Photogeneration of o-Quinone Methides from o-Cycloalkenylphenols

Article abstract of DOI:10.1021/jo034918v

6-Alkylidenecyclohexa-2,4-dienones (o-quinone methides II) have been generated by photolysis of 2-(2′-cycloalkenyl)phenols 1 and trapped by methanol to give the ring-opened products 2. The best results have been obtained with the cyclohexenyl derivatives 1a, 1e, and 1f. In the case of the cyclopentenyl derivative 1b, photoproduct 2b was not observed, whereas only small amounts of 2c and 2d were formed from the seven- and eight-membered ring analogues 1c and 1d. Thus, ring size appears to be a key factor in the formation of o-quinone methides. This experimental result has been rationalized by means of density-functional theory (DFT) calculations. On the other hand, phenol substitution also appears to play a role in the process. Thus, electron-withdrawing groups such as CF₃ (1f) accelerate the reaction, whereas the opposite is true for electron-donating groups such as OCH ₃ (1e). This is explained by an excited-state intramolecular proton transfer (ESIPT) mechanism, as the above results are consistent with the excited-state acidities of the different phenols. The lack of reactivity in the case of ketone 1g, where the intersystem crossing quantum yield is close to unity, allows us to rule out a mechanism involving the triplet state.

Full text of DOI:10.1021/jo034918v

P h otogen er a tion of o-Qu in on e Meth id es fr om
o-Cycloa lk en ylp h en ols
Edgar A. Leo,† J ulio Delgado,† Luis R. Domingo,‡ Amparo Espino´s,† Miguel A. Miranda,*,† and
Rosa Tormos†
Departamento de Qu´ımica-Instituto de Tecnologı´a Quı´mica UPV-CSIC, Universidad Polite´cnica de
Valencia, Camino de Vera s/ n, 46022 Valencia, Spain, and Departamento de Qu´ımica Orga´nica, Instituto
de Ciencia Molecular, Universidad de Valencia, Edificio J eromi Mun˜oz, C/ Dr. Moliner,
50, 46100 Burjassot, Valencia, Spain
mmiranda@qim.upv.es
Received J une 27, 2003
6-Alkylidenecyclohexa-2,4-dienones (o-quinone methides II) have been generated by photolysis of
2-(2′-cycloalkenyl)phenols 1 and trapped by methanol to give the ring-opened products 2. The best
results have been obtained with the cyclohexenyl derivatives 1a , 1e, and 1f. In the case of the
cyclopentenyl derivative 1b, photoproduct 2b was not observed, whereas only small amounts of 2c
and 2d were formed from the seven- and eight-membered ring analogues 1c and 1d . Thus, ring
size appears to be a key factor in the formation of o-quinone methides. This experimental result
has been rationalized by means of density-functional theory (DFT) calculations. On the other hand,
phenol substitution also appears to play a role in the process. Thus, electron-withdrawing groups
such as CF3 (1f) accelerate the reaction, whereas the opposite is true for electron-donating groups
such as OCH3 (1e). This is explained by an excited-state intramolecular proton transfer (ESIPT)
mechanism, as the above results are consistent with the excited-state acidities of the different
phenols. The lack of reactivity in the case of ketone 1g, where the intersystem crossing quantum
yield is close to unity, allows us to rule out a mechanism involving the triplet state.
SCHEME 1. P h otogen er a tion of o-Qu in on e
Meth id es by ESIP T in o-Hyd r oxystyr en es (Left) or
by Deh yd r a tion of o-Hyd r oxyben zyl Alcoh ols
(Righ t)
In tr od u ction
o-Quinone methides (6-alkylidenecyclohexa-2,4-di-
enones) are valuable synthetic intermediates with dual
behavior as electrophilic and nucleophilic reagents.1 They
also have very interesting biological activity, as the actual
cytotoxins responsible for the effect of some antitumor
drugs, antibiotics, and DNA alkylators.2
These intermediates have been generated in several
ways, including excited-state intramolecular proton trans-
fer (ESIPT) in o-hydroxystyrenes or photoinduced water
elimination from o-hydroxybenzyl alcohols (Scheme 1).
