The use of temporary tethers in the meta photocycloaddition reaction

Article abstract of DOI:10.1016/j.tet.2004.01.065

The use of temporary tethers in facilitating meta photocycloaddition reactions between phenol and allyl alcohol derivatives has been investigated. The merits of silicon, carbonate and methylene acetal tethers were assessed, whilst considering strategies for the preparation of the natural products gymnomitrol and gelsemine. The photoadducts were epoxidised, and then subjected to acid catalysed fragmentation with concomitant cleavage of the tether. Depending on whether water or methanol was used during the fragmentation stage of the methylene tethers, the methylene group was either removed altogether or transformed into a MOM group.

Full text of DOI:10.1016/j.tet.2004.01.065

Tetrahedron 60 (2004) 2771–2784
The use of temporary tethers in the
meta photocycloaddition reaction
a
b
a
a
Clive S. Penkett,a Paul W. Byrne, Barry J. Teobald, Benedicte Rola, Aurelie Ozanne
,
*
and Peter B. Hitchcocka
aDepartment of Chemistry, University of Sussex, Falmer, Brighton BN1 9QJ, UK
bAstraZeneca R and D Charnwood, Loughborough LE11 5RH, UK
Received 18 November 2003; revised 16 December 2003; accepted 22 January 2004
Abstract—The use of temporary tethers in facilitating meta photocycloaddition reactions between phenol and allyl alcohol derivatives has
been investigated. The merits of silicon, carbonate and methylene acetal tethers were assessed, whilst considering strategies for the
preparation of the natural products gymnomitrol and gelsemine. The photoadducts were epoxidised, and then subjected to acid catalysed
fragmentation with concomitant cleavage of the tether. Depending on whether water or methanol was used during the fragmentation stage of
the methylene tethers, the methylene group was either removed altogether or transformed into a MOM group.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
sites colliding with each other and thereby increased the rate
of a particular reaction. The lower degrees of freedom of the
unimolecular transition-state will also give rise to increased
levels of regio- and stereoselectivity between the two
reacting partners.
The use of temporary tethers1 to improve the efficiency of
meta photocycloaddition reactions2 has been investigated
for the assembly of the core skeletons of the natural products
gymnomitrol 13 and gelsemine 24 (Scheme 1).
The three main considerations when selecting a suitable
tether are that it is easily coupled to the two reacting
partners via straightforward chemical transformation;
that it is stable to a variety of chemical conditions; and,
when it has served its purpose, that it be selectively
cleaved from the final product, leaving no trace of its
original existence.
1.1. Temporary tethers
Stork5 originally introduced the concept of using a
‘temporary tether’ to convert an intermolecular reaction
into an intramolecular one. The decreased entropic demands
on such a system increased the likelihood of two reacting
Scheme 1.
Keywords: Temporary tethers; Photochemistry; Cycloaddition; Epoxidation; Fragmentation.
*
Corresponding author. Tel.: þ44-1273-877374; fax: þ44-1273-677196; e-mail address: c.s.penkett@sussex.ac.uk
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.01.065

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C. S. Penkett et al. / Tetrahedron 60 (2004) 2771–2784
Figure 1. The meta photocycloaddition product between ethene and benzene is represented in three different forms. The numbering system of the basic meta
photocycloadduct shown above is used throughout this publication, with the letters a and b signifying whether the atoms are derived from the former alkene and
benzene portions, respectively.
Temporary tethers have found extensive use in radical and
thermal cycloaddition reactions, because of the advantages
these types of reaction have when carried out in an
intramolecular sense.1 They have also been applied in
[2þ2] photocycloaddition reactions,6 although their usage
has been somewhat limited.
to occur. Two photoadducts are derived from alkene
addition across the 1,3-positions of the aromatic ring, whilst
the other is derived from alkene addition across the aromatic
2,6-positions (Fig. 3).
Most of the photoadducts reported in this publication have a
four-atom tether between the benzene and alkene portions
and, because the tethers were electron donating, only the
2,6-mode of cycloaddition across the aromatic ring was
observed. The additional flexibility associated with this
longer tether allowed it to link from the b1 position of the
photoadduct to either the a6 or the a7 positions (Fig. 4).
1.2. The meta photocycloaddition reaction
The meta photocycloaddition reaction was initially reported
in 19662a,b and involves the 1,3-addition of an alkene across
the excited state of a benzene derivative. The simplest
version of this reaction between ethene and benzene is
shown in Figure 1, with the former ethene and benzene ring
portions being highlighted in bold.
The regiochemistry of the photocycloaddition reaction is
strongly dependent on the electronic nature of the
substituent on the aromatic ring of the photosubstrate.
Electron-donating groups tend to favour position b1 in the
photoadduct, whilst electron-withdrawing groups favour
positions b2 or b4 (Fig. 2).
Figure 4. The two modes of intramolecular meta photocycloaddition for
benzene linked to an alkene by a four-atom tether involving 2,6 addition of
the olefin across the aromatic ring.
2. Results and discussion
2.1. Gymnomitrol studies
The intramolecular variant of the meta photocycloaddition
reaction was discovered almost by accident,7 whilst
investigating light induced cis/trans isomerism of 6-phenyl-
hex-2-ene. So far the majority of such reactions have
involved a three-atom chain linking the benzene and alkene
portions, for which three modes of meta cycloaddition tend
Whilst investigating the steric effects associated with the
meta photocycloaddition reaction between cyclopentene
and anisole derivatives, Hoye8 attempted to assemble the
Figure 2. Regioselectivity of meta photocycloaddition reactions.
Figure 3. The three possible modes of intramolecular meta photocycloaddition for benzene linked to an alkene by a three-atom tether.

C. S. Penkett et al. / Tetrahedron 60 (2004) 2771–2784
2773
Scheme 2.
core structure of the sesquiterpene gymnomitrol 1 by
irradiating 1-methoxy-2-methylbenzene 3 in the presence
of 1,2-dimethylcyclopentene 4 and then fragmenting the
meta photoadduct 5 using aqueous acid (Scheme 2).
Unfortunately, the desired meta photocycloaddition
between 3 and 4 failed to provide any of the desired
photoadduct 5, leading the authors to conclude that an
intermolecular photoaddition reaction between a di-sub-
stituted aromatic and a tetra-substituted alkene was
disfavoured on the grounds of steric hindrance.
either the a6 or a7 positions). The potential photoadduct 8
represented in Scheme 3 shows the methyl group at position
b8 and the tether attached between the b1 and a6 positions.
Quite which regioisomer would be generated would be
resolved as a result of experimentation. (Note that the same
numbering system in Figure 1 is used, when referring to
meta photocycloadducts).
We prepared a series of simplified model substrates using
2-methylphenol 11 to determine what would be the most
appropriate tether. One priority in considering a suitable
tether was its stability towards silica-based chromatography
since earlier work had shown some silicon-based tethers to
be very labile under these conditions.
We considered that the inherent advantages of carrying out
an intramolecular version of this reaction might overcome
these steric obstacles and proposed using a temporary tether,
X, to assemble the core skeleton of gymnomitrol. Our
strategy was to couple appropriate aromatic and olefin
groups together via a tether to provide the photosubstrate 7
and then initiate an intramolecular meta photocycloaddition
reaction. The predicted photoadduct 8 would be epoxidised
to 9 and hydrolysed under acidic conditions to afford the
keto-diol 10, which would subsequently be converted to
gymnomitrol 1 (Scheme 3).
The first type of tether we chose was the carbonate. The
mixed carbonate 12 was prepared using the procedure of
Larock and Lee9 by sequential reaction of triphosgene with
2-methylphenol and allyl alcohol in the presence of
triethylamine. Unfortunately, irradiation of 12 failed to
yield any of the desired photoadduct 13 (Scheme 4). This
may have been due to internal quenching of the excited state
in the aromatic ring by the adjacent carbonyl group.
Alternatively, the restricted conformation of the various
rotomeric forms associated with the ester-like carbonate
may have prevented close association of the alkene with its
aromatic partner.
The electron-donating oxygen atom on the phenolic ring of
7 should direct the addition of the alkene across the 2,6
positions of the aromatic ring of the photosubstrate during
the meta photocycloaddition reaction2c to give 8. Other
regioisomers could also be formed, which would be related
by the ultimate position of the methyl group derived from
the aromatic ring (at either position b5 or b8 in compound 8)
and the attachment points of the tether (between b1 and
Next, we turned our attention to the preparation of a
methylene acetal tether. To achieve this we required a
source of aryl chloromethyl ether, which could be
Scheme 3.

