Ruthenium-catalyzed enantioselective [3+3] cycloaddition of propargylic alcohols with 2-naphthols

Article abstract of DOI:10.1021/om100097k

Ruthenium-catalyzed enantioselective [3+3] cycloaddition of propargylic alcohols with 2-naphthols affords the corresponding cycloaddition products in moderate to good yields with a high enantioselectivity (up to 99% ee). This cycloaddition proceeds via stepwise reactions of propargylation and intramolecular cyclization, where ruthenium-allenylidene and -vinylidene complexes work as reactive intermediates, respectively.

Full text of DOI:10.1021/om100097k

2126 Organometallics 2010, 29, 2126–2131
DOI: 10.1021/om100097k
Ruthenium-Catalyzed Enantioselective [3þ3] Cycloaddition
of Propargylic Alcohols with 2-Naphthols
Keiichiro Kanao, Yoshihiro Miyake, and Yoshiaki Nishibayashi*
Institute of Engineering Innovation, School of Engineering, The University of Tokyo, Yayoi,
Bunkyo-ku, Tokyo 113-8656, Japan
Received February 8, 2010
Ruthenium-catalyzed enantioselective [3þ3] cycloaddition of propargylic alcohols with 2-naph-
thols affords the corresponding cycloaddition products in moderate to good yields with a high
enantioselectivity (up to 99% ee). This cycloaddition proceeds via stepwise reactions of propargyla-
tion and intramolecular cyclization, where ruthenium-allenylidene and -vinylidene complexes work
as reactive intermediates, respectively.
Introduction
naphthopyran derivatives are limited only to two typical
examples.3
Naphthopyran derivatives represent a structural motif in
a number of biologically active compounds such as anti-
coagulant, spasmolytic, diuretic, anticancer, and antiana-
phylactic agents.1 Therefore, the synthesis of naphthopyran
derivatives has attracted great attention. Several methods
have been successfully developed for this purpose.2 How-
ever, asymmetric reactions for the preparation of chiral
We have previously reported the ruthenium-catalyzed
[3þ3] cycloaddition of propargylic alcohols with 2-naph-
thols via ruthenium-allenylidene4,5 complexes as key inter-
mediates to afford the corresponding naphthopyran deriva-
tives in high yields with complete selectivity.6 In this reaction
system, both of the electrophilic R-carbon and γ-carbon
atoms in the allenylidene ligands4 are subjected to attack
by nucleophiles, as shown in Scheme 1. This catalytic reac-
tion provides a simple and efficient one-pot synthetic method
for a new type of skeleton of naphthopyrans.
As one of our extensive works, we disclosed the ruthe-
nium-catalyzed enantioselective propargylic alkylation of
propargylic alcohols with acetone to afford the correspond-
ing propargylic alkylated products with a high enantioselec-
tivity.7 Similarly, the ruthenium-catalyzed enantioselective
propargylation of aromatic compounds with propargylic
alcohols was also achieved as a novel type of asymmetric
Friedel-Crafts alkylation of aromatic compounds.8 In both
cases, chiral ruthenium-allenylidene complexes worked as
key reactive intermediates. These research backgrounds
prompted us to investigate the enantioselective version of
ruthenium-catalyzed [3þ3] cycloaddition of propargylic
alcohols with 2-naphthols because this cycloaddition also
proceeded via ruthenium-allenylidene complexes as com-
mon intermediates. The reaction may provide a novel useful
method to obtain optically active naphthopyran derivatives.
Herein, we describe the result of the ruthenium-catalyzed
enantioselective [3þ3] cycloaddition of propargylic alcohols
with 2-naphthols.
*To whom correspondence should be addressed. E-mail: ynishiba@
sogo.t.u-tokyo.ac.jp.
(1) (a) Bonsignore, L.; Loy, G.; Secci, D.; Calignano, A. Eur. J. Med.
Chem. 1993, 28, 517. (b) Claessens, S.; Kesteleyn, B.; Van, T. N.; Kimpe,
N. D. Tetrahedron 2006, 62, 8419. (c) Karnik, A. V.; Kulkarni, A. M.;
Malviya, N. J.; Mourya, B. R.; Jadhav, B. L. Eur. J. Med. Chem. 2008, 43,
2615.
(2) (a) Ballini, R.; Bosica, G.; Conforti, M. L.; Maggi, R.; Mazzacani,
A.; Righi, P.; Sartori, G. Tetrahedron 2001, 57, 1395. (b) Jin, T. S.; Zhang,
J. S.; Liu, L. B.; Wang, A. Q.; Li, T. S. Synth. Commun. 2006, 36, 2009.
(c) Zhang, A.-Q.; Zhang, M.; Chen, H.-H.; Chen, J.; Chen, H.-Y. Synth.
Commun. 2007, 37, 231.
