Oxidative kinetic resolution-Claisen rearrangement sequence to enantioenriched arylcycloalkenes

Article abstract of DOI:10.1055/s-2006-958415

The Pd-catalyzed oxidative kinetic resolution of secondary alcohols afforded enantioenriched allylic alcohols with high selectivity. These alcohols were transformed into arylcycloalkenes with enantioenriched tertiary and quaternary stereocenters through a

Full text of DOI:10.1055/s-2006-958415

CLUSTER
3533
Oxidative Kinetic Resolution–Claisen Rearrangement Sequence to
Enantioenriched Arylcycloalkenes
Oxidative Kinetic
a
Resolution–
v
Claise
n
Rea
i
rrange
m
d
ent of Allylic Alc
C
ohols . Ebner, Zoltán Novák, Brian M. Stoltz*
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Fax +1(626)5649297; E-mail: stoltz@caltech.edu
Received 4 September 2006
Pd(sparteine)Cl2 (5 mol%)
(–)-sparteine (15 mol%)
Cs2CO3 (0.5 equiv)
Abstract: The Pd-catalyzed oxidative kinetic resolution of second-
ary alcohols afforded enantioenriched allylic alcohols with high
selectivity. These alcohols were transformed into arylcycloalkenes
with enantioenriched tertiary and quaternary stereocenters through
a two-step vinylation and Lewis acid promoted Claisen rearrange-
ment. Subsequent Pd-catalyzed oxidative cyclization of a Claisen
product afforded a 5,5-fused tetrahydrofuran.
OH
OH
t-BuOH (1.5 equiv)
O2 (1 atm), MS 3 Å
PhCH3, 60 °C
(±)-1
(+)-1
1.5 h, 53% conv., 99% ee, s = 80
Key words: oxidative kinetic resolution, Claisen rearrangement,
Scheme 1
oxidative cyclization, secondary alcohols, palladium catalysis
ing these substrates, affording allylic alcohols with out-
standing selectivity and unprecedented reactivity
(Table 1).
As part of a general program directed toward the design of
new synthetic methodology to facilitate the efficient con-
struction of complex targets, we have developed a number
of Pd(II)-catalyzed oxidative transformations.1,2 These
oxidations take advantage of the versatility of palladium
to selectively perform a variety of processes and utilize
molecular oxygen as an operationally simple and inexpen-
sive stoichiometric oxidant. Recently, our group reported
the oxidative kinetic resolution of secondary alcohols us-
ing a palladium dichloride catalyst precursor [Pd(nbd)Cl2]
in conjunction with the commercially available diamine
(–)-sparteine.1a,3 We subsequently made a number of im-
provements,1b,c rendering these methods more amenable
to synthetic endeavors.4,5
Allylic alcohols with both electron-rich and electron-poor
benzene substituents led to excellent selectivities (entries
1–5), as did substrates containing other aromatic rings
(entries 6 and 7), including a heteroaromatic furan. Impor-
tantly, a 3-substituted allylic alcohol (entry 8) and a cyclo-
hexenyl alcohol (entry 9) were also obtained in high ee
with very short reaction times. For comparison, an alkyl-
cyclopentenol was resolved much less successfully,
affording modest selectivity after prolonged reaction
times (entry 10).
Next, we looked to further elaborate these resolved aryl-
alcohols into other synthetically useful building blocks.
To this end, alcohol (–)-8 was subjected to Claisen re-
arrangement conditions. While both Ireland–Claisen7 and
Johnson orthoester Claisen conditions8 were unsuccessful
in our hands, a two-step protocol involving Hg-promoted
vinylation followed by Claisen rearrangement proved
effective. The vinyl ether was prone to 1,3-rearrangement
in the presence of various Lewis acids and under thermal
conditions. However, we found that treatment of vinyl
ether (+)-11 with DIBAL-H in CH2Cl2 at –40 °C led to
clean Claisen rearrangement followed by reduction of the
intermediate aldehyde (Scheme 2).
While these developments greatly enhanced the reactivity
and selectivity of this oxidative system, the explored
substrate scope remained somewhat limited. In particular,
allylic alcohols were a relatively unexplored class of com-
pounds using our methodology.3c,5 Due to their broad ap-
plication in complex molecule synthesis, their successful
resolution would be an important demonstration of the
utility of the Pd-catalyzed oxidative kinetic resolution.
Herein, we report the resolution of a number of secondary
allylic alcohols, which can be further transformed into
enantioenriched primary alcohols with tertiary and qua-
ternary stereocenters through Claisen rearrangement.
We then applied this two-step sequence to other resolved
alcohols. Though the vinylation gave modest yields, the
majority of the mass balance was recovered starting
material. The DIBAL-H promoted Claisen rearrangement
afforded good to excellent yields of the desired primary
alcohol (Table 2). Allylic alcohols bearing a variety of
aromatic groups were successfully transformed to enan-
tioenriched arylcyclopentenes. This sequence also al-
lowed access to a cyclohexene (entry 9) and a primary
alcohol containing a quaternary stereocenter (entry 8) in
high ee.
Our exploration of the scope of the oxidative kinetic reso-
lution of secondary alcohols led us to investigate a variety
of 2-aryl allylic alcohols. These compounds were readily
prepared by reported methods6 and then subjected to our
enantioselective oxidation conditions (Scheme 1). To our
delight, our system was exceptionally effective in resolv-
SYNLETT 2006, No. 20, pp 3533–3539
1
8
.1
2
.2
0
0
6
Advanced online publication: 08.12.2006
DOI: 10.1055/s-2006-958415; Art ID: Y01306ST
© Georg Thieme Verlag Stuttgart · New York

3534
D. C. Ebner et al.
CLUSTER
Table 1 Oxidative Kinetic Resolution of Allylic Alcoholsa
Entry
1
Alcohol
Reaction time (h)
1.5
Conversionb
53
eec
99
sd
OH
89
(+)-1
2
3
4
5
6
7
8
3.5
1.5
1.5
1.5
1.5
10
58
54
61
63
53
64
53
99
97
99
99
94
99
98
31
46
22
19
36
19
64
OH
Me
(+)-2
OH
MeO
(+)-3
OH
O
O
(+)-4
OH
OH
F3C
(+)-5
(+)-6
OH
O
(+)-7
1
OH
Me
(–)-8
9
3
57
72
97
93
27
OH
(–)-9
10
21
6.5
OH
10
a Reaction conditions: Pd(sparteine)Cl2 (5 mol%), (–)-sparteine (15 mol%), Cs2CO3 (0.5 equiv), t-BuOH (1.5 equiv), O2 (1 atm), 3 Å MS in
toluene (0.25 M allylic alcohol), 60 °C.
b Percent conversion (%) determined by GC relative to internal standard.
c Alcohol percent ee determined by chiral HPLC.
d s = kfast/kslow = ln[(1 – conv)(1 – eealc)]/ln[(1 – conv)(1 + eealc)].
