A short synthesis of (+)-(S)-kurasoin B

Article abstract of DOI:10.1016/j.tetasy.2007.11.018

A short efficient enantioselective synthesis leading directly to (+)-(S)-kurasoin B has been achieved in 5 steps and 25% overall yield from (2E)-ethyl-4-phenylbut-2-enoate using Sharpless asymmetric dihydroxylation and CH₃NO₂-assiste

Full text of DOI:10.1016/j.tetasy.2007.11.018

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 15–18
A short synthesis of (+)-(S)-kurasoin B
Rodney A. Fernandes*
Departamento Orga´nica Sı´ntesis, Instituto de Quı´mica, Universidad Nacional Auto´noma de Me´xico, Circuito Exterior,
Ciudad Universitaria, Coyoacan C.P. 04510, Me´xico D.F., Mexico
Received 7 July 2007; accepted 13 November 2007
Abstract—A short efficient enantioselective synthesis leading directly to (+)-(S)-kurasoin B has been achieved in 5 steps and 25% overall
yield from (2E)-ethyl-4-phenylbut-2-enoate using Sharpless asymmetric dihydroxylation and CH3NO2-assisted, or Yb(OTf)3-catalyzed,
regioselective C-3 coupling of indole as the key steps.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
The structures of 1 and 2 were determined by spectroscopic
analyses and synthesis of the racemates.4 The absolute con-
figuration was later determined by asymmetric synthesis
involving the Sharpless asymmetric epoxidation.2 The syn-
thesis of kurasoin B2 2 from phenylacetaldehyde (5.7%
overall yield) in 4 steps involves an intermediate in 38%
yield and the coupling of indole with the chiral epoxide
intermediate in a low yield of 27%. Grignard addition to a
Weinreb amide leading to racemic 1 or 2 was also reported.4
Since there was only one report on the asymmetric synthesis
of 2, it prompted the author to take up a short, high-yielding
and alternative enantioselective synthesis of (+)-(S)-kuraso-
in B 2. While this work was conceived, a new synthesis of
kurasoin B 2 has appeared involving Yb(OTf)3-catalyzed
coupling of indole with methyl glycidate.5
The protein farnesyltransferase (PFTase) inhibitors kuras-
oin A 1 and B 2 were isolated from the fermentation
broth of the soil fungus, Paecilomyces sp. FO-36841
(Fig. 1). One of the reasons for interest in PFTase inhibi-
tors is their potential anti-cancer properties. They inhibit
farnesyltransferase in a dose-dependent manner. The IC50
values for 1 and 2 against PFTase were 59.0 and 58.7
lM, respectively.2b It has also been found that the stereo-
chemistry of the hydroxyl functional group is important
for eliciting PFTase inhibition.2b Kurasoins A and B are
acyloin compounds which have in common, a 3-hydroxy-
1-phenyl-2-butanone moiety, to which 4-hydroxyphenyl
and 3-indolyl moieties, respectively, are connected at C-4.
This feature holds potential for new lead development in
that several analogues can be synthesized by modifying
the aromatic substituents around the 3-hydroxy-2-buta-
none core unit.3
2. Results and discussion
The Sharpless asymmetric dihydroxylation6a–d and subse-
quent conversion to epoxide function can be envisioned
as powerful tools offering considerable opportunities for
further synthetic manipulations.6e,f Herein, we report a
new and short enantioselective synthesis of (+)-(S)-kurasoin
B 2 from (2E)-ethyl-4-phenylbut-2-enoate 5, employing the
Sharpless asymmetric dihydroxylation as the source of chi-
rality; conversion of the diol to an epoxide and CH3NO2-
assisted, or Yb(OTf)3-catalyzed regioselective C-3 coupling
of indole as the key steps. The retrosynthetic strategy is
outlined in Scheme 1.
O
O
OH
OH
S)-kurasoin B 2
NH
OH
(+)-(
S)-kurasoin A 1
(+)-(
Figure 1. (+)-(S)-Kurasoin A and (+)-(S)-kurasoin B.
