SPINOL-derived phosphoric acids: Synthesis and application in enantioselective Friedel-Crafts reaction of indoles with imines

Article abstract of DOI:10.1021/jo101640z

A new class of chiral phosphoric acids with spirobiindane as scaffold were conveniently synthesized from (S)-1,1′-spirobiindane-7,7′-diol ((S)-SPINOL) and employed to catalyze the asymmetric Friedel-Crafts reaction of indoles with imines to afford 3-indol

Full text of DOI:10.1021/jo101640z

pubs.acs.org/joc
reactions,4,5 the chiral phosphoric acids6 were demonstrated to
SPINOL-Derived Phosphoric Acids: Synthesis and
Application in Enantioselective Friedel-Crafts
Reaction of Indoles with Imines
be efficient.7 These phosphoric acid catalysts possess a biaryl
backbone. Typical examples are BINOL and H8-BINOL-
derived phosphoric acids 1(Figure 1). With regard to the signifi-
cant works on the synthesis of enantiopure 1,10-spirobiindane-7,
70-diol8 (SPINOL, 3) and catalytic applications of its deriva-
tives,9 we synthesized SPINOL-derived phosphoric acids 2 and
investigated their application in enantioselective Friedel-Crafts
reaction of indoles with imines, which furnished 3-indolyl metha-
namines. We herein report the results of this effort.
Fangxi Xu,† Dan Huang,† Chao Han,† Wei Shen,†
Xufeng Lin,*,† and Yanguang Wang*,†,‡
†Department of Chemistry, Zhejiang University, Hangzhou
310027, P. R. China, and ‡State Key Laboratory of Applied
Organic Chemistry, Lanzhou University, Lanzhou 730000,
China
lxfok@zju.edu.cn; orgwyg@zju.edu.cn
Received August 19, 2010
FIGURE 1. Chiral phosphoric acids.
As shown in Scheme 1, the SPINOL-derived phosphoric
acids 2 were synthesized from (S)-SPINOL 3. Initially, (S)-
SPINOL was routinely protected with the MOM group to
afford 4 in 94% yield. Compound 4 underwent lithiation and
(4) For selected examples of chiral metal-complex catalysis, see: (a)
Johannsen, M. Chem. Commun. 1999, 2233. (b) Gathergood, N.; Zhuang,
W.; Jørgensen, K. A. J. Am. Chem. Soc. 2000, 122, 12517. (c) Zhou, J.; Tang,
Y. J. Am. Chem. Soc. 2002, 124, 9030. (d) Evans, D. A.; Scheidt, K. A.;
Fandrick, K. R.; Lam, H. W.; Wu, J. J. Am. Chem. Soc. 2003, 125, 10780. (e)
Evans, D. A.; Fandrick, K. R.; Song, H.-J. J. Am. Chem. Soc. 2005, 127,
8942. (f) Jia, Y. X.; Xie, J. H.; Duan, H. F.; Wang, L. X.; Zhou, Q. L. Org.
A new class of chiral phosphoric acids with spirobiindane
as scaffold were conveniently synthesized from (S)-1,10-
spirobiindane-7,70-diol ((S)-SPINOL) and employed to
catalyze the asymmetric Friedel-Crafts reaction of in-
doles with imines to afford 3-indolyl methanamines. High
yields (68-97%) and excellent enantioselectivities (up to
99% ee) were obtained.
ꢀ
Lett. 2006, 8, 1621. (g) Blay, G.; Fernandez, I.; Pedro, J. R.; Vila, C. Org.
Lett. 2007, 9, 2601. (h) Liu, Z.; Shi, M. Tetrahedron: Asymmetry 2009, 20,
119. (i) Wang, W.; Liu, X.; Cao, W; Wang, J.; Lin, L.; Feng, X. Chem.;Eur.
J. 2010, 16, 1664.
(5) For selected examples of chiral organocatalysis, see: (a) Austin, J. F.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2002, 124, 1172. (b) Wang, Y.-Q.;
Song, J.; Hong, R.; Li, H.; Deng, L. J. Am. Chem. Soc. 2006, 128, 8156. (c)
Qian, Y.; Ma, G.; Lv, A.; Zhu, H. L.; Zhao, J.; Rawal, V. H. Chem. Commun.
