Efficient catalytic asymmetric synthesis of trans-5-aryl-2-substituted cyclohexanones by rhodium-catalyzed conjugate arylation of racemic 6-substituted cyclohexenones

Article abstract of DOI:10.1002/adsc.200600263

Catalytic asymmetric conjugate arylation of racemic 6-substituted cyclohexenones with arylboronic acids was catalyzed by 3 mol% of chiral amidophosphane-[RhCl(C₂H₄)]₂ in a 10:1 mixture of 1,4-dioxane and water at 70°C to a

Full text of DOI:10.1002/adsc.200600263

FULL PAPERS
DOI: 10.1002/adsc.200600263
Efficient Catalytic Asymmetric Synthesis of trans-5-Aryl-2-substi-
tuted Cyclohexanones by Rhodium-Catalyzed Conjugate Aryla-
tion of Racemic 6-Substituted Cyclohexenones
Qian Chen,a Takahiro Soeta,a Masami Kuriyama,a Ken-ichi Yamada,a
and Kiyoshi Tomiokaa,*
a
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo, Kyoto 606-8501, Japan
Fax : (+81)-75-753-4604; e-mail: tomioka@pharm.kyoto-u.ac.jp
Received: June 3, 2006; Accepted: September 20, 2006
Abstract: Catalytic asymmetric conjugate arylation sequently epimerized with sodium ethoxide in etha-
of racemic 6-substituted cyclohexenones with aryl- nol to give thermodynamically stable trans-5-aryl-2-
boronic acids was catalyzed by 3 mol% of chiral substituted cyclohexanones with 99–97% ee in high
amidophosphane-[RhClACTHREU(NG C2H4)]2 in a 10:1 mixture of two-step yields.
1,4-dioxane and water at 708C to afford a nearly 1:1
mixture of trans- and cis-5-aryl-2-substituted cyclo- Keywords: arylation; asymmetric catalysis; conjugate
hexanones in high enantioselectivity, which was sub- addition; cyclohexanones; rhodium
Introduction
reactive enolate intermediate that upon treatment
with an electrophile produces two new chiral centers
The catalytic asymmetric conjugate addition reaction in adjacent C2 and C3 positions of the cyclohexanone
of enones with metal-activated nucleophiles has been skeleton. This technology enables us to synthesize
the significant historical milestone of modern asym- chiral disubstituted cyclohexanones with two chiral
metric reactions.[1] Tremendous efforts have been de- centers starting from achiral cyclohexenone. Although
voted on the discovery of efficient chiral sources for it is remarkable to know that chiral compounds bear-
the reaction with carbon and heteroatom nucleo- ing two chiral centers are produced from an achiral
philes. Chiral phosphorus compounds have been the starting substrate by one-pot operation of an asym-
recently established fruits of chiral sources for this metric reaction, it is much more interesting to devel-
purpose.[2] A familiar touchstone for the evaluation of op a kind of asymmetric reaction which utilizes race-
chiral sources has been the asymmetric reaction of cy- mic substituted cyclohexenone as a substrate to pro-
clohexenone 2 with diorganozinc-copper(I)[3] or aryl- duce chiral disubstituted cyclohexanones bearing two
boronic acid-rhodium(I)[4,5] reagent-catalyst combina- chiral centers in a single operation. It is important to
tions (Scheme 1). We have also engaged in this fasci- remember that racemic substrates are usually consid-
nating challenge and succeeded in the development of ered as a substrate of kinetic resolution in which a
chiral amidophosphane 1-based catalytic asymmetric chiral target is obtained as a recovery of the lesser re-
conjugate addition reaction of 2 with organometallic active starting material among a pair of enantiomers
reagents giving 3 (Scheme 1).[6,7] The advantage of by preferential consumption of more reactive other
conjugate addition reaction lies in the generation of a enantiomer.[8] We have already developed a two-step
asymmetric synthesis of 5-arylcyclohexenones 6,
which utilized racemic 5-(trimethylsilyl)cyclohexen-
one 4 as a substrate in a chiral amidophosphane 1-
rhodium(I)-catalyzed asymmetric conjugate arylation
with arylboronic acids to afford trans- and cis-3-aryl-
5-(trimethylsilyl)cyclohexanones 5 both with high ee
and subsequent dehydrosilylation of the mixture af-
forded 5-arylcylohexenones 6 with high ee in a rea-
sonably high two-step yield (Scheme 2).[9] It should
Scheme 1.
not be omitted to consider the work by Krause and
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Asymmetric Synthesis of trans-5-Aryl-2-substituted Cyclohexanones
FULL PAPERS
Chiral catalyst control changes the situation in
which an enantiofacial selective arylation is operative
over the trans control. Thus, the catalytic asymmetric
conjugate phenylation of racemic 6-methylcyclohexen-
one 7a with phenylboronic acid was conducted in the
presence of 3.3 mol% of a chiral amidophosphane 1,
1.5 mol% of [RhClACTHREU(GN C2H4)2]2 and 1 equivalent of po-
tassium hydroxide in a 10:1 mixture of 1,4-dioxane
and water at 708C for 4 h to give a 50:50 mixture of
trans- and cis-8a both with high ee of 99% and 97%,
respectively, in 95% combined isolated yield
(Scheme 4). Subsequent epimerization of the mixture
Scheme 2.
Alexakis who reported the asymmetric synthesis of
trans-5-alkyl-2-methylcyclohexanones starting from 6-
methylcyclohexenone 7a by a chiral phosphoroami-
dite-copper(I)-catalyzed asymmetric conjugate alkyla-
tion with diorganozinc and subsequent epimeriza-
tion.[10] Now we describe a general, two-step asym-
metric synthesis of trans-5-aryl-2-substituted cyclohex-
anones 8 with sufficiently high ee starting from race-
mic 6-substituted cyclohexenones 7.
Results and Discussion
Catalytic Asymmetric Conjugate Arylation of 6-
Substituted Cyclohexenones
Scheme 4.
Conjugate phenylation of racemic 6-methylcyclohexe-
none 7a with phenylboronic acid was examined using with 2 equivalents of sodium ethoxide in ethanol at
3 mol% of racemic-BINAP-rhodium(I)-catalyst in room temperature for 24 h gave thermodynamically
order to gather information on the stereochemical stable trans-(2S,5S)-8a[13] in 90% yield.[14] The enan-
pathway (Scheme 3). The reaction gave a mixture of tioselectivity of trans-8a was determined to be 98%
racemic trans- and cis-8a in a ratio of 76:24 in 79% ee by a chiral stationary phase HPLC. The high yield
isolated yield.[11] The similar trans-selectivity was also production of highly enantioenriched trans-8a indi-
observed in 3-methoxyphenylation (76:24 in 92%) cates that the new chiral centers of trans- and cis-8a
and 3-chlorophenylation (77:23 in 90%), indicating were created in the same sense of enantiofacial selec-
generality in the stereoselective production of trans-8. tivity. It is remarkable that nearly optically pure
This trans-selectivity is complementary to that in the trans-8a was obtained in 86% total yield starting from
organocopper-mediated conjugate addition of 7a in racemic 7a.
which the cis isomer is obtained as a major prod-
The two-step catalytic asymmetric synthesis of 5-
aryl-2-methylcyclohexanones 8 from racemic 7a was
general to give a 50:50 mixture of trans- and cis-5-(3-
methoxyphenyl)- and 5-(3-chlorophenyl)-2-methylcy-
clohexanones 8 that were then epimerized to trans-8
with 98% and 99% ee, respectively, in high yields
(Table 1, entries 1–3).
uct.[12]
Other 6-substituted cyclohexenones 7b–d bearing
benzyl, phenyl, and tert-butyl group as 6-substituent
were also converted to the corresponding nearly
50:50 mixture of trans- and cis-5-aryl-2-substituted cy-
clohexanones 8 with high ees in high yields. Subse-
quent epimerization of these mixtures gave trans-8
with high ee of over 97% ee in high yields (entries 4–
9). It is important to note that the asymmetric conju-
gate arylation of 7 is general with regard to 6-substitu-
Scheme 3.
Adv. Synth. Catal. 2006, 348, 2604 – 2608
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Qian Chen et al.
FULL PAPERS
Table 1. Catalytic asymmetric conjugate arylation of racemic 7 and subsequent epimerization to trans-8.
Entry
7
R
Ar
Time [h]
trans-8 + cis-8 yield [%]
trans:cis
trans-8 yield [%]
ee [%]
1
2
3
4
5
6
7
8
9
7a
7a
7a
7b
7b
7b
7c
7c
7d
Me
Me
Me
Bn
Bn
Bn
Ph
Ph
4
4
8
4
7
4
7
4
7
95
90
91
97
99
99
97
50:50
51:49
50:50
50:50
50:50
50:50
50:50
90
92
93
98
93
91
95
98
98
99
98
98
98
98
3-MeOC6H4
3-ClC6H4
Ph
3-MeOC6H4
3-FC6H4
Ph
Ph
t-Bu
4-MeOC6H4
Ph
9650:50
75
88
97
63:37
93
98
(11.6mg, 0.033 mmol) and [RhCl ACHTRE(UGN C2H4)]2 (5.8 mg,
ent of 7 to afford the corresponding arylated products
with high ee in high yields. This point is different from
the copper(I)-catalyzed conjugate alkylation reaction
reported by Alexakis and Krause in which 6-methyl-
cyclohexenone 7a is the substrate only applicable.[10]
0.015 mmol) in 0.25 mL of 4M aqueous KOH (1.0 mmol)
and 1,4-dioxane (2.5 mL) was stirred at 708C for 4 h. After
dilution with AcOEt (40 mL), the mixture was washed with
10% NaOH (10 mL) and brine (20 mL), and then dried
over sodium sulfate. Concentration and column chromatog-
raphy (hexane/AcOEt=40/1) gave a 50:50 mixture of trans-
and cis-8a as a colorless oil; yield: 179 mg (95%). The ratio
1
Conclusions
was determined by the integration area of H NMR signals
at 2.97 ppm for trans-8a and 3.26–3.31 ppm for cis-8a.
A solution of the 50:50 mixture of trans- and cis-8a
(112 mg, 0.6mmol) in 6mL of 0.2 m sodium ethoxide
(1.2 mmol) in ethanol was stirred at room temperature for
24 h. The mixture was diluted with diethyl ether (10 mL),
and successively washed with saturated ammonium chloride
(10 mL), satd sodium bicarbonate (10 mL) and brine
(10 mL), and then dried over sodium sulfate. Concentration
and column chromatography (hexane/Et2O=20/1) gave
trans-8a as a white solid; yield: 101 mg (90%); 98% ee; mp
65–668C; [a]2D0: À28.5 (c 1.0, CHCl3). The% ee was deter-
mined to be 98% by HPLC (Daicel Chiralpak AD-H,
hexane/2-propanol=100/1, 254 nm, 0.5 mLminÀ1, 20 and
21 min for major and minor). 1H NMR: d=1.08 (d, J=
6.4 Hz, 3H), 1.50 and 1.94 (dddd, J=13.1, 13.1, 13.1, 3.4 Hz,
each 1H), 2.07 (m, 1H), 2.20 (m, 1H), 2.43–2.56(m, 2H),
2.61 (ddd, J=13.1, 3.8, 2.0 Hz, 1H), 2.97 (m, 1H), 7.22–7.26
(m, 3H), 7.33 (t, J=7.5 Hz, 2H); 13C NMR: d=14.3, 33.2,
35.1, 44.6, 45.8, 49.1, 126.5, 126.7, 128.7, 144.4, 212.1; IR
(KBr): n=1705 cmÀ1; EI-MS: m/z=188 (M+); HR-MS-EI
m/z=188.1204, calcd. for C13H16O (M+): 188.1201.
A general, two-step catalytic asymmetric synthesis of
5-aryl-2-substituted cyclohexanones starting from rac-
emic 6-substituted cyclohexenones was developed by
applying a chiral amidophosphane-rhodium(I)-cata-
lyzed asymmetric conjugate arylation with a variety
of arylboronic acids. The enantioselectivity reached
up to 99%.[15]
Experimental Section
1
All melting points are uncorrected. H and 13C NMR spectra
were measured in CDCl3. Chemical shift values are ex-
pressed in ppm relative to internal tetramethylsilane. Abbre-
viations are as follows: s, singlet; d, doublet; t, triplet; q,
quartet; m, multiplet; br, broad. IR spectra were expressed
in cmÀ1. Purification was carried out by silica gel column
chromatography. Racemic 6-substituted cyclohexenones 7
were prepared according to the procedure analogues to
those reported.[16]
AHCTRE(UNG 2S,5S)-5-(3-Methoxyphenyl)-2-methylcyclohexanone
(trans-8: R=Me, Ar=3-MeOC6H4) (Table 1, entry 2)
Catalytic Asymmetric Conjugate Phenylation of 6-
