[7,1-a]isoquinoline-3-carboxylate (5aj):
+
C29H28ClN2O3 [M+H]+: 487.1783.
hydro[1,2]diazepinoACHTUGNTRENNNUG
G
Ethyl 5-benzoyl-4-phenyl-1,4,5,7,8,12b-hexahydro
G
Yield: 92 (Table 2, entry 10); yellow solid. TLC (EtOAc/pe-
troleum ether 1/5): Rf =0.34; IR (film): nmax =2924, 2853,
1714, 1650, 1602, 1541, 1507, 1456, 1369, 1310, 1239, 1157,
azepino[7,1-a]isoquinoline-3-carboxylate (5af): Yield: 90%
ACHTUNGTRENNUNG
(Table 2, entry 6); yellow solid. TLC (EtOAc/petroleum
1
ether 1/5): Rf =0.38; IR (film): nmax =2929, 1708, 1649, 1541,
1097, 1026, 911, 825, 735, 700, 670 cmÀ1; H NMR (300 MHz,
1491, 1454, 1368, 1311, 1240, 1058, 1028, 912, 744, 699 cmÀ1
CDCl3): d=0.98 (t, J=7.0 Hz, 3H), 2.39–2.51 (m, 2H),
2.66–2.84 (m, 2H), 3.06–3.15 (m, 1H), 3.90–3.98 (m, 3H),
4.15–4.33 (m, 1H), 5.11–5.16 (m, 1H), 5.96 (s, 1H), 6.94–
7.07 (m, 4H), 7.13–7.23 (m, 5H), 7.31–7.39 (m, 1H), 7.47–
7.60 (m, 3H); 13C NMR (75 MHz, CDCl3): d=13.9, 30.6,
37.8, 49.1, 59.6, 60.8, 64.5, 114.8, 115.1, 125.97, 126.03, 126.2,
128.7, 128.8, 129.8, 130.1, 130.2, 133.7, 134.0, 134.6, 136.8,
138.2, 141.5, 165.8, 170.6; HR-MS (ESI): m/z=471.2070,
1H NMR (300 MHz, CDCl3): d=0.95 (t, J=7.1 Hz, 3H),
2.31–2.46 (m, 2H), 2.63–2.84 (m, 2H), 3.05–3.14 (m, 1H),
3.88–3.96 (m, 3H), 4.08–4.33 (m, 1H), 5.13 (dd, J=7.7,
4.9 Hz, 1H), 6.00 (s, 1H), 7.03–7.05 (m, 1H), 7.10–7.19 (m,
3H), 7.22–7.25 (m, 3H), 7.32–7.37 (m, 2H), 7.47–7.72 (m,
5H); 13C NMR (75 MHz, CDCl3): d=13.8, 30.6, 38.0, 49.1,
59.5, 60.7, 65.2, 125.9, 126.0, 126.06, 126.09, 127.7, 128.0,
128.4, 128.6, 128.7, 129.6, 133.9, 134.8, 136.9, 138.0, 138.2,
141.5, 165.9, 170.7; HR-MS (ESI): m/z=453.2166, calcd. for
+
calcd. for C29H28FN2O3 [M+H]+: 471.2078.
Ethyl
5-benzoyl-4-(3-chlorophenyl)-1,4,5,7,8,12b-hexa-
[7,1-a]isoquinoline-3-carboxylate (5ak):
+
C29H29N2O3 [M+H]+: 453.2173.
