New molecular entities via intermolecular meta photocycloaddition

Article abstract of DOI:10.1002/jhet.5570420208

The intermolecular meta photocycloaddition of 1,3-dihydroisobenzofuran and 1,3-dihydroisoindole-2-carboxylic acid methyl ester with cyclopentene and 2,5-dihydrofuran affords two new classes of photoadducts. The photoadducts were identified by the SORT&gen

Full text of DOI:10.1002/jhet.5570420208

March 2005
New Molecular Entities via Intermolecular meta Photocycloaddition
227
*
a
a
b
b
Dennis Piet , Serge de Bruijn , Jane Sum and Gerrit Lodder
aSpecs, Julianalaan 136, 2628 BL Delft, The Netherlands
Leiden University, Leiden Institute of Chemistry, Gorlaeus Laboratories, PO Box 9502,
b
2
300 RA Leiden, The Netherlands
Received July 21, 2004
The intermolecular meta photocycloaddition of 1,3-dihydroisobenzofuran and 1,3-dihydroisoindole-2-
carboxylic acid methyl ester with cyclopentene and 2,5-dihydrofuran affords two new classes of pho-
toadducts. The photoadducts were identified by the SORT&gen algorithm as New Molecular Entities in
two-dimensional scaffold space. The structures of the adducts were established by NMR spectroscopy and
the stereo-, regio- and chemoselectivity of the reactions is discussed.
J. Heterocyclic Chem., 42, 227 (2005).
Introduction.
atom in the tether was protected with an electron-with-
drawing acetyl or carbomethoxy group to give an aza-
triquinane as the major photoadduct [15,16]. The chemi-
cal yield was much larger with carbomethoxy than with
acetyl as the N-protecting group.
As part of our New Molecular Entities (NME) project
the software program SORT&gen was introduced [1].
Using a set of descriptors SORT&gen makes it possible to
define molecules in two-dimensional space on the basis of
their scaffold ring constructions and the position of various
functional groups and heteroatoms. When applied to the
available literature databases this two-dimensional scaf-
fold space appears to be remarkably empty. Based on the
descriptors defining the empty spaces, all of the corre-
sponding 'missing' scaffolds can be generated. This makes
SORT&gen a valuable tool in the search for New
Molecular Entities. The aim of the current research is to
get from these virtual molecules to real molecules, prefer-
ably accessible in a limited number of steps. Out of the
thousands of useful NME's we have identified two which
serve as a proof of the SORT&gen concept and which are
accessible in one single reaction step i.e., the pentacy-
As part of our NME-program we have investigated the
photochemical reaction of 1,3-dihydroisobenzofuran (1a),
1
,3-dihydroisoindole-2-carboxylic acid methyl ester (1b)
and indane (1c) with 2,5-dihydrofuran (2a), 2,5-dihy-
dropyrrole-1-carboxylic acid methyl ester (2b) and
cyclopentene (2c) as shown in Scheme 1. The identity of
the novel photoadducts was established and the regio- and
chemoselectiviy of the reactions is discussed.
Scheme 1
1
,3 2,6
clo[6.3.0.0 .0 ]tetradec-13-ene and the pentacy-
clo[6.3.0.02,12.0 ]tetradec-13-ene framework. Because
the ultimate goal is to obtain novel drug-like molecules, at
least one heteroatom must be part of the scaffold.
