Chiral induction by Cinchona alkaloids in the rhodium(II) catalyzed O-H insertion reaction

Article abstract of DOI:10.1248/cpb.58.872

Cinchona alkaloids are effective additives for enantioselective O-H insertion of α-phenyldiazoacetate and water by rhodium(II) complexes. Addition of silica gel promotes O-H insertion in the reaction rate and the reaction proceeds smoothly at less than the freezing point of water, e.g., -10°C, and provided mandelate in up to 50% ee. The results reported here are the highest asymmetric inductions obtained to date for O-H insertions via a Rh-carbenoid.

Full text of DOI:10.1248/cpb.58.872

872
Note
Chem. Pharm. Bull. 58(6) 872—874 (2010)
Vol. 58, No. 6
Chiral Induction by Cinchona Alkaloids in the Rhodium(II) Catalyzed
O–H Insertion Reaction
Hiroaki SAITO,* Ryo IWAI, Taketo UCHIYAMA, Muneharu MIYAKE, and Shinichi MIYAIRI
School of Pharmacy, Nihon University; 7–7–1 Narashinodai, Funabashi, Chiba 274–8555, Japan.
Received March 2, 2010; accepted March 18, 2010; published online March 23, 2010
Cinchona alkaloids are effective additives for enantioselective O–H insertion of a-phenyldiazoacetate and
water by rhodium(II) complexes. Addition of silica gel promotes O–H insertion in the reaction rate and the reac-
tion proceeds smoothly at less than the freezing point of water, e.g., ꢀ10 °C, and provided mandelate in up to
50% ee. The results reported here are the highest asymmetric inductions obtained to date for O–H insertions via
a Rh-carbenoid.
Key words O–H insertion; enantioselective; rhodium(II); cinchona alkaloid; water
The catalytic insertion reaction into O–H bond with a-dia- rotation with the literature value.23) It is worth noting that
zocarbonyl compounds via a metal-carbenoid intermediate is enantioselectivity for a particular product was provided by
a very useful organic transformation for the synthesis of oxy- the cinchona alkaloids, not by the rhodium catalyst. The
gen-containing compounds.1—3) Remarkable advances, includ- enantiomeric induction in this system may be due to the for-
ing enantioselective insertion, have been made in catalytic mation of a chiral complex between rhodium-carbenenoid
C–H insertions with a-diazocarbonyl compounds using and cinchona alkaoid. To rule out the possibility that the
Rh(II) complexes.4—9) However, only limited success has reaction was catalyzed by quinine (1), we performed the re-
been achieved for asymmetric insertions into O–H bond.2,10—12) action under identical conditions in the absence of Rh2(TPA)4
Recently, Fu and Zhou independently reported asymmetric and observed no background reaction. To further enhance the
insertion reactions into alcoholic,13) phenolic14) and aquatic15) enantioselectivity, we evaluated the abilities of other
O–H bonds with a-diazoacetate using chiral Cu(I) com- dirhodium(II) carboxylate catalysts (Table 1, entries 2—5).
plexes. In contrast, chiral Rh(II) complexes gave poor enan- While a uniform sense of asymmetric induction was ob-
tioselectivity (8% ee) in the O–H insertion reaction,11) while served in all cases, the enantioselectivities were lower than
they have given remarkable results in the C–H insertion reac- that of Rh2(TPA)4. The less reactive dirhodium(II) amidate
tion. Since Rh(II) complexes are unique and powerful cata- catalyst, Rh2(cap)4, was not suitable for this transformation in
lysts in the insertion reaction, we attempted to apply them to terms of both chemical yield and enantiocontrol (Table 1,
the enantioselective O–H insertion reaction.
entry 6). Therefore, Rh2(TPA)4 was chosen as the optimum
Recently, Liang et al. conducted a physicochemical
approach to O–H insertion reactions using density functional
Table 1. Intermolecular O–H Insertion Reaction of Methyl a-Diazophenyl
-
theory (DFT).10) They concluded that Rh(II) complex does acetate with Water Using Rh(II) Complexes and Quinine (1)
not have enough affinity to the oxonium ylide intermediate to
form firmly fixed stereocenter around the metal. Hence, we
sought to design a novel approach to the enantioselective
O–H insertion reaction catalyzed by Rh(II) complexes, inde-
pendent of its own chirality. It is of interest that chiral amine
Rh(II)
complex
Entry
Time (h)
Yield (%)a)
ee (%)b)
additives expressed its own chirality on metal mediated epox-
idation reaction using achiral Mn-salen complex.16)
Accordingly, we envisaged that an intermolecular O–H
insertion of a-aryldiazoacetate and water should produce a
mandelate in an enantioselective manner using cinchona
alkaloids and Rh(II) complexes. Using this method, we now
report that a combination of quinine (1) or quinidine (2) and
dirhodium(II) tetra(triphenylacetate), Rh2(TPA)4, in the O–H
insertion provides mandelate as the sole product in up to
50% ee.
