Enantioselective BINOL-phosphoric acid catalyzed Pictet - Spengler reactions of N-benzyltryptamine

Article abstract of DOI:10.1021/jo8010478

(Chemical Equation Presented) Optically active tetrahydro-β-carbolines were synthesized via an (R)-BINOL-phosphoric acid-catalyzed asymmetric Pictet-Spengler reaction of N-benzyltryptamine with a series of aromatic and aliphatic aldehydes. The tetrahydro-β-carbolines were obtained in yields ranging from 77% to 97% and with ee values up to 87%. The triphenylsilyl- substituted BINOL-phosphoric acid proved to be the catalyst of choice for the reaction with aromatic aldehydes. For the aliphatic aldehydes, 3,5-bistrifluoromethylphenyl-substituted BINOL-phosphoric acid was identified as the best catalyst.

Full text of DOI:10.1021/jo8010478

Enantioselective BINOL-Phosphoric Acid
Catalyzed Pictet-Spengler Reactions of
N-Benzyltryptamine
Nishant V. Sewgobind, Martin J. Wanner, Steen Ingemann,
Rene´ de Gelder,† Jan H. van Maarseveen, and
Henk Hiemstra*
FIGURE 1. Tetrahydro-ꢀ-carbolines obtained via organocatalytic
asymmetric Pictet-Spengler reactions.
SCHEME 1. Pictet-Spengler Reaction
Van’t Hoff Institute for Molecular Sciences, UniVersity of
Amsterdam, Nieuwe Achtergracht 129, 1018 WS, Amsterdam,
The Netherlands
hiemstra@science.uVa.nl
ReceiVed May 15, 2008
Various stereoselective Pictet-Spengler reactions have been
described of which especially Cook’s approach using tryptophan
esters as chiral precursors is noteworthy.4b However, the ester
functionality had to be removed in a multistep sequence.
Recently, an organocatalytic approach toward enantioenriched
tetrahydro-ꢀ-carbolines (e.g., 2 in Figure 1) was developed
mediated by a chiral thiourea catalyst (5-10 mol % catalyst,
65-81% yield, and 85-93% ee).5 This reaction appeared to
be limited to aliphatic aldehydes and, in addition, N-acetyl group
removal proved to be difficult.
List and co-workers developed an asymmetric Pictet-Spengler
cyclization of an iminium diester that provided tetrahydro-ꢀ-
carbolines 3 in 40-96% yield and 62-96% ee with triisopro-
pylphenyl-substituted (S)-BINOL phosphoric acid (20 mol %)
as the catalyst.6 Although both aromatic and aliphatic aldehydes
were accepted in this reaction, the method required the presence
of two ester functionalities and is therefore of limited utility.
Within our research program on the development of asym-
metric reactions of iminium ions catalyzed by chiral Brønsted
acids,7 we recently reported a catalytic asymmetric Pictet-
Spengler reaction via an N-sulfenyliminium ion catalyzed by a
bis-trifluoromethylphenyl-substituted (R)-BINOL phosphoric
acid (5-10 mol %). Both alkyl- and aryl-substituted tetrahydro-
ꢀ-carbolines 4 were obtained in 77-90% yield in two steps
(cyclization and removal of the tritylsulfenyl group in a one-
pot procedure) with ee values up to 87%.8
Optically active tetrahydro-ꢀ-carbolines were synthesized via
an (R)-BINOL-phosphoric acid-catalyzed asymmetric Pictet-
Spengler reaction of N-benzyltryptamine with a series of
aromatic and aliphatic aldehydes. The tetrahydro-ꢀ-carbolines
were obtained in yields ranging from 77% to 97% and with
ee values up to 87%. The triphenylsilyl-substituted BINOL-
phosphoric acid proved to be the catalyst of choice for the
reaction with aromatic aldehydes. For the aliphatic aldehydes,
3,5-bistrifluoromethylphenyl-substituted BINOL-phosphoric
acid was identified as the best catalyst.
Compounds containing the tetrahydro-ꢀ-carboline core (1)
are of great interest because of their inherent biological
activity.1–3 Tetrahydro-ꢀ-carbolines are generally obtained via
the Pictet-Spengler reaction of tryptamine with a variety of
aromatic and aliphatic aldehydes in the presence of a Brønsted
acid (Scheme 1).4
† X-Ray crystal structure determination: Institute for Molecules and Materials,
Radboud University, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands.