3,7
The meta photocycloaddition of benzenes to alkenes is
an elegant method to construct, in one single reaction step,
complex polycyclic ring systems. Numerous examples of
both inter- and intramolecular meta photocycloaddition
reactions are known [2]. Photochemical reactions of
arenes with oxygen-containing alkenes such as 1,3-diox-
ole, dihydrofurans and -pyrans [3-8] are well documented
to give ortho, meta and para adducts. Intramolecular pho-
tocycloaddition reactions of pent-4-enylbenzenes with an
oxygen atom at the α-, β- or γ position of the side chain
give mainly meta adducts [9-11]. Photochemical reactions
of nitrogen containing arenes in which the nitrogen atom is
part of the aromatic ring or adjacent to the ring do not
result in meta addition but yield fragmentation, ortho [12]
and/or para addition [13] and other 1:1-photoaddition
products [13,14]. However, Blackmore and Gilbert
reported the successful intramolecular meta photocycload-
dition of 3-benzylazaprop-1-enes in which the nitrogen
Table 1
Formation of Photoadducts 3 and 4 and their Product Distribution
Arene
Olefin
Adduct [a]
1a
1a
2a
2b
2c
2a
2b
2c
2a
2b
2c
3aa:4aa (9:4)
---
1
1
1
1
a
b
b
b
3ac:4ac (9:4)
---
---
3bc:4bc (8:5)
1c
1c
---
---
---
1
c
[
a] Ratios according to GC in the crude irradiation mixtures prior to workup.

2
28
D. Piet, S. de Bruijn, J. Sum and G. Lodder
Vol. 42
Results and Discussion.
and 3bc, respectively. Therefore photoadducts 3 were
assigned the endo configuration. This assignment is sup-
ported by the chemical shift of H7. Comparison of the
available H NMR data on endo and exo adducts shows
that this shift is a valuable tool to distinguish between both
Irradiation of 1,3-dihydroisobenzofuran (1a) in acetoni-
trile in the presence of 2,5-dihydrofuran (2a) or cyclopen-
tene (2c) at λexc = 254 nm for 76 h resulted in an about
1
6
5% conversion into two regioisomeric photoadducts, the
configurations. In endo adducts H7 is found between δ
propellane derivatives 3 and the tetraquinanes 4 with 35%
of starting arene 1a left. Under identical circumstances
2
2
.90-3.50 while in exo adducts H7 resonates between δ
.10-2.30 [11]. This profound up-field shift of H7 in exo
1
b reacted with 2c to ca 90% of the adducts 3 and 4 with
adducts can be attributed to the shielding effect by the C9-
C10 double bond [20,21]. The chemical shifts of H7 in the
propellane derivatives 3 are all above δ 3.10 (Table 2).
In the case of the tetraquinane photoadducts 4 the dihe-
dral angle between H7 and H8 was PM3-calculated to be
ca 40° for the endo and ca. 85° for the exo configuration.
The coupling between H7 and H8 in exo-adducts has
indeed been shown to be too small to be determined [11].
The J8,7-value of adduct 4ac was found to be 5.9 Hz.
Unfortunately the multiplicity of H8 in 4bc could not be
established as it appeared as a broadened singlet in the
less than 10% of 1b remaining. In all cases more 3 than 4
is produced. All other arene-alkene combinations studied
only yielded either trace amounts of photoproducts which
could not be isolated nor identified or did not react at all.
The formation of photoadducts 3 and 4 and their product
distribution are summarised in Table 1. After evaporation
of the solvent, the irradiation mixtures were taken up in
ethylacetate and polymeric material was filtered off. The
filtrates were evaporated and purified by preparative GC.
The structures of the photoadducts were determined using
1
NMR spectroscopy. The H-NMR data of the relevant
bridgehead protons of the photoadducts 3 and 4 are pre-
sented in Table 2.
1
H-NMR spectrum at δ 3.00. The position of H7 in 4bc
coincides with that of the carbomethoxy group thus
obscuring its multiplicity. However, a relatively strong
correlation between H7 and H8 is observed in the 2D-
NOE spectrum of 4bc. Therefore photoadducts 4 are also
assigned the endo configuration. The low-field position
of H7 of both 4ac (δ 3.56) and 4bc (δ 3.70) is consistent
with this assignment.