*
The target compound can be prepared by regioselective C-3
Tel.: +52 55 56224447; fax: +52 55 56162217; e-mail: fernandr@
servidor.unam.mx
indole coupling with the keto derivative of epoxide 3,
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.11.018

16
R. A. Fernandes / Tetrahedron: Asymmetry 19 (2008) 15–18
Table 1. Coupling of indole with epoxide 8a
O
OH
O
O
Table 1
OH
NH
O
3
O
NH
S)-kurasoin B 2
8
OH
(+)-(
S
)-kurasoin B 2
(+)-(
O
Entry
Lewis acid
(equiv)
Reaction Conditions
2 yield
OEt
(%)
Br
5
4
1
2
3
SnCl4 (0.3)
SnCl4 (1.2)
SnCl4 (1.2)
CH2Cl2, ꢁ5 ꢁC, 8 h
CH2Cl2, ꢁ5 ꢁC, 4 h
CH2Cl2/CH3NO2
18b
26
Scheme 1. Retrosynthetic analysis for (+)-(S)-kurasoin B 2.
49
(4:3), ꢁ5 ꢁC, 25 min
4
Yb(OTf)3 (0.2)
1,2-Dichloroethane, 50 ꢁC, 4 h
62
which in turn would be obtained from (2E)-1-bromo-4-
phenylbut-2-ene 4 by asymmetric dihydroxylation. Allyl
bromide 4 can be derived from the olefin ester 5.
a All reactions were carried out with indole (1.5 equiv) and 8 (1 equiv).
b 20% of indole was recovered.
The synthesis of (+)-(S)-kurasoin B 2 is depicted in Scheme
2. (2E)-Ethyl-4-phenylbut-2-enoate 5 was easily prepared
from phenylacetaldehyde by a Wittig olefination.7 Subse-
quent reduction of the ester function in 5 with DIBAL-H
gave the corresponding allyl alcohol 6 in 95% yield. The
hydroxyl function in 6 was easily converted to the bromide
using Ph3P and NBS8 which afforded the allyl bromide 4 in
95% yield. The Sharpless asymmetric dihydroxylation of
allyl bromide 4 under standard conditions6 and using
(DHQ)2-PHAL as the chiral ligand afforded the intermedi-
ate bromo-diol 7 which, without further purification, was
treated with K2CO3 in dry MeOH to give cleanly the
hydroxy-epoxide 39 in 79% yield and with 95% ee.10 Oxida-
tion of 3 with Jones reagent [CrO3 + H2SO4] gave the inter-
mediate epoxy ketone 82b in 83% yield (Scheme 2).
CH3NO2 as co-solvent, give higher yields.11 This is attrib-
uted to the higher solubility of the intermediate Lewis acid
complex with the indole or epoxide in the reaction media,
thereby reducing the reaction time and increasing the yields
significantly. Gratifyingly, the reaction of the indole with
the epoxy ketone 8 in a mixture of CH2Cl2 and CH3NO2
(4:3) in the presence of the Lewis acid SnCl4 (1.2 equiv,
Table 1, entry 3) gave the C-3 coupled product 2 in a good
20
yield of 49% {½aꢀD ¼ þ30:6 (c 0.2, CHCl3) [lit.2b +31 (c
0.33, CHCl3)]}, which is almost twice the reported yield.2b
5
The same reaction, when catalyzed with Yb(OTf)3 (Table
1, entry 4) in 1,2-dichloroethane gave 2 in 62% yield,
20
½aꢀD ¼ þ30:7 (c 0.15, CHCl3). The physical and spectro-
scopic data of 2 were in full agreement with the literature
data.2b
O
a
b
OEt
OH
Br
5
6
3. Conclusion
OH
(ii)
c (i)
In conclusion, a highly enantioselective and short synthesis
of (+)-(S)-kurasoin B 2 from readily available (2E)-ethyl-4-
phenylbut-2-enoate, employing the Sharpless asymmetric
dihydroxylation and CH3NO2-assisted or Yb(OTf)3-cata-
lyzed, regioselective C-3 coupling of indole as the key steps
has been achieved. The synthetic strategy involves 5 steps
and gives the title compound in 25% overall yield. The
method uses the Sharpless asymmetric dihydroxylation as
the source of chirality to synthesize the title compound
and is a good alternative to known methods.
