A novel photochemical vinylcyclopropane rearrangement yielding 6,7-dihydro-5H-benzocycloheptene derivatives

Article abstract of DOI:10.1021/ol991277a

(formula presented) 1-Substituted 1-(2,2-diphenylvinyl)cyclopropanes with electron-accepting groups at C1 undergo a novel rearrangement to benzocycloheptenes on triplet-sensitized irradiation. In some instances competition between rearrangement to cyclope

Full text of DOI:10.1021/ol991277a

ORGANIC
LETTERS
2000
Vol. 2, No. 2
183-186
A Novel Photochemical
Vinylcyclopropane Rearrangement
Yielding
6,7-Dihydro-5H-benzocycloheptene
Derivatives
Diego Armesto,* Ana Ramos, Elena P. Mayoral, Maria J. Ortiz, and
Antonia R. Agarrabeitia
Departamento de Qu´ımica Orga´nica I, Facultad de Ciencias Qu´ımicas,
UniVersidad Complutense, 28040-Madrid, Spain
darmesto@eucmos.sim.ucm.es
Received November 24, 1999
ABSTRACT
1-Substituted 1-(2,2-diphenylvinyl)cyclopropanes with electron-accepting groups at C1 undergo a novel rearrangement to benzocycloheptenes
on triplet-sensitized irradiation. In some instances competition between rearrangement to cyclopentenes and formation of cycloheptenes
takes place. When electron-acceptor groups are not present at C1, conventional ring opening to cyclopentenes occurs exclusively. A mechanism
involving intramolecular SET from the diphenylvinyl unit to the electron-acceptor group is proposed for this novel photoreaction.
The photochemistry of vinylcyclopropanes has received
considerable attention in the past.1 Studies carried out in this
area have shown that vinylcyclopropanes undergo basically
three types of photoreactions including (1) E/Z isomerization
of the cyclopropane ring and the vinyl unit, (2) ring opening
to conjugated dienes, and (3) rearrangement to cyclo-
pentenes.1 Most of the past efforts have concentrated on all-
carbon systems. However, when functional groups are
incorporated to the cyclopropane ring, alternative reaction
modes have been observed. Thus, in a recent study of the
photoreactivity of 1-substituted 3-(2,2-diphenylvinyl)-2,2-
dimethylcyclopropanes, with different functional groups at
C1 of the cyclopropane ring, we have observed novel
photorearrangements to different heterocycles such as 1,2-
oxazines and furan derivatives.2
We report here a novel photochemical rearrangement of
1-substituted 1-(2,2-diphenylvinyl)cyclopropanes that yields
cycloheptene derivatives. The ring expansion of vinylcyclo-
propanes to seven-membered ring derivatives has been
described in the thermal and photochemical rearrangement
of 1,2-divinylcyclopropanes that yields 1,4-cyclohepta-
dienes.3 However, as far as we are aware, this reaction has
never been observed before in monovinylcyclopropanes.
As part of our studies on the 1-aza-di-π-methane (1-
ADPM) rearrangement4 we were interested at one point in
(1) For reviews see: (a) Hudlicky, T.; Reed, J. W. In ComprehensiVe
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991;
Vol. 5, p 899. (b) Wong, H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip, Y.-C.;
Tanko, J.; Hudlicky, T. Chem. ReV. 1989, 89, 165. (c) Goldschmidt, Z.;
Crammer, B. Chem. Soc. ReV. 1988, 17, 229. (d) Hudlicky, T.; Kutchan,
T. M.; Naqvi, S. M. Org. React. 1985, 33, 247.
(2) Armesto, D.; Ortiz, M. J.; Agarrabeitia, A. R. J. Org. Chem. 1999,
64, 1056.
(3) For a review on the divinylcyclopropane-cycloheptadiene rearrange-
ment, see: Hudlicky, T.; Fan, R.; Reed, J. W.; Gadamasetti, K. G. Org.
React. 1992, 41, 1.
10.1021/ol991277a CCC: $19.00 © 2000 American Chemical Society
Published on Web 01/05/2000