Table 2
1H-NMR data of Photoadducts 3 and 4[a]
Adduct
H-2
H-3
H-7
H-8
H-9
H-10
H-11
The preferred formation of endo adducts has previously
been observed in the irradiation of tetralin and xylenes in
the presence of various alkenes [22-27]. The preference is
the result of an intermolecular hyperconjugation between
3
3
4
3
4
aa
ac
ac
bc
bc
1.84
1.81
---
1.80
---
3.30
3.04
2.62
3.03
2.85
3.39
3.14
3.56
3.12
3.71
---
---
2.81
---
5.63
5.62
5.69
5.62
5.74
5.88
5.81
5.76
5.75
5.80
1.95
1.86
1.96
1.85
1.87
2
3.00
the allylic CH -groups of the alkene and the sp carbon
2
atoms of the aromatic ring [28]. This effect can only occur
in the endo approach of the reagents despite the increased
steric hindrance involved in this mode of addition.
[a] No conclusive spectroscopical data of 4aa could be obtained.
Regioselectivity.
Stereoselectivity.
The ratio in which 3 and 4 are produced (~2:1) is similar
to that of the meta-adducts of o-xylene and cyclopentene
[22,29]. The preference for production of 3 over 4 is
ascribed to the asymmetrical partitioning of complex I,
Cyclic alkenes such as 1a-c can be oriented towards the
arene, when adding, yielding endo-adducts, or away from
the arene, yielding exo-adducts [2,6]. The stereochemical
orientation of the addends in the photoadducts 3 and 4 was
established with NMR spectroscopy. The degree of cou-
pling between vicinal protons can be predicted on the basis
of the magnitude of the dihedral angles. This makes it pos-
sible to distinguish between the endo or exo configuration
of the photoadducts. The dihedral angle between H2 and
H3 in the PM3-optimised [17] structure of propellane 3 is
ca 20° for the endo configuration and 110° for the exo con-
figuration. The Karplus relation [18,19] predicts medium-
sized coupling between H2 and H3 in the case of the endo
adduct and a small or virtually absent one in the case of the
exo adduct. The J2,3-values of the propellane derivatives
were found to be 6.5 Hz, 6.1 Hz and 6.6 Hz for 3aa, 3ac
formed between the S -state of the arene and the S -state
1
0
of the olefin, into adducts 3 and 4 (Figure 1).
The major photoadduct 3 is the result of the formation of
the three-membered ring between C1 and C5 while 4 is the
result of a C1-C3 closure. The direction of the closure is
affected by substituents at the arene [30]. Because there is
a certain degree of charge transfer between the addends
from the cycloalkene to the excited benzene an electron-
accepting substituent at the site of the addition will promote
bond formation at the carbon atom to which it is attached.
3
That carbon atom (C2) will attain sp character earlier than
the other one (C6) and it will draw its neighbours closer
together, thus promoting ring closure on this side. The

March 2005
New Molecular Entities via Intermolecular meta Photocycloaddition
229
Figure 1
opposite will be true for electron-donating substituents at
the arene. Since the –CH XCH – substituent at the arene
Photochemical Reactor RPR 200 fitted with five 254 nm lamps,
placed in a room cooled to 4 °C. The progress of the reactions
was followed by GC. The analyses of the irradiation mixtures
were performed on a Varian 3400 GC (CpSil-5, 25 m x 0.25
2
2
(
X = O, N(COOMe)) is weakly electron donating [32], C2
2
will retain its sp character longer, leading to preferred clo-
sure of the three-membered ring between C1 and C5 and
thus to the preferred formation of 3.
mm, d 0.40 µ, carrier gas H ) equipped with a FID. Mass spec-
f
2
tra were obtained on a HP 5890 GC with a HP5920 MS detector
DBX-4, 25 m x 0.25 mm, d 0.25 µ, carrier gas H ). Accurate
(
f
2
mass measurements were obtained on a VG-70SE mass spec-
trometer at 50 eV and 70 eV. Isolation by means of preparative
gas chromatography was performed on an Intesmat model 120
Chemoselectivity.
Although indane (1c) was been reported to undergo
meta photocycloaddition with vinylacetate [32], it appears
unreactive towards alkenes 2a-c. Tetralin on the other
hand, the next homologue of 1c, has been reported to
undergo meta photocycloaddition with 2c [27]. The lower
quantum yield of the reaction of tetralin with 2c compared
to the reaction of o-xylene with 2c (φ = 0.01 and 0.08,
respectively) indicates that an increase in ring strain leads
to a decrease in quantum yield. The reluctance of the even
more strained 1c to react with cyclopentenes 2a-c is in line
with this observation. The non-reactivity of 1b with 2a
remains unexplained at the moment.
