Complete control of regioselectivity in the intramolecular [2 + 2] photocycloaddition of 2-alkenyl-3(2H)-furanones by the length of the side chain

Article abstract of DOI:10.1021/jo0264372

The 2-(ω-alkenyl)-substituted 2-methyl-3(2H)-furanones 2a and 2b were prepared from biacetyl (3) in four reaction steps and in overall yields of 20% and 21%, respectively. They underwent a clean intramolecular [2 + 2] photocycloaddition upon irradiation a

Full text of DOI:10.1021/jo0264372

Com p lete Con tr ol of Regioselectivity in th e
In tr a m olecu la r [2 + 2] P h otocycloa d d ition
of 2-Alk en yl-3(2H)-fu r a n on es by th e Len gth
of th e Sid e Ch a in
Thorsten Bach,*,† Michael Kemmler,† and
Eberhardt Herdtweck‡
Lehrstuhl fu¨r Organische Chemie I and Lehrstuhl fu¨r
Anorganische Chemie, Technische Universita¨t Mu¨nchen,
D-85747 Garching, Germany
F IGURE 1. Suggested2 structure for lactiflorin (1) and
irradiation precursors 2a and 2b.
thorsten.bach@ch.tum.de
Received September 11, 2002
SCHEME 1. P r ep a r a tion of Com p ou n d s 2a a n d 2b
fr om Bia cetyl (3)
Ab st r a ct : The 2-(ω-alkenyl)-substituted 2-methyl-3(2H)-
furanones 2a and 2b were prepared from biacetyl (3) in four
reaction steps and in overall yields of 20% and 21%,
respectively. They underwent a clean intramolecular [2 +
2] photocycloaddition upon irradiation at λ ) 350 nm.
Whereas compound 2a reacted in the expected manner and
yielded 7-oxabicyclo[3.2.1.03,6]octane 7 (87% yield), the re-
gioselectivity in the photocycloaddition of compound 2b was
completely reversed. The reaction led to compound 8 (92%
yield) with the unusual 9-oxabicyclo[4.2.1.03,8]nonane skel-
eton, the structure of which was established by single-crystal
X-ray crystallography.
In 1983, a new monoterpene glycoside was isolated
from P. lactiflora and was named lactiflorin.1 The same
compound has been isolated more recently from the
related species P. anomala var. intermedia (C. A. Mey.)
O. & B. Fedtsch.2 On the basis of spectral data two
structures2,3 have been proposed for lactiflorin which
mainly differ in the tricyclic monoterpene backbone. One
of the proposed structures is depicted in Figure 1 as
formula 1. It exhibits a 7-oxabicyclo[4.2.1.03,8]nonane
skeleton that could be accessible by an intramolecular
[2 + 2] photocycloaddition of a cyclic oxaenone.4 Along
these lines, 2-(3-butenyl)-2-methyl-3(2H)-furanone 2b
appeared to be a suitable test substrate to evaluate the
regio- and stereochemistry of the photocycloaddition.
Previous work by Margaretha et al.5 had revealed that
the photocycloaddition of a 2-(2-propenyl)-substituted
3(2H)-furanone (vide infra) proceeds with the desired
regioselectivity, i.e., by a C-C bond formation between
the terminal alkene carbon atom and the carbon atom
C-4 of the heterocycle. In this note, we report on the
preparation of compounds 2a and 2b and their intramo-
lecular [2 + 2]-photocycloaddition reactions. Contrary to
our initial considerations, compound 2b delivered a
9-oxabicyclo[4.2.1.03,8]nonan-7-one but not the desired
7-oxabicyclo[4.2.1.03,8]nonane skeleton.
