A multimetallic piano-stool Ir-Sn3 catalyst for nucleophilic substitution reaction of γ-hydroxy lactams through N -acyliminium ions

Article abstract of DOI:10.1021/jo202359e

A multimetallic piano-stool complex [Cp*Ir(SnCl₃) ₂{SnCl₂(H₂O)₂}] (1) having Ir-Sn₃ motif has been synthesized from [Cp*IrCl ₂]₂ and SnCl₂. The multimetallic complex catalytically promotes the nucleophilic substitution reaction (here after α-amidoalkylation reaction) of γ-hydroxylactams generated from phthalimidals to obtain decorated isoindolinones in excellent yields. Succinamidals, however, lead to the substituted pyrrolidinones (thermodynamic control product) via S_N1-type path as well as eliminated pyrrolinones (kinetic control product) via an E1-type path, depending on the reaction parameters. A straightforward application of this methodology is to synthesize benzo-fused indolizidine alkaloid mimics.

Full text of DOI:10.1021/jo202359e

Note
pubs.acs.org/joc
A Multimetallic Piano-Stool Ir−Sn3 Catalyst for Nucleophilic
Substitution Reaction of γ-Hydroxy Lactams through N-Acyliminium
Ions†
Arnab Kumar Maity‡ and Sujit Roy*,§
‡Organometallics & Catalysis Laboratory, Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India
§School of Basic Sciences, Indian Institute of Technology, Bhubaneswar 751013, India
S
* Supporting Information
ABSTRACT: A multimetallic piano-stool complex [Cp*Ir-
(SnCl3)2{SnCl2(H2O)2}] (1) having Ir−Sn3 motif has been synthesized
from [Cp*IrCl2]2 and SnCl2. The multimetallic complex catalytically
promotes the nucleophilic substitution reaction (here after α-amidoalky-
lation reaction) of γ-hydroxylactams generated from phthalimidals to
obtain decorated isoindolinones in excellent yields. Succinamidals,
however, lead to the substituted pyrrolidinones (thermodynamic control
product) via SN1-type path as well as eliminated pyrrolinones (kinetic
control product) via an E1-type path, depending on the reaction parameters. A straightforward application of this methodology is
to synthesize benzo-fused indolizidine alkaloid mimics.
he development of multimetallic catalysis has drawn a
significant attention in modern organic synthesis due to
is the only complex utilized to date.9 In keeping with our
program on multimetallic catalysis, we report here the first
multimetallic piano-stool Ir−Sn3 complex 1 which catalytically
activates γ-hydroxylactams to produce N-acyliminium ions as
intermediates for efficient α-amidoalkylation reaction. The
catalyst also shows unique differential reactivity for phthalimi-
dals versus succinamidals.
T
its superiority in terms of enhanced reactivity and selectivity
over monometal catalysis.1 Like enzymes, in a cooperative
multimetallic catalyst two or more metal centers can
simultaneously activate nucleophiles and electrophiles leading
to higher level of efficiency. This multifunctional synergism has
been well exploited in a number of organic transformations.2
Within the above broad domain, a new class of catalysts can be
envisaged where multiple centers coordinate to bring a stronger
activation of the substrate and thus offer superior activity. Such
multisite interactions between adjacent metal centers are the
essence of cluster catalysis; for example, a metal−metal bond is
viewed as the edge of a cluster, while three metals constitute a
face.3 Our continuing success in illustrating the unique
reactivity of heterobimetallic catalysts4 bearing a transition
metal (Tm) and a main-group metal (Mgm) partner in
carbon−carbon bond forming reactions attracted us in
designing a substrate activation model across Tm−Mgm for
the intermolecular α-amidoalkylation reaction. Related recent
developments of note include the trapping of N-acyliminium
ions by stoichiometric Lewis and Brønsted acids and acidic
additives like TMSCl.5 Therefore, N-acyliminium ion chemistry
justifies development of catalytic version of the α-amidoalky-
lation reaction. Indeed recent excitement in the field testifies
this view with the emergence of thiourea,6 Brønsted acids,7 as
well as Lewis acidic metal triflates and triflimidates as catalysts.8
It is pertinent that in case of catalysis involving a metal
complex, the ligand motif is tunable to achieve desired
selectivity (chemo-, regio-, stereo-, enantio-). Such an
opportunity does not exist in case of “catalysis via simple
metal-salts”. To our knowledge, in the chemistry involving the
generation and utilization of N-acyliminium ion Au(PPh3)OTf
The multimetallic Ir−Sn3 complex 1 was synthesized via
insertion of SnCl2 across the iridium−chlorine bonds of
[Cp*IrCl2]2 in refluxing 1,2-dichloroethane.10 The initially
brick-red solution slowly turned greenish yellow on completion
of the reaction. Upon slow diffusion of n-hexane to this
solution, the product Cp*Ir(SnCl3)2{SnCl2(H2O)2} (1)
crystallized out as greenish yellow blocks in good yield. As
shown in Figure 1A, 1 adopts a perfect three-legged piano-stool
geometry, as is common to the Cp*IrIII complexes.11 In
solution, the three stannyl ligands in complex 1 are equivalent
in NMR time scale due to plausible fluxional behavior.12 The
satellite peaks in 1H and 119Sn NMR spectra of 1 also conclude
1
the presence of direct Ir−Sn bonds. The H−119Sn coupling
constant value (4JH−Sn = 29 Hz) lies in the expected range of
other known complexes.13 On the other hand, the 119Sn
chemical shift and the 117Sn−119Sn coupling constant value
2
(−311 ppm and JSn−Sn = 8 MHz) is well within the expected
region of Tm-SnCl3 complexes.10b We believe that the piano-
stool geometry having three Ir−Sn bonds holds the key to
superior catalytic activity of 1 since the three tin centers provide
an interactive face to bind the alkylating agent R−Y, (Figure
1B; Y = OH in the instant case).
Received: November 23, 2011
Published: February 24, 2012
© 2012 American Chemical Society
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Note
dimethylbenzene, and 1,3,5-trimethoxybenzene) and hetero-
aromatics (thiophene, 2-methylthiophene, 2,5-dimethylfuran,
and indole). Less electron-rich arenes like benzene or toluene
remained unreactive. Organosilicon nucleophiles (allyltrime-
thylsilane) and β-dicarbonyl nucleophiles (4-hydroxycoumarin)
also afforded the alkylated products 3d, 3q, 3t, and 3g almost
quantitatively. Delightfully, in addition to the α-amidoalkylation
of carbon nucleophiles; oxygen (2-propanol and 3-phenyl-
propanol), sulfur (thiophenol and 4-methoxythiophenol), or
nitrogen (N-tosylamine) nucleophiles were also found to
provide the alkylated products 3h−l in excellent yields. All
1
the new compounds were characterized by H NMR, 13C
NMR, HRMS, or elemental analysis data, and the structure of
3r was confirmed by X-ray crystallographic analysis (see the
Supporting Information).
Figure 1. (A) Molecular structure of 1. H-atoms are not shown for
clarity. (B) Proposed electrophilic activation model involving 1. R−Y
= alkylating agent, Nu = nucleophile.
