Catalytic enantioselective synthesis of chiral phthalides by efficient reductive cyclization of 2-acylarylcarboxylates under aqueous transfer hydrogenation conditions

Article abstract of DOI:10.1021/ol901674k

A new diamine ligand for asymmetric transfer hydrogenation (ATH) was discovered. The reductive cyclization of 2-acylarylcarboxylates was found to proceed highly stereoselective by the new Ru complex-catalyzed ATH and subsequent In situ lactonization under aqueous conditions. It enables efficient access to a wide variety of 3-substituted phthalides In enantiomerically pure form.

Full text of DOI:10.1021/ol901674k

ORGANIC
LETTERS
2009
Vol. 11, No. 20
4712-4715
Catalytic Enantioselective Synthesis of
Chiral Phthalides by Efficient Reductive
Cyclization of 2-Acylarylcarboxylates
under Aqueous Transfer Hydrogenation
Conditions
Bo Zhang,† Ming-Hua Xu,*,†,‡ and Guo-Qiang Lin*,†
Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai
200032, China, and Shanghai Institute of Materia Medica, Chinese Academy of
Sciences, 555 Zuchongzhi Road, Shanghai 201203, China
xumh@mail.sioc.ac.cn; lingq@mail.sioc.ac.cn
Received July 22, 2009
ABSTRACT
A new diamine ligand for asymmetric transfer hydrogenation (ATH) was discovered. The reductive cyclization of 2-acylarylcarboxylates was
found to proceed highly stereoselectively by the new Ru complex-catalyzed ATH and subsequent in situ lactonization under aqueous conditions.
It enables efficient access to a wide variety of 3-substituted phthalides in enantiomerically pure form.
Phthalide (1(3H)-isobenzofuranone) frameworks are present
in a large number of natural products and biologically active
compounds.1 Chiral 3-substituted phthalides therefore are
very useful molecules as valuable pharmacological com-
pounds and versatile building blocks for medicinal chemis-
try.2 Over the past two decades, there have been considerable
efforts in the asymmetric synthesis of chiral phthalides, and
a variety of methods toward introducing C-3 chirality have
been developed.3,4 Among them, catalytic approaches appear
to be the most atom economic and thus are of particular
interest. Accordingly, catalytic asymmetric reduction in
combination with the in situ lactonization of 2-acylarylcar-
boxylate compounds represents an attractive and efficient
strategy for chiral phthalide synthesis. However, to our
knowledge, only a few reports on the synthesis of chiral
(3) For selected examples, see: (a) Karnik, A. V.; Kamath, S. S. Synthesis
2008, 1832. (b) Tanaka, K.; Osaka, T.; Noguchi, K.; Hirano, M. Org. Lett.
2007, 9, 1307. (c) Pedrosa, R.; Sayaleroy, S.; Vicente, M. Tetrahedron 2006,
62, 10400. (d) Kosaka, M.; Sekiguchi, S.; Naito, J.; Uemura, M.; Kuwahara,
S.; Watanabe, M.; Harada, N.; Hiroi, K. Chirality 2005, 17, 218. (e)
Witulski, B.; Zimmermann, A. Synlett 2002, 1855. (f) Takahashi, M.; Sekine,
N.; Fujita, T.; Watanabe, S.; Yamaguchi, K.; Sakamoto, M. J. Am. Chem.
Soc. 1998, 120, 12770. (g) Annunziata, R.; Benaglia, M.; Cinquini, M.;
Cozzi, F.; Giaroni, P. J. Org. Chem. 1992, 57, 782. (h) Watanabe, M.;
Hashimoto, N.; Araki, S.; Butsugan, Y. J. Org. Chem. 1992, 57, 742. (i)
Takahashi, H.; Tsubuki, T.; Higashiyama, K. Synthesis 1992, 681. (j) Ogawa,
Y.; Hosaka, K.; Chin, M.; Mitsuhashi, H. Heterocycles 1989, 29, 865. (k)
Kitayama, T. Tetrahedron: Asymmetry 1997, 8, 3765. (l) Ramachandran,
P. V.; Chen, G.-M.; Brown, H. C. Tetrahedron Lett. 1996, 37, 2205. (m)
Meyers, A. I.; Hanagan, M. A.; Trefonas, L. M.; Baker, R. J. Tetrahedron
1983, 39, 1991.
† Shanghai Institute of Organic Chemistry.