Br
4
7
OH
O
OH
d
3
8
O
O
Scheme 2. Reagents and conditions: (a) DIBAL-H (2.2 equiv), CH2Cl2,
0 ꢁC, 2 h, rt, 30 min, 95%; (b) Ph3P (1.2 equiv), NBS (1.2 equiv), CH2Cl2,
ꢁ15 ꢁC, 30 min, rt, 45 min, 95%; (c) (i) K3Fe(CN)6 (3.0 equiv), K2CO3
(3.0 equiv), NaHCO3 (3.0 equiv), MeSO2NH2 (1.0 equiv), (DHQ)2PHAL
(1 mol %), K2OsO4Æ2H2O (0.4 mol %), t-BuOH/H2O (1:1), 0 ꢁC, 24 h; (ii)
K2CO3 (2.1 equiv), MeOH, rt, 10 h, 79% over 2 steps; (d) CrO3, H2SO4,
acetone, rt, 30 min, 83%.
4. Experimental
4.1. General information
The synthesis of (+)-(S)-kurasoin B 2 from epoxy ketone 8
was completed as follows (Table 1). In the previous synthe-
sis,2 the coupling of indole with 8 was carried out in 27%
yield. The reaction of the indole with epoxide 8 using SnCl4
(0.3 equiv) gave only 18% of the coupled product 2
(Table 1, entry 1). When 1.2 equiv of SnCl4 was employed,
the coupled product 2 was obtained in 26% yield (Table 1,
entry 2) similar to that reported in the literature.2 It is
known that similar reactions, carried out employing
Solvents were purified and dried by standard procedures
before use. Commercially available reagents were used as
received. Optical rotations were measured using sodium
D line at 589 nm on a Perkin–Elmer, Model 343 polarime-
ter at 20 ꢁC. IR spectra were recorded on Bruker TENSOR
27 spectrometer as neat thin films. 1H NMR and 13C NMR
were recorded on Eclipse 300 MHz Jeol or Bruker Avance
300 MHz spectrometers with TMS at d = 0.00 ppm and

R. A. Fernandes / Tetrahedron: Asymmetry 19 (2008) 15–18
17
CHCl3 at d = 77.00 ppm as internal standards for 1H
4.4. (2S,3S)-1,2-Epoxy-4-phenylbutan-3-ol 3
NMR and 13C NMR, respectively. Mass spectra were re-
corded on Jeol AX505HA spectrometer. Elemental analy-
ses were carried on a Carlo Erba CHNS-O analyzer.
A mixture of K3Fe(CN)6 (8.42 g, 25.58 mmol, 3.0 equiv),
K2CO3 (3.54 g, 25.58 mmol, 3.0 equiv), NaHCO3 (2.15 g,
25.58 mmol, 3.0 equiv), MeSO2NH2 (0.811 g, 8.53 mmol,
1.0 equiv), (DHQ)2PHAL (66.42 mg, 0.0853 mmol,
1
mol %), K2OsO4Æ2H2O (12.57 mg, 0.0341 mmol, 0.4
mol %) in t-BuOH/H2O (1:1, 90 mL) was stirred for
5 min at room temperature. The two phase mixture was
cooled to 0 ꢁC and the allyl bromide 4 (1.8 g, 8.53 mmol,
1.0 equiv) was added. The reaction mixture was stirred at
0 ꢁC for 24 h and then quenched with solid Na2SO3 (4 g).
Stirring was continued for a further 30 min and the solu-
tion extracted with EtOAc (3 · 50 mL). The combined
organic layers were washed with water (2 · 50 mL), brine,
dried over Na2SO4 and concentrated. To the residue were
added dry MeOH (80 mL) and K2CO3 (2.48 g, 17.94 mmol,
2.1 equiv) and the mixture was stirred at room temperature
for 10 h. Water (50 mL) and EtOAc (50 mL) were added.