Synlett 2006, No. 20, 3533–3539 © Thieme Stuttgart · New York

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Oxidative Kinetic Resolution–Claisen Rearrangement of Allylic Alcohols
3535
Table 2 Vinylation and Claisen Rearrangement of Allylic Alcohols12
Entry
1
Alcohola
Vinyl ether yield (%)b
55
Claisen productc
Claisen product yield (%)b
(+)-1
36
H
HO
(+)-13
2
3
4
5
6
(+)-2
(+)-3
(+)-4
(+)-5
(+)-6
42
36
56
37
47
77
Me
H
HO
(+)-14
91
76
82
86
MeO
H
HO
(+)-15
O
O
H
HO
(+)-16
F3C
H
HO
(+)-17
H
HO
(+)-18
7
8
(+)-7
(–)-8
31
61
87
72
O
H
HO
(+)-19
Me
HO
(+)-12
9
(–)-9
16
83
HO
H
(+)-20
a Reaction conditions: Hg(OAc)2 (0.28 equiv) in ethyl vinyl ether (0.08 M allylic alcohol), 40 °C, 120 h.
b Isolated yield.
c Reaction conditions: DIBAL-H (1.1 equiv, 1 M in PhMe) in CH2Cl2 (0.08 M vinyl ether), –40 °C to 23 °C, 2 h.
Synlett 2006, No. 20, 3533–3539 © Thieme Stuttgart · New York

3536
D. C. Ebner et al.
CLUSTER
Stoltz, B. M. Angew. Chem. Int. Ed. 2004, 43, 6144.
(d) Trend, R. M.; Ramtohul, Y. K.; Stoltz, B. M. J. Am.
Chem. Soc. 2005, 127, 17778.
O
DIBAL-H
CH2Cl2
OEt
(–)-8
(3) Simultaneous to our publication, a related system was
reported, see: (a) Jensen, D. R.; Pugsley, J. S.; Sigman, M. S.
J. Am. Chem. Soc. 2001, 123, 7475. (b) Mueller, J. A.;
Jensen, D. R.; Sigman, M. S. J. Am. Chem. Soc. 2002, 124,
8202. (c) Mandal, S. K.; Jensen, D. R.; Pugsley, J. S.;
Sigman, M. S. J. Org. Chem. 2003, 68, 4600. (d) Mandal,
S. K.; Sigman, M. S. J. Org. Chem. 2003, 68, 7535.
(e) Mueller, J. A.; Sigman, M. S. J. Am. Chem. Soc. 2003,
125, 7005. (f) Jensen, D. R.; Sigman, M. S. Org. Lett. 2003,
5, 63. (g) Mueller, J. A.; Cowell, A.; Chandler, B. D.;
Sigman, M. S. J. Am. Chem. Soc. 2005, 127, 14817.
(h) Sigman, M. S.; Jensen, D. R. Acc. Chem. Res. 2006, 39,
221.
(4) For application to natural product synthesis, see: Tambar, U.
K.; Ebner, D. C.; Stoltz, B. M. J. Am. Chem. Soc. 2006, 128,
11752.
(5) For application to the synthesis of pharmaceutical
intermediates, see: Caspi, D. D.; Ebner, D. C.; Bagdanoff, J.
T.; Stoltz, B. M. Adv. Synth. Catal. 2004, 346, 185.
(6) (a) Ruel, F. S.; Braun, M. P.; Johnson, C. R. Org. Synth.,
Coll. Vol. X; Wiley and Sons: New York, 2004, 467.
(b) Padwa, A.; Blacklock, T. J.; Getman, D.; Hatanaka, N.;
Loza, R. J. Org. Chem. 1978, 43, 1481.
Hg(OAc)2
40 °C
–40 °C to 23 °C
72% yield
Me
Me
HO
(+)-12
61% yield
(+)-11
Scheme 2
These primary alcohols seemed to be ideal substrates for
a Pd-catalyzed oxidative cyclization recently developed
by our laboratories.2 Thus, phenylcyclopentene (+)-12
was exposed to our reported aerobic conditions
(Scheme 3).2d Clean cyclization to 5,5-fused bicycle (–)-
21 was observed. The absence of alcohol oxidation under
these conditions accentuates the exquisite selectivity that
can be obtained in these Pd-catalyzed oxidations by slight
modifications to the system.
Pd(TFA)2 (10 mol%)
pyridine (40 mol%), O2 (1 atm)
Ph
Ph
O
Na2CO3 (4 equiv), MS 3 Å
PhCH3, 80 °C, 17 h
Me
(+)-12
HO
Me
(7) Ireland, R. E.; Mueller, R. H.; Willard, A. K. J. Am. Chem.
Soc. 1976, 98, 2868.
(–)-21
85% yield
(8) Johnson, W. S.; Werthemann, L.; Bartlett, W. R.; Brocksom,
T. J.; Li, T.-t.; Faulker, D. J.; Petersen, M. R. J. Am. Chem.
Soc. 1970, 92, 741.
(9) Kraus, G. A.; Frazier, K. J. Org. Chem. 1980, 45, 2579.
(10) Ito, S.; Kasai, M.; Ziffer, H.; Silverton, J. V. Can. J. Chem.
1987, 65, 574.
(11) The decreased ee for this substrate is presumably due to
competing 1,3-rearrangement, leading to partial
racemization.
Scheme 3
In conclusion, we have employed the Pd-catalyzed oxida-
tive kinetic resolution to obtain allylic alcohol intermedi-
ates in high ee, which can subsequently yield compounds
bearing enantioenriched tertiary and quaternary stereo-
centers through Claisen rearrangement. These Claisen
products can then undergo a second Pd-catalyzed aerobic
oxidation to afford 5,5-fused tetrahydrofurans. Applica-
tion of the oxidative kinetic resolution of secondary alco-
hols to other transformations in the context of complex
molecule synthesis is ongoing in our laboratories.
(12) General Procedure for the Oxidative Kinetic Resolution
of Allylic Alcohols1b
To an oven-dried reaction tube with stir bar was added oven-
dried powdered 3 Å MS (500 mg). After cooling, Pd(nbd)Cl2
(13.5 mg, 0.05 mmol), followed by toluene (2 mL) and then
(–)-sparteine (46.9 mg, 46 mL, 0.20 mmol) were added. The
reaction vessel was then cooled to –78 °C, vacuum
evacuated, and purged with O2 (3×). The reaction was then
heated to 60 °C with vigorous stirring under O2 (1 atm) for
20 min. Finely powdered anhyd Cs2CO3 (162.9 mg, 0.50
mmol) was added, followed by a solution of allylic alcohol
(1.0 mmol), t-BuOH (111.2 mg, 143 mL, 1.5 mmol) and
toluene (2 mL). Reaction progress was monitored by GC
analysis of an aliquot filtered through silica gel (Et2O as
eluent). When the reaction was complete, the reaction was
cooled to r.t., filtered through silica gel (Et2O as eluent),
concentrated under reduced pressure, and purified by flash
chromatography to afford enantioenriched alcohol and
ketone.