‡ Shanghai Institute of Materia Medica.
(1) (a) Devon, T. K.; Scott, A. I. Handbook of Naturally Occurring
Compounds; Academic Press: New York, 1975; Vol. 1, pp 249-264. (b)
Beck, J. J.; Chou, S.-C. J. Nat. Prod. 2007, 70, 891. (c) Atta-ur-Rahman,
H. E. J. Studies in Natural Products Chemistry: BioactiVe Natural Products
(Part L); Elsevier Science, 2006; Vol 32.
(2) (a) Knepper, K.; Ziegert, R. E.; Bra¨se, S. T. Tetrahedron 2004, 60,
8591. (b) Witulski, B.; Zimmermann, A.; Gowans, N. D. Chem. Commun.
2002, 2984. (c) Hung, T. V.; Mooney, B. A.; Prager, R. H.; Tippett, J. M.
Aust. J. Chem. 1981, 34, 383.
10.1021/ol901674k CCC: $40.75
Published on Web 09/18/2009
 2009 American Chemical Society

phthalides by catalytic hydrogenation and transfer hydroge-
nation have been realized to date.4 There still remains a
significant need for a more practical process with broader
substrate scope and higher reaction stereoselectivity. In this
communication, we report a highly enantioselective synthesis
of 3-substituted phthalides by efficient reductive cyclization
of 2-acylarylcarboxylates under ruthenium-catalyzed aqueous
asymmetric transfer hydrogenation conditions using a novel
chiral vicinal diamine ligand.
(2a) is a useful medical agent for the treatment of brain-
related neuro diseases such as ischemic stroke.9 First, we
sought an effective reaction system. The preliminary inves-
tigation revealed that the asymmetric transfer hydrogenation
of 1a can proceed successfully in water with sodium formate
as hydride donor10 by the in situ formed Ru-3a catalyst
(84% yield, 92% ee) (Scheme 1); both of the other two
general conditions in iPrOH and HCOOH-NEt3 were found
not ideal due to competitive side reactions or poor conver-
sion. When Noyori’s catalyst N-(p-toluenesulfonyl)-1,2-
diphenyl-ethylenediamine)/Ru(II) complex (Ru-TsDPEN)
was used to catalyze the same reaction in water, a similar
enantioselectivity was observed (92.7%) after 24 h, but the
yield was much lower (68%). These results prompted us to
envision potential utilization of other 1,2-diaryl-ethylenedi-
amine/Ru(II) complexes as excellent catalysts for this practi-
cal aqueous asymmetric transfer hydrogenation. Accordingly,
a new family of chiral diamine ligands (3b-g) that incor-
porate both electronic and steric factors were prepared using
the established method8 (Figure 1).
Since the breakthrough by Noyori and co-workers,5
transition-metal-catalyzed asymmetric transfer hydrogenation
has been shown to be one of the most powerful and common
methods for the reduction of carbonyl compounds.6 However,
despite the extensive studies of asymmetric reduction of
acetophenone derivatives using various catalysts, transfer
hydrogenation of 2′-substituted acetophenones has been less
developed. In most documented examples,5a,7,10a reduced
enantioselectivities were often observed with these substrates
probably due to the disturbance of the key transition state
by the ortho-substituent. In 2001, the asymmetric transfer
i
hydrogenation of methyl 2-acylbenzoates in PrOH using
ruthenium catalysts has been carefully studied,4c but the
results remained unsatisfactory. Inspired by the previous
success of vicinal diamine preparation,8 we became intrigued
by the possibility of tuning catalyst functionality by introduc-
ing a new diamine backbone for enantioselective synthesis
of 3-substituted phthalides via asymmetric transfer hydro-
genation.
Figure 1. Chiral diamine ligands 3a-g.
Scheme 1
. Synthesis of 3-Butylphthalide 2a by Ru-3a
Catalyzed Transfer Hydrogenation
Screening of the obtained chiral diamine ligands in the
above reductive cyclization of ethyl 2-pentanoylbenzoate (1a)
was next carried out in aqueous HCOONa at 40 °C, and the
results are summarized in Table 1. Simple modification of
the substituents at the 4,4′-positions on the aryl ring with
both electronic and steric changes did not afford the product
with higher enantioselectivity (entries 3 and 4 vs 2).