Starting from biacetyl (3), one carbonyl group of which
was protected via its silyl enol ether, addition of the
appropriate Grignard reagent yielded the alcohols 4a and
4b (Scheme 1). Their conversion to the 3(2H)-furanones
5 was conducted as previously described5 by a Claisen
condensation and a subsequent acid-promoted cycliza-
tion. The hydroxymethyl group was installed by a Bay-
lis-Hillman reaction.6 To the best of our knowledge
3(2H)-furanones have not yet been used as substrates in
this type of reaction.7 In our study, an aqueous solution
(30% w/w) of formaldehyde was employed as the source
of the electrophile (4 equiv).8 Various catalysts (DMAP,
PBu3, DABCO, DBU) were tested to achieve a chemose-
lective and fast transformation. DBU9 promoted an
† Lehrstuhl fu¨r Organische Chemie I.
‡ Lehrstuhl fu¨r Anorganische Chemie.
(1) Lang, H. Y.; Li, S. Z.; Liang, X. T. Acta Pharm. Sin. 1983, 18,
551.
(2) Yu, J .; Elix, J . A.; Iskander, M. N. Phytochemistry 1990, 29, 3859.
(3) Lang, H. Y.; Li, S. Z.; Wang, H. B.; Yu, D. Q.; Liang, X. T.
Tetrahedron 1990, 46, 3123.
(4) Reviews: (a) Fleming, S. A.; Bradford, C. L.; Gao, J . J. Molecular
and Supramolecular Photochemistry: Organic Photochemistry; Rama-
murthy, V., Schanze, K. S., Eds.; Dekker: New York, 1997; Vol. 1, p
187. (b) Bach, T. Synthesis 1998, 683. (c) Pete, J .-P. Adv. Photochem.
1996, 21, 135. (d) Mattay, J .; Conrads, R.; Hoffmann, R. In Methoden
der Organischen Chemie (Houben-Weyl) 4te Aufl.; Helmchen, G.,
Hoffmann, R. W., Mulzer, J ., Schaumann, E., Eds.; Thieme, Stuttgart
1995; Vol. E 21c, p 3085. (e) Crimmins, M. T.; Reinhold, T. L. Org.
React. 1993, 44, 297. (f) Crimmins, M. T. Chem. Rev. 1988, 88, 1453.
(g) Baldwin, S. W. Org. Photochem. 1981, 5, 123.
(6) Review: Ciganek, E. Org. React. 1997, 51, 201.
(7) Baylis-Hillman reaction of a 2(5H)-furanone: Franck, X.; Fi-
gadere, B. Tetrahedron Lett. 2002, 43, 1449.
(5) Gebel, R. C.; Margaretha, P. Helv. Chim. Acta 1992, 75, 1633.
10.1021/jo0264372 CCC: $25.00 © 2003 American Chemical Society
Published on Web 02/01/2003
1994
J . Org. Chem. 2003, 68, 1994-1997

SCHEME 2. In tr a m olecu la r [2 + 2]
P h otocycloa d d ition of Com p ou n d s 2a , 2b, a n d 5b
F IGURE 2. A molecule of compound 8 in the crystal.
tional two dimensional NMR experiments strongly sug-
gested structure 8. A HMBC experiment, for instance,
2
3
revealed a J CH or J CH coupling of the CH2OBz protons
to two quaternary (C-7, C-8) and two tertiary (C-1, C-3)
carbon atoms. Final proof for the structure assignment
was obtained by single-crystal X-ray crystallography
(Figure 2).11
To study the influence of the substituent in 4-position
of the 3(2H)-furanone on the regioselectivity the unsub-
stituted substrate 5b was submitted to the conditions of
a [2 + 2] photocycloaddition. NMR data revealed that the
regioselectivity of this reaction is the same as that
observed for 2b, and structure 9 was consequently
assigned to the product. Again, the reaction proceeded
quantitatively and without the formation of any side
products. In this respect, the intramolecular [2 + 2]
photocycloaddition allows for a rapid and high yielding
access to the hitherto unknown parent 9-oxabicyclo-
[4.2.1.03,8]nonane skeleton.