2010, 46, 3004.
(6) Chiral phosphoric acids were first introduced as organocatalyst by
Terada and Akiyama; see: (a) Akiyama, T.; Itoh, J.; Yokota, K.; Fuchibe, K.
Angew. Chem., Int. Ed. 2004, 43, 1566. (b) Uraguchi, D.; Terada, M. J. Am.
Chem. Soc. 2004, 126, 5356. (c) Uraguchi, D.; Sorimachi, K.; Terada, M.
J. Am. Chem. Soc. 2004, 126, 11804.
(7) For selected examples of asymmetric Friedel-Crafts reactions using
chiral phosphoric acids as catalyst, see: (a) Terada, M.; Sorimachi, K. J. Am.
Chem. Soc. 2007, 129, 292. (b) Kang, Q.; Zhao, Z.-A.; You, S.-L. J. Am.
Chem. Soc. 2007, 129, 1484. (c) Rowland, G. B.; Rowland, E. B.; Liang, Y.;
Perman, J. A.; Antilla, J. C. Org. Lett. 2007, 9, 2609. (d) Terada, M.;
Yokoyama, S.; Sorimachi, K.; Uraguchi, D. Adv. Synth. Catal. 2007, 349,
1863. (e) Jia, Y. X.; Zhong, J.; Zhu, S. F.; Zhang, C. M.; Zhou, Q. L. Angew.
Chem., Int. Ed. 2007, 46, 5565. (f) Itoh, J.; Fuchibe, K.; Akiyama, T. Angew.
Chem., Int. Ed. 2008, 47, 4016. (g) Sun, F. L.; Zheng, X. J.; Gu, Q.; He, Q. L.;
You, S. L. Eur. J. Org. Chem. 2010, 47.
The catalytic asymmetric Friedel-Crafts (F-C) reaction is a
powerful strategy for the construction of carbon-carbon bond
in organic synthesis, providing direct approach to the enantio-
merically enriched arene derivatives.1 Since indoles exhibited
significant nucleophilic reactivity and extensively biological
activities,2 their asymmetric Friedel-Crafts reactions are of
great value.3 Among the published asymmetric Friedel-Crafts
(1) For reviews on asymmetric Friedel-Crafts reaction, see: (a) Bandini,
M.; Melloni, A.; Tommasi, S.; Umani-Ronchi, A. Synlett 2005, 1199. (b)
Sheng, Y.-F.; Zhang, A. J.; Zheng, X.-J.; You, S.-L. Chin. J. Org. Chem.
2008, 28, 605. (c) Poulsen, T.; Jørgensen, K. A. Chem. Rev. 2008, 108, 2903.
(d) You, S.-L.; Cai, Q; Zeng, M. Chem. Soc. Rev. 2009, 38, 2190.
(8) (a) Birman, V. B.; Rheingold, A. L.; Lam, K.-C. Tetrahedron:
Asymmetry 1999, 10, 125. (b) Zhang, J.-H.; Liao, J.; Cui, X.; Yu, K.-B.;
Deng, J.-G.; Zhu, S.-F.; Wang, L.-X.; Zhou, Q.-L.; Chung, L.-W.; Ye, T.
Tetrahedron: Asymmtry 2002, 13, 1363.
(2) (a) Cacchi, S.; Fabrizi, G. Chem. Rev. 2005, 105, 2873. (b) Joule, J. A.;
Mills, K. Heterocyclic Chemistry, 4th ed.; Blackwell Science: Oxford, 2000.
(c) Faulkner, D. J. Nat. Prod. Rep. 2002, 19, 1. (d) Somei, M.; Yamada, F.