Gratifyingly, when more sterically hindered diamine ligands
We chose to examine ethyl 2-pentanoylbenzoate (1a) as
the initial substrate, as the resulting product 3-butylphthalide
(7) (a) Alonso, D. A.; Nordin, S. J. M.; Roth, P.; Tarnai, T.; Andersson,
P. G. J. Org. Chem. 2000, 65, 3116. (b) Matharu, D. S.; Morris, D. J.;
Kawamoto, A. M.; Clarkson, G. J.; Wills, M. Org. Lett. 2005, 7, 5489. (c)
Wang, F.; Liu, H.; Cun, L.-F.; Zhu, J.; Deng, J.-G.; Jiang, Y.-Z. J. Org.
Chem. 2005, 70, 9424. (d) Mao, J.-C.; Wan, B.-S.; Wu, F.; Lu, S.-W.
Tetrahedron Lett. 2005, 46, 7341. (e) Morris, D. J.; Hayes, A. M.; Wills,
M. J. Org. Chem. 2006, 71, 7035. (f) Li, X. H.; Blacker, J.; Houson, I.;
Wu, X. F.; Xiao, J. L. Synlett 2006, 1155.
(4) Catalytic hydrogenation: (a) Kitamura, M.; Ohkuma, T.; Inoue, S.;
Sayo, N.; Kumobayashi, H.; Akutagawa, S.; Ohta, T.; Takaya, H.; Noyori,
R. J. Am. Chem. Soc. 1988, 110, 629. (b) Ohkuma, T.; Kitamura, M.; Noyori,
R. Tetrahedron Lett. 1990, 31, 5509. Transfer hydrogenation: (c) Everaere,
K.; Scheffler, J.-L.; Mortreux, A.; Carpentier, J.-F. Tetrahedron Lett. 2001,
42, 1899. For examples of Ni-catalyzed cross-couplings, see: (d) Lei, J.-
G.; Hong, R.; Yuan, S.-G.; Lin, G.-Q. Synlett 2002, 927. (e) Chang, H.-T.;
Jeganmohan, M.; Cheng, C.-H. Chem.sEur. J. 2007, 13, 4356.
(8) (a) Zhong, Y.-W.; Xu, M.-H.; Lin, G.-Q. Org. Lett. 2004, 6, 3953.
(b) Lin, G.-Q.; Xu, M.-H.; Zhong, Y.-W.; Sun, X.-W. Acc. Chem. Res.
2008, 41, 831.
(5) (a) Hashiguchi, S.; Fujii, A.; Takehara, J.; Ikariya, T.; Noyori, R.
J. Am. Chem. Soc. 1995, 117, 7562. (b) Fujii, A.; Hashiguchi, S.; Uematsu,
N.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1996, 118, 2521. (c) Takehara,
J.; Hashiguchi, S.; Fujii, A.; Inoue, S.; Ikariya, T.; Noyori, R. Chem.
Commun. 1996, 233. (d) Haack, K. J.; Hashikuchi, S.; Fujii, A.; Ikariya,
T.; Noyori, R. Angew. Chem., Int. Ed. 1997, 36, 285.
(9) (a) Barton, D. H. R.; de Vries, J. X. J. Chem. Soc. 1963, 1916. (b)
Zhu, X. Z.; Li, X. Y.; Liu, J. Eur. J. Pharmacol. 2004, 500, 221. (c) Chang,
Q.; Wang, X. L. Acta Pharmacol. Sin. 2003, 24, 796. (d) Wang, X. W.
Drugs Future 2000, 25, 16. (e) Huang, X. X.; Hu, D.; Qu, Z. W.; Zhang,
J. T.; Feng, Y. P. Yaoxue Xuebao 1996, 31, 246.
(6) For reviews, see: (a) Noyori, R.; Hashiguchi, S. Acc. Chem. Res.
1997, 30, 97. (b) Palmer, M. J.; Wills, M. Tetrahedron: Asymmetry 1999,
10, 2045. (c) Everaere, K.; Mortreux, A.; Carpentier, J.-F. AdV. Synth. Catal.
2003, 345, 67. (d) Clapham, S. E.; Hadzovic, A.; Morris, R. H. Coord.
Chem. ReV. 2004, 248, 2201. (e) Gladiali, S.; Alberico, E. Chem. Soc. ReV.