(1) For their use as anti-viral agents, see: (a) Gudmundsson, K. WO
2007002051, 2007. (b) Gudmundsson, K.; Miller, J. F.; Sherrill, R. G.; Turner,
E. M. WO 2006015035, 2006. For the application in the development of
anticancer agents, see:(c) Shen, Y.-C.; Chen, C.-Y.; Hsieh, P.-W.; Duh, C.-Y.;
Lin, Y.-M.; Ko, C.-L. Chem. Pharm. Bull. 2005, 53, 32–36. For their application
in the treatment of male erectile dysfunction, see: (d) Sui, Z.; Guan, J.; Macielag,
M. J.; Jiang, W.; Qiu, Y.; Kraft, P.; Bhattacharjee, S.; John, T. M.; Craig, E.;
Haynes-Johnson, D.; Clancy, J. Bioorg. Med. Chem. Lett. 2003, 13, 761–765.
(2) (a) Kawasaki, T.; Higuchi, K. Nat. Prod. Rep. 2005, 22, 761–793. (b) Yu,
J.; Wang, T.; Liu, X.; Deschamps, J.; Anderson, J. F.; Liao, X.; Cook, J. M. J. Org.
Chem. 2003, 68, 7565–7581. (c) Liao, X.; Zhou, H.; Yu, J.; Cook, J. M. J. Org.
Chem. 2006, 71, 8884–8890. (d) Ma, J.; Yin, W.; Zhou, H.; Cook, J. M. Org. Lett.
2007, 9, 3491–3494.
(4) (a) Pictet, A.; Spengler, T. Ber. Dtsch. Chem. Ges. 1911, 44, 2030–2036.
(b) Cox, E. D.; Cook, J. M. Chem. ReV. 1995, 95, 1797–1842.
(5) Taylor, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 10558–
10559.
(6) Seayad, J.; Seayad, A. M.; List, B. J. Am. Chem. Soc. 2006, 128, 1086–
1087.
(7) For recent reviews on catalysis by chiral Brønsted acids, see: (a) Connon,
S. J. Angew. Chem., Int. Ed. 2006, 45, 3909–3912. (b) Akiyama, T.; Itoh, J.;
Fuchibe, K. AdV. Synth. Catal. 2006, 348, 999–1010. (c) Taylor, M. S.; Jacobsen,
E. N. Angew. Chem., Int. Ed. 2006, 45, 1520–1543. (d) Akiyama, T. Chem.
ReV. 2007, 107, 5744–5758. (e) Connon, S. J. Org. Biomol. Chem. 2007, 5,
3407–3417. For a convenient protocol for the synthesis of these chiral phosphoric
acids, see: (f) Bartoszek, M.; Beller, M.; Deutsch, J.; Klawonn, M.; Ko¨ckritz,
A.; Nemati, N.; Pews-Davtyan, A. Tetrahedron 2008, 64, 1316–1322.
(8) Wanner, M. J.; van der Haas, R. N. S.; de Cuba, K.; van Maarseveen,
J. H.; Hiemstra, H. Angew. Chem., Int. Ed. 2007, 46, 7485–7487.
(3) (a) Herraiz, T. J. Chromatogr. A 2000, 881, 483–499. (b) Herraiz, T.;
Galisteo, J.; Chamorro, C. J. Agric. Food Chem. 2003, 51, 2168–2173.
10.1021/jo8010478 CCC: $40.75
Published on Web 07/11/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 6405–6408 6405

SCHEME 2. Winterfeldt Oxidation and Known
Pyrroloquinolone Derivatives
FIGURE 2. Chiral phosphoric acids.
N-Substituted tetrahydro-ꢀ-carbolines are the starting materi-
als of choice for the pharmaceutically relevant pyrroloquinolones
5 via the Winterfeldt oxidation.9
TABLE 1. Catalyst Screeninga
Pyrroloquinolones (e.g., 6 in Scheme 2) are selective phos-
phodiesterase 5 (PDE5) inhibitors,10 and the related quinolac-
tacins such as 7 are known to play a key role in apoptosis.11,12
Pyrroloquinolone 610h was proven to be superior in selectivity
and potency in the treatment of male erectile dysfunction
compared to the nowadays commercially available Viagra
(sildenafil),13 Levitra (vardenafil),14 and Cialis (tadalafil).15
Pyrroloquinolones such as 6 have been synthesized via an
asymmetric Pictet-Spengler reaction from tryptamine func-
tionalized with 1-naphthalen-1-yl-ethylamine as the chiral
auxiliary.10a Starting from tryptophan a diastereoselective
Pictet-Spengler reaction was achieved and the ester group was
removed in 4 steps.10h Another route starts with (one pot)
consecutive imine formation from tryptamine in boiling toluene,
followed by an acid-catalyzed Pictet-Spengler cyclization and
resolution with a chiral acid to afford the tetrahydro-ꢀ-carboline
intermediate with high optical purity. After installing the
N-benzyl the stage was set for the Winterfeldt oxidation.10e,g
Because N-benzyl-protected tetrahydro-ꢀ-carbolines are the
most commonly used substrates for the Winterfeldt oxidation
we herein report an asymmetric organocatalytic Pictet-Spengler
reaction directly starting from N-benzyltryptamine.