In contrast to phthalimidals, a first set of reactions for
succinamidals with the model hydroxylactam 2d and 2-
methylthiophene in presence of catalyst 1 led to the expected
alkylated product 3u along with an eliminated product 4 (Table
3). The extent to which each product is formed varied with
reaction time and catalyst loading. For example, at 1 mol %
loading of 1, 3u was not observed even after 15 h (Table 3,
entry 2). The result was just reversed at 5 mol % catalyst
loading (entry 6). Further, at initial stage of reaction, 4 was
formed; but with the progress of time, 3u became the major
product (entries 3 versus 4 and 5 versus 6). It is apparent from
the above facts that under our reaction conditions pyrrolidi-
none 3u is a thermodynamically controlled product while N-
benzyl-3-pyrroline-2-one 4 is a kinetically controlled product.
Formation of 4 from 2d can be explained by a prior E1-type
elimination reaction followed by a double bond isomerization
(Scheme 1).14 We conjecture that the formation of 4 from N-
acyliminium ion is reversible and also much faster compared to
the substitution step (SN1-type) which leads to the alkylated
product 3. Gratifyingly, in a separate set of reaction when 4 was
reacted with 2-methylthiophene in presence of catalyst 1 (5
mol %) under similar conditions, 3u was the major product
Initially a model study on the α-amidoalkylation reaction of
thiophene with hydroxylactam 2a was scrutinized under a broad
set of conditions using a variety of Lewis acid catalysts (Table
1). Quantitative conversion was achieved with 1 mol % of 1,
and at 80 °C; the catalytic activity rapidly dropped down at
lower temperature (entries 1−3). We also noted the following:
(i) in terms of catalytic efficiency, 1 is superior over Lewis acids
like Sc(OTf)3, La(OTf)3 or SnCl4 (entries 3, 8, 9, and 11), (ii)
individually [Cp*IrCl2]2, SnCl4, or SnCl2 are poorly active
(entries 12−14), and (iii) the IrI−SnCl3 unit constructed on a
simple ligand-frame showed negligible catalytic activity (entry
7). All of the above observations possibly highlight a
multimetallic synergism in an Ir−Sn3 core that promotes the
alkylation reaction. However, further work is needed to
comprehend the nature of such a synergy.
The scope of the present multimetallic Ir−Sn3-catalyzed
alkylation reaction for phthalimidals is illustrated in Table 2.
Under optimal conditions, quantitative conversions and
excellent yields were achieved in the α-amidoalkylation reaction
with various electron-rich aromatics (anisole, 1-methoxy-3,5-
a
Table 1. Screening and Optimization of α-Amidoalkylation Reaction
b
c
no.
catalyst
x
solvent
temp, °C
conv,
%
yield, %
1
2
1
1
1
1
1
1
1
1
1
1
1
1
1
5
5
5
5
5
5
5
DCE
60
70
80
80
80
80
80
80
80
80
80
80
80
80
12
43
100
17
58
37
5
5
38
96
10
50
30
1
DCE
3
DCE
4
MeCN
MeNO2
toluene
DCE
5
6
7
(COD)2IrSnCl3
Sc(OTf)3
La(OTf)3
PTSA
8
DCE
50
5
22
0
9
DCE
10
11
12
13
14
DCE
10
10
0
0
SnCl4
DCE
5
[Cp*IrCl2]2
SnCl2
DCE
0
DCE
0
0
SnCl2.2H2O
DCE
0
0
a
General conditions: 2a (0.5 mmol), thiophene (1 mmol), catalyst (0.005 mmol for 1 mol % and 0.025 mmol for 5 mol %), solvent (2 mL).
Determined by NMR. Isolated yield.
b
c
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a
Table 2. Scope of α-Amidoalkylation Reaction with Phthalimidals Catalyzed by 1
a
Reactions were performed on a 0.25 mmol scale.
a
Table 3. Elimination vs Substitution Reaction for Succinamidal: Dependency on Catalyst Concentration and Reaction Time
entry
x
time, h
3u, %
4, %
1
2
3
4
5
6
1
1
3
3
5
5
2
15
2
0
0
16
39
35
24
13
0
3
15
2
17
39
50
10
a
General conditions: 2d (0.25 mmol), 2-methylthiophene (0.50 mmol), DCE (2 mL).
formed.15 One may also note the influence of nucleophilicity of
arene in the reaction of succinamidals. While highly electron
rich 1,3-dimethoxybenzene and 1,3,5-trimethoxybenzene gave
the corresponding alkylated products 3w and 3x in excellent
yields, anisole did not promote alkylation even after 20 h; the
elimination product 4 remained the only product (Scheme
2).16 However, it may be noted that hydroxylactams derived
from phthalimide were directly transformed to substituted
isoindolinones 3a−t via SN1-type pathway as elimination
reaction is not an option here.
Supporting Information), Lewis acidic nature of the hard tin
centers to interact with −OH group is well established.4,8b
Although at this stage the exact role of iridium is unclear,
whether it directly activates the substrate or it helps the tin
centers to do it and overall maintains an electrophilic
environment around the Ir−Sn3 motif for sustainable
catalysis.17 Although Sn−Cl bonds (as in SnCl4) are susceptible
for hydrolysis, those in “Ir−Sn3” are very inert; in fact, 1 is
stable enough to crystallize out even after catalysis (as
confirmed by crystal structure analysis). As water is producing
as a byproduct in our case, somehow, the multimetallic Ir−Sn3
system manages to overpower the hydrolytic decomposition
and thus as little as 1% of the catalyst 1 is sufficient for
We propose that the catalyst 1 acts as a mild and controlled
Lewis acid to activate and remove the −OH group of the
substrate. Further, from the NMR spectroscopic study (see the
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Note
a
Scheme 1. Proposed Reaction Mechanism
Scheme 3. Synthesis of Indolizidine Skeletons
a
Reagents and conditions: (a) Grubbs-I (1 mol %)/DCM/50 °C/12
h; (b) H2/Pd−C/MeOH/rt/12 h.
EXPERIMENTAL SECTION
■
General Procedures. All reactions were carried out under an
argon atmosphere in flame-dried glassware using standard Schlenk
techniques. Solvents are dried prior to use. Column chromatography
was performed on 100−200 mesh silica gel.