(3) (a) Wang, X.-S.; Yang, G.-S.; Zhao, G. Tetrahedron: Asymmetry
2008, 19, 709. (b) Wang, X.-S.; Yang, G.-S.; Zhao, G. Tetrahedron:
Asymmetry 2008, 19, 2699.
(4) For recent reviews of transition metal-allenylidene complexes,
see: (a) Bruneau, C.; Dixneuf, P. H. Angew. Chem., Int. Ed. 2006, 45,
2176. (b) Metal Vinylidenes and Allenylidenes in Catalysis: From Reac-
tivity to Applications in Synthesis; Bruneau, C., Dixneuf, P. H., Eds.;
Wiley-VCH: Weinheim, 2008. (c) Cadierno, V.; Gimeno, J. Chem. Rev.
2009, 109, 3512.
(5) (a) Nishibayashi, Y.; Milton, M. D.; Inada, Y.; Yoshikawa, M.;
Wakiji, I.; Hidai, M.; Uemura, S. Chem.;Eur. J. 2005, 11, 1433.
(b) Ammal, S. C.; Yoshikai, N.; Inada, Y.; Nishibayashi, Y.; Nakamura, E.
J. Am. Chem. Soc. 2005, 127, 9428. (c) Onodera, G.; Nishibayashi, Y.;
Uemura, S. Organometallics 2006, 25, 35. (d) Yamauchi, Y.; Onodera, G.;
Sakata, K.; Yuki, M.; Miyake, Y.; Uemura, S.; Nishibayashi, Y. J. Am. Chem.
Soc. 2007, 129, 5175. (e) Yamauchi, Y.; Yuki, M.; Tanabe, Y.; Miyake, Y.;
Inada, Y.; Uemura, S.; Nishibayashi, Y. J. Am. Chem. Soc. 2008, 130, 2908.
(f) Daini, M.; Yoshikawa, M.; Inada, Y.; Uemura, S.; Kanao, K.; Miyake, Y.;
Nishibayashi, Y. Organometallics 2008, 27, 2046. (g) Yada, Y.; Miyake, Y.;
Nishibayashi, Y. Organometallics 2008, 27, 3614. (h) Miyake, Y.; Endo, M.;
Yuki, M.; Tanabe, Y.; Nishibayashi, Y. Organometallics 2008, 27, 6039.
(i) Yamauchi, Y.; Miyake, Y.; Nishibayashi, Y. Organometallics 2009, 28,
48. (j) Tanabe, Y.; Kanao, K.; Miyake, Y.; Nishibayashi, Y. Organometallics
2009, 28, 1138. (k) Sakata, K.; Miyake, Y.; Nishibayashi, Y. Chem. Asian J.
2009, 4, 81. (l) Fukamizu, K.; Miyake, Y.; Nishibayashi, Y. Angew. Chem.,
Int. Ed. 2009, 48, 2534. (m) Nishibayashi, Y.; Uemura, S. Curr. Org. Chem.
2006, 10, 135, and references therein.
(6) Nishibayashi, Y.; Inada, Y.; Hidai, M.; Uemura, S. J. Am. Chem.
Soc. 2002, 124, 7900.
(7) (a) Nishibayashi, Y.; Onodera, G.; Inada, Y.; Hidai, M.; Uemura,
S. Organometallics 2003, 22, 873. (b) Inada, Y.; Nishibayashi, Y.; Uemura,
S. Angew. Chem., Int. Ed. 2005, 44, 7715.
(8) (a) Matsuzawa, H.; Miyake, Y.; Nishibayashi, Y. Angew. Chem.,
Int. Ed. 2007, 46, 6488. (b) Matsuzawa, H.; Kanao, K.; Miyake, Y.;
Nishibayashi, Y. Org. Lett. 2007, 9, 5561. (c) Kanao, K.; Matsuzawa, H.;
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r
pubs.acs.org/Organometallics
Published on Web 03/19/2010
2010 American Chemical Society

Article
Organometallics, Vol. 29, No. 9, 2010 2127
Scheme 1
Table 1. Ruthenium-Catalyzed Enantioselective [3þ3] Cycload-
dition of Propargylic Alcohols (2) with 2-Naphtholsa
propargylic
alcohol
run
2-naphthol
yieldb (%)
eec (%)
Scheme 2
1
2
3
4
5
6
7
8
9
10
2a, Ar = Ph
X = H
X = H
X = H
X = H
X = H
X = H
X = H
X = Br
X = Br
X = Br
3a, 46
3b, 57
3c, 76
3d, 49
3e, 32
3f, 43
3g, 42
3h, 28
3i, 32
3j, 53
72
61
47
64
69
96
81
83
69
99
2b, Ar = p-FC6H4
2c, Ar = p-ClC6H4
2d, Ar = p-MeC6H4
2e, Ar = p-PhC6H4
2f, Ar = 3,5-Ph2C6H3
2g, Ar = 2-naphthyl
2a, Ar = Ph
2b, Ar = p-PhC6H4
2f, Ar = 3,5-Ph2C6H3
a All reactions of 2 (0.20 mmol) with 2-naphthol (1.0 mmol) were
carried out in the presence of ruthenium complex la and NH4BF4 (0.020
mmol) in ClCH2CH2C1 (5 mL) at 40 °C for 48 h. b Isolated yield of 3.
c Determined by HPLC.
