One-pot synthesis of pyrrolo[1,2-a]indoles by chiral N-triflyl phosphoramide catalyzed Friedel-Crafts alkylation of 4,7-dihydroindole with β,γ-unsaturated α-keto esters

Article abstract of DOI:10.1002/cjoc.201200759

Chiral N-triflyl phosphoramide was found an efficient catalyst for the enantioselective Friedel-Crafts alkylation reaction of 4,7-dihydroindole with β,γ-unsaturated α-keto esters. In the presence of 5 mol% of the optimized catalyst, various pyrrolo[1,2-a]indoles were obtained in excellent enantioselectivity, moderate yields and up to 3:1 diastereoselectivity based on the one-pot synthesis including the Friedel-Crafts alkylation reaction and the subsequent p-benzoquinone oxidation.

Full text of DOI:10.1002/cjoc.201200759

FULL PAPER
DOI: 10.1002/cjoc.201200759
One-Pot Synthesis of Pyrrolo[1,2-a]indoles by Chiral N-Triflyl
Phosphoramide Catalyzed Friedel-Crafts Alkylation of
4,7-Dihydroindole with β,γ-Unsaturated α-Keto Esters
Zeng, Mi(曾蜜)
Zhang, Wei*(张玮)
You, Shuli*(游书力)
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, Shanghai 200032, China
Chiral N-triflyl phosphoramide was found an efficient catalyst for the enantioselective Friedel-Crafts alkylation
reaction of 4,7-dihydroindole with β,γ-unsaturated α-keto esters. In the presence of 5 mol% of the optimized catalyst,
various pyrrolo[1,2-a]indoles were obtained in excellent enantioselectivity, moderate yields and up to 3∶1 di-
astereoselectivity based on the one-pot synthesis including the Friedel-Crafts alkylation reaction and the subsequent
p-benzoquinone oxidation.
Keywords N-triflyl phosphoramide, Friedel-Crafts, enantioselective, 4,7-dihydroindole, one-pot synthesis
Introduction
O
Pyrrolo[1,2-a]indole represents a common structural
moiety widely existing in natural products or pharma-
ceuticals with interesting biological activities (Figure 1).
For example, the mitomycin family has been studied as
potent antitumor antibiotics.[1a,1b] Yuremamine has been
isolated with psychoactive property.[1c] JTT-010 is a
new structural class of protein kinase C-β-selective in-
hibitor.[1d] Flinderole C is a novel drug candidate which
shows impressive antimalarial activity against the
Plasmodium falciparum.[1e] Although several method-
ologies have been developed to synthesize the pyrrolo-
[1,2-a]indole derivatives,[2] the enantioselective variants
of these reactions are still rare.[3] Thus, the exploration
of efficient methodologies for the construction of these
optically pure polycyclic ring structures in a single op-
eration is highly desirable.
HN
O
O
OCONH2
OMe
O
NH
Ph
H2N
Me
N
NH
N
.
NH2 TFA
mitomycin C
NMe2
JTT-010
OH
NMe2
Me
Me
N
OH
OH
N
NMe2
Me
HN
HO
OH
Chiral phosphoric acids[4] have been demonstrated to
be efficient catalysts for the asymmetric Friedel-Crafts
alkylation reactions[5] of aromatic rings with imines,[6]
enamides,[7] α,β-unsaturated carbonyls,[8] nitroolefins,[9]
and various other electrophilic partners.[10] Meanwhile,
introduced by Yamamoto and co-workers, chiral
N-triflyl phosphoramides have been widely applied to
asymmetric catalytic reactions due to their even stronger
acidity than phosphoric acids.[11,12] We recently reported
a highly enantioselective Friedel-Crafts reaction of
4,7-dihydroindoles with β,γ-unsaturated α-keto esters
catalyzed by the chiral N-triflyl phosphoramide.[13,14,6m,8d]
As part of our ongoing efforts to develop highly
OH
yuremamine
flinderole C
Figure 1 Representative compounds containing pyrrolo[1,2-a]-
indole cores.
efficient chiral phosphoramide catalyzed asymmetric
Friedel-Crafts alkylation reactions,[15] we envisaged the
one-pot enantioselective synthesis of pyrrolo[1,2-a]-
indoles including the Friedel-Crafts alkylation reaction
of 4,7-dihydroindole with β,γ-unsaturated α-keto esters
catalyzed by chiral N-triflyl phosphoramide and the
subsequent p-benzoquinone oxidation (Scheme 1).
*
E-mail: zhangwei@sioc.ac.cn or slyou@sioc.ac.cn; Fax: 0086-021-54925087
Received July 24, 2012; accepted August 24, 2012; published online XXXX, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200759 or from the author.
Chin. J. Chem. 2012, XX, 1—9
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1

Zeng, Zhang & You
Table 1 Screening of chiral phosphoramides
FULL PAPER
Herein, we report the results from this study.
R1
Scheme 1
O
P
O
NHR2
Ph
Ph
*
O
O
N
CO2Et
*
NH
R1
O
HO CO2Et
Ph
CO2Et
O
(S)-1 (5 mol%)
NH
*
B-H
。
Ph
CO2Et toluene, 5 A MS
+
NH
-78 oC, 30 min
3a
2) [O]
1)*B-H
2
Ph
*
4
Ph
*
4
4
Entrya
1
R1, R2
NH
O
N
Yieldb/% eec/%
*
CO2Et
HO CO2Et
1
2
1a 2,4,6-(i-Pr)3-C6H2, Tf
73
29
44
46
73
57
58
58
74
52
54
59
31
87
－29
24
27
8
*
B-H
1b 4-NO2-C6H4, Tf
1c 9-anthryl, Tf
3
Results and Discussion
4
1d 9-phenanthryl, Tf
1e 1-naphthyl, Tf
We began our study by examining the reaction of
4,7-dihydroindole (2) with β,γ-unsaturated α-keto ester
3a. To our great delight, with 5 mol% of chiral phos-
phoramide (S)-1a as the catalyst, the reaction sequence
proceeded smoothly, and the desired pyrrolo-
[1,2-a]indole compound 5a was obtained in an overall
64% yield with 75% ee after an oxidation by p-benzo-
quinone (Eq. 1).
5
6
1f SiPh3, Tf
9
7
1g 4-biphenyl, Tf
8
8
1h 4-3',5'-(CF3)2-biphenyl, Tf
1i pyrenyl, Tf
16
8
9
10
11
12
13d
1j 3,5-(CH3)2-C6H3, Tf
1k 3,5-(CF3)2-C6H3, SO2C4F9
1l 2,4,6-(i-Pr)3-C6H2, SO2C8F17
1a 2,4,6-(i-Pr)3-C6H2, Tf
0
4
1) (S)-1a (5 mol%)
84
81
O
toluene, -78 oC
Ph
CO2Et
a
2) p-benzoquinone (4.0 equiv.)