Starting Materials. [Cp*IrCl2]2 and [(COD)2Ir(SnCl3)] were
synthesized according to the literature procedures.20 Organic starting
materials 2a, 2b, and 2d were synthesized by NaBH4 reduction,8a and
2c was synthesized by Grignard reagent PhMgBr addition to imides
according to the literature procedures.21
2-Benzyl-3-hydroxyisoindolin-1-one (2a). White solid.22
2-Allyl-3-hydroxyisoindolin-1-one (2b). White solid.21
2-Allyl-3-hydroxy-3-phenylisoindolin-1-one (2c). White
solid.21
1-Benzyl-5-hydroxypyrrolidin-2-one (2d). White solid.23
Synthesis of Cp*Ir(SnCl3)2{SnCl2(H2O)2}·3H2O (1). To
[Cp*IrCl2]2 (40 mg, 0.05 mmol) in 2 mL of dichloroethane was
added anhydrous SnCl2 (60 mg, 0.3 mmol). The mixture was heated at
80 °C for 3 h. The initially brick red solution slowly turned a greenish
yellow color after completion of the reaction. After the mixture was
cooled to room temperature, the greenish yellow solution was taken
out from the reaction flask and slow diffusion of n-hexane to this
solution causes greenish yellow block like crystals: yield 90 mg (80%);
mp >300 °C; solubility: highly soluble in DMSO, MeCN, acetone;
moderately soluble in methanol, DCM, DCE, CHCl3; insoluble in
benzene, toluene and other hydrocarbons; 1H NMR (200 MHz,
acetone-d6) δ 2.29 (s, 15H, C5(CH3)5) with tin satellites (JH−Sn = 29
Hz); 13C NMR (54.6 MHz, acetone-d6) δ 10.4 (C5(CH3)5), 98.0
(C5(CH3)5); 119Sn NMR (149 MHz, acetone-d6) δ −311 with tin
satellites (JSn−Sn = 8000 Hz). Anal. Calcd for C10H25Cl8IrO5Sn3
(1057.59): C, 11.36; H, 2.38. Found: C, 11.53; H, 2.56.
Scheme 2. Elimination vs Substitution Reaction for
Succinamidal: Dependency on Nucleophilicity of Arenes
a
a
General conditions: 2d (0.25 mmol), NuH (0.50 mmol), DCE (2
mL)
quantitative organic transformation while the traditional Lewis
acids like SnCl4 fails (see Table 1).18 One worth noticing is that
the combination of high valent iridium and stannyl ligand as in
Ir−Sn3 motif is necessary for superior catalytic activity. Detailed
studies on the exact roles of these two metal partners in Ir−Sn3
motif are ongoing and will be reported in due course.
Alkaloids incorporating the indolizidine skeletons comprise a
large group of natural compounds having an interesting range
of biological activity.19 In this context, we perceive that there
remains a great applicability of the present route toward the
synthesis of benzo-fused indolizidine alkaloid mimics. As a
proof-of-principle, we constructed the desired indolizidine
skeletons from the alkylated products (3q or 3t) by ring
closing metathesis followed by olefin hydrogenation (Scheme
3). Significantly, compound 7b is a non-nucleoside HIV-1
reverse transcriptase inhibitor.19a
In summary, we have synthesized a new multimetallic Ir−Sn3
catalyst, Cp*Ir(SnCl3)2{SnCl2(H2O)2}, having piano-stool
geometry for amidoalkylation reaction. The differential
reactivity of succinamidals (over phthalimidals) toward
elimination and substitution reaction is yet another discrete
outcome of this study. Asymmetric induction and further
synthetic elaboration are underway.
General Procedure for the Nucleophilic Substitution
Reaction of γ-Hydrxylactams 2a−d Catalyzed by Complex 1.
To a solution of γ-hydroxylactam 2a (60 mg, 0.25 mmol) in 2 mL of
DCE were added under an argon atmosphere thiophene (40 μL, 0.5
mmol) and 1 (2.6 mg, 0.0025 mmol). The reaction mixture was stirred
at 80 °C. When the reaction was over (monitored by TLC using ethyl
acetate/petroleum ether 60−80 °C 1:3 v/v), a saturated aqueous
solution of sodium hydrogencarbonate was added. The aqueous layer
was then extracted two times with CH2Cl2 (2 × 5 mL). The combined
organic layers were dried over Na2SO4; the solvent was removed under
reduced pressure. The resulting product was purified by column
chromatography on silica gel to give the expected coupled product 3.
2-Benzyl-3-(thiophene-2-yl)isoindolin-1-one (3a): crystalline
1
white solid (73 mg, 96%); mp 125−127 °C; H NMR (400 MHz,
CDCl3) δ 3.89 (d, 1H, J = 14.8 Hz), 5.40 (d, 1H, J = 14.8 Hz), 5.57 (s,
1H), 7.00−7.04 (m, 2H), 7.23−7.33 (m, 7H), 7.46−7.51 (m, 2H),
7.92−7.96 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 43.6, 58.7, 123.2,
123.8, 126.7, 126.9, 127.6, 127.7, 128.4, 128.6, 128.7, 131.1, 131.9,
137.0, 140.0, 145.6, 167.8; 13C DEPT-135 NMR (100 MHz, CDCl3) δ
43.7 (CH2), 58.7 (CH), 123.3 (CH), 123.8 (CH), 126.8 (CH), 127.0
(CH), 127.7 (CH), 127.8 (CH), 128.5 (CH), 128.76 (CH), 128.79
(CH), 132.0 (CH). Anal. Calcd for C19H15NOS (305.09): C, 74.72;
H, 4.95; N, 4.59. Found: C, 74.91; H, 5.13; N, 4.41.
2-Benzyl-3-(5-methylthiophene-2-yl)isoindolin-1-one (3b):
1
white crystalline solid (75 mg, 94%); mp 110−112 °C; H NMR
(200 MHz, CDCl3) δ 2.43 (s, 3H), 3.91 (d, 1H, J = 14.8 Hz), 5.40 (d,
1H, J = 15 Hz), 5.48 (s, 1H), 6.66 (d, 1H, J = 2.4 Hz), 6.85 (d, 1H, J =
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Note
3.2 Hz), 7.23−7.31 (m, 6H), 7.47−7.51 (m, 2H), 7.91−7.95 (m, 1H);
13C NMR (54.6 Hz, CDCl3) δ 16.5, 44.6, 60.0, 124.2, 124.7, 125.8,
128.5, 128.9, 129.5, 129.6, 129.7, 132.2, 132.9, 138.1, 138.4, 142.6,
146.7, 168.7; HRMS (ESI) calcd for C20H17NOS + H+ 320.1109,
found 320.1103.
(CH), 132.0 (CH). Anal. Calcd for C18H19NO2 (281.14): C, 76.84; H,
6.81; N, 4.98. Found: C, 76.62; H, 6.98; N, 4.81.
2-Benzyl-3-(3-phenylpropoxy)isoindolin-1-one (3i): colorless
oil (85 mg, 96%); 1H NMR (400 MHz, CDCl3) δ 1.75−1.85 (m, 2H),
2.62 (t, 2H, J = 7.6 Hz), 2.97 (dt, 1H, J = 6.4 Hz, 15.6 Hz), 3.14 (dt,
1H, J = 6.4 Hz, 15.2 Hz), 4.25 (d, 1H, J = 14.8 Hz), 5.15 (d, 1H, J =
14.4 Hz), 5.75 (s, 1H), 7.14−7.21 (m, 3H), 7.26−7.38 (m, 7H), 7.47−
7.58 (m, 3H), 7.87 (d, 1H, J = 6.8 Hz); 13C NMR (100 MHz, CDCl3)
δ 31.1, 32.3, 43.2, 61.6, 85.4, 123.4, 123.6, 125.9, 127.6, 128.2, 128.3,
128.5, 128.7, 129.8, 132.0, 132.6, 136.9, 141.0, 141.5, 167.4; 13C
DEPT-135 NMR (100 MHz, CDCl3) δ 31.2 (CH2), 32.4 (CH2), 43.3
(CH2), 61.7 (CH2), 85.5 (CH), 123.5 (CH), 123.7 (CH), 125.9
(CH), 127.6 (CH), 128.3 (CH), 128.4 (CH), 128.6 (CH), 128.7
(CH), 129.9 (CH), 132.1 (CH). Anal. Calcd for C24H23NO2 (357.17):
C, 80.64; H, 6.49; N, 3.92. Found: C, 80.81; H, 6.65; N, 3.77.