Nat. Prod. Rep. 2004, 21, 278. (e) Agarwal, S.; Caemmerer, S.; Filali, S.;
(9) For selected examples, see: (a) Hu, A. G.; Fu, Y.; Xie, J. H.; Zhou, H.;
Wang, L. X.; Zhou, Q. L. Angew. Chem., Int. Ed. 2002, 41, 2348. (b) Xie,
J. H.; Wang, L. X.; Fu, Y.; Zhu, S. F.; Fan, B. M.; Duan, H. F.; Zhou, Q. L.
J. Am. Chem. Soc. 2003, 125, 4404. (c) Zhu, S. F.; Xie, J. B.; Zhang, Y. Z.; Li,
S.; Zhou, Q. L. J. Am. Chem. Soc. 2006, 128, 12886. (d) Yang, Y.; Zhu, S. F.;
Duan, H. F.; Zhou, C. Y.; Wang, L. X.; Zhou, Q. L. J. Am. Chem. Soc. 2007,
129, 2248. (e) Xie, J. H.; Zhou, Q. L. Acc. Chem. Res. 2008, 41, 581. (f) Xie,
J. B.; Xie, J. H.; Liu, X. Y.; Kong, W. L.; Li, S.; Zhou, Q. L. J. Am. Chem.
Soc. 2010, 132, 4538. (g) Zhu, S. F.; Cai, Y.; Mao, H. X.; Xie, J. H.; Zhou,
Q. L. Nat. Chem. 2010, 2, 546.
€
Froehner, W.; Knoell, J.; Krahl, M. P.; Reddy, K. R.; Knolker, H.-J. Curr.
Org. Chem. 2005, 9, 1601. (f) O’Connor, S. E.; Maresh, J. J. Nat. Prod. Rep.
2006, 23, 532. (g) Humphrey, G. R.; Kuethe, J. T. Chem. Rev. 2006, 106, 2875.
(3) For reviews, see: (a) Bandini, M.; Eichholzer, A. Angew. Chem., Int.
Ed. 2009, 48, 9608. (b) Bandini, M.; Melloni, A.; Umani-Ronchi, A. Angew.
Chem., Int. Ed. 2004, 43, 550. (c) Z., M.; You, S. L. Synlett 2010, 1289.
DOI: 10.1021/jo101640z
r
Published on Web 11/17/2010
J. Org. Chem. 2010, 75, 8677–8680 8677
2010 American Chemical Society

Xu et al.
JOCNote
SCHEME 1. Synthesis of SPINOL-Derived Phosphoric Acids 2
subsequent iodination, followed by deprotection of hydroxyl
groups, to gave 6,60-diiodo compound 5 in 73% yield. Suzuki
coupling reaction of 5 using 5% Pd/C as catalyst resulted in
6a-f in excellent yields (85-97%) with convenient opera-
tion. Finally, phosphorylation of 6 afforded the correspond-
ing phosphoric acids 2a-f in high yields (83-92%).
To our delight, the catalyst 2f, bearing two 1-naphthyl groups at
the 6,60-positions of the SPINOL backbone, gave high yield
(90%) and good enantioselectivity (89% ee) at room tempera-
ture. Further improvement of the enantioselectivity was achieved
at lower reaction temperature (Table 1, entries 7-9). Up to 96%
ee enantioselectivity and 80% yield were obtained when the
reaction was performed at -60 °C for 36 h (Table 1, entry 9).
The substrate scope of the enantioselective Friedel-Crafts
reaction of indoles 7 with imines 8 was then evaluated and is
summarized in Table 2. Interestingly, both the reactivity and
the enantioselectivity were enhanced by changing the tosyl
group of N-sulfonylphenylimines to the more electron-with-
drawing p-bromobenzenesulfonyl group (Table 2, entries 1-3).
Indoles bearing different substituents were then examined for
the reaction with imines 8a or 8c, and the result showed a good
tolerance in this catalytic system (Table 2, entries 4-9),
although the introduction of an electron-withdrawing group
onto the indole ring led to a lower reactivity (Table 2, entries
8 and 9). For aryl imines 8d-i, the reactions went smoothly
to give the corresponding products in 68-93% yield and
91->99% ee (Table 2, entries 10-16). In the case of 8i derived
from 1-naphthaldehyde, excellent enantioselectivity (97% ee)
was obtained at higher temperature (0 °C) (Table 2, entry 16). In
addition, heteroaryl imine 8j also gave excellent yield (96%) and
enantioselectivity (97% ee) (Table 2, entry 17). For alkyl imine
8k, however, we obtained the adduct in lower yield (47%) and
moderate enantioselectivity (79% ee) (Table 2, entry 18). The S-
configuration adduct product 9ad was confirmed by the X-ray
crystal structure analysis (see Supporting Information).