N
Reaction conditions: 2.0 equiv. of 2, 5 mol% of (S)-1, 0.20
mol/L of 3a, 100 mg 5 Å MS, －78 ℃ in toluene. b Isolated
H
CH3CN, r.t.
2
3a
c
yields.
d Without 5 Å MS.
Determined by HPLC analysis (Chiralcel OD-H).
Ph
N
summarized in Table 2, the reaction proceeded
smoothly in various common solvents and toluene re-
mained to be the optimal one. Unfortunately, when the
reaction was conducted at higher temperature, the enan-
tioselectivity was decreased (Entries 5—7, Table 2).
The ratio of 4,7-dihydroindole (2) and β,γ-unsatu-
rated α-keto ester 3a has also been examined. The re-
sults are summarized in Table 3. Interestingly, increas-
ing the amount of dihydroindole 2 caused the decrease
of yield (Entries 1—5, Table 3), and utilization of 1.5
equivalents of dihydroindole 2 provided the best result
(82% yield, 86% ee; Entry 2, Table 3). Notably, when
β,γ-unsaturated α-keto ester 3a was added to the reac-
tion by syringe pump over 15 min, the desired product 4
was obtained in 95% yield with 91% ee (Entry 6, Table
3).
Under the optimized reaction conditions [1.5 equiv.
of 2, 0.20 mol/L 3 in toluene, 5 mol% of (S)-1a, －78
℃, 100 mg 5 Å MS, and 3 was added to the reaction by
syringe pump over 15 min], the one-pot synthesis of
pyrrolo[1,2-a]indoles including the Friedel-Crafts alky-
lation reaction and the subsequent p-benzoquinone oxi-
dation was explored. Simple work-up was performed to
(1)
HO CO2Et
5a
64% yield, dr = 3:1, 75% ee
To further optimize the reaction conditions, various
chiral phosphoramides were screened for the enantiose-
lective Friedel-Crafts alkylation reaction between
4,7-dihydroindole (2) and β,γ-unsaturated α-keto ester
3a. The reaction was performed in toluene at －78 ℃
with 100 mg 5 Å MS for 30 min. In the presence of 5
mol% of the chiral phosphoramides, all the reactions of
3a with 2 equivalents of 2 worked well to give the de-
sired product 4. The best result (73% yield, 87% ee) was
obtained using N-triflyl phosphoramide 1a bearing the
bulky 2,4,6-(i-Pr)3-C6H2 groups (Entry 1, Table 1).
Chiral phosphoramide 1l also catalyzed the Friedel-
Crafts alkylation well giving similar results (84% ee vs.
87% ee; Entry 12, Table 1). It was found that the mo-
lecular sieves were critical for obtaining reasonable
yield (Entry 13, Table 1).
With the optimal catalyst (S)-1a in hand, reaction
temperatures and solvents were then examined. As
2
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Chin. J. Chem. 2012, XX, 1—9

One-Pot Synthesis of Pyrrolo[1,2-a]indoles by Friedel-Crafts Alkylation
Table 2 Screening of reaction conditions
good substrates, and 5g—5h were achieved with satis-
factory enantioselectivity (Scheme 2). Meanwhile,
β,γ-unsaturated α-keto esters 3 bearing heteroaromatic
rings such as 1-furyl or 1-thienyl were also tested. As
shown in Scheme 3, 5j was obtained with excellent en-
antioselectivity (96% ee) and 5i was obtained with a
moderate enantioselectivity (77% ee). However, the
diastereoselectivity of this reaction sequence was only
poor to moderate, and anti-selective products were ob-
O
CO2Et
Ph
NH
O
(S)-1a (5 mol %)
。
NH
5 A MS
+
Ph
CO2Et
solvent, T oC
3a
2
4
Entrya
Solvent
THF
T/℃
－78
－78
－78
－78
－60
－40
－20
－20
Yieldb/%
ee/%
40
tained as major ones for most substrates[16]
.
To show the synthetic value of this enantioselective
reaction sequence, the reaction of 4,7-dihydroindole (2)
and β,γ-unsaturated α-keto ester 3e was performed on a
gram scale with 5 mol% of catalyst (Eq. 2). To our great
delight, the desired product 5e could be obtained with-
out notable loss of yield as well as enantioselectivity
following the same reaction conditions and work-up
procedure (48% yield, 75∶25 anti∶syn, 96% ee). Fur-
thermore, absolute configuration of anti-5e was deter-
mined to be (1S,3S) by an X-ray crystallographic analy-
sis (Figure 2).[16] Thus, the absolute configuration of 4,
the product for the first Friedel-Crafts alkylation reac-
tion, should be (S).
1
2
3
4
5
6
7
8
51
54
61
73
67
90
59
66
Et2O
43
CH2Cl2
toluene
toluene
toluene
toluene
o-xylene
58
87
74
60
47
51
a
Reaction conditions: 2.0 equiv. of 2, 5 mol% of (S)-1a, 0.20
mol/L of 3a, 100 mg 5 Å MS in solvent. b Isolated yields. c De-
termined by HPLC analysis (Chiralcel OD-H).
Table 3 Screening of ratio of the substrates
O
1) (S)-1a (5 mol%)
toluene, 5 A MS, -78 oC
O
CO2Et
。
NH
+
CO2Et
Ph
O
NH
2) p-benzoquinone (3.0 equiv.)
(S)-1a (5 mol%)
。
3e
(1.0 g)
Br
CH3CN, r.t.
+
Ph
CO2Et
NH
5 A MS
2
toluene, -78 oC
3a
Br
+
Br
2
1.0 equiv.
x equiv.
4
Entrya
x
Yieldb/%
eec/%
74
(2)
N
N
1
2
1.1
81
82
73
42
55
95
HO CO2Et
HO CO2Et
86
1.5
2
anti-5e
syn-5e
3
87
48% yield, anti/syn = 75/25, 96% ee
4
3
4
89
5
6d
89
1.5
91
a
Reaction conditions: x equiv. of 2, 5 mol% of (S)-1a, 0.20
mol/L of 3a, 100 mg 5 Å MS, －78 ℃ in toluene. b Isolated
yields. c Determined by HPLC analysis (Chiralcel OD-H). d 3a
was added to the reaction mixture over 15 min.
the reaction mixture after the completion of the first step,
and 3 equiv. of p-benzoquinone were then introduced to
the next step. As summarized in Scheme 2, in general,
all the tested β,γ-unsaturated α-keto ester 3 were trans-
formed to the corresponding pyrrolo[1,2-a]indoles 5 in
moderate to good yields (48%—87%) for two steps.
Either electron-withdrawing or electron-donating sub-
stituents on the phenyl moiety of β,γ-unsaturated α-keto
ester 3 were well tolerated to give the desired products 5
with satisfactory enantioselectivity (5a—5f, 5k, Scheme
2). β,γ-Unsaturated α-keto esters 3 bearing bulky sub-
stituents such as 1-naphthyl or 2-naphthyl were also
Figure 2 The X-ray structure of (1S,3S)-5e.