Results and Discussion
Treatment of 1-phenyl-2-propyn-1-ol (2a) with 2-naph-
thol in 1,2-dichloroethane in the presence of 5 mol % of
optically active thiolate-bridged diruthenium complex9 (1a)
and NH4BF4 at 60 °C for 14 h afforded 1-phenyl-1H-
naphtho[2,1-b]pyran (3a) in 21% isolated yield with 37%
ee (Scheme 2). The reaction at a slightly lower reaction
temperature such as 40 °C proceeded similarly to afford 3a
with a higher enantioselectivity (72% ee), although a pro-
longed reaction time was necessary. Use of another optically
active diruthenium complex (1b), which worked as an effec-
tive catalyst for the enantioselective propargylation of aro-
matic compounds,8 did not give the expected cycloaddition
product 3a.10
Figure 1. ORTEP drawing of (R)-3h.
Reactions of various propargylic alcohols with 2-naph-
thols were carried out in the presence of 5 mol % of 1a as a
catalyst. Typical results are shown in Table 1. Introduction
of a fluoro, chloro, methyl, or phenyl group to the benzene
ring of propargylic alcohol did not affect much the enantios-
electivity of the cycloaddition product (Table 1, runs 2-5).
Interestingly, the introduction of two phenyl groups at the
3- and 5-positions of the benzene ring of propargylic alcohol
dramatically improved the enantioselectivity (Table 1, run
6). On the other hand, a slightly higher enantioselectivity was
achieved when 1-(2-naphthyl)-2-propyn-1-ol was used as
a substrate (Table 1, run 7). In addition to 2-naphthol,
6-bromo-2-naphthol was also available (Table 1, runs 8-10).
After one recrystallization of the cycloaddition product 3h
(83% ee), enantiomerically pure 3h was obtained and its
absolute configuration (R) was determined by X-ray analy-
sis. An ORTEP drawing of (R)-3h is shown in Figure 1. The
absolute configuration of (R)-3j was also determined by
X-ray analysis from single crystals of enantiomerically pure
3j. An ORTEP drawing of (R)-3j is shown in Figure 2.
Figure 2. ORTEP drawing of (R)-3j.
As described in Table 1, we have achieved the high
enantioselectivity of the cycloaddition products in the
reactions of 1-(3,5-diphenyl)phenyl-2-propyn-1-ol (2f) with
2-naphthols (Table 1, runs 6 and 10). However, unfortu-
nately, the yields of cycloaddition products were moderate in
both cases, because of the formation of the propargylated
naphthols as side-products. In fact, after the detailed inves-
tigation of the cycloaddition of 2f with 6-bromo-2-naphthol,
the propargylated naphthol (4j) was isolated in 26% isolated
yield with 87% ee (S) (Scheme 3). The absolute configura-
tion at the benzylic position of (S)-4j is opposite that of
(R)-3j. Separately, it was disclosed that (S)-4j (99% ee)
was converted to (S)-3j (99% ee) in 52% isolated yield by
heating at 60 °C for 5 h in the presence of 5 mol % of
(9) Fukamizu, K.; Miyake, Y.; Nishibayashi, Y. J. Am. Chem. Soc.
2008, 130, 10498.
(10) No formation of the cycloaddition product 3a was observed, but
instead the corresponding propargylated naphthol was obtained in 39%
yield with 51% ee (R). This result indicates that propargylation of
2-naththol proceeded enantioselectively when 1b was used as a catalyst.

2128 Organometallics, Vol. 29, No. 9, 2010
Kanao et al.
Scheme 3
Scheme 6
this is the first successful example of the kinetic resolution,
where ruthenium-vinylidene complexes work as key and
reactive intermediates.14
Scheme 4
On the basis of the experimental result described in this
paper, we propose a reaction pathway for the enantioselec-
tive cycloaddition of propargylic alcohols with 2-naphthols
as shown in Scheme 7. At first, the propargylation of
2-naphthol with propargylic alcohol occurs to give the
corresponding (R)-propargylated naphthol 4 with a low to
moderate enantioselectivity.15 Then, the cyclization of (R)-4
proceeds enantioselectively to afford (R)-3 with a high
enantioselectivity, and unreacted (S)-4 is recovered with a
high enantioselectivity. Thus, the enantioselectivity of cy-
cloaddition product 3 depends on the efficiency of the kinetic
resolution of 4. The process from 4 to 3 may involve the
ruthenium-vinylidene complex (A) and the corresponding
alkenyl complex (B) as shown in Scheme 8. Here, the
cyclization of (R)-4j giving (R)-3j proceeds more smoothly
than that of (S)-4j giving (S)-3j via an intramolecular nu-
cleophilic attack of the oxygen atom of the hydroxyl group of
2-naphthol to the R-carbon of the vinylidene complex be-
cause the steric repulsion between the two phenyl groups in
the substrate and chiral ligand may inhibit the formation of
(S)-3j, as shown in Scheme 9.