2-Benzyl-3-(4-methoxyphenylthio)isoindolin-1-one (3j):
2-Benzyl-3-(2,5-dimethylfuran-3-yl)isoindolin-1-one (3c):
1
colorless oil (76 mg, 96%); H NMR (200 MHz, CDCl3) δ 2.07 (s,
3H), 2.16 (s, 3H), 3.83 (d, 1H, J = 14.8 Hz), 5.15 (s, 1H), 5.35 (s,
1H), 5.37 (d, 1H, J = 14.8 Hz), 7.15−7.31 (m, 6H), 7.45−7.49 (m,
2H), 7.90−7.95 (m, 1H); 13C NMR (54.6 MHz, CDCl3) δ 11.5, 13.5,
43.7, 55.4, 104.8, 115.5, 123.0, 123.7, 127.5, 128.3, 128.7, 131.7, 137.3,
145.8, 148.8, 150.9, 168.1; 13C DEPT-135 NMR (100 MHz, CDCl3) δ
11.5 (CH3), 13.5 (CH3), 44.2 (CH2), 55.4 (CH), 104.7 (CH), 123.0
(CH), 123.7 (CH), 127.5 (CH), 128.2 (CH), 128.3 (CH), 128.6
(CH), 131.7 (CH). Anal. Calcd for C21H19NO2 (317.14): C, 79.47; H,
6.03; N, 4.41. Found: C, 79.33; H, 6.27; N, 4.25.
1
white solid (86 mg, 96%); H NMR (400 MHz, CDCl3) δ 3.68 (s,
3-Allyl-2-benzylisoindolin-1-one (3d): colorless oil (63 mg,
1
3H), 4.55 (d, 1H, J = 14.4 Hz), 5.40 (s, 1H), 5.44 (d, 1H, J = 14.8 Hz),
6.57 (d, 2H, J = 8.4 Hz), 6.94 (d, 2H, J = 8.4 Hz), 7.26−7.36 (m, 6H),
7.52 (t, 1H, J = 7.6 Hz), 7.58−7.59 (m, 2H). 13C NMR (100 MHz,
CDCl3) δ 43.0, 55.1, 65.7, 114.1, 117.7, 123.3, 123.7, 127.6, 128.4,
128.5, 128.7, 131.5, 131.5, 136.7, 137.2, 143.0, 160.4, 167.3; 13C
DEPT-135 NMR (100 MHz, CDCl3) δ 43.1 (CH2), 55.2 (CH3), 65.8
(CH), 114.1 (CH), 123.3 (CH), 123.7 (CH), 127.7 (CH), 128.5
(CH), 128.6 (CH), 128.8 (CH), 131.6 (CH), 137.3 (CH). Anal.
Calcd for C22H19NO2S (361.11): C, 73.10; H, 5.30; N, 3.88. Found:
C, 73.31; H, 5.12; N, 4.13.
95%); H NMR (200 MHz, CDCl3) δ 2.56−2.80 (m, 2H), 4.17 (d,
1H, J = 15.2 Hz), 4.42 (t, 1H, J = 5.2 Hz), 4.96−5.07 (m, 2H), 5.24−
5.41 (m, 1H), 5.42 (d, 1H, J = 15.2 Hz), 7.22−7.55 (m, 8H), 7.87−
7.91 (m, 1H); 13C NMR (54.6 MHz, CDCl3) δ 35.2, 43.9, 58.0, 119.3,
122.4, 123.8, 127.6, 128.1, 128.8, 131.2, 131.4, 132.3, 137.1, 144.9,
168.5. Anal. Calcd for C18H17NO (263.13): C, 82.10; H, 6.51; N, 5.32.
Found: C, 82.31; H, 6.37; N, 5.44.
2-Benzyl-3-(4-methoxy-2,6-dimethylphenyl)isoindolin-1-
one (3e). Mixture of ortho and para regioisomers and isolated as
1
colorless oil (82 mg, 92%): H NMR (200 MHz, CDCl3) δ 1.52 (s,
3H), 1.58 (s, 3H), 2.03 (s, 3H), 2.33 (s, 3H), 3.62 (d, 1H, J = 14.6
Hz), 3.70 (s, 3H), 3.71 (d, 1H, J = 14.6 Hz), 3.79 (s, 3H), 5.27 (d, 1H,
J = 14.4 Hz), 5.43 (d, 1H, J = 14.6 Hz), 5.72 (s, 1H), 6.30 (s, 1H),
6.48 (s, 2H), 6.61−6.66 (m, 2H), 7.07−7.30 (m, 11H), 7.40−7.48 (m,
5H), 7.87−7.97 (m, 2H); 13C NMR (54.6 MHz, CDCl3) δ 18.3, 18.9,
21.0, 21.5, 43.8, 44.0, 55.1, 55.5, 55.7, 59.1, 109.6, 114.1, 115.8, 118.2,
122.3, 122.6, 123.3, 123.5, 123.7, 125.4, 127.3, 127.6, 127.8, 128.1,
128.3, 128.5, 128.7, 128.8, 131.6, 131.8, 132.5, 132.7, 137.2, 137.4,
139.4, 139.9, 145.4, 145.9, 158.9, 168.6. Anal. Calcd for C24H23NO2
(357.17): C, 80.64; H, 6.49; N, 3.92. Found: C, 80.79; H, 6.66; N,
3.80.
2-Allyl-3-(phenylthio)isoindolin-1-one (3k): colorless oil (67
mg, 95%); H NMR (200 MHz, CDCl3) δ 4.07 (dd, 1H, J = 7.8 and
1
15.4 Hz), 4.77 (dd, 1H, J = 4.2 and 15.4 Hz), 5.18−5.25 (m, 2H), 5.72
(s, 1H), 5.83 (dddd, 1H, J = 1.4 Hz, 7.0 Hz, 11.2 and 18.8 Hz), 7.04−
7.19 (m, 5H), 7.34 (t, 1H, J = 7.4 Hz), 7.50−7.66 (m, 3H); 13C NMR
(54.6 MHz, CDCl3) δ 41.9, 66.0, 118.4, 123.2, 123.8, 128.1, 128.6,
129.0, 131.6, 132.5, 135.2, 142.9, 167.1; 13C DEPT-135 NMR (100
MHz, CDCl3) δ 41.9 (CH2), 66.0 (CH), 118.4 (CH2), 123.2 (CH),
123.8 (CH), 128.6 (CH), 128.7 (CH), 129.0 (CH), 131.6 (CH),
132.5 (CH), 135.2 (CH). Anal. Calcd for C17H15NOS (281.09): C,
72.57; H, 5.37; N, 4.98. Found: C, 72.43; H, 5.18; N, 5.21.
