Influence of the -CH2X substituent on the regioselectivity of intramolecular meta -photocycloaddition reactions

Article abstract of DOI:10.1021/jo5028613

In studies related to the synthesis of the bicyclo[3.2.1]octane core of enterocin by an intramolecular meta-photocycloaddition, it was found that the regioselectivity of the reaction depends strongly on the substituent -CH₂X in the ortho-positi

Full text of DOI:10.1021/jo5028613

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Influence of the -CH2X Substituent on the Regioselectivity
of Intramolecular meta-Photocycloaddition Reactions
Marcus Wegmann, and Thorsten Bach
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo5028613 • Publication Date (Web): 14 Jan 2015
Downloaded from http://pubs.acs.org on January 22, 2015
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Influence of the -CH2X Substituent on the Regioselectivity of
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Intramolecular meta-Photocycloaddition Reactions
Marcus Wegmann,1 Thorsten Bach1*
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1 Lehrstuhl für Organische Chemie I, Technische Universität München, Lichtenbergstr. 4, 85747
Garching, Germany
Corresponding Author
*Email: thorsten.bach@ch.tum.de
ABSTRACT
In studies related to the synthesis of the bicyclo[3.2.1]octane core of enterocin by an
intramolecular metaꢀphotocycloaddition it was found that the regioselectivity of the reaction
depends strongly on the substituent –CH2X in orthoꢀposition to the tether. Electropositive groups
X (X = H, Me, TMS, TES) gave preferentially the linear isomer (regioisomeric ratio = 87/13 to
>95/5) while electronegative substituents (X = OH, OAc, F) showed a clear preference for the
angular isomer (regioisomeric ratio = 75/25 to >95/5). The silylated and fluorinated products
were obtained as single isomers in moderate yield.
Based on our interest in the synthesis of oxygenated polyketide natural products derived from
marine actinomycetes1 we have recently started to evaluate different routes for the synthesis of
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(−)ꢀenterocin (1).2 It occurred to us that the bicyclo[3.2.1]octane core of the natural product might
be accessible by a metaꢀphotocycloaddition reaction.3 This powerful photochemical
transformation has been successfully applied to natural product synthesis,4 mostly, however, to
the total synthesis of diꢀ and triquinanes with a bicyclo[3.3.0]octane core.5,6 An issue associated
with the intramolecular version of the metaꢀphotocycloaddition is its regioselectivity. In typical
substrates, in which an electronꢀdonating substituted is located in orthoꢀposition relative to the
chain, linear and angular products (e.g. 2 and 3) are formed in variable ratios.3ꢀ7 In the present
case, we felt that generation of the linear isomer 2 would be desirable because its double bond
would be ideally located to allow introduction of the two hydroxy groups in positions C3 and C4
of the bicyclo[3.2.1]octane skeleton (Figure 1). In this regard, we were pleased to note that the
respective methyl compound (X = H) had been previously prepared by a metaꢀ
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photocycloaddition with high regioselectivity.8 However, since a methyl group at C8 of the
bicyclo[3.2.1]octane seemed not ideal for synthetic purposes, we undertook a comprehensive
study, in which we investigated the influence of the –CH2X group on the regioselectivity of the
metaꢀphotocycloaddition. The results of this study are summarized in this paper.
F
IGURE 1. Structure of enterocin (1), of its carbocyclic bicyclo[3.2.1]octane core and of linear and
angular metaꢀphotocycloaddition products 2 and 3.
O
Ph
O
O
O
OH
HO
4
OH
3
2
3
X
8
HO
1
O
bicyclo[3.2.1]octane
O
X
MeO
O
1
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Two approaches were used to prepare appropriate precursors for the metaꢀphotocycloaddition
reaction. In the first approach, readily available benzylic alcohols 4bꢀ4e were allylated upon
treatment with sodium hydride and allyl bromide in THF (75ꢀ90%, Scheme 1). The parent
compound 5a (X = H) had been similarly prepared from commercially available orthoꢀ
methylbenzyl alcohol (4a).8 The orthoꢀsilylmethylꢀsubstituted alcohol 4c (X = TMS) has been
previously synthesized by directed metalation of 4a and subsequent trimethylsilylation.9 In the
same fashion, the triethylsilyl analogue 4d (X = TES) was obtained from 4a (68% yield). Mono
silylation of orthoꢀdi(hydroxymethyl)benzene10 delivered the tertꢀbutyldimethylsilyl (TBS) ether
4e (X = OTBS).11
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S
CHEME 1. Synthesis of metaꢀphotocycloaddition precursors 5bꢀ5e by allylation of benzylic
alcohols 4bꢀ4e.
Br
NaH,
0 °C
X
X
rt (THF)
OH
O
4b
4c
4d
4e
X = Me
90%
75%
78%
5b
5c
5d
5e
X = TMS
X = TES
X = OTBS 90%
In the second approach, benzylic alcohol 5f,12 which was in our hands most cleanly available by
deprotection of silyl ether 5e (TBAF in THF, 98%), was transformed in various benzylic
derivatives (Scheme 2). Oꢀmethylation delivered ether 5g (X = OMe), while the respective
benzylic cyanide 5h (X = CN) was prepared in two steps via the bromide. Acylation reactions
were favorably performed in the presence of catalytic amounts of N,Nꢀdimethylaminopyridine
(DMAP)13 and gave pivaloate 5i (X = OPiv) in 82% yield and acetate 5j (X = OAc) in 86% yield.
Fluorination of alcohol 5f was achieved with diethylaminosulfur trifluoride (DAST) to furnish
product 5k (X = F).
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S
CHEME 2. Synthesis of metaꢀphotocycloaddition precursors 5gꢀ5k by functional group
transformations on benzylic alcohol 5f.
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NaH, MeI
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1. NBS, PPh3 (DMF)
0 °C
rt (THF)
2. NaCN (DMF)
OMe
O
CN
O
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76%
58%
5g
5h
OH
O
O
5f
O
O
R
DAST
RCOCl, NEt3
0 °C (CH2Cl2)
78 °C (CH2Cl2)
F
O
5i R = tBu
5j
48%
82%
86%
R = Me
5k
Photochemical reactions with substrates 5 were performed with lowꢀpressure mercury lamps (λ =
254 nm)14 in quartz vessels at ambient temperature (Table 1). The previously reported8 substrate
5a delivered the known linear photocycloaddition product 2a in 44% yield (entry 1). The
formation of orthoꢀphotocycloaddition products was observed in minor quantities but upon
column chromatographic purification only a single metaꢀphotocycloaddition product was
isolated. The ethylꢀsubstituted substrate 5b showed a diminished chemoselectivity, possibly due
to competitive hydrogen abstraction reactions (entry 2). The linear product 2b was the only
isolable product (29%). Pleasingly, the synthetically useful silylmethylꢀsubstituted substrates 5c
and 5d reacted smoothly and in decent yields (entries 3, 4). The angular isomer 3c was not
detectable in the reaction of the former substrate, while minor amounts of the angular isomer 3d
were found to accompany linear product 2d in the reaction of the latter substrate. In general, the
1HꢀNMR coupling pattern of the olefinic protons allowed a facile structural assignment of either
isomer. The linear isomers exhibit two doublets of doublets (dd) as each olefinic proton couples
also to an adjacent methine proton, while in the angular isomers one olefinic proton is adjacent to
a quaternary center resulting in a plain doublet. Partial separation of the linear and angular isomer
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was possible by column chromatography in most cases. The data given in Table 1 refer, however,
to the mixture of the two isomers. Their ratio remained after purification unchanged as compared
to the ratio in the crude product mixture.
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T
ABLE 1. Regioselectivity in the formation of linear and angular metaꢀphotocycloaddition
products 2 and 3 depending on the functional group X.
yieldc
[%]
entrya
substrate
X
r.r. (2/3)b
1
2
H
Me
>95/5
>95/5
>95/5
87/13
44/56
25/75
41/59
40/60
33/67
16/84
<5/95
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29
49
62
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47
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5a
5b
5c
5d
5e
5f
3
TMS
TES
OTBS
OH
4
5
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7
OMe
CN
5g
5h
5i
8
9
OPiv
OAc
F
10
11
5j
5k
a All metaꢀphotocycloaddition reactions were conducted for sixteen hours at ambient temperature (airꢀcooled) in
quartz tubes using a merryꢀgoꢀround reactor with sixteen lowꢀpressure mercury lamps (λ = 254 nm)14 as the
irradiation source in dry, deaerated cyclohexane (c = 0.04 mM). b The ratio of regioisomers (r.r.) was determined
both in the crude reaction mixture and in the isolated product by 1HꢀNMR. c Yield (mixture of 2/3) after
chromatographic purification.
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Surprisingly, the regioselectivity of the metaꢀphotocycloaddition changed drastically upon
introducing an oxygen substituent at the methylene group. The angular products 3eꢀ3g became
major products (entries 5ꢀ7) with the most pronounced regioselectivity observed for the
hydroxymethylꢀsubstituted substrate 5f (entry 6). The cyanide 5h reacted similarly in favor of the
angular product (entry 8). Pivaloylꢀprotection of the hydroxy group (substrate 5i) did not improve
the yield nor the regioselectivity as compared to the unprotected compound (entry 9).
