Copper(I)-catalyzed intramolecular photocycloadditions of dicyclopentadiene derivatives linked by removable tethers

Article abstract of DOI:10.1016/S0040-4039(00)00273-2

Cu(I)-catalyzed intramolecular [2+2] photocycloadditions of two dicyclopentadiene derivatives linked by an alkyl chain have been studied. These reactions are regio- and stereoselective and proceed considerably faster than the corresponding intermolecular reactions. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00273-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 2831–2834
Copper(I)-catalyzed intramolecular photocycloadditions of
dicyclopentadiene derivatives linked by removable tethers
Ravikrishna Chebolu, Wei Zhang, Elena Galoppini and Richard Gilardi b
a
a
a,∗
a
Department of Chemistry, Rutgers University, 73 Warren Street, Newark, NJ 07102, USA
b
Laboratory for the Structure of the Matter, The Naval Research Laboratory, Washington D.C. 20375, USA
Received 27 December 1999; accepted 27 January 2000
Abstract
Cu(I)-catalyzed intramolecular [2+2] photocycloadditions of two dicyclopentadiene derivatives linked by an
alkyl chain have been studied. These reactions are regio- and stereoselective and proceed considerably faster than
the corresponding intermolecular reactions. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: intramolecular photocycloaddition; copper catalyzed; dicyclopentadiene; polycyclic compounds.
The Cu(I)-catalyzed [2+2] photocycloaddition of strained alkenes is a valuable methodology
1
2
for the synthesis of carbocyclic compounds. The photodimerizations of norbornenes, endo-
2
b
3
dicyclopentadienes and other polycyclic derivatives have been thoroughly studied, because of
the perspective to build, in one step and from simple molecules, complex and useful organic
frameworks incorporating cyclobutane rings. Such dimerizations were conducted intermolecularly
4
and often produced several isomers. Intramolecular [2+2] photocycloadditions are usually regio-
and stereoselective and yield isomers not observed in the corresponding intermolecular reactions, for
example cis,syn,cis-fused cyclobutane rings. Similarly, intramolecular photocycloadditions of polycyclic
compounds could provide selective routes to polycarbocyclic molecules and to hitherto unknown
isomers. However, this particular application has never been reported.
To this end, we initiated the study of Cu(I)-catalyzed intramolecular photocycloadditions of dicy-
clopentadiene derivatives linked by removable tethers to determine the regio- and stereoselectivity of
such reactions and also to examine whether the configuration of the cyclobutane ring formed in the
cycloaddition is controlled by the tether’s length and rigidity. Herein we report the study of the first
two substrates, I and II, made of endo-dicyclopentadiene derivatives tethered at the oxygen atom by a
six-membered alkyl chain.
∗
Corresponding author.
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00273-2
tetl 16553

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The synthesis and photoreactions of I and II are illustrated in Scheme 1. Reduction of the enone moiety
5
6
in endo-dicyclopentadienones 1 and 4 using NaBH produced the corresponding α-alcohols 2a and 5a,
4
leaving only the ‘norbornene’ double bond available for the cycloaddition. Reaction of two moles of 2 or
5
with one mole of suberic acid dichloride provided esters I or II, respectively. All photocycloadditions
shown in Scheme 1, inter- and intramolecular, were carried out in THF and occurred only in the presence
7
of a catalytic amount of CuOTf.
Scheme 1. Reagents and conditions: (a) NaBH
5%, diastereomeric mixture; the photolysis was performed on one isolated diastereomer (II). (c) CH
hν, THF, CuOTf, 1 week. (e) hν, THF, CuOTf, 3 h
4
, MeOH, 0–5°C, 80%. (b) ClCO(CH
2
)
6
COCl, pyridine, C
6 6
H , ∆, 10–12 h,
7
3
I, NaH, THF, 82%. (d)
In the photocycloaddition reactions of 2b and I, we observed that the ketal group was cleaved during
prolonged irradiation, and it is likely that the resulting ketone participated in photoreactions leading to

