Design of chiral bifunctional quaternary phosphonium bromide catalysts possessing an amide moiety

Article abstract of DOI:10.1021/ol4013926

Novel bifunctional quaternary phosphonium bromides possessing an amide moiety were designed for the highly enantioselective sulfenylation and chlorination of β-ketoesters under base-free phase-transfer conditions. The tuning of an amide moiety of the cata

Full text of DOI:10.1021/ol4013926

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Design of Chiral Bifunctional Quaternary
Phosphonium Bromide Catalysts
Possessing an Amide Moiety
Seiji Shirakawa, Takashi Tokuda, Atsuyuki Kasai, and Keiji Maruoka*
Laboratory of Synthetic Organic Chemistry and Special Laboratory of Organocatalytic
Chemistry, Department of Chemistry, Graduate School of Science, Kyoto University,
Sakyo, Kyoto 606-8502, Japan
maruoka@kuchem.kyoto-u.ac.jp
Received May 17, 2013
ABSTRACT
Novel bifunctional quaternary phosphonium bromides possessing an amide moiety were designed for the highly enantioselective sulfenylation
and chlorination of β-ketoesters under base-free phase-transfer conditions. The tuning of an amide moiety of the catalyst was crucial to achieve
high reactivity and enantioselectivity.
Asymmetric phase-transfer catalysis has been recog-
nized as a powerful method for producing useful chiral
compounds, and various types of chiral quaternary onium
salts have been developed for this purpose in the past two
decades.1 In these areas, the design of bifunctional cata-
lysts has obtained much attention in recent years,2À5 and
further advances in the design of structurally well-defined
bifunctional chiral onium salts are highly desirable for
achieving truly efficient asymmetric phase-transfer reac-
tions. In the course of our design of effective chiral
bifunctional phase-transfer catalysts, we recently reported
a valuable set of chiral bifunctional quaternary phospho-
nium salts of type (S)-1, which possess a hydroxy group;
these were easily synthesized from commercially available
chiral phosphine compounds (Figure 1).4e In this study, we
(1) For recent reviews on asymmetric phase-transfer catalysis, see:
(a) O’Donnell, M. J. Aldrichimica Acta 2001, 34, 3. (b) Maruoka, K.;
Ooi, T. Chem. Rev. 2003, 103, 3013. (c) O’Donnell, M. J. Acc. Chem. Res.
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Angew. Chem., Int. Ed. 2007, 46, 4222. (g) Ooi, T.; Maruoka, K.
Aldrichimica Acta 2007, 40, 77. (h) Hashimoto, T.; Maruoka, K. Chem.
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679. (j) Jew, S.-s.; Park, H.-g. Chem. Commun. 2009, 7090. (k) Maruoka,
K. Chem. Rec. 2010, 10, 254. (l) Shirakawa, S.; Maruoka, K. Angew.
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transfer catalysts, see: (a) He, R.; Shirakawa, S.; Maruoka, K. J. Am. Chem.
Soc. 2009, 131, 16620. (b) Wang, L.; Shirakawa, S.; Maruoka, K. Angew.
Chem., Int. Ed. 2011, 50, 5327. (c) Shirakawa, S.; Terao, S. J.; He, R.;
Maruoka, K. Chem. Commun. 2011, 47, 10557. (d) Shirakawa, S.; Ota, K.;
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S.; Kasai, A.; Tokuda, T.; Maruoka, K. Chem. Sci. 2013,4, 2248. See also: (f)
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(2) For a review of chiral bifunctional quaternary ammonium salts,
see: Novacek, J.; Waser, M. Eur. J. Org. Chem. 2013, 637.
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J. Am. Chem. Soc. 1984, 106, 446. (b) Loupy, A.; Zaparucha, A. Tetra-
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K. J. Am. Chem. Soc. 2004, 126, 6844. (d) Wang, X.; Lan, Q.; Shirakawa, S.;
Maruoka, K. Chem. Commun. 2010, 46, 321. (e) Provencher, B. A.;
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r
10.1021/ol4013926
XXXX American Chemical Society