They have been detected by laser flash photolysis of both
precursors and exhibit characteristic transient absorption
bands at 400 nm.3-5
In the presence of water, o-quinone methides undergo
hydronium-ion-catalyzed hydration by a reaction mech-
anism involving rapid equilibrium protonation on the
carbonyl oxygen followed by rate-determining nucleo-
philic addition of water to the ensuing carbocation. The
only photoproducts are the corresponding benzyl alcohols.
Other nucleophiles (MeOH, SCN-, Br-, etc.) or electron
rich alkenes can also be used for trapping to give addition
or cycloaddition products, respectively (Scheme 2).4,5
o-Allylphenols are one-carbon homologues of o-hy-
droxystyrenes and are also known to undergo ESIPT
upon irradiation; subsequent photocyclization of the
resulting zwitterions leads to five- (or six-) membered
ring ethers (see Scheme 3, for instance).6-9 Thus, inser-
tion of a methylene group between the phenol and the
† Universidad Polite´cnica de Valencia.
‡ Universidad de Valencia.
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1998, 11, 1113-1127. (c) Pande, P.; Shearer, J .; Yang, J .; Greenber,
W. A.; Rokita, S. E. J . Am. Chem. Soc. 1999, 121, 6773-6779.
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Wan, P. J . Photochem. Photobiol., A 1997, 104, 91-96.
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10.1021/jo034918v CCC: $25.00 © 2003 American Chemical Society
Published on Web 11/11/2003
J . Org. Chem. 2003, 68, 9643-9647
9643

Leo et al.
SCHEME 2. Rea ction of o-Qu in on e Meth id es w ith
CHART 1
Nu cleop h iles a n d Dien op h iles
SCHEME 3. P h otocycliza tion of o-Allylp h en ol
The absorption spectra of 1a -g showed their most
intense band below 300 nm, so the irradiation experi-
ments were performed using quartz-filtered light. All
samples (in methanolic solution) were deoxygenated with
argon before irradiation. The photomixtures were ana-
lyzed by GC, GC-MS, and 1H NMR. Then, they were
submitted to column chromatography to isolate the pure
photoproducts.
Ring-opened methanol adducts (2) were obtained in all
cases except for 1b and 1g. These photoproducts present
characteristic signals in 1H NMR, mainly due to the
terminal olefinic protons, the methoxy group, and a very
deshielded H-bonded hydroxylic proton. The mass spec-
tral fragmentation was also very characteristic; the base
peak always corresponded to the benzylic fragmentation.
All carbon atoms gave distinct signals in 13C NMR in the
expected δ ranges.
Effect of th e Cycloa lk en yl Rin g Size. Although the
methanol adducts 2 were the only well-defined photo-
products, cycloalkenyl ring size was a critical factor as
regards the reaction efficiency. The best results for the
unsubstituted phenols were obtained with the six-
membered ring compound 1a (ca. 55% yield after 6 h; in
addition, 10% of the unreacted starting material was
recovered and ca. 35% of an unidentified polymer was
formed). In the case of the cyclopentenyl derivative 1b,
not even traces of any product assignable to 2b were
detected by GC-MS or 1H NMR. With the seven- and
eight-membered ring analogues 1c and 1d , only small
amounts of the corresponding photoproducts 2c and 2d
(ca. 5%) were obtained under the same reaction condi-
tions. Prolonged irradiation of 1b-d resulted in the
formation of significant amounts of polymer.
Effect of P h en ol Su bstitu tion . Three para-substi-
tuted phenols were selected with different electron donor
or withdrawing groups. Compound 1g, with an acetyl
substituent, was photostable so that no photoproduct was
observed. The relative photoreaction rates for 1e and 1f
are shown in Figure 1, using the unsubstituted compound
1a for comparison. From these data, it is clear that
electron-withdrawing substituents (such as CF3) acceler-
ate the process, whereas electron-donating groups (such
as OMe) have the opposite effect. Nonetheless, the
reaction was clean in the three cases, and moderate to
good yields of the photoproducts were obtained (up to 43%
olefin moieties appears to prevent formation of o-quinone
methides, which have never been observed in the pho-
tolysis of o-allylphenols.