Synthetically useful selectivities were, however, achieved with the acetate 5j (entry 10) and the
fluoride 5k (entry 11). In both cases, the angular regioisomers 3j and 3k clearly prevailed and in
both cases, the yields were at least moderate. It should be noted that it was not attempted to
optimize the yield but rather were identical conditions applied to all eleven substrates. Given the
product complexity, the high modeꢀ, regioꢀ and stereoselectivity achieved for products 2c and 2d
and for products 3j and 3k are remarkable.
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When considering the factors determining the regioselectivity, it should be noted that no change
of the regioisomeric ratio15 (2/3) with time was observed in any of the reactions, in which the
reaction course was followed by GLC (substrates 5a, 5c, 5e, 5k). It seems therefore likely that the
regioselectivity is kinetically controlled. In previous work,8,16 it was argued that it is the length
and flexibility of the threeꢀatom tether, which determines the regioselectivity of the
intramolecular metaꢀphotocycloaddition reaction. It was assumed that the short allyloxymethyl
substituent leads to a significant sp3ꢀhybridization at the carbon atom C1 to which the substituent
is attached and at which CꢀC bond formation occurs (Figure 2).17 This hybridization change
affects also the adjacent positions C2 and C6, which favors cyclopropane bond formation
between these centers leading to the linear product. If the terminal olefin is linked to the arene by
a threeꢀatom chain with greater bond distances between the atoms (e.g. a propylene16a or a
methylsilylmethyl16c tether) and larger bond angles the regioselectivity is shifted to the angular
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product because the sp3ꢀhybridization at carbon atom C3 occurs earlier at the reaction
hypersurface favoring a cyclopropane bond formation between carbon atoms C2 and C4.
Following this line of arguments, it is likely that conformation 5’ accounts for the preferred
formation of the linear products 2 (Figure 2) as previously postulated.8 For electronegative
substituents X, an electrostatic repulsion of their lone pairs and the olefinic π system (↔)18 could
alter the conformation positioning the terminal end of the double bond in closer proximity to C3
(conformation 5’’) thus favoring formation of the angular products 3.
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F
IGURE 2. Preferred conformation 5’ and 5’’ leading to formation of linear (2) or angular (3)
metaꢀphotocycloaddition products.
3
3
X
X
2
2
X
4
X
1
3
O
1
O
1
6
O
O
5'
5''
In summary, the substituent X in substrates 5 plays a crucial role in determining the
regioselectivity of their intramolecular metaꢀphotocycloaddition. This previously unknown fact
can be synthetically useful because the selective formation of either the linear or the angular
isomer is desired in many applications. In our case, the formation of the linear products isomers
2c and 2d appear to be most promising for further studies towards the total synthesis of enterocin.
EXPERIMENTAL SECTION
General Methods:
All reactions, sensitive to air or moisture, were carried out in flameꢀdried glassware under
positive pressure of argon using standard Schlenk techniques. Flash chromatography was
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performed on silica gel 60 (230−400 mesh) with the eluent mixtures given for the corresponding
procedures. Thin layer chromatography (TLC) was performed on silica coated glass plates (silica
gel 60 F 254). Compounds were detected by UV (λ = 254 nm, 366 nm) and KMnO4
(potassium permanganate solution). Technical solvents (nꢀpentane, ethyl acetate, diethyl ether)
employed for preparative column chromatography were purified by distillation prior to use.
Chemical shifts are reported relative to the solvent [CHCl3 δ(1H) = 7.26 ppm, δ(13C) = 77.0 ppm]
as reference. HRMS data were recorded by electron ionization (EI) or electron spray ionization
(ESI) on a transmission quadrupole mass spectrometer.
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Benzylic alcohols 4c9, 4e11 and orthoꢀdi(hydroxymethyl)benzene10 were synthesized according to
literature procedures. Alcohol 5f12 was synthesized from TBSꢀether 5e by deprotection with
TBAF. The spectra obtained were identical to literature data.11 All other chemicals were used as
received from commercial suppliers.
1-Allyloxymethyl-2-ethylbenzene (5b)
Sodium hydride (238 mg, 5.94 mmol, 60% suspension in mineral oil, 2.0 equiv.) was suspended
in 5 mL of THF and cooled to 0 °C. A solution of 2ꢀethylbenzyl alcohol (400 µL, 404 mg, 2.97
mmol, 1.0 equiv.) in 5 mL of THF was added dropwise at 0 °C and the mixture was stirred for 30
minutes. Then, a solution of allyl bromide (385 µL, 539 mg, 4.45 mmol, 1.5 equiv.) in 5 mL of
THF was added and the reaction mixture was warmed to room temperature over night. The
reaction was quenched with 3 mL of water, the layers were separated and the aqueous layer was
extracted with ether (3 × 10 mL). The combined organic layers were washed with sat. NaCl
solution (5 mL) and dried over Na2SO4. The drying agent was removed by filtration and the
volatile components were evaporated in vacuo. Purification by column chromatography (nꢀ
pentane/ether = 99/1) gave 473 mg (2.68 mmol, 90%) of the product as a colorless oil. TLC (nꢀ
ꢀ1
1
~
pentane/ether = 99/1): Rf = 0.39 [UV, KMnO4]. IR (ATR):
ν
= 3065, 2965, 2871, 1453 cm . Hꢀ
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NMR (CDCl3, 300 K, 360 MHz): δ (ppm) = 1.23 (t, 3J = 7.7 Hz, 3 H), 2.71 (q, 3J = 7.7 Hz, 2 H),
4.05 (dt, 3J = 5.7 Hz, 4J = 1.3 Hz, 2 H), 4.55 (s, 2 H), 5.21 (virt. dq, 3J = 10.3 Hz, 2J ≅ 4J = 1.4
Hz, 1 H), 5.32 (virt. dq, 3J = 17.3 Hz, 2J ≅ 4J = 1.6 Hz, 1 H), 5.97 (ddt, 3J = 17.3 Hz, 3J = 10.3
Hz, 3J = 5.7 Hz,1 H), 7.18 (td, 3J = 7.3 Hz, 4J = 1.4 Hz, 1 H), 7.21 (d, 3J = 7.3 Hz, 1 H), 7.26 (td,
3J = 7.3 Hz, 4J = 1.4 Hz, 1H), 7.35 (d, 3J = 7.3 Hz, 1H). 13C{1H}ꢀNMR (CDCl3, 300 K, 91 MHz):
δ (ppm) = 15.4 (q), 25.4 (t), 70.3 (t), 71.4 (t), 117.2 (t), 125.9 (d), 128.2 (d), 128.6 (d), 129.1 (d),
135.0 (d), 135.7 (s), 142.9 (s). MS (EI, 70 eV): m/z (%) = 176 (2, M+), 118 (100, [MꢀOC3H5]+).
HRMS (ESI) m/z: [M+NH4]+ calcd. for C12H20NO: 194.1539; found: 194.1539.
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2-(Allyloxymethyl)benzyltrimethylsilane (5c)
Sodium hydride (20.6 mg, 514 µmol, 60% suspension in mineral oil, 2.0 equiv.) was suspended
in 1 mL of THF and cooled to 0 °C. Subsequently, a mixture of alcohol 4c (50.0 mg, 257 µmol,
1.0 equiv.) and allyl bromide (111µL, 156 mg, 1.29 mmol, 5.0 equiv.) in 2 mL of THF was added
dropwise and the mixture was allowed to warm to room temperature over night. The reaction was
quenched by the addition of 1 mL water, the layers were separated and the aqueous layer was
extracted with ether (3 × 5 mL). The combined organic layers were washed with 2 mL sat. NaCl
solution, dried over Na2SO4 and the drying agent was removed by filtration. After removal of the
volatile components in vacuo, the crude product was purified by column chromatography (nꢀ
pentane/ether = 99/1) to give 46.0 mg (196 µmol, 76%) of the product as a colorless oil. TLC (nꢀ
ꢀ1
1
~
pentane/ether = 99/1): Rf = 0.39 [UV, KMnO4]. IR (ATR):
ν
= 3069, 2952, 1489 cm . HꢀNMR
(CDCl3, 300 K, 360 MHz): δ (ppm) = 0.00 (s, 9 H), 2.17 (s, 2 H), 4.03 (dt, 3J = 5.7 Hz, 4J = 1.4
Hz, 2 H), 4.46 (s, 2 H), 5.21 (virt. dq, 3J = 10.3 Hz, 2J ≅ 4J = 1.5 Hz, 1 H), 5.32 (virt. dq, 3J = 17.4
Hz, 2J ≅ 4J = 1.6 Hz, 1 H), 5.97 (ddt, 3J = 17.4 Hz, 3J = 10.3 Hz, 3J = 5.7 Hz, 1 H), 7.00 (d, 3J =
7.7 Hz, 1 H), 7.07 (td, 3J = 7.5 Hz, 4J = 1.2 Hz, 1 H), 7.16 (td, 3J = 7.5 Hz, 4J = 1.2 Hz, 1 H), 7.32
(d, 3J = 7.5 Hz, 1 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 91 MHz): δ (ppm) = –1.2 (q), 23.0 (t), 70.7
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(t), 71.4 (t), 117.3 (t), 124.3 (d), 127.6 (d), 129.2 (d), 129.3 (d), 134.6 (s), 135.1 (d), 139.4 (s).
MS (EI, 70 eV): m/z (%) = 234 (3, M+), 104 (100, [C8H8]+). HRMS (EI) m/z: [C14H22OSi]+
calcd.: 234.1444; found: 234.1449.