2006, 35, 226. (f) Wu, X. F.; Xiao, J. L. Chem. Commun. 2007, 2449. (g)
Wang, C.; Wu, X. F.; Xiao, J. L. Chem. Asian J. 2008, 3, 1750.
(10) For leading references of asymmetric transfer hydrogenation by
HCOONa in water, see: (a) Wu, X.; Li, X.; Hems, W.; King, F.; Xiao,
J. L. Org. Biomol. Chem. 2004, 2, 1818. (b) Wu, X.; Li, X.; King, F.; Xiao,
J.-L. Angew. Chem., Int. Ed. 2005, 44, 3407. (c) Wu, X. F.; Vinci, D.;
Ikariya, T.; Xiao, J. L. Chem. Commun. 2005, 4447. (d) Wu, X. F.; Li,
X. H.; Zanotti-Gerosa, A.; Pettman, A.; Liu, J.; Mills, A. J.; Xiao, J. L.
Chem.sEur. J. 2008, 14, 2209. For an excellent review, see ref 6f.
Org. Lett., Vol. 11, No. 20, 2009
4713

3d-g were used, much increased enantioselectivities were
observed (entries 5-8). It appeared that the steric property
of the substituents on the diphenyl backbone had an obvious
impact on the reaction enantioselectivity. Among those
diamines examined, 3g (TsDBuPEN) having four bulky tert-
butyl groups at the 3,3′- and 5,5′-positions of the phenyl
moieties proved to be the best ligand, giving the correspond-
ing (S)-3-butylphthalide ((S)-2a) with 98% ee (entry 8).
Further studies with an added surfactant showed that the use
of 4 mol % of CTAB (cetyltrimethylammonium bromide)
was greatly helpful in accelerating the reaction and achieving
an excellent yield while maintaining the enantioselectivity
(92% yield, 98% ee, entry 9). Other surfactants such as
Tween 20, Triton X100, SDS, and TBAB were all not
superior to CTAB.11 Notably, in an experiment with lower
catalyst loading (0.5 mol %, S/C ) 200) of 3g (TsDBuPEN)
under the optimal conditions, the same excellent yield (92%)
and enantioselectivity (98%) could be achieved as well after
prolonged (16 h) reaction (entry 10).
Scheme 2. Improved Synthesis of 2-Acylarylcarboxylates 1
hydrogenation followed by in situ lactonization went smoothly,
giving the desired phthalide products in over 90% isolated
yields with uniformly high enantioselectivities (98-99%).
It appeared that both the ee and yield were not sensitive to
the R1 and R2 substitution. The reactions of the 2-acylaryl-
carbonylates 1e-u, which bear aromatic R1 substituents at
the acyl moiety, were carried out in aqueous HCOONa with
CH2Cl2 as cosolvent to accelerate the conversion further
(entries 4-21). This is due to the relatively poor aqueous
solubilities of these substrates as they are mostly in solid or
viscous liquid state. It is noteworthy that, in the case of 1e,
very high enantioselectivity (99%) was again maintained
under much reduced catalyst loading of 0.2 mol % (entry
5). Several heteroatom-containing enantiomerically enriched
phthalides 2m, 2o, 2p, and 2q were also obtained (entries
13 and 15-17), which might be interesting for biological
screening. Assuming an analogous reaction mechanism, the
absolute stereochemistry of the newly formed carbon center
was assigned as in the structure by comparison of optical
rotation value with that reported for 2a, 2b, 2c, and 2e.14,3c,l
We believe that the origins of the excellent stereocontrol
come from the more preferable chirality-determining transi-
tion state of the Ru-TsDBuPEN (3g) complex with the ethyl
2-acylarylcarboxylate substrates, although the exact model
remains unclear.15 In addition, as illustrated in Figure 2, a
possible hydrogen bonding involvement of the neighboring
ester function group of the 2-acylarylcarboxylate substrate
might also be responsible for the observed selectivity. It was
found that the ee (59%) dramatically dropped with 2-me-
thylacetophenone as substrate, which has an ortho-methyl
group instead of a carbonyl-containing ester group. More-
over, phthalide was the only product observed during the
reaction, suggesting a very good cooperative processing of
the asymmetric reduction and lactonization.