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C. S. Penkett et al. / Tetrahedron 60 (2004) 2771–2784
Scheme 4.
Table 1. The preparation, irradiation and oxidation of methylene acetal tethered meta photocycloadducts
Entry
R1
R2
R3
Yield of 18
(%)
Yield of 19
(%)
Yield of 20
(%)
a
b
c
d
e
f
H
H
H
Me
Me
Me
H
Me
H
H
Me
H
H
H
Me
H
H
Me
77
71
0
0
0
13
17
7b
—
—
—
100
100
100
72a
79
86
78a
a
Obtained as a 4:1 mixture of E/Z isomers.
Only E isomer underwent meta photocycloaddition.
b
subsequently coupled to various allylic alcohols. The highly
efficient procedure of Benneche and Undheim10 was
employed, which involved decarbonylation of a phenoxy-
acetyl chloride by heating with Wilkinson’s catalyst at
170 8C. 2-Methylphenyl chloromethyl ether 17 was
prepared as gymnomitrol required the aromatic ring to be
substituted with a methyl group. We also prepared phenyl
chloromethyl ether 16, to assess the effect of removing the
2-methyl group on the photoreaction. Both aryl chloro-
methyl ethers were then coupled to three allylic alcohols to
give six potential methylene acetal photosubstrates 18a–f.
Each were separately dissolved in cyclohexane (0.1 M) and
irradiated in a quartz immersion-well photoreactor for 7
days using a 6 W low-pressure mercury vapour lamp. We
found that only the photosubstrates 18d–f derived from
2-methylphenol underwent meta photocycloaddition.
Irradiation of the photosubstrates 18a–c derived from
phenol led to unreacted starting material and the formation
of a complex polymeric mixture. At this point, we resolved
the regiochemical issues spoken of earlier and found that the
former aromatic methyl group was incorporated at the b5
position of the photoadducts 19d–f with the tether attached
between the b1 and a7 positions (see Fig. 1 for photoadduct
numbering system). In the case of 18f, which was a 4:1
mixture of E and Z alkenes, only the E isomer underwent
meta photocycloaddition. After chromatographic purifi-
cation, the 1,3-cycloadducts 19d–f were oxidised to
their corresponding exo-epoxides using dimethyl dioxir-
ane.11 The results of these experiments are summarised
in Table 1.
Alternative methods for fragmentating the epoxides 20d–f
was next investigated. Epoxide 20e was fragmented using
aqueous acid to produce the hydroxy-ketone 21e, which
existed in equilibrium with its hemi-acetal 22e. This mixture
was converted to the methoxyacetal 23e by stirring in
acidified methanol for a few days, which had the effect of
protecting the primary hydroxyl group and the bridgehead
ketone and leaving the allylic alcohol free for further
chemical manipulation (Scheme 5).
Whilst trying to convert epoxides 20d and 20f directly to
23d and 23f using only acidified methanol, a different
transformation was observed. The methylene oxonium ion
24, which must have formed initially, was trapped with
methanol rather than water. This had the effect of protecting
the primary hydroxyl as a MOM group, whilst the bridge-
head position remained as an unprotected ketone
(Scheme 6). Extended exposure of either 25d or 25f to
acidified methanol led only to significant decomposition.
Scheme 5.

C. S. Penkett et al. / Tetrahedron 60 (2004) 2771–2784
2775
Scheme 6.
Having established these encouraging results with a
methylene acetal tether, (2-methylcyclopent-1-enyl)methanol
26 was prepared according to the procedure of Inouye et al.12
and reacted with 2-methylphenyl chloromethyl ether 17 using
phase transfer conditions again. Unfortunately, irradiation of
27 led to none of the desired meta photocycloadduct 28 being
isolated (Scheme 7). This indicated that even the inherent
steric advantages of an intramolecular reaction were insuffi-
cient to overcome the steric encumbrance involved with a
tetra-substituted olefin reacting with a di-substituted aromatic
ring.
centre at C20, the allylic alcohol group could be used to
introduce the oxindole unit at C7 and the silicon group could
be oxidatively cleaved and replaced by nitrogen at C5 using
a Curtius rearrangement. The shortcoming of this approach
was that it would not allow the incorporation of the endo
oxymethylene group at C17, as the appropriate E disubsti-
tuted olefin photosubstrate would be extremely unstable due
to elimination (Scheme 9).
The obvious solution to this problem was to introduce an
additional oxygen atom between the removable tether and
the allyl group. We could not use a methylene acetal tether,
as we had already discovered allyloxymethoxybenzene 18a
would not undergo the desired meta photocycloaddition
reaction, so we chose the more labile silicon tether instead.
Preliminary studies were performed with allyloxydimethyl-
phenoxysilane 35, which was prepared by the reaction of
chlorodimethylphenoxysilane14 33 with the lithium salt of
allyl alcohol 34. A solution of the silicon-tethered photo-
substrate 35 in cyclohexane was irradiated in a quartz
immersion-well photoreactor using a 16 W low-pressure
mercury vapour lamp. The silicon tether was very prone to
hydrolysis during silica-based chromatography, although
we managed to isolate both the b1–a6 and b1–a7 tethered
2.2. Gelsemine studies
We have already shown how the core skeleton of gelsemine
2 might be assembled with a silicon tethered meta
photocycloaddition protocol13 (Scheme 8).
The hydroxyketone 31, which formed as a result of an
epoxidation-fragmentation reaction on photoadduct 30,
contained suitable functionality at all positions to complete
a possible gelsemine synthesis, except at what would
become C16 (gelsemine numbering, Scheme 8). The
carbonyl group could be used to create the quarternary
Scheme 7.
Scheme 8.
Scheme 9.

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C. S. Penkett et al. / Tetrahedron 60 (2004) 2771–2784
Scheme 10.
Scheme 11.
Scheme 12.
meta photocycloadducts 36 and 37 together as a 1:2
inseparable mixture (Scheme 10).
isolated with the bridgehead ketone intact and not protected
as a dimethyl acetal. Further exposure to acidic methanol at
elevated temperatures led to the formation of dimethyl
acetal 43, however, the silyl-protecting group was
hydrolysed as a consequence.
The losses we encountered whilst attempting to isolate 36
and 37, caused us to irradiate 35, oxidise and then fragment
in one pot. A 1:1 mixture of the ketodiols 38 and 39 was
obtained in 16% overall yield (Scheme 11) and the
diastereomeric pair could be separated at this stage. In
each case the primary hydroxyl group did not cyclise onto
the bridgehead position, which was protected as a dimethyl
acetal. Interestingly, the diols 38 and 39 were isolated as a
1:1 mixture in contrast to the 1:2 mixture of photoadducts
36 and 37 after irradiation.
3. Conclusion
This methodology allows the formation of unique tetra-
cyclic compounds, which would otherwise be inaccessible
through conventional means. We have shown that
temporary tethers can play an important role in promoting
certain meta photocycloaddition reactions, although they
require an additional degree of complexity in their
formation. It has also been demonstrated that methylene
acetal tethers can act as alternatives to silicon tethers. Their
increased stability has advantages in their purification and
they can also be converted into useful protecting groups
(e.g., a MOM group) after they have served their initial
purpose.
Diol 38 provided strong encouragement for the preparation
of the gelsemine skeleton, because if a trans oxymethylene
group could be introduced onto the terminus of the olefin of
35, the resulting endo oxymethylene group would be
incorporated at what would become C16 of the gelsemine
structure after the photochemical stage. E-4-(tButyl-
dimethylsilanyloxy)-but-2-en-1-ol 40, prepared by mono-
silylation15 of the corresponding diol,16 was chosen as the
alkene partner to accomplish this, and was coupled to
chlorodimethylphenoxysilane 33. The resulting silicon
tethered photosubstrate 41 was irradiated, epoxidised and
hydrolysed to afford the single keto-diol 42 in 16% overall
yield from 41 (Scheme 12).
4. Experimental
4.1. General
1H NMR spectra were recorded on Bruker DPX300, Varian
unityINOVA-300, Varian unityINOVA-400 or Bruker
AMX500 Fourier transform spectrometers at 300, 400 or
500 MHz, respectively. Chemical shifts (d) are quoted in
ppm using tetramethylsilane or residual chloroform as
internal reference (d¼0.00 ppm), and coupling constants (J)
are quoted in Hz. 13C NMR spectra were recorded using the
same instruments, and chemical shifts (d) are quoted in ppm
using CDCl3 as internal reference ((d)¼77.0 ppm).
There were significant differences between the preparation
of 42 from 41 compared with the corresponding reaction
using 35 (Scheme 11). Only one diol product 42 was
formed, which indicated that one mode of photocyclo-
addition had occurred. During the photoaddition step, the
tether was attached at the a7 exo position (see Fig. 1) in a
manner similar to 39 and none of the a6 exo regioisomer
was formed. Unlike compounds 38 and 39, the diol 42 was

