Asymmetric synthesis of β-hydroxy acid via stereoselective dirhodium(II)-catalyzed C-H insertion of α-alkoxydiazoketone

Article abstract of DOI:10.1248/cpb.51.471

A new methodology for the asymmetric synthesis of β-hydroxy acid was developed. Dirhodium(II)-catalyzed C-H insertion of α-alkoxydiazoketone (3), which was prepared from primary alkyl halide (1) and readily available chiral α-hydroxy acid (2), gave stereo

Full text of DOI:10.1248/cpb.51.471

April 2003
Notes
Chem. Pharm. Bull. 51(4) 471—473 (2003)
471
b
Asymmetric Synthesis of -Hydroxy Acid via Stereoselective
a
Dirhodium(II)-Catalyzed C–H Insertion of -Alkoxydiazoketone
Takayuki YAKURA,* Takeshi TANAKA, Masazumi IKEDA, and Jun’ichi UENISHI
Kyoto Pharmaceutical University; Misasagi, Yamashina-ku, Kyoto 607–8412, Japan.
Received December 25, 2002; accepted February 3, 2003; published online February 4, 2003
A new methodology for the asymmetric synthesis of b-hydroxy acid was developed. Dirhodium(II)-catalyzed
C–H insertion of a-alkoxydiazoketone (3), which was prepared from primary alkyl halide (1) and readily avail-
able chiral a-hydroxy acid (2), gave stereoselectively 2,5-cis-disubstituted 3(2H)-furanone (4). The Baeyer-Villiger
reaction of 4 followed by treatment with an acid afforded chiral b-hydroxy acid (6) with high optical purity.
Key words b-hydroxy acid; a-alkoxydiazoketone; C–H insertion; dirhodium(II); 3(2H)-furanone
The development of new methodologies for the synthesis ing bulkier ligand than that of Rh2(oct)4 decreased cis-selec-
of chiral b-hydroxy acids is highly desired because of their tivity to 3.8 : 1 (Entry 2). The stereostructure of the major
utility in organic synthesis.1—3) We have been investigating a product was deduced from differential nuclear Overhauser
new strategy for the synthesis of chiral b-hydroxy acids, effect (NOE) experiments: positive NOEs were observed be-
which is based on the stereoselective dirhodium(II)-catalyzed tween 2-H and 5-H. The reaction of butoxy derivative (3b)
C–H insertion4—8) of a-alkoxydiazoketone, and report herein with Rh2(oct)4 in CH2Cl2 (0.017 M) gave exclusively cis-4b in
our preliminary results.
53% yield (Entry 4). A low concentration (0.005 M) gave a
Our strategy is outlined in Chart 1. Primary alkyl halide slight increase in the yield (Entry 5). In benzene, the reaction
(1) is easily transformed into a-alkoxydiazoketone (3) by at room temperature gave a higher yield (Entry 6) and the
treatment with a-hydroxy acid (2), which can be prepared best result (70% yield) was obtained in the reaction at high
from a-amino acid in an optically active form, followed by temperature (Entry 7).
diazomethylation. The dirhodium(II)-catalyzed reaction of 3
stereoselectively affords the 2,5-cis-disubstituted 3(2H)-fura-
none (4).9—11) Oxidation of 4 with m-chloroperbenzoic acid
(m-CPBA) regio- and stereoselectively gives protected b-hy-
droxy acid (5), which is easily converted into b-hydroxy acid
by treatment with an acid and is also an important intermedi-
ate for the synthesis of syn- and anti-1,3-diols.12,13) The chi-
rality of the resultant b-hydroxy acid is transferred from that
of the used a-hydroxy acid (2). From the literature,9—11) we
expected that the reaction of a-alkoxydiazoketone having a
bulky group at a-position would give good cis-selectivity in
the formation of 2,5-disubstituted 3(2H)-furanone. Thus, we
investigated the C–H insertion reaction of 3 which has an
isopropyl group at the a-position of the keto group (R1ꢀi-
Pr). The requisite a-hydroxy acid 2 (R1ꢀi-Pr, R2ꢀH) can be
easily obtained in both optically active forms from valine.14)
First, we investigated the reactions of racemic diazoke-
tones (3) with catalytic amounts of various dirhodium(II) cat-
alysts. The results are shown in Table 1. Starting diazoke-
tones (3a and 3b) were prepared from a-alkoxyester (7) by a
standard manner.15) After hydrolysis of 7 into the correspond-
ing carboxylic acid, the acid was converted into its mixed an-
hydride using ethyl chloroformate, and then treated with ex-
cess diazomethane to afford 3 (Chart 2).