Methylcyclohexenone (7a: R=Me) and Subsequent
Epimerization to Trans-ACHTREU(NG 2S,5S)-2-Methyl-5-phenyl-
cyclohexanone (8a: R=Me, Ar=Ph) (Table 1,
A 49:51 mixture of trans- and cis-8 (determined by the inte-
1
gration area of H NMR signals at 2.95 ppm for trans-8 and
3.22–3.27 ppm for cis-8) was epimerized to give, after chro-
matography (hexane/Et2O=25/1), trans-8 as a colorless oil;
[a]2D0: À21.0 (c 1.2, CHCl3); 98% ee (Daicel Chiralpak AD-
H, hexane/2-propanol=100/1, 254 nm, 0.5 mLminÀ1, 38 and
41 min for major and minor); 1H NMR: d=1.08 (d, J=
entry 1)
A
mixture of 6-methylcyclohexenone (7a) (110 mg,
1.0 mmol), phenylboronic acid (610 mg, 5.0 mmol), ligand 1
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Asymmetric Synthesis of trans-5-Aryl-2-substituted Cyclohexanones
FULL PAPERS
6.4 Hz, 3H), 1.49 and 1.93 (dddd, J=13.0, 13.0, 13.0, 3.7 Hz,
each 1H), 2.07 (m, 1H), 2.20 (m, 1H), 2.45–2.54 (m, 2H),
2.60 (ddd, J=13.0, 3.7, 2.2 Hz, 1H), 2.95 (m, 1H), 3.81 (s,
3H), 6.77–6.83 (m, 3H), 7.24 (m, 1H); 13C NMR: d=14.3,
33.1, 35.0, 44.7, 45.8, 49.1, 55.1, 111.6, 112.7, 118.9, 129.7,
146.0, 159.9, 212.1; IR (neat): n=1682 cmÀ1; EI-MS: m/z=
218 (M+); HR-MS-EI: m/z=218.1300; calcd. for C14H18O2
(M+): 218.1307.
anal. calcd. for C20H22O: C 81.60, H 7.53; found: C 81.32, H
7.55.
AHCTRE(UNG 2R,5S)-2-Benzyl-5-(3-fluorophenyl)cyclohexanone
(8: R=Bn, Ar=3-FC6H4) (Table 1, entry 6)
A 50:50 mixture of 8 (determined by the integration area of
1H NMR signals at 3.00 ppm for trans-8 and 3.15–3.19 ppm
for cis-8) was epimerized to give, after chromatography
(hexane/Et2O=25/1), trans-8 as a white solid; mp 65–678C;
[a]2D0: +8.7 (c 1.0, CHCl3); 98% ee (Daicel Chiralpak AD-
H, hexane/2-propanol=100/1, 254 nm, 0.5 mLminÀ1, 24 and
20 min for major and minor); 1H NMR: d=1.46and 1.82
(dddd, J=13.0, 13.0, 13.0, 3.5 Hz, each 1H), 2.04 (m, 1H),
2.14 (m, 1H), 2.45 (dd, J=14.0, 8.6Hz, 1H), 2.54 (dd, J=
13.3, 13.3 Hz, 1H), 2.61–2.67 (m, 2H), 3.00 (m, 1H), 3.30
(dd, J=14.0, 4.9 Hz, 1H), 6.90–6.94 (m, 2H), 6.98 (d, J=
7.6Hz, 1H), 7.18–7.31 (m, 6H); 13C NMR: d=32.2, 32.9,
35.1, 45.6, 49.2, 51.7, 113.4 (d, J=21.7 Hz), 113.6(d, J=
20.7 Hz), 122.2 (d, J=3.1 Hz), 126.1, 128.4, 129.2, 130.1 (d,
J=8.2 Hz), 140.2, 146.7 (d, J=7.2 Hz), 163.0 (d, J=245 Hz),
210.6; IR (KBr): n=1713 cmÀ1; EI-MS: m/z=282 (M+);
anal. calcd. for C19H19FO: C 80.82, H 6.78; found: C 80.80,
H 6.98.
ACHTREUNG(2S,5S)-5-(3-Chlorophenyl)-2-methylcyclohexanone
(trans-8: R=Me, Ar=3-ClC6H4) (Table 1, entry 3)
A 50:50 mixture of trans- and cis-8 (determined by the inte-
1
gration area of H NMR signals at 2.95 ppm for trans-8 and
3.23–3.28 ppm for cis-8) was epimerized to give, after chro-
matography (hexane/Et2O=25/1), trans-8 as a white solid;
mp 70–728C; [a]2D0: À19.3 (c 1.1, CHCl3); 99% ee (Daicel
Chiralpak AD-H, hexane/2-propanol=100/1, 254 nm,
0.5 mLminÀ1, 20 and 22 min for major and minor);
1H NMR: d=1.09 (d, J=6.4 Hz, 3H), 1.49 and 1.92 (dddd,
J=13.0, 13.0, 13.0, 3.4 Hz, each 1H), 2.07 (m, 1H), 2.21 (m,
1H), 2.43–2.53 (m, 2H), 2.59 (ddd, J=13.1, 4.0, 2.2 Hz, 1H),
2.95 (m, 1H), 7.10 (d, J=7.6Hz, 1H), 7.21–7.28 (m, 3H);
13C NMR: d=14.2, 33.0, 34.8, 44.6, 45.4, 48.8, 124.8, 126.7,
126.9, 130.0, 134.4, 146.3, 211.6; IR (KBr): n=1713 cmÀ1
;
EI-MS: m/z=222 (M+); anal. calcd. for C13H15ClO: C 70.11,
H 6.79; found: C 70.19, H 6.89.