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2-(Allyloxymethyl)benzyltriethylsilane (5d)
A solution of 2ꢀmethylbenzyl alcohol (500 mg, 4.09 mmol, 1.0 equiv.) in 4 mL of THF was
cooled to 0 °C and nꢀbutyl lithium (4.09 mL, 2.5
M in hexanes, 10.2 mmol, 2.5 equiv.) was added
dropwise. The mixture was stirred for 16 hours at room temperature, before triethylsilyl chloride
(1.72 mL, 1.54 g, 10.2 mmol, 2.5 equiv.) was added dropwise while the mixture was cooled in a
water bath. The suspension was stirred for additional two hours before being quenched with 2 mL
of water. The layers were separated and the aqueous layer was extracted with ether (3 × 8 mL).
The organic layers were combined, washed with sat. NaCl solution (5 mL) and dried over
Na2SO4. The drying agent was removed by filtration and the volatile components were
evaporated in vacuo. The crude product was dissolved in 30 mL of THF and 9 mL of water and
15 mL acetic acid was added. The mixture was stirred over night, before being basified with 4
NaOH. The aqueous layer was extracted with ether (3 × 10 mL), the organic layers were
N
combined and washed with sat. NaCl solution (5 mL). The mixture was dried over Na2SO4, and
separated from the drying agent. After removal of the volatile components in vacuo, a yellow oil
was obtained which was directly used for the next step. Sodium hydride (639 mg, 60%
suspension in mineral oil, 16.0 mmol, 3.0 equiv.) was suspended in 6 mL of THF and cooled to 0
°C. Subsequently, the crude product dissolved in 6 mL of THF was added dropwise, and the
mixture was stirred for 30 minutes. Allyl bromide (1.84 mL, 2.58 g, 21.3 mmol, 4.0 equiv.) was
added dropwise and the mixture was allowed to warm to room temperature over night. The
reaction was quenched by the addition of 5 mL of water, the layers were separated and the
aqueous layer was extracted with ether (3 × 15 mL). The combined organic layers were washed
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with 8 mL sat. NaCl solution, dried over Na2SO4 and separated from the drying agent. The
volatile components were removed in vacuo and the crude product was purified by column
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chromatography (nꢀpentane/ether = 99/1) to give 583 mg (3.62 mmol, 68%) of the product as a
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colorless oil. TLC (nꢀpentane/ether = 99/1): Rf = 0.43 [UV, KMnO4]. IR (ATR):
ν
= 3071,
2950, 1453 cmꢀ1. HꢀNMR (CDCl3, 300 K, 360 MHz): δ (ppm) = 0.54 (q, 3J = 8.1 Hz, 6 H), 0.89
(t, 3J = 8.1 Hz, 9 H), 2.17 (s, 2 H), 4.05 (d, 3J = 5.8 Hz, 2 H), 4.47 (s, 2 H), 5.22 (d, 3J = 10.5 Hz,
1 H), 5.34 (d, 3J = 17.4 Hz, 1 H), 5.97 (ddt, 3J = 17.4 Hz, 3J = 10.5 Hz, 3J = 5.8 Hz, 1 H), 7.02 (d,
1
3J = 7.7 Hz, 1 H), 7.06 (virt. t, 3J ≅ J = 7.7 Hz, 1 H), 7.14 (virt. t, 3J ≅ 3J = 7.3 Hz), 7.29 (d, 3J =
3
7.3 Hz, 1 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 91 MHz): δ (ppm) = 3.7 (t), 7.4 (q), 17.9 (t), 70.7
(t), 71.5 (t), 117.3 (t), 124.2 (d), 127.6 (d), 129.1 (d), 129.4 (d), 134.7 (s), 135.1 (d), 139.5 (s).
MS (EI, 70 eV): m/z (%) = 277 (2, M+), 247 (12, [MꢀEt]+), 104 (100, [C8H8]+). HRMS (EI) m/z:
[MꢀEt]+ calcd. for C15H23OSi: 247.1513; found: 247.1511.
(2-(Allyloxymethyl)benzyloxy)(tert-butyl)dimethylsilane (5e)
Sodium hydride (65.9 mg, 1.65 mmol, 60% suspension in mineral oil, 1.5 equiv.) was suspended
in 1 mL of THF and cooled to 0 °C. A solution of alcohol 4e (277 mg, 1.10 mmol, 1.0 equiv.) in
1 mL of THF was added dropwise and the mixture was stirred for 30 min. Then, a solution of
allyl bromide (114 µL, 160 mg, 1.32 mmol, 1.2 equiv.) in 1 mL of THF was added and the
reaction mixture was allowed to warm to room temperature over night. The reaction was
quenched by the addition of 3 mL water. The layers were separated and the aqueous layer was
extracted with ether (3 × 10 mL). The organic layers were combined, washed with 5 mL sat.
NaCl solution, dried over Na2SO4 and separated from the drying agent. After evaporation of the
volatile components in vacuo, the crude product was purified by column chromatography (nꢀ
pentane/ether = 99/1) to give 245 mg (83.9 µmol, 76%) of the product as a colorless oil. TLC (nꢀ
ꢀ1
1
~
pentane/ether = 99/1): Rf = 0.42 [UV, KMnO4]. IR (ATR):
ν
= 3077, 2954, 1471 cm . HꢀNMR
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(CDCl3, 300 K, 360 MHz): δ (ppm) = 0.09 (s, 6 H), 0.94 (s, 9 H), 4.01 (virt. dt, 3J = 5.7 Hz, 4J ≅
4J = 1.3 Hz, 2 H), 4.56 (s, 2 H), 4.80 (s, 2 H), 5.20 (virt. dq, 3J = 10. 4 Hz, 2J ≅ 4J = 1.3 Hz, 1 H),
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5.30 (virt. dq, 3J = 17.3 Hz, 2J ≅ 4J = 1.6 Hz, 1 H), 5.95 (ddt, 3J = 17.3 Hz, 3J = 10. 4 Hz, 3J = 5.7
Hz, 1 H), 7.24 (t, 3J = 7.6 Hz, 1 H), 7.30 (t, 3J = 7.6 Hz, 1 H), 7.34 (d, 3J = 7.6 Hz, 1 H), 7.48 (d,
3J = 7.6 Hz, 1 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 91 MHz): δ (ppm) = –5.1 (q), 18.6 (s), 26.1 (q),
62.7 (t), 70.0 (t), 71.3 (t), 117.2 (t), 126.9 (d) 127.0 (d), 127.9 (d), 128.5 (d), 134.9 (d), 135.1 (s),
139.8 (s). MS (EI, 70 eV): m/z (%) = 235 (31), 75 (100, [Me2Si=OH]+). HRMS (EI) m/z: [Mꢀ
Me]+ calcd. for C16H25O2Si: 277.1618; found: 277.1627.
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1-Allyloxymethyl-2-methoxymethylbenzene (5g)
Sodium hydride (50.5 mg, 1.26 mmol, 60 % suspension in mineral oil, 1.5 equiv.) was suspended
in 2 mL of THF and cooled to 0 °C. A solution of 5f (150 mg, 841 µmol, 1.0 equiv.) in 2 mL of
THF was added dropwise and the mixture was stirred for 30 min. Then, a solution of methyl
iodide (62.9 µL, 143 mg, 1.01 mmol, 1.2 equiv.) was added dropwise and the mixture was
allowed to warm to room temperature over night. The reaction was quenched by the addition of 3
mL of sat. ammonium chloride solution, the layers were separated and the aqueous layer was
extracted with ether (3 × 10 mL). The combined organic layers were washed with 5mL sat. NaCl
solution and dried over Na2SO4. The drying agent was removed and the volatile components were
evaporated under reduced pressure. Purification by column chromatography (nꢀpentane/ether =
99/1) gave 123 mg (637 µmol, 76%) of the product as a colorless oil. TLC (nꢀpentane/ether =
~
99/1): Rf = 0.62 [UV, KMnO4]. IR (ATR):
ν
= 3075, 2981, 1454 cmꢀ1. 1HꢀNMR (CDCl3, 300 K,
360 MHz): δ (ppm) = 3.39 (s, 3 H), 4.04 (dt, 3J = 5.6 Hz, 4J = 1.4 Hz, 2 H), 4.54 (s, 2 H), 4.59 (s,
2 H), 5.23 (virt. dq, 3J = 10.4 Hz, 2J ≅ 4J = 1.5 Hz), 5.32 (virt. dq, 3J = 17.2 Hz, 2J ≅ 4J = 1.5 Hz,
1 H), 5.96 (ddt, 3J = 17.2 Hz, 3J = 10.4 Hz, 3J = 5.6 Hz, 1 H), 7.26–7.32 (m, 2 H), 7.36–7.44 (m,
2 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 91 MHz): δ (ppm) = 58.3 (q), 69.8 (t), 71.4 (t), 72.4 (t),
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117.3 (t), 127.9 (d), 128.8 (d), 128.9 (d), 134.9 (s), 136.6 (s). MS (EI, 70 eV): m/z (%) = 178 (3,
[MꢀMe]+), 160 (26, [MꢀOMe]+), 120 (100, [MꢀCH2OC3H5]+).HRMS (ESI) m/z: [M+H]+ calcd.
for C12H17O2: 193.1223; found: 193.1218.