a-Benzyloxydiazoketone (3a) was reacted with 1 mol% of
dirhodium(II) tetraacetate [Rh2(OAc)4] in CH2Cl2 (0.017 M)
at room temperature for 10 min. The only 2-isopropyl-5-
phenyldihydrofuran-3-one (4a) was isolated in 30% yield as
a 1.4 : 1 mixture of cis and trans isomers (Entry 1).16) Both
chemical yield and diastereoselectivity were influenced by
the ligand of dirhodium(II) catalyst. Treatment of 3a with
dirhodium(II) tetraoctanoate [Rh2(oct)4] gave 4a in 39%
yield with high cis-selectivity (17 : 1) (Entry 3). However, the
use of dirhodium(II) tetra(triphenylacetate) [Rh2(TPA)4] hav-
Chart 1
Chart 2
Table 1. Dirhodium(II)-Catalyzed Reaction of 3a)
Entry
3
Rh(II)
Solvent Temp. Yield (%) cis : transb)
1
2
3
a
a
a
b
b
b
b
Rh2(OAc)4 CH2Cl2
Rh2(TPA)4 CH2Cl2
rt
rt
rt
rt
rt
rt
30
39
39
53
59
62
70
1.4 : 1
3.8 : 1
17 : 1
cis
cis
cis
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
CH2Cl2
CH2Cl2
CH2Cl2
benzene
4
5c)
6
7
benzene reflux
cis
a) Reactions were carried out in 0.017 M solution. All reactions were completed in
10 min. b) Determined by 1H-NMR. c) Concentration was 0.005 M.
* To whom correspondence should be addressed. e-mail: yakura@mb.kyoto-phu.ac.jp
© 2003 Pharmaceutical Society of Japan

472
Vol. 51, No. 4
then 10% hydrochloric acid was added until pH was 2. The mixture was ex-
tracted with Et2O and the extract was dried (MgSO4) and concentrated to
give crude 2-benzyloxy-3-methylhexanoic acid. According to the procedure
of Seebach et al.,15) a solution of the crude acid in THF (20 ml) was cooled
to ꢁ15 °C and Et3N (400 mg, 3.96 mmol) and ClCO2Et (430 mg, 3.96 mmol)
were added. After 30 min, the suspension was allowed to warm to 0 °C and
stirred for further 30 min. Then a solution of CH2N2 in Et2O was added at
the same temperature until a strong yellow color persisted. The suspension
was allowed to warm to room temperature and stirred for 5 h. The excess of
CH2N2 was destroyed by the addition of a few drops of AcOH. The mixture
was diluted with H2O, and extracted with Et2O. The organic layer was
washed with aqueous saturated NaHCO3 solution, aqueous saturated NH4Cl
solution and brine, and dried (MgSO4) and concentrated. The residue was
chromatographed on silica gel (5% EtOAc in hexane) to give 3a (551 mg,
62% in 3 steps) as a yellow oil. 1H-NMR (CDCl3) d: 0.96 (3H, d, Jꢀ6.8 Hz),
0.98 (3H, d, Jꢀ6.8 Hz), 1.93—2.09 (1H, m), 3.58 (1H, d, Jꢀ5.7 Hz), 4.44
(1H, ABq, Jꢀ11.6 Hz), 4.64 (1H, ABq, Jꢀ11.6 Hz), 5.71 (1H, s), 7.21—
7.39 (5H, m). IR (neat) cmꢁ1: 2104, 1634. FAB-MS m/z: 233.1286 (Calcd
for C13H17N2O2: 233.1290).