Acknowledgment
The authors are grateful to the NIH-NIGMS (R01 GM65961-01),
NDSEG and NSF (predoctoral fellowships to D.C.E.), The
Hungarian-American Enterprise Scholarship Fund (postdoctoral
fellowship to Z.N.), A. P. Sloan Foundation, Research Corporation,
Bristol-Myers Squibb, Amgen, Merck, Pfizer, Novartis, Lilly,
Roche, Abbott, AstraZeneca, and Caltech for financial support.
References and Notes
(1) For oxidative kinetic resolutions, see: (a) Ferreira, E. M.;
Stoltz, B. M. J. Am. Chem. Soc. 2001, 123, 7725.
2-Phenylcyclopent-2-enol [(+)-1]
Rf = 0.20 (4:1 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 7.60–7.54 (comp. m, 2 H), 7.39–7.22 (comp. m, 3 H),
6.32 (t, J = 2.5 Hz, 1 H), 5.29–5.21 (m, 1 H), 2.74–2.60 (m,
1 H), 2.51–2.34 (m, 2 H), 2.02–1.90 (m, 1 H). 13C NMR (75
MHz, CDCl3): d = 144.8, 135.1, 130.2, 128.8, 127.8, 126.4,
77.4, 34.3, 30.7. IR (thin film/NaCl): 3220, 2883, 1496,
1322, 1050, 759, 691 cm–1. HRMS-EI: m/z [M]+ calcd for
[C11H12O]+: 160.0888; found: 160.0881. [a]D25 +14.0 (c 1.4,
CHCl3; 99% ee). HPLC: Chiralcel OD-H column, 3%
EtOH–hexane, 1 mL/min flow rate, major peak tR = 21.1
min, minor peak tR = 16.9 min.
(b) Bagdanoff, J. T.; Ferreira, E. M.; Stoltz, B. M. Org. Lett.
2003, 5, 835. (c) Bagdanoff, J. T.; Stoltz, B. M. Angew.
Chem. Int. Ed. 2004, 43, 353. (d) Trend, R. M.; Stoltz, B. M.
J. Am. Chem. Soc. 2004, 126, 4482. (e) Nielson, R. J.;
Keith, J. M.; Stoltz, B. M.; Goddard, W. A. III J. Am. Chem.
Soc. 2004, 126, 7967.
(2) For oxidative cyclizations, see: (a) Trend, R. M.; Ramtohul,
Y. K.; Ferreira, E. M.; Stoltz, B. M. Angew. Chem. Int. Ed.
2003, 42, 2892. (b) Ferreira, E. M.; Stoltz, B. M. J. Am.
Chem. Soc. 2003, 125, 9578. (c) Zhang, H.; Ferreira, E. M.;
Synlett 2006, No. 20, 3533–3539 © Thieme Stuttgart · New York

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Oxidative Kinetic Resolution–Claisen Rearrangement of Allylic Alcohols
3537
2-(4-Methylphenyl)cyclopent-2-enol [(+)-2]
928, 733 cm–1. HRMS-EI: m/z [M]+ calcd for [C9H10O2]+:
150.0681; found: 150.0680. [a]D25 +30.9 (c 1.1, CHCl3;
99% ee). HPLC: Chiralcel OB-H column, 4% EtOH–
hexane, 1 mL/min flow rate, major peak tR = 17.0 min,
minor peak tR = 10.5 min.
Rf = 0.35 (7:3 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 7.46 (d, J = 8.0 Hz, 2 H), 7.16 (d, J = 8.1 Hz, 2 H), 6.26
(t, J = 2.5 Hz, 1 H), 5.22 (m, 1 H), 2.73–2.59 (m, 1 H), 2.49–
2.32 (m, 2 H), 2.34 (s, 3 H), 2.01–1.88 (m, 1 H). 13C NMR
(75 MHz, CDCl3): d = 144.7, 137.3, 132.2, 129.5, 129.2,
126.3, 77.4, 34.2, 30.7, 21.4. IR (thin film/NaCl): 3337,
2921, 1512, 1043, 813 cm–1. HRMS-EI: m/z [M]+ calcd for
[C12H14O]+: 174.1045; found: 174.1042. [a]D25 +4.5 (c 1.6,
CHCl3; 98.5% ee). HPLC: Chiralcel OB-H column, 8%
EtOH–hexane, 1 mL/min flow rate, major peak tR = 15.3
min, minor peak tR = 7.8 min.
3-Methyl-2-phenylcyclopent-2-enol [(–)-8]
Rf = 0.24 (4:1 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 7.41–7.22 (comp. m, 5 H), 5.16 (br d, J = 5.5 Hz, 1 H),
2.74–2.58 (m, 1 H), 2.44–2.30 (m, 2 H), 1.87–1.75 (m, 1 H),
1.85 (d, J = 1.1 Hz, 3 H). 13C NMR (75 MHz, CDCl3): d =
139.8, 138.5, 136.7, 128.6, 128.5, 126.9, 80.5, 36.9, 32.7,
15.9. IR (thin film/NaCl): 3370, 2930, 1442, 699 cm–1.
HRMS-EI: m/z [M]+ calcd for [C12H14O]+: 174.1045; found:
174.1037. [a]D25 –2.4 (c 1.2, CHCl3; 99% ee). HPLC:
Chiralcel OB-H column, 2% EtOH–hexane, 1 mL/min flow
rate, major peak tR = 13.2 min, minor peak tR = 10.4 min.
2-Phenylcyclohex-2-enol [(–)-9]
2-(4-Methoxyphenyl)cyclopent-2-enol [(+)-3]
Rf = 0.30 (7:3 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 7.51 (d, J = 8.8 Hz, 2 H), 6.88 (d, J = 8.8 Hz, 2 H), 6.18
(t, J = 2.4 Hz, 1 H), 5.19 (m, 1 H), 3.81 (s, 3 H), 2.72–2.56
(m, 1 H), 2.48–2.31 (m, 2 H), 2.00–1.87 (m, 1 H). 13C NMR
(75 MHz, CDCl3): d = 159.1, 144.2, 128.1, 127.8, 127.6,
114.2, 77.5, 55.5, 34.3, 30.6. IR (thin film/NaCl): 3249,
2958, 2892, 2846, 1052, 1033, 824 cm–1. HRMS-EI: m/z
[M]+ calcd for [C12H14O2]+: 190.0994; found: 190.0995.