In a preliminary communication, we have reported the
generation of an o-quinone methide from 2-(2′-cyclohex-
enyl)phenol (1a ) by initial ESIPT from the phenolic
subunit to the double bond and subsequent C-C bond
fragmentation, with concomitant ring opening.10 Now we
report our results in full, with special emphasis on the
effect of ring size and phenol substitution. Theoretical
density-functional theory (DFT) calculations on the reac-
tion pathways have also been performed to rationalize
the experimental data.
Resu lts a n d Discu ssion
P r od u ct Stu d ies. 2-(2′-Cycloalkenyl)phenols 1a -g
(see structures in Chart 1) were prepared following the
literature methods.11 Compounds 1a ,b,6 1c,12 and 1e13
were known; their structures were confirmed by com-
parison of their spectroscopic data with those reported
in the literature. The unknown analogues 1d , 1f, and 1g
were fully characterized.
(7) Horspool, W. M.; Pauson, P. L. J . Chem. Soc., Chem. Commun.
1967, 22, 196-197.
(8) (a) Shani, A.; Mechoulam, R. Tetrahedron 1971, 27, 601-606.
(b) Chow, Y. L.; Zhou, X. M.; Gaitan, T. J .; Wu, Z. Z. J . Am. Chem.
Soc, 1989, 111, 3813-3818.
(9) (a) Miranda, M. A.; Tormos, R. J . Org. Chem. 1993, 58, 3304-
3307. (b) Bosch-Montalva´, M. T.; Domingo, L. R.; J ime´nez, M. C.;
Miranda, M. A.; Tormos, R. J . Chem. Soc., Perkin Trans. 2 1998, 2175-
2180.
(10) Delgado, J .; Espino´s, A.; J ime´nez, M. C.; Miranda, M. A. Chem.
Commun. 2002, 2636-2637.
(11) Tarbell, D. S. The Claisen rearrangement. In Organic Reactions;
Adams, R., Ed.; Wiley: New York, 1944; Vol. 2, pp 1-48.
(12) Cristol, S. J .; Ilenda, C. S. J . Am. Chem. Soc. 1975, 97, 5862-
5867.
(13) Hosokawa, T.; Miyagi, S.; Murahashi, S.; Sonoda, A.; Matsuura,
Y.; Tanimoto, S.; Kakudo, M. J . Org. Chem. 1978, 43, 719-724.
9644 J . Org. Chem., Vol. 68, No. 25, 2003

o-Quinone Methides from o-Cycloalkenylphenols
TABLE 1. Excited -Sin glet-Sta te Acid ities (p Ka *) for
P h en ols 1a , 1e, a n d 1f in Meth a n ol, Ca lcu la ted Usin g th e
F o1r ster Cycle
a
-a
b
EHA
EA
pKa
pKa*
1a
1e
1f
100.7
93.3
101.2
93.0
86.6
93.1
10.00
10.21
8.68
4.52
5.29
2.71
a
Singlet energies of the phenols (EHA) and their conjugated
b
-
bases (EA ) in kcal/mol. pKa values were taken from the litera-
ture.15,18 They were assumed to be approximately the same in
water and in methanol, which was also used for the absorption-
fluorescence measurements.
TABLE 2. Tota l (in a u ) a n d Rela tivea (in k ca l/m ol, in
P a r en th eses) En er gies of th e Rea cta n ts, In ter m ed ia tes,
a n d Tr a n sition Sta tes (TS) In volved in th e Isom er iza tion
of 1a a n d 1b in to IIa a n d IIb
F IGURE 1. Kinetics of the photoreaction for 1a (×), 1e (O),
and 1f (b).
(S0)b
(S1)c
1a
Ia
TSa
IIa
1b
Ib
TSb
IIb
-540.915 165
-540.735 429
-540.772 471
-540.754 279
-540.774 704
-501.415 133
-501.465 569
-501.435 332
-501.459 647
(112.8)
(89.5)
(101.0)
(88.1)
(114.2)
(82.6)
(101.6)
(86.3)
SCHEME 4. Mech a n ism Wh ich Exp la in s th e
F or m a tion of 2a by Ir r a d ia tion of 1a in Meth a n ol
-540.834 771
-540.874 457
-501.597 181
(50.4)
(25.5)
-501.516 561
-501.560 293
(50.6)
(23.1)
a
b
Relative to 1a (S0) and 1b (S0). B3LYP/6-31G* calculations.
c CIS (singlet) calculations.
of 2e and 88% of 2f) when the irradiations were conve-
niently prolonged.