reported that the hydroxy group of catalyst (S)-1 was
crucial for obtaining high enantioselectivity in the conju-
gate additions of 3-substituted oxindoles. Based on this
observation, we became interested in the design of new
bifunctional phosphonium salts6,7 of type (S)-2 and (S)-3,
which possess an amide moiety instead of a hydroxy group.5
The acidity of the amide (NH) in these catalysts can be easily
tuned by introducing different substituents to the nitrogen
(XÀR). Additionally, the steric environment of the catalysts
(S)-2 and 3 can be controlled by tuning the steric size of the R
group on the amide moiety as well as the aryl methyl group
on the phosphorus (Figure 1). Here we report the design of
new effective bifunctional phosphonium salts for the asym-
metric sulfenylation8 and chlorination9 of β-ketoesters under
base-free phase-transfer conditions.4
phosphonium enolate intermediate, and the carbonyl
groups of N-(phenylthio)phthalimide can potentially in-
teract with the amide moiety (NH) of catalysts (S)-2 and 3
via hydrogen-bonding.2 Although several examples of asym-
metric sulfenylation of β-ketoesters have been reported,
none of them have succeeded in the sulfenylation of 1-oxo-
2-indanecarboxylate in a highly enantioselective manner.8
The reaction between tert-butyl 1-oxo-2-indanecarboxy-
late and N-(phenylthio)phthalimide in H2O/toluene (10:1)
took place in the presence of hydroxylated (S)-1a4e (1mol%)
at room temperature (25 °C) over 24 h and afforded the
sulfenylation product 4a in good yield with moderate en-
antioselectivity (82% yield, 42% ee, entry 1 in Table 1). On
the other hand, hydroxy-protected catalyst (S)-1b (R = Me)
gave the product 4a in low yield and enantioselectivity (29%
yield, 17% ee, entry 2). These results suggested that the
bifunctional design of the catalysts was benefiting the reac-
tion. The screening of different aryl methyl groups on the
phosphorus of (S)-1did not show significant improvement of
the enantioselectivity (entries 3 and 4). These results pro-
mpted us to examine the chiral bifunctional phosphonium
bromides possessing an amide moiety (S)-2 and 3, which
were easily synthesized from known chiral phosphine com-
pounds.10 To our delight, benzamide substituted catalyst
(S)-2a gave the product 4a with high enantioselectivity (92%
ee, entry 5), and further screening of the aryl methyl group of
the catalyst (2b and c, entries 6 and 7) improved the yield and
enantioselectivity further (98% yield, 94% ee, entry 7). A
change of the benzamide group in the catalyst to acetamide
(2d), pivalamide (2e), and sulfonamides (3a and b) reduced
both the yields and enantioselectivities (entries 8À11). These
results indicated that fine-tuning of the amide moiety of the
catalyst was important to achieve high enantioselectivity.
The absolute configuration of product 4a was determined by
X-ray diffraction analysis (Figure 2).11
Figure 1. Bifunctional quaternary phophonium salts and a possible
working model.
As a model reaction to examine the ability of bifunctional
phosphonium salts 1À3, the asymmetric sulfenylation of
1-oxo-2-indanecarboxylate with N-(phenylthio)phthalimide
was selected (Table 1). In this reaction, the β-ketoester is
activated by the phosphonium bromide to produce a
With an effective chiral bifunctional quaternary phos-
phonium salt (S)-2c in hand, we studied the substrate
generality of the asymmetric sulfenylation of various
1-oxo-2-indanecarboxylates under base-free phase-transfer
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Adv. Synth. Catal. 2009, 351, 1469. (b) Enders, D.; Nguyen, T. V. Org.
Biomol. Chem. 2012, 10, 5327.
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Bohsako, A.; Higashiyama, M.; Asakura, C. ACS Symp. Ser. 1997, 659,
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B
Org. Lett., Vol. XX, No. XX, XXXX