extremely fast reaction but delivered several side prod-
ucts, which were difficult to separate from the desired
product. Side reactions were also observed with varying
amounts of DMAP or PBu3. The use of DABCO (0.2
equiv) in THF turned out to be superior. It allowed a
clean conversion to the desired products, although the
reaction velocity was not fully satisfactory. Routinely, the
reactions were stopped after 48 h at about 50% conver-
sion. The separation of the products 6 was easy, and the
starting materials 5 could be recovered. The yields given
in Scheme 1 for the transformation 5 f 6 are based on
recovered starting material. A subsequent benzoylation
of the corresponding primary alcohols 6 with benzoyl (Bz)
chloride and pyridine in CH2Cl2 delivered the desired
photocycloaddition substrates.
The question why this mode of C-C bond formation is
so strongly favored and why the regioselectivity is
completely reversed while going from 2a to 2b or from
Irradiation in benzene at λ ) 350 nm (Rayonet RPR
3500 Å) converted compound 2a exclusively into the
tricyclic product 7 (Scheme 2). The regioselectivity was
proven by comparison of the spectral data with those of
the previously reported parent 7-oxabicyclo[3.2.1.03,6]-
octan-2-one.5 The hydrogen atom H-6 accounts for a
(11) (a) Crystal structure analysis of 8: C17H18O4, Mr ) 286.31,
triclinic, space group P1h, a ) 7.408(2), b ) 10.275(5), c ) 10.768(3) Å,
R ) 68.44(3)°, â ) 84.42(2)°, γ ) 69.68(3)°, V ) 714.4(5) Å3; Z ) 2;
Fcalc ) 1.331 g cm-3, F000 ) 304, µ ) 0.094 mm-1. A suitable single
crystal for the X-ray diffraction study was obtained from a EA/P
solution at 4 °C. The selected crystal was coated with perfluorinated
ether, fixed in a capillary, and transferred to the diffractometer and
the cold nitrogen flow. Preliminary examination and data collection
were carried out on a four-circle diffractometer with graphite mono-
chromated Mo KR radiation (λ ) 0.71073 Å; sealed tube). Data
collection were performed at 153 K within the θ range of 2.03° < θ <
25.98°. A total of 5579 reflections were integrated and corrected for
Lorentz and polarization effects. After merging (Rint ) 0.0254), 2795
[2406: Io > 2σ(Io)] independent reflections remained and all were used
to refine 262 parameters. The structure was solved by a combination
of direct methods and difference Fourier syntheses. All non-hydrogen
atoms were refined anisotropically. All hydrogen atom positions were
found in the difference Fourier map calculated from the model
containing all non-hydrogen atoms. The hydrogen positions were
refined with individual isotropic displacement parameters. Full-matrix
doublet at 5.05 ppm with a coupling constant of J HH
)
4.3 Hz. By a COSY experiment the hydrogen atom H-5
was identified as the atom responsible for the J HH
coupling to H-6, and it was unambiguously proven by a
HMQC experiment that this hydrogen atom is attached
to a tertiary carbon atom (C-5). As previously alluded to,
this regioselectivity was expected on the basis of the
charge distribution in the excited state (T1).4a,10
The intramolecular photocycloaddition of substrate 2b
proceeded smoothly and yielded a single product. The
NMR data of the product did, however, not match the
expected structure. The hydrogen atom next to the furan
oxygen atom, which resonates at 4.56 ppm and which is
the direct analogue to H-6 in compound 7, did not produce
a doublet. It rather gave a doublet of doublets with
J HH ) 4.5 Hz and J HH ) 5.2 Hz. This result and addi-
2
2 2
least-squares were carried out by minimizing w(Fo - Fc
) and
converged with R1 ) 0.0360 [Io > 2σ(Io)], wR2 ) 0.0989 [all data],
GOF ) 1.044 and shift/error < 0.001. Neutral atom scattering factors
for all atoms and anomalous dispersion corrections for the non-
hydrogen atoms were taken from International Tables for Crystal-
lography. Crystallographic data (excluding structure factors) for the
structure reported in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publication
no. CCDC-197904. Copies of the data can be obtained free of charge
on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(fax: (+44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk); a CIF file
is available as Supporting Information. (b) Altomare, A.; Cascarano,
G.; Giacovazzo, C.; Guagliardi, A.; Burla, M. C.; Polidori, G.; Camalli,
M. SIR92. J . Appl. Crystallogr. 1994, 27, 435. (c) Spek, A. L. PLATON,
A Multipurpose Crystallographic Tool; Utrecht University: Utrecht,
The Netherlands, 2001. (d) Sheldrick, G. M. SHELXL-97; Universita¨t
Go¨ttingen: Go¨ttingen, Germany, 1998.