In summary, we have found that the ruthenium-catalyzed
enantioselective [3þ3] cycloaddition of propargylic alcohols
with 2-naphthols afforded the corresponding naphthopyran
derivatives in moderate to good yields with a high enantios-
electivity (up to 99% ee). This cycloaddition is considered to
proceed via stepwise reactions of propargylation and intra-
molecular cyclization, where ruthenium-allenylidene and -
vinylidene complexes work as key reactive intermediates,
respectively. The reactions described in this article provide a
novel method for the preparation of chiral naphthopyrans.
Further work is currently in progress to broaden its synthetic
applicability to natural products and pharmaceuticals.
Scheme 5
[Cp*RuCl(μ2-SMe)]2 (Scheme 4). These results indicate that
the cycloaddition proceeds via an initial propargylation of
2-naphthol followed by the cyclization of produced pro-
pargylated naphthol 4,11 where the cyclization of 4 into the
corresponding cycloaddition product 3 takes place without
loss of optical purity at the propargylic position of 4.
As shown in the previous reports,12 the propargylation of
aromatic compounds with propargylic alcohols occurs via
ruthenium-allenylidene complexes as key intermediates
(Scheme 5). On the other hand, the cyclization of 4 into 3
may occur via ruthenium-vinylidene complexes as key inter-
mediates (Scheme 5). The route of the direct transformation
from 2 into 3 without the formation of 4 as reactive inter-
mediates (Scheme 5: dotted arrow step), however, cannot yet
be excluded in the present catalytic reactions.
Experimental Section
General Methods. 1H NMR (270 MHz) and 13C NMR (67.8
MHz) spectra were recorded on a JEOL Excalibur 270 spectro-
meter using CDCl3. Elemental analyses were performed at
Microanalytical Center of The University of Tokyo. Mass
spectra were measured on a JEOL JMS-700 mass spectrometer.
HPLC analyses were performed on a Hitachi L-7100 apparatus
equipped with a UV detector using 25 cm ꢀ 4.6 mm DAICEL
To get more information on the reaction pathway, we
investigated the transformation of racemic 4j to 3j in di-
chloroethane in the presence of 5 mol % of 1a at 40 °C for 48
h (Scheme 6). As a result, the cycloaddition product (R)-3j
(53% ee) in 55% yield was obtained together with recovered
4j (99% ee (S)) in 33% recovery. This result indicates that the
kinetic resolution occurred efficiently in the cyclization step
of 4 into 3. The efficiency of the kinetic resolution, the kf/ks
value, is estimated to be 18.13 To the best of our knowledge,
(14) (a) The first example of an asymmetric reaction via a chiral ruthe-
nium-vinylidene complex was reported by our group; see: Nishibayashi, Y.;
Takei, I.; Hidai, M. Organometallics 1997, 16, 3091. (b) Trost, B. M.; Vidal, B.;
Thommen, M. Chem.;Eur. J. 1999, 5, 1055.
(11) Nishibayashi, Y.; Yoshikawa, M.; Inada, Y.; Hidai, M.;
Uemura, S. J. Org. Chem. 2004, 69, 3408.
(12) (a) Nishibayashi, Y.; Inada, Y.; Hidai, M.; Uemura, S. J. Am.
Chem. Soc. 2002, 124, 11846. (b) Inada, Y.; Yoshikawa, M.; Milton, M. D.;
Nishibayashi, Y.; Uemura, S. Eur. J. Org. Chem. 2006, 881.
(13) (a) Noyori, R.; Tokunaga, M.; Kitamura, M. Bull. Chem. Soc.
Jpn. 1995, 68, 36. (b) Keith, J. M.; Larrow, J. F.; Jacobsen, E. N. Adv. Synth.
Catal. 2001, 343, 5. (c) Vedejs, E.; Jure, M. Angew. Chem., Int. Ed. 2005,
44, 3974.
(15) We previously observed no kinetic resolution in the ruthenium-
catalyzed enantioselective propargylation of aromatic compounds.8a On
the basis of this result, we consider that the chirality at the propargylic
position of the propargylic alcohols did not affect the reactivity of
propargylic alcohols in this ruthenium-catalyzed enantioselective cy-
cloaddition because the first step of the cycloaddition reaction is the
propargylation of aromatic compounds.