The organic layer was separated and the aqueous layer
extracted with EtOAc (2 · 50 mL). The combined organic
layers were washed with water, brine, dried (Na2SO4) and
concentrated. The residue was purified by flash column
chromatography on silica gel using hexane/EtOAc (7:3)
4.2. (2E)-4-Phenylbut-2-ene-1-ol 6
To a stirred solution of (2E)-ethyl-4-phenylbut-2-enoate 5
(3.2 g, 16.82 mmol) in dry CH2Cl2 (50 mL) at 0 ꢁC under
argon was added DIBAL-H (37 mL, 1.0 M in CH2Cl2,
37.0 mmol, 2.2 equiv) and the mixture stirred for 2 h. It
was warmed to room temperature and stirred for 30 min.
The mixture was quenched at 0 ꢁC with 2 M HCl
(50 mL) and extracted with CH2Cl2 (3 · 50 mL). The com-
bined organic layers were washed with water, brine, dried
over Na2SO4 and concentrated. The residue was purified
by flash column chromatography on silica gel using
hexane/EtOAc (4:1) as eluent to give 6 (2.37 g, 95%) as a
colourless oil. IR (neat): m = 3358, 3084, 3061, 3027,
2903, 2867, 1668, 1602, 1493, 1452, 1431, 1332, 1304,
1222, 1197, 1093, 1073, 1000, 971, 914, 745, 699 cmꢁ1. H
1
NMR (300 MHz, CDCl3/TMS): d = 1.93 (s, 1H, OH),
3.37 (d, J = 6.5 Hz, 2H, 4-H), 4.08 (dd, J = 5.8, 1.2 Hz,
2H, 1-H), 5.62–5.72 (m, 1H, olefin-H), 5.77–5.88 (m, 1H,
olefin-H), 7.15–7.22 (m, 3H, Ph), 7.24–7.35 (m, 2H, Ph).
13C NMR (75 MHz, CDCl3/CHCl3): d = 38.57, 63.32,
126.07, 128.40 (2C), 128.50 (2C), 130.38, 131.36, 140.01.
MS (EI), m/z (%): 148 [M+] (55.5), 130 [M+ꢁ18] (71.6),
117 (100), 115 (56.8), 92 (64.4), 91 (80.7), 78 (12.6), 57
(23.6). HRMS: [M] calcd for C10H12O, 148.0888; found,
148.0893.
as eluent to give 3 (1.114 g, 79%) as a colourless oil.
20
½aꢀD ¼ þ6:42 (c 1.8, CHCl3) [lit.9 +6.29 (c 1.080, CHCl3)].
IR (CHCl3): m = 3419, 3061, 3028, 3000, 2924, 1603,
1495, 1453, 1424, 1392, 1302, 1257, 1106, 1080, 1047,
990, 925, 886, 847, 746, 701, 645 cmꢁ1
.
1H NMR
(300 MHz, CDCl3/TMS): d = 2.55 (dd, J = 5.0, 3.0 Hz,
1H, 4-H), 2.71 (dd, J = 5.0, 4.2 Hz, 1H, 40-H), 2.82–2.97
(m, 2H, 1-H), 2.98–3.02 (m, 1H, 2-H), 3.60–3.69 (m, 1H,
3-H), 7.20–7.24 (m, 3H, Ph), 7.26–7.32 (m, 2H, Ph). 13C
NMR (75 MHz, CDCl3/CHCl3): d = 40.72, 44.98, 54.69,
72.40, 126.43, 128.35 (2C), 129.23 (2C), 137.17. MS (EI),
m/z (%): 164 [M+] (3.5), 146 (16), 133 (20.3), 118 (11.9),
103 (11.8), 92 (100), 91 (96.3), 77 (7.1), 65 (11.8), 45 (5.6).