introduction of electron-withdrawing and -donating sub-
stituents to the aromatic ring of 1-oxo-2-indanecarboxylate
uniformly gave the products (4aÀd) in excellent yields and
enantioselectivities (93À95% ee) at low catalyst loadings.
Furthermore, a variety of N-(arylthio)- and N-(benzylthio)-
phthalimides were tolerated in the reaction, giving the pro-
ducts 4eÀi with high enantioselectivities (92À95% ee). It
should be noted that triarylphosphine catalyst (S)-5 did not
show any catalytic activity in the present reaction; i.e., the
quaternary phosphonium bromide moiety of catalyst (S)-2c
was essential for the sulfenylation. Also, the reactions under
homogeneous conditions in toluene without H2O proceeded
very sluggishly, indicating the importance of the coexistence
of H2O.4
Table 1. Effect of Catalystsa
Scheme 1. Asymmetric Sulfenylation of 1-Oxo-2-indanecar-
boxylates
yield
(%)b
ee
(%)c
entry
catalyst
1
(S)-1a
(S)-1b
(S)-1c
(S)-1d
(S)-2a
(S)-2b
(S)-2c
(S)-2d
(S)-2e
(S)-3a
(S)-3b
82
29
60
98
80
80
98
38
56
5
42
17
44
48
92
94
94
84
5
2
3
4
5
6
7
8
9
10
11
60
48
6
a Reaction conditions: tert-Butyl 1-oxo-2-indanecarboxylate (0.050 mmol),
N-(phenylthio)phthalimide (0.060 mmol) in the presence of catalyst
(1 mol %) in H2O (2 mL)/toluene (0.2 mL) at room temperature (25 °C)
for 24 h. b Yield of isolated product. c Determined by chiral HPLC analysis.
The asymmetric sulfenylations of tert-butyl 2-oxocyclo-
pentanecarboxylate with N-(arylthio)phthalimides were also
examined (Scheme 2), and sulfenylation products 6aÀc
were obtained with high enantioselectivities (92À93% ee).12
The absolute configuration of product 6a was confirmed
Figure 2. X-ray crystal structure of 4a.
conditions (Scheme 1). To demonstrate the practicality of
the present reaction, only 0.1 mol % of the chiral catalyst
(S)-2c was used in these asymmetric sulfenylations. The
(12) Unfortunately, 2-oxocyclohexanecarboxylates and acyclic
β-ketoesters showed low reactivity under similar reaction conditions.
Org. Lett., Vol. XX, No. XX, XXXX
C

Scheme 3. Asymmetric Chlorination of β-Ketoesters
Scheme 2. Asymmetric Sulfenylation of 2-Oxocyclopentane-
carboxylate
by comparison of the optical rotation with the literature
value.8b,e
Insummary, we have successfullydesignednovel bifunc-
tional quaternary phosphonium salts that possess an
amide moiety which function as effective chiral phase-
transfer catalysts. These catalysts were applied in the
highly enantioselective sulfenylation and chlorination of
β-ketoesters under base-free phase-transfer conditions,
and we found that fine-tuning of an amide moiety of the
catalyst was important to achieve efficient asymmetric
reactions. Further application of these bifunctional phos-
phonium bromides to other asymmetric reactions is cur-
rently underway in our group.
To further expand the synthetic utility of our bifunc-
tional quaternary phosphonium bromides with an amide
moiety, we also examined the asymmetric chlorination
of β-ketoesters under base-free phase-transfer conditions
(Scheme 3).9 Although the reaction with benzamide sub-
stituted catalyst (S)-2c gave product 7a with moderate
enantioselectivity (53% ee), benzenesulfonamide substi-
tuted catalyst (S)-3a improved the enantioselectivity to
give the chlorination product 7a in high yield and enantios-
electivity (92% ee).13 These results suggest that the tunable
acidity of an amide moiety of the catalyst could open up
further possibilities for realizing other types of asymmetric
transformation using these bifunctional catalysts. Various
β-ketoesters could be employed for the chlorination with
catalyst (S)-3a, and products 7b and 7c were obtained with
good to high enantioselectivity (81À94% ee). The absolute
configuration of product 7b was confirmed by comparison
of the optical rotation with the literature value.9h,l,n
Acknowledgment. This work was partially supported
by a Grant-in-Aid for Scientific Research from JSPS and
MEXT (Japan).
Supporting Information Available. Experimental de-
tails, characterization data for new compounds, and
crystallographic data (CIF). This material is available
free of charge via the Internet at http://pubs.acs.org.
(13) pKa of amides in DMSO: PhCONH2, 23.3; PhSO2NH2, 16.1.
Bordwell, F. G.; Fried, H. E.; Hughes, D. L.; Lynch, T.-Y.; Satish, A. V.;
Whang, Y. E. J. Org. Chem. 1990, 55, 3330.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX