Asymmetric meta-arene-alkene photocycloaddition controlled by a 2,4-pentanediol tether

Article abstract of DOI:10.1016/j.tetasy.2004.03.017

Photo-irradiation of a substrate having phenyl and vinyl groups resulted in a stereocontrolled meta-arene-alkene cycloaddition when the two groups were connected by a chiral 2,4-pentanediol tether. The regioselectivity during the ring closing step after the initial addition was dependent on the stereochemistry of the tether and the photolysis conditions. The substrate bearing a p-tolyl or 3,5-xylyl group instead of the phenyl also underwent strict stereocontrolled addition. In the case of the o- and m-tolyl substrates, the regioselectivity due to the unsymmetric substitution of the arene moiety was also fully controlled.

Full text of DOI:10.1016/j.tetasy.2004.03.017

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 1409–1417
Asymmetric meta-arene–alkene photocycloaddition controlled by a
2,4-pentanediol tether
Kazutake Hagiya, Akiko Yamasaki, Tadashi Okuyama and Takashi Sugimura*
Graduate School of Material Science, Himeji Institute of Technology, University of Hyogo, 3-2-1 Kohto, Kamigori, Ako-gun,
Hyogo 678-1297, Japan
Received 13 January 2004; revised 2 March 2004; accepted 2 March 2004
Available online 9 April 2004
Abstract—Photo-irradiation of a substrate having phenyl and vinyl groups resulted in a stereocontrolled meta-arene–alkene
cycloaddition when the two groups were connected by a chiral 2,4-pentanediol tether. The regioselectivity during the ring closing
step after the initial addition was dependent on the stereochemistry of the tether and the photolysis conditions. The substrate
bearing a p-tolyl or 3,5-xylyl group instead of the phenyl also underwent strict stereocontrolled addition. In the case of the o- and
m-tolyl substrates, the regioselectivity due to the unsymmetric substitution of the arene moiety was also fully controlled.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
cient differential activation energy to attain high stereo-
selectivity is expected to be difficult due to its highly
energetic excited state process having a low energy
barrier. Nevertheless, several photocycloadditions pro-
ceed under sufficient stereocontrol especially when the
two reaction sites are connected by a chiral tether and
the addition is intermolecular.1 In 1994, we reported
such an example using 2,4-pentanediol (PD) as a chiral
tether for the meta-arene–alkene photocycloaddition,
which produced synthetically useful tricyclic products
having five new stereogenic centers (Scheme 1).2;3 The
Photoreactions are useful for organic synthesis because
of their characteristic products, which are unobtainable
by ground-state reactions. Many of the photoreactions
consist of cleavage of a photo-excited p-bond to produce
a new r-bond, and thus, convert a flat and achiral
reaction site to a three-dimensional and chiral moiety.
Accordingly, an optically active compound can be
obtained by incorporation of an appropriate chiral
source into a photoreaction, though induction of a suffi-
OMe
OMe
OMe
X
X
hν
h
ν
+
OMe
X
X
Si-face of olefin in exo-adduct
(Re-face in endo-adduct)
OMe
Introduction of
PD tether
OMe
X
hν
*
*
OMe
X
X
O
O
2
4
Re-face of olefin in exo-adduct
(Si-face in endo-adduct)
6-substituted
7-substituted
1a (2R, 4R)
1b (2R, 4S)
Scheme 1.
* Corresponding author. E-mail: sugimura@sci.himeji-tech.ac.jp
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.03.017

1410
K. Hagiya et al. / Tetrahedron: Asymmetry 15 (2004) 1409–1417
observed addition was strictly stereocontrolled, and
when the arene moiety was unsymmetrical, the regiose-
lectivity was also very high.
exchange by the conventional method gave 1a (79%) and
1b (75%); the stereochemical purities of both 1a and 1b
were confirmed to be over 99.6% by the GLC analysis.
The photo-irradiation of benzene or benzenoid in the
presence of an appropriate alkene results in meta-arene–
alkene-cycloaddition, the effectiveness of which depends
on the combination of aromatic and olefinic compounds.
Anisole is a good aromatic substrate and can regio-
selectively react with various nonelectron deficient
alkenes at the 2,6-positions.3a–c Reaction with a mono-
substituted alkene proceeds through the formation of
enantiomeric pairs of the initial adducts. Each of the
adducts gives a pair of regioisomers, 6- and 7-substituted
tricyclic products, which may interconvert under pho-
tochemical conditions, as shown in Scheme 1. Intro-
duction of a PD tether to the reactants provides
substrates 1a and 1b. The tether is sufficiently flexible and
long enough to allow the addition without notable strain,
but is not too long to give endo-stereochemistry at the
X-substituent. The PD tether is a promising stereo-
controller judging from other ground state reactions
using it,4 though it may be too long to perform the
meta-arene–alkene-cycloaddition based on the known
examples.5
When a solution of 1a in pentane (1 mmol dmꢀ3) was
irradiated by a low pressure mercury lamp through a
Vycor filter, two intramolecular adducts were produced
with total consumption of 1a. Column chromatography
of the reaction mixture after the irradiation over 9 h
gave 3a and 4a in 40% and 15% yield, respectively. The
side reactions were those at the vinyl ether group to give
2a and insoluble polymeric products as detected from
the product analysis. Thus, the intramolecular photo-
cycloaddition with 1a was found to be highly stereo-
controlled with the initial addition at the Si-face of the
vinyl moiety (Scheme 3).
O
O
254 nm
254 nm
+
+
O
1a
O
O
3a
4a
O
O
O
1b
2. Results and discussion
3b
(6-substituted)
4b
(7-substituted)
2.1. Stereochemical effect of the PD tether
Scheme 3.
Substrates 1a and 1b were synthesized from stereo-
chemically pure PD as illustrated in Scheme 2. The
cyclohexanone acetal prepared from (R,R)-PD (98%
yield) was converted to the a,a0-dibromoacetal with
excess pyridinium perbromide (79%) followed by treat-
ment with excess sodium methoxide in DMSO to give 2a
in 93% yield. Its diastereomer 2b was synthesized from
2a by the Mitsunobu inversion at the hydroxy group
(92%). Alternatively, 2b was prepared in one step from
(S,S)-PD by the addition of phenol under Mitsunobu
conditions.6 Formation of 2b proceeded under complete
inversion (99% yield), and was faster than the reaction
of 2b with a second phenol molecule. The conversion of
2b to 2a was also possible (94%). The vinyl ether
The reaction with 1b was more effective with the sub-
strate consumed within 4 h under similar conditions. In
this case, the formation of 3b was minimal (<2%) and 4b
was obtained in 70% yield after the column chroma-
tography. The relative stereochemistry between 4a and
4b was determined to be the same based on the CD
spectra (Fig. 1). Their stereochemistries as well as that of
3a were determined by the chemical correlation as
indicated in Section 2.3.
2.2. Analysis of factors controlling the reaction
From the photoreaction of 1a and 1b, the two diaste-
reomeric PD tethers were found to have strict stereo-
controllability, which is mainly due to the chirality at the
2-position of the tether, since the (2R)-configuration at
the tether forces the reaction to occur at the Si-face of
the vinyl group irrespective of the configuration at the
4-position. The lower total yield with 1a than that with
1b suggests that the (4S)-configuration cooperates to
achieve the stereocontrol with the (2R)-configuration,
while the (4R)-configuration does not. The difference in
the efficiency of the photocycloaddition was confirmed
by monitoring the reaction. A solution of the substrate
was irradiated under controlled conditions in the pres-
ence of an internal standard (decane) for analysis and
the reaction course was monitored by GLC. The con-
version of 1b (Fig. 2b) was confirmed to be faster than
that of 1a (Fig. 2a) while the reactivity ratio 1b/1a
R
R
O
O
e
O
OH
O
O
a, b
2a
1a
d
d
S
S
OH OH
+
c
e
O
OH
O
O
phenol
2b
1b
Scheme 2. Reagents and conditions: (a) pyridinium perbromide
(3 equiv)/CH2Cl2; (b) NaOMe/DMSO; (c) diethyl azodicarboxylate/
PPh3; (d) diethyl azodicarboxylate/PPh3/PhCOOH, then aq NaOH; (e)
ethyl vinyl ether/Hg(OAc)2.