1
2
3
4
5
6
Rh2(TPA)4
Rh2(OAc)4
Rh2(piv)4
Rh2(oct)4
Rh2(pfb)4
Rh2(cap)4
4
28
2
22
0.3
230
82
59
80
73
54
59
38
34
31
32
29
15
a) Isolated yield. b) Determined by HPLC (Daicel Chiralcel OD-H).
In our initial studies, we explored the intermolecular O–H
insertion of methyl phenydiazoacetate in dichloromethane
17,18)
using 1 mol% of Rh2(TPA)4
and 2 mol% of quinine (1)
(Table 1, entry 1).19—22) As expected, the reaction proceeded
smoothly at 23 °C to completion within 4 h, giving methyl
mandelate in 82% yield. The enantioselectivity in this reac-
tion was 38% ee, as determined by HPLC (Daicel Chiralcel
OD-H). The preferred absolute stereochemistry was (S),
which was established by comparing the sign of the optical
Fig. 1. Structures of Rh(II) Complexes and Cinchona Alkaloids
© 2010 Pharmaceutical Society of Japan
∗ To whom correspondence should be addressed. e-mail: saito.hiroaki@nihon-u.ac.jp

June 2010
873
Table 2. Effects of Cinchona Alkaloids (1—4) and Their Quantities on
Enantioselectivities
Table 3. Enantioselective O–H Insertion of a-Diazophenylacetate and
Water with Silica Gel as a Solid Support
Entry
X (°C)
Time (h)
Yield (%)a)
ee (%)b)
X
Time
(h)
Yield
(%)a)
Entry Additive
ee (%)b) Confign.
(mol%)
1
23
0
0
ꢁ10
ꢁ20
0.5
2
56
2
79
97
86
90
89
36
45
45
50
46
2
1
2
3
4
5
6
7
1
2
3
4
1
1
1
2
2
2
2
No
5
4
82
80
84
77
30
69
61
38
38
30
27
rac
37
36
S
R
R
S
—
S
3c)
4
23
15
45
0.3
31
76
5
4
a) Isolated yield. b) Determined by HPLC (Daicel Chiralcel OD-H). c) Silica
gel was not used.
10
S
than thermodynamics. However, as the reaction temperature
was further decreased to ꢁ20 °C, enantioselectivity of the
product dropped to 46% (Table 3, entry 5).
a) Isolated yield. b) Determined by HPLC (Daicel Chiralcel OD-H).
catalyst in terms of enantioselectivity, and was used for fur-
ther study.24)
In summary, we have developed a highly efficient method
for the catalytic enantioselective O–H insertion reaction of
We then investigated other cinchona alkaloids as additives a-phenyldiazoacetate. The enantioselectivity of 50% is the
and their optimal quantities. A clear pseudo-enantiomeric highest achieved in Rh(II) catalyzed O–H insertion reactions
effect was observed for quinine (1) and quinidine (2) (Table to date. While the mechanism of Rh(II) complex/cinchona
2, entries 1, 2). Structurally similar cinchona alkaloids, cin- alkaloid catalyzed O–H insertion reactions remains unclear,
chonine (3) and cinchonidine (4), were not the additives of it is apparent that the enantioselectivity is substantially influ-
choice with respect to reaction rate and enantioselectivity enced by the stereochemistry of the cinchona alkaloids. Fur-
(Table 2, entries 3, 4).25) Interestingly, quinine (1) and cin- ther studies on substituent effects as well as the design of
chonine (3) afforded the opposite absolute configurations of chiral additives to further enhance enantioselectivity are cur-
the products. The only structural difference was the sub- rently underway in our laboratories.
stituent on the 6ꢀ-methoxy group on quinoline ring, which
suggests that the methoxy group affects the conformation of
these cinchona alkaloids, which is important in terms of
Experimental
General Procedure for the Preparation of (S)-Methyl Mandelate23)
(Table 3, Entry 4) To a solution of Rh2(TPA)4 (2.8 mg, 0.002 mmol) and
enantiomeric induction. Without quinine (1), no asymmetric
induction was observed and the product yield was reduced as
the formation of dimer and methyl benzoylformate (Table 2,
entry 5).26) With the amount of quinine (1) increased to 5
mol% and 10 mol%, similar enantiocontrol was observed, but
chemical yields decreased to 69% and 61%, respectively
(Table 2, entries 1 vs. 6, 7). The reactivity of the Rh(II) com-
plex should be decreased by the coordination of the tertiary
nitrogen in quinine (1) to the Rh(II) catalyst.