C. S. Penkett et al. / Tetrahedron 60 (2004) 2771–2784
2777
IR spectra were recorded on Perkin–Elmer Spectrum One
Fourier transform instruments, either using a liquid film
between sodium chloride plates (LF) or by the method of
attenuated total reflectance (ATR). Frequencies (nmax) are
quoted in wavenumbers (cm21).
(film) 3085, 3029, 2985, 2954, 1762, 1720, 1649, 1585,
1492, 1461 cm21; MS (EI) m/z 192 (2, Mþ), 148 (23), 133
(29), 107 (25), 91 (20), 77 (23), 41 (100). Sample
decomposed prior to accurate mass measurement.
4.1.2. [(2-Propenyloxy)methoxy]benzene 18a. Fifty
percent aqueous sodium hydroxide (60 ml) and tetra-
butylammonium chloride (0.834 g, 3.0 mmol) were added
to a solution of (chloromethoxy)benzene8 16 (4.29 g,
30 mmol) and 2-propen-1-ol (2.0 ml, 29 mmol) in benzene
(60 ml). The resulting two-phase mixture was stirred
vigorously at rt for 4 h and then separated. The organic
phase was washed with brine, dried (MgSO4) and
concentrated in vacuo to give a colourless liquid (4.94 g).
Distillation afforded the pure product 18a (3.72 g, 77%) as a
colourless liquid (bp 52–54 8C at 1 mm Hg).
Low- and high-resolution electron impact (EI) and chemical
impact (CI) mass spectra were recorded using a Fisons
Autospec instrument. High-resolution electrospray
ionisation (ESI) mass spectra were recorded using a Bruker
Daltonics APEXIII instrument.
The starting materials for the synthesis of the compounds
were obtained from the usual suppliers (Sigma-Aldrich-
Fluka, Lancaster, Fisher etc.) unless otherwise stated. The
anhydrous solvents, tetrahydrofuran and diethyl ether
(ether), were obtained from Aldrich Chemicals in Sure/
Seale bottles and were used without further purification.
Petrol refers to petroleum ether with a boiling range of
40–60 8C. Flash column chromatography was performed
using Fisher Matrex 60 (35–70 mm) silica, and the same
silica was used for silver nitrate impregnation by the method
of Li et al.17 Analytical thin layer chromatography (TLC)
1H NMR (300 MHz, CDCl3) d 7.25–7.32 (2H, m, Ar-H),
6.98–7.07 (3H, m, Ar-H), 5.85–5.98 (1H, m, (CH2)CHv),
5.19–5.34 (2H, m, vCH2), 5.25 (2H, s, OCH2O), 4.21 (2H,
d, J¼5.5 Hz, OCH2C); 13C NMR (75 MHz, CDCl3) d 157.3,
133.8, 129.4, 121.8, 117.6, 116.2, 92.4, 69.1; IR (film) 3074,
3042, 3020, 2958, 2896, 1648, 1598, 1589 cm21; MS (EI)
m/z 164 (30, Mþ), 134 (69), 119 (25), 107 (25), 94 (33), 77
(43), 65 (21), 41 (100); HRMS (ESI) m/z calcd for
C10H12NaO2 ([MþNa]þ) 187.0730, found 187.0733.
˚
was performed using Whatman K6F silica gel plates (60 A
porosity) developed with UV light or an alkaline solution of
potassium permanganate followed by heating to give yellow
spots. Analytical silver nitrate impregnated plates were also
prepared from these and developed simply by heating to
give black spots.
4.1.3. [[(2-Methyl-2-propenyl)oxy]methoxy]benzene
18b. Fifty percent aqueous sodium hydroxide (60 ml) and
tetrabutylammonium chloride (0.840 g, 3.0 mmol) were
added to a solution of (chloromethoxy)benzene8 16 (4.30 g,
30 mmol) and 2-methyl-2-propen-1-ol (2.52 ml, 30 mmol)
in benzene (60 ml). The resulting two-phase mixture was
stirred vigorously at rt for 1 h and then separated. The
organic phase was washed with brine, dried (MgSO4) and
concentrated in vacuo to give a colourless liquid (6.11 g).
Distillation afforded the pure product 18b (3.79 g, 71%) as a
colourless liquid (bp 65–67 8C at 1 mm Hg).
Irradiations were carried out in 75 ml and 150 ml quartz
immersion well reactors fitted with 6- or 125-watt mercury
vapour lamps as supplied by Photochemical Reactors Ltd,
Reading, UK. Oxygen free solvent for the irradiation
experiments was simply obtained by passing a vigorous
stream of nitrogen gas through a sintered glass tube into the
solvent for 15 min at rt. Experiments were conducted with
gentle stirring of the reaction solution under an atmosphere
of nitrogen and with cold-water cooling of the lamp and
vessel contents throughout.
1H NMR (300 MHz, CDCl3) d 7.25–7.32 (2H, m, Ar-H),
6.98–7.08 (3H, m, Ar-H), 5.24 (2H, s, OCH2O), 5.00 (1H, s,
vC(H)H), 4.91 (1H, s, vC(H)H), 4.10 (2H, s, OCH2C),
1.73 (3H, s, Me); 13C NMR (75 MHz, CDCl3) d 157.3,
141.3, 129.4, 121.8, 116.2, 112.7, 92.3, 72.0, 19.5; IR (film)
3075, 3042, 3041, 2973, 2946, 2909, 1659, 1599,
1589 cm21; MS (EI) m/z 178 (12, Mþ), 148 (22), 133
(58), 94 (31), 77 (27), 55 (100); HRMS (ESI) m/z calcd for
C11H14NaO2 ([MþNa]þ) 201.0886, found 210.0886.
4.1.1. 2-Methylphenyl 2-propenyl carbonate 12. Follow-
ing the procedure of Larock and Lee9 a solution of
triethylamine (6.44 ml, 46.2 mmol) in ether (20 ml) was
added dropwise over 45 min to an ice-cold solution of
2-methylphenol 11 (5.00 g, 46.6 mmol) and triphosgene
(4.59 g, 15.5 mmol) in ether (50 ml) to form a dense white
suspension. More ether (50 ml) was added to aid stirring,
followed by triethylamine (6.44 ml, 46.2 mmol) in one
portion. A solution of 2-propen-1-ol (3.14 ml, 46.2 mmol)
in ether (20 ml) was added dropwise over 20 min to the ice-
cold suspension, which was then slowly allowed to warm to
rt by stirring overnight. The dense suspension was filtered
and the filtrate was concentrated in vacuo to afford an
orange oil (8.17 g). Distillation afforded the pure product 12
(5.53 g, 62%) as a colourless liquid (bp 90–94 8C at
1 mm Hg).
4.1.4. [(2-Butenyloxy)methoxy]benzene 18c. Fifty percent
aqueous sodium hydroxide (60 ml) and tetrabutyl-
ammonium chloride (0.830 g, 3.0 mmol) were added to a
solution of (chloromethoxy)benzene8 16 (4.32 g, 30 mmol)
and 2-buten-1-ol (2.55 ml, 30 mmol) in benzene (60 ml).
The resulting two-phase mixture was stirred vigorously at rt
for 4 h and then separated. The organic phase was washed
with brine, dried (MgSO4) and concentrated in vacuo to give
a pale yellow liquid (5.01 g). Distillation afforded 18c
(3.86 g, 72%) as a colourless liquid (bp 70–74 8C at
1 mm Hg), which was a 4:1 mixture of (E)/(Z) alkenes.
1H NMR (300 MHz, CDCl3) d 7.09–7.26 (4H, m, Ar-H),
5.94–6.07 (1H, m, (CH2)CHvC), 5.32–5.46 (2H, m,
vCH2), 4.74 (2H, d, J¼5.8 Hz, OCH2C), 2.24 (3H, s,
Ar-Me); 13C NMR (75 MHz, CDCl3) d 153.3, 149.6, 131.2,
131.1, 130.0, 127.0, 126.3, 121.4, 119.4, 69.1, 15.9; IR
1H NMR (300 MHz, CDCl3) d [(E)-major isomer] 7.25–
7.32 (2H, m, Ar-H), 6.97–7.08 (3H, m, Ar-H), 5.66–5.81