(8) For examples of the Baylis-Hillman reaction of cyclic enones
with formaldehyde, see: (a) Rezgui. F.; El Gaied, M. M. Tetrahedron
Lett. 1998, 39, 5965. (b) Banwell, M. G.; Crasto, C. F.; Easton, C. J .;
Karoli, T.; March, D. R. Nairn, M. R.; O’Hanlon, J . O.; Oldham, M. D.;
Willis, A. C.; Yue, W. Chem. Commun. 2001, 2210. (c) Aggarwal V.
K.; Dean, D. K.; Mereu, A.; Williams, R. J . Org. Chem. 2002, 67, 510.
(d) Kabat, M. M.; Kiegiel; J . Cohen, N.; Wovkulich, P. M.; Uskokovic,
M. R. J . Org. Chem. 1996, 61, 118.
(9) Aggarwal, V. K.; Mereu, A. Chem. Commun. 1999, 2311.
(10) Margaretha, P. Chimia 1975, 29, 203.
J . Org. Chem, Vol. 68, No. 5, 2003 1995

3-Hyd r oxy-3-m eth yl-h ep t-6-en -2-on e (4b) was prepared
from biacetyl (3, 3.50 mL, 40 mmol) according to a previously
published procedure.17 The product was purified by distillation
(2 mbar, 57-60 °C) to give product 4b (3.24 g, 22.8 mmol, 57%)
as a colorless oil: 1H NMR (250 MHz, CDCl3) δ 1.36 (s, 3 H),
1.75 (br s, 1 H), 1.85-1.70 (m, 2 H), 2.21 (s, 3 H), 2.35-2.11 (m,
2 H), 4.91-4.95 (dm, J ) 9.5 Hz, 1 H), 4.96-5.03 (dm, J ) 17.2
Hz, 1 H), 5.68-5.82 (m, 1 H); 13C NMR (62.9 MHz) δ 23.6 (q),
25.4 (q), 27.7 (t), 38.4 (t), 78.5 (s), 115.0 (t), 137.7 (d), 212.1 (s).
Anal. Calcd for C8H14O2 (142.20): C, 67.57; H, 9.92. Found: C,
67.50; H, 10.00.
2-Bu t-3-en yl-2-m eth yl-fu r a n -3-on e (5b) was prepared from
4b (3.30 g, 23.2 mmol) according to a previously published
procedure.5 The product was purified by distillation (15 mbar,
70-72 °C) to give compound 5b (1.72 g, 11.4 mmol, 49%) as a
colorless oil: 1H NMR (250 MHz, CDCl3) δ 1.33 (s, 3 H), 1.75-
2.20 (m, 4 H), 4.89-4.93 (dm, J ) 9.4 Hz, 1 H), 4.93-5.00 (dm,
J ) 16.4 Hz, 1 H), 5.62 (d, J ) 3.3 Hz, 1 H), 5.62-5.76 (m, 1 H),
8.17 (d, J ) 3.3 Hz, 1 H); 13C NMR (62.9 MHz) δ 21.6 (q), 27.2
(t), 35.4 (t), 89.5 (s), 105.9 (d), 115.1 (t), 137.1 (d), 176.6 (d), 207.2
(s). Anal. Calcd for C9H12O2 (152.19): C, 71.03; H, 7.95. Found:
C, 70.46; H, 8.01.