Next, we attempted to use silica gel in the O–H insertion
reaction of a-phenyldioazoacetate and water. Silica gel is a
good solid support for organic transformations.27—30) In this
reaction system, water was employed as a substrate, which
limits the temperature to no less than 0 °C. Silica gel can
absorb water molecules on its surface, thus its surface may
quinine (1.3 mg, 0.004 mmol) in CH2Cl2 (1 ml) was added silica gel (30 mg,
Wako gel® C-200) and H2O (3.6 ml, 0.20 mmol). A solution of methyl 2-
diazo-2-phenylacetate (36 mg, 0.20 mmol) in CH2Cl2 (1 ml) was added to the
reaction mixture at ꢁ10 °C. After stirring at the same temperature for 2 h,
filtration and evaporation in vacuo furnished the crude product, which was
purified by preparative TLC (3 : 1 hexane/EtOAc) to provide methyl mande-
late (30 mg, 90%) as a colorless needle. The enantiomeric excess was deter-
mined by HPLC with a chiral stationary phase column.
1
Rfꢂ0.15 (5 : 1 hexane/EtOAc). H-NMR (CDCl3) d: 3.43 (1H, d, Jꢂ5.5
Hz), 3.76 (3H, s), 5.18 (1H, d, Jꢂ5.5 Hz), 7.33—7.43 (5H, m). [a]D22 ꢃ82.0
(cꢂ1.2, CHCl3) for 50% ee [lit.,23) [a]D20 ꢃ180.5 (cꢂ1.3, CHCl3) for 97.1%
ee of (S)-form]. HPLC tR (major enantiomer)ꢂ8.2 min (74.8%); tR (minor
enantiomer)ꢂ12.1 min (25.2%) (Daicel Chiralcel OD-H, 9 : 1 hexane/iPrOH,
1.0 ml/min, detection 254 nm).
Acknowledgement This research was supported in part by a grant from
the “Academic Frontier” Project for Private Universities and a matching
fund subsidy from MEXT (Ministry of Education, Culture, Sports, Science
serve to enhance the reaction rate at a temperature less than and Technology) 2007—2010. The authors thank Prof. Shunichi Hashimoto
and Dr. Masahiro Anada, Hokkaido University for their helpful suggestions.
The authors also thank Dr. Koichi Metori (Analytical Center, School of
Pharmacy, Nihon University) for performing the mass measurement.
the freezing point of water. As expected, the reaction rate was
8 times faster at 23 °C without affecting the yield and enan-
tioselectivity (Table 2, entry 1 vs. Table 3, entry 1). Further,
the reaction proceeded smoothly at 0 °C to completion within
References and Notes
2 h, providing the product quantitatively in 45% ee (Table 3,
1) Ye T., McKervey M. A., Chem. Rev., 94, 1091—1160 (1994).
entry 2). Without silica gel, 56 h was needed for completion
of this transformation with a slight decrease in chemical
yield (Table 3, entry 3). We were gratified to find that the
enantioselectivity was further enhanced up to 50% ee by low-
ering the temperature to ꢁ10 °C without affecting the reac-
tion rate (Table 3, entry 4). This result suggested that the
reaction seems to be controlled by rather reaction kinetics
2) Doyle M. P., McKervey M. A., Ye T., “Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds,” Wiley-Interscience, New
York, 1998, pp. 433—486.
3) Miller D. J., Moody C. J., Tetrahedron, 51, 10811—10843 (1995).
4) Doyle M. P., Forbes D. C., Chem. Rev., 98, 911—936 (1998).
5) Sulikowski G. A., Cha K. L., Sulikowski M. M., Tetrahedron: Asym-
metry, 9, 3145—3169 (1998).
6) Doyle M. P., “Catalytic Asymmetric Synthesis,” ed. by Ojima I.,

874
Vol. 58, No. 6
Wiley-VCH, New York, 2000, pp. 191—228.