exploring the possibility of extending the reaction to cyclo-
propane derivatives such as 1a. 1-ADPM rearrangement of
1a would bring about the formation of the spirocyclopentane
2. Spirocyclopentanes units are present in active pirethroids.5
Thus, the 1-ADPM reaction might serve as a possible method
for synthesis of these substances.
To test this proposal 1a was synthesized by a route starting
with methyl 1-formylcyclopropanecarboxylate 3a,6 which is
transformed to 1b by Horner-Emmons olefination with
diethyl diphenylmethylphosphonate.7 Reduction of 1b by
using LAH (f 1c), followed by PCC oxidation, yielded the
corresponding aldehyde that was transformed into 1a by
sequential reaction with hydroxylamine hydrochloride and
acetyl chloride.8
the reaction mixture was refluxed in toluene for 10 h to
promote the quantitative conversion of oxime acetates into
the corresponding nitriles. Column chromatography of the
mixture on silica gel (hexane/Et2O 95:5) yielded the nitrile
1d (76%), which arises by elimination of acetic acid in 1a,
and a new product (12%) whose mass spectral data suggest
1
that it is an isomer of nitrile 1d. The H NMR spectrum
showed a doublet at δ 6.25 corresponding to a vinyl hydrogen
and three multiplets at 2.48, 2.63, and 3.03 corresponding
to aliphatic hydrogens. These resonances are not compatible
with those expected for the ADPM-derived spirocyclopentane
2. The 13C NMR spectrum is particularly helpful in the
assignment of structure since it shows three high-field
saturated carbon atoms at δ 27.9, 30.8, and 40.0 correspond-
ing to a methyne and two methylenes respectively, as well
as signals for two alkene carbons, one cyano group, and two
phenyl rings. The combined spectroscopic data are compat-
ible with a structure of benzocycloheptene 4b, which would
arise by thermal AcOH elimination from photoproduct 4a.
To determine the scope of this new reaction, the study
was extended to compounds 1b and 1e. Irradiation of 1b
for 2 h, with m-metoxyacetophenone used as a sensitizer,
followed by column chromatography on silica gel, yielded
the benzocycloheptene 4c10 (16%) and an inseparable mixture
(56%) of cyclopentene 5a and recovered starting material
(by 1H NMR). To achieve separation, the mixture was reacted
with LAH to form the corresponding alcohols 1c and 5b.
These were separated by column chromatography on silica
gel, yielding 22% of 5b11 and 65% of 1c.12
The identity of 4c was demonstrated by independent
synthesis,13 which was begun by Michael’s addition of HCN
2,3-benzocyclohepta-2,6-dienone14 to form 6. Hydrolysis of
6 yields the ketoacid 7. Reaction of 7 with phenylmagnesium
bromide affords a mixture of the acid 8 and the lactone 9.
Finally, the ester 4c is obtained from both the acid 8 and
the lactone 9, by treatment with acidic methanol (Scheme
1). The comparison of the spectral data for 4c with those
obtained for 4b confirmed its assigned structure.
A solution of cyclopropane 1a (224 mg, 0.8 mmol) in CH2-
Cl2 was irradiated for 80 min, with acetophenone (7 g, 58
mmol) used as a sensitizer.9 Under these conditions a
complex mixture of oxime acetate and nitrile products (as
judged by inspection of the 1H NMR spectrum of the crude
photolyzate) was obtained. To facilitate product isolation,
Scheme 1
(4) For reviews see: (a) Zimmerman, H. E.; Armesto, D. Chem. ReV.
1996, 96, 3065. (b) Armesto, D. CRC Handbook of Organic Photochemistry
and Photobiology; CRC Press: New York, 1995; p 915.
(5) Naumann, K. Chemistry of Plant Protection, Synthetic Pyrethroid
Insecticides: Structure and Properties; Springer-Verlag: Berlin, 1990; Vol.
4, p 192.
(6) Nicolaou, K. C.; Petasis, N. A.; Li, W. S.; Ladduwahetty, T.; Randall,
J. L.; Webber, S. E.; Hernandez, P. E. J. Org. Chem. 1983, 48, 5400.
(7) Zimmerman, H. E.; Klun, R. T. Tetrahedron 1978, 34, 1775.
(8) For experimental conditions on the transformation of esters into oxime
acetates, see: Armesto, D.; Ortiz, M. J.; Ramos, A.; Horspool, W. M.;
Mayoral, E. P. J. Org. Chem. 1994, 59, 8115.
(9) The photolyses were carried out in a quartz immersion well apparatus
with a Pyrex filter and a 400-W medium-pressure Hg arc lamp. Solutions
of the compounds and the sensitizer in dry CH2Cl2 (420 mL) were purged
for 1 h with argon and irradiated under a positive pressure of argon. After
completion of the irradiation, the solvent and the sensitizer were removed
under reduced pressure, and the products were separated by flash column
chromatography on silica gel.
In the case of 1b, the novel rearrangement to form
cycloheptene 4c competes with the conventional vinylcy-
clopropane ring expansion to generate 5a. However, irradia-
184
Org. Lett., Vol. 2, No. 2, 2000