Rea ction Mech a n ism . The proposed reaction mech-
anism to explain the formation of 2a is outlined in
Scheme 4. This mechanism could be extended to all of
the o-cycloalkenylphenols studied.
Initial ESIPT would occur from the phenol subunit to
the cycloalkenyl double bond, generating the zwitterionic
intermediate Ia . Subsequently, Ia would undergo C-C
bond fragmentation with concomitant ring opening, lead-
ing to o-quinone methide IIa . Because irradiations were
performed using methanol as the solvent, intermediate
IIa would be readily trapped to give the final product
2a .
The involved excited state must be of singlet nature,
because compound 1g (where the intersystem-crossing
quantum yield must be near unity, as expected for a
substituted acetophenone)14 is unreactive.
Excited -Sta te Acid ity. To understand the effect of
the phenol substituent on the reaction rates, the acidity
of the lowest lying singlet excited state (pKa*) was
determined for phenols 1a , 1e, and 1f, as this property
must be directly related to the feasibility of the key
ESIPT step. This was achieved by using the Fo¨rster cycle,
which is based on the known acidities in the ground state
(pKa) and on the singlet energies of the phenols and their
conjugated bases (phenolates), obtained from the inser-
tion point of both normalized absorption and fluorescence
spectra in neutral and basic methanolic media.15-18 The
results are shown in Table 1.
Qualitatively, the obtained pKa* values are consistent
with the relative photoreaction rates. Thus, 1f was the
most reactive of the three phenols, followed by 1a and
then by 1e; the same order was found for the excited-
state acidities. Hence, the relative reactivities of the three
substrates support the proposed ESIPT mechanism.
Th eor etica l Ca lcu la tion s. The reaction mechanism
for the photoisomerization of 2-(2′-cyclohexenylphenol) 1a
to the o-quinone methide IIa was theoretically studied
using density-functional theory (DFT) methods (see
Computational Methods in the Experimental Section).
After exhaustive exploration of the potential energy
surface (PES) for the isomerization process at the ground
state (S0), a transition structure (TS) connecting both
isomers was found and characterized: TSa . The total and
relative energies of the stationary points located at the
S0 state, together with the computed S1 energies, are
presented in Table 2, and the geometries of the different
species 1a , Ia , IIa , and TSa are given in Figure 2.
Thermal isomerization of 2-(2′-cyclohexenyl)phenol 1a
(S0) to the o-quinone methide IIa (S0) presents a barrier
of 50.4 kcal/mol. This very large value clearly prevents
the isomerization process. In addition, the reaction is very
endothermic, 25.5 kcal/mol. Therefore, under thermal
equilibration conditions, formation of o-quinone methide
IIa is kinetically and thermodynamically very unfavor-
able.
The calculated energy for the configuration interactions
including only single electronic vertical excitation (CIS)
of 1a (S0) to 1a (S1) is 112.8 kcal/mol. This species could
be converted into the more stable Ia (S1), which lies 23.3
kcal/mol below 1a (S1). The CIS barrier for the transfor-
mation of Ia (S1) into IIa (S1), via TSa (S1), is 11.5 kcal/
(14) Murov, S. L.; Carmichael, I.; Hug, G. L. Handbook of Photo-
chemistry, 2nd ed.; Marcel Dekker: New York, 1993; p 4.
(15) Wehry, E. L.; Rogers, L. B. J . Am. Chem. Soc. 1965, 87, 4234-
4238.
(16) Marciniak, B.; Kozubek, H.; Paszyc, S. J . Chem. Educ. 1992,
69, 247-249.
(17) Fo¨rster, T. Z. Elektrochem. 1950, 54, 521-535.
(18) Liotta, C. L.; Smith, D. F.; Hopkins, H. P.; Rhodes, K. A. J .
Phys. Chem. 1972, 76, 1909-1912.