Photoadducts were also not detected in the reaction of
alkene 2b with arenes 1a-c. Efficient quenching of the flu-
orescence of aromatic compounds by carbamates has been
reported by several groups [33,34]. The quenching pre-
sumably involves partial electron transfer away from the
excited arene, a process that is known to be detrimental to
the formation of meta photocycloadducts [22,35].
1
13
(10% CP-sil-5, 25 m x 25 mm, carrier gas H2). H- and C-
NMR spectrometry was performed on a Varian VXR 400S
1
13
operating at 400 MHz for H-NMR and at 100 MHz for C-
NMR. All spectra were recorded in CDCl with TMS as the
3
internal standard.
Starting Materials.
Compounds 1a, 1c, 2a and 2c are commercially available
(Acros) and were used without further purification.
1,3-Dihydroisoindole-2-carboxylic Acid Methyl Ester (1b).
To a suspension of 1,2-bis-bromomethylbenzene (5.00 g, 18.9
mmol) and NaH (60% in mineral oil, 1.65 g, 40.7 mmol) in 10 ml
of dry dimethylformamide was added dropwise at 0 ºC a solution
of methyl carbamate (1.25 g, 16.7 mmol) in 5 ml of dry dimethyl-
formamide. The reaction mixture was stirred overnight at room
temperature and poured on ice. The resulting precipitate was col-
lected and purified by flash chromatography (silica gel, 3:1 petro-
leum ether (bp 40-60 ºC)/ethylacetate) to yield 1b (1.46 g, 8.25
mmol, 49%) as light yellow crystals, mp 88-89 ºC (lit 89 ºC) [36];
1H-NMR δ 7.30 (m, 4H), 4.85 (d, 4H), 3.67 (s, 3H).
2
,5-Dihydropyrrole-1-carboxylic Acid Methyl Ester (2b).
In conclusion, this work shows that new molecules with
unique scaffolds can be synthesized in a quite limited num-
ber of steps. Thus, in a single reaction step the meta pho-
tocycloaddition reaction of functionalized indanes and
cyclopentenes yields some new molecular entities (NME)
which occupy an empty scaffold space as identified by the
SORT&gen program. Our research towards the synthesis
of NME's continues.
To a suspension of 2,5-dihydro-1H-pyrrole (1.00 g, 14.7
mmol) and potassium carbonate (4.02 g, 29.1 mmol) in 10 ml of
water cooled to 0 °C was added dropwise methyl chloroformate
(1.40 g, 14.8 mmol). The reaction mixture was stirred for 30
minutes at room temperature and extracted with 3 x 20 ml of
ether. The combined organic layers were washed with 25 ml of
brine, dried over magnesium sulfate and evaporated to yield 2b
(1.45 g, 11.4 mmol, 78%) as a colorless oil which solidified on
1
standing, mp: 37-38 °C (lit. 37-39 °C) [37]; H-NMR δ 5.82 (d,
2
H), 4.11 (d, 4H), 3.67 (s, 3H).
EXPERIMENTAL
Photoproducts.
The irradiations were carried out using spectroscopic grade
acetonitrile as solvent in quartz vessels in a Rayonet
Mixtures of 0.5 M of 1,3-dihydroisobenzofuran (1a) and 1.5 M
of 2,5-dihydrofuran (2a), 0.5 M of 1,3-dihydroisobenzofuran (1a)

230
D. Piet, S. de Bruijn, J. Sum and G. Lodder
Vol. 42
and 1.5 M of cyclopentene (2c) and of 0.5 M of 1,3-dihydroisoin-
dole-2-carboxylic acid methyl ester (1b) and 1.5 M of cyclopen-
tene (2c) were irradiated for 76 h followed by the removal of the
solvent. Irradiation of 1a in the presence of 2a and 2c resulted in
a ca 65% conversion into the two photoadducts 3 and 4 in a 9:4
ratio with 35% of starting arene 1a left. Under identical circum-
stances 1b reacted with 2c to ca 90% of the adducts 3 and 4 in an
(15), 143 (210, 142 (16), 130 (37), 129 (84), 128 (36), 119 (43),
117 (25), 115 (57), 92 (75), 91 (100), 78 (21), 77 (28), 68 (23), 65
(30). HRMS: Calcd. for 188.1201, found: 188.1200.