Table 1. Catalytic Effects of the Chiral Diamine Ligands 3a-ga
,
entry
ligand
time (h) additive yield (%)b ee (%)c d
1
2
3
4
5
6
7
8
(R,R)-TsDPEN
(S,S)-3a
(S,S)-3b
(S,S)-3c
(S,S)-3d
(R,R)-3e
(S,S)-3f
(S,S)-3g
(S,S)-3g
(S,S)-3g
24
24
24
24
24
24
24
24
-
-
-
-
-
-
-
-
68
84
63e
83
95
76
83
61e
92
92
93 (R)
92 (S)
86 (S)
90 (S)
95 (S)
95 (R)
95 (S)
98 (S)
98 (S)
98 (S)
9
8.5
16
CTABg
10f
CTABg
a Unless otherwise noted, all the reactions were performed with 0.5
mmol of 1a, 5 equiv of HCOONa, and in situ prepared Ru-3 (1 mol %,
S/C ) 100), in 1 mL of H2O at 40 °C. b Isolated yield. c Determined by
HPLC on a chiral column. d The configuration was determined by comparing
the [R]D with known data. e Not full conversion of 1a after 24 h. f 1.0 mmol
of 1a, with 0.5 mol % of Ru-3g (S/C ) 200). g 4 mol % was used.
To explore this transfer hydrogenation in a broad range
of substrates, we improved the synthesis of 2-acylarylcar-
boxylates. The general procedure12 for the preparation of
2-acylbenzoic acids by the reaction of phthalic anhydride
with cadmium reagents has to face the low yield, poor
operability, and high toxicity. Taking advantage of the
condensation methods for alkenylphthalides (4) synthesis
from related phthalic anhydrides,13a a variety of ethyl
2-acylarylcarboxylates (1) were easily accessed by a one-
pot, three-step sequence reaction (Scheme 2).
(13) Representative methods: (a) Shriner, R. L.; Keyser, L. S J. Org.
Chem. 1940, 5, 200. (b) Castro, C. E.; Gaughan, E. G.; Owsley, D. C. J.
Org. Chem. 1966, 31, 4071. (c) Weiss, R. Org. Synth. 1943, 2, 61. Improved
methods: (d) Patil, S. R. Synth. Commun. 1990, 20, 167. (e) La´cova´, M.;
ˇ
Chovancova´, J.; Veverkova´, E.; Toma, S Tetrahedron 1996, 52, 14995. (f)
Safari, J.; Naeimi, H.; Khakpour, A. A.; Jondani, R. S.; Khalili, S. D. J.
Mol. Catal. A 2007, 270, 236. (g) Landge, S. M.; Berryman, M.; To¨ro¨k, B.
Tetrahedron Lett. 2008, 49, 4505.
(14) Takahashi, H.; Tsubuki, T.; Higashiyama, K. Chem. Pharm. Bull.
1991, 39, 3136
.
With the optimized conditions identified and diverse
substrates in hand, the scope and generality of the reaction
were then investigated (Table 2). In all examples, the transfer
(15) For related mechanistic studies on asymmetric transfer hydrogena-
tion, see: (a) Yamakawa, M.; Ito, H.; Noyori, R. J. Am. Chem. Soc. 2000,
122, 1466. (b) Noyori, R.; Yamakawa, M.; Hashiguchi, S. J. Org. Chem.
2001, 66, 7931. (c) Sandoval, C. A.; Ohkuma, T.; Utsumi, N.; Tsutsumi,
K.; Murata, K.; Noyori, R. Chem. Asian. J. 2006, 1-2, 102. (d) Alonso,
D. A.; Brandt, P.; Nordin, S. J. M.; Andersson, P. G. J. Am. Chem. Soc.
1999, 121, 9580. (e) Samec, J. S. M.; Ba¨ckvall, J.-E.; Andersson, P. G.;
Brandt, P. Chem. Soc. ReV. 2006, 35, 237. (f) Handgraaf, J.-W.; Meijer,
E. J. J. Am. Chem. Soc. 2007, 129, 3099. (g) Wu, X. F.; Liu, J. K.;
Tommaso, D. D.; Iggo, J. A.; Catlow, C. R. A.; Bacsa, J.; Xiao, J. L.
Chem.sEur. J. 2008, 14, 7699.
(11) Abbreviations: Tween 20 is polyoxyethylene sorbitan monolaurate;
Triton X100 is polyethylene glycol p-(1,1,3,3-tetramethylbutyl)-phenyl ether;
SDS is sodium monododecyl sulfate; TBAB is tetrabutylammonium
bromide.