TABLE 1. Optimization for Enantioselective Friedel-Crafts Reactiona
entry
catalyst
temp
rt
rt
rt
rt
rt
rt
0 °C
-40 °C
-60 °C
time
yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
2f
2f
2f
40 min
7 h
3 h
80
89
87
75
100
90
92
85
11
72
73
72
56
89
90
94
96
4 h
10 min
30 min
75 min
8 h
36 h
80
aThe reaction was carried out with 0.5 mmol of 7a, 0.1 mmol of 8a,
b
and 10 mol % of catalyst 2 in 0.5 mL toluene. Isolated yield. Deter-
c
mined by HPLC analysis on a Chiralcel OD-H column.
To test the potential applications of our catalysts, the reaction
of indole (7a) with N-tosylimine 8a was chosen as a model
reaction, which has been well promoted by chiral metal com-
plex,4f,h chiral thiourea,5b and BINOL-derived phosphoric acid
catalysts.7b The products of this asymmetric Friedel-Crafts reac-
tion provide easy access to the synthesis of enantiopure 3-indolyl
methanamine derivatives. In our initial investigation, nonsub-
stituted 2a was used as catalyst with 10 mol % loading, and the
product was obtained in 80% yield with 11% ee (entry 1, Table 1),
while BINOL phosphoric acid gave only racemic products.7b
Inspired by this result, we then tested the substituent effect at the
6,60-positions of the catalysts with various aryl groups at room
temperature and found the substituent effect to be remarkable
(Table 1, entries 1-6). The reactions using 2b-das catalyst pro-
ceeded in similar yields and enantioselectivities, except that 2b
took a longer reaction time (Table 1, entries 2-4). When cata-
lyst 2e was employed, a quantitative yield as well as a moderate
ee value (56%) were obtained within 10 min (Table 1, entry 5).
Recently, Simon and Goodman10 provided both data and
computation models to identify the specific indolyl metha-
mine product for Friedel-Crafts reactions of indole with N-
tosylimines catalyzed by BINOL-phosphoric acids. On the
basis of this result, we propose a possible model for the
asymmetric induction of our catalytic system as shown in
Scheme 2. Phosphoric acid (S)-2 as a bifunctional catalyst
combines two substrates through hydrogen bonding. In this
model, indole attacks N-tosylimine from the re face prefer-
entially, leading to a S-configuration adduct.
In conclusion, we have synthesized a new class of chiral phos-
phoric acids with a spirobiindane backbone, which could effi-
ciently promote the enantioselective Friedel-Crafts reaction
of indoles with imines to afford 3-indolyl methanamines. Up
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(10) Simon, L.; Goodman, J. M. J. Org. Chem. 2010, 75, 589.
8678 J. Org. Chem. Vol. 75, No. 24, 2010

Xu et al.
JOCNote
TABLE 2. Enantioselective Friedel-Crafts Reaction Catalyzed by 2fa
aUnless otherwise noted, reactions were carried out with 0.5 mmol of 7, 0.1 mmol of 8, and 10 mol % of 2f in 0.5 mL of toluene at -60 °C. bIsolated
yield. cDetermined by HPLC analysis on a Chiralcel OD-H column. dReaction at -40 °C. eReaction at 0 °C. fAbsolute configuration determined by
X-ray single-crystal analysis.
SCHEME 2. Proposed Reaction Model
iodine (1.83 g, 7.2 mmol) in Et2O (20 mL) was carefully added. The
resulted suspension was warmed to room temperature, stirred over-
night, quenched by saturated Na2SO3, and stirred for an additional
1 h. The organic layer was separated, and the aqueous layer was
extracted by ether. The combined organic layer was washed with
brine, dried over Na2SO4, passed through a pad of silica, and concen-
trated in vacuo, giving the crude (S)-6,60-diiodo-7,70-bis(1-methoxy-
methoxy)-1,10-spirobiindane as brown solid, which was used without
further purification in the next step. The crude (S)-6,60-diiodo-7,70-
bis(1-methoxymethoxy)-1,10-spirobiindane was dissolved in CHCl3
(12 mL) and MeOH (18 mL), and conc HCl (12 mL) was added.