K. Hagiya et al. / Tetrahedron: Asymmetry 15 (2004) 1409–1417
1411
was determined to be 2:6. Since the UV absorption of
1a and 1b at 254 nm are almost the same, the ratio
can be attributed to the quantum yield of the photo-
reaction.
6
4
3a
4a
4b
During this study, it was also found that 4 is not the
initial product from 1, but 3 is in the reactions of both
1a and 1b, while the isomerization rate of 3 to 4 is much
different between the two substrates. Such an intercon-
version between the meta-adducts is attributable to the
secondary photoreaction, and the ratio of the product
governing the regioselectivity must be controlled by the
absorption coefficient of the product. In fact, 3b has a
stronger absorption at 254 nm than 4b as shown in
Figure 3. Photochemical conversion of 3b to 4b as well
as interconversion between 3a and 4a was confirmed
independently.
2
0
-2
-4
-6
200
220
240
260
280
300
Wavelength/nm
0.5
Figure 1. CD spectra of 3a, 4a, and 4b in pentane.
3b
4b
0.4
0.3
0.2
0.1
0
1
(a) Reaction of 1a
0.8
0.6
0.4
0.2
200
210
220
230
240
250
260
Wavelength/nm
0
1
0
1
2
3
4
5
6
7
8
Figure 3. UV spectra of 3b and 4b in pentane.
Time/h
(b) Reaction of 1b
2.3. Reaction of the photoproducts 3 and 4
0.8
0.6
0.4
0.2
0
The cycloadducts 3 and 4 were converted into the
bicyclic acetal 6, of which the absolute stereochemistry
has been established.7 Acid treatment of 3a and 3b
resulted in the cleavage at the cyclopropyl group, regio-
selectively,8 with subsequent hydrogenation over a Pd–C
catalyst giving 5 in 40% yield (Scheme 4). The structure
of the intermediate was determined by the spin–decou-
pling experiments. Since the same acid treatment of 4a
and 4b only resulted in complex mixtures, the olefinic
function in 4 was first removed by hydrogenation over
Pd–C, and then the cyclopropyl group was cleaved
regioselectivity by the oxymercuration/reduction proce-
dure to give 5 (50%).9 Protection of the ketone in 5
followed by the conventional elimination of the PD
moiety resulted in 6, the specific rotation of which is
negative and indicates its stereochemistry to be
(1R,5S,6R).
0
1
2
3
4
Time/h
Figure 2. Normalized concentration of 1 (open circles), 3 (filled cir-
cles), and 4 (open squares) during the photoreactions.

1412
K. Hagiya et al. / Tetrahedron: Asymmetry 15 (2004) 1409–1417
and ethyl vinyl ether.10 Hence, the advantage of the
O
O
intramolecular reaction in controlling the reaction
selectivity was again disclosed. The regio- and stereo-
controlled addition caused as a result of the stereoface
differentiation both at the arene and alkene moieties is
schematically expressed in Figure 4. The photo-irradia-
tion of 7c and 7d gave similar results though these
reactions did not require the stereoface-differentiation
at the aromatic moiety. The low total yields with the
methyl-substituted 7a–d are attributable to the low
quantum yield for the addition probably due to the
faster internal conversion process of the excited aro-
matic rings having a substituent.
a
b
O
O
OH
d
3a
O
OH
5
c
O
b
O
4a or 4b
OH
O
6
Scheme 4. Reagents and conditions: (a) 4 M HCl/acetone; (b) H2/Pd–
C; (c) Hg(OAc)2/THF–H2O then NaBH4; (d) i. ethylene glycol/Hþ,
ii. PCC/CH2Cl2, and iii. K2CO3/methanol/H2O.
O
2.4. Application to substituted aromatic groups
O
O
O
The effectiveness and stereocontrollability in the meta-
arene–alkene photocycloaddition of 1b prompted us to
study the generality of this reaction design. Substrates 7
and antipodes of 1b in the tether moiety, were prepared
from (R,R)-PD via a Mitsunobu reaction. The use of
o-cresol, m-cresol, p-cresol, and 3,5-dimethylphenol
gave 7a, 7b, 7c, and 7d, respectively, as stereochemically
pure forms in 63–73% yield in two steps. Photo-irradi-
ation of 7a under the same conditions for the synthetic
runs with 1 took 24 h to consume the substrate, with the
two cycloadducts 8 and 9 isolated in 18% and 11% yield,
respectively (Scheme 5). Products 8 and 9 are photo-
convertible regioisomers corresponding to the antipodes
of 3b and 4b confirmed by the comparison of their CD
spectra and were determined to be the 8-methyl 8 and
For 7a
For 7b
Figure 4. Schematic expression of the photo-addition of 7a and 7b.
3. Conclusion
Asymmetric meta-arene–alkene photocycloaddition has
been found to be efficiently stereocontrolled by the PD
tether. The PD-tethered reactions have been extensively
developed after the first report for the meta-arene–
alkene photocycloaddition with 1a and 1b,2 and the
reaction selectivity is now believed to be controlled by
the differential activation entropy.11 The two methyl
groups in the PD tether cooperate or compete with each
other for the stereocontrol of the reaction, and the
cooperating case (1b in the present reaction) showed a
higher acceleration of the intramolecular reaction to
give a major stereoisomer mainly due to the entropy
term. The acceleration by the methyl substitutions on
the tether in 1b (and even 7) is obvious because general
intramolecular meta-arene–alkene photocycloadditions
are not effective when the arene and alkene moieties
are separated by five or six bonds.5 Entropy-control
may be a reason why the PD tether sufficiently con-
trols the highly exothermic and very fast photocyclo-
addition process. Although the substitution on the
arene reduces the product yield from 70% with unsub-
stitued 1b to 29–33% with the mono-substituted 7a–c
and to 19% with the bis-substituted 7d, the present
method is still useful because no other asymmetric
synthesis is yet available for meta-arene–alkene addi-
tions to perform the short-step syntheses of polyquinane
terpenoids.12
1
5-methyl derivative 9 by H NMR analysis. Neither the
diastereomers nor other regioisomers were found in
the reaction mixture. Thus, the PD tether controls the
addition to both stereofaces of the alkene and the arene
to produce only two products out of eight possible ones.
It should be noted that many more isomers of intra-
molecular cycloadducts are possible if the reaction
occurred at other positions than the 2,6-positions on the
aromatic moiety.
4
Me
O
7
2 Me
254 nm
24 h
+
O
O
O
2
O
O
Ar
4
6
7a. Ar = o-MePh
7b. Ar = m-MePh
7c. Ar = p-MePh
8a. 8-Me (18%)
8b. 2-Me (16%)
8c. 3-Me (13%)
9a. 5-Me (11%)
9b. 4-Me (17%)
9c. 3-Me (16%)
9d. 2,4-diMe (8%)
7d. Ar = 3,5-diMePh
8d. 2,4-diMe (11%)
Scheme 5.