Butyl 2-Butoxy-3-methylbutanoate (7b) A solution of 2-hydroxy-3-
methylbutanoic acid (1 g, 8.47 mmol) in DMF (20 ml) was added to a sus-
pension of NaH (447 mg, 18.6 mmol) in DMF (10 ml) at 0 °C under nitrogen
atmosphere and the mixture was stirred for 30 min at the same temperature.
A solution of 1-bromobutane (2.79 g, 20.3 mmol) in DMF (10 ml) and tetra-
butylammonium iodide (313 mg, 0.85 mmol) were added. After 30 min, the
mixture was allowed to warm to room temperature and stirred overnight.
The mixture was quenched with H2O, and extracted with Et2O. The extract
was washed with H2O and brine, dried (MgSO4), and concentrated. The
residue was chromatographed on silica gel (5% EtOAc in hexane) to give 7b
Chart 3
On the basis of the above mentioned results, we attempted
the asymmetric synthesis of a chiral b-hydroxy acid (Chart
3). Treatment of benzyl bromide with methyl (S)-2-hydroxy-
3-methylbutanoate [(S)-2a]14) in the presence of sodium hy-
dride in dimethylformamide (DMF) gave (S)-7a14,17) in an
optically active form (90.8% ee) in 59% yield. Conversion of
(S)-7a into (S)-3a was performed using the same procedure
as that for racemic 7a. Fortunately, the dirhodium(II)-cat-
alyzed reaction of (S)-3a in refluxing benzene gave excellent
1
(639 mg, 33%) as a colorless oil. H-NMR (CDCl3) d: 0.91 (3H, t, Jꢀ7.3
Hz), 0.94 (3H, t, Jꢀ7.2 Hz), 0.95 (3H, d, Jꢀ6.6 Hz), 0.96 (3H, d, Jꢀ6.6 Hz),
1.32—1.48 (4H, m), 1.52—1.69 (4H, m), 1.95—2.11 (1H, m), 3.29 (1H, dt,
Jꢀ9.2, 6.6 Hz), 3.53 (1H, d, Jꢀ5.9 Hz), 3.57 (1H, dt, Jꢀ9.2, 6.4 Hz), 4.08—
4.22 (2H, m). IR (neat) cmꢁ1: 1749. CI-MS m/z: 231.1954 (Calcd for
stereoselectivity and a high yield. Thus, (S)-3a was reacted C13H27O3: 231.1960).
3-Butoxy-1-diazo-4-methylpentan-2-one (3b) According to a proce-
with 1 mol% of Rh2(oct)4 in benzene (0.017 M) under reflux
for 10 min to afford (2S,5S)-4a as a single isomer in 75%
yield. Then, treatment of (2S,5S)-4a with m-CPBA in CH2Cl2
at room temperature for 10 h gave the protected b-hydroxy
acid (5a) in 85% yield. The cis configuration of 5a was de-
termined by NOE experiments. The absolute configuration of
5a was confirmed by conversion into known chiral b-hydroxy-
ester (8) via treatment with hydrochloric acid, followed by
esterification with diazomethane. The spectroscopic data and
the specific rotation of 8 were identical with those of an au-
thentic sample18) and the optical purity (90.4% ee) was deter-
mined by HPLC analysis using Chiralcel ADH (hexane/
EtOH, 95/5, 1 ml/min).
In summary, we showed a new methodology for the syn-
thesis of chiral b-hydroxy acid from primary alkyl halide
employing stereoselective dirhodium(II)-catalyzed C–H in-
sertion as a key step. The chirality of the resultant b-hydroxy
acid was effectively transferred from that of the used a-hy-
droxy acid.