entry
catalyst
conversion (%)b
ee (%)c
1
2
3
4
5
6
7
8
9
9a
9b
9c
9d
9e
9f
10a
10b
10c
10d
11
92
62
100
76
50
40
93
90
56
93
28
43
49
85
35
28
10
48
78
10
19
15
10
11
a Reaction was conducted with 8 (0.05 mmol), 12 (3 equiv), and
powdered 4 Å MS (75 mg) in toluene (0.5 mL) with 2 mol % catalyst
at 70 °C for 24 h. Determined by H NMR spectroscopy. c Determined
b
1
by HPLC on a chiral column (Chiralcel OD).
As 2,3-dihydrobenzofuran-5-carboxaldehyde 12 is employed
in the synthesis of PDE5 inhibitors,10 we have chosen this
particular aldehyde to study the enantioselective Pictet-Spengler
reaction starting from N-benzyltryptamine 8 providing tetrahy-
dro-ꢀ-carboline 13. A series of enantiopure phosphoric acid
catalysts were screened (see Figure 2) and the results are listed
in Table 1.
Low ee values were obtained with the binol phosphoric acids
9a-f, except when triphenylsilyl catalyst 9c was used (Table
1, entry 3). The H8-BINOL phosphoric acids 10a and 10b gave
almost full conversions and similar ee values as the related
BINOL phosphoric acids. VAPOL hydrogen phosphate 11
proved to be unsuitable for this reaction as only low conversion
and enantioselectivity were obtained.
With catalyst 9c giving the best result, we then investigated
the influence of catalyst loading and reaction temperature for
this catalyst. In the absence of catalyst, it appeared that 13 was
formed as a racemic mixture in a yield of 23-35% after 24 h
(as observed in three different experiments).16 Increasing the
amount of catalyst to 5 mol % gave full conversion after 13 h
(9) (a) Winterfeldt, E. Liebigs Ann. Chem. 1971, 745, 23–30. (b) Warneke,
J.; Winterfeldt, E. Chem. Ber. 1972, 105, 2120–2125. (c) Boch, M.; Korth, T.;
Nelke, J. M.; Pike, D.; Radunz, H.; Winterfeldt, E. Chem. Ber. 1972, 105, 2126–
2142.
(10) (a) Jiang, W.; Sui, Z.; Chen, X. Tetrahedron Lett. 2002, 43, 8941–8945.
(b) Jiang, W.; Sui, Z.; Chen, X. Org. Lett. 2003, 5, 43–46. (c) Jiang, W.; Sui,
Z.; Macielag, M. J.; Walsh, S. P.; Fiordeliso, J. J.; Lanter, J. C.; Guan, J.; Qiu,
Y.; Kraft, P.; Bhattacharjee, S.; Craig, E.; Haynes-Johnson, D.; John, T. M.;
Clancy, J. J. Med. Chem. 2003, 46, 441–444. (d) Lanter, J. C.; Sui, Z.; Macielag,
M. J.; Fiordeliso, J. J.; Jiang, W.; Qiu, Y.; Bhattacharjee, S.; Kraft, P.; John,
T. M.; Haynes-Johnson, D.; Craig, E.; Clancy, J. J. Med. Chem. 2004, 47, 656–
662. (e) Li, X.; Branum, S.; Russell, R. K.; Jiang, W.; Sui, Z. Org. Process Res.
DeV. 2005, 9, 640–645. (f) Jiang, W.; Guan, J.; Macielag, M. J.; Zhang, S.; Qiu,
Y.; Kraft, P.; Bhattacharjee, S.; John, T.M. ; Haynes-Johnson, D.; Lundeen, S.;
Sui, Z. J. Med. Chem. 2005, 48, 2126–2133. (g) Willemsens, B.; Vervest, I.;
Ormerod, D.; Aelterman, W.; Fannes, C.; Mertens, N.; Marko´, I. E.; Lemaire,
S. Org. Process Res. DeV. 2006, 10, 1275–1281. (h) Lemaire, S.; Willemsens,
B.; Marko´, I. E. Synlett 2007, 5, 709–712.