F IGURE 3. Possible conformations of compounds 5a and 5b
resulting in a regioselective [2 + 2] photocycloaddition.
5a to 5b is not fully clear. There is analogy to the work
by McMurry et al., who studied the photocycloaddition
of 5-(ω-alkenyl)-substituted 3-phenylcyclopent-2-enones.12
If the substituent was a 2-propenyl group, they obtained
bicyclo[3.2.1.03,6]octan-2-ones exclusively, whereas the
irradiation (Hanovia 450 W, Pyrex filter) of the 3-butenyl-
substituted 3-phenylcyclopen-2-enone gave a 2:1 mixture
of bicyclo[4.2.1.03,8]nonan-7-one and bicyclo[4.2.1.03,8]-
nonan-9-one. Upon further irradiation the product ratio
changed in favor of the nonan-7-one as the result of a
photochemically induced equilibration. The authors in-
voke conformational and stereoelectronic factors13 that
govern the outcome of the reaction. In our case, we did
not observe any other regioisomer throughout the reac-
tions, and a conformation as depicted for 3(2H)-furanone
5a in Figure 3 is most likely to be involved in the product
formation 2a f 7. In line with previous results obtained
with 5a ,5 the first C-C bond is formed between carbon
atom C-5 of the ring and the internal carbon atom (CH)
of the side chain to yield a 1,4-biradical, which subse-
quently collapses to the product. Given a similar confor-
mation for compound 5b (and for 2b), the first C-C bond
can only be established between carbon atom C-4 of the
ring and the internal carbon atom, leading exclusively
to the opposite regioisomer.14
Gen er a l P r oced u r e A for Ba ylis-Hillm a n Rea ction of
3(2H)-F u r a n on es. To a solution of the 3(2H)-furanone (6.58
mmol) in THF (15 mL) were added formaldehyde (30% w/w, 2.26
mL, 22.6 mmol) and DABCO (148 mg, 1.07 mmol), and the
resulting mixture was stirred at ambient temperature for 48 h.
After evaporation of the solvent the crude product was purified
by column chromatography.
2-Allyl-4-h yd r oxym eth yl-2-m eth yl-fu r a n -3-on e (6a ) was
prepared from 5a according to general procedure A. The product
was purified by column chromatography (silica, P/CH2Cl2/EA )
10/5/2 as eluent) to give 453 mg (3.28 mmol, 50%) of unchanged
5a and 364 mg (2.17 mmol, 33%) of the desired product 6a as a
colorless oil: 1H NMR (360 MHz, CDCl3) δ 1.32 (s, 3 H), 2.41 (d,
J ) 7.3 Hz, 2 H), 2.96 (br s, 1 H), 4.27 (s, 2 H), 5.06-5.08 (dm,
J ) 9.0 Hz, 1 H), 5.08-5.11 (dm, J ) 17.8 Hz, 1 H), 5.57-5.65
(m, 1 H), 8.14 (s, 1 H); 13C NMR (62.9 MHz) δ 20.9 (q), 40.5 (t),
53.2 (t), 90.1 (s), 118.2 (s), 119.8 (t), 130.5 (d), 174.0 (d), 206.3
(s). HRMS (EI) calcd for C9H12O3 168.07864, found 168.07864.