(12) (a) de Benneville, P. L. J. Org. Chem. 1941, 6, 462. (b) Mitra,
R. B.; Kulkarni, G. H.; Khanna, P. N. Synthesis 1977, 415.
4714
Org. Lett., Vol. 11, No. 20, 2009

Table 2. Asymmetric Synthesis of 3-Substituted Phthalides by
Ru-TsDBuPEN (3g) Catalyzed Transfer Hydrogenationa
Figure 2. Proposed transition state.
yield
ee
entry
substrate 1
t (h)
2
(%)d (%)e
In summary, a highly enantioselective asymmetric transfer
hydrogenation of challenging 2-acylarylcarboxylates 1 has
been successfully achieved in aqueous HCOONa by using a
new diamine (TsDBuPEN, 3g)/Ru(II) catalyst. The method
offers a mild, facile, and practical access to a wide variety
of 3-substituted phthalides in enantiomerically pure form. It
represents one of the most efficient and general syntheses
of highly optically active phthalides reported to date. Given
the importance of chiral phthalides, this method should find
potential applications in asymmetric synthesis and medicinal
chemistry.
1b
2b
3b
4
1b: R1 ) H, R2 ) H
10
15
18
4
2b
2c
2d
2e
2e
2f
2g
2h
2i
97
95
95
96
92
98
93
96
99
96
98
93
97
98
94
94
97
90
93
98
97
98
98
99
99
99
99
99
99
99
99
99
99
99
99
98
98
98
99
99
98
98
1c: R1 ) CH3, R2 ) H
1d: R1 ) ClCH2(CH2)2, R2 )H
1e: R1 ) Ph, R2 ) H
5c
1e: R1 ) Ph, R2 ) H
24
4
6
1f: R1 ) 4-ClC6H4, R2 ) H
1g: R1 ) 4-MeC6H4, R2 ) H
1h: R1 ) 4-MeOC6H4, R2 ) H
1i: R1 ) 4-MeSC6H4, R2 ) H
1j: R1 ) 4-CF3C6H4, R2 ) H
1k: R1 ) 3,5-F2C6H3, R2 ) H
1l: R1 ) 3,4-(MeO)2C6H3, R2 ) H
1m: R1 ) 2-thienyl, R2 ) H
1n: R1 ) 1-naphthyl, R2 ) H
1o: R1 ) 4-quinolyl, R2 ) H
1p: R1 ) 4-Cl-phenoxyl, R2 ) H
1q: R1 ) 4-Cl-phenylthio, R2 ) H
1r: R1 ) Ph, R2 ) 4-Br
7
4
8
4
9
4
10
11
12
13
14
15
16
17
18
19
20
21
4
2j
2k
2l
4
4
4
2m
2n
2o
2p
2q
2r
2s
2t
11
12
4
Acknowledgment. Financial support from the National
Natural Science Foundation of China (20672126, 20672123,
20721003), the Chinese Academy of Sciences, the Shanghai
Municipal Committee of Science and Technology (07JC14063,
08QH14027), and the Major State Basic Research Develop-
ment Program (2006CB806106) is acknowledged.
4
5
1s: R1 ) Ph, R2 ) 5-Br
4
1t: R1 ) Ph, R2 ) 4,5-Cl2
4
1u: R1 ) Ph, R2 ) 4,5-C4H4
4
2u
a The reactions were performed with 0.5 mmol of 1, 5 equiv of
HCOONa, 4 mol % of CTAB, and in situ prepared Ru-3g (1 mol %, S/C
) 100), in 1 mL of H2O and 0.5 mL of CH2Cl2 at 40 °C, unless otherwise
noted. b The reactions were performed with 1 mmol of 1, 5 equiv of
HCOONa, 4 mol % of CTAB, and in situ prepared Ru-3g (0.5 mol %,
S/C ) 200), in 1 mL of H2O at 40 °C. c With 0.2 mol % of Ru-3g (S/C
) 500), 2.5 mmol of 1, 5 equiv of HCOONa, 4 mol % of CTAB, in 2 mL
of H2O and 0.5 mL of CH2Cl2. d Isolated yield. e Determined by HPLC on
a chiral column.
Supporting Information Available: Explicit experimental
details, including characterization data for chiral diamine
ligands 3a-g, phthalide products 2a-u, and copies of HPLC
and NMR spectra. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL901674K
Org. Lett., Vol. 11, No. 20, 2009
4715