After being refluxed for 3 h, the mixture was poured into water and
extracted by CH2Cl2. The organic layer was washed with saturated
NaHCO3, dried over Na2SO4, and concentrated. The residue was
purified by silica gel column chromatography (ethyl acetate/petro-
leum ether = 1:10) to give the product 5 (0.88 g, 73% yield) as
white solid. Mp 149-150 °C; [R]20D=-187.2 (c 1.0, CHCl3);
1H NMR (400 MHz, CDCl3) δ 2.18-2.24 (m, 2 H), 2.29-2.37
(m, 2 H), 2.94-3.06 (m, 4 H), 5.11 (s, 2H), 6.65 (d, J=8.0 Hz,
2 H), 7.52 (d, J=7.6 Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ
31.1, 37.7, 59.8, 83.2, 119.2, 133.0, 137.7, 146.7, 151.1; ATR-FTIR
3479, 2935, 1571, 1436, 1323, 1290, 1233, 1188, 1061, 1000, 796,
to 97% yield and up to 99% ee enantioselectivity were obtained.
Further catalytic applications of the SPINOL-derived phospho-
ric acids in other enantioselective reactions are in progress.
Experimental Section
Synthesis of (S)-6,60-Diiodo-1,10-spirobiindane-7,70-diol (5). To a
solution of (S)-49d (0.81 g, 2.4 mmol) and TMEDA (0.75 mL,
5 mmol) in Et2O (15 mL) was added n-BuLi (2.5 M in hexane,
2.88 mL, 7.2 mmol) at -78 °C. After being stirred at room tempera-
ture for 6 h, the mixture was cooled to -78 °C, and a solution of
J. Org. Chem. Vol. 75, No. 24, 2010 8679

Xu et al.
JOCNote
-
754 cm-1; HRMS (ESI) calcd for C17H13I2O2 ([M - H]-):
2902, 1612, 1398, 1249, 1059, 871, 802, 777 cm-1; HRMS (ESI)
calcd for C37H26O4P- ([M - H]-): 565.1569. Found: 565.1541.
Typical Procedure for the Enantioselective Friedel-Crafts
Reaction. To a mixture of N-sulfonyl imine 8 (0.1 mmol) and cata-
lyst 2f (0.01 mmol) was added toluene (0.5 mL). Then the mixture
was stirred for 10 min at room temperature. Indole 7 (0.5 mmol)