[a]D25 +10.6 (c 1.9, CHCl3; 99% ee); HPLC: Chiralpak AS
column, 4% EtOH–hexane, 1 mL/min flow rate, major peak
tR = 11.5 min, minor peak tR = 15.9 min.
Characterization data matched that in the literature;9 [a]D
25
–109.5 (c 1.3, CHCl3; 99% ee) {lit.10 [a]D +114.5 (c 1.6,
CHCl3)}. HPLC: Chiralpak AD column, 3% EtOH–hexane,
1 mL/min flow rate, major peak tR = 22.5 min, minor peak
tR = 17.3 min.
General Procedure for the Vinylation of Allylic Alcohols
To a flame-dried 1-dram vial was added allylic alcohol (0.23
mmol), freshly distilled ethyl vinyl ether (3 mL), and then
Hg(OAc)2 (20.3 mg, 0.64 mmol, 0.28 equiv). The reaction
mixture was stirred at 40 °C for 120 h. After cooling to
23 °C, K2CO3 (173 mg, 1.25 mmol, 5.4 equiv) was added,
and the suspension was stirred for 30 min. Then, the mixture
was filtered, and the solution was concentrated under
reduced pressure. Purification by preparative TLC (10:1
hexane–EtOAc as eluent) afforded the vinyl ether and
starting allylic alcohol.
3-Methyl-2-phenyl-1-vinyloxy-2-cyclopentene [(+)-11]
Rf = 0.75 (10:1 hexane–EtOAc). 1H NMR (300 MHz,
CDCl3): d = 7.38–7.36 (comp. m, 4 H), 7.31–7.24 (m, 1 H),
6.45 (dd, J = 13.8, 6.3 Hz, 1 H), 5.25 (br d, J = 6.9 Hz, 1 H),
4.31 (dd, J = 14.4, 1.8 Hz, 1 H), 4.04 (dd, J = 6.6, 1.5 Hz, 1
H), 2.79–2.68 (m, 1 H), 2.48–2.22 (m, 2 H), 2.06–1.97 (m, 1
H). 13C NMR (75 MHz, CDCl3): d = 150.5, 142.3, 136.4,
134.7, 128.2, 128.1, 126.6, 88.0, 87.1, 37.1, 28.9, 15.7. IR
(thin film/NaCl): 3055, 3029, 2975, 2938, 2912, 2845, 1631,
1608, 1492, 1444, 1379, 1350, 1317, 1189, 1099, 1058,
1016, 989, 964, 872, 816 cm–1. HRMS-ES: m/z [M]+ calcd
for [C14H16O]+: 200.1201; found: 200.1213. [a]D26 +6.1 (c
0.80, CH2Cl2).
2-{Benzo[1,3]dioxol-5-yl}cyclopent-2-enol [(+)-4]
Rf = 0.27 (7:3 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 7.08–7.03 (comp. m, 2 H), 6.82–6.76 (m, 1 H), 6.16 (t,
J = 2.5, 1 H), 5.95 (s, 2 H), 5.15 (m, 1 H), 2.71–2.57 (m, 1
H), 2.47–2.30 (m, 2 H), 1.99–1.87 (m, 1 H). 13C NMR (75
MHz, CDCl3): d = 148.1, 147.1, 144.3, 129.5, 128.8, 120.0,
108.5, 106.8, 101.2, 77.5, 34.3, 30.6. IR (thin film/NaCl):
3354, 2894, 1490, 1503, 1226, 1041, 937 cm–1. HRMS-EI:
m/z [M]+ calcd for [C12H12O3]+: 204.0787; found: 204.0793.
[a]D25 +9.6 (c 1.6, CHCl3; 99% ee). HPLC: Chiralcel OB-H
column, 10% EtOH–hexane, 1 mL/min flow rate, major
peak tR = 27.1 min, minor peak tR = 12.0 min.
2-[4-(Trifluoromethyl)phenyl]cyclopent-2-enol [(+)-5]
Rf = 0.34 (7:3 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 7.67 (d, J = 8.5 Hz, 2 H), 7.58 (d, J = 8.5 Hz, 2 H), 6.43
(t, J = 2.6 Hz, 1 H), 5.24 (m, 1 H), 2.77–2.62 (m, 1 H), 2.54–
2.37 (m, 2 H), 2.02–1.86 (m, 1 H). 13C NMR (75 MHz,
CDCl3): d = 143.4, 138.4, 132.6, 127.7, 126.3, 125.4 (q,
JF = 3.8 Hz), 77.1, 34.1, 30.5. 19F NMR (282 MHz, CDCl3):
d = –63.5. IR (thin film/NaCl): 3239, 1326, 1112, 827 cm–1.
HRMS-EI: m/z [M]+ calcd for [C12H11OF3]+: 228.0762;
found: 228.0752. [a]D25 +16.0 (c 2.5, CHCl3; 99% ee).
HPLC: Chiralcel OD-H column, 2% EtOH–hexane, 1 mL/
min flow rate, major peak tR = 15.0 min, minor peak tR = 13.7
min.
2-Phenyl-1-vinyloxy-2-cyclopentene
Rf = 0.75 (10:1 hexane–EtOAc). 1H NMR (300 MHz,
CDCl3): d = 7.49–7.46 (comp. m, 2 H), 7.35–7.22 (comp. m,
3 H), 6.50–6.43 (m, 2 H), 5.37 (dt, J = 6.9, 2.4 Hz, 1 H), 4.35
(dd, J = 14.4, 1.8 Hz, 1 H), 4.11 (dd, J = 6.6, 1.5 Hz, 1 H),
2.76–2.64 (m, 1 H), 2.54–2.26 (m, 2 H), 2.15–2.12 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 150.1, 141.1, 134.6, 132.0,
128.4, 127.3, 125.9, 88.3, 83.1, 31.0, 30.1. IR (thin film/
NaCl): 3057, 2934, 2846, 1632, 1610, 1496, 1447, 1358,
1318, 1188, 1048, 1032, 962, 822 cm–1. HRMS-ES: m/z
[M]+ calcd for [C13H14O]+: 186.1045; found: 186.1042.
[a]D25 +32.5 (c 0.38, CH2Cl2).
2-(2-Naphthyl)cyclopent-2-enol [(+)-6]
Rf = 0.37 (7:3 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 8.00 (s, 1 H), 7.87–7.67 (comp. m, 4 H), 7.50–7.40
(comp. m, 2 H), 6.45 (t, J = 2.5 Hz, 1 H), 5.37 (m, 1 H),
2.80–2.65 (m, 1 H), 2.56–2.38 (m, 2 H), 2.07–1.95 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 144.7, 133.9, 133.0, 132.4,
130.9, 128.5, 128.4, 127.9, 126.4, 126.1, 125.0, 124.8, 77.4,
34.4, 30.9. IR (thin film/NaCl): 3385, 1044, 819, 476 cm–1.