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1-Allyloxymethyl-2-bromomethylbenzene
NBS (59.9 mg, 337 µmol, 1.2 equiv.) was dissolved in 1 mL DMF, before PPh3 (88.3 mg, 337
µmol, 1.2 equiv.) was added in small portions accompanied by gentle warming of the solution.
After reaching room temperature, a solution of alcohol 5f (50.0 mg, 281 µmol, 1.0 equiv.) in 0.5
mL DMF was added dropwise. The mixture was stirred for one hour before being diluted with 2
mL ether. Water (2 mL) was added, the layers were separated and the aqueous layer was
extracted with ether (3 × 5 mL). The organic layers were combined and washed with 4 mL sat.
NaCl solution. After drying over Na2SO4, the drying agent was removed by filtration. Removal
of the volatile components in vacuo yielded the crude product, which was purified by column
chromatography (nꢀpentane/ether = 99/1) yielding 47.2 mg (196 µmol, 70%) of the desired
~
product as a colorless oil. TLC (nꢀpentane/ether = 99/1): Rf = 0.43 [UV, KMnO4]. IR (ATR):
ν
=
3073, 2857, 1455 cmꢀ1. 1HꢀNMR (CDCl3, 300 K, 360 MHz): δ (ppm) = 4.07 (d, 3J = 5.7 Hz, 2
H), 4.64 (s, 2 H), 4.66 (s, 2 H), 5.23 (virt. dq, 3J = 10.5 Hz, 2J ≅ 4J = 1.2 Hz, 1 H), 5.34 (virt. dq,
3J = 17.3 Hz, 2J ≅ 4J = 1.3 Hz, 1 H), 5.98 (ddt, 3J = 17.3 Hz, 3J = 10.5 Hz, 3J = 5.7 Hz, 1 H),
7.28–7.33 (m, 2 H), 7.36–7.40 (m, 2 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 91 MHz): δ (ppm) = 31.3
(t), 69.8 (t), 71.7 (t), 117.6 (t), 128.6 (d), 129.0 (d), 129.8 (d), 130.8 (d,), 134.7 (d), 136.9 (s). MS
(EI, 70 eV): m/z (%) = 242 (2, M(81Br)+), 240 (2, M(79Br)+), 184 (78, [M(81Br)ꢀ OC3H5]+), 182
(78, [M(79Br)ꢀ OC3H5]+), 104 (100, [C8H8]+). HRMS (EI) m/z: [C11H1379BrO]+ calcd: 240.0150;
found: 240.0153.
2-(2-(Allyloxymethyl)phenyl)acetonitrile (5h)
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The prepared benzylbromide (51.2 mg, 212 µmol, 1.0 equiv.) was dissolved in 1.5 mL of DMF.
Sodium cyanide (11.8 mg, 241 µmol, 1.1 equiv.) was added and the mixture was stirred at room
temperature over night. The reaction was quenched by the addition of 1 mL water and the
aqueous layer was extracted with ether (3 × 5 mL). The combined organic layers were washed
with 4 mL sat. NaCl solution, dried over Na2SO4 and the drying agent was removed by filtration.
After evaporation of the volatile components in vacuo, the crude product was purified by column
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chromatography (nꢀpentane/ether = 9/1) giving 39.7 mg (212 µmol, 100%) of the product as a
~
colorless oil. TLC (nꢀpentane/ether = 9/1): Rf = 0.34 [UV, KMnO4]. IR (ATR):
ν
= 3073, 2854,
2247, 1455 cmꢀ1. 1HꢀNMR (CDCl3, 300 K, 360 MHz): δ (ppm) = 3.88 (s, 2 H), 4.02 (dt, 3J = 5.8
Hz, 4J = 1.4 Hz, 2 H), 4.56 (s, 2 H), 5.23 (virt. dq, 3J = 10.5 Hz, 2J ≅ 4J = 1.3 Hz, 1 H), 5.31 (virt.
dq 3J = 17.3 Hz, 2J ≅ 4J = 1.5 Hz, 1 H), 5.94 (ddt, 3J = 17.3 Hz, 3J = 10.5 Hz, 3J = 5.8 Hz, 1 H),
7.30–7.39 (m, 3 H), 7.46 (d, 3J = 7.5 Hz, 1 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 91 MHz): δ (ppm)
= 21.2 (t), 70.7 (t), 71.5 (t), 117.9 (s), 117.9 (t), 128.4 (d), 129.1 (d), 129.4 (d), 129.7 (s), 130.2
(d), 134.3 (d), 135.8 (s). MS (EI, 70 eV): m/z (%) = 187 (2, M+), 130 (100, [Mꢀ OC3H5]+). HRMS
(EI) m/z: [C12H13NO]+ calcd.: 187.0992; found: 187.0984.
2-(Allyloxymethyl)benzyl pivaloate (5i)
Alcohol 5f (50.0 mg, 281 µmol, 1.0 equiv.), DMAP (3.43 mg, 28.1 µmol, 0.1 equiv.) and NEt3
(117 µL, 84.5 mg, 842 µmol, 3.0 equiv.) were dissolved in 1 mL of CH2Cl2. Then, a solution of
pivalic acid chloride (41.4 µL, 40.6 mg, 337 µmol, 1.2 equiv.) in 1 mL of CH2Cl2 was added. The
mixture was stirred for 90 min before being quenched by the addition of 1 mL water. The layers
were separated and the aqueous layer was extracted with ether (3 × 5 mL). The organic layers
were combined, washed with sat. NaHCO3 solution (2 × 5 mL) and 5 mL of sat. NaCl solution
and dried over Na2SO4. The filter agent was removed and the volatile components were
evaporated in vacuo before the crude product was purified by column chromatography (nꢀ
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pentane/ether = 9/1) to give 60.0 mg (229 µmol, 82%) of the product as a colorless oil. TLC (nꢀ
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ꢀ1
1
~
pentane/ether): Rf = 0.57 [UV, KMnO4]. IR (ATR):
ν
= 3078, 2974, 1729, 1479 cm . HꢀNMR
(CDCl3, 300 K, 360 MHz): δ (ppm) = 1.22 (s, 9 H), 4.05 (dt, 3J = 5.7 Hz, 4J = 1.4 Hz, 2 H), 4.59
(s, 2 H), 5.19 (s, 2 H), 5.22 (virt. dq, 3J = 10.5 Hz, 2J ≅ 4J = 1.6 Hz, 1 H), 5.31 (virt. dq, 3J = 17.2
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Hz, 2J ≅ 4J = 1.6 Hz, 1 H), 5.96 (ddt, 3J = 17.2 Hz, 3J = 10.5 Hz, 3J = 5.7 Hz, 1 H), 7.29–7.34 (m,
2 H), 7.36–7.42 (m, 2 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 91 MHz): δ (ppm) = 27.9 (q), 39.0 (s),
63.9 (t), 69.9 (t), 71.6 (t), 117.5 (t), 128.1 (d), 128.3 (d), 128.9 (d), 129.0 (d), 134.8 (d), 134.9 (s),
136.6 (s), 178.4 (s). MS (EI, 70 eV): m/z (%) = 205 (4, [MꢀtBu]+), 160 (55, [MꢀOPiv]+), 57 (100,
[C4H9]+). HRMS (EI) m/z: [MꢀOPiv]+ calcd. for C11H12O: 160.0883; found: 160.0879.
2-(Allyloxymethyl)benzyl acetate (5j)
Alcohol 5f (150 mg, 843 µmol, 1.0 equiv.), DMAP (10.3 mg, 84.2 µmol, 0.1 equiv.) and NEt3
(352 µL, 254 mg, 2.52 mmol, 3.0 equiv.) were dissolved in 4 mL CH2Cl2 and cooled to 0 °C.
Acetyl chloride (72.1 µL, 79.3 mg, 1.01 mmol, 1.2 equiv.) in 4 mL CH2Cl2 was added dropwise
and the mixture was stirred for one hour. After addition of 10 mL of ether, the layers were
separated and the organic layer was washed with sat. NaHCO3 solution (2 × 5 mL) and 5 mL of
sat. NaCl solution. After removal of the volatile components in vacuo, the crude product was
purified by column chromatography (nꢀpentane/ethyl acetate = 9/1) to give 160 mg (725 µmol,
86%) of the product as a colorless oil. TLC (nꢀpentane/ethyl acetate = 4/1): Rf = 0.76 [UV,
ꢀ1
1
~
KMnO4]. IR (ATR):
ν
= 3076, 2930, 1739, 1455 cm . HꢀNMR (CDCl3, 300 K, 360 MHz): δ
(ppm) = 2.09 (s, 3 H), 4.04 (d, 3J = 5.7 Hz, 2 H), 4.58 (s), 5.21 (s, 2 H), 5.22 (virt. dq, 3J = 10.4
Hz, 2J ≅ 4J = 1.3 Hz, 1 H), 5.32 (virt. dq, 3J = 17.1 Hz, 2J ≅ 4J = 1.3 Hz, 1 H), 5.94 (ddt, 3J = 17.1
Hz, 3J = 10.4 Hz, 3J = 5.7 Hz, 1 H), 7.30–7.35 (m, 2 H), 7.36–7.42 (m, 2 H). 13C{1H}ꢀNMR
(CDCl3, 300 K, 91 MHz): δ (ppm) = 21.9 (q), 64.0 (t), 70.0 (t), 71.6 (t), 117.5 (t,), 128.2 (d),
128.6 (d), 129.3 (d), 129.7 (d), 134.5 (d), 134.7 (s), 136.8 (s), 173.2 (s). MS (EI, 70eV): m/z (%)
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= 176 (3, [MꢀAc]+), 160 (59, [MꢀOAc]+), 119 (100, [C8H8O]+). HRMS (ESI) m/z: [M+H]+ calcd.
for C13H17O3: 221.1172; found: 221.1166.