The strict stereo- and regiocontrol during the initial
addition step was extended to the meta-substituted
substrate 7b to give only a pair of regioisomers. Spectral
analysis of isolated 8b and 9b showed the same stereo-
chemistry as those of 8a and 9a except for the methyl-
4. Experimental
4.1. General
substituted positions,
2 and 4, respectively. The
regioselectivity found with 7b was not observed in the
corresponding intermolecular reaction of m-methylanisole
All the products were characterized by NMR spec-
trometry using a JEOL EXcaliber-400 spectrometer at

K. Hagiya et al. / Tetrahedron: Asymmetry 15 (2004) 1409–1417
1413
400 MHz for the proton spectra and 100 MHz for the
carbon spectra, and by IR with a JASCO IR-88 spec-
trophotometer. Optical rotations were measured with
a Perkin–Elmer 243B polarimeter. CD spectra were
obtained using a JASCO J-720. High resolution MS was
obtained by a JEOL JMS-AX505HF or a JEOL JMS-
T100LC. Analytical GLC was performed on a Shima-
dzu GC17A. MPLC was carried out using FMI pump
(10 mL minꢀ1) and a Lover column (Merck Si-60, type
B). All solvents were purified by distillation with proper
drying agents.
graphy on silica gel (30% ethyl acetate in hexane) to give
3.76 g of 2b as a colorless oil (93.1% yield).
4.5. Synthesis of 1a and 1b
A solution of 2a (10.27 g) in ethyl vinyl ether (300 mL)
was heated with mercuric acetate (3.47 g, 0.2 equiv) to
reflux for 23 h. Pentane (50 g) was added and a mixed
solvent (ca. 50 mL) containing generated ethanol was
distilled off. This co-distillation procedure was repeated
two more times, and then all the solvent removed under
vacuum. The residue was purified by column chroma-
4.2. Synthesis of 2a from (R,R)-PD
tography on alumina (activity 3, hexane) to give 9.29 g
of 1a (79% yield). ½aꢁ ¼ ꢀ81:6 (c 1.2, methanol); IR
20
D
(KCl, neat) 2950, 1640, 1600, 1590, 1500, 1380, 1240,
(R,R)-2,4-Pentanediol acetal of cyclohexanone (5.2 g)
was dissolved in THF (200 mL), and cooled to )50 ꢁC.
To this solution was added pyridinium perbromide
(32.0 g, 3 equiv). After the mixture was warmed up to rt
over 1.5 h, at which point pyridine (5 mL), satd aqueous
NaHCO3 (125 mL) and Na2SO3 (2 g) were added in this
order. The mixture was extracted with benzene
(100 mL · 3), dried over MgSO4, concentrated and
purified by a column chromatography on silica gel (3%
ethyl acetate in hexane) to afford 7.7 g of 2,6-dibromide
as a diastereomeric mixture (79% yield). A part of this
(2.5 g) was added to a mixture of NaOMe (4 equiv)
and DMSO (35 mL) at rt, and allowed to stand over-
night. Extraction and silica gel column chromatography
1
1180, 1150, 1100 cmꢀ1; H NMR (CDCl3) d 7.25 (m,
2H), 6.95–6.89 (m, 3H), 6.23 (dd, J ¼ 14:2, 6.6 Hz, 1H),
4.58 (m, 1H), 4.26 (dd, J ¼ 14:2, 4.5 Hz, 1H), 4.16 (m,
1H), 3.29 (dd, J ¼ 14:2, 1.5 Hz, 1H), 4.16 (m, 1H), 3.92
(dd, J ¼ 6:6, 1.5 Hz, 1H), 1.86–1.81 (m, 2H), 1.29–1.24
(m, 6H). Anal. Calcd for C13H18O2: C, 75.69; H, 8.79.
Found: C, 75.64; H, 8.77. The diastereomer 1b was
prepared by the same procedure (74.3% yield).
20
D
½aꢁ ¼ ꢀ35:9 (c 0.9, methanol); IR (KCl, neat) 2970,
1640, 1600, 1500, 1240, 1200, 1100 cmꢀ1
;
1H NMR
(CDCl3) d 7.25 (m, 2H), 6.93–6.88 (m, 3H), 6.32 (dd,
J ¼ 14:4, 6.6 Hz, 1H), 4.50 (m, 1H), 4.31 (dd, J ¼ 14:4,
1.5 Hz, 1H), 4.11 (m, 1H), 4.01 (dd, J ¼ 6:6, 1.5 Hz, 1H),
2.18 (m, 1H), 1.64 (m, 1H), 1.31 (d, J ¼ 6:1 Hz, 3H),
1.23 (d, J ¼ 6:4 Hz, 1H). Anal. Calcd for C13H18O2: C,
75.69; H, 8.79. Found: C, 74.87; H, 8.62.
(30% ethyl acetate in hexane) gave 1.1 g of 2a
20
D
methanol); IR(KBr) 3400, 2950, 2830, 1600, 1580,
(93% yield). Mp 39.0–39.8 ꢁC; ½aꢁ ¼ ꢀ79:2 (c 1.1,
1240, 1170, 1150, 1100, 1040 cmꢀ1; H NMR (CDCl3)
1
d 7.26 (m, 2H), 6.95–6.90 (m, 3H), 4.67 (m, 1H), 4.11 (m,
1H), 2.59 (br s, 1H), 1.86–1.68 (m, 2H), 1.31 (d,
J ¼ 6:4 Hz, 3H), 1.22 (d, J ¼ 6:4 Hz, 3H). Anal. Calcd
for C11H16O2: C, 73.30; H, 8.95. Found: C, 72.87; H,
8.92.
4.6. Photoreaction of 1 (synthetic runs)
A solution of 1 in pentane (ca. 1 mmol dmꢀ3) was placed
in a quartz photoreactor and de-aerated by argon bub-
bling. This was irradiated by a low pressure mercury
lamp (100 W, Eiko-sha, Japan) at room temperature.
The reaction was continued until all the reactant was
consumed as monitored by TLC analysis. The concen-
trate was purified by MPLC on silica gel (15% ethyl
acetate in hexane). The primary adduct 3b was obtained
4.3. Synthesis of 2b from 2a
Inversion of the hydroxy group in 2a by the Mitsunobu
reaction using benzoic acid/triphenylphosphine/diethyl
azodicarboxylate followed by the hydrolysis was carried
by the reaction interrupted before the consumption of
20
25
D
(KCl, neat) 2950, 2925, 1400, 1380, 1240, 1190, 1140,
out by the reported method.4 ½aꢁ ¼ ꢀ15:3 (c 1.1,
1b. Compound 3a: ½aꢁ ¼ þ120 (c 1.0, methanol); IR
D
methanol); IR (KCl, neat), 3370, 2950, 1600, 1490, 1240,
1110 cmꢀ1
;
1H NMR (CDCl3) d 7.30–7.25 (m, 2H),
1080, 780 cmꢀ1; H NMR (CDCl3) d 5.53 (dd, J ¼ 5:6,
1
6.98–6.91 (m, 3H), 4.60 (m, 1H), 4.05 (m, 1H), 2.19 (br s,
1H), 1.95 (m, 1H), 1.69 (ddd, J ¼ 6:4, 4.6, 3.2 Hz, 1H),
1.31 (d, J ¼ 6:4 Hz, 3H), 1.22 (d, J ¼ 6:4 Hz, 3H). Anal.
Calcd for C11H16O2: C, 73.30; H, 8.95. Found: C, 72.93;
H, 8.67.