hydro[1,2]diazepinoACHTUGNTRENNNUG
G
Ethyl 5-benzoyl-4-(o-tolyl)-1,4,5,7,8,12b-hexahydro
[1,2]di-
Yield: 75% (Table 2, entry 11); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.36; IR (film): nmax =3062, 2980,
1714, 1651, 1596, 1575, 1493, 1475, 1446, 1429, 1368, 1311,
azepino[7,1-a]isoquinoline-3-carboxylate (5ag): Yield: 42%
ACHTUNGTRENNUNG
(Table 2, entry 7); yellow solid. TLC (EtOAc/petroleum
ether 1/5): Rf =0.33; IR (film): nmax =2920, 1716, 1647, 1541,
1242, 1189, 1059, 1026, 787, 752, 701 cmÀ1 1H NMR
;
1488, 1456, 1410, 1362, 1339, 1260, 735 cmÀ1
;
1H NMR
(300 MHz, CDCl3): d=1.00 (t, J=7.1 Hz, 3H), 2.45–2.53
(m, 2H), 2.71–2.85 (m, 2H), 3.06–3.16 (m, 1H), 3.91–4.00
(m, 3H), 4.17–4.34 (m, 1H), 5.12–5.16 (m, 1H), 5.97 (m,
1H), 7.07–7.22 (m, 7H), 7.36–7.48 (m, 6H); 13C NMR
(75 MHz, CDCl3): d=13.8, 30.5, 38.0, 49.2, 59.6, 60.8, 64.7,
126.0, 126.2, 126.7, 127.9, 128.5, 128.7, 128.8, 129.3, 129.8,
133.2, 133.8, 134.6, 136.7, 138.1, 140.2, 165.6, 170.7; HR-MS
(300 MHz, CDCl3): d=1.00 (t, J=7.1 Hz, 3H), 2.01 (s, 3H),
2.19–2.39 (m, 2H), 2.56–2.90 (m, 2H), 3.16 (dt, J=18.1,
5.2 Hz, 1H), 3.86–4.05 (m, 3H), 4.11–4.33 (m, 1H), 5.08 (dd,
J=8.1, 5.0 Hz, 1H), 6.11 (s, 1H), 7.02–7.10 (m, 3H), 7.12–
7.22 (m, 4H), 7.41–7.47 (m, 4H), 7.49–7.73 (m, 2H);
13C NMR (75 MHz, CDCl3): d=13.8, 19.3, 30.5, 38.7, 49.1,
59.3, 60.7, 62.4, 125.2, 125.9, 126.1, 126.3, 126.5, 127.8, 128.3,
128.6, 129.6, 130.0, 130.1, 134.7, 134.8, 135.4, 136.3, 136.6,
138.4, 141.7, 165.9, 170.6; HR-MS (ESI): m/z=467.2338,
+
(ESI): m/z=487.1819, calcd. for C29H28ClN2O3 [M+H]+:
487.1783.
Ethyl
5-benzoyl-4-(4-chlorophenyl)-1,4,5,7,8,12b-hexa-
[7,1-a]isoquinoline-3-carboxylate (5al):
+
calcd. for C30H31N2O3 [M+H]+: 467.2329.
hydro[1,2]diazepinoACHTUGNTRENNNUG
G
Ethyl 5-benzoyl-4-(m-tolyl)-1,4,5,7,8,12b-hexahydro
[1,2]-
Yield: 84% (Table 2, entry 12); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.36; IR (film): nmax =2924, 2854,
1714, 1650, 1541, 1489, 1456, 1368, 1309, 1241, 1091, 1015,
diazepino[7,1-a]isoquinoline-3-carboxylate (5ah): Yield:
ACHTUNGTRENNUNG
55% (Table 2, entry 8); yellow solid. TLC (EtOAc/petrole-
um ether 1/5): Rf =0.34; IR (film): nmax =2930, 1714, 1651,
1491, 1446, 1368, 1313, 1243, 1157, 1096, 1059, 1038, 778,
912, 852, 748, 709, 670 cmÀ1 1H NMR (300 MHz, CDCl3):