2-Bu t-en yl-4-h yd r oxym eth yl-2-m eth yl-fu r a n -3-on e (6b)
was prepared from 5b according to general procedure A. The
product was purified by column chromatography (silica, P/CH2-
Cl2/EA ) 10/5/2 as eluent) to give 530 mg (3.48 mmol, 53%) of
unchanged 5b and 471 mg (2.59 mmol, 40%) of the desired
product 6b as a colorless oil: 1H NMR (360 MHz, CDCl3) δ 1.37
(s, 3 H), 1.80-2.13 (m, 4 H), 2.15 (br s, 1 H), 4.33 (d, J ) 0.7 Hz,
2 H), 4.92-4.96 (dm, J ) 11.5 Hz, 1 H), 4.95-5.02 (dm, J )
17.5 Hz, 1 H), 5.69-5.77 (m, 1 H), 8.16 (s, 1 H); 13C NMR (90.6
MHz) δ 21.5 (q), 27.3 (t), 35.5 (t), 53.6 (t), 90.6 (s), 115.2 (s),
118.3 (t), 137.1 (d), 173.8 (d), 206.6 (s). HRMS (EI) calcd for
C10H14O3 182.09430, found 182.09438.
Gen er a l P r oced u r e B for Ben zoyla tion of Alcoh ols. A
solution of the alcohol (0.5 mmol) in CH2Cl2 (5 mL) was stirred
at 0 °C. Pyridine (42 µL, 0.52 mmol) and benzoyl chloride (61
µL, 0.52 mmol) were then added dropwise. The resulting mixture
was allowed to warm to room temperature and stirred for
another 3 h. CH2Cl2 (10 mL) and a saturated NH4Cl solution
(10 mL) were added. The organic layer was separated, and the
aqueous layer was extracted with CH2Cl2 (3 × 5 mL). The
combined organic layers were washed with a saturated NaCl
solution (10 mL) and dried (Na2SO4). After filtration and
evaporation of the solvent the crude product was purified by
column chromatography.
In summary, the intramolecular photocycloaddition of
the 2-propenyl-substituted 3(2H)-furanones 2b and 5b
produced the 9-oxabicyclo[4.2.1.03,8]nonan-7-ones 8 and
9 in almost quantitative yields (90-92%). The regiose-
lectivity is opposite to the selectivity observed with the
nor-analogues 2a and 5a . Possible synthetic applications
of the products are currently being studied.
Exp er im en ta l Section
Gen er a l. For general remarks, see ref 15. All solvents, ethyl
acetate (EA), pentane (P), and diethyl ether, for column chro-
matography were distilled prior to use. Benzene used as solvent
in irradiation experiments was thoroughly degassed immediately
prior to use by pump and freeze methodology. Allylmagnesium-
bromid and homoallylmagnesiumbromid were prepared accord-
ing to standard procedures.16 Compounds 4a 17 and 5a 5 have been
previously described. All other chemicals were commercially
available and were used without further purification.
(12) (a) McMurry, T. B. H.; Work, A.; McKenna, B. J . Chem. Soc.,
Perkin Trans. 1 1991, 811. (b) Gowda, G.; McMurry, T. B. H. J . Chem.
Soc., Perkin Trans. 1 1980, 1516.
(13) Gleiter, R.; Sander, W. Angew. Chem., Int. Ed. Engl. 1985, 24,
566.
(14) For a more detailed discussion on the influence of substituents
in similar photocycloaddition reactions based on an analysis of the
intermediate biradicals, see: (a) Cruciani, G.; Margaretha, P. Helv.
Chim. Acta 1990, 73, 288. (b) Busque´, F.; de March, P.; Figuerdo, M.;
Font, J .; Margaretha, P.; Raya, J . Synthesis 2001, 1143.
(15) Bach, T.; Bergmann, H.; Grosch. B.; Harms. K. J . Am. Chem.
Soc. 2002, 124, 7982.