2
833
a complex mixture of products. However, there was a distinct difference between the intermolecular
and intramolecular processes. In the intermolecular reaction of 2b the ketal cleavage was faster than the
cycloaddition and no photodimers were recovered. The intramolecular photocycloaddition of I proceeded
in 30% conversion in 3 h, yielding dimer 3 as a mixture of two isomers (1:1). Further irradiation led
to ketal deprotection and degradation processes. Although NMR spectral data and FAB-MS clearly
indicated formation of 3, determination of the stereochemistry was not possible as the two isomers could
not be separated.
Conversely, the photocycloadditions of substrates 5b and II proceeded in high yields. Irradiation of
5
7
b for 7 days afforded unreacted starting material and four photodimers: exo–trans–exo regioisomers
and 8 in 1:1 ratio and a small amount of two additional isomers. The photoadducts 7 and 8 were
8
separated by column chromatography and their single-crystal X-ray structures clearly established the
exo–trans–exo configuration of the cyclobutane ring. The intramolecular photocycloaddition of one
isolated diastereomer II, which was complete only in 3 h, led to the exo–trans–exo 6, isolated in 75%
8
1
yield. The H NMR spectrum of the crude reaction mixture indicated the presence of only traces of other
isomers. The exo–trans–exo stereochemistry in 6 was unambiguously deduced through single-crystal X-
9
ray diffraction analysis and is shown in Fig. 1. The tether, both in 3 and 6, was readily cleaved upon
reduction with LiAlH4.
Fig. 1. A perspective drawing of the (R,R) diastereomer of 6, showing one conformer of three seen in the crystal structure. All
three show the identical exo–trans–exo fused ring system seen here, but differ in their torsion angles along the tether-chain
Since the tether in I and II is a long and flexible alkyl chain, we did not expect a change in the
configuration of the cyclobutane ring with respect to the intermolecular reaction. We are currently
investigating how the stereochemistry of the reaction is controlled by variations in the tether’s length
and rigidity.
In summary, the intramolecular photocycloadditions of I and II in the presence of CuOTf, proceeded
considerably faster than the corresponding intermolecular reactions and are regio- and stereoselective.
A study of intramolecular cycloadditions of a variety of functionalized dicyclopentadienes linked by
removable tethers that can produce synthetically useful polycyclic cages is in progress.