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1-Allyloxymethyl-2-fluoromethylbenzene (5k)
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Benzyl alcohol 5f (80.0 mg, 449 µmol, 1.0 equiv.) was dissolved in 1 mL of CH2Cl2 and cooled
to −78 °C. Subsequently, a solution of DAST (118 µL, 114 mg, 898 µmol, 2.0 equiv.) in 0.5 mL
CH2Cl2 was added. The mixture was stirred for 30 min, before 0.5 mL ethanol was added and the
mixture was warmed to 0 °C. Due to the volatility of the product, the solvent was removed by
passing a nitrogen stream over the solution. The crude product was purified by column
chromatography (nꢀpentane/ether = 99/1) to give 42.0 mg (233 µmol, 48%) of the product as a
~
volatile, colorless oil. TLC (nꢀpentane/ether = 99/1): Rf = 0.20 [UV, KMnO4]. IR (ATR):
ν
=
3075, 2856, 1455 cmꢀ1. 1HꢀNMR (CDCl3, 300 K, 360 MHz): δ (ppm) = 4.02 (dt, 3J = 5.6 Hz, 4J =
1.4 Hz, 2 H), 4.59 (s, 2 H), 5.22 (virt. dq, 3J = 10.4 Hz, 2J ≅ 4J = 1.3 Hz, 1 H), 5.31 (virt. dq, 3J =
17.2 Hz, 2J ≅ 4J = 1.6 Hz, 1 H), 5.51 (d, 2J = 48.1 Hz, 2 H), 5.95 (ddt, 3J = 17.2 Hz, 3J = 10.4 Hz,
3J = 5.6 Hz, 1 H), 7.33–7.37 (m, 2 H), 7.39–7.44 (m, 2 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 91
MHz): δ (ppm) = 69.9 (t), 71.5 (t), 82.6 (td, 1J = 165.4 Hz), 117.5 (t), 128.3 (d), 128.6 (d), 128.7
(d), 128.9 (d), 129.0 (s), 129.2 (s), 134.7 (d). MS (EI, 70 eV): m/z (%) = 180 (4, M+), 123 (100,
[Mꢀ OC3H5]+). HRMS (ESI): [M+NH4]+ calcd. for C11H17FNO: 198.1289; found: 198.1291.
General procedure for the irradiation of allyl benzyl ethers
A 15ꢀmL quartz tube with a rubber seal was charged with the respective allyl benzyl ether and
anhydrous cyclohexane under argon, and the solution was degassed by purging with argon in an
ultrasonicating bath for 15 min. The tube was irradiated at r.t. (λ = 254 nm, Rayonet RPRꢀ2537
Å) for 16 hours. The solvent was removed under reduced pressure, the isomer ratio was
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determined by crude NMR and the residue was directly subjected to purification by flash silica
gel column chromatography to give a mixture of metaꢀphotocycloaddition products.
1-Ethyl-4-oxatetracyclo[6.3.0.02,6.02,11]undec-9-ene (2b)
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According to the general procedure, 100 mg (567 µmol) of benzyl ether 5b were irradiated in 10
mL of cyclohexane. After column chromatography (nꢀpentane/ether = 99/1), 28.6 mg (162 µmol,
29%) of the linear metaꢀphotocycloaddition product 2b was obtained. TLC (nꢀpentane/ether =
ꢀ1
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~
99/1): Rf = 0.25 [KMnO4]. IR (ATR):
ν
= 3051, 2959, 1454 cm . HꢀNMR (CDCl3, 300 K, 360
MHz): δ (ppm) = 1.01 (t, 3J = 7.2 Hz, 3 H), 1.50 (virt. sext., 2J ≅ 2 × 3J = 14.4 Hz, 3J = 7.2 Hz, 1
H), 1.65 (virt. sext., 2J ≅ 2 × 3J = 14.4 Hz, 3J = 7.2 Hz, 1 H), 1.72 (br s, 1 H), 1.77 (ddd, 2J =11.5
Hz, 3J = 9.5 Hz, 3J = 5.1 Hz, 1 H), 1.85 (dd, 2J = 11.5 Hz, 3J = 6.4 Hz, 1 H), 2.38 (virt. dtd, 3J =
9.9 Hz, 3J ≅ 3J = 7.5 Hz, 3J = 3.5 Hz, 1 H), 3.10 (dd, 3J = 5.0 Hz, 3J = 2.1 Hz, 1 H), 3.60–3.70 (m,
3 H), 3.90 (dd, 2J = 8.7 Hz, 3J = 7.5 Hz, 1 H), 5.46 (dd, 3J = 5.5 Hz, 3J = 2.1 Hz, 1 H), 5.67 (dd,
3J = 5.5 Hz, 3J = 2.4 Hz, 1 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 91 MHz): δ (ppm) = 11.5 (q), 21.9
(t), 37.4 (d), 42.8 (d), 46.0 (t), 51.5 (s), 51.6 (s), 55.4 (d), 67.5 (t), 73.7 (t), 129.2 (d), 133.4 (d).
MS (EI, 70 eV): m/z (%) = 176 (4, M+), 118 (100, [Mꢀ OC3H5]+). HRMS (ESI) m/z: [M+H]+
calcd. for C12H16O: 177.1274; found: 177.1268.
(4-Oxatetracyclo[6.3.0.02,6.02,11]undec-9-en-1-yl)-methyltrimethylsilane (2c)
Following the general procedure, 40.0 mg (171 µmol) of the silane 5c were irradiated in 4 mL
cyclohexane. Purification by column chromatography (nꢀpentane/ether = 99/1) gave 19.8 mg
(84.5 µmol, 50%) of the photocycloaddition product 2c. TLC (nꢀpentane/ether = 99/1): Rf = 0.21
ꢀ1
1
~
[KMnO4]. IR (ATR):
ν
= 3051, 2936, 1411 cm . HꢀNMR (CDCl3, 300 K, 360 MHz): δ (ppm)
= 0.03 (s, 9 H), 0.57 (d, 2J = 15.1 Hz, 1 H), 0.99 (d, 2J = 15.1 Hz, 1 H), 1.63 (br s, 1 H), 1.75–
1.85 (m, 2 H), 2.37 (virt. dtd, 3J = 10.0 Hz, 3J ≅ 3J = 7.3 Hz, 3J = 3.5 Hz, 1 H), 3.00–3.04 (m, 1
H), 3.60 (d, 2J = 9.7 Hz, 1 H), 3.64 (dd, 2J = 9.0 Hz, 3J = 3.5 Hz, 1 H), 3.67 (d, 2J = 9.7 Hz, 1 H),
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3.89 (dd, 2J = 9.0 Hz, 3J = 7.9 Hz, 1 H), 5.47 (dd, 3J = 5.4 Hz, 3J = 2.4 Hz, 1 H), 5.69 (dd, 3J =
5.4 Hz, 3J = 2.3 Hz, 1 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 91 MHz): δ (ppm) = –0.3 (q), 16.2 (t),
38.1 (d), 42.7 (d), 45.3 (t), 48.2 (s), 51.4 (s), 57.7 (d), 67.5 (t), 73.8 (t), 129.4 (d), 133.3 (d). MS
(EI, 70 eV): m/z (%) = 234 (3, M+), 104 (100, [C8H8]+). HRMS (EI) m/z: [C14H22OSi]+ calcd.:
234.1434; found: 234.1425.
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(4-Oxatetracyclo[6.3.0.02,6.02,11]undec-9-en-1-yl)-methyltriethylsilane (2d) and (6-
oxatetracyclo [6.3.0.02,11.04,8]undec-9-en-1-yl)-methyltriethylsilane (3d)
According to the general procedure, 48.8 mg (177 µmol) of the silyl ether 5d were irradiated in 5
mL cyclohexane. Purification by column chromatography (nꢀpentane/ether = 99/1) gave 32.1 mg
(116 µmol, 66%) of the mixture of metaꢀphotocycloaddition products. The isomer ratio was
~
2d/3d = 87/13. Data of 2d: TLC (nꢀpentane/ether = 99/1): Rf = 0.17 [KMnO4]. IR (ATR):
ν
=
3055, 2949, 1457 cmꢀ1. 1HꢀNMR (CDCl3, 300 K, 500 MHz): δ (ppm) = 0.50–0.58 (m, 7 H), 0.93
(t, 3J = 8.0 Hz, 9 H), 1.03 (d, 2J = 15.4 Hz, 1 H), 1.75–1.85 (m, 2 H), 2.37 (virt. dtd, 3J = 9.9 Hz,
3J ≅ 3J = 7.2 Hz, 3J = 3.4 Hz, 1 H), 2.97–3.00 (m, 1 H), 3.60 (d, 2J = 9.1 Hz, 1 H), 3.64 (dd, 2J =
9.0 Hz, 3J = 3.4 Hz, 1 H), 3.68 (d, 2J = 9.1 Hz, 1 H), 3.89 (dd, 2J = 9.0 Hz, 3J = 7.2 Hz, 1 H), 5.46
(dd, 3J = 5.5 Hz, 3J = 2.5 Hz, 1 H), 5.68 (dd, 3J = 5.5 Hz, 3J = 2.1 Hz, 1 H). 13C{1H}ꢀNMR
(CDCl3, 300 K, 125 MHz): δ (ppm) = 4.1 (t), 7.7 (q), 10.3 (t), 38.2 (d), 42.6 (d), 45.5 (t), 47.7 (s),
51.5 (s), 57.7 (d), 67.4 (t), 73.8 (t), 129.4 (d), 130.3 (d). MS (EI, 70 eV): m/z (%) = 276 (2, M+),
247 (6, [MꢀEt]+), 87 (100). HRMS (EI) m/z: [C17H28OSi]+ calcd.: 276.1904; found: 276.1907.