1
0-Azapentacyclo[6.3.01,3.02,6]tetradec-13-ene 10-Carboxylic
2
,12 3,7
Acid Methyl Ester (3bc) and 3-Azapentacyclo[6.3.0 .0 ]-
tetradec-13-ene 10-Carboxylic Acid Methyl Ester (4bc).
8
:5 ratio with less than 10% of 1b remaining. The resulting mix-
The irradiation and purification procedure yielded 19 mg of
1
tures were taken up in ethylacetate and polymeric material was
filtered off. The filtrates were evaporated and purified by prepar-
ative GC.
3bc and 7 mg of 4bc, both as colourless oils. Adduct 3bc H-
NMR: (CDCl3) δ 5.75 (dd, 1H, H-10, J10,9 = 5.3 Hz, J10,11 = 2.1
Hz), 5.62 (d, 1H, H-9, J9,10 = 5.0 Hz), 3.88 (m, 1H, H-12), 3.65
(
3
s, 3H, -CH ), 3.60 (m, 2H, H-12', H-13), 3.20 (m, 1H, H-13'),
.12 (m, 1H, H-7), 3.03 (m, 1H, H-3), 1.87 (m, 1H, H-4), 1.85
3
6
,10-Dioxapentacyclo[6.3.01,3.02,6]tetradec-13-ene (3aa).
The irradiation and purification procedure yielded 17 mg of
aa and 4 mg of a mixture of 3aa and 4aa. From the later mix-
(m, 1H, H-11), 1.80 (broadened t, 1H, H-2, J = 6.6 Hz), 1.60-1.45
1
3
3
(m, 5H, H-4', H-5, H-6). C-NMR [38]: δ 155.73 (s),
135.67/135.42 (2d), 131.84/131.81 (2d), 69.68/68.66 (2s), 67.94
(d), 60.62/59.81 (2s), 53.89/53.49 (2t), 52.34 (q), 50,69 (d),
48.27/47.88 (2t), 36.47 (d), 35.71 (d), 30.05 (t), 29.53 (t), 25.67
(t). MS (m/e): 245 (55), 230 (14), 216 (10), 176 (40), 162 (99),
158 (24), 157 (26), 156 (27), 143 (24), 129 (75), 128 (53), 118
(49), 117 (36), 116 (27), 115 (62), 102 (31), 91 (48), 77 (27), 67
(23), 59 (100). HRMS: Calcd. for 245.1416, found 245.1416.