Anal. Calcd for C10H12O2 (164.2): C 73.15; H, 7.36. Found:
C 73.28; H 7.10. HRMS: [M] calcd for C10H12O2, 164.0837;
found, 164.0841. The ee was determined by converting
compound 3 into the corresponding (S)-Mosher’s ester by
reaction with (R)-(ꢁ)-a-methoxy-a-(trifluoromethyl)phenyl
acetyl chloride (CH2Cl2/DMAP, Et3N, 0 ꢁC, 4 h, 88%
yield). The enantiomeric purity of compound 3 was esti-
mated to be 95%.
4.3. (2E)-1-Bromo-4-phenylbut-2-ene 4
To a stirred solution of 6 (1.4 g, 9.45 mmol) in dry CH2Cl2
(60 mL) under argon at ꢁ15 ꢁC was added PPh3 (2.97 g,
11.34 mmol, 1.2 equiv) followed by NBS (2.02 g,
11.34 mmol, 1.2 equiv) and the mixture stirred for
30 min. It was then warmed to room temperature and
stirred for 45 min, after which it was poured into water
(50 mL) and the layers were separated. The aqueous layer
was extracted with CH2Cl2 (2 · 50 mL). The combined
organic layers were washed with water, brine, dried over
Na2SO4 and concentrated. The residue was purified by
flash column chromatography on silica gel using hexane/
EtOAc (19:1) as eluent to give 4 (1.9 g, 95%) as colourless
oil. IR (neat): m = 3083, 3061, 3028, 2962, 2902, 2836, 1659,
1602, 1494, 1452, 1432, 1328, 1263, 1205, 1135, 1074, 1029,
967, 926, 746, 699 cmꢁ1. 1H NMR (300 MHz, CDCl3/TMS):
d = 3.41 (d, J = 6.6 Hz, 2H, 4-H), 3.97 (dd, J = 7.3, 0.9 Hz,
2H, 1-H), 5.78 (ddt, J = 15.4, 7.6, 1.4 Hz, 1H, olefin-H),
5.87–5.98 (m, 1H, olefin-H), 7.14–7.24 (m, 3H, Ph), 7.27–
7.34 (m, 2H, Ph). 13C NMR (75 MHz, CDCl3/CHCl3):
d = 32.87, 38.30, 126.23, 127.53, 128.45 (2C), 128.48 (2C),
134.67, 139.21. MS (EI), m/z (%): 212 [M+, 81Br] (5.5),
210 [M+, 79Br] (5.6), 132 (12.3), 131 (100), 116 (10.4), 91
(52.7), 77 (6.7), 65 (6.8), 51 (6.2). HRMS: [M] calcd for
C10H11Br, 210.0044; found, 210.0051.
4.5. (2S)-1,2-Epoxy-4-phenylbutan-3-one 8
To a solution of 3 (1 g, 6.09 mmol) in acetone (50 mL) at
room temperature was added Jones reagent (13 mL,
5.83 g of CrO3 in 5.2 mL H2SO4 and 22.5 mL of H2O)
and the solution stirred for 30 min. The mixture was
quenched with iso-propanol (2 mL) and extracted with
CH2Cl2 (3 · 50 mL). The combined organic layers were
washed with water, dried over Na2SO4 and concentrated.