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C. S. Penkett et al. / Tetrahedron 60 (2004) 2771–2784
(1H, m, vCH(Me)), 5.51–5.62 (1H, m, –(H2C)HCv),
5.23 (2H, s, OCH2O), 4.13 (2H, d, J¼6.2 Hz, OCH2C), 1.71
(3H, d, J¼6.2 Hz, vC(H)Me); d [(Z)-minor isomer] 7.25–
7.32 (2H, m, Ar-H), 6.97–7.08 (3H, m, Ar-H), 5.66–5.81
(1H, m, vCH(Me)), 5.51–5.62 (1H, m, –(H2C)HCv),
5.24 (2H, s, OCH2O), 4.27 (2H, d, J¼6.7 Hz, OCH2C), 1.66
(3H, d, J¼6.7 Hz, vC(H)Me); 13C NMR (75 MHz, CDCl3)
[(E)/(Z) mixture ,4:1] d [(E)-major isomer] 157.3, 130.6,
129.4, 126.5, 121.7, 116.2, 92.1, 68.8, 17.8; d [(Z)-minor
isomer] 157.3, 129.4, 129.0, 125.7, 121.7, 116.2, 92.2, 63.3,
13.1; IR (film) 3064, 3027, 2963, 2943, 2916, 2859, 1674,
1599 cm21; MS (EI) m/z 178 (36, Mþ), 148 (60), 107 (54),
94 (94); HRMS (ESI) m/z calcd for C11H14NaO2
([MþNa]þ) 201.0886, found 210.0886.
Fifty percent aqueous sodium hydroxide (60 ml) and
tetrabutylammonium chloride (0.835 g, 3.0 mmol) were
added to a solution of 1-(chloromethoxy)-2-methylbenzene8
17 (4.70 g, 30 mmol) and 2-buten-1-ol (2.5 ml, 29 mmol) in
benzene (60 ml). The resulting two-phase mixture was
stirred vigorously at rt for 1 h and then separated. The
organic phase was washed with brine, dried (MgSO4) and
concentrated in vacuo to give a yellow liquid (6.42 g).
Distillation afforded 18f (4.37 g, 78%) as a colourless liquid
(bp 64–74 8C at 1 mm Hg), which was a 4:1 mixture of
(E)/(Z) alkenes.
1H NMR (400 MHz, CDCl3) d [(E)-major isomer] 7.12–
7.15 (2H, Ar-H), 7.05–7.09 (1H, m, Ar-H), 6.88–6.92 (1H,
m, Ar-H), 5.67–5.79 (1H, m, vCH(Me)), 5.53–5.62 (1H,
m, –(H2C)HCv), 5.25 (2H, s, OCH2O), 4.13 (2H, d,
J¼6.4 Hz, OCH2C), 2.24 (3H, s, Ar-Me), 1.71 (3H, d,
J¼6.4 Hz, vC(H)Me); d [(Z)-minor isomer] 7.12–7.15
(2H, m, Ar-H), 7.05–7.09 (1H, m, Ar-H), 6.88–6.92 (1H,
m, Ar-H), 5.67–5.79 (1H, m, vCH(Me)), 5.53–5.62 (1H,
m, –(H2C)HCv), 5.26 (2H, s, OCH2O), 4.27 (2H, d,
J¼6.9 Hz, vCH(Me)), 2.25 (3H, s, Ar-Me), 1.66 (3H, d,
J¼6.9 Hz, vC(H)Me); 13C NMR (75 MHz, CDCl3) d [(E)-
major isomer] 155.4, 130.7, 130.4, 127.3, 126.8, 126.6,
121.4, 113.8, 92.1, 68.9, 17.8, 16.3; d [(Z)-minor isomer]
155.4, 130.7, 129.0, 127.3, 126.8, 125.8, 121.4, 113.8, 92.1,
63.2, 16.3, 13.1; IR (film) 3024, 2946, 2917, 2859, 1602,
1591, 1495, 1463 cm21; MS (EI) m/z 192 (12, Mþ), 162
(24), 108 (100), 55 (84), 39 (96); HRMS (EI) m/z calcd for
C12H16O2 (Mþ) 192.1150, found 192.1163.
4.1.5. 1-Methyl-2-[(2-propenyloxy)methoxy]benzene
18d. Fifty percent aqueous sodium hydroxide (60 ml) and
tetrabutylammonium chloride (0.832 g, 3.0 mmol) were
added to a solution of 1-(chloromethoxy)-2-methylbenzene8
17 (4.70 g, 30 mmol) and 2-propen-1-ol (2.0 ml, 29 mmol)
in benzene (60 ml). The resulting two-phase mixture was
stirred vigorously at rt for 75 min and then separated. The
organic phase was washed with brine, dried (MgSO4) and
concentrated in vacuo to give a pale yellow liquid (5.59 g).
Distillation afforded the pure product 18d (4.10 g, 79%) as a
colourless liquid (bp 62–66 8C at 1 mm Hg).
1H NMR (300 MHz, CDCl3) d 7.07–7.16 (3H, m, Ar-H),
6.89–6.93 (1H, m, Ar-H), 5.86–5.99 (1H, m, (CH2)CHv),
5.27 (2H, s, OCH2O), 5.26 (2H, m, vCH2), 4.21 (2H, d,
J¼5.6 Hz, OCH2C), 2.24 (3H, s, Ar-Me); 13C NMR
(75 MHz, CDCl3) d 155.4, 133.9, 130.7, 127.3, 126.8,
121.5, 117.5, 113.9, 92.4, 69.1, 16.3; IR (film) 3080, 3024,
2951, 2908, 1648, 1602, 1591, 1495, 1463 cm21; MS (EI)
m/z 178 (41, Mþ), 148 (57), 133 (32), 107 (42), 91 (35), 77
(27), 41 (100); HRMS (EI) m/z calcd for C11H14O2 (Mþ)
178.0993, found 178.1007.
4.1.8. 2,4-Dioxa-11-methyl-tetracyclo[6.4.0.01,8.06,7]-
dodec-9-ene 19d. Under an atmosphere of nitrogen, a
solution of 18d (1.34 g, 7.5 mmol) in oxygen free
cyclohexane (75 ml) was irradiated with a 6-watt low-
pressure mercury vapour lamp for 7 days using a 75 ml
quartz immersion-well photo reactor. The solution was
removed from the reactor and concentrated in vacuo to leave
a pale yellow oil (1.30 g). The oil was purified by flash
chromatography on silica (65 g) eluted with increasing
concentrations of dichloromethane in petrol (30, 50 and
100%). Five components were isolated: (in order of
increasing polarity) unchanged starting material (0.78 g,
58%); possible intermolecular by-product (0.013 g, 1%);
impure uncharacterised by-product (0.008 g, 0.6%); impure
meta-addition product (0.324 g, 24%); and possible unstable
ortho-addition product (0.069 g, 5%).
4.1.6. 1-Methyl-2-[[(2-methyl-2-propenyl)oxy]methoxy]-
benzene 18e. Fifty percent aqueous sodium hydroxide
(60 ml) and tetrabutylammonium chloride (0.836 g,
3.0 mmol) were added to a solution of 1-(chloromethoxy)-
2-methylbenzene8 17 (4.70 g, 30 mmol) and 2-methyl-2-
propen-1-ol (2.53 ml, 30 mmol) in benzene (60 ml). The
resulting two-phase mixture was stirred vigorously at rt for
1 h and then separated. The organic phase was washed with
brine, dried (MgSO4) and concentrated in vacuo to give a
pale yellow liquid (8.16 g). Distillation afforded the
pure product 18e (4.97 g, 86%) as a colourless liquid
(bp 74–76 8C at 1 mm Hg).
The impure meta-addition product was purified further by
flash chromatography on silver nitrate impregnated silica17
(30 g) and eluted with methanol/dichloromethane/petrol
(5:20:75) to afford another uncharacterised by-product
(0.049 g, 4%) and the pure meta-addition product 19d as a
pale yellow oil (0.178 g, 13%).
1H NMR (400 MHz, CDCl3) d 7.08–7.15 (3H, m, Ar-H),
6.89–6.92 (1H, m, Ar-H), 5.26 (2H, s, OCH2O), 5.00 (1H, s,
vC(H)H), 4.91 (1H, s, vC(H)H), 4.11 (2H, s, OCH2C),
2.24 (3H, s, Ar-Me), 1.73 (3H, s, Me); 13C NMR (100 MHz,
CDCl3) d 155.5, 141.5, 130.7, 127.3, 126.8, 121.5, 113.9,
112.6, 92.5, 72.1, 19.5, 16.3; IR (film) 3077, 3026, 2973,
2948, 2915, 2862, 1656, 1603, 1591, 1495, 1461 cm21; MS
(EI) m/z 192 (52, Mþ), 162 (80), 147 (100), 121 (43), 107
(79), 91 (67), 79 (83), 55 (37), 41 (54); HRMS (EI) m/z
calcd for C12H16O2 (Mþ) 192.1150, found 192.1143.
1H NMR (400 MHz, CDCl3) d 5.62 (1H, d, J¼5.6 Hz,
H-10), 5.46 (1H, dd, J¼5.6, 2.6 Hz, H-9), 5.31 (1H, d,
4.1.7. 1-[(2-Butenyloxy)methoxy]-2-methylbenzene 18f.

C. S. Penkett et al. / Tetrahedron 60 (2004) 2771–2784
2779
J¼6.1 Hz, H-3endo), 4.68 (1H, d, J¼6.1 Hz, H-3exo), 3.80
(1H, dd, J¼11.2, 1.9 Hz, H-5endo), 3.42 (1H, d, J¼11.2 Hz,
H-5exo), 2.87 (1H, d, J¼7.0 Hz, H-6), 2.73 (1H, ddd, J¼8.2,
2.6, 1.4 Hz, H-8), 1.87 (1H, dd, J¼12.7, 7.0 Hz, H-12endo),
1.59 (1H, d, J¼2.7 Hz, H-12exo), 1.47 (1H, d, J¼8.2 Hz,
H-7), 1.30 (3H, s, 11-Me); 13C NMR (75 MHz, CDCl3) d
145.9, 121.3, 98.7, 85.3, 83.0, 57.9, 48.1, 46.9, 42.4, 37.8,
17.6; IR (film) 3059, 3039, 2949, 2927, 2869, 1604, 1456,
1449 cm21; MS (EI) m/z 178 (18, Mþ), 97 (28), 81 (49), 69
(100), 57 (56), 41 (64). Sample decomposed prior to
accurate mass measurement.
flash chromatography on silver nitrate impregnated silica17
(42 g) eluted with methanol/dichloromethane/petrol
(5:20:175) to afford the still impure meta-addition product
(0.343 g, 12%). Another purification by flash chromatography
on silica (100 g) eluted with 7.5% 2-methoxy-2-methylpro-
pane in petrol gave an uncharacterised by-product (0.063 g,
2%) and the pure meta-addition product 19f (0.194 g, 7%) as a
pale yellow low-melting solid mp ,20 8C.
4.1.9. 2,4-Dioxa-6endo,11-dimethyl-tetracyclo[6.4.0.01,8
6,7]dodec-9-ene 19e. Under an atmosphere of nitrogen, a
.
0
solution of 18e (1.45 g, 7.5 mmol) in oxygen free cyclohexane
(75 ml) was irradiated with a 6-watt low-pressure mercury
vapour lamp for 16 days using a 75 ml quartz immersion-well
photo reactor. The solution was removed from the reactor and
concentrated in vacuo to leave a pale yellow oil (1.37 g). The
oil was purified by flash chromatography (dichloromethane/
petrol 1:1) then neat dichloromethane. Four components were
isolated: (in order of increasing polarity) unchanged starting
material (0.882 g, 61%); possible intermolecular by-product
(0.013 g, 0.9%); possible ortho-addition product (0.012 g,
0.8%);and pure meta-addition product 19e as a pale yellow oil
(0.250 g, 17%).
1H NMR (400 MHz, CDCl3) d 5.56 (1H, dd, J¼5.5, 2.4 Hz,
H-9), 5.52 (1H, d, J¼5.5 Hz, H-10), 5.28 (1H, d, J¼6.0 Hz,
H-3endo), 4.65 (1H, d, J¼6.0 Hz, H-3exo), 3.89 (1H, dd,
J¼11.3, 1.8 Hz, H-5endo), 3.42 (1H, d, J¼11.3 Hz, H-5exo),
2.73 (1H, ddd, J¼8.2, 2.4, 1.5 Hz, H-8), 2.43 (1H, m, H-6),
2.06 (1H, q, J¼7.4 Hz, H-12), 1.34 (1H, d, J¼8.2 Hz, H-7),
1.21 (3H, s, 11-Me), 0.85 (3H, d, J¼7.4 Hz, 12-Me); 13C
NMR (100 MHz, CDCl3) d 141.2, 122.6, 98.1, 87.5, 82.2,
60.6, 54.7, 48.9, 47.5, 35.2, 17.4, 17.1; IR (ATR) 3062,
2957, 2915, 2861, 1609 cm21; MS (EI) m/z 192 (1, Mþ),
162 (27), 147 (21), 119 (44), 108 (100), 91 (47), 77 (23), 55
(47); HRMS (ESI) m/z calcd for C12H16NaO2 ([MþNa]þ)
215.1043, found 215.1035.
4.1.11. 2,4-Dioxa-11-methyl-tetracyclo[6.4.0.01,8.06,7]-
dodec-9-ene oxide 20d. A 0.1 M solution of ice cold
dimethyldioxirane9 in acetone (27 ml, 2.7 mmol) was added
to the meta photoadduct 19d (53 mg, 0.30 mmol) and
allowed to warm to rt overnight. The remaining solvent was
removed in vacuo and any residual water was removed by
addition of ethyl acetate (20 ml), drying (MgSO4), filtering
and concentrating in vacuo to give the product 20d (57 mg,
100%) as a pale yellow crystalline solid mp 79–80 8C.
1H NMR (400 MHz, CDCl3) d 5.62 (1H, d, J¼5.6 Hz,
H-10), 5.49 (1H, dd, J¼5.6, 2.6 Hz, H-9), 5.29 (1H, d,
J¼5.9 Hz, H-3endo), 4.69 (1H, d, J¼5.9 Hz, H-3exo), 3.53
(1H, d, J¼11.0 Hz, H-5endo), 3.23 (1H, d, J¼11.0 Hz,
H-5exo), 2.66 (1H, ddd, J¼8.2, 2.6, 1.3 Hz, H-8), 1.79 (1H,
d, J¼12.6 Hz, H-12exo), 1.60 (1H, dd, J¼12.6, 1.3 Hz,
H-12endo), 1.29 (3H, s, 11-Me), 1.28 (1H, m, H-7), 1.18 (3H,
s, 6-Me); 13C NMR (100 MHz, CDCl3) d 146.2, 121.4, 98.1,
88.7, 85.2, 58.3, 53.7, 49.5, 47.7, 40.6, 19.0, 17.9; IR (ATR)
2927, 2866, 1605 cm21; MS (EI) m/z 192 (1, Mþ), 132
(100), 117 (84), 91 (31). Sample decomposed prior to
accurate mass measurement.
1H NMR (500 MHz, CDCl3) d 5.26 (1H, dd, J¼5.9, 0.5 Hz,
H-3endo), 4.47 (1H, d, J¼5.9 Hz, H-3exo), 3.92 (1H, dd,
J¼11.4, 1.8 Hz, H-5endo), 3.45 (1H, br d, J¼11.3 Hz,
H-5exo), 3.35 (1H, dd, J¼3.3, 1.3 Hz, H-9), 2.95 (1H, dd,
J¼3.3, 1.3 Hz, H-10), 2.88 (1H, ddd, J¼8.9, 1.3, 1.2 Hz,
H-8), 2.65 (1H, br d, J¼6.7 Hz, H-6), 1.65 (1H, ddd,
J¼13.4, 6.7, 1.2 Hz, H-12endo), 1.57 (1H, br d, J¼13.4 Hz,
H-12exo), 1.33 (3H, s, 11-Me), 1.31 (1H, dd, J¼8.9, 1.8 Hz,
H-7); 13C NMR (125 MHz, CDCl3) d 99.1, 81.6, 74.3, 62.5,
53.7, 52.2, 49.3, 42.0, 40.2, 35.2, 16.0; IR (ATR) 2981,
2928, 2869, 1485, 1457, 1383 cm21; MS (EI) m/z 194 (25,
Mþ), 169 (35); HRMS (ESI) m/z calcd C22H28Na O6
([2MþNa]þ) 411.1778, found 411.1774.
4.1.10. 2,4-Dioxa-11,12endo-dimethyl-tetracyclo[6.4.0.
1,8.06,7]dodec-9-ene 19f. Under an atmosphere of nitrogen,
0
a solution of 18f (2.88 g, 15.0 mmol) in oxygen free
cyclohexane (150 ml) was irradiated with a 125-watt low-
pressure mercury vapour lamp for 13 days using a 150 ml
quartz immersion-well photo reactor. The solution was
removed from the reactor and concentrated in vacuo to leave
a pale yellow oil (2.72 g). The oil was purified by flash
chromatography using increasing concentrations of
dichloromethane with petrol (30, 50 and 100%). Four
components were isolated: (in order of increasing polarity)
unchanged starting material (1.31 g, 45%); impure
uncharacterised by-product (0.014 g, 0.5%); impure meta-
addition product (0.422 g, 15%); and possible unstable
ortho-addition product (0.104 g, 4%).
4.1.12. 2,4-Dioxa-6endo,11-dimethyl-tetracyclo[6.4.0.
1,8.06,7]dodec-9-ene oxide 20e. An ice-cold solution of
0
the meta photoadduct 19e (0.100 g, 0.52 mmol) in dichloro-
methane (10 ml) was treated with small aliquots of a
,0.1 M solution of dimethyldioxirane9 in acetone, over 1 h,
The impure meta-addition product was purified further by