dure similar to that described for the preparationo of 3a, 3b (320 mg, 34% in
1
3 steps) was obtained from 7b (1.1 g, 4.8 mmol) as a yellow oil. H-NMR
(CDCl3) d: 0.93 (3H, t, Jꢀ7.3 Hz), 0.94 (3H, d, Jꢀ6.8 Hz), 0.96 (3H, d,
Jꢀ6.8 Hz), 1.33—1.48 (2H, m), 1.52—1.62 (2H, m), 1.87—2.03 (1H, m),
3.35 (1H, dt, Jꢀ9.2, 6.6 Hz), 3.41 (1H, d, Jꢀ5.5 Hz), 3.55 (1H, dt, Jꢀ9.2,
6.4 Hz), 5.67 (1H, s). IR (neat) cmꢁ1: 2104, 1638. FAB-MS m/z: 199.1453
(Calcd for C10H19N2O2: 199.1447).
General Procedure for the Dirhodium(II)-Catalyzed C–H Insertion of
a-Alkoxydiazoketone A solution of 3 (0.2 mmol) in an appropriate sol-
vent (2 ml) was added to a solution of dirhodium(II) catalyst (0.002 mmol)
in an appropriate solvent (10 ml) at room temperature or under reflux, and
the mixture was stirred for 10 min at the same temperature and the reaction
mixture was concentrated. The residue was chromatographed on silica gel.
Dirhodium(II)-Catalyzed C–H Insertion of 3a Entry 1: According to
the general procedure, 3a (47 mg, 0.2 mmol) was treated with Rh2(OAc)4 (1
mg, 0.002 mmol) in CH2Cl2 (12 ml) and the crude material was chro-
matographed on silica gel (10% EtOAc in hexane) to give a 1.4 : 1 mixture
of cis and trans isomers of 4a (12 mg, 30%) as a colorless oil. The ratio of
cis-4a and trans-4a was estimated to be 1.4 : 1 by integration of the intensi-
ties of the peak heights of the signals due to the methine proton at 5-position
which appeared at d 5.11 (dd) and 5.42 (t), respectively.
Entry 3: According to the general procedure, 3a (47 mg, 0.2 mmol) was
treated with Rh2(oct)4 (2 mg, 0.002 mmol) in CH2Cl2 (12 ml) and the crude
material was chromatographed on silica gel (10% EtOAc in hexane) to give
Experimental
Melting points are uncorrected. IR spectra were recorded using a JASCO a 17 : 1 mixture of cis and trans isomers of 4a (16 mg, 39%) as a colorless
FT/IR-410 spectrophotometer. 1H-NMR (300 MHz) and 13C-NMR oil. The mixture was re-chromatographed on silica gel (5% EtOAc in
(75.4 MHz) spectra were determined with a JEOL JNM-AL 300 spectrome-
ter, using CDCl3 as a solvent and tetramethylsilane as an internal standard. (cis-4a) as a colorless oil. 1H-NMR (CDCl3) d: 1.02 (3H, d, Jꢀ7.0 Hz), 1.13
All 13C-NMR spectra were determined with complete proton decoupling.
(3H, d, Jꢀ7.0 Hz), 2.11—2.27 (1H, m), 2.39 (1H, dd, Jꢀ17.8, 11.2 Hz),
hexane) to give pure (2S*,5S*)-2-isopropyl-5-phenyldihydrofuran-3-one
High resolution MS were determined with JEOL JMS-SX 102A (FAB-MS) 2.82 (1H, dd, Jꢀ17.8, 5.7 Hz), 3.81 (1H, d, Jꢀ3.7 Hz), 5.11 (1H, dd,
and JEOL JMS-BU 20 (EI- and CI-MS) instruments. Optical rotations were Jꢀ11.2, 5.7 Hz), 7.32—7.45 (5H, m). 13C-NMR (CDCl3) d: 17.0, 19.0, 30.3,
measured with a JASCO DIP-360 polarimeter. Column chromatography was 46.6, 76.8, 86.0, 126.0, 128.2, 128.6 (3), 140.4, 215.7. IR (neat) cmꢁ1: 1756.
1
performed on Silica gel 60 (0.063—0.200 mm) (MERCK).