A plausible reaction pathway was proposed, as de-
picted in Scheme 3. Chiral N-triflyl phosphoramide ac-
tivates 3a through the hydrogen bonding with the car-
Chin. J. Chem. 2011, XX, 1—X
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3

Zeng, Zhang & You
FULL PAPER
Scheme 2 Substrate scope for the one-pot synthesis of pyrrolo[1,2-a]indoles
R
1) (S)-1a (5 mol%)
toluene, 5 A MS, -78 oC
O
。
CO2Et
+
N
N
H
2) p-benzoquinone (3.0 equiv.)
CH3CN, r.t.
R
HO CO2Et
2
3
5
OMe
Cl
O
O
N
N
N
N
HO CO2Et
HO CO2Et
HO CO2Et
HO CO2Et
5b
5a
64% yield
dr = 75/25
anti: 91% ee
syn: 93% ee
5c
5d
53% yield
dr = 55/45
anti: 94% ee
syn: 93% ee
60% yield
dr = 52/48
anti: 90% ee
syn: N.A.
52% yield
dr = 52/48
anti: 92% ee
syn: 92% ee
Br
Br
N
N
N
N
HO CO2Et
HO CO2Et
HO CO2Et
HO CO2Et
5e
5f
5g
5h
54% yield
dr = 75/25
anti: 96% ee
syn: 96% ee
51% yield
dr = 60/40
anti: 96% ee
syn: N.A.
54% yield
dr = 53/47
anti: 94% ee
syn: 92% ee
52% yield
dr = 54/46
anti: 93% ee
syn: 90% ee
NO2
O
S
N
N
N
HO CO2Et
HO CO2Et
HO CO2Et
5i
5j
5k
55% yield
48% yield
87% yield
dr = 46/54
anti: 77% ee
syn: 75% ee
dr = 46/54
anti: 96% ee
syn: 99% ee
dr = 60/40
anti: 91% ee
syn: 90% ee
Scheme 3 Plausible reaction pathway
Ph
*B H
O
N
+
N
H
Ph
CO2Et
HO CO2Et
2
3a
5a
[O]
H
O
O
Ph
Ph
H
O
Ph
NH
OH
CO2Et
N
H
N
N
H
CO2Et
O
4
HO CO2Et
6
7
O
bonyl group, enabling the first Friedel-Crafts alkylation
between 2 and 3a in highly enantioselective control.
The obtained product (S)-4, which is highly reactive,
can either further react with 2 in an intermolecular
4
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Chin. J. Chem. 2012, XX, 1—9

One-Pot Synthesis of Pyrrolo[1,2-a]indoles by Friedel-Crafts Alkylation
manner to provide 6 or react in an intramolecular man-
ner to provide 7. Further oxidation of 7 delivers the final
product 5a. It should be pointed out that compound 7
can be isolated to support our hypothesis.
tography [V(ethyl acetate)/V(petroleum ether)＝1/10—
1/5] to afford compound 5.
(1S)-Ethyl 3-hydroxy-1-phenyl-2,3-dihydro-1H-
pyrrolo[1,2-a]indole-3-carboxylate (5a)
Yellow
solid, 64% yield, dr＝75/25 (anti/syn). anti-5a: 91% ee;
1H NMR (300 MHz, CDCl3) δ: 1.16 (t, J＝7.2 Hz, 3H),
3.09—3.13 (m, 2H), 4.26—4.31 (m, 2H), 4.78 (s, H),
4.80 (t, J＝8.4 Hz, 1H), 6.10 (s, 1H), 7.10—7.20 (m,
3H), 7.26—7.37 (m, 5H), 7.52—7.55 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ: 13.9, 41.5, 51.8, 63.7, 86.3,
95.2, 109.4, 120.4, 121.0, 121.4, 127.1, 127.8, 128.7,
130.7, 134.0, 141.8, 147.0, 171.8; DEPT δ: CH/CH3
13.9, 41.5, 95.2, 109.4, 120.4, 121.0, 121.4, 127.1,
127.8, 128.7; CH2: 51.8, 63.7; C: 86.3, 130.7, 134.0,
141.8, 147.0, 171.8; IR (thin film) νmax: 3390, 3058,
2959, 2925, 2853, 1732, 1604, 1557, 1494, 1453, 1365,
1333, 1304, 1260, 1212, 1158, 1097, 1023, 971, 752,
Conclusions
In conclusion, chiral N-triflyl phosphoramide was
found an efficient catalyst for the enantioselective
Friedel-Crafts alkylation reaction of 4,7-dihydroindole
with β,γ-unsaturated α-keto esters. In the presence of 5
mol% of the optimized catalyst, various pyrrolo[1,2-a]-
indoles were obtained in excellent enantioselectivity,
moderate yields and up to 3∶1 diastereoselectivity
based on the one-pot synthesis including the Friedel-
Crafts alkylation reaction and the subsequent p-benzo-
quinone oxidation. A plausible mechanism was also
provided.
－
1
699, 667, 508 cm ; MS (EI, m/z, rel. intensity) 321
(M＋, 71), 248 (100); HRMS (EI) calcd for C20H19NO3
(M＋): 321.1365, found 321.1363; the enantiomeric ratio
was determined by Daicel Chiralcel OD-H (25 cm),
Hexanes/IPA＝60/40, 0.5 mL/min, λ＝254 nm, t(major)
＝15.09 min, t(minor)＝19.14 min; [α]2D0 ＋14.0 (c＝
Experimental
General methods
Unless stated otherwise, all reactions were carried
out in flame-dried glassware under a dry argon atmos-
phere. All solvents were purified and dried according to
standard methods prior to use. 1H and 13C NMR spectra
were recorded on a Varian instrument (300/400 MHz
and 75/100 MHz, respectively) and internally refer-
enced to tetramethylsilane signal or residual protio sol-
vent signals. Data for 1H NMR are recorded as follows:
chemical shift (δ), multiplicity (s＝singlet, d＝doublet, t
＝triplet, m＝multiplet or unresolved, br＝broad singlet,
coupling constant(s) in Hz, integration). Data for 13C
NMR are reported in terms of chemical shift (δ).
1
0.255, CH2Cl2). syn-5a: 93% ee. H NMR (300 MHz,
CDCl3) δ: 1.19 (t, J＝7.2 Hz, 3H), 2.75 (dd, J＝7.8,
13.8, 1H), 3.47 (dd, J＝9.0, 13.8 Hz, 1H), 4.18—4.35
(m, 2H), 4.64 (t, J＝8.4 Hz, 1H), 4.80 (s, 1H), 6.08 (s,
1H), 7.10—7.14 (m, 2H), 7.24—7.41 (m, 6H), 7.52—
7.54 (m, 1H); the enantiomeric ratio was determined by
Daicel Chiralcel OD-H (25 cm), Hexanes/IPA＝60/40,
0.5 mL/min, λ＝254 nm, t(minor)＝10.68 min, t(major)
＝12.68 min; [α]2D0 －47.9 (c＝0.195, CH2Cl2).