The residue was purified by flash column chromatography
on silica gel using hexane/EtOAc (9:1) as eluent to give 8
20
(0.82 g, 83%) as a colourless oil. ½aꢀD ¼ ꢁ36:4 (c 1.5,
CHCl3) [lit.2b ꢁ36.0 (c 1.14, CHCl3)]. IR (neat): m = 3064,
3031, 3005, 2923, 2854, 1720, 1621, 1603, 1584, 1497,
1454, 1399, 1369, 1318, 1271, 1246, 1178, 1127, 1111,
1
1071, 1029, 962, 867, 732, 714, 700, 604 cmꢁ1. H NMR

18
R. A. Fernandes / Tetrahedron: Asymmetry 19 (2008) 15–18
(300 MHz, CDCl3/TMS): d = 2.86 (dd, J = 5.9, 2.6 Hz,
1H, 1-H), 2.98 (dd, J = 5.6, 4.7 Hz, 1H, 10-H), 3.49 (dd,
J = 4.5, 2.4 Hz, 1H, 2-H), 3.65 (d, J = 15.3 Hz, 1H, 4-H),
3.75 (d, J = 15.3 Hz, 1H, 40-H), 7.19–7.23 (m, 2H, Ph),
7.25–7.36 (m, 3H, Ph). 13C NMR (75 MHz, CDCl3/
CHCl3): d = 43.64, 46.06, 53.07, 127.04, 128.31, 128.57,
129.42, 130.0, 133.51, 204.42. MS (EI), m/z (%): 162 [M+]
(13.5), 134 (4.6), 118 (24.7), 105 (13.8), 92 (14.1), 91
(100), 77 (7.5), 65 (11.9), 51 (5.6), 43 (5.5). Anal. Calcd
for C10H10O2 (162.2): C 74.05; H, 6.21. Found: C 74.18;
H 6.11. HRMS: [M] calcd for C10H10O2, 162.0681; found,
162.0687.
(2 · 20 mL). The combined organic layers were washed
with brine, dried over Na2SO4 and concentrated. The resi-
due was purified by flash column chromatography on silica
gel using CHCl3/MeOH (40:1) as eluent to give 2 (0.106 g,
62%) as brown oil. Analytical sample was obtained by pre-
20
parative TLC using CHCl3/MeOH (30:1). ½aꢀD ¼ þ30:7 (c
0.15, CHCl3).
Acknowledgement
´
Financial support from Instituto de Quımica, UNAM is
gratefully acknowledged.
4.6. (S)-3-Hydroxy-4-(1H-indol-3-yl)-1-phenylbutan-2-one,
(+)-kurasoin B 2 employing CH3NO2/CH2Cl2 and SnCl4
References
To a stirred solution of indole (0.218 g, 1.86 mmol,
1.5 equiv) in CH2Cl2 (6 mL) under argon at ꢁ5 ꢁC was
added SnCl4 (0.390 g, 0.18 mL, 1.49 mmol, 1.2 equiv) and
stirred for 5 min. A solution of compound 8 (0.2 g,
1.24 mmol) in CH3NO2 (4.5 mL) was added and the mix-
ture stirred for 25 min. It was then quenched with ice-water
and extracted with EtOAc (2 · 40 mL). The combined
organic layers were washed with brine, dried over Na2SO4
and concentrated. The residue was purified by flash column
chromatography on silica gel using CHCl3/MeOH (40:1) as
eluent to give 2 (0.168 g, 49%) as a brown oil. An analytical
1. Uchida, R.; Shiomi, K.; Inokoshi, J.; Masuma, R.; Kawa-
kubo, T.; Tanaka, H.; Iwai, Y.; Omura, S. J. Antibiot. 1996,
49, 932.
2. Short communication: (a) Sunazuka, T.; Hirose, T.; Zhi-
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Antibiot. 1997, 50, 453; Full paper (b) Hirose, T.; Sunazuka,
T.; Zhi-Ming, T.; Handa, M.; Uchida, R.; Shiomi, K.;
Harigaya, Y.; Omura, S. Heterocycles 2000, 53, 777.
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(b) Kohl, N. E.; Omer, C. A.; Conner, M. W.; Anthony, N.
J.; Davide, J. P. Nat. Med. 1995, 1, 792.
4. Uchida, R.; Shiomi, K.; Sunazuka, T.; Inokoshi, J.; Nishiz-
awa, A.; Hirose, T.; Tanaka, H.; Iwai, Y.; Omura, S. J.
Antibiot. 1996, 49, 886.
5. Tsuchiya, S.; Sunazuka, T.; Shirahata, T.; Hirose, T.; Kaji,
E.; Omura, S. Heterocycles 2007, 72, 91.