CI-MS m/z: 205.1234 (Calcd for C13H17O2: 205.1228). The H-NMR spec-
3-Benzyloxy-1-diazo-4-methylpentan-2-one (3a) Lithium hydroxide trum of the mixture of cis and trans isomers of 4a exhibited the following
monohydrate (404 mg, 9.63 mmol) was added to a solution of known methyl signals of the trans-4a, d: 1.01 (3H, d, Jꢀ6.9 Hz), 1.09 (3H, d, Jꢀ6.9 Hz),
2-benzyloxy-3-methylhexanoate (7a)14) (855 mg, 3.85 mmol) in MeOH (30
2.05—2.20 (1H, m), 2.63 (1H, dd, Jꢀ18.2, 6.4 Hz), 2.89 (1H, dd, Jꢀ18.2,
ml) and H2O (6.2 ml) and the mixture was stirred at room temperature 7.7 Hz), 3.87 (1H, d, Jꢀ5.1 Hz), 5.42 (1H, t, Jꢀ7.2 Hz), 7.32—7.49 (5H,
overnight. The resulting mixture was concentrated under reduced pressure,
m).

April 2003
473
(cꢀ1.00, EtOH). [lit.18) [a]D24 ꢁ18.8° (cꢀ4.735, EtOH)]. HPLC:19) tR (R)-8,
21.96 min (4.8%); tR (S)-8, 24.33 min (95.2%) (Chiralcel ADH; hexane/
EtOH, 95/5; flow rate 1 ml/min; UV 254 nm).
Dirhodium(II)-Catalyzed C–H Insertion of 3b According to the gen-
eral procedure, 3b (20 mg, 0.1 mmol) was treated with Rh2(oct)4 (1 mg,
0.001 mmol) in refluxing benzene (6 ml) and the crude material was chro-
matographed on silica gel (5% EtOAc in hexane) to give (2S*,5R*)-2-iso-
propyl-5-propyldihydrofuran-3-one (cis-4b) (12 mg, 70%) as a colorless oil.
1H-NMR (CDCl3) d: 0.90 (3H, d, Jꢀ6.8 Hz), 0.97 (3H, t, Jꢀ7.3 Hz), 1.03
(3H, d, Jꢀ7.0 Hz), 1.32—1.84 (4H, m), 1.97—2.13 (1H, m), 2.04 (1H, dd,
Jꢀ17.7, 10.9 Hz), 2.49 (1H, dd, Jꢀ17.7, 5.4 Hz), 3.62 (1H, d, Jꢀ3.9 Hz),
4.02—4.16 (1H, m). 13C-NMR (CDCl3) d: 14.1, 16.8, 18.6, 18.8, 30.1, 37.7,
44.3, 75.2, 85.6, 217.0. IR (neat) cmꢁ1: 1754. CI-MS m/z: 171.1391 (Calcd
for C10H19O2: 171.1385).
Methyl (S)-2-Benzyloxy-3-methylhexanoate [(S)-7a] A solution of
methyl (S)-2-hydroxy-3-methylbutanoate [(S)-2a] (125 mg, 0.95 mmol),
which was prepared from L-valine,14) in DMF (0.5 ml) was added to a sus-
pension of NaH (18 mg, 0.75 mmol) in DMF (1 ml) at 0 °C under nitrogen
atmosphere and the mixture was stirred for 45 min at the same temperature.
A solution of benzyl bromide (162 mg, 0.95 mmol) in DMF (0.5 ml) was
added and stirred at 0 °C for 2 h. The mixture was quenched with saturated
aqueous NH4Cl, and extracted with Et2O. The extract was washed with H2O
and brine, dried (MgSO4), and concentrated. The residue was chro-
matographed on silica gel (20% EtOAc in hexane) to give the starting hy-
droxyester (26 mg, 21%) and (S)-7a14) (99 mg, 47%, 59% based on recovery
of starting material) as a colorless oil. [a]D24 ꢁ72.0° (cꢀ1.61, CH2Cl2), [a]D23
ꢁ73.5° (cꢀ2.44, CHCl3). [lit.17) for (R)-7a, [a]D20 ꢂ77.3° (cꢀ2.44, CHCl3)].