2.2 Hz, 1H), 5.49 (ddd, J ¼ 5:6, 2.2, 1.5 Hz, 1H), 4.45
(m, 1H), 4.33 (m, 1H), 4.22 (dm, J ¼ 4:4 Hz, 1H), 3.48
(m, 1H), 2.38 (dm, J ¼ 7:6 Hz, 1H), 2.06–2.00 (m, 2H),
1.94 (ddd, J ¼ 15:4, 6.6, 2.7 Hz, 1H), 1.74 (dm,
J ¼ 13:7 Hz, 1H), 1.67 (ddd, J ¼ 15:4, 6.6, 3.5 Hz, 1H),
1.26 (d, J ¼ 6:6 Hz, 3H), 1.17 (d, J ¼ 6:6 Hz, 3H); 13C
NMR (CDCl3) d 129.6, 128.1, 88.0, 85.1, 70.4, 66.3,
58.2, 45.6, 39.5, 34.8, 27.8, 26.2, 21.8; HRMS
4.4. Syntheses of 2b from (S,S)-PD
(M þ Naþ) m=z calcd for C13H18O2Na 229.1205, found
25
D
To a solution of (S,S)-2,4-pentanediol (2.77 g), phenol
(2.12 g, 1.0 equiv), and triphenylphosphine (7.01 g,
1.2 equiv) in THF (100 mL) was added a solution
of diisopropyl azodicarboxylate (5.02 mL, 1.2 equiv) in
THF (50 mL) for 90 min at rt. After 24 h, the mixture
was concentrated and purified by column chromato-
229.1179. Compound 4a: ½aꢁ ¼ þ68:8 (c 0.8, metha-
nol); IR (KCl, neat) 2950, 1720, 1460, 1380, 1140, 1100,
1060, 760 cmꢀ1; 1H NMR (CDCl3) d 5.72 (ddm, J ¼ 5:5,
2.9 Hz, 1H), 5.45 (dd, J ¼ 5:5, 2.2 Hz, 1H), 4.63 (d,
J ¼ 6:3 Hz, 1H), 4.21 (m, 1H), 4.12 (m, 1H), 3.31 (dt,
J ¼ 8:5, 2.2 Hz, 1H), 2.45 (ddd, J ¼ 15:5, 8.5, 0.9 Hz,

1414
K. Hagiya et al. / Tetrahedron: Asymmetry 15 (2004) 1409–1417
1H), 2.28–2.18 (m, 3H), 1.63 (m, 1H), 1.41 (d,
J ¼ 14:7 Hz, 1H), 1.35 (d, J ¼ 6:8 Hz, 3H), 1.24 (d,
J ¼ 6:4 Hz, 3H); 13C NMR (CDCl3) d 139.7, 123.4, 83.3
(2C), 74.0, 61.9, 53.5, 45.4, 44.3, 40.1, 39.5, 26.1, 21.9;
HRMS (M þ Naþ) m=z calcd for C13H18O2Na 229.1205,
1.16 (d, J ¼ 6:2 Hz, 3H), 1.15 (d, J ¼ 6:2 Hz, 3H); 13C
NMR (CDCl3) d 214.9, 133.8, 125.0, 78.8, 71.9, 64.6,
50.9, 45.5, 45.1, 41.3, 39.6, 24.0, 20.2. Hydrogenation of
this in ethyl acetate (13 mL) over 5% Pd-on-carbon
25
D
0.8, methanol); IR (KCl, neat) 3430, 2955, 2930, 1745,
resulted in 31 mg of essentially pure 5a. ½aꢁ ¼ ꢀ73:5 (c
found 229.1205. Compound 3b: (colorless oil)
20
1
½aꢁ ¼ þ70:7 (c 0.9, methanol); IR (KCl, neat) 2970,
1160, 1120, 1080, 1060 cmꢀ1; H NMR (CDCl3) d 4.08–
D
1
1380, 1200, 1140, 1100 cmꢀ1; H NMR (CDCl3) d 5.57
4.02 (m, 2H), 3.79 (m, 1H), 2.42 (dq, J ¼ 9:4, 2.4 Hz,
1H), 2.26–2.16 (m, 2H), 2.08–1.85 (m, 6H), 1.65–1.46
(m, 4H), 1.17 (d, J ¼ 6:4 Hz, 3H), 1.16 (d, J ¼ 6:4 Hz,
3H); 13C NMR (CDCl3) d 221.2, 75.6, 71.3, 65.8, 52.8,
45.7, 36.5, 34.6, 33.9, 31.1, 24.4, 20.0, 18.2; HRMS
(M þ Naþ) m=z calcd for C13H20O3Na 247.1310, found
247.1300.
(dd, J ¼ 5:4, 2.0 Hz, 1H), 5.40 (ddd, J ¼ 5:4, 2.4, 1.5 Hz,
1H), 4.22 (m, 1H), 4.09 (s like, 1H), 4.01 (m, 1H), 3.82 (s
like, 1H), 2.31 (dm, J ¼ 8:3 Hz, 1H), 2.07 (t like,
J ¼ 7:3 Hz, 1H), 1.91–1.83 (m, 2H), 1.57 (d,
J ¼ 14:6 Hz, 1H), 1.47 (dd, J ¼ 14:6 Hz, 2.9 Hz, 1H),
1.20 (d, J ¼ 6:3 Hz, 3H), 1.17 (d, J ¼ 6:3 Hz, 3H); 13C
NMR (CDCl3) d 129.2, 127.9, 85.0, 85.6, 73.2, 70.7,
52.4, 47.1, 38.4, 33.4, 32.5, 24.9, 23.9; MS (Mþ), m=z (%)
206 (13.8), 191 (61.5), 175 (61.5), 121 (77.7), 105 (96.2),
94 (76.9), 77 (52.4), 69 (100); HRMS, m=z (Mþ) calcd for
By the same acid-catalyzed procedure, 3b was converted
25
D
to the bicyclic compound. ½aꢁ ¼ ꢀ3:4 (c 1.6, methanol);
1
IR (KCl, neat) 3450, 2980, 2950, 1760, 1380 cmꢀ1; H
C13H18O2 206.1307, found 206.1334. Compound 4b: mp
NMR (CDCl3) d 5.87 (m, 1H), 5.47 (td, J ¼ 6:3, 3.2 Hz,
1H), 4.09 (dd, J ¼ 8:5, 4.4 Hz, 1H), 3.92 (m, 1H), 3.67
(m, 1H), 2.96 (m, 1H), 2.67 (dd, J ¼ 13:3, 8.5 Hz, 1H),
2.62–2.57 (m, 2H), 2.37 (m, 1H), 1.90 (m, 1H), 1.66–1.46
(m, 3H), 1.16 (d, J ¼ 6:1 Hz, 3H), 1.14 (d, J ¼ 6:3 Hz,
3H); HRMS (M þ Naþ) m=z calcd for C13H22O3Na
249.1467, found 249.1452. The hydrogenation of this
gave 5b identical with that obtained below.
25
D
66.5–67.5 ꢁC; ½aꢁ ¼ þ21:3 (c 0.2, methanol); IR (KBr)
1
2950, 1420, 1380, 1220, 1160, 1100, 760 cmꢀ1; H NMR
(CDCl3) d 5.61 (dd, J ¼ 5:6, 1.7 Hz, 1H), 5.43 (dd,
J ¼ 5:6, 1.7 Hz, 1H), 4.48 (dd, J ¼ 6:8, 2.4 Hz, 1H), 4.30
(m, 1H), 4.05 (m, 1H), 3.25 (dd, J ¼ 8:3, 2.7 Hz, 1H),
2.49–2.43 (m, 3H), 2.32 (m, 1H), 2.08 (ddd, J ¼ 14:1,
6.8, 1.0 Hz, 1H), 1.58 (d, J ¼ 17:3 Hz, 1H), 1.22 (d,
J ¼ 6:3 Hz, 6H). Anal. Calcd for C13H18O2: C, 75.69; H,
8.79. Found C, 75.24; H, 8.79.
4.9. Hydrogenation/oxymercuration procedure for ring
opening of 4a and 4b
4.7. Time course of the reaction of 1 to give 3 and 4
Hydrogenation of 4a (50 mg) and 4b (80 mg) in ethyl
acetate over Pd-on-carbon proceeded smoothly to give
the corresponding dihydro-derivatives without other
side-reactions. This was treated with mercuric acetate
(1.2 equiv) in THF/water (10 mL, ratio ¼ 3:4) and stir-
red for 5 h at rt. The resulting mixture was treated with a
saturated aqueous solution of sodium borohydride (ca.