~
Data of 3d: TLC (nꢀpentane/ether = 99/1): Rf = 0.09 [KMnO4]. IR (ATR):
ν
= 3055, 2949, 1457
cmꢀ1. 1HꢀNMR (CDCl3, 300 K, 500 MHz): δ (ppm) = 0.50 (q, 3J = 7.9 Hz, 6 H), 0.93 (t, 3J = 7.9
Hz, 9 H), 1.04 (d, 2J = 15.0 Hz, 1 H), 1.36 (d, 2J = 15.0 Hz, 1 H), 1.62–1.82 (m, 4 H), 2.36 (ddd,
3J = 10.7 Hz, 3J = 7.9 Hz, 3J = 5.7 Hz, 1 H), 3.57 (dd, 2J = 10.8 Hz, 3J = 7.9 Hz, 1 H ), 3.73 (d, 2J
= 9.0 Hz, 1 H), 3.84 (virt. t, 2J ≅ 3J = 8.0 Hz, 1 H), 4.12 (d, 2J = 9.0 Hz, 1 H), 5.38 (d, 3J = 5.4 Hz,
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1 H), 5.63 (dd, 3J = 5.4 Hz, 3J = 2.2 Hz, 1 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 125 MHz): δ (ppm)
= 4.6 (t), 7.7 (q), 11.9 (t), 24.3 (t), 36.3 (d), 37.0 (d), 47.7 (s), 59.1 (d), 69.7 (t), 71.0 (t), 127.4 (d),
132.2 (d). MS (EI, 70 eV): m/z (%) = 276 (2, M+), 247 (7, [MꢀEt]), 87 (100). HRMS (EI) m/z:
[C17H28OSi]+ calcd.: 276.1904; found: 276.1910.
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4-Oxa-1-(tert-butyldimethylsilyloxymethyl)tetracyclo[6.3.0.02,6.02,11]undec-9-ene (2e) and
6-oxa-1-(tert-butyldimethylsilyloxymethyl)tetracyclo [6.3.0.02,11.04,8]undec-9-ene (3e)
Following the general procedure, reaction of 100 mg (342 µmol) of substrate 5e in 10 mL
cyclohexane gave after column chromatography (nꢀpentane/ether = 99/1) 67.5 mg (231 µmol,
68%) of a mixture of the metaꢀphotocycloaddition products in a ratio of 2e/3e = 46/54. Data of
~
2e: TLC (nꢀpentane/ether = 99/1): Rf = 0.16 [KMnO4]. IR (ATR):
ν
= 3055, 2950, 1471 cmꢀ1.
1HꢀNMR (CDCl3, 300 K, 500 MHz): δ (ppm) = 0.04 (s, 6 H), 0.89 (s, 9 H), 1.79–1.90 (m, 2 H),
1.96 (s, 1 H), 2.37–2.47 (m, 1 H), 3.23 (s, 1 H), 3.60 (dd, 2J = 8.9 Hz, 3J = 4.9 Hz, 1 H), 3.65 (d,
2J = 9.0 Hz, 1 H), 3.73 (d, 2J = 11.3 Hz), 3.80 (d, 2J = 9.0 Hz), 3.97 (virt. t, 2J ≅ 3J = 8.0 Hz, 1 H),
3.98 (d, 2J =11.3 Hz, 1 H), 5.50 (dd, 3J = 5.4 Hz, 3J = 2.2 Hz, 1 H), 5.66 (dd, 3J = 5.4 Hz, 3J = 2.1
Hz, 1 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 91 MHz): δ (ppm) = –5.2 (q), 18.4 (s), 26.0 (q), 36.9
(d), 43.3 (d), 45.5 (t), 51.2 (s), 51.4 (s), 55.6 (d), 61.2 (t), 67.7 (t), 73.8 (t), 128.5 (d), 133.8 (d).
MS (EI, 70 eV): m/z (%) = 292 (31, M+), 235 (63, [MꢀtBu]+), 160 (21, [MꢀOTBS]+), 75 (100,
[Me2Si=OH]+). HRMS (EI) m/z: [C17H28O2Si]+ calcd.: 292.1853; found: 292.1850. Data of 3e:
ꢀ1
1
~
TLC (nꢀpentane/ether = 99/1): Rf = 0.13 [KMnO4]. IR (ATR):
ν
= 3051, 2928, 1471 cm . Hꢀ
NMR (CDCl3, 300 K, 500 MHz): δ (ppm) = 0.04 (s, 6 H), 0.88 (s, 9 H), 1.85–1.90 (m, 2 H), 2.26
(d, 3J = 5.2 Hz, 1 H), 2.38 (virt. qd, 3J ≅ 3J = 7.7 Hz, 3J = 3.2 Hz, 1 H), 3.31–3.55 (m, 1 H), 3.64
(d, 2J = 10.8 Hz, 1 H), 3.71 (dd, 2J = 9.0 Hz, 3J = 3.2 Hz, 1 H), 3.79 (d, 2J = 9.2 Hz, 1 H), 3.82 (d,
2J = 9.2 Hz, 1 H), 3.84 (d, 2J = 10.8 Hz, 1 H), 3.91 (dd, 2J = 9.0 Hz, 3J = 7.7 Hz, 1 H), 5.48 (dd,
3J = 5.5 Hz, 3J = 2.4 Hz, 1 H), 5.64 (d, 3J = 5.5 Hz, 1 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 91
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MHz): δ (ppm) = –5.2 (q), 18.5 (s), 26.1 (q), 42.7 (d), 43.5 (d), 47.2 (t), 47.3 (s), 52.6 (s), 52.8
(d), 63.5 (t), 70.0 (t), 73.5 (t), 130.5 (d), 133.9 (d). MS (EI, 70 eV): m/z (%) = 292 (7, M+), 235
(42, [M−tBu]+), 75 (100, [Me2Si=OH]+). HRMS (EI) m/z: [C17H28O2Si]+ calcd.: 292.1853; found:
292.1847.
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4-Oxa-1-hydroxymethyltetracyclo[6.3.0.02,6.02,11]undec-9-ene (2f) and 6-oxa-1-
hydroxymethyltetracyclo[6.3.0.02,11.04,8]undec-9-ene (3f)
Following the general procedure, 47.9 mg (296 µmol) of alcohol 5f were irradiated in 5 mL
cyclohexane. After purification by colum chromatography (nꢀpentane/ethyl acetate = 1/1), 14.8
mg (91.8 µmol, 44%) of a mixture of photocycloaddition products were obtained. The isomer
ratio was 2f/3f = 25/75. Data of 2f: TLC (nꢀpentane/ethyl acetate = 1/1): Rf = 0.20 [KMnO4]. IR
ꢀ1
1
~
(ATR):
ν
= 3394, 3051, 2929, 1360 cm . HꢀNMR (CDCl3, 300 K, 360 MHz): δ (ppm) = 1.88–
2.00 (m, 2 H), 2.06 (s, 1 H), 2.38–2.46 (m, 1 H), 3.34 (br s, 1 H), 3.67 (d, 2J = 9.3 Hz, 1 H), 3.71–
3.78 (m, 3 H), 3.88 (dd, 2J = 9.0 Hz, 3J = 7.4 Hz, 1 H), 3.99 (d, 3J = 12.4 Hz, 1 H), 5.52 (dd, 3J =
5.5 Hz, 3J = 2.5 Hz, 1 H), 5.67 (dd, 3J = 5.5 Hz, 3J = 2.1 Hz, 1 H). 13C{1H}ꢀNMR (CDCl3, 300 K,
91 MHz): δ (ppm) = 36.9 (d), 42.1 (d), 47.1 (t), 52.0 (s), 52.4 (s), 54.9 (d), 62.6 (t), 67.5 (t), 73.9
(t), 128.3 (d), 134.1 (d). MS (EI, 70 eV): m/z (%) = 178 (5, M+), 160 (18, [M−H2O]+), 91 (100,
[C7H7]+). HRMS (EI) m/z: [C11H14O2]+ calcd.: 178.0988; found: 178.0990. Data of 3f: TLC (nꢀ
ꢀ1
~
pentane/ethyl acetate = 1/1): Rf = 0.19 [KMnO4]. IR (ATR):
ν
= 3357, 3047, 2932, 1355 cm .