Ben zoic a cid 5-a llyl-5-m eth yl-4-oxo-4,5-d ih yd r ofu r a n -3-
ylm eth ylester (2a ) was prepared from 6a according to general
procedure B. The product was purified by column chromatog-
raphy (silica, P/CH2Cl2/EA ) 20/1/1 as eluent) to give 114 mg
(0.42 mmol, 83%) of 2a as a colorless oil: 1H NMR (360 MHz,
CDCl3) δ 1.36 (s, 3 H), 2.44 (d, J ) 7.3 Hz, 2 H), 4.94 (s, 2 H),
5.01-5.04 (dm, J ) 10.0 Hz, 1 H), 5.06-5.12 (dm, J ) 17.0 Hz,
1 H), 5.57-5.64 (m, 1 H), 7.38-7.42 (m, 2 H), 7.50-7.58 (m, 1
H), 7.95-8.05 (m, 2 H), 8.39 (s, 1 H); 13C NMR (90.6 MHz, CDCl3)
δ 20.8 (q), 40.6 (t), 54.4 (t), 90.3 (s), 78.5 (s), 114.2 (s), 119.8 (t),
(16) See, for example: Harding, K. E.; Burks, S. R. J . Org. Chem.
1984, 49, 40.
(17) Compain, P.; Gore, J .; Vatele, J . M. Tetrahedron 1996, 52, 6647.
1996 J . Org. Chem., Vol. 68, No. 5, 2003

128.3 (d), 129.6 (d), 129.9 (s), 130.3 (d), 133.0 (d), 166.6 (s), 176.7
(s), 204.5 (s). Anal. Calcd for C16H16O4 (272.30): C, 70.57; H,
5.92. Found: C, 70.39; H, 6.03.
procedure C. The product was purified by column chromatog-
raphy (silica, P/CH2Cl2/Et2O ) 20/1/1 as eluent) to give 131 mg
(0.46 mmol, 92%) of 8 as a colorless solid: 1H NMR (360 MHz,
CDCl3) δ 1.34 (s, 3 H), 1.56-1.70 (m, 2 H), 2.05-2.20 (m, 2 H),
2.41-2.51 (m, 1 H), 2.81-2.88 (m, 1 H), 2.91-2.99 (m, 1 H), 4.56
(dd, J ) 5.2 Hz, 4.5 Hz, 1 H), 4.58 (d, J ) 11.8 Hz, 1 H), 4.65 (d,
J ) 11.8 Hz, 1 H), 7.41-7.46 (m, 2 H), 7.54-7.60 (m, 1 H), 7.99-
8.04 (m, 2 H); 13C NMR (90.6 MHz, CDCl3) δ 19.3 (q), 23.1 (t),
32.3 (t), 40.1 (t), 42.8 (d), 53.7 (s), 60.3 (t), 72.4 (d), 81.2 (s), 128.4
(d), 129.6 (d), 129.7 (s), 133.2 (d), 166.4 (s), 214.3 (s). Anal. Calcd
for C17H18O4 (286.31): C, 71.31; H, 6.34. Found: C, 71.38; H,
6.30.
6-Meth yl-9-oxa-tr icyclo[4.2.1.03,8]n on an -7-on e (9) was pre-
pared from 5b according to general procedure C. The product
was purified by column chromatography (silica, P/CH2Cl2/
Et2O ) 20/1/1 as eluent) to give 69 mg (0.45 mmol, 90%) of 9 as
a colorless oil: 1H NMR (360 MHz, CDCl3) δ 1.25 (s, 3 H), 1.56-
1.62 (m, 2 H), 2.02-2.11 (m, 2 H), 2.36-2.46 (m, 1 H), 2.71-
2.78 (m, 1 H), 3.07-3.13 (m, 2 H), 4.52 (dt, J ) 5.2 Hz, 4.1 Hz,
1 H); 13C NMR (90.6 MHz, CDCl3) δ 19.3 (q), 23.2 (t), 34.1 (t),
40.4 (d), 40.7 (t), 46.7 (d), 70.1 (d), 80.2 (s), 216.7 (s). Anal. Calcd
for C9H12O2 (152.19): C, 71.03; H, 7.95. Found: C, 70.86; H, 7.82.