200 lL). Extraction and purification by column chro-
matography on silica gel (20% ethyl acetate in hexane)
afforded 5 (45–50% yield). The 5a obtained was identical
Solutions of 1a and 1b (1.58 mg) in pentane (2.50 mL)
containing decane (0.46 mg) were placed in UV cells,
de-aerated by argon bubbling and photo-irradiated by a
low pressure mercury lamp under the same conditions.
A part of the solution was taken out by a microsyringe
every hour during the photo-irradiation and subjected
to the GLC analysis. When a OV-1 column (i.d.
0.25 mm · 25 m, 120 ꢁC, 30 cm sꢀ1) was employed, the
retention times were as follows (min), decane: 5.14, 1a:
10.7, 1b: 12.9, 3a: 21.7, 4a: 18.3, 3b: 20.1, 4b: 16.3.
Concentrations of 1, 3, and 4 were determined by the
ratio of the peak integration using the decane peak as a
standard. The sensitivities among 1, 3, and 4 were
assumed to be the same. The results are shown in Figure
1. Conversion reactions of 3a to 4a, 4a to 3a, and 3b to
4b were also performed in pentane (0.5–0.9 mM) under
photo-irradiation and products obtained analyzed by
NMR.
with that obtained from 3a above. Compound 5b:
25
½aꢁ ¼ þ21:9 (c 0.8, methanol); IR (KCl, neat) 3450,
D
2950, 2850, 1760, 1380, 1120, 1080, 1060 cmꢀ1; 1H NMR
(CDCl3) d 4.04 (dd, J ¼ 8:3, 2.5 Hz, 1H), 3.92 (m, 1H),
3.68 (m, 1H), 2.85 (m, 1H, OH), 2.43 (m, 1H), 2.34 (br s,
1H), 2.27 (dd, J ¼ 14:4, 8.3 Hz, 1H), 2.04–1.90 (m, 5H),
1.66–1.55 (m, 5H), 1.49 (ddd, J ¼ 14:4, 4.0, 2.8 Hz, 1H),
1.18 (d, J ¼ 5:9 Hz, 3H), 1.14 (d, J ¼ 6:4 Hz, 3H);
HRMS (Naþ) m=z calcd for C13H22O3Na 249.1467,
found 249.1447.
4.8. Acid-catalyzed ring opening of 3a and 3b
4.10. Elimination of the PD moiety in 5
A solution of 3a (83 mg) in acetone (12 mL) and 4 M
HCl (3 mL) was heated to 40 ꢁC for 20 h. Extraction
with dichloromethane and MPLC purification on silica
A solution of 5a (48 mg), ethylene glycol (1 mL) and
catalytic amount of pyridinium p-toluenesulfonate in
benzene (60 mL) was heated to reflux under removing
water by a Dean–Stark apparatus. Extraction and
purification by a silica gel column chromatography gave
the acetal (58 mg, 84% yield). IR (KCl, neat) 3440, 2930,
gel (60% ethyl acetate in hexane) afforded a colorless oil
25
(30 mg, 34%). ½aꢁ ¼ ꢀ118 (c 0.8, methanol); IR (KCl,
D
neat) 3450, 2975, 2950, 1760, 1120, 1080 cmꢀ1; 1H NMR
(CDCl3) d 5.86 (m, 1H), 5.46 (td, J ¼ 6:3, 3.2 Hz, 1H),
4.01–3.99 (m, 2H), 3.76 (m, 1H), 2.93 (m, 1H), 2.66–2.56
(m, 3H), 2.31 (m, 1H), 1.93 (m, 1H), 1.62–1.50 (m, 2H),
1
2830, 1360, 1060, 1030 cmꢀ1; H NMR (CDCl3) d 4.09
(m, 1H), 3.96–3.84 (m, 6H), 2.07 (m, 1H), 1.66 (m, 1H),

K. Hagiya et al. / Tetrahedron: Asymmetry 15 (2004) 1409–1417
1415
20
mono-ether as a colorless oil in 81.5% yield. ½aꢁ ¼ þ14:6
;
1380, 1320, 1160, 1060, 840 cmꢀ1 1H NMR (CDCl3)
d 6.60 (s, 1H), 6.52 (s, 2H), 4.59 (m, 1H), 4.06 (m, 1H),
3.24 (br s, 1H), 2.31 (s, 6H), 2.02 (ddd, J ¼ 14:2, 8.3,
5.9 Hz, 1H), 1.66 (ddd, J ¼ 14:2, 8.3, 4.9 Hz, 1H), 1.32 (d,
J ¼ 5:9 Hz, 3H), 1.26 (d, J ¼ 6:4 Hz, 3H); 13C NMR
(CDCl3) d 157.00, 138.78, 122.55, 113.69, 72.85, 66.14,
45.37, 23.46, 21.17, 17.84; HRMS, m=z (Mþ) calcd for
C13H20O2 208.1463, found 208.1502.
1.86–1.77 (m, 4H), 1.70–1.53 (m, 3H), 1.45–1.31 (m,
2H), 1.25–1.22 (m, 2H), 1.20 (d, J ¼ 6:4 Hz, 3H), 1.16
(d, J ¼ 6:4 Hz, 3H). Oxidation of this by PCC (70 mg) in
dichloromethane (3 mL) at rt and a succeeding silica gel
column chromatography (20% ethyl acetate in hexane)
gave the precursor of 6 (45 mg, 81% yield). IR (KCl,
neat) 2950, 2860, 1710, 1360, 1170, 1120, 1100,
1060 cmꢀ1; 1H NMR (CDCl3) d 3.97–3.87 (m, 6H), 2.77
(dd, J ¼ 15:4, 7.3 Hz, 1H), 2.40 (dd, J ¼ 15:4, 5.4 Hz,
1H), 2.20 (s, 3H), 2.03 (s, 1H), 1.92–1.85 (m, 5H), 1.41–
1.34 (m, 2H), 1.25–1.20 (m 2H), 1.17 (d, J ¼ 6:4 Hz,
3H). This was dissolved in methanol (3 mL) with K2CO3
(ca. 50 mg) and stirred overnight. Extraction and puri-
fication by passing a short silica gel column (30% ethyl
D
(c 1.2, methanol); IR (KCl, neat) 3400, 2980, 1620, 1480,
Preparation of the vinyl ether 7 from the mono-ether
was achieved by the same method shown in Section 4.5.
20
D
2.0, methanol); IR (KCl, neat) 2970, 1635, 1600, 1490,
Compound 7a: (colorless oil, 82.7%) ½aꢁ ¼ þ28:9 (c
acetate in hexane) gave 28.6 mg of 6 (99% yield).
24
D
1
½aꢁ ¼ ꢀ13:0 (c 0.3, methanol, lit.7¼ ꢀ16:0); IR (KCl,
1240, 1190, 1120 cmꢀ1; H NMR (CDCl3) d 7.15–7.11
neat) 2940, 2850, 1140, 1120, 1030 cmꢀ1
;
1H NMR
(m, 2H), 6.86–6.82 (m, 2H), 6.34 (dd, J ¼ 14:2, 6.6 Hz,
1H), 4.53 (m, 1H), 4.32 (dd, J ¼ 14:2, 1.7 Hz, 1H), 4.15
(m, 1H), 4.02 (dd, J ¼ 6:6, 1.7 Hz, 1H), 2.23 (ddd,
J ¼ 13:9, 7.1, 6.8 Hz, 1H), 2.20 (s, 3H), 1.68 (ddd,
J ¼ 13:9, 6.4, 6.1 Hz, 1H), 1.33 (d, J ¼ 6:1 Hz, 3H), 1.25
(d, J ¼ 6:1 Hz, 3H); HRMS, m=z (Mþ) calcd for
(CDCl3) d 3.98–3.92 (m, 5H), 2.43 (br s, 1H), 2.10–2.03
(m, 2H), 1.83–1.77 (m, 2H), 1.75–1.70 (ddd, J ¼ 13:4,
5.9, 2.7 Hz, 1H), 1.58 (m, 1H), 1.42–1.35 (m, 2H), 1.19
(m, 1H). By the same procedure with a smaller scale
(24 mg) and without purification of the intermediate, 6
24
D
was obtained from 5b. ½aꢁ ¼ ꢀ14 (c 0.1, methanol).