(1S)-Ethyl 3-hydroxy-1-(4-methoxyphenyl)-2,3-
dihydro-1H-pyrrolo[1,2-a]indole-3-carboxylate (5b)
Brown solid, 52% yield, dr＝52/48 (anti/syn). anti-5b:
1
General procedure for the one-pot synthesis (asym-
metric Friedel-Crafts reaction/oxidation)
92% ee; H NMR (300 MHz, CDCl3) δ: 1.20 (t, J＝6.9
Hz, 3H), 3.02—3.16 (m, 2H), 3.81 (s, 3H), 4.26—4.38
(m, 2H), 4.70 (s, 1H), 4.78 (t, J＝8.7 Hz, 1H), 6.09 (s,
1H), 6.88 (d, J＝8.4 Hz, 2H), 7.08—7.20 (m, 3H), 7.29
(d, J＝8.4 Hz, 2H), 7.52—7.55 (m, 1H); 13C NMR (100
MHz, CDCl3) δ: 14.0, 40.8, 52.0, 55.3, 63.7, 86.3, 95.0,
109.4, 114.1, 120.4, 121.0, 121.4, 128.8, 130.8, 133.8,
134.1, 147.5, 158.7, 171.8; IR (thin film) νmax: 3459,
3053, 2958, 2926, 2853, 1736, 1611, 1584, 1557, 1513,
1453, 1422, 1363, 1327, 1304, 1249, 1208, 1178, 1157,
In a dry Schlenk tube, 4,7-dihydroindole 2 (0.15
mmol), N-triflyl phosphoramide 1 (0.005 mmol) and
100 mg 5 Å MS were dissolved in toluene (0.5 mL) un-
der argon. The solution was stirred for 5 min at room
temperature and then for another 5 min at －78 ℃.
Subsequently, β,γ-unsaturated α-keto ester 3 was added
to the reaction by syringe pump over 15 min at －78
℃. After the reaction was complete (monitored by
TLC), saturated aqueous NaHCO3 (3 mL) was added to
quench the reaction. The mixture was resumed to room
temperature, extracted with CH2Cl2. The organic layer
was separated and dried over anhydrous Na2SO4. The
solvents were removed under reduced pressure and the
residue was dissolved in 2 mL CH3CN, then p-benzo-
quinone (32.4 mg, 0.30 mmol) was added to the vial.
After the reaction was complete (monitored by 1H
NMR), The reaction was diluted with 20 mL of CH2Cl2
and the organic layer was washed with 2 mol/L NaOH
(20 mL×2), brine (20 mL), and dried over anhydrous
Na2SO4. The organic layer was concentrated in vacuo.
The residue was purified by silica gel column chroma-
－
1
1102, 1033, 859, 833, 779, 751, 582, 528 cm ; MS (EI,
m/z, rel. intensity) 351 (M＋, 3), 84 (100); HRMS (EI)
calcd for C21H21NO4 (M＋): 351.1471, found 351.1466;
the enantiomeric ratio was determined by Daicel
Chiralpak AD-H (25 cm), Hexanes/IPA＝90/10, 1.0
mL/min, λ＝254 nm, t(minor)＝16.09 min, t(major)＝
21.44 min; [α]2D0 ＋38.2 (c＝0.085, CH2Cl2). syn-5b:
92% ee; 1H NMR (300 MHz, CDCl3) δ: 1.19 (t, J＝6.9
Hz, 3H), 2.71 (dd, J＝7.5, 13.5 Hz, 1H), 3.44 (dd, J＝
9.0, 13.5 Hz, 1H), 3.81 (s, 3H),4.16—4.38 (m, 2H), 4.60
(t, J＝8.4 Hz, 1H), 4.78 (s, 1H), 6.07 (s, 1H), 6.88 (d,
J＝8.7 Hz, 2H), 7.08—7.16 (m, 2H), 7.29—7.34 (m,
3H), 7.53 (d, J＝8.4 Hz, 1H); 13C NMR (100 MHz,
Chin. J. Chem. 2011, XX, 1—X
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5

Zeng, Zhang & You
FULL PAPER
CDCl3) δ: 14.0, 41.4, 50.8, 55.3, 63.5, 87.1, 94.8, 109.8,
114.1, 120.4, 120.9, 121.1, 128.8, 130.8, 134.1, 146.8,
158.6, 171.7; the enantiomeric ratio was determined by
Daicel Chiralpak AD-H (25 cm), Hexanes/IPA＝90/10,
1.0 mL/min, λ＝254 nm, t(major)＝26.36 min, t(minor)
＝37.42 min; [α]2D0 －12.5 (c＝0.210, CH2Cl2).
125.8, 126.3, 127.8, 129.1, 131.1, 131.3, 134.1, 137.7,
145.6, 171.6; the enantiomeric ratio was determined by
Daicel Chiralpak AD-H (25 cm), Hexanes/IPA＝90/10,
1.0 mL/min, λ＝254 nm, t(major)＝17.77 min, t(minor)
＝26.47 min; [α]2D0 －34.1 (c＝0.170, CH2Cl2).