;
d=0.99 (t, J=7.1 Hz, 3H), 2.43–2.52 (m, 2H), 2.68–2.84 (m,
2H), 3.05–3.15 (m, 1H), 3.89–3.98 (m, 3H), 4.16–4.33 (m,
1H), 5.11–5.15 (m, 1H), 5.95 (s, 1H), 7.05–7.19 (m, 6H),
7.24–7.25 (m, 1H), 7.27 (s, 1H), 7.33–7.36 (m, 1H), 7.47 (s,
4H); 13C NMR (75 MHz, CDCl3): d=13.9, 30.6, 37.8, 49.2,
59.6, 60.8, 64.6, 125.9, 126.0, 126.2, 128.2, 128.7, 128.8, 129.8,
133.5, 133.6, 134.6, 136.7, 138.1, 141.8, 165.7, 170.7; HR-MS
1
734, 701, 677 cmÀ1; H NMR (300 MHz, CDCl3): d=0.98 (t,
J=7.1 Hz, 3H), 2.31 (s, 3H), 2.44–2.49 (m, 2H), 2.67–2.85
(m, 2H),3.05–3.15 (m, 1H), 3.92–3.97 (m, 3H), 4.17–4.34
(m, 1H), 5.11–5.15 (m, 1H), 5.97 (s, 1H), 7.04–7.09 (m, 4H),
7.12–7.20 (m, 4H), 7.30–7.39 (m, 1H), d 7.48–7.53 (m, 4H);
13C NMR (75 MHz, CDCl3): d=13.8, 21.4, 30.6, 38.0, 49.1,
59.5, 60.7, 65.2, 125.6, 125.9, 126.1, 127.8, 128.4, 128.6, 128.7,
129.1, 129.6, 133.9, 134.8, 137.0, 137.4, 137.9, 138.3, 141.3,
166.0, 170.7; HR-MS (ESI): m/z=467.2425, calcd. for
+
(ESI): m/z=487.1775, calcd. for C29H28ClN2O3 [M+H]+:
487.1783.
Ethyl
5-benzoyl-4-(4-bromophenyl)-1,4,5,7,8,12b-hexa-
[7,1-a]isoquinoline-3-carboxylate (5am):
+
C30H31N2O3 [M+H]+: 467.2329.
hydro[1,2]diazepinoACHTUGNTRENNNUG
G
Ethyl 5-benzoyl-1-(p-tolyl)-1,4,5,7,8,12b-hexahydro
[1,2]-
Yield: 93% (Table 2, entry 13); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.33; IR (film): nmax =2930, 1713,
1650, 1540, 1487, 1445, 1368, 1308, 1241, 1158, 1071, 910,
diazepino[7,1-a]isoquinoline-2-carboxylate (5ai): Yield: 71%
ACHTUNGTRENNUNG
(Table 2, entry 9); yellow solid. TLC (EtOAc/petroleum
ether 1/5): Rf =0.34; IR (film): nmax =2927, 1714, 1650, 1541,
1509, 1491, 1370, 1311, 1240, 1096, 1025, 911, 855, 788, 732,
851, 803, 734, 704, 647, 503 cmÀ1
;
1H NMR (300 MHz,
CDCl3): d=0.99 (t, J=7.1 Hz, 3H), 2.44–2.53 (m, 2H),
2.68–2.84 (m, 2H), 3.05–3.13 (m, 1H), 3.89–3.98 (m, 3H),
4.16–4.33 (m, 1H), 5.11–5.15 (m, 1H), 5.93 (s, 1H), 7.05–
7.20 (m, 6H), 7.33–7.42 (m, 4H), 7.47 (s, 3H); 13C NMR
1
700, 674 cmÀ1; H NMR (300 MHz, CDCl3): d=0.98 (t, J=
7.1 Hz, 3H), 2.34 (s, 3H), 2.47 (d, J=13.7 Hz, 2H), 2.69–
2.85 (m, 2H), 2.99–3.24 (m, 1H), 3.86–4.01 (m, 3H), 4.25 (d,
Adv. Synth. Catal. 2012, 354, 1023 – 1034
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1031

Chengfeng Jing et al.