1HꢀNMR (CDCl3, 300 K, 360 MHz): δ (ppm) = 1.88–1.97 (m, 2 H), 2.31 (d, 3J = 5.3 Hz, 1 H),
2.39 (virt. qd, 3J ≅ 3J = 7.0 Hz, 3J = 3.2 Hz, 1 H), 3.35–3.41 (m, 1 H), 3.62 (d, 2J = 9.2 Hz, 1 H),
3.72 (dd, 2J = 9.0 Hz, 3J = 3.2 Hz, 1 H), 3.75–3.85 (m, 3 H), 3.93 (dd, 2J = 9.0 Hz, 3J = 7.5 Hz, 1
H), 5.54 (dd, 3J = 5.4 Hz, 3J = 2.4 Hz, 1 H), 5.72 (d, 3J = 5.4 Hz, 1 H). 13C{1H}ꢀNMR (CDCl3,
300 K, 91 MHz): δ (ppm) = 42.9 (d), 44.1 (d), 47.3 (t), 47.6 (s), 53.0 (d), 53.3 (s), 63.6 (t), 69.7
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(t), 73.6 (t), 129.9 (d), 135.0 (d). MS (EI, 70 eV): m/z (%) = 178 (4, M+), 160 (12, [M−H2O]+), 92
(100, [C7H8]+). HRMS (EI) m/z: [C11H14O2]+ calcd.: 178.0988; found: 178.0991.
1-Methoxymethyl-4-oxatetracyclo[6.3.0.02,6.02,11]undec-9-ene (2g)
and 1-methoxymethyl-6-oxatetracyclo[6.3.0.02,11.04,8]undec-9-ene (3g)
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Following the general procedure, 50.0 mg (260 µmol) of benzyl ether 5g were irradiated in 5 mL
of cyclohexane. Purification by column chromatography (nꢀpentane/ether = 4/1) yielded 12.9 mg
(67.1 µmol, 26%) of the mixture of metaꢀphotocycloaddition products. The isomer ratio was
~
2g/3g = 41/59. Data of 2g: TLC (nꢀpentane/ether = 4/1): Rf = 0.20 [KMnO4]. IR (ATR):
ν
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3051, 2927, 1450 cmꢀ1. 1HꢀNMR (CDCl3, 300 K, 360 MHz): δ (ppm) = 1.85–1.89 (m, 2 H), 2.01
(br s, 1 H), 2.41 (virt. dtd, 3J = 11.4 Hz, 3J ≅ 3J = 8.0 Hz, 3J = 3.6 Hz, 1 H), 3.27 (br s, 1 H), 3.35
(s, 3 H), 3.59 (d, 2J = 11.2 Hz, 1 H), 3.62 (d, 2J = 11.2 Hz, 1 H), 3.66 (d, 2J = 9.4 Hz, 1 H), 3.67
(dd, 2J = 9.0 Hz, 3J = 3.6 Hz, 1 H), 3.73 (d, 2J = 9.4 Hz, 1 H), 3.91 (virt. t, 2J ≅ 3J = 8.5 Hz, 1 H),
5.51 (dd, 3J = 5.6 Hz, 3J = 2.6 Hz, 1 H), 5.68 (dd, 3J = 5.6 Hz, 3J = 2.0 Hz, 1 H). 13C{1H}ꢀNMR
(CDCl3, 300 K, 91 MHz): δ (ppm) = 37.1 (d), 42.7 (d), 45.9 (t), 50.1 (s), 51.9 (s), 53.3 (d), 58.8
(q), 67.5 (t), 71.9 (t), 73.5 (t), 128.5 (d), 133.9 (d). MS (EI, 70 eV): m/z (%) = 192 (25, M+), 160
(24, [M−MeOH]+), 91 (100, [C7H7]+). HRMS (EI) m/z: [C12H16O2]+ calcd.: 192.1145; found:
~
192.1144. Data of 3g: TLC (nꢀpentane/ether = 4/1): Rf = 0.17 [KMnO4]. IR (ATR):
ν
= 3059,
2925, 1456 cmꢀ1. 1HꢀNMR (CDCl3, 300 K, 360 MHz): δ (ppm) = 1.85–1.94 (m, 2 H), 2.30 (d, 3J
= 5.3 Hz, 1 H), 2.39 (virt. dtd, 3J = 9.8 Hz, 3J ≅ 3J = 7.2 Hz, 3J = 2.9 Hz, 1 H), 3.35 (s, 3 H),
3.34–3.36 (m, 1 H), 3.43 (s, 2 H), 3.72 (dd, 2J = 9.2 Hz, 3J = 3.2 Hz, 1 H), 3.75 (d, 2J = 9.3 Hz, 1
H), 3.82 (d, 2J = 9.3 Hz, 1 H), 3.90 (dd, 2J = 9.2 Hz, 3J = 7.3 Hz, 1 H), 5.51 (dd, 3J = 5.4 Hz, 3J =
2.2 Hz, 1 H), 5.71 (d, 3J = 5.4 Hz, 1 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 91 MHz): δ (ppm) = 42.4
(d), 44.6 (d), 45.2 (s), 47.3 (t), 52.8 (d), 53.0 (s), 59.0 (q), 69.8 (t), 73.5 (t), 73.6 (t), 130.4 (d),
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134.3 (d). MS (EI, 70 eV): m/z (%) = 192 (3, M+), 177 (4, [M−Me]+), 91 (100, [C7H7]+). HRMS
(EI) m/z: [C12H16O2]+ calcd.: 192.1145; found: 192.1143.
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oxatetracyclo[6.3.0.02,11.04,8]undec-9-en-1-yl)acetonitrile (3h)
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According to the general procedure, 35.8 mg (191 µmol) of the benzylic cyanide 5h were
irradiated in 4 mL cyclohexane. Purification by column chromatography (nꢀpentane/ether = 2/1)
gave 13.3 mg (70.7 µmol, 37%) of the mixture of metaꢀphotocycloaddition products. The isomer
~
ratio was 2h/3h = 40/60. TLC (nꢀpentane/ether = 2/1): Rf = 0.09 [KMnO4]. IR (ATR):
ν
= 3051,
2940, 2248, 1422 cmꢀ1. 1HꢀNMR (CDCl3, 300 K, 500 MHz): δ (ppm) = 1.87–1.95 (m, 2 H), 2.06
(d, 3J = 2.2 Hz, 0.4 H), 2.30 (d, 3J = 5.4 Hz, 0.6 H), 2.38–2.48 (m, 1 H), 2.57 (s, 1.2 H), 2.63 (d,
2J = 17.7 Hz, 0.4 H), 2.72 (d, 2J = 17.7 Hz, 0.4 H), 3.25–3.28 (m, 0.4 H), 3.41–3.45 (m, 0.6 H),
3.67 (dd, 2J = 9.3 Hz, 3J = 3.6 Hz, 0.4 H), 3.74 (dd, 2J = 9.1 Hz, 3J = 3.4 Hz, 0.6 H), 3.77 (d, 2J =
9.0 Hz, 0.6 H), 3.85 (d, 2J = 9.0 Hz, 0.6 H), 3.89–3.97 (m, 1 H), 5.54 (dd, 3J = 5.5 Hz, 3J = 2.6
Hz, 0.4 H), 5.59 (dd, 3J = 5.4 Hz, 3J = 2.5 Hz, 0.6 H), 5.63 (d, 3J = 5.4 Hz, 0.6 H), 5.69 (dd, 3J =
5.5 Hz, 3J = 2.2 Hz, 0.4 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 90 MHz) of 3h: δ (ppm) = 20.2 (t),
42.9 (d), 44.8 (d), 45.8 (t), 55.0 (s, d), 69.1 (t), 73.8 (t), 118.0 (s), 129.1 (d), 135.7 (d). MS (EI, 70
eV): m/z (%) = 187 (2, M+), 82 (100). HRMS (EI) m/z: [C12H13NO]+ calcd.: 187.0992; found:
187.0987.
4-Oxa-1-pivaloyloxymethyltetracyclo[6.3.0.02,6.02,11]undec-9-ene (2i) and 6-oxa-1-
pivaloyloxymethyltetracyclo[6.3.0.02,11.04,8]undec-9-ene (3i)
According to the general procedure, 60.0 mg (229 µmol) of the ester 5i were irradiated in 6 mL
cyclohexane. After purification by column chromatography (nꢀpentane/ether = 4/1), 20.4 mg
(77.8 µmol, 34%) of the mixture of photocycloaddition products were obtained. The isomer ratio
~
was 2i/3i = 33/67. Data of 2i: TLC (nꢀpentane/ether = 4/1): Rf = 0.29 [KMnO4]. IR (ATR):
ν
=
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3058, 2935, 1725, 1482 cmꢀ1. 1HꢀNMR (CDCl3, 300 K, 360 MHz): δ (ppm) = 1.21 (s, 9 H),
1.86–1.90 (m, 2 H), 2.07 (br s, 1 H), 2.43 (virt. dtd, 3J = 11.5 Hz, 3J ≅ 3J = 7.7 Hz, 3J = 3.8 Hz, 1
H), 3.29 (br s, 1 H), 3.64 (dd, 2J = 9.1 Hz, 3J = 3.8 Hz, 1 H), 3.68 (d, 2J = 9.5 Hz, 1 H), 3.74 (d, 2J
= 9.5 Hz, 1 H), 3.93 (virt. t, 2J ≅ 3J = 8.1 Hz, 1 H), 4.17 (d, 2J = 12.2 Hz, 1 H), 4.49 (d, 2J = 12.2
Hz, 1 H), 5.51 (dd, 3J = 5.4 Hz, 3J = 2.4 Hz, 1 H), 5.66 (dd, 3J = 5.6 Hz, 3J = 2.1 Hz, 1 H).