(1S)-Ethyl 1-(4-bromophenyl)-3-hydroxy-2,3-di-
1-(Benzo[d][1,3]dioxol-5-yl)-3-hydroxy-2,3-dihy-
hydro-1H-pyrrolo[1,2-a]indole-3-carboxylate
(5e)
dro-1H-pyrrolo[1,2-a]indole-3-carboxylate
(5c)
Yellow solid, 54% yield, dr＝75/25 (anti/syn). anti-5e:
96% ee; H NMR (300 MHz, CDCl3) δ: 1.17 (t, J＝7.2
1
Brown solid, 60% yield, dr＝52/48 (anti/syn). anti-5c:
1
90% ee; H NMR (300 MHz, CDCl3) δ: 1.21 (t, J＝7.2
Hz, 3H), 2.99—3.16 (m, 2H), 4.23—4.35 (m, 2H), 4.75
(t, J＝8.1 Hz, 1H), 4.78 (s, 1H), 6.08 (s, 1H), 7.11—
7.23 (m, 5H), 7.45 (d, J＝8.1 Hz, 2H), 7.53—7.56 (m,
1H); 13C NMR (100 MHz, CDCl3) δ: 13.9, 40.9, 51.7,
63.7, 86.3, 95.2, 109.4, 120.5, 120.9, 121.0, 121.5,
129.5, 130.7, 131.7, 133.9, 140.9, 146.3, 171.6; IR (thin
film) νmax: 3401, 3054, 2982, 2925, 2850, 1732, 1614,
1557, 1488, 1452, 1366, 1302, 1260, 1215, 1159, 1099,
Hz, 3H), 3.01—3.16 (m, 2H), 4.28—4.39 (m, 2H), 4.70
(s, 1H), 4.76 (t, J＝8.4 Hz, 1H), 5.95 (s, 2H), 6.10 (s,
1H), 6.76—6.87 (m, 3H), 7.11—7.18 (m, 2H), 7.52—
7.56 (m, 2H); IR (thin film) νmax: 3467, 2924, 2854,
1736, 1610, 1504, 1488, 1452, 1377, 1305, 1250, 1207,
－
1
1157, 1102, 1039, 935, 894, 861, 811, 747, 601 cm ;
MS (EI, m/z, rel. intensity) 365 (M＋, 10), 57 (100);
HRMS (EI) calcd for C21H19NO5 (M＋): 365.1263, found
365.1267; the enantiomeric ratio was determined by
Daicel Chiralpak AD-H (25 cm), Hexanes/IPA＝90/10,
1.0 mL/min, λ＝254 nm, t(minor)＝22.38 min, t(major)
＝27.96 min; [α]2D0 ＋4.6 (c＝0.130, CH2Cl2). syn-5c:
1H NMR (300 MHz, CDCl3) δ: 1.19 (t, J＝6.9 Hz, 3H),
2.69 (dd, J＝7.5, 13.5 Hz, 1H), 3.44 (dd, J＝9.0, 13.5
Hz, 1H), 4.19—4.35 (m, 2H), 4.57 (t, J＝9.0 Hz, 1H),
4.78 (s, 1H), 5.94 (s, 2H), 6.09 (s, 1H), 6.75—6.79 (m,
1H), 6.85—6.86 (m, 1H), 6.87 (s, 1H), 7.11—7.16 (m,
2H), 7.29—7.34 (m, 1H), 7.52—7.57 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ: 14.0, 41.9, 50.7, 63.5, 87.1,
94.9, 101.0, 108.1, 108.2, 109.9, 120.5, 120.8, 120.9,
121.2, 130.8, 134.0, 136.0, 146.5, 146.7, 148.0, 171.6;
[α]2D0 －22.4 (c＝0.235, CH2Cl2).
－
1
1074, 1011, 928, 859, 826, 751, 667, 511 cm ; MS (EI,
m/z, rel. intensity) 399 (M＋, 56), 326 (100); HRMS (EI)
＋
calcd for C20H18BrNO3 (M ): 399.0470, found
399.0471; the enantiomeric ratio was determined by
Daicel Chiralpak AD-H (25 cm), Hexanes/IPA＝90/10,
1.0 mL/min, λ＝254 nm, t(minor)＝13.64 min, t(major)
＝15.85 min; [α]2D0 －11.4 (c＝1.0, CH2Cl2). syn-5e:
1
96% ee; H NMR (300 MHz, CDCl3) δ: 1.10 (t, J＝7.2
Hz, 3H), 2.63 (dd, J＝7.5, 13.8 Hz, 1H), 3.41 (dd, J＝
9.3, 13.8 Hz, 1H), 4.14—4.22 (m, 2H), 4.55 (t, J＝7.8
Hz, 1H), 5.01 (s, 1H), 6.04 (s, 1H), 7.07—7.12 (m, 2H),
7.19 (d, J＝8.1 Hz, 2H), 7.33—7.49 (m, 1H), 7.38 (d,
J＝8.1 Hz, 2H), 7.50 (d, J＝6.3 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ: 13.8, 41.4, 50.3, 63.4, 87.0, 94.9, 109.8,
120.4, 120.7, 120.8, 121.2, 129.4, 130.7, 131.6, 133.8,
141.0, 145.7, 171.2; the enantiomeric ratio was
determined by Daicel Chiralpak AD-H (25 cm),
Hexanes/IPA＝90/10, 1.0 mL/min, λ＝254 nm, t(major)
＝18.52 min, t(minor)＝25.78 min; [α]2D0 －21.1 (c＝
1.0, CH2Cl2).
(1S)-Ethyl 1-(4-chlorophenyl)-3-hydroxy-2,3-di-
hydro-1H-pyrrolo[1,2-a]indole-3-carboxylate
(5d)
Brown solid, 53% yield, dr＝55/45 (anti/syn). anti-5d:
1
94% ee; H NMR (300 MHz, CDCl3) δ: 1.19 (t, J＝7.2
Hz, 3H), 3.02—3.19 (m, 2H), 4.23—4.40 (m, 2H), 4.72
(s, 1H), 4.80 (t, J＝8.4 Hz, 1H), 6.10 (s, 1H), 7.11—
7.17 (m, 3H), 7.28—7.33 (m, 4H), 7.54—7.57 (m, 1H);
13C NMR (100 MHz, CDCl3) δ: 13.9, 41.0, 51.8, 63.8,
86.3, 95.3, 109.4, 120.6, 121.1, 121.6, 128.8, 129.2,
130.8, 132.9, 134.0, 140.4, 146.5, 171.7; IR (thin film)
(1S)-Ethyl 1-(3-bromophenyl)-3-hydroxy-2,3-di-
hydro-1H-pyrrolo[1,2-a]indole-3-carboxylate
(5f)
Yellow solid, 51% yield, dr＝60/40 (anti/syn). anti-5f:
96% ee; 1H NMR (300 MHz, CDCl3) δ: 1.20 (t, J＝7.2
Hz, 3H), 3.09—3.22 (m, 2H), 4.22—4.40 (m, 2H), 4.75
(s, 1H), 4.79 (t, J＝8.4 Hz, 1H), 6.13 (s, 1H), 7.13—
7.24 (m, 4H), 7.29—7.32 (m, 1H), 7.42 (d, J＝7.8 Hz,
1H), 7.51 (s, 1H), 7.55—7.58 (m, 1H); 13C NMR (100
MHz, CDCl3) δ: 13.9, 41.1, 51.6, 63.9, 86.3, 95.5, 109.5,
120.6, 121.1, 121.6, 122.8, 126.6, 130.2, 130.3, 130.8,
ν
max: 3478, 3053, 2959, 2924, 2853, 1736, 1612, 1557,
1492, 1452, 1410, 1391, 1362, 1334, 1302, 1257, 1208,
1157, 1143, 1091, 1015, 859, 830, 783, 747, 707, 514
－
＋
1
cm ; MS (EI, m/z, rel. intensity) 355 (M , 3), 57 (100);
HRMS (EI) calcd for C20H18ClNO3 (M＋): 355.0975,
found 355.0979; the enantiomeric ratio was determined
by Daicel Chiralpak AD-H (25 cm), Hexanes/IPA＝
90/10, 1.0 mL/min, λ＝254 nm, t(minor)＝15.22 min,
t(major)＝32.82 min; [α]2D0 ＝＋7.3 (c＝0.335, CH2Cl2).