(11) Clark, B.; Capon, R. J.; Lacey, E.; Tennant, S.; Gill, J. H. Org. Biomol.
Chem 2006, 4, 1512–1519, and references cited therein.
(12) Zhang, X.; Jiang, W.; Sui, Z. J. Org. Chem. 2003, 68, 4523–4526.
(13) Brook, G. Drugs Today 2000, 26, 125–134.
(14) Sorbera, L. A.; Martin, L.; Rabasseda, X.; Castaner, J. Drugs Future
2001, 26, 141–144.
(15) (a) Sorbera, L. A.; Martin, L.; Leeson, P. A.; Castaner, J. Drugs Future
2001, 26, 15–19. For the discovery of tadalafil, see: (b) Daugan, A.; Grondin,
P.; Ruault, C.; Gouville, A.-C. L. M.; Coste, H.; Kirilovsky, J.; Hyafil, F.;
Labaudinie`re, R. J. Med. Chem. 2003, 46, 4525–4532. (c) Daugan, A.; Grondin,
P.; Ruault, C.; Gouville, A.-C. L. M.; Coste, H.; Kirilovsky, J.; Linget, J.-M.;
Hyafil, F.; Labaudinie`re, R. J. Med. Chem. 2003, 46, 4533–4542.
(16) See for an uncatalyzed Pictet-Spengler reaction with N-benzyltryptamine
see: Soerens, D.; Sandrin, J.; Ungemach, F.; Mokry, P.; Wu, G. S.; Yamanaka,
E.; Hutchins, L.; DiPierro, M.; Cook, J. M. J. Org. Chem. 1979, 44, 535–545.
6406 J. Org. Chem. Vol. 73, No. 16, 2008

TABLE 2. Solvent and Additive Screeninga
TABLE 3. Scope of the Reactiona
entry
R
product
yield (%)b
ee (%)c
1
2e
3
4
5
p-BrC6H5
14a
14b
14c
14d
14e
14f
14g
13
14h
14i
14j
14k
14l
92
95
97
92
82
84
92
80
84
88
95
83
90
77
0
85d
entry
solvent
additive
conversionb
ee (%)c
p-NO2C6H5
p-CF3C6H5
m-ClC6H5
3,5-(CF3)2C6H4
furfuryl
87f
83d
20g
racg
80d,h
82g
85d
80g
74f
1
2
3
4
5d
6
7
8
9
toluene
xylenes
C6H6
incomplete
full
full
incomplete
incomplete
full
full
full
incomplete
41
79
79
57
35
76
85
79
67
4 Å MS
4 Å MS
4 Å MS
4 Å MS
3 Å MS
4 Å MS
5 Å MS
Na2SO4
6
DCE
7e
8
piperonyl
MeCN
toluene
toluene
toluene
toluene
dihydrobenzofuryl
p-MeOC6H5
3,4,5-(OMe)3C6H2
C6H5
2,4-Me2C6H5
i-Pr
n-pentyl
benzyl
2-phenylethyl
9
10e
11
12
13i
14i
15i
16i
72g
61g
81g
68g
a Reaction was conducted with 8 (0.05 mmol), 12 (3 equiv), and
drying agent (75 mg) in 0.5 mL of solvent with 2 mol % 9c at 70 °C
for 24 h. b Reaction monitored by TLC. c Determined by HPLC on a
chiral column (Chiralcel OD). d Stirred for 48 h.
14m
14n
14o
93
8g
a Reaction was conducted with 8 (0.2 mmol), aldehyde (3 equiv), and
powdered 4 Å MS (300 mg) in 2 mL of toluene with 2 mol % of 9c at
70 °C for 24 h unless otherwise stated. b Isolated yield. c Determined by
HPLC on a chiral column. d With Chiralcel OD. e 5 mol % of 9c was
used. f With Chiralpak AD. g With Chiralcel OD-H. h A different
workup procedure was performed to prevent racemization, see the
Supporting Information. i Reaction performed with catalyst 9a (2 mol
%) at room temperature.
and 13 was obtained with an ee of 85%. With 10 mol % catalyst
the reaction was complete in 4 h and afforded 13 with essentially
the same ee (86%) as obtained with a catalyst loading of 2 or
5 mol % (see also Table 1). The best results in terms of ee
were obtained at a temperature of 70 °C; at 50 °C the reaction
of 8 with 12 was complete in 48 h (81% ee) and at 90 °C full
conversion was observed after 12 h (82% ee) with a catalyst
loading of 2 mol %.