HPLC: tR (R)-7a, 4.01 min (4.6%); tR (S)-7a, 7.27 min (95.4%) (Chiralcel
OJ; hexane/i-PrOH, 90/10; flow rate 1 ml/min; UV 254 nm). The spectro-
scopic properties (1H-NMR and IR) were identical with those of the authen-
tic sample.14,17)
Acknowledgement This authors wish to thank Professor Yoshihiko Ito
for helpful discussions.
References
1) Ohkuma T., Kitamura M., Noyori R., “Catalytic Asymmetric Synthe-
sis,” 2nd ed., Chap. 1, ed. by Ojima I., Wiley-VCH, New York, 2000.
2) Carreira E. M., “Comprehensive Asymmetric Catalysis,” Vol. III
Chap. 29.1, eds. by Jacobssen E. N., Pfaltz A., Yamamoto H.,
Springer-Verlag, Berlin, 1999.
3) Wang Y.-C., Yan T.-H., J. Org. Chem., 65, 6752—6755 (2000) and ref-
erences cited therein.
4) Doyle M. P., McKervey M. A., Ye T., “Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds,” John Wiley & Sons, New
York, 1998.
5) Yakura T., Yakugaku Zasshi, 120, 1309—1322 (2000).
6) Yakura T., Ueki A., Kitamura T., Tanaka K., Nameki M., Ikeda M.,
Tetrahedron, 55, 7461—7470 (1999).
7) Yakura T., Yamada S., Azuma M., Ueki A., Ikeda M., Synthesis, 1998,
973—974 (1998).
8) Yakura T., Yamada S., Kunimune Y., Ueki A., Ikeda M., J. Chem. Soc.,
Perkin Trans. 1, 1997, 3643—3649 (1997).
9) Adams and co-workers reported that the C–H insertion reaction of a-
alkoxydiazoketone (9) (R1ꢀMe, n-Pr, R2ꢀMe, Ph, CH2OBn) with 1
weight % of Rh2(OAc)4 in CH2Cl2 gave the corresponding 3-furanone
(10) in moderate yield (34—47%) in good stereoselectivity
(cis : transꢀ3 : 1—8 : 1), see: Adams J., Poupart M.-A., Grenier L.,
Schaller C., Ouimet N., Frenette R., Tetrahedron Lett., 30, 1749—
1752 (1989).
(S)-3-Benzyloxy-1-diazo-4-methylpentan-2-one [(S)-3a] According to
the procedure for the conversion of racemic 7a into 3a, (S)-3a was obtained
from (S)-7a as a colorless oil. [a]D23 ꢁ106.1° (cꢀ0.95, CHCl3). The spectro-
scopic properties (1H-NMR and IR) were identical with those of racemic
sample.
Dirhodium(II)-Catalyzed C–H Insertion of (S)-3a According to the
general procedure, (S)-3a (200 mg, 0.86 mmol) was treated with Rh2(oct)4
(7 mg, 0.009 mmol) in refluxing benzene (51 ml) and the crude material was
chromatographed on silica gel (10% EtOAc in hexane) to give (2S,5S)-4a
(131 mg, 75%) as a colorless oil. [a]D23 ꢁ185.3° (cꢀ0.77, CHCl3). The spec-
troscopic properties (1H-NMR and IR) were identical with those of racemic
sample.
10) Adams J., Poupart M.-A., Grenier L., Tetrahedron Lett., 30, 1753—
1756 (1989).