tion of 1e, obtained from 1c by standard methods, for 2 h,
under the same conditions used for 1b, yielded 5c (6%) and
recovered starting material 1e (76%), exclusively. The
corresponding benzocycloheptene derivative was not detected
in the product mixture. Cyclopentenes 5a and 5c are the
products expected to result from conventional vinylcyclo-
propane rearrangement.1 However, the formation of 4a and
4c is surprising since, as far as we are aware, the photo-
chemical ring expansion of vinylcyclopropanes to benzocy-
cloheptenes has not been previously observed. The formation
this process.15 This SET process forms zwitterionic biradical
12 that then undergoes ring opening to produce dipolar
intermediate 13. Electrophilic addition to the aromatic ring
in 13 is quite plausible; this yields intermediate 11, the
precursor of 4c. In accord with this mechanistic proposal,
the formation of the five-membered compound 5a and the
seven-membered derivative 4c in the irradiation of 1b could
be due to a competition between the biradical path, yielding
5a and the SET route that affords 4c.
To test this mechanistic hypothesis, the ester 14 was
synthesized16 and irradiated under the same conditions used
for 1a. The presence of p-methoxy groups in the phenyl rings
should decrease the ionization potential of the alkene unit
and favor intervention of the intramolecular SET route.
Triplet-sensitized irradiation of 14 for 90 min yielded the
benzocycloheptene 15 (19%) and recovered starting material
(56%). The isomeric cyclopentene was not detected as a
product of the photoreaction of 14, a fact which can be
explained by the increased efficiency of the SET path leading
to the cycloheptene.
Scheme 2
At this point it was considered necessary to obtain
additional evidence that would demonstrate that in the
absence of electron-acceptor groups at C1, the ring expansion
to cycloheptenes would not take place. Thus, cyclopropane
1f17 was irradiated under the same conditions used for 1b,
for 5 h. In this instance, the only photoproduct obtained is
the cyclopentene 5d (10%).
of 4a, 4c, 5a, and 5c can be interpreted by the operation of
a conventional biradical mechanism (Scheme 2 for 1b). Thus,
excitation of 1b to its triplet excited state is followed by
homolytic rupture of the C1-C2 cyclopropane bond to
produce biradical 10. Radical recombination of 10 provides
11. Compound 4c results from the alternative cyclization
mode involving addition of the primary radical to one of
the phenyl rings affording the seven-membered-ring inter-
mediate 11. Hydrogen migration within 11 yields benzocy-
cloheptene 4c. Although this mechanism reasonably explains
the products formed in these reactions, it leaves in question
why the biradical intermediate 10 undergoes cyclization to
cycloheptenes in the reactions of 1a and 1b while this path
is not followed in reaction of 1e.
At this point, a possible alternative mechanism for the ring
expansion to benzocycloheptenes was considered. The ac-
etoxyimino and methoxycarbonyl groups present in 1a and
1b, respectively, could act as good electron acceptors for
single-electron transfer (SET) from the triplet excited state
of the diphenylvinyl chromophore (Scheme 3 for 1b).
Previous studies carried out by us support the feasibility of
The study was extended to cyclopropanes 1g and 1h. The
presence of a methyl in 1g and a phenyl in 1h at C2 of the
cyclopropane ring should facilitate the ring opening of the
cyclopropane. These two compounds were synthesized by a
route analogous to that used to prepare 1a, starting from 3b
and 3c, respectively.18 Irradiation of 1g, as a 7:3 mixture of
(Z:E) diastereoisomers,19 for 50 min, under the same condi-
tions used for 1a, followed by thermal elimination of AcOH,
yielded cycloheptene 4d (17%) and the nitrile 1i (53%) as a
3:1 mixture of (Z:E) diastereoisomers. This result shows that
(10) Spectral Data for 4c: 1H NMR (300 MHz, CDCl3) δ 2.42 (m,
1H), 2.61 (m, 3H), 2.99 (m, 1H), 3.69 (s, 3H), 6.61 (d, J ) 6.6 Hz, 1H),
6.98-7.82 (m, 9H); 13C NMR (63 MHz, CDCl3) δ 31.5, 39.7, 42.8, 59.7,
125.5-142.6, 175.3.
(11) Spectral Data for 5b: 1H NMR (300 MHz, CDCl3) δ 1.63 (s, 1
H), 2.48 (m, 2 H), 2.62 (m, 2 H), 4.26 (s, 2 H), 6.08 (s, 1 H), 7.17-7.29
(m, 10 H); 13C NMR (63 MHz, CDCl3) δ 32.2, 40.0, 61.3, 62.3, 126.0-
148.8.
(12) These yields are calculated from the mixture of 5a and 1b.
(13) For experimental details on the synthesis of 4c see the Supporting
Information.
(14) Hart, H.; Dunkenblum, E. J. Am. Chem. Soc. 1978, 100, 5141.
(15) (a) Armesto, D.; Ramos, A.; Ortiz, M. J.; Manchen˜o, M. J.; Mayoral,
E. P. Recl. TraV. Chim. Pays-Bas 1995, 114, 514. (b) Armesto, D.; Austin,
M. A.; Griffiths, O. J.; Horspool, W. M.; Carpintero, M. Chem. Commun.
1996, 2715.
(16) The synthesis is analogous to that used for 1b with the only
difference that diethyl bis(p-methoxyphenyl)methylphosphonate is used in
the Horner-Emmons step.
Scheme 3
(17) Zimmerman, H. E.; Samuel, C. J. J. Am. Chem. Soc. 1975, 97, 4025.
(18) (a) Compounds 3b and 3c were obtained by DIBALH reduction
(ref 18b) of the previously reported diethyl 2-methylcyclopropane-1,1-
dicarboxylate and diethyl 2-phenylcyclopropane-1,1-dicarboxylate, respec-
tively (ref 18c). (b) Davis, C. R.; Swenson, D. C.; Burton, D. J. J. Org.
Chem. 1993, 58, 6843. (c) Landor, S. R.; Punja, N. J. Chem. Soc. (C) 1967,
2495.
(19) The configurations of compounds 1g and 1h were established by
means of NOE difference measurements.
Org. Lett., Vol. 2, No. 2, 2000
185