HRMS-EI: m/z [M]+ calcd for [C15H14O]+: 210.1045; found:
210.1043. [a]D25 +46.4 (c 2.0, CHCl3; 99% ee); HPLC:
Chiralpak AS column, 3% EtOH–hexane, 1 mL/min flow
rate, major peak tR = 11.5 min, minor peak tR = 13.3 min.
2-(2-Furyl)cyclopent-2-enol [(+)-7]
2-(4-Methylphenyl)-1-vinyloxy-2-cyclopentene
Rf = 0.75 (10:1 hexane–EtOAc). 1H NMR (300 MHz,
CDCl3): d = 7.41 (d, J = 6.3 Hz, 2 H), 7.17 (d, J = 8.1 Hz, 2
H), 6.52 (dd, J = 14.4, 6.9 Hz, 1 H), 6.42 (t, J = 2.4 Hz, 1 H),
5.37 (dt, J = 7.2, 2.4 Hz, 1 H), 4.37 (dd, J = 14.4, 1.8 Hz, 1
H), 4.12 (dd, J = 6.6, 1.8 Hz, 1 H), 2.74–2.65 (m, 1 H), 2.54–
2.43 (m, 1 H), 2.36 (s, 3 H), 2.39–2.27 (m, 1 H), 2.16–2.09
(m, 1 H). 13C NMR (75 MHz, CDCl3): d = 150.1, 141.0,
137.0, 131.8, 131.0, 129.1, 125.9, 88.3, 83.1, 31.0, 30.1,
21.2. IR (thin film/NaCl): 2921, 2849, 1631, 1609, 1513,
Rf = 0.26 (7:3 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 7.38 (d, J = 1.6 Hz, 1 H), 6.43 (d, J = 3.4 Hz, 1 H), 6.40
(dd, J = 3.3, 1.7 Hz, 1 H), 5.11 (m, 1 H), 2.74–2.60 (m, 1 H),
2.49–2.30 (m, 2 H), 1.95–1.84 (m, 1 H). 13C NMR (75 MHz,
CDCl3): d = 151.2, 142.0, 135.7, 128.4, 111.4, 106.8, 77.3,
55.9, 30.8. IR (thin film/NaCl): 3344, 2934, 2849, 1044,
Synlett 2006, No. 20, 3533–3539 © Thieme Stuttgart · New York

3538
D. C. Ebner et al.
CLUSTER
1449, 1352, 1317, 1187, 1048, 1030, 963, 813 cm–1. HRMS-
ES: m/z [M]+ calcd for [C14H16O]+: 200.1201; found:
200.1201. [a]D25 +20.8 (c 0.16, CH2Cl2).
30.1. IR (thin film/NaCl): 2924, 2850, 1633, 1611, 1487,
1349, 1317, 1189, 1153, 1051, 1028, 962, 916, 884, 806
cm–1. HRMS-ES: m/z [M]+ calcd for [C11H12O2]+: 176.0837;
found: 176.0842. [a]D25 +39.1 (c 0.35, CH2Cl2).
2-(4-Methoxyphenyl)-1-vinyloxy-2-cyclopentene
Rf = 0.75 (10:1 hexane–EtOAc). 1H NMR (300 MHz,
CDCl3): d = 7.44 (d, J = 8.7 Hz, 2 H), 6.89 (d, J = 9.0 Hz, 2
H), 6.51 (dd, J = 14.4, 6.9 Hz, 1 H), 6.33 (t, J = 2.7 Hz, 1 H),
5.37 (dt, J = 7.2, 2.1 Hz, 1 H), 4.36 (dd, J = 14.4, 2.1 Hz, 1
H), 4.11 (dd, J = 6.6, 1.8 Hz, 1 H), 3.81 (s, 3 H), 2.75–2.62
(m, 1 H), 2.52–2.42 (m, 1 H), 2.38–2.56 (m, 1 H), 2.14–2.05
(m, 1 H). 13C NMR (75 MHz, CDCl3): d = 158.9, 150.1,
140.5, 129.9, 127.4, 127.2, 113.8, 88.3, 83.3, 55.2, 30.9,
30.1. IR (thin film/NaCl): 2918, 2848, 2359, 2340, 1632,
1609, 1512, 1463, 1353, 1317, 1269, 1257, 1180, 1112,
1036, 963, 891, 824 cm–1. HRMS-ES: m/z [M]+ calcd for
[C14H16O2]+: 216.1150; found: 216.1155. [a]D26 +18.8 (c
0.43, CH2Cl2).
2-{Benzo[1,3]dioxol-5-yl}-1-vinyloxy-2-cyclopentene
Rf = 0.75 (10:1 hexane–EtOAc). 1H NMR (300 MHz,
CDCl3): d = 7.00 (d, J = 1.8 Hz, 1 H), 6.97 (dd, J = 13.8, 1.5
Hz, 1 H), 6.79 (d, J = 7.8 Hz, 1 H), 6.49 (q, J = 6.9 Hz, 1 H),
6.30 (t, J = 2.4 Hz, 1 H), 5.94 (s, 2 H), 5.29 (dt, J = 7.2, 2.4
Hz, 1 H), 4.35 (dd, J = 14.4, 2.1 Hz, 1 H), 4.11 (dd, J = 6.9,
1.8 Hz, 1 H), 2.73–2.61 (m, 1 H), 2.51–2.40 (m, 1 H), 2.37–
2.25 (m, 1 H), 2.13–2.04 (m, 1 H). 13C NMR (75 MHz,
CDCl3): d = 150.0, 147.7, 146.9, 140.6, 130.6, 119.7, 108.2,
106.4, 100.9, 88.4, 83.2, 30.9, 30.0. IR (thin film/NaCl):
2898, 2849, 2359, 2340, 1632, 1610, 1503, 1490, 1447,
1366, 1317, 1227, 1187, 1106, 1040, 969, 936, 889, 808
cm–1. HRMS-ES: m/z [M]+ calcd for [C14H14O3]+: 230.0943;
found: 230.0933. [a]D26 +20.8 (c 0.075, CH2Cl2).