The study of the effects of solvent and additives is sum-
marized in Table 2. The reaction proceeded at best in aromatic
solvents with a clear preference for toluene. In the absence of
mol sieves, the reaction was incomplete after 24 h and the
product was obtained with a modest ee only (41%). A
comparable result was obtained by using sodium sulfate as the
drying agent. Slightly lower ee values were obtained when 3 Å
and 5 Å MS were employed as compared to 4 Å MS. Possibly,
water is able to break up the tight complex between the BINOL-
phosphate and the cyclization precursor.
FIGURE 3. X-ray crystal structure of 14a.
gave the lowest ee and with the easy enolizable phenylacetal-
dehyde no product could be obtained (entry 15).
In our final optimization experiments, the stability of the
Pictet-Spengler product was examined. We exposed enan-
tiopure (S)-13 to the reaction conditions (2 mol % of 9c, 2 equiv
of 13, 4 Å MS, toluene, 70 °C, 24 h) and no racemization was
observed. By application of the same reaction conditions to the
racemic product 13 no enantiomeric enrichment was observed
thus suggesting that the BINOL-phosphoric acid catalyzed
Pictet-Spengler reaction of N-benzyltryptamine with 12 is
irreversible under our reaction conditions.
The Pictet-Spengler reactions with 2,3-dihydrobenzofuran-
5-carboxaldehyde 12 and p-bromobenzaldehyde were also
performed on a 1 mmol scale giving 13 and 14a in similar yields
and ee values. Both products were readily recrystallized to
enantiomeric purity. From 14a an X-ray crystallographic
structure (Figure 3) was obtained revealing the absolute con-
figuration which was found to be (S). This is in analogy with
our previous results obtained for the Pictet-Spengler reaction
with N-tritylsulfenyltryptamine.8 The required biologically active
(R)-enantiomer of benzofuran 13 was prepared with comparable
yield and ee by using the corresponding (S)-triphenylsilyl-
substituted BINOL catalyst 9c.
With the optimal reaction conditions identified, we investi-
gated the reaction with a series of aliphatic and aromatic
aldehydes. The results are presented in Table 3.
All reactions proceeded smoothly to give the corresponding
products 13 and 14 in good to high yields (77-97%). Both
aromatic (bearing electron donating and electron withdrawing
groups) and aliphatic aldehydes are tolerated. Moderate to good
ee values were obtained in the range of 61-87%, with the best
result with p-nitrobenzaldehyde (Table 3, entry 2). Remarkably,
low ee values (0-20%) were obtained with m-chlorobenzalde-
hyde and with 3,5-bis(trifluoromethyl)benz-aldehyde (entries 4
and 5). The reason for the low ee in these two cases is unclear.
Of the aliphatic aldehydes tested, 3-phenylpropanal (entry 16)
In conclusion, we have developed an organocatalyzed asym-
metric Pictet-Spengler reaction of N-benzyltryptamine (8) with
a variety of aldehydes. Both aromatic and aliphatic aldehydes
can be used in this reaction catalyzed by an enantiopure BINOL-
derived phosphoric acid. The corresponding adducts are obtained
in good to high yields and moderate to good ee values in one
step. In addition, our scaleable method shortens the synthesis
toward the pharmaceutically very relevant PDE5 inhibitors of
the pyrroloquinolone class by three steps.
J. Org. Chem. Vol. 73, No. 16, 2008 6407

108.8, 71.3, 64.1, 58.1, 48.4, 29.6, 21.2; IR (film) ν 3407, 3027,
2896, 2842, 2794, 1613, 1489; HRMS (FAB) m/z calcd for [M +
H]+ C26H25N2O 381.1967, found 381.1972.
Experimental Section
(S)-2-Benzyl-1-dihydrobenzofuryl-1,2,3,4-tetrahydro-ꢀ-carbo-
line (13). A mixture of N-benzyltryptamine (8, 250 mg, 1 mmol),
4 Å (powdered) molecular sieves (1.5 g), and catalyst 9c (17.3 mg,
0.02 mmol) in 10 mL of toluene was stirred for 5 min at room
temperature. Subsequently, 2,3-dihydrobenzofuran-5-carboxalde-
hyde (12, 178 mg, 1.2 mmol) was added and the mixture was stirred
at 70 °C for 24 h under a nitrogen atmosphere. The reaction mixture
was then cooled to room temperature and 3 g of silica gel was
added followed by 5 mL of petroleum ether (PE). The resulting
slurry was stirred for 5 min and filtered over a Celite path containing
2 g of silica gel (glass filter) and rinsed with 90 mL of eluent (PE:
EtOAc ) 5:1). Concentration of the filtrate afforded tetrahydro-
ꢀ-carboline 13 in a yield of 69% (262.3 mg, 84% ee).