2-Benzyl-3-(2,4,6-trimethoxyphenyl)isoindolin-1-one (3f):
colorless crystalline solid (93 mg, 96%); 120−122 °C; 1H NMR
(200 MHz, CDCl3) δ 3.25 (s, 3H), 3.69 (s, 3H), 3.79 (s, 3H), 3.83 (d,
1H, J = 14.6 Hz), 5.13 (d, 1H, J = 14.6 Hz), 5.91 (d, 1H, J = 2.0 Hz),
5.98 (s, 1H), 6.16 (d, 1H, J = 2.0 Hz), 7.09−7.23 (m, 6H), 7.35−7.39
(m, 2H), 7.86−7.91 (m, 1H); 13C NMR (54.6 Hz, CDCl3) δ 44.2,
54.8, 55.3, 55.8, 90.4, 91.2, 103.8, 121.8, 123.0, 127.0, 127.1, 128.1,
128.6, 130.9, 132.9, 137.8, 147.0, 160.1, 160.5, 161.7, 169.0; 13C
DEPT-135 NMR (100 MHz, CDCl3) δ 44.2 (CH2), 54.8 (CH3), 55.3
(CH3), 55.4 (CH3), 55.8 (CH), 90.4 (CH), 91.2 (CH), 121.8 (CH),
123.0 (CH), 127.0 (CH), 127.1 (CH), 128.1 (CH), 128.6 (CH),
130.9 (CH); HRMS (ESI) calcd for C24H23NO4 + H+ 390.1705, found
390.1701.
2-Benzyl-3-(4-hydroxy-2-oxo-2H-chromen-3-yl)isoindolin-1-
one (3g): off-white solid (92 mg, 96%); 1H NMR (200 MHz, CDCl3)
δ 4.32 (d, 1H, J = 14.8 Hz), 4.90 (d, 1H, J = 14.8 Hz), 6.09 (s, 1H),
7.07−7.65 (m, 12H), 8.34 (d, 1H, J = 7.8 Hz); 13C NMR (100 MHz,
CDCl3) δ 45.1, 57.6, 99.1, 115.8, 116.9, 122.4, 122.9, 123.3, 124.2,
127.5, 128.0, 128.1, 128.2, 128.5, 131.5, 132.0, 132.8, 136.0, 145.3,
153.1, 164.0, 164.3, 170.5; 13C DEPT-135 NMR (100 MHz, CDCl3) δ
45.2, 57.7, 117.0, 122.5, 123.0, 123.5, 124.4, 127.7, 128.2, 128.3, 128.6,
132.1, 132.9; HRMS (ESI) calcd for C24H17NO4 + Na+ 406.1055,
found 406.1055.
N-(2-Allyl-3-oxoisoindolin-1-yl)-4-methylbenzenesulfona-
mide (3l): white solid (80 mg, 95%); 1H NMR (400 MHz, CDCl3) δ
2.48 (s, 3H), 3.49 (dd, 1H, J = 6.8 and 16.0 Hz), 3.87 (d, 1H, J = 14.4
Hz), 4.95 (d, 1H, J = 17.2 Hz), 5.06 (d, 1H, J = 10.4 Hz), 5.60 (ddd,
1H, J = 3.0 Hz, 9.0 and 13.4 Hz), 5.71 (d, 1H, J = 10.0 Hz), 6.38 (d,
1H, J = 10.0 Hz), 6.88 (s, 1H), 7.37−7.41 (m, 4H), 7.62 (s, 1H), 7.87
(d, 2H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3) δ 21.5, 41.0, 67.4,
117.6, 123.0, 123.4, 126.9, 129.6, 129.9, 130.9, 131.8, 132.4, 138.5,
142.2, 143.9, 167.0; 13C DEPT-135 NMR (100 MHz, CDCl3) δ 21.6
(CH3), 41.1 (CH2), 67.5 (CH), 117.7 (CH2), 123.1 (CH), 123.5
(CH), 126.9 (CH), 129.7 (CH), 130.0 (CH), 131.9 (CH), 132.5
(CH). Anal. Calcd for C18H18N2O3S (342.10): C, 63.14; H, 5.30; N,
8.18. Found: C, 62.90; H, 5.14; N, 8.01.
2-Allyl-3-(1H-indol-3-yl)isoindolin-1-one (3m): colorless crys-
1
talline solid (66 mg, 92%); mp 138−140 °C; H NMR (200 MHz,
CDCl3) δ 3.47 (dd, 1H, J = 7.2 and 15.6 Hz), 4.65 (dd, 1H, J = 4.0 and
15.6 Hz), 5.05−5.18 (m, 2H), 5.82 (dddd, 1H, J = 2.1 Hz, 4.9 Hz, 12.1
and 19.3 Hz), 5.86 (s, 1H), 6.88−6.94 (m, 2H), 7.09−7.18 (m, 1H),
7.26−7.53 (m, 5H), 7.98−8.02 (m, 1H), 9.45 (s, 1H); 13C NMR (54.6
MHz, CDCl3) δ 42.5, 57.9, 110.1, 111.8, 117.4, 118.9, 119.9, 122.4,
123.4, 125.2, 125.3, 128.3, 131.9, 133.2, 137.1, 146.3, 168.4; 13C
DEPT-135 NMR (100 MHz, CDCl3) δ 42.5 (CH2), 57.8 (CH), 111.7
(CH), 117.4 (CH2), 118.9 (CH), 119.9 (CH), 122.4 (CH), 123.4
(CH), 123.4 (CH), 125.1 (CH), 128.3 (CH), 131.8 (CH), 133.2
(CH); HRMS (ESI) calcd for C19H16N2O + H+ 289.1341, found
289.1334.
2-Benzyl-3-isopropoxyisoindolin-1-one (3h): colorless oil (65
1
mg, 90%); H NMR (200 MHz, CDCl3) δ 1.07 (d, 3H, J = 6.2 Hz),
1.21 (d, 3H, J = 6.0 Hz), 3.64 (septet, 1H, J = 6.0 Hz), 4.25 (d, 1H, J =
15.0 Hz), 5.27 (d, 1H, J = 15.0 Hz), 5.64 (s, 1H), 7.26−7.31 (m, 5H),
7.48−7.57 (m, 3H), 7.85 (d, 1H, J = 7.4 Hz); 13C NMR (100 MHz,
CDCl3) δ 23.4, 23.7, 43.1, 68.7, 85.2, 123.5, 127.5, 128.2, 128.4, 128.7,
129.7, 131.9, 132.3, 137.0, 142.2, 167.3; 13C DEPT-135 NMR (100
MHz, CDCl3) δ 23.5 (CH3), 23.8 (CH3), 43.2 (CH2), 68.7 (CH),
85.2 (CH), 123.5 (CH), 127.6 (CH), 128.2 (CH), 128.7 (CH), 129.7
2-Allyl-3-(4-methoxyphenyl)isoindolin-1-one (3n): colorless
1
oil (64 mg, 92%); H NMR (200 MHz, CDCl3) δ 3.31 (dd, 1H, J
= 7.6 and 15.4 Hz), 3.78 (s, 3H), 4.64 (dd, 1H, J = 4.2 and 15.4 Hz),
5.01−5.17 (m, 2H), 5.41 (s, 1H), 5.77 (dddd, 1H, J = 2.1 Hz, 7.7 Hz,
11.9 and 19.7 Hz), 6.85 (d, 2H, J = 8.8 Hz), 7.01 (d, 2H, J = 8.6 Hz),
7.13−7.17 (m, 1H) 7.39−7.49 (m, 2H), 7.84−7.91 (m, 1H); 13C
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The Journal of Organic Chemistry
Note
NMR (54.6 MHz, CDCl3) δ 42.5, 55.3, 63.4, 114.4, 117.9, 123.1,
123.5, 128.2, 128.6, 129.0, 131.5, 131.8, 133.0, 146.6, 159.8, 168.2;
HRMS (ESI) calcd for C18H17NO2 + H+, 280.1338; found, 280.1331.