2-Phenyl-1-vinyloxy-2-cyclohexene
Rf = 0.75 (10:1 hexane–EtOAc). 1H NMR (300 MHz,
CDCl3): d = 7.43–7.22 (comp. m, 5 H), 6.43 (dd, J = 14.1,
6.6 Hz, 1 H), 6.35 (t, J = 3.3 Hz, 1 H), 4.78 (t, J = 3.0 Hz, 1
H), 4.41 (dd, J = 14.1, 1.5 Hz, 1 H), 4.08 (dd, J = 6.6, 1.8 Hz,
1 H), 2.40–2.30 (m, 1 H), 2.25–2.14 (m, 2 H), 1.91–1.64
(comp. m, 3 H). 13C NMR (75 MHz, CDCl3): d = 150.5,
140.4, 135.6, 130.6, 128.3, 126.9, 125.6, 88.5, 72.5, 27.6,
25.9, 16.8. IR (thin film/NaCl): 3023, 2933, 2865, 2829,
2359, 2340, 1632, 1610, 1496, 1445, 1376, 1355, 1330,
1312, 1260, 1185, 1094, 1062, 1011, 977, 946, 917, 870,
813, 756, 695 cm–1. HRMS-ES: m/z [M]+ calcd for
[C14H16O]+: 200.1201; found: 200.1207. [a]D25 –115.8 (c
0.17, CH2Cl2).
General Procedure for Claisen Rearrangement of Vinyl
Ethers
To a flame-dried 1-dram vial was added vinyl ether (0.041
mmol) and CH2Cl2 (0.5 mL). The solution was cooled to
–40 °C, and DIBAL-H (1 M in toluene, 45 mL, 0.045 mmol)
was added dropwise. The reaction mixture was allowed to
warm to 23 °C and stir for 2 h, after which it was quenched
with excess Na2SO4·10H2O. After 30 min stirring, the
cloudy suspension was filtered, and the solution was
concentrated under reduced pressure. Purification by
preparative TLC (9:2 hexane–EtOAc as eluent) afforded the
primary alcohol.
1-(2-Hydroxyethyl)-1-methyl-2-phenyl-2-cyclopentene
[(+)-12]
2-[4-(Trifluoromethyl)phenyl]-1-vinyloxy-2-
cyclopentene
Rf = 0.16 (10:1 hexane–EtOAc). 1H NMR (300 MHz,
CDCl3): d = 7.35–7.20 (comp. m, 5 H), 5.80 (t, J = 2.4 Hz, 1
H), 3.75–3.58 (m, 2 H), 2.42–2.35 (m, 2 H), 2.10–2.01 (m, 1
H), 1.89–1.77 (comp. m, 3 H), 1.34 (s, 1 H), 1.25 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 150.6, 137.9, 128.9, 128.1,
127.3, 126.6, 60.7, 48.7, 48.5, 39.2, 30.1, 26.8. IR (thin film/
NaCl): 3369, 3054, 2951, 2866, 1598, 1492, 1453, 1376,
1099, 1054, 1020, 759, 700 cm–1. HRMS-ES: m/z [M]+ calcd
for [C14H18O]+: 202.1358; found: 202.1355. [a]D25 +27.5 (c
0.66, CH2Cl2; 87% ee). HPLC: Chiralcel OD-H column, 3%
EtOH–hexane, 1 mL/min flow rate, major peak tR = 13.1
min, minor peak tR = 10.7 min.
1-(2-Hydroxyethyl)-2-phenyl-2-cyclopentene [(+)-13]
Rf = 0.13 (5:1 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 7.42–7.19 (comp. m, 5 H), 6.07–6.05 (m, 1 H), 3.75–3.63
(m, 2 H), 3.29 (m, 1 H), 2.53–2.21 (m, 2 H), 2.20–2.14 (m,
1 H), 1.94–1.75 (m, 2 H), 1.55–1.45 (m, 1 H), 1.42 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 146.3, 136.2, 128.4, 126.9,
126.7, 126.1, 61.7, 41.5, 36.5, 31.5, 29.8. IR (thin film/
NaCl): 3350, 3053, 2935, 2847, 1598, 1494, 1445, 1330,
1055, 755, 694 cm–1. HRMS-ES: m/z [M]+ calcd for
[C13H16O]+: 188.1201; found: 188.1208. [a]D24 +62.3 (c
0.27, CH2Cl2; 97.9% ee). HPLC: Chiralcel OJ column, 2%
EtOH–hexane, 1 mL/min flow rate, major peak tR = 32.6
min, minor peak tR = 22.8 min.
Rf = 0.75 (10:1 hexane–EtOAc). 1H NMR (300 MHz,
CDCl3): d = 7.58 (m, 4 H), 6.58 (t, J = 2.7 Hz, 1 H), 6.50 (dd,
J = 14.4, 6.6 Hz, 1 H), 5.37 (dt, J = 7.2, 2.1 Hz, 1 H), 4.37
(dd, J = 14.1, 1.8 Hz, 1 H), 4.15 (dd, J = 6.6, 1.8 Hz, 1 H),
2.80–2.67 (m, 1 H), 2.58–2.47 (m, 1 H), 2.42–2.30 (m, 1 H),
2.17–2.08 (m, 1 H). 13C NMR (75 MHz, CDCl3): d = 149.9,
140.2, 134.6, 126.2, 125.5, 125.4, 125.3, 125.3, 88.8, 82.9,
31.2, 30.0. IR (thin film/NaCl): 2917, 2846, 2141, 1731,
1660, 1633, 1614, 1507, 1414, 1365, 1317, 1246, 1190,
1164, 1122, 1071, 1033, 1016, 963, 829, 733 cm–1. HRMS-
ES: m/z [M]+ calcd for [C14H13OF3]+: 254.0919; found:
254.0913. [a]D26 +31.0 (c 0.32, CH2Cl2).
2-(2-Naphthyl)-1-vinyloxy-2-cyclopentene
Rf = 0.75 (10:1 hexane–EtOAc). 1H NMR (300 MHz,
CDCl3): d = 7.87–7.80 (comp. m, 4 H), 7.70–7.67 (m, 1 H),
7.51–7.43 (comp. m, 2 H), 6.61 (t, J = 2.7 Hz, 1 H), 6.58 (dd,
J = 14.4, 6.9 Hz, 1 H), 5.51 (dt, J = 7.2, 2.7 Hz, 1 H), 4.43
(dd, J = 14.1, 1.8 Hz, 1 H), 4.18 (dd, J = 6.9, 1.8 Hz, 1 H),
2.83–2.71 (m, 1 H), 2.60–2.49 (m, 1 H), 2.44–2.32 (m, 1 H),
2.23–2.13 (m, 1 H). 13C NMR (75 MHz, CDCl3): d = 150.1,
141.1, 133.5, 1327, 131.9, 128.3, 127.9, 127.5, 126.0, 125.8,
124.7, 124.3, 88.5, 83.1, 31.2, 30.1. IR (thin film/NaCl):
3282, 3055, 2929, 2848, 1632, 1610, 1507, 1449, 1317,
1187, 1048, 1030, 963, 947, 894, 815, 746, 665 cm–1.
HRMS-ES: m/z [M]+ calcd for [C17H16O]+: 236.1201; found:
236.1207. [a]D26 +48.7 (c 0.53, CH2Cl2).