6. Reviews: (a) Lohray, B. B. Tetrahedron: Asymmetry 1992, 3,
1317; (b) Johnson, R. A.; Sharpless, K. B. In Asymmetric
Catalysis in Organic Synthesis; Ojima, I., Ed.; VCH: New
York, 1993; p 227; (c) Kolb, H. C.; VanNieuwenhze, M. S.;
Sharpless, K. B. Chem. Rev. 1994, 94, 2483; (d) Bolm, C.;
Hildebrand, J. P.; Muniz, K. In Catalytic Asymmetric
Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-VCH: New York,
2000; p 399; (e) Fernandes, R. A.; Kumar, P. Tetrahedron
2002, 58, 6685; (f) Kumar, P.; Naidu, S. V. J. Org. Chem.
2005, 70, 4209.
sample was obtained by preparative TLC using CHCl3/
20
MeOH (30:1). ½aꢀD ¼ þ30:6 (c 0.2, CHCl3) [lit.2b +31 (c
0.33, CHCl3)]. IR (neat): m = 3400, 3033, 3038, 2928,
2855, 1710, 1614, 1601, 1454, 1319, 1328, 1277, 1078,
1039, 912, 748, 735, 700 cmꢁ1 1H NMR (300 MHz,
.
CDCl3/TMS): d = 3.19 (dd, J = 14.3, 7.2 Hz, 1H, 4-H),
3.35 (dd, J = 14.3, 4.7 Hz, 1H, 40-H), 3.78 (d,
J = 16.0 Hz, 1H, 1-H), 3.82 (d, J = 16.0 Hz, 1H, 10-H),
4.62 (m, 1H, 3-H), 7.19–7.23 (m, 8H, Ph, indolyl), 7.41
(d, J = 7.5 Hz, 1H, indolyl), 7.62 (d, J = 7.5 Hz, 1H, indo-
lyl). 13C NMR (75 MHz, CDCl3/CHCl3): d = 31.26, 46.16,
77.87, 111.12, 112.41, 119.63, 119.91, 122.45, 124.77,
127.65, 127.78, 129.01, 129.41 (2C), 130.84, 135.43,
138.11, 212.71. MS (EI), m/z (%): 279 [M+] (3.5), 261
(14.6), 160 (11.2), 149 (12.7), 130 (12.2), 119 (4.1), 91
(100), 77 (5.5), 65 (3.9), 51 (15.6), 43 (10.5). HRMS: [M]
calcd for C18H17NO2, 279.1260; found, 279.1268.
7. Kondekar, N. B.; Kandula, S. R. V.; Kumar, P. Tetrahedron
Lett. 2004, 45, 5477.
8. For a similar hydroxyl to bromide conversion with NBS and
Ph3P see: Roethle, P. A.; Hernandez, P. T.; Trauner, D. Org.
Lett. 2006, 8, 5901.
4.7. (S)-3-Hydroxy-4-(1H-indol-3-yl)-1-phenylbutan-2-one,
(+)-kurasoin B 2 employing Yb(OTf)3
9. Awano, K.; Yanai, T.; Watanabe, I.; Takagi, Y.; Kitahara,
T.; Mori, K. Biosci., Biotech., Biochem. 1995, 59, 1251.
10. The ee was determined by converting compound 3 into the
corresponding (S)-Mosher’s ester by reaction with (R)-(ꢁ)-a-
methoxy-a-(trifluoromethyl)phenyl acetyl chloride (CH2Cl2/
DMAP, Et3N, 0 ꢁC, 4 h, 88% yield). The enantiomeric purity
of compound 3 was estimated to be 95%.
To a stirred solution of indole (0.109 g, 0.93 mmol,
1.5 equiv) in 1,2-dichloroethane (3 mL) under argon was
added Yb(OTf)3 (77 mg, 0.124 mmol, 0.2 equiv) and stirred
for 5 min. A solution of compound 8 (0.1 g, 0.62 mmol) in
1,2-dichloroethane (1 mL) was added and the mixture stir-
red at 50 ꢁC for 4 h. It was then cooled to room tempera-
ture, quenched with ice-water and extracted with EtOAc
11. Ottoni, O.; Neder, A. de V. F.; Dias, A. K. B.; Cruz, R. P. A.;
Aquino, L. B. Org. Lett. 2001, 3, 1005.