AHCTRE(UNG 2R,5S)-2,5-Diphenylcyclohexanone (trans-8:
R=Ar=Ph) (Table 1, entry 7)
ACHTREUNG(2R,5S)-2-Benzyl-5-phenylcyclohexanone (trans-8:
R=Bn, Ar=Ph) (Table 1, entry 4)
A 50:50 mixture of trans- and cis-8 (determined by the inte-
1
gration area of H NMR signals at 3.17 ppm for trans-8 and
A 50:50 mixture of trans- and cis-8 (determined by the inte-
3.30–3.36ppm for cis-8) was epimerized to give, after chro-
matography (hexane/Et2O=30/1), trans-8 as a white solid;
mp 150–1528C; [a]2D0: +27.2 (c 1.2, CHCl3); 98% ee (Daicel
1
gration area of H NMR signals at 3.00 ppm for trans-8 and
3.15–3.21 ppm for cis-8) was epimerized to give, after chro-
matography (hexane/Et2O=50/1), trans-8 as a white solid;
mp 75–778C; [a]2D0: +4.5 (c 1.0, CHCl3); 98% ee (Daicel
Chiralpak AD-H, hexane/2-propanol=100/1, 254 nm,
0.5 mLminÀ1, 46and 39 min for major and minor);
1H NMR: d=1.47 and 1.84 (dddd, J=13.0, 13.0, 13.0,
3.6Hz, each 1H), 2.04 (m, 1H), 2.14 (m, 1H), 2.45 (dd, J=
14.0, 8.7 Hz, 1H), 2.54–2.68 (m, 3H), 3.00 (m, 1H), 3.31 (dd,
J=14.0, 4.6Hz, 1H), 7.19–7.34 (m, 10H); 13C NMR: d=
32.4, 33.1, 35.2, 46.0, 49.4, 51.8, 126.0, 126.5, 126.7, 128.4,
128.7, 129.2, 140.3, 144.2, 211.1; IR (KBr): n=1705 cmÀ1; EI-
MS: m/z=264 (M+); HR-MS-EI: m/z=264.1510, calcd. for
C19H20O (M+): 264.1514.
Chiralpak
AD-H,
hexane/2-propanol=10/1,
254 nm,
0.5 mLminÀ1, 18 and 20 min for major and minor);
1H NMR: d=2.08–2.25 (m, 3H), 2.41 (m, 1H), 2.69–2.78 (m,
2H), 3.17 (m, 1H), 3.68 (dd, J=12.6, 5.6 Hz, 1H), 7.18 (d,
J=7.0 Hz, 2H), 7.25–7.31 (m, 4H), 7.35–7.39 (m, 4H);
13C NMR: d=33.4, 34.3, 45.7, 49.5, 56.9, 126.5, 126.8, 127.1,
128.4, 128.7, 128.8, 138.5, 144.1, 208.9; IR (KBr): n=
1713 cmÀ1
;
EI-MS: m/z=250 (M+); HR-MS-EI: m/z=
250.1355, calcd. for C18H18O (M+): 250.1358.