Article
Organometallics, Vol. 29, No. 9, 2010 2129
Scheme 7
(144.1 mg, 1.0 mmol), the reaction flask was kept at 40 °C for 48
h. The solvent was concentrated under reduced pressure, and
then the residue was purified by column chromatography on
silica gel (n-hexane) to give 3a6 (23.5 mg, 0.091 mmol, 46%
isolated yield). The optical purity of 3a was determined by
HPLC analysis; DAICEL Chiralcel OD, n-hexane/iPrOH,
98/2, flow rate = 0.5 mL/min, λ = 254 nm; retention time =
Scheme 8
12.0 min (minor) and 14.6 min (major), 72% ee. [R]25 þ238
D
(c 1.18, CHCl3).
Spectroscopic data and isolated yields of other 3 are as
follows.
Scheme 9
3b:6 57% isolated yield. The optical purity of 3b was deter-
mined by HPLC analysis; DAICEL Chiralcel OD, n-hexane/i-
PrOH, 99:1, flow rate = 0.5 mL/min, λ = 254 nm, retention
time = 13.5 min (minor) and 15.5 min (major), 61% ee. [R]25
D
þ200 (c 1.59, CHCl3).
3c: 76% isolated yield; yellow oil. 1H NMR: δ 5.15-5.21 (m,
2H), 6.62 (d, J = 5.4 Hz, 1H), 7.11-7.23 (m, 5H), 7.30-7.35 (m,
2H), 7.56-7.60 (m, 1H), 7.71-7.77 (m, 2H). 13C NMR: δ 37.2,
106.3, 113.8, 117.9, 123.3, 124.2, 126.6, 128.4, 128.8, 128.9,
129.1, 131.0, 131.7, 132.1, 138.5, 145.0, 149.2. HRMS (EI):
calcd for C19H13ClO [M] 292.0655, found 292.0652. The optical
purity of 3c was determined by HPLC analysis; DAICEL
Chiralcel OD, n-hexane/iPrOH, 99/1, flow rate = 0.5 mL/min,
λ = 254 nm, retention time = 13.7 min (minor) and 15.8 min
(major), 47% ee. [R]25D þ156 (c 2.24, CHCl3).
1
3d: 49% isolated yield; yellow oil. H NMR: δ 2.25 (s, 3H),
5.14 (d, J = 4.8 Hz, 1H), 5.22 (dd, J = 4.8 and 5.9 Hz, 1H), 6.60
(d, J = 5.9 Hz, 1H), 7.02-7.11 (m, 4H), 7.20 (d, J = 8.9 Hz, 1H),
7.28-7.32 (m, 2H), 7.65-7.76 (m, 3H). 13C NMR: δ 21.0, 37.3,
107.0, 114.6, 117.9, 123.6, 124.0, 126.4, 127.4, 128.3, 128.7,
129.5, 131.0, 131.9, 135.9, 138.1, 143.7, 149.2. HRMS (EI):
calcd for C20H16O [M] 272.1201, found 272.1205. The optical
purity of 3d was determined by HPLC analysis; DAICEL
Chiralcel OD, n-hexane/iPrOH, 99/1, flow rate = 0.5 mL/min,
λ = 254 nm, retention time = 12.0 min (minor) and 13.5 min
(major), 64% ee. [R]25D þ203 (c 1.35, CHCl3).
Chiralcel OD, OZ-H columns. All reactions were carried out
under a dry nitrogen atmosphere. Solvents were dried by usual
methods and distilled before use. [Cp*RuCl(μ2-SR*)]2 (1a)9 and
5
[Cp*RuCl(μ2-SMe)]2 were prepared according to previously
3e: 32% isolated yield; brown solid; mp 149.5-149.7 °C. 1H
NMR: δ 5.23-5.30 (m, 2H), 6.65 (d, J = 5.8 Hz, 1H), 7.23-7.41
(m, 8H), 7.45-7.53 (m, 4H), 7.69-7.79 (m, 3H). 13C NMR: δ
37.5, 106.7, 114.3, 117.9, 123.6, 124.1, 126.5, 127.0, 127.1, 127.5,
127.9, 128.4, 128.7, 128.9, 131.0, 131.9, 138.4, 139.2, 140.8,
145.6, 149.2. HRMS (EI): calcd for C25H18O [M] 334.1358,
found 334.1354. The optical purity of 3e was determined by
HPLC analysis; DAICEL Chiralcel OD, n-hexane/iPrOH, 99/1,
flow rate = 0.5 mL/min, λ = 254 nm, retention time = 13.4 min
reported procedures. 1-Phenyl-2-propyn-1-ol (2a), 2-naphthol,
and 6-bromo-2-naphthol are commercially products. Prepara-
tion of propargylic alcohols (2b,16 2c,16 2d,16 2e,8 2f,8 2g16) was
carried out according to the literature methods.