2780
C. S. Penkett et al. / Tetrahedron 60 (2004) 2771–2784
until TLC indicated that all of the starting material had been
consumed (total volume added: 9.3 ml, ,0.93 mmol). After
stirring at ice temperature for 1 h, the solution was
concentrated in vacuo to give the product 20e (0.108 g,
100%) as a colourless waxy solid mp 79–80 8C.
residue was purified by flash chromatography on silica (6 g)
eluted with 3% methanol in dichloromethane to afford the
major product as a pale yellow oil (31 mg, 55%). 1H NMR
spectrum indicated that this was a mixture of ketone 21e and
hemiacetal 22e.
This mixture (31 mg, 0.16 mmol) was dissolved in a 0.01 M
solution of HCl in anhydrous methanol (2 ml) and stirred at
rt for 4 days. Flash silica (0.25 g) was then added and the
mixture was concentrated in vacuo. The residue was
purified by flash chromatography on silica (3 g) eluted
with 2% methanol in dichloromethane to afford the
product 23e (10 mg, 30%) as a white crystalline solid mp
71.5–73.5 8C.
1H NMR (400 MHz, CDCl3) d 5.24 (1H, d, J¼5.9 Hz,
H-3endo), 4.49 (1H, d, J¼5.9 Hz, H-3exo), 3.68 (1H, d,
J¼11.2 Hz, H-5endo), 3.37 (1H, dd, J¼3.3, 1.3 Hz, H-9),
3.28 (1H, dd, J¼11.2, 1.1 Hz, H-5exo), 2.96 (1H, dd, J¼3.3,
1.2 Hz, H-10), 2.80 (1H, ddd, J¼8.8, 1.3, 1.2 Hz, H-8), 1.73
(1H, dd, J¼13.3, 1.2 Hz, H-12exo), 1.37 (1H, dd, J¼13.3,
1.1 Hz, H-12endo), 1.31 (3H, s, 11-Me), 1.13 (1H, dd, J¼8.8,
1.2 Hz, H-7), 1.06 (3H, s, 6-Me); 13C NMR (100 MHz,
CDCl3) d 98.5, 87.2, 74.5, 62.7, 54.0, 52.2, 49.0, 48.4, 47.4,
1H NMR (400 MHz, CDCl3) d 5.93 (1H, dd, J¼9.5, 4.3 Hz,
H-7), 5.72 (1H, dd, J¼9.5, 6.3 Hz, H-6), 3.66 (2H, m, H-3),
3.53 (1H, dd, J¼11.5, 4.3 Hz, H-8), 3.37 (3H, s, 1-OMe),
2.88 (1H, d, J¼11.5 Hz, 8-OH), 2.42 (1H, dd, J¼6.3,
0.9 Hz, H-5), 1.35 (1H, dd, J¼12.7, 0.9 Hz, H-10exo), 1.28
(1H, dd, J¼12.7, 2.7 Hz, H-10endo), 1.20 (3H, s, 9-Me), 0.98
(3H, s, 4-Me); 13C NMR (100 MHz, CDCl3) d 132.0, 124.3,
111.6, 77.9, 76.6, 52.3, 47.7, 46.5, 45.8, 45.5, 16.0, 15.5; IR
38.7, 18.6, 16.3; IR (ATR) 2999, 2956, 2932, 2861 cm21
;
MS (EI) m/z 208 (5, Mþ), 178 (17), 133 (22), 119 (72), 105
(100), 97 (24), 91 (89), 83 (38), 65 (20), 55 (25), 41 (36).
Sample decomposed prior to accurate mass measurement.
4.1.13. 2,4-Dioxa-11,12endo-dimethyl-tetracyclo-
[6.4.0.01,8.06,7]dodec-9-ene oxide 20f. A 0.1 M solution
of ice cold dimethyldioxirane9 in acetone (27 ml, 2.7 mmol)
was added to the meta photoadduct 19f (62 mg, 0.32 mmol)
and allowed to warm to rt overnight. The remaining solvent
was removed in vacuo and any residual water was removed
by addition of ethyl acetate (20 ml), drying (MgSO4),
filtering and concentrating in vacuo to give the product
20f (67 mg, 100%) as a pale yellow crystalline solid mp
81–82 8C.
(ATR) 3536, 3034, 2971, 2960, 2932, 2871, 1645 cm21
;
MS (EI) m/z 210 (2, Mþ), 121 (25), 110 (26), 105 (29), 95
(100); HRMS (ESI) m/z calcd C12H18NaO3 ([MþNa]þ)
233.1148, found 233.1156.
4.1.15. 4exo-Hydroxy-7exo-methoxymethoxymethyl-5-
methyl-bicyclo[3.2.1]oct-2-en-8 one 25d. Epoxide 20d
(17 mg, 0.087 mmol) was stirred in a 0.01 M solution of
HCl in methanol (5 ml) for 1 h. The residue was isolated by
concentration in vacuo and then passed through a small plug
of silica eluting with petrol/ethyl acetate (1:2) to yield the
product 25d as a yellow oil (15 mg, 76%).
1H NMR (500 MHz, CDCl3) d 5.25 (1H, dd, J¼6.0, 0.5 Hz,
H-3endo), 4.47 (1H, d, J¼6.0 Hz, H-3exo), 3.98 (1H, dd,
J¼11.3, 1.9 Hz, H-5endo), 3.43 (1H, dd, J¼3.2, 1.4 Hz, H-9),
3.39 (1H, ddd, J¼11.3, 0.8, 0.8 Hz, H-5exo), 3.14 (1H, dd,
J¼3.2, 1.3 Hz, H-10), 2.84 (1H, ddd, J¼8.8, 1.4, 1.4 Hz,
H-8), 2.33 (1H, m, H-6), 2.10 (1H, br q, J¼7.7 Hz, H-12exo),
1.27 (3H, s, 11-Me), 1.22 (1H, br d, J¼8.9 Hz, H-7), 1.02
(1H, d, J¼7.7 Hz, 12endo-Me); 13C NMR (125 MHz) d 98.7,
81.2, 76.0, 59.7, 55.0, 53.2, 52.0, 50.4, 46.9, 34.9, 15.3,
15.0; HRMS (ESI) m/z calcd C12H16NaO3 ([MþNa]þ)
231.0992, found 231.0983. Structure also confirmed by
single crystal X-ray analysis.18
1H NMR (500 MHz, CDCl3) d 6.15 (1H, dd, J¼8.9, 7.1 Hz,
H-2), 5.76 (1H, dd, J¼9.0, 3.8 Hz, H-3), 4.57 (2H, s,
OCH2OMe), 4.30 (1H, m, H-4), 3.42 (1H, dd, J¼9.6,
5.0 Hz, 7-CH(H)O), 3.34 (3H, s, OMe), 3.32 (1H, dd, J¼9.6,
6.8 Hz, 7-CH(H)O), 2.70 (1H, dd, J¼11.0, 7.0 Hz, H-1),
2.35 (1H, m, H-7), 2.08 (1H, dd, J¼14.0, 9.5 Hz, H-6endo),
1.63 (1H, dd, J¼14.0, 2.0 Hz, H-6exo), 1.56 (1H, br s,
4-OH), 1.19 (3H, s, 5-Me); 13C NMR (125 MHz, CDCl3) d
216.4, 135.0, 128.4, 96.5, 85.0, 70.4, 55.4, 50.6, 39.3, 34.4,
30.9, 15.8; IR (film) 3430, 2930, 1749, 1635 cm21; HRMS
(EI) m/z calcd for C12H18O4 (Mþ) 226.1205, found
226.1223.
4.1.14. 2-Oxa-8exo-hydroxy-1-methoxy-4,9-dimethyl-tri-
cyclo[4.4.0.04,5.0.9,10]dec-6-ene 23e. A single drop of
2.0 M aqueous hydrochloric acid was added to an ice-cold
solution of epoxide 20e (60 mg, 0.29 mmol) in acetone
(12 ml). The solution was stirred for 1 h and allowed to
warm to rt, after which flash silica (0.75 g) was added and
the resulting mixture was concentrated in vacuo. The
4.1.16. 4exo-Hydroxy-7exo-methoxymethoxymethyl-
5,6endo-dimethyl-bicyclo[3.2.1]oct-2-en-8-one 25f. Epoxide

C. S. Penkett et al. / Tetrahedron 60 (2004) 2771–2784
2781
20f (11 mg, 0.053 mmol) was stirred in a 0.01 M solution of
HCl in methanol (5 ml) for 1 h. The residue was isolated by
concentration in vacuo and thenpassedthrough a small plugof
silicaelutingwithpetrol/ethylacetate(1:2)toyieldtheproduct
25f as a yellow oil (10 mg, 78%).
salts. The orange solution was then concentrated in vacuo
and distilled under high vacuum to yield 33 a colourless oil
(18.85 g, 81%)
1H NMR (300 MHz, CDCl3) d 7.30 (2H, dd, J¼7.5, 8.5 Hz,
Ar-H), 7.07 (1H, t, J¼7.4 Hz, Ar-H), 7.00 (2H, d, J¼8.5 Hz,
Ar-H), 0.63 (6H, s, Si–Me2); 13C NMR (75 MHz, CDCl3) d
153.3, 129.6, 122.7, 120.0, 2.4; IR (film) 3065, 3041, 2970,
1596 cm21; MS (EI) m/z 186 (70%, [M]þ), 171 (78), 151
(50), 93 (98), 77 (100); HRMS (EI) m/z calcd for
C8H11OSiCl (Mþ) 186.0268, found 186.0284.
1H NMR (500 MHz, CDCl3) d 6.21 (1H, dd, J¼9.0, 7.2 Hz,
H-2), 5.78 (1H, dd, J¼9.0, 3.9 Hz, H-3), 4.57 (2H, s,
OCH2OMe), 4.47 (1H, m, H-4), 3.41 (1H, dd, J¼9.6,
5.0 Hz, 7-CH(H)O), 3.35 (3H, s, OMe), 3.27 (1H, dd, J¼9.6,
7.0 Hz, 7-CH(H)O), 2.63 (1H, d, J¼7.2 Hz, H-1), 1.91 (1H,
ddd, J¼7.0, 5.1, 4.2 Hz, H-7), 1.82 (1H, m, H-6exo), 1.38
(1H, br d, J¼10 Hz, 4-OH), 1.20 (3H, s, 5-Me), 1.82 (1H, d,
J¼11.0 Hz, 6exo-Me); 13C NMR (1 MHz, CDCl3) d 216.3,
136.2, 128.7, 96.5, 87.2, 70.1, 55.4, 54.0, 50.1, 47.6, 40.0,
4.1.19. Allyloxydimethylphenoxysilane 35. To a stirred
solution of allyl alcohol (2.2 ml, 32.2 mmol) in dry
tetrahydrofuran (60 ml) at 0 8C was added a solution of
n-butyllithium (12.9 ml, 2.5 M, 32.2 mmol) dropwise. This
was then added dropwise to a solution of chlorodimethyl-
phenoxysilane 33 (6.00 g, 32.2 mmol) in dry tetrahydro-
furan (125 ml) and allowed to stir at rt for 2 days. The
solvent was removed in vacuo and the residue was dissolved
in ethyl acetate (50 ml), filtered and concentrated in vacuo
leaving a yellow liquid, which was distilled under high
vacuum to give 35 as a colourless oil (3.75 g, 56%).
16.1, 15.2; IR (film) 3418, 2962, 2929, 1747, 1640 cm21
;
HRMS (EI) m/z calcd for C13H20O4 (Mþ) 240.1362, found
240.1379.
1H NMR (300 MHz, CDCl3) d 7.25 (2H, m, Ar-H), 6.99
(3H, m, Ar-H), 5.97 (1H, ddt, J¼17.1, 10.4, 4.9 Hz,
(H2C)HCv), 5.31 (1H, dt, J¼17.1, 1.7 Hz, vC(H)H),
5.14 (1H, dt, J¼10.4, 1.5 Hz, vC(H)H), 4.34 (2H, dd,
J¼4.9, 1.6 Hz, OCH2), 0.30 (6H, s, 4-H); 13C NMR
(75 MHz, CDCl3) d 154.3, 136.3, 129.4, 121.7, 119.7,
114.9, 63.6, 22.8; IR (film) 2965, 1597 cm21; MS (EI) m/z
208 (100, [Mþ]), 193 (60), 175 (61), 151 (94); HRMS (EI)
m/z calcd for C11H16O2Si (Mþ) 208.0919, found 208.0899.
4.1.17. 1-Methyl-2-[[(2-methyl-1-cyclopenten-1-
yl)methoxy]methoxy]benzene 27. Fifty percent aqueous
sodium hydroxide (33 ml) and tetrabutylammonium
chloride (0.460 g, 1.7 mmol) were added to a solution of
1-(chloromethoxy)-2-methylbenzene8 17 (2.58 g, 16 mmol)
and 2-methyl-1-cyclopentene-1-methanol10 26 (1.85 g,
16 mmol) in benzene (33 ml). The resulting two-phase
mixture was stirred vigorously at rt for 5 h and then
separated. The organic phase was washed with brine, dried
(MgSO4) and concentrated in vacuo to give a pale yellow
liquid (5.10 g). Distillation afforded a colourless liquid (bp
94–96 8C at 1 mm Hg) (2.62 g), which was still impure.
Further purification by flash chromatography on silica
(130 g) eluted with 10% dichloromethane in petrol afforded
the product 27 as a colourless liquid (2.04 g, 53%).
4.1.20. 2,4-dioxa-3-(dimethylsilyl)tetracyclo-[6.4.0.
0
1,9.06,12]dodec-10-ene 36 and 2,4-dioxa-3-(dimethyl-
silyl)tetracyclo[6.4.0.01,8.06,7]dodec-9-ene 37. A stirred
solution of allyloxydimethylphenoxysilane 35 (650 mg) in
cyclohexane (180 ml) was irradiated for 19 h with a 6 W
low-pressure mercury vapour lamp in a quartz immersion-
well photo reactor. The solvent was removed in vacuo and
the residue was subjected to column chromatography (silica
gel, petrol/ethyl acetate 20:1) to yield a mixture of 36 and 37
in a 1:2 ratio as a colourless oil (123 mg, 19%).
1H NMR (400 MHz, CDCl3) d 7.11–7.15 (2H, m, Ar-H),
7.07–7.09 (1H, m, Ar-H), 6.88–6.92 (1H, m, Ar-H), 5.22
(2H, s, OCH2O), 4.23 (2H, s, OCH2C), 2.31–2.39 (4H, m),
2.25 (3H, s, Ar-Me), 1.75–1.83 (2H, m), 1.69 (3H, s, Me);
13C NMR (100 MHz, CDCl3) d 155.6, 138.3, 130.9, 130.7,
127.2, 126.8, 121.3, 113.9, 92.0, 64.0, 38.8, 34.7, 21.6, 16.3,
13.9; IR (ATR) 2949, 2843, 1603, 1591, 1494 cm21; MS
(EI) m/z 232 (10, Mþ), 202 (18), 163 (7), 141 (55), 121 (70);
HRMS (EI) m/z calcd for C15H20O2 (Mþ) 232.1463, found
232.1478.
Minor isomer 36
4.1.18. Chlorodimethylphenoxysilane 33. To a stirred
solution of phenol (11.75 g, 125 mmol) in dry tetrahydro-
furan (90 ml) at 0 8C under an atmosphere of nitrogen was
added dropwise a solution of n-butyllithium (50 ml, 2.5 M
in hexanes). After addition, the phenoxide solution was
allowed to warm to rt and added dropwise to a stirred
solution of freshly distilled dichlorodimethylsilane
(113.7 ml, 938 mmol) in dry tetrahydrofuran (100 ml) at
278 8C. The reaction mixture was left to stir overnight
allowing it to warm to rt whereby it was concentrated in
vacuo, washed with petrol and filtered to remove the white
1H NMR (500 MHz, CDCl3) d 5.58 (1H, dd, J¼5.8, 2.5 Hz,
H-11), 5.51 (1H, dddd, J¼5.8, 2.7, 1.5, 0.9 Hz, H-10), 4.03
(1H, ddd, J¼11.5, 1.7, 0.9 Hz, H-5), 3.96 (1H, dd, J¼11.5,
2.3 Hz, H-5), 2.97 (1H, dd, J¼2.5, 2.5 Hz, H-12), 2.37 (1H,
ddddd, J¼8.0, 1.1, 1.1, 1.1, 1.1 Hz, H-9), 1.97 (1H, ddd,
J¼13.6, 6.5, 2.3 Hz, H-7), 2.11 (1H, m, H-6), 1.74 (1H, ddd,
J¼8.1, 6.5, 1.7 Hz, H-8), 1.69 (1H, dddd, J¼13.7, 5.9, 1.9,
0.9 Hz, H-7), 0.27 (3H, s, Si–Me), 0.18 (3H, s, Si–Me); 13C
NMR (75 MHz, CDCl3) d 130.4, 127.5, 83.8, 70.5, 59.7,
52.3, 38.8, 33.4, 27.3, 21.5.