AHCTRE(UNG 2R,5S)-5-(4-Methoxyphenyl)-2-phenylcyclohexanone
(trans-8: R=Ph, Ar=4-MeOC6H4) (Table 1, entry 8)
ACHTREUNG(2R,5S)-2-Benzyl-5-(3-methoxyphenyl)cyclohexanone
(trans-8: R=Bn, Ar=3-MeOC6H4) (Table 1, entry 5)
A 50:50 mixture of trans- and cis-8 (determined by the inte-
1
gration area of H NMR signals at 3.11 ppm for trans-8 and
A 50:50 mixture of 8 was epimerized to give, after chroma-
tography (hexane/Et2O=25/1), trans-8 as a white solid; mp
64–668C; [a]2D0: +4.7 (c 1.2, CHCl3); 98% ee (Daicel Chiral-
3.28–3.34 ppm for cis-8) was epimerized to give, after chro-
matography (hexane/Et2O=20/1), trans-8 as a white solid;
mp 131–1338C; [a]2D0: +24.7 (c 1.0, CHCl3); 97% ee (Daicel
pak
0.5 mLminÀ1, 37 and 32 min for major and minor);
1H NMR: d=1.46and 1.83 (dddd,
J=13.0, 13.0, 13.0,
3.5 Hz, each 1H), 2.04 (m, 1H), 2.13 (m, 1H), 2.45 (dd, J=
14.0, 8.8 Hz, 1H), 2.56(ddd, J=13.0, 13.0, 1.3 Hz, 1H),
2.60–2.67 (m, 2H), 2.97 (m, 1H), 3.30 (dd, J=14.0, 4.6Hz,
1H), 3.80 (s, 3H), 6.75–6.81 (m, 3H), 7.18–7.31 (m, 6H);
13C NMR: d=32.4, 33.0, 35.1, 46.0, 49.4, 51.8, 55.1, 111.7,
112.6, 118.8, 126.0, 128.4, 129.2, 129.7, 140.3, 145.9, 159.9,
211.1; IR (KBr): n=1705 cmÀ1; EI-MS: m/z=294 (M+);
AD-H,
hexane/2-propanol=100/1,
254 nm,
Chiralpak
AD-H,
hexane/2-propanol=10/1,
254 nm,
0.5 mLminÀ1, 23 and 26min for major and minor);
1H NMR: d=2.01–2.22 (m, 3H), 2.39 (m, 1H), 2.67 (dd, J=
13.1, 13.1 Hz, 1H), 2.73 (ddd, J=13.1, 4.2, 1.6Hz, 1H), 3.11
(m, 1H), 3.68 (dd, J=12.6, 5.4 Hz, 1H), 3.81 (s, 3H), 6.90
(d, J=8.2 Hz, 2H), 7.17–7.21 (m, 4H), 7.28 (m, 1H), 7.35–
7.38 (m, 2H); 13C NMR: d=33.6, 34.3, 44.9, 49.8, 55.2, 56.9,
114.1, 127.1, 127.4, 128.4, 128.7, 136.3, 138.5, 158.4, 209.0; IR
(KBr): n=1705 cmÀ1; EI-MS: m/z=280 (M+); anal. calcd.
for C19H20O2: C 81.40, H 7.19; Found: C 81.10; H 7.42.
Adv. Synth. Catal. 2006, 348, 2604 – 2608
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Qian Chen et al.
FULL PAPERS
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Sugita, K. Yoshida, J. Am. Chem. Soc. 2005, 127,
11934–11935.
ACHTREUNG
A 63:27 mixture of trans- and cis-8 (determined by the inte-
gration area of H NMR signals at 2.99 ppm for trans-8 and
1
3.28–3.33 ppm for cis-8) was epimerized to give, after chro-
matography (hexane/Et2O=50/1), trans-8 as a white solid;
mp 85–878C, [a]2D0: À4.5 (c 1.0, CHCl3), 98% ee (Daicel
Chiralpak AD-H, hexane/2-propanol=100/1, 254 nm,
0.5 mLminÀ1, 12 and 13 min for major and minor),
1H NMR: d=1.04 (s, 9H), 1.59 and 1.89 (dddd, J=12.8,
12.8, 12.8, 3.7 Hz, each 1H), 2.12 (m, 1H), 2.23–2.31 (m,
2H), 2.47–2.57 (m, 2H), 2.99 (m, 1H), 7.21–7.24 (m, 3H),
7.32 (t, J=7.4 Hz, 2H); 13C NMR: d=27.6, 28.6, 31.7, 33.9,
46.6, 51.1, 59.6, 126.5, 126.7, 128.7, 144.3, 211.3; IR (KBr):
n=1713 cmÀ1; EI-MS: m/z=230 (M+); anal. calcd. for
C16H22O: C 83.43, H 9.63; found: C 83.13, H 9.83.
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Acknowledgements
This research was partially supported by the 21 st Century
COE (Center of excellence) Program “Knowledge Informa-
tion Infrastructure for Genome Science” and a Grant-in-Aid
for Scientific Research on Priority Areas “Advanced Molecu-
lar Transformations of Carbon Resources” from the Ministry
of Education, Culture, Sports, Science and Technology,
Japan.
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