Ruthenium-Catalyzed Enantioselective [3þ3] Cycloaddition of
Propargylic Alcohols with 2-Naphthols. A typical experimental
procedure for the reaction of 2a with 2-naphthol catalyzed by 1a
is describe below. In a 20 mL Schlenk flask were placed 1a
(11.5 mg, 0.010 mmol) and NH4BF4 (2.1 mg, 0.020 mmol) under
N2. Anhydrous 1,2-dichloroethane (5 mL) was added, and the
mixture was magnetically stirred at room temperature for 5 min.
After the addition of 2a (26.5 mg, 0.20 mmol) and 2-naphthol
(major) and 15.3 min (minor), 69% ee. [R]25 þ233 (c 1.09,
D
CHCl3).
3f: 43% isolated yield; pale yellow solid; mp 82.5-83.0 °C. 1H
NMR: δ 5.30-5.34 (m, 2H), 6.67 (d, J = 4.5 Hz, 1H), 7.21-7.43
(m, 11H), 7.52-7.59 (m, 5H), 7.71-7.79 (m, 3H). 13C NMR: δ
38.1, 106.8, 114.2, 118.0, 123.5, 124.1, 124.4, 125.5, 126.6, 127.3,
127.4, 128.4, 128.7, 129.0, 131.0, 131.9, 138.6, 141.0, 142.2,
147.7, 149.3. HRMS (EI): calcd for C31H22O [M] 410.1671,
(16) (a) Bagley, M. C.; Dale, J. W.; Ohnesorge, M.; Xiong, X.; Bower,
J. J. Comb. Chem. 2003, 5, 41. (b) Kumar, M. P.; Liu, R.-S. J. Org. Chem.
2006, 71, 4951.

2130 Organometallics, Vol. 29, No. 9, 2010
Kanao et al.
Table 2. Crystallographic Data for (R)-3h and (R)-3j
found 410.1685. The optical purity of 3f was determined by
HPLC analysis; DAICEL Chiralcel OD, n-hexane/iPrOH, 98/2,
flow rate = 0.5 mL/min, λ = 254 nm, retention time = 23.7 min
(R)-3h
(R)-3j
(major) and 35.4 min (minor), 96% ee. [R]25 þ152 (c 1.79,
D
chemical forumula
fw
cryst size
cryst color, habit
cryst syst
space group
C
337.22
19H13BrO
C31H21BrO
489.41
CHCl3).
0.45 ꢀ 0.10 ꢀ 0.07
colorless, needle
monoclinic
P21 (no. 4)
13.393(4)
5.7699(18)
20.266(6)
90
0.45 ꢀ 0.05 ꢀ 0.05
colorless, needle
orthorhombic
P212121 (no. 19)
6.1089(8)
13.4009(18)
27.796(3)
90
3g: 42% isolated yield; pale yellow solid; mp 124.0-124.8 °C.
1H NMR: δ 5.27 (dd, J = 4.6 and 5.9 Hz, 1H), 5.36 (d, J = 4.6
Hz, 1H), 6.65 (d, J = 5.9 Hz, 1H), 7.23-7.29 (m, 3H), 7.31-7.44
(m, 3H), 7.67-7.77 (m, 7H). 13C NMR: δ 38.1, 106.6, 114.2,
117.9, 123.6, 124.1, 125.5, 125.7, 126.0, 126.1, 126.5, 127.6,
127.7, 128.3, 128.7, 129.0, 131.0, 132.0, 132.2, 133.6, 138.4,
143.9, 149.3. HRMS (EI): calcd for C23H16O [M] 308.1201,
found 308.1207. The optical purity of 3g was determined by
HPLC analysis; DAICEL Chiralcel OD, n-hexane/iPrOH, 99/1,
flow rate = 0.5 mL/min, λ = 254 nm, retention time = 18.0 min
˚
a (A)
˚
b (A)
˚
c (A)
R (deg)
β (deg)
γ (deg)
107.784(5)
90
90
90
3
˚
V (A )
Z
1491.3(8)
4
1.502
680
27.597
2275.5(5)
4
1.428
1000
18.338
(minor) and 19.1 min (major), 81% ee. [R]25 þ339 (c 1.29,
D
Dcalcd (g cm-3
F(000)
)
CHCl3).
3h:6 28% isolated yield. The optical purity of 3h was deter-
mined by HPLC analysis; DAICEL Chiralcel OD, n-hexane/i-
PrOH, 98/2, flow rate = 0.5 mL/min, λ = 254 nm, retention
time = 10.7 min (minor) and 14.7 min (major), 83% ee.
[R]25D þ187 (c 0.98, CHCl3).