syn-5d: 93% ee; 1H NMR (300 MHz, CDCl3) δ: 1.19 (t,
J＝7.2 Hz, 3H), 2.70 (dd, J＝7.2, 13.8 Hz, 1H), 3.48
(dd, J＝9.0, 13.8 Hz, 1H), 4.19—4.35 (m, 2H), 4.62 (t,
J＝8.1 Hz, 1H), 4.80 (s, 1H), 6.07 (s, 1H), 7.09—7.19
(m, 3H), 7.32—7.38 (m, 4H), 7.49—7.59 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ: 14.1, 38.6, 49.7, 63.6, 87.2,
95.6, 109.9, 120.6, 120.9, 121.3, 123.1, 124.8, 125.7,
130.9, 134.0, 144.4, 146.1, 171.7; IR (thin film) νmax
:
3370, 2924, 2853, 1732, 1596, 1568, 1474, 1453, 1426,
1367, 1259, 1216, 1160, 1099, 1073, 1024, 997, 927,
－
1
860, 758, 692, 668 cm ; MS (EI, m/z, rel. intensity)
399 (M ＋ , 37), 57 (100); HRMS (EI) calcd for
C20H18BrNO3 (M＋): 399.0470, found 399.0475; the
enantiomeric ratio was determined by Daicel Chiralpak
AD-H (25 cm), Hexanes/IPA＝90/10, 1.0 mL/min, λ＝
254 nm, t(minor)＝12.56 min, t(major)＝13.91 min;
[α]2D0 －17.5 (c＝0.765, CH2Cl2). syn-5f: 1H NMR (400
MHz, CDCl3) δ: 1.19 (t, J＝7.2 Hz, 3H), 2.72 (dd, J＝
6
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, XX, 1—9

One-Pot Synthesis of Pyrrolo[1,2-a]indoles by Friedel-Crafts Alkylation
1
7.2, 13.8 Hz, 1H), 3.48 (dd, J＝8.7, 13.8, 1H), 4.19—
4.35 (m, 2H), 4.60 (t, J＝8.7 Hz, 1H), 4.80 (s, 1H), 6.10
(s, 1H), 7.12—7.17 (m, 2H), 7.21 (t, J＝6.0 Hz, 1H),
7.40—7.42 (m, 1H), 7.53—7.57 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ: 14.0, 41.7, 50.4, 63.6, 87.0, 95.2,
109.9, 120.6, 121.0, 121.4, 122.7, 126.4, 130.2, 130.3,
130.8, 130.9, 134.0, 144.4, 145.5, 171.5.
[α]2D0 －79.9 (c＝0.195, CH2Cl2). syn-5h: 90% ee; H
NMR (300 MHz, CDCl3) δ: 1.24 (t, J＝7.2 Hz, 3H),
2.84 (dd, J＝7.5, 13.8 Hz, 1H), 3.70 (dd, J＝9.3, 13.8
Hz, 1H), 4.23—4.44 (m, 2H), 4.75 (s, 1H), 5.42 (t, J＝
8.4 Hz, 1H), 6.20 (s, 1H), 7.15—7.17 (m, 2H), 7.35—
7.38 (m, 1H), 7.40—7.44 (m, 1H), 7.52—7.62 (m, 4H),
7.81 (d, J＝8.4 Hz, 1H), 7.93 (d, J＝8.4 Hz, 1H), 8.10
(d, J＝7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ:
14.1, 41.5, 50.5, 63.6, 87.1, 95.1, 109.9, 120.6, 121.0,
121.4, 125.8, 128.9, 129.1, 130.8, 132.9, 134.0, 140.7,
145.9, 171.5; the enantiomeric ratio was determined by
Daicel Chiralpak AD-H (25 cm), Hexanes/IPA＝90/10,
1.0 mL/min, λ＝254 nm, t(minor)＝19.47 min, t(major)
＝21.53 min; [α]2D0 －19.8 (c＝0.165, CH2Cl2).
(1R)-Ethyl 1-(furan-2-yl)-3-hydroxy-2,3-dihydro-
1H-pyrrolo[1,2-a]indole-3-carboxylate (5i) Brown
solid, 55% yield, dr＝46/54 ( anti/syn ). anti-5i: 75% ee;
1H NMR (300 MHz, CDCl3) δ: 1.19 (t, J＝7.2 Hz, 3H),
3.09 (dd, J＝8.4, 13.8 Hz, 1H), 3.28 (dd, J＝7.8, 13.2
Hz, 1H), 4.24—4.37 (m, 2H), 4.73 (s, 1H), 4.91 (t, J＝
8.4 Hz, 1H), 6.23—6.24 (m, 1H), 6.28 (s, 1H), 6.34—
6.35 (m, 1H), 7.10—7.20 (m, 2H), 7.31—7.33 (m, 1H),
7.39 (m, 1H), 7.55—7.58 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ: 13.9, 35.1, 47.8, 63.7, 86.3, 95.3, 105.9,
109.5, 110.3, 120.5, 121.1, 121.6, 130.8, 133.9, 142.0,
143.8, 154.0, 171.7; IR (thin film) νmax: 3478, 3119,
3053, 2925, 2854, 1736, 1613, 1560, 1506, 1453, 1355,
1335, 1304, 1256, 1208, 1156, 1105, 1012, 927, 896,
(1S)-Ethyl 3-hydroxy-1-(naphthalen-2-yl)-2,3-di-
hydro-1H-pyrrolo[1,2-a]indole-3-carboxylate
(5g)
Brown solid, 54% solid, dr＝53/47 (anti/syn ). anti-5g:
1
94% ee; H NMR (300 MHz, CDCl3) δ: 1.19 (t, J＝7.2
Hz, 3H), 3.22 (d, J＝8.7 Hz, 1H), 4.26—4.39 (m, 2H),
4.76 (s, 1H), 5.00 (t, J＝8.7 Hz, 1H), 6.14 (s, 1H), 7.13
—7.23 (m, 3H), 7.43—7.58 (m, 4H), 7.79—7.86 (m,
4H); 13C NMR (100 MHz, CDCl3) δ: 14.0, 41.7, 51.8,
63.8, 86.4, 95.4, 109.4, 120.5, 121.1, 121.5, 125.8,
125.9, 126.3, 126.4, 127.6, 127.7, 128.6, 132.1, 132.6,
133.4, 134.1, 139.1, 147.0, 171.9; IR (thin film) νmax
:
3479, 3053, 2925, 2854, 1756, 1634, 1601, 1558, 1508,
1453, 1369, 1350, 1334, 1303, 1257, 1206, 1157, 1143,
1127, 1104, 1021, 894, 858, 820, 749, 667, 606, 478
－
＋
1
cm ; MS (EI, m/z, rel. intensity) 371 (M , 86), 298
(100); HRMS (EI) calcd for C24H21NO3 (M＋): 371.1521,
found 371.1519; the enantiomeric ratio was determined
by Daicel Chiralpak AD-H (25 cm), Hexanes/IPA＝
90/10, 1.0 mL/min, λ＝254 nm, t(minor)＝13.53 min,
t(major)＝17.01 min; [α]2D0 ＋34.8 (c＝0.290, CH2Cl2).
syn-5g: 92% ee; 1H NMR (300 MHz, CDCl3) δ: 1.22 (t,
J＝7.2 Hz, 3H), 2.85 (dd, J＝7.5, 13.8 Hz, 1H), 3.54
(dd, J＝8.7, 13.8 Hz, 1H), 4.21—4.38 (m, 2H), 4.82 (t,
J＝8.1 Hz, 1H), 4.84 (s, 1H), 6.11 (s, 1H), 7.10—7.18
(m, 2H), 7.37 (d, J＝7.2 Hz, 1H), 7.46—7.56 (m, 4H),
7.79 —7.86 (m, 4H); the enantiomeric ratio was
determined by Daicel Chiralpak AD-H (25 cm),
Hexanes/IPA＝90/10, 1.0 mL/min, λ＝254 nm, t(major)
＝27.26 min, t(minor)＝29.68 min; [α]2D0 ＋7.6 (c＝
0.155, CH2Cl2).