FULL PAPERS
(75 MHz, CDCl3): d=13.9, 30.6, 37.8, 49.2, 59.7, 60.8, 64.6,
121.8, 125.96, 126.03, 126.3, 128.7, 128.8, 129.8, 130.2, 131.2,
133.4, 134.6, 136.7, 137.3, 138.1, 141.8, 165.7, 170.7; HR-MS
5H), 7.23–6.91 (m, 3H), 6.00 (s, 1H), 5.10–5.05 (m, 1H),
4.26–4.16 (m, 1H), 3.96–3.85 (m, 3H), 3.13–3.03 (m, 1H),
2.83–2.57 (m, 2H), 2.43–2.39 (m, 2H), 0.96 (t, J=7.1 Hz,
3H); 13C NMR (75 MHz, CDCl3): d=170.8, 165.8, 140.8,
140.4, 138.1, 136.7, 134.0, 133.9, 130.4, 129.8, 129.3, 129.0,
128.8, 128.4, 128.1, 127.8, 126.1, 119.6, 65.3, 60.8, 59.3, 48.9,
37.3, 30.1, 13.8; HRMS (ESI): m/z=531.1255, calcd. for
+
(ESI): m/z=531.1258, calcd. for C29H28BrN2O3 [M+H]+:
531.1278.
Ethyl
5-benzoyl-9-methyl-4-phenyl-1,4,5,7,8,12b-hexa-
[7,1-a]isoquinoline-3-carboxylate (5bf):
hydro[1,2]diazepinoACHTUGNTRENNNUG
G
+
C29H28BrN2O3 [M+H]+: 531.1278.
Yield: 73% (Table 3, entry 1); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.36; IR (film): nmax =3060, 3028,
2978, 2926, 2855, 1955, 1710, 1648, 1600, 1534, 1492, 1465,
1452, 1388, 1368, 1310, 1240, 1191, 1159, 1096, 1074, 1060,
1028, 1092, 977, 904, 875, 857, 844, 783, 735, 700, 674, 648,
Ethyl
5-benzoyl-11-chloro-1-phenyl-1,4,5,7,8,12b-hexa-
[7,1-a]isoquinoline-2-carboxylate (5ff):
hydro[1,2]diazepinoACHTUGNTRENNNUG
G
Yield: 62% (Table 3, entry 5); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.38; IR (film): nmax =3059, 3018,
2927, 2852, 1709, 1648, 1650, 1484, 1452, 1392, 1368, 1310,
1241, 1159, 1158, 1097, 1077, 1059, 1038, 1026, 973, 924, 912,
625, 567, 505, 467 cmÀ1 1H NMR (300 MHz, CDCl3): d=
;
7.56–7.34 (m, 5H), 7.32–7.11 (m, 5H), 7.09–7.00 (m, 3H),
5.98 (s, 1H), 5.17 (t, J=8.9 Hz, 1H), 4.29–4.15 (m, 1H),
3.94–3.87 (m, 3H), 3.14–3.04 (m, 1H), 2.84–2.74 (m, 1H),
2.46–2.44 (m, 3H), 2.19 (t, J=7.1 Hz, 3H), 0.95 (t, J=
8.9 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=170.8, 165.9,
141.4, 138.2, 137.0, 136.0, 133.8, 133.4, 129.7, 128.8, 128.4,
128.0, 127.7, 127.6, 126.0, 125.7, 123.8, 65.3, 60.6, 59.7, 49.0,
37.5, 27.6, 19.4, 13.8; HR-MS (ESI): m/z=467.2332, calcd.
855, 843, 810, 735, 699, 678, 648, 531 cmÀ1
;
1H NMR
(300 MHz, CDCl3): d=7.55–7.48 (m, 5H), 7.35–7.31 (m,
3H), 7.23–6.97 (m, 3H), 6.00 (s, 1H), 5.10–5.05 (m, 1H),
4.29–4.16 (m, 1H), 3.96–3.86 (m, 3H), 3.13–3.04 (m, 1H),
2.83–2.59 (m, 2H), 2.44–2.40 (m, 2H), 0.96 (t, J=7.1 Hz,
3H); 13C NMR (75 MHz, CDCl3): d=170.8, 165.8, 140.8,
140.0, 138.0, 136.7, 134.0, 133.4, 131.6, 130.1, 129.8, 128.8,
128.4, 128.1, 127.8, 126.4, 126.1, 65.3, 60.8, 59.4, 49.0, 37.3,
30.0, 13.8; HR-MS (ESI): m/z=487.1763, calcd. for
+
for C30H31N2O3 [M+H]+: 467.2329.