ture no conclusive spectroscopic data could be obtained. Adduct
1
3
aa H-NMR: (CDCl ) δ 5.88 (dd, 1H, H-10, J
= 5.2 Hz,
3
10,9
J10,11 = 2.1 Hz), 5.63 (d, 1H, H-9, J9,10 = 5.2 Hz), 4.19 (d, 1H, H-
2, J12,12'=9.1 Hz), 3.96 (d, 1H, H-13, J13,13' = 9.1 Hz), 3.92 (d,
H, H-12', J12',12 = 9.1Hz), 3.73 (dd, 1H, H-4, J4,3 = 10.0 Hz, J4,4'
1
1
=
8.1Hz), 3.72 (d, H1, H-6, J6,6' = 9.5 Hz), 3.60 (dd, 1H, H-4',
J4',4 = 8.1 Hz, J4',3 = 6.2 Hz), 3.53 (dd, 1H, H-6', J6',6 = 9.5 Hz,
J6',7 = 5.5 Hz), 3.49 (d, 1H, H-13', J13',13 = 9.1 Hz), 3.39 (dd, 1H,
H-7, J7,3 = 10.0 Hz, J7,6' = 5.5 Hz), 3.30 (tt, 1H, H-3, J3,4 = 10.0
Hz, J3,7 = 10.0 Hz, J3,2 = 6.2Hz, J3,4' = 6.2Hz), 1.95 (dd, 1H, H-
1, J11,2 = 6.5 Hz, J11,10 = 2.1 Hz), 1.84 (broadened t, 1H, H-2,
J2,3 = 6.5 Hz, J2,11 = 6.5 Hz). 13C-NMR: δ 133.26 (d), 131.45 (d),
4.45 (t), 72,68 (s), 70.90 (t), 68.00 (t), 68.22 (d), 68.17 (t), 63.24
s), 49.54 (d), 34.20 (d), 33.07 (d). MS (m/e): 190 (0), 142 (3),
31 (8), 130 (22), 129 (100), 128 (42), 117 (13), 115 (67), 92
22), 91 (40), 77 (14). HRMS: Calcd. for 190.0994, found
1
Adduct 4bc H-NMR: δ 5.80 (dd, 1H, H-10, J10,9 = 5.6 Hz,
J10,11 = 2.4 Hz), 5.74 (ddd, 1H, H-9, J9,10 = 5.6 Hz, J9,8 = 2.7 Hz,
J9,11 = 0.7 Hz) 3.90 (d, 1H, H-12. J=10.5Hz), 3.75-3.50 (m, 3H,
H-7, H-12', H-13), 3.64 (s, 3H, -CH3), 3.40 (d, 1H, H-13', J13',13
= 11.0 Hz), 3.00 (broadened t, 1H, H-8), 2.85 (m, 1H, H-3), 1.90
(m, 1H, H-4), 1.87 (m, 1H, H-11), 1.65-1.50 (m, 5H). 13C-NMR
[38]: δ 155.34 (s), 136.41/136.34 (2d), 130.22/130.16 (2d), 68.56
1
7
(
1
(
(d), 63.17/62.35 (2s), 56.53/56.02 (2t), 53.31 (d), 52.94 (d), 52.22
(q), 49.23/48.73 (2t), 47.48/46.59 (2s), 43.74 (d), 30.12 (t), 29.49
(t), 25.97 (t). MS (m/e): 245 (30), 177 (17), 176 (51), 163 (10),
1
90.0988.
1
62 (100), 158 (19), 157 (14), 143 (12), 130 (21), 129 (42), 128
1
0-Oxapentacyclo[6.3.01,3.02,6]tetradec-13-ene (3ac) and 3-
(
(
27), 118 (39), 117 (30), 116 (18), 115 (36), 102 (10), 91 (36), 89
11), 78 (11), 77 (18), 67 (16), 59 (72). HRMS: Calcd. for
Oxapentacyclo[6.3.0 .03,7]tetradec-13-ene (4ac).
2,12
The irradiation and purification procedure yielded 22 mg of
ac and 16 mg of 4ac, both as colourless oils. Adduct 3ac H-
245.1416, found 245.1418.
1
3
Acknowledgment.
NMR: (CDCl ) δ 5.81 (dd, 1H, H-10, J
= 5.2 Hz, J10,11 = 2.0
3
10,9
Hz), 5.62 (dd, 1H, H-9, J9,10 = 5.2 Hz, J9,11 = 0.7 Hz), 4.16 (d,
We thank Dr. R.V.A. Orru and Mr. R. Schmitz of the Free
University of Amsterdam, The Netherlands for their hospitality
and help with the preparative GC. We also appreciate the fruitful
discussions with Prof. Dr. J. Cornelisse of Leiden University.