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References
1
. (a) Langer, K.; Mattay, J. CRC Handbook of Organic Photochemistry and Photobiology; Horspool, W. M.; Song, P.-S., Eds.;
C.R.C. Press: Boca Raton, 1995; pp. 84–104. (b) Salomon, R. G. Tetrahedron 1983, 39, 485.
. (a) Arnold, D. R.; Trecker, D. J.; Whipple, E. B. J. Am. Chem. Soc. 1965, 87, 2596. (b) Salomon, R. G.; Kochi, J. K. J. Am.
Chem. Soc. 1974, 96, 1137. (c) Chow, T. J.; Chao, Y.-S.; Liu, L.-K. J. Am. Chem. Soc. 1987, 109, 797.
. Marchand, A. P.; Earlywine, A. D.; Heeg, M. J. J. Org. Chem. 1986, 51, 4096.
2
3
4
. (a) Comins, D. L.; Lee, Y. S.; Boyle, P. D. Tetrahedron Lett. 1998, 187. (b) Hertel, R.; Mattay, J.; Runsink, J. J. Am. Chem.
Soc. 1991, 113, 657.
5
6
7
. Chapman, N. B.; Key, J. M.; Toyne, K. J. J. Org. Chem. 1970, 35, 3860.
. Woodward, R. B.; Katz, T. J. Tetrahedron 1959, 5, 70.
. General procedure for photocycloadditions: Intramolecular: 0.1 mmol of starting material was dissolved in 20 mL of dry
THF and placed in a dry quartz tube shielded with a vycor filter. A catalytic amount (3–5 mol%) of CuOTf was added and
the solution was irradiated with a 450 W Hanovia medium pressure Hg lamp. The reaction was monitored by TLC and
NMR. After irradiation was complete, THF was removed in vacuo and the crude residue was purified by silica gel column
chromatography to obtain the pure products. Intermolecular: Reactions were carried out in a similar manner with 0.5 mmol
of starting material in 10 mL of THF. The reaction was monitored by TLC and GC–MS.
1
8
. Selected data for I: H NMR (500 MHz, CDCl
2
3
): δ 6.21 (m, 4H), 5.09 (m, 2H), 3.88 (m, 4H), 3.78 (m, 4H), 3.16 (m, 2H),
1
3
.81 (m, 2H), 2.66 (m, 2H), 2.57 (m, 2H), 2.29 (t, 4H, J=10 Hz), 1.83 (m, 2H), 1.56–1.65 (m, 8H), 1.34–1.41 (m, 6H);
C
NMR (125 MHz, CDCl
Compound II: H NMR (500 MHz, CDCl
3
): δ 173.3, 135.4, 131.6, 127.3, 76.8, 64.8, 64.1, 50.7, 49.3, 46.6, 42.4, 34.4, 34.1, 28.8, 24.8, 24.5.
): δ 6.06 (m, 4H), 4.97 (m, 2H), 2.92 (m, 2H), 2.76 (m, 2H), 2.69 (m, 2H), 2.59
1
3
1
3
(m, 2H), 2.26 (t, 4H, J=8 Hz), 1.72 (m, 2H), 1.41–1.62 (m, 8H), 1.24–1.36 (m, 12H); C NMR (125 MHz, CDCl
3
): δ 173.3,
1
1
37.3, 134.0, 77.1, 52.0, 49.1, 46.9, 45.7, 44.5, 34.3, 32.7, 28.7, 24.8, 24.3. Compound 3 (mixture of two isomers): H NMR
): δ 5.17 (m, 2H), 5.11 (m, 2H), 3.88 (m, 12H), 3.79 (m, 6H), 3.70 (m, 2H), 3.59 (m, 2H), 3.42 (m, 2H),
(500 MHz, CDCl
3
+
1
2
2
1
2
2
3
.45 (m, 4H), 1.59–2.05 (series of m, 52H); FABMS: 554 (M ). Compound 6: H NMR (500 MHz, CDCl ): δ 4.93 (m, 2H),
.67 (m, 2H), 2.50 (m, 2H), 2.35 (m, 2H), 2.17 (m, 4H), 2.09 (m, 2H), 2.01 (m, 2H), 1.85–1.93 (m, 6H), 1.60–1.67 (m, 8H),
.37–1.42 (m, 8H); 13C NMR (125 MHz, CDCl
3
): δ 173.3, 77.6, 45.3, 43.9, 43.0, 42.1, 40.4, 38.3, 37.2, 36.1, 32.2, 29.6,
): δ 3.74 (m, 2H), 3.36 (s, 6H), 2.36 (m, 2H), 2.27 (m, 2H), 2.21 (m,
1
6.0, 22.0; Compound 7: H NMR (500 MHz, CDCl
3
H), 2.14 (d, 2H, J=10 Hz), 2.06 (d, 2H, J=5 Hz), 2.00 (d, 2H, J=5 Hz), 1.85 (m, 4H), 1.55 (m, 2H), 1.40 (m, 4H), 1.30 (d,
H, J=10 Hz); 13C NMR (125 MHz, CDCl
): δ 84.5, 57.8, 45.1, 44.1, 42.6, 41.9, 40.2, 38.6, 37.3, 32.6, 22.7. Compound 8:
): δ 3.74 (m, 2H), 3.36 (s, 6H), 2.33 (m, 2H), 2.20 (d, 2H, J=5 Hz), 2.14 (d, 2H, J=10 Hz), 2.11
2
3
1
H NMR (500 MHz, CDCl
d, 2H, J=5 Hz), 1.94 (d, 2H, J=5 Hz), 1.83 (m, 4H), 1.55 (m, 4H), 1.37 (m, 4H), 1.30 (d, 2H, J=10 Hz); C NMR (125 MHz,
3
1
3
(
CDCl ): δ 84.4, 57.9, 45.0, 44.1, 42.7, 42.1, 40.7, 38.1, 37.4, 32.7, 22.6.
3
9
. Crystal data for 6: C28
H
38
O
4
3
, F.W.=438.58, monoclinic space group P2
1
; a=7.765(1), b=17.781(2), c=24.799(3) Å,
−3
β=90.376(9)°, V=3424.1(8) Å , Z=6, and D(X-ray)=1.276 mg mm . 7010 data measured to a 2θ max of 116°. R=0.0640,
wR2=0.1498 for 4464 unique reflections with I>2sigma(I). X-Ray intensity data were measured on a Bruker diffractometer
with CuKa radiation (λ=1.54178 Å) at T=294 K. Crystallographic data for 6, 7 and 8 have been deposited with the Cambridge
Crystallographic Data Center. Copies 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).