Ethyl
hexahydro
5-benzoyl-11-methyl-4-phenyl-1,4,5,7,8,12b-
[1,2]diazepino[7,1-a]isoquinoline-3-carboxylate
+
C29H28ClN2O3 [M+H]+: 487.1783.
N
ACHTUNGTRENNUNG
(5cf): Yield: 68% (Table 3, entry 2); yellow solid. TLC
(EtOAc/petroleum ether 1/5): Rf =0.38; IR (film): nmax
=
3058, 3028, 2979, 2927, 2866, 1891, 1710, 1649, 1601, 1578,
1536, 1504, 1493, 1452, 1393, 1368, 1311, 1240, 1186, 1158,
1097, 1075, 1039, 1059, 1027, 972, 960, 942, 909, 876, 844,
Acknowledgements
815, 736, 700, 677, 649, 678, 560, 536, 470, 457 cmÀ1
;
This study was supported by the National Scientific and Tech-
nology Supporting Program of China (2011BAE06B05-5),
the National Natural Science Foundation of China (No.
21172253), the startup research funding from China Agricul-
tural University, Chinese Universities Scientific Fund (Nos.
2011JS029 and 2011JS031), the Key Technologies R&D Pro-
gram of China (No. 2012BAK25B03), and Nutriechem Com-
pany.
1H NMR (300 MHz, CDCl3): d=7.57–7.49 (m, 5H), 7.38–
7.27 (m, 5H), 6.99–6.96 (m, 3H), 6.01 (s, 1H), 5.12–5.08 (m,
1H), 4.31–4.17 (m, 1H), 3.96–3.88 (m, 3H), 3.13–3.03 (m,
1H), 2.85–2.77 (m, 1H), 2.75–2.77 (m, 1H), 2.41–2.39 (m,
2H), 2.34 (s, 3H), 0.97 (t, J=7.1 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=170.7, 165.9, 141.6, 138.0, 137.0, 135.3,
133.8, 131.7, 129.6, 128.7, 128.4, 128.0, 127.6, 127.0, 126.6,
126.0, 65.2, 60.6, 59.5, 49.2, 38.0, 30.1, 21.1, 13.8; HR-MS
+
(ESI): m/z=467.2324, calcd. for C30H31N2O3 [M+H]+:
467.2329.
Ethyl
References
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[7,1-a]isoquinoline-3-carboxylate (5df):
hydro[1,2]diazepinoACHTUGNTRENNNUG
G
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troleum ether 1/5): Rf =0.32; IR (film): nmax =2922, 2851,
1709, 1647, 1482, 1452, 1368, 1309, 1239, 1058, 1026, 851,
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(m, 5H), 7.35–7.25 (m, 5H), 7.23–7.03 (m, 3H), 6.01 (s, 1H),
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Ethyl
5-benzoyl-11-bromo-4-phenyl-1,4,5,7,8,12b-hexa-
[7,1-a]isoquinoline-3-carboxylate (5ef):
hydro[1,2]diazepinoACHTUGNTRENNNUG
G
Yield: 62% (Table 3, entry 4); yellow solid. TLC (EtOAc/
petroleum ether 1/5): Rf =0.38; IR (film): nmax =3059, 3028,
2927, 2852, 1709, 1649, 1600, 1484, 1452, 1392, 1368, 1310,
1189, 1158, 1127, 1097, 1077, 1059, 1038, 1026, 973, 954, 912,
855, 843, 810, 735, 699, 678, 648, 531 cmÀ1
;
1H NMR
(300 MHz, CDCl3): d=7.55–7.48 (m, 5H), 7.35–7.25 (m,
1032
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 1023 – 1034

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[17] Crystallographic data for 4ef and 5df have been depos-
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under the numbers CCDC 838502 and CCDC 838503.
These data can be obtained free of charge from The
Cambridge
Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif or by contacting
The Cambridge Crystallographic Data Centre, 12
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asc.wiley-vch.de
1033

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Adv. Synth. Catal. 2012, 354, 1023 – 1034