1-(2-Hydroxyethyl)-2-(4-methylphenyl)-2-cyclopentene
[(+)-14]
2-(2-Furyl)-1-vinyloxy-2-cyclopentene
Rf = 0.15 (5:1 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 7.32 (d, J = 7.8 Hz, 2 H), 7.14 (d, J = 8.1 Hz, 2 H), 6.02–
6.00 (m, 1 H), 3.73–3.65 (m, 2 H), 3.26 (m, 1 H), 2.52–2.44
(m, 2 H), 2.34 (s, 3 H), 2.26–2.13 (m, 1 H), 1.94–1.74 (m, 2
H), 1.55–1.43 (m, 1 H), 1.34 (s, 1 H). 13C NMR (75 MHz,
CDCl3): d = 146.1, 136.6, 129.1, 126.0, 125.8, 61.7, 41.5,
36.5, 31.5, 29.8, 21.1. IR (thin film/NaCl): 3337, 3048,
3023, 2936, 2844, 1901, 1617, 1566, 1511, 1437, 1379,
1335, 1307, 1185, 1111, 1056, 1019, 981, 879, 803 cm–1.
Rf = 0.75 (10:1 hexane–EtOAc). 1H NMR (300 MHz,
CDCl3): d = 7.38 (d, J = 1.8 Hz, 1 H), 6.49 (q, J = 6.6 Hz, 1
H), 6.39 (dd, J = 3.6, 2.1 Hz, 1 H), 6.36 (t, J = 3.0 Hz, 1 H),
6.30 (d, J = 3.3 Hz, 1 H), 5.23 (dt, J = 7.2, 2.7 Hz, 1 H), 4.34
(dd, J = 14.4, 1.8 Hz, 1 H), 4.10 (dd, J = 6.9, 1.8 Hz, 1 H),
2.75–2.63 (m, 1 H), 2.53–2.42 (m, 1 H), 2.37–2.25 (m, 1 H),
2.09–1.99 (m, 1 H). 13C NMR (75 MHz, CDCl3): d = 150.5,
150.2, 141.9, 132.2, 130.1, 111.1, 106.9, 88.5, 83.3, 31.1,
Synlett 2006, No. 20, 3533–3539 © Thieme Stuttgart · New York

CLUSTER
Oxidative Kinetic Resolution–Claisen Rearrangement of Allylic Alcohols
3539
HRMS-ES: m/z [M]+ calcd for [C14H18O]+: 202.1358; found:
[C17H18O]+: 238.1358; found: 238.1354. [a]D25 +25.4 (c
0.47, CH2Cl2; 98.8% ee). HPLC: Chiralcel OJ column, 4%
EtOH–hexane, 1 mL/min flow rate, major peak tR = 12.7
min, minor peak tR = 14.1 min.
202.1353. [a]D24 +51.5 (c 0.075, CH2Cl2; 96.8% ee). HPLC:
Chiralcel OJ column, 2% EtOH–hexane, 1 mL/min flow
rate, major peak tR = 13.4 min, minor peak tR = 15.3 min.
1-(2-Hydroxyethyl)-2-(4-methoxyphenyl)-2-
1-(2-Hydroxyethyl)-2-(2-furyl)-2-cyclopentene [(+)-19]
Rf = 0.15 (5:1 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 7.35 (d, J = 1.5 Hz, 1 H), 6.38 (dd, J = 3.3, 1.8 Hz, 1 H),
6.26 (d, J = 3.3 Hz, 1 H), 6.07 (s, 1 H), 3.77–3.67 (m, 2 H),
3.09 (br s, 1 H), 2.60–2.37 (m, 2 H), 2.19–2.09 (m, 1 H),
2.02–1.91 (m, 1 H), 1.83–1.74 (m, 1 H), 1.68–1.54 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 151.9, 141.4, 136.6, 125.4,
110.9, 105.8, 61.6, 41.6, 36.7, 31.3, 29.8. IR (thin film/
NaCl): 3368, 2938, 2873, 1654, 1487, 1459, 1329, 1056,
1008, 920, 885, 800, 733, 681 cm–1. HRMS-ES: m/z [M]+
cyclopentene [(+)-15]
Rf = 0.15 (5:1 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 7.36 (d, J = 8.7 Hz, 2 H), 6.87 (d, J = 8.7 Hz, 2 H), 5.94
(s, 1 H), 3.80 (s, 3 H), 3.72–3.64 (m, 2 H), 3.26 (br s, 1 H),
2.50–2.44 (m, 2 H), 2.24–2.11 (m, 1 H), 1.92–1.73 (m, 2 H),
1.54–1.42 (m, 1 H), 1.44 (s, 1 H). 13C NMR (75 MHz,
CDCl3): d = 158.5, 145.6, 128.9, 127.2, 124.7, 113.7, 61.7,
55.2, 41.6, 36.4, 31.4, 29.8. IR (thin film/NaCl): 3392, 2934,
2836, 1607, 1510, 1462, 1441, 1294, 1252, 1178, 1037, 804
cm–1. HRMS-ES: m/z [M]+ calcd for [C14H18O2]+: 218.1307;
found: 218.1299. [a]D25 +66.9 (c 0.27, CH2Cl2; 98.6% ee).
HPLC: Chiralcel OJ column, 4% EtOH–hexane, 1 mL/min
flow rate, major peak tR = 13.6 min, minor peak tR = 16.2
min.
24
calcd for [C11H14O2]+: 178.0994; found: 178.0995. [a]D
+23.4 (c 0.29, CH2Cl2; 48.6% ee).11 HPLC: Chiralcel OJ
column, 4% EtOH–hexane, 1 mL/min flow rate, major peak
tR = 12.3 min, minor peak tR = 10.9 min.
1-(2-Hydroxyethyl)-2-phenyl-2-cyclohexene [(+)-20]
Rf = 0.15 (5:1 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 7.32–7.21 (comp. m, 5 H), 5.92 (t, J = 4.2 Hz, 1 H), 3.59
(t, J = 6.0 Hz, 2 H), 2.89 (br s, 1 H), 2.21–2.15 (m, 2 H),
1.87–1.43 (comp. m, 7 H). 13C NMR (75 MHz, CDCl3): d =
142.6, 141.7, 128.3, 126.5, 126.5, 126.2, 61.2, 36.5, 30.0,
27.3, 26.0, 18.5. IR (thin film/NaCl): 3351, 3021, 2930,
2861, 2832, 1639, 1598, 1493, 1443, 1430, 1058, 1032,
1013, 986, 757, 698 cm–1. HRMS-ES: m/z [M]+ calcd for
[C14H18O]+: 202.1358; found: 202.1358. [a]D25 +107.2 (c
0.050, CH2Cl2; 97.0% ee). HPLC: Chiralcel OJ column, 2%
EtOH–hexane, 1 mL/min flow rate, major peak tR = 14.2
min, minor peak tR = 19.2 min.