(2R,3S)-2-Isopropyl-6-phenyl-1,3-dioxan-4-one (5a) A suspension of
(2S,5S)-4a (131 mg, 0.64 mmol), m-CPBA (221 mg, 1.28 mmol), and
NaHCO3 (54 mg, 0.64 mmol) in CH2Cl2 (6 ml) was stirred at room tempera-
ture for 10 h. The mixture was washed with saturated aqueous Na2S2O3, sat-
urated aqueous NaHCO3, and brine, dried (MgSO4), and concentrated. The
residue was chromatographed on silica gel (10% EtOAc in hexane) to give
5a (120 mg, 85%) as a colorless oil. 1H-NMR (CDCl3) d: 1.07 (3H, d,
Jꢀ7.0 Hz), 1.08 (3H, d, Jꢀ6.8 Hz), 2.02—2.18 (1H, m), 2.71 (1H, dd, Jꢀ
17.6, 10.8 Hz), 2.94 (1H, dd, Jꢀ17.6, 4.4 Hz), 4.93 (1H, dd, Jꢀ10.8, 4.4
Hz), 5.28 (1H, d, Jꢀ4.2 Hz), 7.33—7.44 (5H, m). 13C-NMR (CDCl3) d:
16.06, 16.13, 32.8, 38.1, 75.6, 106.5, 125.4, 128.6, 128.8 (3), 139.2, 167.6.
11) Clark et al. reported that treatment of diazoketone (11) with
Rh2(TPA)4 gave 2,5-cis-3-furanone (12) in 65% yield, see: Clark J. S.,
Dossetter A. G., Whittingham W. G., Tetrahedron Lett., 37, 5605—
5608 (1996).
12) Rychnovsky S. D., Buckmelter A. J., Dahanukar V. H., Skalitzky D. J.,
J. Org. Chem., 64, 6849—6860 (1999).
13) Powell N. A., Rychnovsky S. D., J. Org. Chem., 64, 2026—2037
(1999) and references cited therein.
14) Li W.-R., Ewing W. R., Harris B. D., Joullié M. M., J. Am. Chem. Soc.,
112, 7659—7672 (1990).
15) Gademann K., Seebach D., Helv. Chim. Acta, 84, 2924—2937 (2001).
16) Clark and co-workers reported that the similar C–H insertion reaction
of a-alkoxydiazoketone with dirhodium(II) catalyst gave an acetal de-
rivative as a by-product, see: Clark J. S., Dossetter A. G., J. Org.
Chem., 62, 4910—4911 (1997).
17) Ko K.-Y., Frazee W. J., Eliel E. L., Tetrahedron, 40, 1333—1343
(1984).
18) Boaz N. W., J. Org. Chem., 57, 4289—4292 (1992).
19) Denmark S. E., Winter S. B. D., Su X., Wong K.-T., J. Am. Chem. Soc.,
118, 7404—7405 (1996).
IR (neat) cmꢁ1
: 1747. CI-MS m/z: 220.1098 (Calcd for C13H16O3:
220.1099). [a]D23 ꢁ75.4° (cꢀ0.37, CHCl3).
Methyl (S)-3-Hydroxy-3-phenylpropanoate (8) A 10% HCl solution
(2 ml) was added to a solution 5a (60 mg, 0.27 mmol) in Et2O (2 ml) and the
mixture was vigorously sttired for 1 h. The organic layer was dried (MgSO4)
and concentrated. The residue was dissolved in Et2O and treated with excess
CH2N2. The solution was allowed to warm to room temperature and stirred
for 30 min. The excess of CH2N2 was destroyed by the addition of few drops
of AcOH. The mixture was diluted with H2O, and extracted with Et2O. The
organic layer was washed with aqueous saturated NaHCO3 solution and
brine, and dried (MgSO4) and concentrated. The residue was chro-
matographed on silica gel (20% EtOAc in hexane) to give 8 (20 mg, 41% in
2 steps) as a colorless oil. 1H-NMR (CDCl3) d: 2.71 (1H, dd, Jꢀ16.2,
4.4 Hz), 2.78 (1H, dd, Jꢀ16.2, 8.4 Hz), 3.20 (1H, br s), 3.73 (3H, s), 5.14
(1H, dd, Jꢀ8.4, 4.4 Hz), 7.24—7.50 (5H, m). 13C-NMR (CDCl3) d: 43.1,
51.9, 70.3, 125.6 (2), 127.8, 128.5 (2), 142.5, 172.8. IR (neat) cmꢁ1: 3422,
1734. EI-MS m/z: 180.0788 (Calcd for C10H12O3: 180.0786). [a]D23 ꢁ21.5°