(S)-2-Benzyl-1-(p-bromophenyl)-1,2,3,4-tetrahydro-ꢀ-carbo-
line (14a). Compound 14a was obtained in a yield of 92% (384.7
mg, 87% ee) following the procedure described for 13 with
p-bromobenzaldehyde (222.0 mg, 1.2 mmol). Crystals were formed
as described for (S)-13 to give 41.2 mg (10% yield, 10% ee) of
solid. The filtrate was concentrated to a small volume and diluted
with PE (2 mL). After standing in the refrigerator for 18 h, 343.5
mg (82% yield, 98% ee) of solid was obtained. Recrystallization
from EtOH gave enantiomerically pure (S)-14a (>99% ee deter-
mined on a Chiralcel OD column of heptane:isopropanol ) 97:3,
1 mL/min, tr major ) 12.3 min, tr minor ) 16.4 min) which was
used for X-ray crystal structure analysis. Mp 171-172.5 °C; [R]22
D
To obtain crystals the solid was dissolved in 0.5 mL of hot EtOAc
and diluted with 1 to 2 mL of PE. The resulting solution was kept
for 18 h in the refrigerator to give 35.3 mg (9% yield) of racemic
crystals. The filtrate was concentrated to a small volume and diluted
with PE (2 mL). After standing in the refrigerator for 18 h, 227
mg (60% yield, 96% ee) of solid was obtained. Recrystallization
from EtOH gave enantiomerically pure (S)-13 (99% ee determined
by chiral HPLC on a Chiralcel OD column of heptane:isopropanol
) 98:2, 0.8 mL/min, tr major ) 21.0 min, tr minor ) 24.3 min).
Mp 167-168 °C. [R]22D +70 (c 0.25, CHCl3); 1H NMR (400 MHz;
CDCl3) δ 7.57-7.55 (m, 1H), 7.43-7.34 (m, 5H), 7.31-7.28 (m,
2H), 7.24-7.18 (m, 2H), 7.16-7.11 (m, 2H), 6.80 (d, J ) 8.1 Hz,
1H), 4.62-4.58 (m, 3H), 3.98 (d, J ) 13.6 Hz, 1H), 3.40 (d, J )
13.6 Hz, 1H), 3.30-3.24 (m, 1H), 3.23-3.13 (m, 2H), 2.99-2.92
(m, 1H), 2.85-2.80 (m, 1H), 2.73-2.68 (m, 1H); 13C NMR (75.5
MHz; CDCl3) δ 160.0, 139.5, 136.2, 135.3, 133.2, 128.9, 128.7,
128.2, 127.7, 127.2, 126.8, 125.4, 121.4, 119.3, 118.2, 110.7, 108.9,
+67.4 (c 0.23, CHCl3); 1H NMR (400 MHz; CDCl3) δ 7.56-7.50
(m, 3H), 7.36-7.31 (m, 6H), 7.30-7.24 (m, 2H), 7.24-7.21 (m,
1H), 7.18-7.11 (m, 2H), 4.65 (s, 1H), 3.89 (d, J ) 13.6 Hz, 1H),
3.42 (d, J ) 13.6 Hz, 1H), 3.26-3.21 (m, 1H), 2.96-2.88 (m,
1H), 2.85-2.80 (m, 1H), 2.73-2.67 (m, 1H); 13C NMR (75.5 MHz;
CDCl3) δ 140.7, 139.3, 136.4, 134.1, 131.9, 130.7, 128.7, 128.4,
127.2, 127.1, 122.0, 121.8, 119.5, 118.4, 110.9, 109.3, 63.7, 58.3,
48.1, 21.1; IR (NaCl) ν 3406, 2796, 1483; HRMS (FAB) m/z calcd.
for [M + H]+ C24H22N2Br 417.0966, found 417.0954.
Supporting Information Available: Analytical and spectral
1
data, copies of H and 13C NMR spectra, and chromatograms
of the compounds in Table 3, as well as of the catalysts 10a
and 10b, and detailed experimental procedures. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO8010478
6408 J. Org. Chem. Vol. 73, No. 16, 2008