the new rearrangement to benzocycloheptenes can be ex-
tended to vinylcyclopropanes substituted at C2.
etoxyimino and methoxycarbonyl) at C1, undergo a novel
photorearrangement to form benzocycloheptene derivatives
on triplet-sensitized irradiation. The normal vinylcyclopro-
pane rearrangement to cyclopentenes competes with this
process in some cases. In the absence of electron-accepting
groups, rearrangement to cyclopentenes is the only reaction
pathway observed. The replacement of the 2,2-diphenylvinyl
unit for a 2,2-bis(p-methoxyphenyl)vinyl moiety increases
the efficiency of the cycloheptene formation and suppresses
formation of the corresponding cyclopentene. A mechanism
involving intramolecular SET from the vinyl unit to the
electron-acceptor group is proposed to account for this novel
rearrangement reaction. As far as we are aware, these are
the first examples of photochemical vinylcyclopropane
rearrangements that yield benzocycloheptene derivatives.
Further studies are in progress to determine the scope and
synthetic applications of this novel reaction.
The absence of the corresponding cyclopentene product
in this process is reasonable, since the methyl at C2 should
have a greater stabilizing effect on the dipolar intermediate
13 than the biradical 10. Therefore, ring opening via the
dipolar intermediate is favored over the biradical alternative
in this process.
Irradiation of (Z)-1h, for 90 min, using m-methoxy-
acetophenone as a sensitizer, followed by acetic acid
elimination, gives benzocycloheptene 4e (20%), cyclopentene
5e (25%), and the nitrile 1j (22%) as a 3:2 mixture of (E:Z)
diastereoisomers. The formation of cyclopentene 5e in this
reaction is surprising since 1g yields the corresponding
benzocycloheptene 4d exclusively. A possible explanation
for this result is that the incorporation of a phenyl group at
C2 promotes the thermal cyclopropane rearrangement of 1h
to the cyclopentene 5e. To test the validity of this postulate
compound 1h was heated in refluxing toluene for 5 h. Under
these conditions 1h yielded the cyclopentene 5e in 89%
yield.20
Acknowledgment. We thank the Direccion General de
Investigacion Cientifica y Tecnica (grant no. PB 97/0235)
for financial support. We acknowledge the support provided
by the Centro de Resonancia Magnetica, the Centro de
Microanalisis, and the Servicio de Espectrometria de Masas
of the Universidad Complutense.
The results obtained in the irradiation of compounds 1g
and 1h demonstrate that in addition to rearrangements to
cyclopentenes and benzocycloheptenes, isomerization of the
cyclopropane ring also occurs in the triplet excited states of
these compounds.
Supporting Information Available: Experimental pro-
cedures for preparation of compound 1b and for the
independent synthesis of 4c, and analytical and spectral data
for compounds 4b, 4d, 4e, 5c, 5d, 5e, and 15. This material
is available free of charge via the Internet at http://pubs.acs.org.
In summary, 1-substituted 1-(2,2-diphenylvinyl)cyclopro-
panes, containing electron-accepting groups (such as ac-
(20) None of the other vinylcyclopropanes 1 rearrange to cyclopentenes
under these reaction conditions.
OL991277A
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Org. Lett., Vol. 2, No. 2, 2000