was subsequently added in one portion at -60 °C. After the
reaction was complete, it was quenched by 2 M NaOH and
extracted with ethyl acetate. The organic layer was washed with
brine, dried over Na2SO4, and concentrated in vacuo. The residue
was purified by silica gel column chromatography (ethyl acetate/
petroleum ether=1:3) to give the corresponding product 9. Prod-
uct 9ac was obtained in 89% yield after chromatography and 99%
ee as determined by HPLC [Daicel Chiralcel OD-H, n-hexane/
i-propanol=70:30, 0.8 mL/min, λ=254 nm, tR (minor)=15.69 min,
tR (major)=35.37 min]. Mp 135-136 °C; [R]20D=-88.3 (c 0.80,
502.9005. Found: 502.8989.
Typical Synthesis of (S)-6,60-Diphenyl-1,10-spirobiindane-7,70-
diol (6b). A solution of (S)-5 (151 mg, 0.3 mmol), phenylboronic
acid (128 mg, 1.05 mmol), K2CO3 (0.145 g, 1.05 mmol), and 5%
Pd/C (13 mg; 0.006 mmol) in dioxane/water (1:1, 6 mL) was
stirred at 80 °C for 2 h and then diluted with ethyl acetate and
3 N HCl. The organic layer was washed with brine, dried over
Na2SO4, and concentrated in vacuo. The residue was purified by
silica gel column chromatography (ethyl acetate/petroleum
ether = 1:15) to give the product 6b (117 mg, 97% yield) as
white solid. Mp 203-204 °C; [R]20D = -281.5 (c 0.9, CHCl3);
1H NMR (400 MHz, CDCl3) δ 2.34-2.46 (m, 4 H), 3.02-3.15
(m, 4 H), 5.07 (s, 2H), 6.93 (d, J = 7.6 Hz, 2 H), 7.19 (d, J = 7.6
Hz, 2 H), 7.30 (t, J = 7.2 Hz, 2 H), 7.39 (t, J = 7.2 Hz, 4 H), 7.47
(d, J = 7.6 Hz, 4 H); 13C NMR (100 MHz, CDCl3) δ 31.1, 37.7,
58.4, 117.4, 126.9, 127.2, 128.6, 129.3, 130.5, 132.0, 137.4, 145.2,
149.4; ATR-FTIR 3510, 2943, 1616, 1580, 1499, 1472, 1420,
1253, 1228, 1180, 1074, 998, 814, 753, 698 cm-1; HRMS (ESI)
calcd for C29H23O2- ([M - H]-): 403.1698. Found: 403.1683.
Typical Synthesis of (S)-1,10-Spirobiindane-7,70-diyl phosphate
(2f). To a solution of (S)-6f (252 mg, 0.5 mmol) in pyridine (3 mL)
was added POCl3 (92 μL, 1.0 mmol) dropwise at 0 °C, and the
resulting mixture was heated to 70 °C and stirred for 3 h. After the
mixture cooled to 0 °C, 3 mL of water was carefully added, and the
resulting suspension was stirred at 110 °C for an additional 4 h.
Dichloromethane was added, and the pyridine was removed by
reverse extraction with 4 N HCl. The organic layer was dried over
Na2SO4 and concentrated. The residue was purified by silica gel
column chromatography (dichloromethane/methanol = 1:20 to
1:10) to give the product 2f (257 mg, 91% yield) as a foamy solid.
Mp >300 °C; [R]20D = -362.2 (c 0.50, CHCl3); 1H NMR (400
MHz, CHCl3) δ2.34-2.51 (m, 4H), 2.90-2.97 (m, 2H), 3.19-3.25
(m, 2H), 6.95-7.02 (m, 2H), 7.19-7.25 (m, 6H), 7.36-7.49 (m,
4H), 7.56-7.61 (m, 2H), 7.70-7.81 (m, 4H); 13C NMR (100 MHz,
CHCl3) δ 30.3, 39.1, 59.9, 120.7, 121.9, 125.2, 125.8, 126.5, 127.8,
129.8, 131.3, 131.7, 132.5, 132.7, 133.4, 137.4, 140.5, 144.4, 145.6;
31P NMR (202 MHz, CDCl3) δ -9.9; ATR-FTIR 3668, 2982,
1
Acetone); H NMR (400 MHz, CDCl3) δ 5.24 (d, J=7.2 Hz,
1 H), 5.91 (d, J=7.2 Hz, 1H), 6.65 (s, 1 H), 7.06 (t, J=7.6 Hz,
1 H), 7.18-7.22 (m, 6 H), 7.30-7.38 (m, 4 H), 7.42 (d, J = 8.0
Hz, 2 H), 7.99 (br, 1 H); 13C NMR (100 MHz, CDCl3) δ 55.2,
111.4, 115.8, 119.3, 120.1, 122.6, 123.8, 125.3, 126.9, 127.2,
127.5, 128.38, 128.44, 131.6, 136.5, 139.4, 139.6; ATR-FTIR
3669, 3411, 2982, 2902, 1399, 1323, 1249, 1157, 1071, 896, 740
cm-1; HRMS (ESI) calcd for C21H17BrN2O2SNaþ (M þ Naþ):
463.0092. Found: 463.0072.
Acknowledgment. We thank the National Natural Science
Foundation of China (No. 20872128; J0830413), the Funda-
mental Research Funds for the Central Universities
(2009QNA3011), and the Natural Science Foundation of
Zhejiang Province (R407106) for financial support of this
research.
Supporting Information Available: Detailed experimental
procedures, characterization data, CIF file, and copies of H
1
and 13C NMR and HPLC spectra. This material is available free
of charge via the Internet at http://pubs.acs.org.
8680 J. Org. Chem. Vol. 75, No. 24, 2010