1
H, H-12, J12,12' = 9.0 Hz), 3.89 (2d, 2H, H-12', H-13, J12',12
=
9
.0 Hz, J13,13' = 9.0 Hz), 3.51 (d, 1H, H-13', J13',13 = 9.0 Hz), 3.14
(
m, 1H, H-7), 3.04 (m as broadened dq, 1H, H-3, J3,4 = 9.1 Hz,
J3,7 = 9.1 Hz, J3,2 = 6.1 Hz, J3,4' = 6.1 Hz), 1.86 (dd, 1H, H-11,
J11,2 = 7.0 Hz, J11,10 = 2.0 Hz), 1.81 (dd, 1H, H-2, J = 7.0 Hz,
2,11
REFERENCES AND NOTES
1
3
J2,3 = 6.1 Hz), 1.70-1.40 (m, 6H, H-4, H-5, H-6). C-NMR: δ
1
6
2
34.76 (d), 132.76 (d), 75.24 (t), 73.00 (s), 69.30 (t), 66.35 (d),
3.22 (s), 51.55 (d), 36.02 (d), 33.61 (d), 30.50 (t), 29.82 (t),
5.97 (t). MS(m/e): 188 (15), 159 (11), 157 (13), 143 (14), 130
*
Corresponding author. tel.: +31-15-2577930; fax: +31-15-
2
566090; e-mail: dennis.piet@specs.net
1] A. De Laet, J. J. Hehenkamp and R. L. Wife, J. Heterocyclic
Chem. 37, 669 (2000).
[
(36), 129 (100), 128 (39), 119 (16), 117 (18), 116 (23), 115 (56),
9
2 (34), 91 (55), 77 (18), 67 (15), 65 (16), 51 (14). HRMS: Calcd.
[
2] For comprehensive reviews see: [a] P. A. Wender, L. Siggel
1
for 188.1201, found: 188.1212. Adduct 4ac H-NMR: (CDCl ) δ
5
Hz), 5.69 (ddd, 1H, H-9, J9,10 = 5.2 Hz, J9.8 = 2.8 Hz, J9,11 = 0.7
Hz), 4.12 (d, 1H, H-12, J12,12' = 7.9 Hz), 3.98 (d, 1H, H-13, J13,13'
and J. M. Nuss, in Comprehensive Organic Synthesis, Vol 5, B.M. Trost,
I. Fleming and L. A. Paquette, eds. Pergamon, Elmsford, New York,
1991, pp 357-473; [b] J. Cornelisse, Chem. Rev. 93, 615-669 (1993); [c]
P. A. Wender and T. M. Dore, in Handbook of Organic Photochemistry
and Photobiology; W. S. Horspool and P.-S. Son, eds. CRC Press Inc,
Boca Raton, FL. 1995, pp 280-290; [d] N. Hoffmann, Synthesis, 481
2004).
3] R. J. Atkins, G. I. Fray, M. G. B. Drew, A. Gilbert and G. N.
Taylor, Tetrahedron Lett. 2945 (1978).
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577 (1979).
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3
.76 (ddd, 1H, H10, J10,9 = 5.7 Hz, J10,11 = 2.3 Hz, J10,8 = 0.9
=
8.5 Hz), 3.89 (d, 1H, H-12', J12',12 = 7.9 Hz), 3.72 (d, 1H, H-13',
J13'13 = 8.6 Hz), 3.56 (m, 1H, H-7), 2.81 (dd, 1H, H-8, J8,7 = 5.9
Hz, J8.9 = 2.8 Hz), 2.62 (ddd as q, 1H, H-3, J3,7 = 9.6 Hz, J3,4
(
=
[
9
4
.6 Hz, J3,4' = 9.6 Hz), 1.96 (m, 1H, H-11), 1.70-1.40 (m, 6H, H-
, H-5, H-6). 13C-NMR: δ 136.88 (d), 131.04 (d), 77.40 (t), 69.93
[
(d), 69.07 (t), 66.46 (s), 52,12 (d), 51.97 (d), 49.41 (s), 42.80 (d),
3
0.79 (t), 30.20 (t), 26.75 (t). MS(m/e): 188 (17), 158 (15), 157

March 2005
New Molecular Entities via Intermolecular meta Photocycloaddition
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[
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13
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bond is observed in both photoadducts 3bc and 4bc. Especially in the C-
NMR spectra double resonances were observed for the vinylic carbons as
well as the secondary and quaternary carbons of the pyrrolidine ring.
[