2782
C. S. Penkett et al. / Tetrahedron 60 (2004) 2771–2784
Major isomer 37
(1H, ddd, J¼6.8, 2.0, 6.0 Hz, H-5), 2.38 (1H, m, H-1), 1.86
(1H, br s, CH2OH), 1.73 (1H, m, H-7endo), 1.64 (1H, dd,
J¼12.1, 9.0 Hz, H-6exo), 1.47 (1H, ddd, J¼12.1, 6.2, 6.0 Hz,
H-6endo); 13C NMR (75 MHz, CDCl3) d 130.8, 128.4, 109.2,
75.0, 65.9, 50.1, 48.0, 43.7, 40.9, 40.5, 32.0; IR (film) 3433,
2952 cm21; MS (EI) m/z 213 (1, [M2H]þ), 197 (4,
[M2OH]þ), 183 (5), 101 (100); HRMS (EI) m/z calcd for
C11H17O3 ([M2OH]þ) 197.1178, found 197.1182.
1H NMR (500 MHz, CDCl3) d 5.66 (1H, dddd, J¼5.8, 2.8,
0.8, 0.8 Hz, H-10), 5.53 (1H, dd, J¼5.8, 2.5 Hz, H-9), 3.82
(1H, dd, J¼10.4, 1.1 Hz, H-5), 3.72 (1H, dd, J¼10.4,
2.1 Hz, H-5), 3.18 (1H, dddd, J¼8.3, 2.8, 1.5, 0.9 Hz, H-11),
2.79 (1H, dddd, J¼7.7, 2.1, 2.1, 1.1 Hz, H-6), 2.44 (1H, dd,
J¼8.4, 2.5 Hz, H-8), 2.22 (1H, ddd, J¼12.9, 8.3, 2.1 Hz,
H-12exo), 1.56 (1H, ddd, J¼12.9, 7.7, 1.5 Hz, H-12endo),
1.44 (1H, br d, J¼8.4 Hz, H-7), 0.26 (3H, s, Si–Me), 0.17
(3H, s, Si–Me); 13C NMR (75 MHz, CDCl3) d 139.9, 123.9,
83.6, 73.9, 56.6, 46.4, 41.7, 40.7, 35.5, 20.5.
6-Hydroxymethyl-8,8-dimethoxy-bicyclo[3.2.1]oct-3-en-2-
ol 39
1H NMR (500 MHz, CDCl3) d 5.98 (1H, ddd, J¼9.4, 7.1,
0.5 Hz, H-4), 5.65 (1H, ddd, J¼9.4, 3.6, 1.4 Hz, H-3), 3.92
(1H, br d, J¼9.9 Hz, H-2), 3.54 (2H, d, J¼6.2 Hz, 7-CH2O),
3.39 (1H, br d, J¼10.6 Hz, 2-OH), 3.20 (3H, s, 8-OMe),
3.13 (3H, s, 8-OMe), 2.51 (1H, br s, OH), 2.50 (1H, dd,
J¼7.5, 1.6 Hz, H-1), 2.39 (1H, dd, J¼7.1, 2.0 Hz, H-5), 2.08
(1H, m, H-6endo), 1.58 (1H, ddd, J¼13.8, 7.5, 5.3 Hz,
H-7exo), 1.45 (1H, dd, J¼13.8, 9.7 Hz, H-7endo); 13C NMR
(75 MHz, CDCl3) d 132.0, 128.7, 109.7, 74.5, 65.9, 50.3,
47.5, 47.0, 43.2, 42.7, 26.1; IR (film) 3412, 2948 cm21; MS
(EI) m/z 197 (9, [M2OH]þ), 183 (22), 149 (16), 131 (100);
HRMS (EI) m/z calcd for ([M2OH]þ) 197.1178, found
197.1187.
For the mixture: MS (EI) m/z 208 (98, [Mþ]), 193 (71), 176
(76), 151 (89), 75 (100); HRMS (EI) m/z calcd for
C11H16O2Si (Mþ) 208.0919, found 208.0901.
4.1.21. 7-Hydroxymethyl-8,8-dimethoxy-bicyclo-
[3.2.1]oct-3-en-2-ol 38 and 6-hydroxymethyl-8,8-
dimethoxy-bicyclo[3.2.1]oct-3-en-2-ol 39.
A
stirred
solution of allyloxydimethylphenoxysilane 35 (1.00 g,
4.8 mmol) in cyclohexane (180 ml) was irradiated for 19 h
with a 6 W low-pressure mercury vapour lamp in a quartz
immersion-well photo reactor. The solution was filtered and
concentrated in vacuo, whereby the resultant oil was
dissolved in CH2Cl2 (20 ml). With stirring, a solution of
basewashed m-CPBA (4.8 mmol) in CH2Cl2 (10 ml) was
added slowly at rt. After 2 h 2-methyl-2-butene (1.5 ml) was
added and the solution was allowed to stir for a further 0.5 h,
before adding a saturated solution of NaHCO3.The organic
phase was separated and washed with saturated brine, dried
with MgSO4, filtered and concentrated in vacuo. The
resultant oil was dissolved in a solution of PTSA (0.100 g)
in methanol (20 ml) and stirred under an atmosphere of
nitrogen for 3 days at rt. Ethyl acetate (20 ml) was added
and the solution was concentrated in vacuo until approxi-
mately 5 ml remained, this process was repeated a further
3 times. After a further addition of ethyl acetate (20 ml) the
organic material was washed with saturated NaHCO3
solution, then saturated brine, dried (MgSO4), filtered and
concentrated in vacuo. The residue was purified by silica
chromatography (Et2O/acetone 9:1) to yield 38 (80 mg, 8%)
and 39 (80 mg, 8%) as colourless oils.
4.1.22. 4-(tert-Butyl-dimethyl-silanyloxy)-but-2-en-1-ol
40. This preparation followed the procedure of McDougal
et al.15 for the monosilylation of symmetrical diols. To a
stirred solution of NaH (4.54 g, 114 mmol, 60% dispersion
in oil) in dry tetrahydrofuran (100 ml) was added dropwise
E-but-2-ene-1,4-diol16 (10.0 g, 114 mmol) in dry tetra-
hydrofuran (60 ml) at rt. This was stirred for 45 min after
which tertbutyldimethylsilylchloride (17.1 g, 114 mmol) in
tetrahydrofuran (15 ml) was added in one portion and
allowed to stir for a further 45 min. Ether (450 ml) was
added and the solution washed with 10% K2CO3 (300 ml)
and then brine. The aqueous layers were washed with Et2O
and the organic layers combined, dried (MgSO4), filtered
and concentrated in vacuo to leave a yellow liquid, which
was subjected to silica chromatography (petrol/ethyl acetate
4:1) to yield 40 (20.4 g, 89%)
1H NMR (300 MHz, CDCl3) d 5.81 (2H, m), 4.13 (4H, m),
1.62 (1H, brs, OH), 0.89 (9H, s), 0.05 (6H, s); 13C NMR
(75 MHz, CDCl3) d 130.9, 128.9, 63.2, 63.1, 25.9, 18.4,
25.3; IR (film) 3367, 2955, 2930, 2857 cm21; MS (EI) m/z
171 (5, [M2CH2OH]þ), 145 (63), 127 (41), 75 (100);
HRMS (EI) m/z calcd for C9H19OSi ([M2CH2OH]þ)
171.1205, found 171.1206
7-Hydroxymethyl-8,8-dimethoxy-bicyclo[3.2.1]oct-3-en-2-
ol 38
4.1.23. {[4-(tert-Butyl-dimethyl-silanyloxy)-but-2-enyl-
oxy]-dimethyl-silanyloxy}-benzene 41. To
a stirred
1H NMR (500 MHz, CDCl3) d 5.85 (1H, dd, J¼9.4, 6.8 Hz,
H-4), 5.65 (1H, ddd, J¼9.4, 3.9, 1.5 Hz, H-3), 3.92 (1H, m,
H-2), 3.62 (1H, br d, J¼11.5 Hz, 2-OH), 3.54 (1H, dd,
J¼10.3, 6.6 Hz, 7-C(H)H), 3.48 (1H, dd, J¼10.3, 7.7 Hz,
7-C(H)H), 3.17 (3H, s, 8-OMe), 3.13 (3H, s, 8-OMe), 2.48
solution of 4-(tert-butyl-dimethyl-silanyloxy)-but-2-en-1-
ol 40 (7.44 g, 36.8 mmol) in dry tetrahydrofuran (60 ml)
at 0 8C under an atmosphere of nitrogen was added dropwise
a solution of n-butyllithium (14.7 ml, 2.5 M in hexanes).
The solution had turned yellow and after stirring for a