C14H20O2 220.1463, found 220.1470. Compound 7b:
20
(colorless oil, 69.1%) ½aꢁ ¼ þ35:2 (c 1.0, methanol); IR
D
(KCl, neat) 2970, 1635, 1600, 1490, 1240, 1190,
4.11. Preparation of 7a–d
1120 cmꢀ1 1H NMR (CDCl3) d 7.19–7.12 (m, 2H),
;
6.76–6.69 (m, 2H), 6.33 (dd, J ¼ 14:2, 6.6 Hz, 1H), 4.48
(m, 1H), 4.33 (dd, J ¼ 14:2, 1.5 Hz, 1H), 4.10 (m, 1H),
4.03 (dd, J ¼ 6:6, 1.5 Hz, 1H), 2.32 (s, 3H), 2.19 (ddd,
J ¼ 13:9, 7.1, 6.8 Hz, 1H), 1.64 (ddd, J ¼ 13:9, 6.1,
5.9 Hz, 1H), 1.32 (d, J ¼ 5:9 Hz, 3H), 1.25 (d,
J ¼ 6:4 Hz, 3H); 13C NMR (CDCl3) d 157.6, 150.5,
139.4, 129.1, 121.4, 116.6, 112.5, 111.89, 88.3, 72.7, 70.3,
43.0, 20.0, 20.0; HRMS, m=z (Mþ) calcd for C14H20O2
By the procedure shown in Section 4.4, (R,R)-2,4-pen-
tanediol was converted to the mono-ether under complete
stereo-inversion. The reaction with o-cresol gave the
20
D
mono-ether as a colorless oil in 79.1% yield. ½aꢁ ¼ þ25:1
(c 1.0, methanol); IR (KCl, neat) 3400, 1500, 1460, 1380,
1290, 1240, 1120, 1050, 960, 750 cmꢀ1; 1H NMR (CDCl3)
d 7.16–7.13 (m, 2H), 6.90–6.85 (m, 2H), 4.62 (m, 1H), 4.07
(m, 1H), 2.74 (br s, 1H), 2.25 (s, 3H), 1.98 (ddd, J ¼ 14:4,
9.0, 8.8 Hz, 1H), 1.73 (ddd, J ¼ 14:4, 4.2, 2.9 Hz, 1H),
1.29 (d, J ¼ 6:1 Hz, 3H), 1.23 (d, J ¼ 6:4 Hz, 3H); 13C
NMR (CDCl3) d 155.1, 130.9, 127.8, 126.6, 120.8, 113.4,
73.8, 67.0, 45.7, 23.7, 20.1, 16.5; HRMS, m=z (Mþ) calcd
for C12H18O2 194.1307, found 194.1275. The reaction
220.1463, found 220.1460. Compound 7c: (colorless oil,
20
D
79.8%) ½aꢁ ¼ þ20:2 (c 1.4, methanol); IR (KCl, neat)
2980, 1640, 1620, 1515, 1385, 1330, 1300, 1240, 1200,
1110, 1050, 980, 955, 830 cmꢀ1; 1H NMR (CDCl3) d 7.05
(d, J ¼ 8:3 Hz, 2H), 6.78 (d, J ¼ 8:3 Hz, 2H), 6.31 (dd,
J ¼ 14:2, 6.6 Hz, 1H), 4.44 (m, 1H), 4.30 (dd, J ¼ 14:2,
1.5 Hz, 1H), 4.09 (m, 1H), 4.00 (dd, J ¼ 6:6, 1.5 Hz, 1H),
2.26 (s, 3H), 2.16 (ddd, J ¼ 13:9, 7.1, 6.8 Hz, 1H), 1.64
(ddd, J ¼ 13:9, 6.1, 5.8 Hz, 1H), 1.29 (d, J ¼ 6:1 Hz,
3H), 1.23 (d, J ¼ 6:4 Hz, 3H); 13C NMR (CDCl3) d
155.5, 150.5, 129.9, 129.9, 115.8, 88.3, 72.7, 70.7, 43.0,
20.5, 20.0, 19.9; HRMS, m=z (Mþ) calcd for C14H20O2
220.1463, found 220.1459. Compound 7d: (colorless oil,
83.9%) IR (KCl, neat) 2974, 1594, 1460, 1378, 1320,
with m-cresol gave the mono-ether as a colorless oil in
20
D
neat) 3430, 2940, 1590, 1460, 1260, 1120, 1050, 950, 880,
90.2% yield. ½aꢁ ¼ þ13:5 (c 1.0, methanol); IR (KCl,
1
700 cmꢀ1; H NMR (CDCl3) d 7.12 (m, 1H), 6.77–6.63
(m, 3H), 4.57 (m, 1H), 4.06 (m, 1H), 2.32 (s, 3H), 1.93
(ddd, J ¼ 14:4, 8.8, 8.8 Hz, 1H), 1.69 (ddd, J ¼ 14:4, 4.4,
3.2 Hz, 1H), 1.30 (d, J ¼ 6:1 Hz, 3H), 1.22 (d, J ¼ 6:4 Hz,
3H); 13C NMR (CDCl3) d 139.5, 129.2, 122.0, 117.2,
113.1, 100.5, 73.8, 67.0, 45.6, 23.8, 20.6, 20.1; HRMS, m=z
(Mþ) calcd for C12H18O2 194.1307, found 194.1309. The
1
1295, 1155, 1055, 830, 690 cmꢀ1; H NMR (CDCl3) d
6.56 (s, 1H), 6.52 (s, 2H), 6.32 (dd, J ¼ 14:2, 6.8 Hz,
1H), 4.46 (m, 1H), 4.31 (dd, J ¼ 14:2, 1.5 Hz, 1H), 4.09
(m, 1H), 4.01 (dd, J ¼ 6:8, 1.5 Hz, 1H), 2.26 (s, 6H), 2.17
(m, 1H), 1.62 (dt like, J ¼ 14:2, 5.9 Hz, 1H), 1.29 (d,
J ¼ 6:0 Hz, 3H), 1.23 (d, J ¼ 5:8 Hz, 3H); 13C NMR
(CDCl3) d 157.7, 150.5, 139.1, 122.4, 113.5, 88.3, 72.7,
70.2, 43.0, 21.5, 20.0, 20.0; HRMS, m=z (Mþ) calcd for
C15H22O2 234.1620, found 234.1622.