2-Allyl-3-(2,4,6-trimethoxyphenyl)isoindolin-1-one (3o): col-
orless crystalline solid (80 mg, 96%); mp 128−130 °C; 1H NMR (200
MHz, CDCl3) δ 3.28 (s, 3H), 3.38 (dd, 1H, J = 7.0 and 15.2 Hz), 3.81
(s, 3H), 3.89 (s, 3H), 4.48 (dd, 1H, J = 5.0 and 15.4 Hz), 4.96−5.08
(m, 2H), 5.78 (dddd, 1H, J = 3.2 Hz, 8 Hz, 13.2 and 20.2 Hz), 5.96 (d,
1H, J = 2.0 Hz), 6.15 (s, 1H), 6.20 (d, 1H, J = 2.0 Hz), 7.15−7.19 (m,
1H), 7.38−7.42 (m, 2H), 7.88−7.92 (m, 1H); 13C NMR (54.6 MHz,
CDCl3) δ 43.0, 55.1, 55.5, 55.6, 56.2, 90.7, 91.5, 104.4, 117.1, 122.0,
123.1, 127.3, 131.0, 133.2, 133.7, 147.2, 160.4, 160.7, 161.8, 168.9; 13C
DEPT-135 NMR (100 MHz, CDCl3) δ 42.8 (CH2), 55.0 (CH3), 55.3
(CH3), 55.4 (CH3), 56.0 (CH), 90.5 (CH), 91.3 (CH), 116.9 (CH2),
121.8 (CH), 123.0 (CH), 127.1 (CH), 130.8 (CH), 133.4 (CH);
HRMS (ESI) calcd for C20H21NO4 + H+ 340.1549, found 340.1544.
2-Allyl-3-(2,5-dimethylfuran-3-yl)isoindolin-1-one (3p): col-
2.08 (m, 1H), 2.38−2.53 (m, 5H), 2.64−2.72 (m, 1H), 3.64 (d, 1H, J
= 14.8 Hz), 4.62−4.65 (m, 1H), 5.09 (d, 1H, J = 14.8 Hz), 6.61−6.62
(m, 1H), 6.66 (d, 1H, J = 3.6 Hz), 7.17−7.19 (m, 2H), 7.26−7.34 (m,
3H); 13C NMR (54.6 MHz, CDCl3) δ 15.4, 28.6, 30.1, 44.1, 56.9,
124.6, 126.0, 127.4, 128.4, 128.5, 136.5, 140.3, 142.0, 174.4; 13C
DEPT-135 NMR (100 MHz, CDCl3) δ 15.5 (CH3), 28.6 (CH2), 30.2
(CH2), 44.1 (CH2), 57.0 (CH), 124.6 (CH), 126.1 (CH), 127.5
(CH), 128.5 (CH), 128.6 (CH). Anal. Calcd for C16H17NOS
(271.10): C, 70.81; H, 6.31; N, 5.16. Found: C, 70.95; H, 6.12; N,
5.02.
1-Benzyl-5-(2,4-dimethoxyphenyl)pyrrolidin-2-one (3w): col-
1
orless oil (65 mg, 83%); H NMR (400 MHz, CDCl3) δ 1.84−1.92
(m, 1H), 2.26−2.36 (m, 1H), 2.41−2.49 (m, 1H), 2.55−2.64 (m, 1H),
3.53 (d, 1H, J = 14.4 Hz), 3.70 (s, 3H), 3.81 (s, 3H), 4.72 (dd, 1H, J =
4.0 and 8.4 Hz), 5.03 (d, 1H, J = 14.4 Hz), 6.45−6.47 (m, 2H), 6.92
(d, 1H, J = 8.0 Hz), 7.09 (d, 2H, J = 6.0 Hz), 7.22−7.28 (m, 3H); 13C
NMR (100 MHz, CDCl3) δ 26.2, 30.2, 44.3, 55.2, 55.3, 56.3, 98.8,
104.0, 120.5, 127.2, 128.0, 128.3, 136.6, 158.2, 160.5, 175.7; 13C
DEPT-135 NMR (100 MHz, CDCl3) δ 26.3 (CH2), 30.3 (CH2), 44.4
(CH2), 55.3 (CH3), 55.4 (CH3), 56.3 (CH), 98.9 (CH), 104.1 (CH),
127.3 (CH), 128.1 (CH), 128.4 (CH). Anal. Calcd for C19H21NO3
(311.15): C, 73.29; H, 6.80; N, 4.50. Found: C, 73.11; H, 6.93; N,
4.34.
1
orless viscous oil (63 mg, 95%); H NMR (200 MHz, CDCl3) δ 2.11
(s, 3H), 2.25 (s, 3H), 3.36 (dd, 1H, J = 7.8 and 15.6 Hz), 4.61 (dd,
1H, J = 4.0 and 15.4 Hz), 5.03−5.16 (m, 2H), 5.29 (s, 1H), 5.33 (s,
1H), 5.76 (dddd, 1H, J = 1.9 Hz, 7.7 Hz, 11.7 and 19.5 Hz), 7.18−7.22
(m, 1H), 7.38−7.50 (m, 2H), 7.82−7.86 (m, 1H); 13C NMR (54.6
MHz, CDCl3) δ 11.6, 13.4, 42.3, 55.6, 104.7, 115.6, 117.5, 123.0,
123.5, 128.2, 131.6, 131.8, 133.3, 145.7, 148.7, 150.8, 167.8; 13C
DEPT-135 NMR (100 MHz, CDCl3) δ 11.6 (CH3), 13.4 (CH3), 42.3
(CH2), 55.6 (CH), 104.7 (CH), 117.5 (CH2), 123.0 (CH), 123.4
(CH), 128.2 (CH), 131.6 (CH), 133.3 (CH). Anal. Calcd for
C17H17NO2 (267.13): C, 76.38; H, 6.41; N, 5.24. Found: C, 76.53; H,
6.59; N, 5.11.