Ben zoic a cid 5-bu t-3-en yl-5-m eth yl-4-oxo-4,5-d ih yd r o-
fu r a n -3-ylm eth ylester (2b) was prepared from 6b according
to general procedure B. The product was purified by column
chromatography (silica, P/CH2Cl2/EA ) 20/1/1 as eluent) to give
1
129 mg (0.45 mmol, 90%) of 2a as a colorless oil. H NMR (360
MHz, CDCl3) δ 1.38 (s, 3 H), 1.82-2.18 (m, 4 H), 4.90-4.93 (dm,
J ) 10.5 Hz), 4.93-4.98 (dm, J ) 17.0 Hz, 1 H), 4.97 (s, 2 H),
5.65-5.75 (m, 1 H), 7.40-7.44 (m, 2 H), 7.53-7.57 (m, 1 H),
8.00-8.04 (m, 2 H), 8.42 (s, 1 H); 13C NMR (90.6 MHz, CDCl3)
δ 21.5 (q), 27.2 (t), 35.5 (t), 54.5 (t), 90.9 (s), 114.4 (s), 115.2 (t),
128.4 (d), 129.6 (d), 129.9 (s), 133.1 (d), 137.0 (d), 166.7 (s), 177.0
(s), 204.9 (s). Anal. Calcd for C17H18O4 (286.32): C, 71.31; H,
6.34. Found: C, 71.09; H, 6.14.
Gen er a l P r oced u r e C for [2 + 2] P h otocycloa d d ition of
En on es. The appropriate 3(2H)-furanone (0.50 mmol) was
dissolved in benzene (10 mL) and irradiated at 350 nm (light
source Rayonet RPR 3500 Å) at room temperature for 8 h. The
solvent was then removed in vacuo ,and the residue was purified
by column chromatography.
Ben zoic a cid 1-m eth yl-2-oxo-7-oxa -tr icyclo[3.2.1.03,6]oct-
3-ylm eth ylester (7) was prepared from 2a according to general
procedure C. The product was purified by column chromatog-
raphy (silica, P/CH2Cl2/Et2O ) 20/1/1 as eluent) to give 118 mg
(0.44 mmol, 87%) of 7 as a colorless oil: 1H NMR (360 MHz,
CDCl3) δ 1.51 (d, J ) 12.2 Hz, 1 H), 1.52 (s, 3 H), 1.79 (d, J )
12.5 Hz, 1 H), 1.83-1.88 (m, 1 H), 2.21-2.30 (m, 1 H), 2.93-
2.99 (m, 1 H), 4.44 (d, J ) 11.8 Hz, 1 H), 4.50 (d, J ) 11.8 Hz,
1 H), 5.05 (d, J ) 4.3 Hz, 1 H), 7.42-7.46 (m, 2 H), 7.54-7.59
(m, 1 H), 8.01-8.04 (m, 2 H); 13C NMR (90.6 MHz, CDCl3) δ
13.3 (q), 30.6 (t), 36.4 (d), 41.2 (t), 53.9 (s), 61.4 (t), 79.6 (d), 85.1
(s), 128.4 (d), 129.7 (d), 129.8 (s), 133.1 (d), 166.3 (s), 210.3 (s).
Anal. Calcd for C16H16O4 (272.30): C, 70.57; H, 5.92. Found: C,
70.21; H, 5.81.
Ack n ow led gm en t. Support of this research by the
Deutsche Forschungsgemeinschaft (Ba 1372-6/2) and by
the Fonds der Chemischen Industrie is gratefully ac-
knowledged.
Su p p or tin g In for m a tion Ava ila ble: IR and MS data for
all new compounds;13C NMR spectra of compounds 6a , 6b, and
9; crystal data and details of the structure in the solid state
together with PLATON graphics of compound 8; crystal-
lographic data for 8 in CIF format. This material is available
free of charge via the Internet at http://pubs.acs.org.
Ben zoic acid 6-m eth yl-7-oxo-9-oxa-tr icyclo[4.2.1.03,8]n on -
8-ylm eth ylester (8) was prepared from 2b according to general
J O0264372
J . Org. Chem, Vol. 68, No. 5, 2003 1997