reaction with p-cresol gave the mono-ether as a colorless
20
D
oil in 92.2% yield. ½aꢁ ¼ þ10:3 (c 1.0, methanol);
IR (KCl, neat) 3400, 2970, 1520, 1390, 1290, 1240, 1120,
1040, 820 cmꢀ1; 1H NMR (CDCl3) d 7.08 (d, J ¼ 8:3 Hz,
2H), 6.86–6.80 (m, 2H), 4.52 (m, 1H), 4.05 (m, 1H), 2.68
(br s, 1H), 2.32 (s, 3H), 1.92 (ddd, J ¼ 14:4, 8.8, 8.8 Hz,
1H), 1.68 (ddd, J ¼ 14:4, 4.4, 2.9 Hz, 1H), 1.28 (d,
J ¼ 5:9 Hz, 3H), 1.22 (d, J ¼ 6:4 Hz, 3H); 13C NMR
(CDCl3) d 154.9, 130.5, 129.9, 116.3, 74.1, 66.9, 45.6, 23.7,
20.5, 20.0; MS m=z (%) 194 (15.3, Mþ), 186 (16.6), 162
(43.7), 149 (23.2), 121 (26.8), 108 (100), 107 (22.0);
HRMS, m=z (Mþ) calcd for C12H18O2 194.1307, found
194.1286. The reaction with 3,5-dimethylphenol gave the
4.12. Photoreaction of 7a–d
A pentane solution of 7 (30–40 mg, ca. 1 mmol dmꢀ3
was de-aerated by argon bubbling and then irradiated
)

1416
K. Hagiya et al. / Tetrahedron: Asymmetry 15 (2004) 1409–1417
by a low pressure mercury lamp for 24 h at rt. The
concentrate was purified by silica gel column chroma-
tography to give 8 and 9, the yields of which are shown
250 nm (De þ 0:9), 210 nm (De )2.9); IR (KCl, neat)
1
2929, 1723, 1448, 1377, 1103 cmꢀ1; H NMR (CDCl3) d
5.14 (s, 1H), 4.47 (dd, J ¼ 6:8, 2.4 Hz, 1H), 4.28 (m, 1H),
4.01 (m, 1H), 3.15 (d, J ¼ 8:4 Hz, 1H), 2.41 (ddd,
J ¼ 14:7, 8.4, 2.5 Hz, 1H), 2.39 (d, J ¼ 8:8 Hz, 1H), 2.30
(m, 1H), 2.34 (d, J ¼ 8:8 Hz, 1H), 2.07 (dd, J ¼ 14:7,
6.9 Hz, 1H), 1.69 (s, 3H), 1.55 (d, J ¼ 16:1 Hz, 1H), 1.21
(d, J ¼ 6:4 Hz, 3H), 1.20 (d, J ¼ 6:4 Hz, 3H); 13C NMR
(CDCl3) d 133.6, 131.3, 88.0, 80.0, 78.4, 72.8, 54.6, 49.3,
44.6, 44.1, 39.9, 26.9, 24.3, 16.4; HRMS, m=z (Mþ) calcd
20
in Scheme 5. Compound 8a: (colorless oil) ½aꢁ ¼ ꢀ61:5
D
(c 0.4, methanol); CD (methanol) kext 220 nm (De þ 6:3);
IR (KCl, neat) 2930, 1455, 1375, 1172, 1091, 738 cmꢀ1
;
1H NMR (CDCl3) d 5.62 (dd, J ¼ 5:4, 2.4 Hz, 1H), 5.38
(dd, J ¼ 5:4, 2.4 Hz, 1H), 4.17 (m, 1H), 4.05 (br s, 1H),
3.97 (m, 1H), 3.90 (br s, 1H), 1.87 (br s, 1H), 1.68 (dd,
J ¼ 13:7, 2.9 Hz, 1H), 1.59 (m, 1H), 1.65–1.51 (m, 2H),
1.58 (d, J ¼ 16:1 Hz, 1H), 1.31 (s, 3H), 1.19 (d,
J ¼ 6:4 Hz, 3H), 1.15 (d, J ¼ 6:3 Hz, 3H); 13C NMR
(CDCl3) d 130.8, 127.5, 87.9, 84.5, 72.9, 71.1, 52.4, 48.0,
44.1, 39.9, 38.4, 25.0, 24.3, 17.6; HRMS, m=z (Mþ) calcd
for C14H20O2 220.1463, found 220.1415. Compound 8d:
20
D
(colorless oil) ½aꢁ ¼ ꢀ18:9 (c 0.2, methanol); CD
(methanol) kext 230 nm (De þ 4:8), 205 nm (De þ 4:5); IR
(KCl, neat) 2928, 1638, 1446, 1376, 1095 cmꢀ1; 1H NMR
(CDCl3) d 5.06 (d, J ¼ 1:6 Hz, 1H), 4.18 (m, 1H), 4.13
(d, J ¼ 6:9 Hz, 1H), 4.04 (m, 1H), 3.51 (s, 1H), 2.26 (br
s, 1H), 1.93 (ddd, J ¼ 17:6, 10.3, 7.3 Hz, 1H), 1.84 (ddd,
J ¼ 14:2, 6.9, 3.0 Hz, 1H), 1.66 (d, J ¼ 1:6 Hz, 3H), 1.55
(d, J ¼ 17:6 Hz, 1H), 1.54 (s, 3H), 1.50 (dm,
J ¼ 14:2 Hz, 1H), 1.20 (d, J ¼ 6:3 Hz, 3H), 1.18 (d,
J ¼ 6:3 Hz, 3H); HRMS, m=z (Mþ) calcd for C15H22O2
for C14H20O2 220.1463, found 220.1466. Compound 9a:
20
D
(white solid) ½aꢁ ¼ þ20:2 (c 0.4, methanol); CD
(methanol) kext 220 nm (De )17.2); IR (KBr) 2961, 1455,
1375, 1205, 1089, 753 cmꢀ1; 1H NMR (CDCl3) d 5.45 (d,
J ¼ 2:0 Hz, 2H), 4.34 (dd, J ¼ 6:9, 3.0 Hz, 1H), 4.28 (m,
1H), 4.04 (m, 1H), 2.50 (d, J ¼ 9:2 Hz, 1H), 2.43 (dd,
J ¼ 9:2, 2.0 Hz, 1H), 2.21 (m, 1H), 2.09 (dd, J ¼ 14:2,
3.0 Hz, 1H), 1.56 (d, J ¼ 17:6 Hz, 1H), 1.29 (s, 3H), 1.21
(d, J ¼ 5:9 Hz, 3H), 1.19 (t like, J ¼ 6:4 Hz, 3H); 13C
NMR (CDCl3) d 142.8, 121.9, 86.6, 78.4, 77.9, 72.7,
56.9, 56.4, 44.4, 41.1, 40.1, 26.8, 24.1, 19.0; HRMS, m=z
234.1620, found 234.1613. Compound 9d: (colorless oil)
20
½aꢁ ¼ ꢀ10:0 (c 0.2, methanol); CD (methanol) kext
D
215 nm (De )10.0); IR (KCl, neat) 2928, 1594, 1456,
1376, 1208, 1101, 817 cmꢀ1; 1H NMR (CDCl3) d 4.87 (d,
J ¼ 1:6 Hz, 1H), 4.23 (dd, J ¼ 6:9, 2.5 Hz, 1H), 4.26 (m,
1H), 3.95 (m, 1H), 2.94 (d, J ¼ 8:4 Hz, 1H), 2.39 (ddd,
J ¼ 14:6, 8.4, 2.5 Hz, 1H), 2.26 (br s, 1H), 2.24 (m, 1H),
2.05 (dd, J ¼ 14:6, 6.9 Hz, 1H), 1.57 (d, J ¼ 1:6 Hz, 3H),
1.31 (s, 3H), 1.29 (d, J ¼ 16:8 Hz, 1H), 1.22 (d,
J ¼ 6:8 Hz, 3H), 1.21 (d, J ¼ 5:9 Hz, 3H); 13C NMR
(CDCl3) d 145.9, 122.7, 90.6, 79.8, 79.4, 72.7, 58.9, 47.7,
44.9, 44.2, 30.9, 26.9, 24.3, 16.7, 14.8; HRMS, m=z (Mþ)
calcd for C15H22O2 234.1620, found 234.1644.
(Mþ) calcd for C14H20O2 220.1463, found 220.1432.