－
1
884, 860, 783, 742, 599 cm ; LRMS-ESI m/z: 312.0
[M ＋H], 334.0 [M ＋Na]; HRMS (MALDI/DHB):
Calcd for C18H18NO4 [M ＋ H]: 312.1230, found
312.1239; the enantiomeric ratio was determined by
Daicel Chiralpak AD-H (25 cm), Hexanes/IPA＝90/10,
1.0 mL/min, λ＝254 nm, t(minor)＝14.31 min, t(major)
＝24.78 min; [α]2D0 －5.2 (c＝0.345, CH2Cl2). syn-5i:
1
75% ee; H NMR (300 MHz, CDCl3) δ: 1.15 (t, J＝7.2
Hz, 3H), 2.90 (dd, J＝7.5, 13.5 Hz, 1H), 3.42 (dd, J＝
8.7, 13.5 Hz, 1H), 4.15—4.26 (m, 2H), 4.73 (s, 1H),
4.74 (t, J＝8.7 Hz, 1H), 6.24 (s, 1H), 6.25—6.28 (m,
1H), 6.33—6.35 (m, 1H), 7.08—7.15 (m, 2H), 7.31—
7.33 (m, 1H), 7.38—7.39 (m, 1H), 7.54—7.58 (m, 1H);
13C NMR (100 MHz, CDCl3) δ: 14.0, 35.4, 47.1, 63.5,
87.0, 95.2, 105.8, 110.0, 110.4, 120.5, 121.0, 121.4,
130.9, 133.8, 142.0, 143.1, 154.1, 171.3; the
enantiomeric ratio was determined by Daicel Chiralpak
AD-H (25 cm), Hexanes/IPA＝90/10, 1.0 mL/min, λ＝
254 nm, t(major)＝14.25 min, t(minor)＝21.20 min;
[α]2D0 －80.1 (c＝0.250, CH2Cl2).
(1S)-Ethyl 3-hydroxy-1-(naphthalen-1-yl)-2,3-di-
hydro-1H-pyrrolo[1,2-a]indole-3-carboxylate
(5h)
Brown solid, 52% yield, dr＝54/46 (anti/syn). anti-5h:
93% ee; 1H NMR (300 MHz, CDCl3) δ: 1.12 (t, J＝6.9
Hz, 3H), 3.19 (dd, J＝7.8, 13.5 Hz, 1H), 3.38 (dd, J＝
9.0, 13.8 Hz, 1H), 4.22—4.30 (m, 2H), 4.81 (s, 1H),
5.56 (t, J＝8.4 Hz, 1H), 6.21 (s, 1H), 7.13—7.20 (m,
3H), 7.42 (t, J＝8.1 Hz, 1H), 7.52—7.62 (m, 4H), 7.82
(d, J＝8.1 Hz, 1H), 7.91—7.94 (m, 1H), 8.08—8.11 (m,
1H); 13C NMR (100 MHz, CDCl3) δ: 13.9, 38.5, 50.7,
63.7, 86.5, 95.8, 109.5, 120.5, 121.0, 121.4, 123.4,
125.0, 125.6, 125.7, 126.2, 127.8, 129.0, 130.9, 131.4,
(1R)-Ethyl
3-hydroxy-1-(thiophen-2-yl)-2,3-di-
(5j)
134.0, 134.1, 137.3, 146.1, 172.0; IR (thin film) νmax
:
hydro-1H-pyrrolo[1,2-a]indole-3-carboxylate
3478, 3050, 2924, 2853, 1733, 1598, 1510, 1453, 1397,
1363, 1334, 1305, 1259, 1208, 1157, 1144, 1126, 1104,
Brown solid, 48% yield, dr＝46/54 (anti/syn). anti-5j:
96% ee; H NMR (300 MHz, CDCl3) δ: 1.16 (t, J＝7.2
1
－
1
1080, 1012, 860, 801, 779, 748 cm ; MS (EI, m/z, rel.
intensity) 371 (M＋, 86), 298 (100); HRMS (EI) calcd
for C24H21NO3 (M＋): 371.1521, found 371.1526; the
enantiomeric ratio was determined by Daicel Chiralpak
AD-H (25 cm), Hexanes/IPA＝90/10, 1.0 mL/min, λ＝
254 nm, t(major)＝16.48 min, t(minor)＝19.00 min;
Hz, 3H), 3.20 (d, J＝8.4 Hz, 2H), 4.26—4.36 (m, 2H),
4.73 (s, 1H), 5.13 (t, J＝7.8 Hz, 1H), 6.28 (s, 1H), 6.98
—7.00 (m, 1H), 7.06—7.07 (m, 1H), 7.12—7.20 (m,
3H), 7.24 (d, J＝8.4 Hz, 1H), 7.56—7.59 (m, 1H); 13C
NMR (75 MHz, CDCl3) δ: 14.1, 36.7, 51.9, 63.8, 86.2,
95.6, 109.4, 120.5, 121.2, 121.7, 124.3, 124.9, 126.8,
Chin. J. Chem. 2011, XX, 1—X
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
7

Zeng, Zhang & You
FULL PAPER
130.8, 133.8, 144.8, 146.0, 171.7; IR (thin film) νmax
:
Hz, 1H), 5.81 (dt, J＝2.1, 15.9 Hz, 2H), 7.23—7.34 (m,
5H), 7.54 (s, 1H); 13C NMR (75 MHz, CDCl3) δ: 13.9,
23.8, 24.8, 39.0, 45.5, 62.6, 104.2, 113.6, 122.7, 123.7,
125.7, 127.0, 127.6, 127.9, 128.5, 128.7, 132.2, 142.2,
160.6, 193.1; IR (thin film) νmax: 3412, 3060, 3027,
2982, 2890, 2856, 2826, 1728, 1656, 1604, 1492, 1454,
1369, 1342, 1260, 1150, 1083, 1069, 1038, 967, 952,
857, 750, 702, 667 cm ; LRMS-ESI (m/z): 324.2 [M＋
H]; HRMS (MALDI/DHB) calcd for C20H22NO3 [M＋
H]: 324.1594, found 324.1603.