7) Davies H. M. L., Manning J. R., Nature (London), 451, 417—424
(2008).
8) Saito H., Oishi H., Kitagaki S., Nakamura S., Anada M., Hashimoto
S., Org. Lett., 4, 3887—3890 (2002).
cloaddition reaction between ethyl glyoxylate and trimethylsilylketene
in the presence of 1 mol% of chiral dirhodium(II) carboxamidates and
10 mol% of quinine gave b-lactone derivative in up to 99% ee, see:
Forslund R. E., Cain J., Colyer J., Doyle M. P., Adv. Synth. Catal., 347,
87—92 (2005).
9) Minami K., Saito H., Tsutsui H., Nambu H., Anada M., Hashimoto S.,
Adv. Synth. Catal., 347, 1483—1487 (2005).
10) Liang Y., Zhou H., Yu Z.-X., J. Am. Chem. Soc., 131, 17783—17785
(2009).
21) For examples of enantioselective transformation using achiral
dirhodium(II) carboxylates and chiral co-catalysts, see: Suga H., Inoue
K., Inoue S., Kakehi A., J. Am. Chem. Soc., 124, 14836—14837
(2002).
11) Bulugahapitiya P., Landais Y., Parra-Rapado L., Planchenault D., 22) Hu W., Xu X., Zhou J., Liu W.-J., Huang H., Hu J. Yang L., Gong L.
Weber V., J. Org. Chem., 62, 1630—1641 (1997).
12) Li Z., Davies H. M. L., J. Am. Chem. Soc., 132, 396—401 (2010).
13) Maier T. C., Fu G. C., J. Am. Chem. Soc., 128, 4594—4595 (2006).
14) Chen C., Zhu S.-F., Liu B., Wang L.-X., Zhou Q.-L., J. Am. Chem.
Soc., 129, 12616—12617 (2007).
-Z., J. Am. Chem. Soc., 130, 7782—7783 (2008).
23) Wang C.-J., Sun X., Zhang X., Synlett, 2006, 1169—1172 (2006).
24) We also investigated a combination of 1 mol% of Rh2(TPA)4 and
2 mol% of quinine for O–H insertion reaction between methyl phenyl-
diazoacetate and methanol, ethanol, isopropyl alcohol and phenol. Re-
action times, chemical yields and enantioselectivities as follows;
15) Zhu S.-F., Chen C., Cai Y., Zhou Q.-L., Angew. Chem. Int. Ed., 47,
932—934 (2008).
i
MeOH, 5 h, 13%, 34% ee; EtOH, 4.5 h, 18%, 36% ee; PrOH, 5 h,
16) Hashihayata T., Ito Y., Katsuki T., Tetrahedron, 53, 9541—9552
(1997).
17) Hashimoto S., Watanabe N., Ikegami S., J. Chem. Soc., Chem. Com-
mun, 1508—1510 (1992).
31%, 37% ee, PhOH, 3.5 h, 64%, 1% ee.
25) Reaction times, chemical yields and enantioselectivities obtained with
other chiral additives are as follows: (ꢁ)-sparteine, 0.5 h, 50%, 3% ee
(R); brucine, 22 h, 72%, 5% ee (S).
18) Hashimoto S., Watanabe N., Ikegami S., Tetrahedron Lett., 33, 2709—
2712 (1992).
26) Lu C.-D., Liu H., Chen Z.-Y., Hu W.-H., Mi A.-Q., Chem. Commun.,
2624—2626 (2005).
19) Nelson and co-workers reported that the properties of Rh(II) catalysts 27) Kumar K. H., Muralidharan D., Perumal P. T., Synthesis, 2004, 63—68
could be modified by the presence of additives such as tetramethyl
urea or Hünig’s base for intermolecular O–H insertion reactions, see:
(2004).
28) Basu B., Das P., Hossain I., Synlett, 2004, 2630—2632 (2004).
Nelson T. D., Song Z. J., Thompson A. S., Zhao M., DeMarco A., 29) Sekimura N., Saito H., Miyairi S., Takabatake T., Heterocycles, 65,
Reamer R. A., Huntington M. F., Grabowski E. J. J., Reider P. J., Tetra-
hedron Lett., 41, 1877—1881 (2000).
20) Doyle and co-workers reported that the enantioselective [2ꢃ2]-cy-
1589—1600 (2005).
30) Sumiyoshi Y., Saito H., Miyairi S., Takabatake T., Heterocycles, 78,
905—909 (2009).