20
D
methanol); IR (KCl, neat) 2970, 2929, 1600, 1457, 1376,
Compound 8b: (colorless oil) ½aꢁ ¼ ꢀ258:2 (c 0.5,
1193, 1123, 763 cmꢀ1 1H NMR (CDCl3) d 5.44 (d,
;
J ¼ 5:6 Hz, 1H), 5.35 (dd, J ¼ 5:6, 2.9 Hz, 1H), 4.14 (m,
1H), 4.07 (br d, J ¼ 3:0 Hz, 1H), 4.02 (m, 1H), 3.76 (br s,
1H), 1.91 (m, 1H), 1.85 (ddd, J ¼ 14:2, 6.5, 2.5 Hz, 1H),
1.60 (d, J ¼ 6:5 Hz, 1H), 1.57 (d, J ¼ 15:6 Hz, 1H), 1.50
(dd, J ¼ 14:2, 3.0 Hz, 1H), 1.32 (s, 3H), 1.20 (d,
J ¼ 6:4 Hz, 3H), 1.18 (d, J ¼ 6:4 Hz, 3H); 13C NMR
(CDCl3) d 134.0, 126.4, 86.8, 85.7, 73.5, 70.4, 54.1, 46.4,
43.0, 33.5, 31.0, 25.1, 23.8, 14.4; HRMS, m=z (Mþ) calcd
Acknowledgements
for C14H20O2 220.1463, found 220.1461. Compound 9b:
20
D
neat) 2968, 1716, 1419, 1376, 1140, 816, 692, 654,
(colorless oil) ½aꢁ ¼ ꢀ32:9 (c 0.5, methanol); IR (KCl,
The authors would like to thank Professor G. Lodder of
Leiden University for his helpful suggestions. A part of
this study was supported by KAKENHI from JSPS (No
13440192).
1
592 cmꢀ1; H NMR (CDCl3) d 4.99 (s, 3H), 4.47 (dd,
J ¼ 6:9, 2.1 Hz, 1H), 4.32–4.25 (m, 1H), 4.04 (m, 1H),
2.96 (d, J ¼ 8:4 Hz, 1H), 2.46 (ddd, J ¼ 14:6, 8.4,
2.1 Hz, 1H), 2.39–2.25 (m, 2H), 2.30 (d, J ¼ 7:9 Hz, 1H),
2.06 (dd, J ¼ 14:6, 6.9 Hz, 1H), 1.60 (s, 3H), 1.56 (d,
J ¼ 16:6 Hz, 1H), 1.21 (d, J ¼ 6:4 Hz, 3H), 1.20 (d,
J ¼ 6:4 Hz, 3H); 13C NMR (CDCl3) d 147.9, 117.3, 88.4,
79.8, 78.4, 72.7, 58.0, 48.4, 44.5, 40.2, 38.8, 26.8, 24.3,
15.1; HRMS, m=z (Mþ) calcd for C14H20O2 220.1463,
References and notes
1. Inoue, Y. Chem. Rev. 1992, 92, 741–770; Everitt, S. R. L.;
Inoue, Y. In Organic Molecular Photochemistry; Rama-
murthy, V., Schanze, K. S., Eds.; Dekker: New York,
1999; pp 71–130.
2. A part of this study has been published as a communi-
cation. Sugimura, T.; Nishiyama, N.; Tai, A.; Hakushi, Y.
Tetrahedron: Asymmetry 1994, 5, 1163–1166.
found 220.1468. Compound 8c: (colorless oil)
20
D
½aꢁ ¼ ꢀ46:9 (c 0.9, CH2Cl2); CD (methanol) kext
250 nm (De þ 0:9), 210 nm (De )2.7); IR (KCl, neat)
1
2928, 1638, 1446, 1376, 1095 cmꢀ1; H NMR (CDCl3) d
3. For reviews of meta-arene–alkene photocycloaddition, see:
(a) Wender, P. A.; Siggel, L.; Nuss, J. M. In Organic
Photochemistry; Padwa, A., Ed.; Dekker: New York,
1989; Vol. 10, pp 357–473; (b) Wender, P. A.; Siggel, L.;
Nuss, J. M. In Comprehensive Organic Synthesis; Trost, B.
M., Ed.; Pergamon: Oxford, 1991; Vol. 5, pp 645–673; (c)
Cronelisse, J. Chem. Rev. 1993, 93, 615–669; (d) De
Keukeleire, D. Aldrichimica Acta 1994, 27, 41–51;
Wender, P. A.; Dore, T. M. In CRC Handbook of Organic
Photochemistry and Photobiology; Horspool, W. H., Ed.;
CRC: Baca Raton, 1995, 280–290.
4.96 (d, J ¼ 1:0 Hz, 1H), 4.241 (m, 1H), 4.07 (br s, 1H),
3.98 (m, 1H), 3.75 (br s, 1H), 2.14 (d, J ¼ 8:4 Hz, 1H),
2.04 (dd, J ¼ 14:2, 6.5 Hz, 1H), 1.88–1.82 (m, 2H), 1.69
(s, 3H), 1.55 (d, J ¼ 15:6 Hz, 1H), 1.42 (dd, J ¼ 14:2,
1.6 Hz, 1H), 1.20 (d, J ¼ 6:4 Hz, 3H), 1.16 (d,
J ¼ 6:4 Hz, 3H); 13C NMR (CDCl3) d 139.3, 130.0, 86.4,
86.0, 73.2, 70.8, 51.7, 47.3, 41.5, 41.5, 33.1, 25.0, 24.1,
16.8; HRMS, m=z (Mþ) calcd for C14H20O2 220.1463,
found 220.1493. Compound 9c: (colorless oil)
20
D
½aꢁ ¼ ꢀ13:1 (c 0.4, methanol); CD (methanol) kext

K. Hagiya et al. / Tetrahedron: Asymmetry 15 (2004) 1409–1417
1417
4. For other PD-tethered reactions, see: Sugimura, T. In
Recent Research Developments in Organic Chemistry;
Pandalai, S. G., Ed.; Transworld Research Network:
Trivandrum, 1998; Vol. 2, pp 47–53.
5. Gilbert, A.; Taylor, G. N. J. Chem. Soc., Chem. Commun.
1979, 229–230; Gilbert, A.; Taylor, G. N. J. Chem. Soc., Perkin
Trans. 1 1980, 1761–1768; Ellis-Davies, G. C. R.; Gilbert, A.;
Heath, P.; Lane, J. C.; Warrington, J. V.; Westover, D. L. J.
Chem. Soc., Perkin Trans. 2 1984, 1833–1841.
6. Tei, T.; Sato, Y.; Hagiya, K.; Tai, A.; Okuyama, T.;
Sugimura, T. J. Org. Chem. 2002, 67, 6593–6598.
7. Lightner, D. A.; Crist, B. V.; Kalyanam, N.; May,
L. M.; Jachman, D. E. J. Org. Chem. 1985, 50, 3867–3881.
8. Ors, J. A.; Srinivasan, R. J. Org. Chem. 1977, 42, 1321–
1327; Wender, P. A.; Howbert, J. J. J. Am. Chem. Soc.
1981, 103, 688–690.
9. For a similar conversion, see: Wender, P. A.; Fisher, K.
Tetrahedron Lett. 1986, 27, 1857–1860.
10. Jans, A. W. H.; van Arkel, B.; van Dijk-Knepper, J. J.;
Cornelisse, J. Tetrahedron Lett. 1982, 3827–3831.
11. Sugimura, T. Euro. J. Org. Chem. 2004, 1185–1192.
12. For reviews, see: Paquette, L. A. In Topics in Current
Chemistry; Springer: Berlin, 1984; Vol. 119; Paquette, L.
A.; Doherty, A. M. Polyquinane Chemistry; Springer:
Berlin, 1987; Mehta, G.; Srikrishna, A. Chem. Rev. 1997,
97, 671–719.