3362, 2923, 2853, 1735, 1655, 1616, 1522, 1456, 1376,
1304, 1258, 1215, 1158, 1097, 1021, 761, 699, 668
－
＋
1
cm ; MS (EI, m/z, rel. intensity) 327 (M , 12), 84
(100); HRMS (EI) calcd for C18H17NO3S (M ＋ ):
327.0929, found 327.0926; [α]2D0 －11.9 (c＝0.375,
CH2Cl2). syn-5j: 99% ee; 1H NMR (300 MHz, CDCl3) δ:
1.20 (t, J＝7.2 Hz, 3H), 2.86 (dd, J＝8.1, 13.5 Hz, 1H),
3.49 (dd, J＝8.4, 13.5 Hz, 1H), 4.18—4.35 (m, 2H),
4.76 (s, 1H), 4.95 (t, J＝8.4 Hz, 1H), 6.25 (s, 1H), 6.97
—7.00 (m, 1H), 7.07—7.15 (m, 3H), 7.23 (d, J＝8.4 Hz,
1H), 7.34 (d, J＝8.4 Hz, 1H), 7.55—7.57 (m, 1H); 13C
NMR (75 MHz, CDCl3) δ: 14.0, 37.1, 50.7, 63.6, 86.9,
95.4, 109.9, 120.5, 121.1, 121.4, 124.3, 124.8, 126.9,
130.8, 133.8, 144.8, 145.2, 171.4; the enantiomeric ratio
was determined by Daicel Chiralpak AD-H (25 cm),
Hexanes/IPA＝90/10, 1.0 mL/min, λ＝254 nm, t(major)
＝20.33 min, t(minor)＝30.64 min; [α]2D0 －26.7 (c＝
0.32, CH2Cl2).
－
1
Ethyl
3-hydroxy-1-phenyl-2,3,5,8-tetrahydro-
1H-pyrrolo[1,2-a]indole-3-carboxylate (7) 1H NMR
(300 MHz, CDCl3) δ: 1.27 (t, J＝7.5 Hz, 3H), 2.88—
3.05 (m, 3H), 3.15—3.23 (m, 3H), 4.24—4.40 (m, 2H),
4.46 (s, 1H), 4.64 (t, J＝8.1 Hz, 1H), 5.61 (s, 1H), 5.76
—5.88 (m, 2H), 7.25—7.38 (m, 5H); 13C NMR (75
MHz, CDCl3) δ: 14.0, 22.7, 25.4, 41.3, 52.1, 63.6, 86.5,
99.4, 118.7, 120.6, 122.1, 125.6, 126.8, 127.5, 127.6,
128.5, 138.9, 142.8, 172.2; IR (thin film) νmax: 3479,
3061, 3027, 2960, 2919, 2850, 1732, 1652, 1603, 1558,
1520, 1496, 1454, 1430, 1368, 1304, 1261, 1188, 1161,
1142, 1095, 1057, 1022, 951, 861, 799, 749, 699, 667,
(1S)-Ethyl
3-hydroxy-1-(3-nitrophenyl)-2,3-di-
(5k)
hydro-1H-pyrrolo[1,2-a]indole-3-carboxylate
Brown solid, 87% yield, dr＝60/40 (anti/syn). anti-5k:
91% ee; 1H NMR (300 MHz, CDCl3) δ: 1.18 (t, J＝7.5
Hz, 3H), 3.12 (dd, J＝7.8, 13.8 Hz, 1H), 3.26 (dd, J＝
9.0, 13.8 Hz, 1H), 4.25—4.41 (m, 2H), 4.82 (s, 1H),
4.94 (t, J＝8.1 Hz, 1H), 6.12 (s, 1H), 7.09—7.24 (m,
3H), 7.50—7.58 (m, 2H), 7.72 (d, J＝7.8 Hz, 1H), 8.16
(d, J＝8.1 Hz, 1H), 8.25 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ: 13.9, 41.0, 51.5, 63.9, 86.3, 95.6, 109.5,
120.7, 121.2, 121.8, 122.2, 122.7, 129.6, 130.8, 133.9,
－
＋
1
632 cm ; MS (EI, m/z, rel. intensity) 324 (M , 22), 208
(100); LRMS-ESI m/z: 312.0 [M＋H], 334.0 [M＋Na];
HRMS (MALDI/DHB) calcd for C20H22NO3 [M＋H]:
324.1594, found 324.1608.
Acknowledgement
We thank the National Basic Research Program of
China (973 Program 2009CB825300), the National
Natural Science Foundation of China (Nos. 21025209,
21102160, 21121062), and the Chinese Academy of
Sciences for generous financial support.
134.1, 144.3, 145.4, 148.5, 171.4; IR (thin film) νmax
:
3478, 3055, 2926, 2854, 1736, 1614, 1582, 1530, 1477,
1452, 1350, 1305, 1250, 1210, 1159, 1100, 1024, 927,
－
1
808, 750, 684 cm ; LRMS-ESI m/z: 367.0 [M＋H],
389.0 [M ＋Na]; HRMS (MALDI/DHB): calcd for
C20H19N2O5 [M＋H]: 367.1288, found 367.1299; the
enantiomeric ratio was determined by Daicel Chiralpak
AD-H (25 cm), Hexanes/IPA＝90/10, 1.0 mL/min, λ＝
254 nm, t(minor)＝20.88 min, t(major)＝32.16 min;
[α]2D0 －16.1 (c＝1.0, CHCl3). syn-5k: 90% ee; 1H NMR
(400 MHz, CDCl3) δ: 1.21 (t, J＝7.2 Hz, 3H), 2.74 (dd,
J＝7.2, 14.0 Hz, 1H), 3.56 (dd, J＝8.8, 13.6 Hz, 1H),
4.23—4.37 (m, 2H), 4.76 (t, J＝7.8 Hz, 1H), 4.87 (s,
1H), 6.12 (s, 1H), 7.14—7.19 (m, 2H), 7.33 (d, J＝8.0
Hz, 1H), 7.50—7.56 (m, 2H), 7.75 (t, J＝7.6 Hz, 1H),
8.13—8.16 (m, 1H), 8.29 (t, J＝2.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ: 14.0, 41.6, 50.2, 63.8, 87.0, 95.5,
109.9, 120.8, 121.1, 121.7, 122.3, 122.9, 129.8, 130.9,
133.9, 144.3, 144.8, 148.4, 171.3; the enantiomeric ratio
was determined by Daicel Chiralpak AD-H (25 cm),
Hexanes/IPA＝90/10, 1.0 mL/min, λ＝254 nm, t(major)
＝25.03 min, t(minor)＝31.22 min; [α]2D0 －10.7 (c＝
0.37, CHCl3).
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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[16] See the Supporting Information for detailed information.
(Zhao, X.)
Chin. J. Chem. 2011, XX, 1—X
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
9