1-(2-Hydroxyethyl)-2-{2-Benzo[1,3]dioxol-5-yl}-2-
cyclopentene [(+)-16]
Rf = 0.15 (5:1 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 6.92 (s, 1 H), 6.89 (dd, J = 8.4, 1.2 Hz, 1 H), 6.78 (d,
J = 8.4 Hz), 5.94 (s, 2 H), 5.93 (s, 1 H), 3.72–3.64 (m, 2 H),
3.32 (br s, 1 H), 2.49–2.43 (m, 2 H), 2.23–2.11 (m, 1 H),
1.92–1.73 (m, 2 H), 1.54–1.42 (m, 1 H), 1.49 (s, 1 H). 13
NMR (75 MHz, CDCl3): d = 147.7, 146.5, 145.8, 130.6,
125.4, 119.6, 108.1, 106.6, 100.9, 61.6, 41.7, 36.3, 31.3,
C
29.7. IR (thin film/NaCl): 3350, 3041, 2935, 2888, 2777,
2063, 1850, 1604, 1503, 1489, 1443, 1356, 1223, 1126,
1104, 1040, 986, 937, 862, 806 cm–1. HRMS-ES: m/z [M]+
24
calcd for [C14H16O3]+: 232.1100; found: 232.1091. [a]D
Tetrahydrofuran (–)-21
+62.2 (c 0.27, CH2Cl2; 93.1% ee). HPLC: Chiralcel OJ
column, 4% EtOH–hexane, 1 mL/min flow rate, major peak
tR = 17.8 min, minor peak tR = 21.1 min.
1-(2-Hydroxyethyl)-2-[4-(trifluoromethyl)phenyl]-2-
cyclopentene [(+)-17]
To an oven-dried reaction tube with stir bar was added oven-
dried powdered 3 Å MS (120 mg). After cooling, Pd(TFA)2
(4.1 mg, 0.012 mmol), anhyd Na2CO3 (52.6 mg, 0.50 mmol),
followed by toluene (2.5 mL), pyridine (3.9 mg, 4.0 mL,
0.050 mmol), and alcohol (+)-12 (25.1 mg, 0.12 mmol). The
reaction vessel was then cooled to –78 °C, vacuum
evacuated, and purged with O2 (3×). The reaction was then
heated to 80 °C with vigorous stirring under O2 (1 atm).
After 15.5 h, the reaction was complete by TLC analysis.
The reaction was cooled to r.t., filtered through silica gel
(EtOAc as eluent), and concentrated under reduced pressure
to afford tetrahydrofuran (–)-21 (21.0 mg, 85% yield) as a
colorless oil. Further purification by preparative TLC (4:1
hexane–EtOAc as eluent) afforded an analytically pure
sample: Rf = 0.62 (4:1 hexane–EtOAc). 1H NMR (300 MHz,
CDCl3): d = 7.34–7.20 (comp. m, 5 H), 6.07 (ddd, J = 5.8,
2.4, 2.4 Hz, 1 H), 5.65 (ddd, J = 5.8, 2.1, 2.1 Hz, 1 H), 4.07
(ddd, J = 8.6, 6.8, 4.3 Hz, 1 H), 3.82 (ddd, J = 8.6, 8.6, 6.2
Hz, 1 H), 2.53 (ddd, J = 17.3, 2.2, 2.2 Hz, 1 H), 2.34 (ddd,
J = 17.3, 2.2, 2.2 Hz, 1 H), 1.96 (ddd, J = 12.0, 6.1, 4.4 Hz,
1 H), 1.89 (ddd, J = 11.9, 8.6, 6.8 Hz, 1 H), 0.69 (s, 3 H). 13C
NMR (75 MHz, CDCl3): d = 142.7, 134.6, 133.4, 128.0,
127.0, 126.2, 100.0, 65.9, 51.4, 47.6, 43.6, 25.5. IR (thin
film/NaCl): 2956, 1722, 1492, 1448, 1047 cm–1. HRMS-EI:
m/z [M]+ calcd for [C14H16O]+: 200.1201; found: 200.1203.
[a]D26 –16.1 (c 1.6, CH2Cl2; 86% ee). Chiral GC: G-TA
column, 100 °C initial temperature, ramp 1 °C/min, 1 mL/
min carrier gas flow, major peak tR = 28.8 min, minor peak
tR = 29.2 min.
Rf = 0.15 (5:1 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 7.58 (dd, J = 8.4, 21.6 Hz, 4 H), 6.17 (s, 1 H), 3.72–3.67
(m, 2 H), 3.30 (br s, 1 H), 2.52–2.50 (m, 2 H), 2.29–2.16 (m,
1 H), 1.90–1.78 (m, 2 H), 1.52–1.42 (m, 1 H), 1.37 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 145.3, 139.8, 129.4, 126.3,
125.4, 125.4, 125.3, 61.5, 41.5, 36.3, 31.6, 29.7. IR (thin
film/NaCl): 3368, 2937, 2846, 1615, 1412, 1326, 1164,
1123, 1110, 1069, 1015, 850, 831, 815 cm–1. HRMS-ES:
m/z [M]+ calcd for [C14H15OF3]+: 256.1075; found:
256.1073. [a]D26 +48.5 (c 0.20, CH2Cl2; 97.1% ee). HPLC:
Chiralcel OJ column, 2% i-PrOH–hexane, 1 mL/min flow
rate, major peak tR = 21.6 min, minor peak tR = 18.5 min.
1-(2-Hydroxyethyl)-2-(2-naphthyl)-2-cyclopentene
[(+)-18]
Rf = 0.15 (5:1 hexane–EtOAc). 1H NMR (300 MHz, CDCl3):
d = 7.83–7.78 (comp. m, 4 H), 7.63 (d, J = 8.7 Hz, 1 H),
7.49–7.41 (m, 1 H), 6.22 (s, 1 H), 3.80 (s, 3 H), 3.72 (t,
J = 5.1 Hz, 2 H), 3.41 (br s, 1 H), 2.62–2.46 (m, 2 H), 2.31–
2.18 (m, 1 H), 2.10–1.81 (m, 2 H), 1.61–1.49 (m, 1 H), 1.44
(s, 1 H). 13C NMR (75 MHz, CDCl3): d = 146.2, 133.6,
133.5, 132.5, 128.0, 127.9, 127.52, 127.46, 126.1, 125.6,
124.8, 124.5, 61.7, 41.5, 36.4, 31.6, 29.8. IR (thin film/
NaCl): 3369, 3055, 2933, 2847, 1627, 1595, 1505, 1435,
1354, 1273, 1197, 1145, 1128, 1056, 989, 962, 946, 893,
858, 812, 747 cm–1. HRMS-ES: m/z [M]+ calcd for
Synlett 2006, No. 20, 3533–3539 © Thieme Stuttgart · New York