13C{1H}ꢀNMR (CDCl3, 300 K, 91 MHz): δ (ppm) = 27.4 (q), 37.8 (d), 39.7 (s), 42.9 (d), 46.0 (t),
49.3 (s), 52.3 (s), 55.8 (d), 63.9 (t), 67.6 (t), 73.7 (t), 128.1 (d), 133.9 (d), 178.5 (s). MS (EI, 70
eV): m/z (%) = 262 (8, M+), 178 (6, [M−Piv]+), 57 (100, [C4H9]+). HRMS (EI) m/z: [C16H22O3]+
calcd.: 262.1563; found: 262.1562. Data of 3i: TLC (nꢀpentane/ether = 4/1): Rf = 0.23 [KMnO4].
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ꢀ1
1
~
IR (ATR):
ν
= 3047, 2937, 1725, 1479 cm . HꢀNMR (CDCl3, 300 K, 360 MHz): δ (ppm) =
1.20 (s, 9 H), 1.85–1.95 (m, 2 H), 2.34 (d, 3J = 5.3 Hz, 1 H), 2.39 (virt. dtd, 3J = 9.7 Hz, 3J ≅ 3J =
7.3 Hz, 3J = 3.2 Hz, 1 H), 3.35 (br s, 1 H), 3.72 (dd, 2J = 9.0 Hz, 3J = 3.2 Hz, 1 H), 3.78 (s, 2 H),
3.91 (dd, 2J = 9.0 Hz, 3J = 7.3 Hz, 1 H), 4.08 (d, 2J = 11.9 Hz, 1 H), 4.19 (d, 2J = 11.9 Hz, 1 H),
5.49 (dd, 3J = 5.4 Hz, 3J = 2.3 Hz, 1 H), 5.63 (d, 3J = 5.4 Hz, 1 H). 13C{1H}ꢀNMR (CDCl3, 300
K, 91 MHz): δ (ppm) = 27.4 (q), 39.0 (s), 42.6 (d), 44.3 (s), 44.7 (d), 47.1 (t), 52.9 (d), 53.4 (s),
65.0 (t), 69.7 (t), 73.7 (t), 129.7 (d), 134.5 (d), 178.7 (s). MS (EI, 70 eV): m/z (%) = 262 (3, M+),
178 (7, [M−Piv]+), 57 (100, [C4H9]+). HRMS (EI) m/z: [C16H22O3]+ calcd.: 262.1563; found:
262.1562.
1-Acetoxymethyl-4-oxatetracyclo[6.3.0.02,6.02,11]undec-9-ene (2j) and 1-acetoxymethyl-6-
oxatetracyclo[6.3.0.02,11.04,8]undec-9-ene (3j)
According to the general procedure, 65.4 mg (297 µmol) of benzyl acetate 5j were irradiated in 7
mL cyclohexane. After purification by column chromatography (nꢀpentane/ether = 4/1), 31.7 mg
(144 µmol, 48%) of the mixture of photocycloaddition products were obtained. The isomer ratio
~
was 2j/3j = 16/84. Data of 2j: TLC (nꢀpentane/ether = 4/1): Rf = 0.19 [KMnO4]. IR (ATR):
ν
=
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3045, 2934, 1737, 1375 cmꢀ1. 1HꢀNMR (CDCl3, 300 K, 360 MHz): δ (ppm) = 1.84–1.90 (m, 2
H), 2.05–2.08 (m, 1 H), 2.06 (s, 3 H), 2.41 (virt. dtd, 3J = 11.5 Hz, 3J ≅ 3J = 8.0 Hz, 3J = 3.7 Hz, 1
H), 3.28 (br s, 1 H), 3.63–3.69 (m, 2 H), 3.73 (d, 2J = 9.4 Hz, 1 H), 3.90 (virt.t, 2J ≅ 3J = 8.4 Hz, 1
H), 4.22 (d, 2J = 12.3 Hz, 1 H), 4.42 (d, 2J = 12.3 Hz, 1 H), 5.52 (dd, 3J = 5.4 Hz, 3J = 2.2 Hz, 1
H), 5.66 (dd, 3J = 5.4 Hz, 3J = 2.2 Hz, 1 H). 13C{1H}ꢀNMR (CDCl3, 300 K, 91 MHz): δ (ppm) =
21.1 (q), 38.0 (d), 42.7 (d), 46.0 (t), 49.1 (s), 52.5 (s), 55.6 (d), 64.1 (t), 67.5 (t), 73.5 (t), 128.3
(d), 136.6 (d), 171.5 (s). MS (EI, 70 eV): m/z (%) = 220 (5, M+), 178 (17, [M−Ac]+), 130 (100).
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HRMS (EI) m/z: [C13H16O3]+ calcd.: 220.1094; found: 220.1098. Data of 3j: TLC (nꢀ
~
pentane/ether = 4/1): Rf = 0.15 [KMnO4]. IR (ATR):
ν
= 3051, 2941, 1735, 1376 cmꢀ1. 1HꢀNMR
(CDCl3, 300 K, 360 MHz): δ (ppm) = 1.85–1.95 (m, 2 H), 2.07 (s, 3 H), 2.34 (d, 3J = 5.3 Hz, 1
H), 2.37–2.44 (m, 1 H), 3.36 (br s, 1 H), 3.73 (dd, 2J = 9.0 Hz, 3J = 3.0 Hz, 1 H), 3.76 (d, 2J = 9.0
Hz, 1 H), 3.79 (d, 2J = 9.0 Hz, 1 H), 3.92 (virt. t, 2J ≅ 3J = 8.3 Hz, 1 H), 4.12 (d, 2J = 11.9 Hz, 1
H), 4.15 (d, 2J = 11.9 Hz, 1 H) 5.51 (dd, 3J = 5.5 Hz, 3J = 2.4 Hz, 1 H), 5.65 (d, 3J = 5.5 Hz, 1 H).
13C{1H}ꢀNMR (CDCl3, 300 K, 91 MHz): δ (ppm) = 21.1 (q), 42.6 (d), 44.0 (s) 44.7 (d), 47.1 (t),
53.0 (d), 53.6 (s), 65.2 (t), 69.6 (t), 73.7 (t), 129.8 (d), 134.7 (d), 171.2 (s). MS (EI, 70 eV): m/z
(%) = 220 (5, M+), 160 (100, [MꢀOAc]+). HRMS (EI) m/z: [C13H16O3]+ calcd.: 220.1094; found:
220.1094.
1-Fluormethyl-6-oxatetracyclo[6.3.0.02,11.04,8]undec-9-ene (3k)
Following the general procedure, 33.0 mg (183 µmol) of fluoro compound 5k were irradiated in
4 mL cyclohexane. After purification by column chromatography, 16.4 mg (91 µmol, 50%) of the
photocycloaddition product 3k was isolated. TLC (nꢀpentane/ether = 9/1): Rf = 0.31 [KMnO4]. IR
ꢀ1
1
~
(ATR):
ν
= 3047, 2938, 1468 cm . HꢀNMR (CDCl3, 300 K, 360 MHz): δ (ppm) = 1.88–1.98
(m, 2 H), 2.40 (d, 3J = 5.0 Hz, 1 H), 2.40–2.46 (m, 1 H), 3.37 (br s, 1 H), 3.74 (dd, 2J = 9.1 Hz, 3J
= 3.3 Hz, 1 H), 3.77 (d, 2J = 8.9 Hz, 1 H), 3.87 (d, 2J = 8.9 Hz„ 1 H), 3.92 (dd, 2J = 9.1 Hz, 3J =
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7.6 Hz, 1 H), 4.33 (dd, 2JHF = 48.6 Hz, 2J = 10.5 Hz, 1 H), 4.58 (dd, 2JHF = 48.6 Hz, 2J = 10.5 Hz,
1 H), 5.55 (dd, 3J = 5.5 Hz, 3J = 2.5 Hz, 1 H), 5.73 (d, 3J = 5.5 Hz, 1 H). 13C{1H}ꢀNMR (CDCl3,
300 K, 91 MHz): δ (ppm) = 42.4 (d), 44.7 (dd, 3JCF = 8.0 Hz), 45.1 (dd, 2JCF = 23.9 Hz), 47.2 (t),
52.8 (d), 53.8 (dd, 3JCF = 5.2 Hz), 69.5 (t), 73.5 (t), 84.6 (dt, 1JCF = 167.2 Hz), 129.1 (d), 135.2
(d). MS (EI, 70 eV): m/z (%) = 180 (6, M+), 160 (5, [MꢀF]+), 123 (100, [C8H7F]+). HRMS (EI)
m/z: [C11H13FO]+ calcd.: 180.0945; found: 180.0945.
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ACKNOWLEDGEMENT
This work was supported by the Fonds der Chemischen Industrie (Ph.D. scholarship to M. W.).
We thank Anil Candas for excellent technical assistance.
SUPPORTING INFORMATION
Product distributions of selected metaꢀphotocycloaddition reactions and 1Hꢀ and 13Cꢀ NMR
spectra of compounds 2b-k, 3b-k and 5b-k. This information is available free of charge via the
Internet at http://pubs.acs.org.
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