1-Benzyl-5-(2,4,6-trimethoxyphenyl)pyrrolidin-2-one (3x):
1
colorless oil (72 mg, 85%); H NMR (200 MHz, CDCl3) δ 1.85−
2.75 (m, 4H), 3.49 (d, 1H, J = 14.4 Hz), 3.63−3.70 (m, 6H), 3.81 (s,
3H), 4.79 (d, 1H, J = 14.6 Hz), 5.14 (dd, 1H, J = 4.8 and 9.6 Hz), 6.06
(s, 2H), 7.04−7.08 (m, 2H), 7.19−7.23 (m, 3H); 13C NMR (100
MHz, CDCl3) δ 23.4, 31.1, 44.3, 51.5, 55.2, 55.4, 90.0, 90.7, 108.0,
126.8, 127.9, 128.5, 137.1, 160.9, 175.5. 13C DEPT-135 NMR (100
MHz, CDCl3) δ 23.5 (CH2), 31.9 (CH2), 44.4 (CH2), 51.6 (CH3),
55.3 (CH3), 55.5 (CH3), 90.1 (CH), 90.8 (CH), 126.9 (CH), 127.9
(CH), 128.0 (CH), 128.6 (CH); HRMS (ESI) calcd for C20H23NO4 +
H+, 342.1705; found, 342.1700.
2,3-Diallylisoindolin-1-one (3q). Colorless oil (50 mg, 93%) and
identified by spectral comparison with literature data.8a
2-Allyl-3-(thiophene-2-yl)isoindolin-1-one (3r): white crystal-
line solid (58 mg, 92%); mp 95−97 °C; 1H NMR (200 MHz, CDCl3)
δ 3.47 (dd, 1H, J = 7.8 and 15.6 Hz), 4.66 (dd, 1H, J = 4.4 and 15.4
Hz), 5.07−5.20 (m, 2H), 5.69−5.89 (m, 1H), 5.78 (s, 1H), 6.97−7.14
(m, 2H), 7.29−7.35 (m, 2H), 7.44−7.56 (m, 2H), 7.86−7.93 (m, 1H);
13C NMR (54.6 MHz, CDCl3) δ 42.5, 59.0, 118.1, 123.2, 123.6, 126.6,
126.9, 127.6, 128.7, 131.2, 131.9, 132.8, 140.2, 145.6, 167.6; 13C
DEPT-135 NMR (100 MHz, CDCl3) δ 42.5 (CH2), 59.0 (CH), 118.1
(CH2), 123.2 (CH), 123.7 (CH), 126.6 (CH), 126.9 (CH), 127.5
(CH), 128.7 (CH), 131.9 (CH), 132.8 (CH); HRMS (ESI) calcd for
C15H13NOS + Na+ 278.0616, found, 278.0616.
1-Benzyl-1H-pyrrol-2(5H)-one (4). Colorless oil (25 mg, 57%)
and identified by spectral comparison with literature data.24
1,10b-Dihydropyrido[2,1-a]isoindol-6(4H)-one (6a). Com-
pound 6a was synthesized as an off-white solid (72 mg, 78%)
according to the literature procedure.25a
10b-Phenyl-1,10b-dihydropyrido[2,1-a]isoindol-6(4H)-one
(6b). Compound 6b was prepared similarly as above: off-white solid
1
(105 mg, 80%); H NMR (400 MHz, CDCl3) δ 2.34−2.41 (m, 1H),
2-Allyl-3-(5-methylfuran-2-yl)isoindolin-1-one (3s): white
crystalline solid (60 mg, 96%); mp 115−117 °C; 1H NMR (200
MHz, CDCl3) δ 2.18 (s, 3H), 3.58 (dd, 1H, J = 7.2 and 15.4 Hz), 4.57
(dd, 1H, J = 4.6 Hz, 15.4 Hz), 5.07−5.16 (m, 2H), 5.51 (s, 1H), 5.76
(dddd, 1H, J = 3.1 Hz, 7.7 Hz, 12.1 and 19.5 Hz), 5.91 (d, 1H, J = 2.2
Hz), 6.19 (d, 1H, J = 3.0 Hz), 7.30−7.34 (m, 1H), 7.43−7.54 (m, 2H),
7.85−7.89 (m, 1H); 13C NMR (54.6 MHz, CDCl3) δ 13.6, 43.0, 57.6,
106.3, 110.7, 117.7, 123.0, 123.6, 128.6, 131.6, 132.0, 132.9, 143.2,
147.2, 153.3, 167.8; 13C DEPT-135 NMR (100 MHz, CDCl3) δ 13.5
(CH3), 43.0 (CH2), 57.6 (CH), 106.3 (CH), 110.7 (CH), 117.7
(CH2), 123.0 (CH), 123.6 (CH), 128.5 (CH), 131.6 (CH), 132.9
(CH); HRMS (ESI) calcd for C16H15NO2 + H+ 254.1181, found
254.1175.
3.43−3.53 (m, 2H), 4.72−4.79 (m, 1H), 5.70−5.75 (m, 1H), 5.91−
5.96 (m, 1H), 7.21−7.35 (m, 6H), 7.43−7.49 (m, 2H), 7.92−7.94 (m,
1H); 13C NMR (100 MHz, CDCl3) δ 33.0, 38.2, 64.6, 121.6, 122.4,
123.9, 124.4, 126.0, 127.8, 128.1, 128.8, 130.5, 131.9, 138.6, 151.9,
167.1; 13C DEPT-135 NMR (100 MHz, CDCl3) δ 33.0 (CH2), 38.2
(CH2), 121.6 (CH), 122.4 (CH), 123.9 (CH), 124.4 (CH), 126.0
(CH), 127.8 (CH), 128.1 (CH), 128.8 (CH), 131.9 (CH). Anal.
Calcd for C18H15NO (261.12): C, 82.73; H, 5.79; N, 5.36. Found: C,
82.87; H, 5.99; N, 5.21.
1,2,3,4-Tetrahydropyrido[2,1-a]isoindol-6(10bH)-one (7a).
Compound 7a was synthesized as a colorless oil (90 mg, 95%)
according to the literature procedure25a and identified by spectral
comparison with literature data.25b
2,3-Diallyl-3-phenylisoindolin-1-one (3t): colorless oil (70 mg,
10b-Phenyl-1,2,3,4-tetrahydropyrido[2,1-a]isoindol-6-
(10bH)-one (7b). Prepared similarly as above. Off-white solid (125
mg, 96%). The product was and identified by spectral comparison with
literature data.19a
1
96%); H NMR (400 MHz, CDCl3) δ 3.23 (d, 2H, J = 6.8 Hz), 3.70
(dd, 1H, J = 7.2 and 15.6 Hz), 4.07 (dd, 1H, J = 5.6 and 15.6 Hz),
4.87−5.07 (m, 4H), 5.13−5.24 (m, 1H), 5.69−5.79 (m, 1H), 7.08 (d,
1H, J = 7.2 Hz), 7.16 (d, 2H, J = 6.4 Hz), 7.25−7.31 (m, 3H), 7.38−
7.46 (m, 2H), 7.86 (d, 1H, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3)
δ 38.3, 43.2, 70.4, 117.3, 119.6, 122.1, 123.3, 126.7, 128.0, 128.6, 131.0,
131.5, 131.9, 133.5, 139.7, 149.8, 168.7; 13C DEPT-135 NMR (100
MHz, CDCl3) δ 40.9 (CH2), 45.8 (CH2), 119.9 (CH2), 122.2 (CH2),
124.7 (CH), 126.0 (CH), 129.3 (CH), 130.6 (CH), 131.2 (CH),
133.6 (CH), 134.5 (CH), 136.1 (CH). Anal. Calcd for C20H19NO
(289.15): C, 83.01; H, 6.62; N, 4.84. Found: C, 83.20; H, 6.50; N,
4.98.