μ
calcd (cm-1
)
transmn factors range
no. measd reflns
no. unique reflns
no. refined params
R1a (I > 2σ(I))
wR2b (all data)
GOFc
0.445-0.824
14 465
6645
406
0.0537
0.232-0.912
18 121
5086
316
0.0634
3i: 32% isolated yield; orange solid; mp 142.2-142.6 °C. 1H
NMR: δ 5.18 (d, J = 4.8 Hz, 1H), 5.24-5.28 (m, 1H), 6.64 (d,
J = 5.9 Hz, 1H), 7.23-7.31 (m, 4H), 7.35-7.41 (m, 3H),
7.45-7.54 (m, 4H), 7.73-7.71 (m, 2H), 7.91 (d, J = 2.0 Hz,
1H). 13C NMR: δ 37.4, 106.6, 114.6, 118.0, 119.1, 125.4, 127.0,
127.2, 127.6, 127.9, 128.0, 128.7, 129.8, 130.3, 130.5, 132.2,
138.3, 139.5, 140.7, 145.2, 149.4. HRMS (EI): calcd for
C25H17BrO [M] 412.0463, found 412.0465. The optical purity
of 3i was determined by HPLC analysis; DAICEL Chiralcel
OD, n-hexane/iPrOH, 98/2, flow rate = 0.5 mL/min, λ = 254
nm, retention time = 13.5 min (major) and 16.4 min (minor),
69% ee. [R]25D þ203 (c 1.31, CHCl3).
0.1564
1.000
0.2271
1.000
Flack param
max./min. residual
0.000(15)
þ3.71/-3.99
0.05(2)
þ0.65/-0.66
-
3
peaks (e /A )
˚
aR1 = Σ Fo| - |Fc /Σ|Fo|. b wR2 = [Σ(w(Fo - Fc2)2)/Σw(Fo2)2]1/2
;
2
2
w = 4Fo2/[pFo þ qσ(Fo2)]; p = 0 (3h), 0.001 (3j); q = 0.76 (3h), 0.556
(3j). c GOF = [Σw(Fo2 - Fc2)2/(Nobs - Nparam)]1/2
.
(0.7 mg, 0.007 mmol) under N2. Anhydrous 1,2-dichloroethane
(5 mL) was added, and the mixture was magnetically stirred at
room temperature. After the addition of (S)-4j (33.7 mg, 0.069
mmol, 99% ee), the reaction flask was kept at 60 °C for 5 h. The
solvent was concentrated under reduced pressure, and then the
residue was purified by column chromatography on silica gel
(n-hexane) to give (S)-3j (18.7 mg, 0.036 mmol, 52% isolate
yield). The optical purity of (S)-3j was determined by HPLC
analysis; DAICEL Chiralcel OD, n-hexane/iPrOH, 98/2, flow
rate = 0.5 mL/min, λ = 254 nm, retention time = 16.1 min
(minor) and 26.7 min (major), 99% ee.
3j: 53% isolated yield; pale yellow solid; mp 89.8-90.2 °C. 1H
NMR: δ 5.24 (d, J = 4.8 Hz, 1H), 5.31 (dd, J = 4.8 and 5.9 Hz,
1H), 6.65 (d, J = 5.9 Hz, 1H), 7.23 (d, J = 9.1 Hz, 1H),
7.28-7.43 (m, 9H), 7.50-7.55 (m, 4H), 7.58-7.63 (m, 3H), 7.88
(d, J = 2.0 Hz, 1H). 13C NMR: δ 38.0, 106.7, 114.5, 118.0, 119.1,
124.6, 125.3, 125.4, 127.3, 127.5, 128.1, 128.7, 129.8, 130.3,
130.5, 132.2, 138.5, 140.9, 142.3, 147.3, 149.4. HRMS (EI):
calcd for C31H21BrO [M] 488.0776, found 488.0768. The optical
purity of 3j was determined by HPLC analysis; DAICEL
Chiralcel OD, n-hexane/iPrOH, 98/2, flow rate = 0.5 mL/min,
λ = 254 nm, retention time = 16.5 min (major) and 26.8 min
(minor), 99% ee. [R]25D þ239 (c 2.60, CHCl3).
X-ray Diffraction Studies of (R)-3h and (R)-3j. Colorless
needles of (R)-3h or (R)-3j suitable for X-ray analysis were
obtained in an enantiomerically pure form by further recrystal-
lization of 3h from ethanol or 3j from hot ethanol/dichloro-
methane (4:1). Diffraction data were collected at -100 °C on a
Rigaku RAXIS RAPID imaging plate area detector with gra-
Isolation of 4j. In a 20 mL Schlenk flask were placed 1a (11.7
mg, 0.010 mmol) and NH4BF4 (2.2 mg, 0.020 mmol) under N2.