C. S. Penkett et al. / Tetrahedron 60 (2004) 2771–2784
2783
further 1 h the solution was allowed to reach rt before it was
added dropwise to a solution of chlorodimethylphenoxy-
silane 33 (6.87 g, 36.82 mmol) in dry tetrahydrofuran
(90 ml) at 278 8C under an atmosphere of nitrogen. After
addition the solution was allowed to warm to rt over a period
of 14 h and then concentrated in vacuo, washed with petrol,
filtered and again concentrated in vacuo. The brown oil was
then distilled under high vacuum and the highest boiling
fraction was further subjected to silica chromatography
(petrol/CH2Cl2 1:1) to yield 41 (1.99 g, 15%).
64.0, 54.0, 48.7, 45.4, 39.4, 25.6, 18.0, 25.2; IR (film) 3400,
2954, 2929, 2857, 1754, 1471 cm21; MS (CI) m/z 330 (4,
[MþNH4]þ), 298 (100); HRMS (CI) m/z calcd for
C16H32NSiO4 ([MþNH4]þ) 330.2101, found 330.2101.
4.1.25. 6,7-Bis-hydroxymethyl-8,8-dimethoxy-bicyclo-
[3.2.1]-oct-3-en-2-ol 43. A stirred solution of 42 (11 mg,
35 mmol) and PPTS (48 mg) in methanol (5 ml) was heated
to reflux for 4 h. After cooling to rt, ethyl acetate (25 ml)
was added and the solution was partially concentrated in
vacuo until ca. 5 ml remained and a white solid formed.
Ethyl acetate (10 ml) was added and the solution was
washed with NaHCO3 then brine and the organic layer was
separated and dried (MgSO4), filtered and concentrated in
vacuo. The residue was then subjected to silica chromato-
graphy (petrol/ethyl acetate 1:4) to yield 43 as a colourless
oil (6 mg, 70% yield).
1H NMR (300 MHz, CDCl3) d 7.10 (5H, m, Ar-H), 5.82
(2H, s, HCvCH), 4.33 (2H, s, OCH2), 4.18 (2H, s, OCH2),
0.93 (9H, s, SiC(Me)3), 0.29 (6H, s, SiMe2), 0.08 (6H, s,
SiMe2); 13C NMR (75 MHz, CDCl3) d 154.5, 130.5, 129.5,
128.0, 121.7, 119.8, 63.1, 62.9, 25.9, 18.4, 22.6, 25.3; IR
(film) 2956, 2929, 2857, 1597 cm21; MS (CI) m/z 370 (100,
[MþNH4]þ), 308 (22), 242 (16), 221 (16), 185 (11); HRMS
(CI) m/z calcd for C18H36NO3Si2 ([MþNH4]þ) 370.2234,
found 370.2231.
4.1.24. 6-(tert-Butyl-dimethyl-silanyloxymethyl)-4-
hydroxy-7-hydroxymethyl-bicyclo[3.2.1]oct-en-8-one
42. A stirred solution of 41 (520 mg, 1.48 mmol) in
cyclohexane (180 ml) was irradiated for 4hrs with a 6 W
low-pressure mercury vapour lamp in a quartz immersion-
well photo reactor. The solvent was removed in vacuo, the
crude material taken up in CH2Cl2 (5 ml) and then a solution
of base-washed m-CPBA (2.5 mmol, 7.5 ml, 0.33 M) in
CH2Cl2 was added. After 1 h 2-methyl-2-butene (0.3 ml,
2.83 mmol) was added to ensure removal of excess
m-CPBA and the resultant solution was washed and
extracted from NaHCO3 solution, then brine and the organic
phase dried (MgSO4), filtered and concentrated in vacuo.
The yellow oil was then dissolved in methanol (10 ml) and
PPTS (0.05 g) added. This was allowed to stir for 4 days
before ethyl acetate (30 ml) was added and the solution was
partially concentrated in vacuo until 10 ml remained. Ethyl
acetate (30 ml) was again added and the process repeated 2
more times. The solution was then washed with NaHCO3,
then brine and dried (MgSO4), filtered and concentrated in
vacuo. The residue was then subjected to silica chromato-
graphy (petrol/ethyl acetate 1:2) to provide 42 as a
colourless oil (49 mg, 11%).
1H NMR (500 MHz, CDCl3) d 6.12 (1H, dd, J¼7.3, 9.2 Hz,
H-4), 5.62 (1H, dd, J¼3.7, 9.2 Hz, H-3), 4.73 (1H, dd,
J¼3.8, 6.6 Hz, H-2), 4.14 (1H, dd, J¼7.6, 8.5 Hz, –CH2O),
3.65 (2H, m, –CH2O), 3.62 (1H, dd, J¼2.6, 8.7 Hz,
–CH2O), 3.26 (3H, s, 8-OMe), 3.14 (3H, s, 8-OMe), 2.91
(1H, ddd, J¼1.5, 6.6, 7.1 Hz, H-1), 2.50 (2H, m), 2.35 (1H,
brs, OH, absent with CD3OD), 1.93 (1H, m); 13C NMR
(75 MHz, CDCl3) d 132.6, 126.9, 79.5, 74.9, 65.8, 58.3,
53.4, 51.1, 49.4, 48.1, 42.4, 41.8; IR (film) 3402,
2952 cm21; MS (CI) m/z 262 (3, [MþNH4]þ), 231 (100);
HRMS (CI) m/z calcd for C12H24NO5 ([MþNH4]þ)
262.1654, found 262.1654.
Acknowledgements
We would like to thank the EPSRC for providing a
studentship for P.W.B. and Tocris-Cookson for additional
funding. B.J.T. would like to thank AstraZeneca for the
opportunity to undertake a part-time MSc course at the
University of Sussex. We would also like to thank Dr. A. G.
Avent for NMR studies.
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(1H, dd, J¼10.3, 6.3 Hz, 7exo-CH(H)), 3.44 (1H, dd,
J¼10.6, 7.0 Hz, 7exo-CH(H)), 2.73 (1H, br d, J¼7.6 Hz,
H-5), 2.55 (1H, dd, J¼7.2, 1.2 Hz, H-1), 2.28 (1H, dddd,
J¼7.8, 7.8, 7.7, 4.3 Hz, H-6exo), 1.96 (1H, ddd, J¼6.6, 6.6,
4.5 Hz, H-7endo), 0.90 (9H, s, H-11), 0.83 (6H, s, H-10); 13
C
NMR (75 MHz, CDCl3) d 213.3, 135.9, 128.6, 75.1, 65.2,

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