Experimental Procedure To Study the Elimination vs
Substitution Reaction for Succinamidal. To a solution of
succinamidal 2d (24 mg, 0.125 mmol) in 2 mL of DCE were added
under an argon atmosphere 2-methylthiophene (25 μL, 0.25 mmol),
triphenylmethane (7.3 mg, 0.03 mmol) as internal standard, and 1 (1.3
mg for 1 mol % loading). The reaction mixture was stirred at 80 °C. At
different time interval 100 μL of aliquot was taken out, solvent was
1
removed under reduced pressure, and H NMR was recorded using
CDCl3 as NMR solvent.
1-Benzyl-5-(5-methylthiophene-2-yl)pyrrolidin-2-one (3u):
colorless oil (35 mg, 50%); H NMR (400 MHz, CDCl3) δ 2.01−
X-ray Crystallographic Analysis of 1 and 3r. The X-ray
diffraction intensity data for all compounds were collected at 293K
1
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Note
using a CCD diffractometer (graphite-monochromated Mo Kα
radiation, λ = 0.71073 Å). The structures were solved by direct
methods with SHELXS-86 or SHELXS-97 and refined with SHELXL-
97. The non-hydrogen atoms were refined anisotropically. Hydrogen
atoms were refined isotropically.
(7) For Brønsted acid catalyzed reactions, see: (a) Rueping, M.;
Nachtsheim, B. J. Synlett 2010, 119. (b) Holloway, C. A.; Muratore, M.
E.; Storer, R. L.; Dixon, D. J. Org. Lett. 2010, 12, 4720. (c) Yu, X.; Lu,
A.; Wang, Y.; Wu, G.; Song, H.; Zhou, Z.; Tang, C. Eur. J. Org. Chem.
2011, 892 and references cited therein.
1 (CCDC 805407): C10H15Cl8IrO5Sn3, Fw = 1047.17, monoclinic,
P21/a (No. 14), a = 9.5026(4) Å, b = 34.1358(13) Å, c = 9.7418(4) Å,
β = 116.9220(9)°, U = 2817.6(2) Å3, Z = 4, Dc = 2.468 mg/m3, μ =
8.112 mm−1, F(000) =1912, GOF = 1.299.
(8) For metal salt catalyzed reactions, see: (a) Pin, F.; Comesse, S.;
Garrigues, B.; Marchalin, S.; Daich, A. J. Org. Chem. 2007, 72, 1181.
(b) Othman, R. B.; Affani, R.; Tranchant, M. -J.; Antoniotti, S.; Dalla,
V.; Dunach, E. Angew. Chem., Int. Ed. 2010, 49, 776.
3r (CCDC 805408): C15H13NOS, Fw = 255.33, orthorhombic,
Pc21n (No. 33), a = 5.985(5) Å, b = 7.913(5) Å, c = 27.626(5) Å, U =
1308.3(14) Å3, Z = 4, Dc = 1.296 mg/m3, μ = 0.234 mm−1, F(000) =
536, GOF = 1.06.
(9) The Au(I) catalyst promotes an interesting N-acyliminium ion
cyclization cascade; see: Yang, T.; Campbell, L.; Dixon, D. J. J. Am.
Chem. Soc. 2007, 129, 12070.
(10) For transition metal−tin chemistry, see: (a) Petz, W. Chem. Rev.
1986, 86, 1019. (b) Holt, M. S.; Wilson, W. L.; Nelson, J. H. Chem.
Rev. 1989, 89, 11.
ASSOCIATED CONTENT
■
(11) The geometry of the central iridium atom is formally octahedral
with the Cp* ligand occupying three coordination positions and the
others occupied by two SnCl3 groups and one SnCl2(H2O)2 group.
Unlike the SnCl3− ligand, tin atom in SnCl2(H2O)2 is pentacoordinate
with distorted trigonal bipyramidal geometry; the two oxygen atoms
are in axial positions, and the IrSnCl2 unit in the equatorial plane. For
five-coordinate tin(II) chloride compounds, see: Balch, A. L.; Oram,
D. E. Organometallics 1988, 7, 155.
S
* Supporting Information
Spectra for all new compounds; NMR experiments; X-ray
crystallographic data for 1 and 3r (CIF). This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
(12) 119Sn NMR of complex 1 at room temperature shows only one
singlet, indicating that the stannyl ligands are equivalent on NMR time
scale. For instance, see: (a) Cokoja, M.; Gemel, C.; Steinke, T.;
*Tel: +91-674-2576021. Fax: +91-674-2306303. E-mail:
sujitroy.chem@gmail.com, sroychem@iitbbs.ac.in.
Schroder, F.; Fischer, R. A. Dalton Trans. 2005, 44. (b) Dilsky, S. J.
Organomet. Chem. 2007, 692, 2887.
(13) Moreno., B.; Sabo-Etienne., S.; Dahan., F.; Chandret., B. J.
̈
Notes
The authors declare no competing financial interest.
Organomet. Chem. 1995, 498, 139.
ACKNOWLEDGMENTS
■
(14) (a) Guzman, A.; Romero, M.; Muchowski, J. Can. J. Chem.
1990, 68, 791. (b) Akue-Gedu, R.; Ebrik, S. A. A.; Witczak-Legrand,
A.; Fasseur, D.; Ghammarti, S. E.; Couturier, D.; Decroix, B.; Othman,
M.; Debacker, M.; Rigo, B. Tetrahedron 2002, 58, 9239.
(15) A similar observation was found; see: Xie, Y.; Zhao, Y.; Qian, B.;
Yang, L.; Xia, C.; Huang, H. Angew. Chem., Int. Ed. 2011, 50, 5682.
(16) For an assessment of nucleophilicity of commonly used arenes
and heteroarenes, see: Pratihar, S.; Roy, S. J. Org. Chem. 2010, 75,
4957.
(17) For iridium (III) acting as a Lewis acid catalyst, see: Vaidya, T.;
Manbeck, G. F.; Chen, S.; Frontier, A. J.; Eisenberg., R. J. Am. Chem.
Soc. 2011, 133, 3300.
(18) Kobayashi, S.; Manabe, K. Pure Appl. Chem. 2000, 72, 1373.
(19) Selected lead references on indolizidine alkaloids: (a) Mertens,
A.; Zilch, H.; Konig, B.; Schafer, W.; Poll, T.; Kampe, W.; Seidel, H.;
Leser, U.; Leinert, H. J. Med. Chem. 1993, 36, 2526. (b) Comins, D. L.;
Higuchi, K. Beil. J. Org. Chem. 2007, 3, 42. (c) Michael, J. P. Nat. Prod.
Rep. 2007, 24, 191.
S.R. and A.K.M. thank DST and UGC for funds and
fellowships. S.R. thanks Prof. M. Bhattacharjee and Sanjay
Pratihar, and A.K.M. thanks Niladri Karan and Nirmal Das
Adhikari for useful discussions and help.
DEDICATION
■
†Dedicated to the fond memory of Prof. B. D. Gupta
(1949−2011), Chemistry Department, IIT Kanpur.
REFERENCES
■
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