Anhydrous 1,2-dichloroethane (5 mL) was added, and the
mixture was magnetically stirred at room temperature. After
the addition of 2f (56.9 mg, 0.20 mmol) and 6-bromo-2-naphthol
(223.1 mg, 1.0 mmol), the reaction flask was kept at 40 °C for
48 h. The solvent was concentrated under reduced pressure, and
then the residue was purified by column chromatography on
silica gel (n-hexane/ethyl acetate, 100/0 to 70/30) to give 4j as a
crude oil. Further purification of the crude oil by GPC (CHCl3)
gave 4j as a pale brown solid, mp 166.7-167.2 °C (25.5 mg, 0.052
mmol, 26% isolated yield). 1H NMR: δ 2.60 (d, J = 2.6 Hz, 1H),
6.07 (br, 1H), 6.15 (br, 1H), 7.08 (d, J = 8.9 Hz, 1H), 7.07-7.65
(m, 15H), 7.87-7.91 (m, 2H). 13C NMR: δ 32.9, 74.2, 83.1,
117.2, 117.6, 119.8, 124.8, 125.1, 125.2, 127.3, 127.5, 128.8,
129.1, 130.0, 130.6, 130.7, 130.9, 139.8, 140.8, 142.2, 151.9.
HRMS (EI): calcd for C31H21BrO [M] 488.0776, found
488.0779. The optical purity of 4j was determined by HPLC
analysis; DAICEL Chiralcel OZ-H, n-hexane/iPrOH, 98:2, flow
rate = 0.5 mL/min, λ = 254 nm, retention time = 23.8 min
˚
phite-monochromated Mo KR (λ = 0.71075 A) radiation.
Reflections were collected for the 2θ range of 5° to 55°. Intensity
data were corrected for numerical ((R)-3h) or empirical ((R)-3j)
absorptions and for Lorentz and polarization effects. A correc-
tion for secondary extinction was further applied to (R)-3j
(coefficient, 67(22)). The structure solution and refinements
were carried out by using the CrystalStructure package.17
The positions of non-hydrogen atoms were determined by
direct methods (SIR-97)18 and subsequent Fourier syntheses
2
(DIRDIFF-99)19 and were refined on Fo using all unique
(17) (a) CrystalStructure 3.80: Single Crystal Structure Analysis
Software; Rigaku Corp: Tokyo, Japan, and MSC: The Woodlands, TX,
pp 2000-2007. (b) Carruthers, J. R.; Rollett, J. S.; Betteridge, P. W.; Kinna,
D.; Pearce, L.; Larsen, A.; Gabe, E. CRYSTALS Issue 11; Chemical
Crystallography Laboratory: Oxford, UK, 1999.
(18) Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.;
Giacovazzo, C.; Guagliardi, A.; Moliterni, A. G. G.; Polidori, G.;
Spagna, R. J. Appl. Crystallogr. 1999, 32, 115.
(major) and 39.7 min (minor), 87% ee. [R]25 þ36.3 (c 1.28,
D
(19) Beurskens, P. T.; Beurskens, G.; de Gelder, R.; Garcıa-Granda,
CHCl3).
Cyclization of (S)-4j. In a 20 mL Schlenk flask were placed
[Cp*RuCl(μ2-SMe)]2 (2.2 mg, 0.0035 mmol) and NH4BF4
€
S.; Gould, R. O.; Israel, R.; Smits, J. M. M. The DIRDIF-99 Program
System; Crystallography Laboratory, University of Nijmegen: Nijmegen,
The Netherlands, 1999.

Article
Organometallics, Vol. 29, No. 9, 2010 2131
reflections by full-matrix least-squares with anisotropic thermal
parameters except for the C(6) atom in (R)-3j, which was refined
isotropically. All the hydrogen atoms were placed at the calcu-
Acknowledgment. This work was supported by Grants-
in-Aid for Scientific Research for Young Scientists (S)
(No. 19675002) and for Scientific Research on Priority
Areas (No. 18066003) from the Ministry of Education,
Culture, Sports, Science and Technology, Japan. Y.N.
thanks Ube Industries Ltd. K.K. acknowledges the Global
COE Program for Chemistry Innovation.
˚
lated positions [C-H distance of 0.95 A] with fixed isotropic
parameters. The crystal of (R)-3h contains two crystallographi-
cally independent structures whose absolute configurations were
the same (only one of the structures is shown in Figure 1).
Refinement of the Flack parameters of 3h (0.000(15)) and 3j
(0.05(2)) demonstrated that the absolute configurations of the
major isomers of 3h and 3j were both R, as shown in Figures 1
and 2. Details of crystal and data collection parameters are
summarized in Table 2.
Supporting Information Available: Crystallographic data for
(R)-3h and (R)-3j are available in CIF format. This material is
available free of charge via the Internet at http://pubs.acs.org.