J . Org. Chem, Vol. 68, No. 25, 2003 9645

Leo et al.
F IGURE 2. Structures of the stationary points involved in the photoisomerization of 1a and 1b into IIa and IIb. Compounds 1a
and 1b present an intramolecular OH-C interaction between the phenol hydrogen atom and the π system of the C2-C3 double
bond, indicated with dotted lines.
also computed. This reaction was chosen because it was
the least efficient in the series. Again, the relative
energies are given in Table 2, and the corresponding
geometries are shown in Figure 2. In the ground state,
the isomerization process for 2-(2′-cyclopentenyl)phenol
1b is slightly less endothermic, 23.1 kcal/mol, than for
the 2-(2′-cyclohexenyl)phenol 1a . It presents a similar
barrier (50.6 kcal/mol), but it is still unfavorable. In the
excited state, the barrier for the ring-opening process at
intermediate Ib (S1) is 19.0 kcal/mol, significantly higher
than the value found for Ia . In addition, transformation
of Ib (S1) into IIb (S1) is endothermic by 3.7 kcal/mol.
These results could explain the lack of isomerization of
1b into IIb. The larger barrier found for the bond-
breaking process at the intermediate Ib compared to Ia
is attributable to the larger stabilization of the former
(see Table 2). This stabilization is associated with the
relief of strain when hybridization changes from sp2 to
sp3 at the C2 carbon atom belonging to the cyclopentene
ring present in 1b (S1).
Con clu sion
In summary, we have gained further mechanistic
insight into the formation of 6-alkylidenecyclohexa-2,4-
dienones (o-quinone methides) by photolysis of o-cy-
cloalkenylphenols. Ring size appears to be a critical factor
in the process; the best results are obtained with the
cyclohexenyl derivatives. This is rationalized by DFT
calculations. The reaction efficiency also depends on
phenol substitution: electron-withdrawing groups ac-
celerate the reaction, whereas the reverse is true for
electron-donating substituents. This is consistent with
an ESIPT mechanism, as evidenced by the relative
acidity of the different phenols in their singlet excited
states. Finally, the reaction does not take place for the
F IGURE 3. Energy profile (in kcal/mol) for the isomerization
of 1a into IIa and 1b into IIb, at the S0 and S1 states.
excited triplet states, as shown by the lack of reaction in
the case of ketone 1g.
mol. In addition, transformation of Ia (S1) into IIa (S1)
is slightly exothermic by 1.4 kcal/mol. These values allow
us to understand the conversion of intermediate Ia (S1)
into IIa (S1). Finally, deexcitation of IIa (S1) allows
formation of IIa (S0). A schematic representation of the
PES for the transformation of 1a into IIa at the S0 and
S1 states is given in Figure 3.
To investigate the effects of ring size on the photo-
isomerization process, the S1 energies for the experimen-
tally unfavorable transformation of 2-cyclopentenylphe-
nol 1b into its corresponding o-quinone methide IIb were
Exp er im en ta l Section
2-(2′-Cycloocten yl)p h en ol (1d ). Oil. FTIR νmax (cm-1):
1
3610 (OH), 3498 (OH). H NMR (CDCl3, 300 MHz, δ): 7.22-
6.82 (m, 4H), 5.90 (m, 1H), 5.49 (t, 1H, J ) 10 Hz), 5.33 (s,
1H), 4.00-3.86 (m, 1H), 2.55-2.15 (m, 2H), 2.00-1.20 (m, 8H).
13C NMR (CDCl3, 75 MHz, δ): 154.2 (C), 132.9 (CH), 132.3
(CH), 131.8 (C), 127.3 (CH), 126.6 (CH), 120.8 (CH), 115.9
(CH), 35.3 (CH), 33.9 (CH2), 29.7 (CH2), 26.7 (CH2), 26.6 (CH2),
9646 J . Org. Chem., Vol. 68, No. 25, 2003

o-Quinone Methides from o-Cycloalkenylphenols
25.6 (CH2). MS m/z (%): 202 (M+, 75), 159 (34), 145 (46), 131
(32), 120 (84), 107 (100), 95 (37), 91 (23), 77 (23). HRMS m/z:
calcd for C14H18O, 202.1358; found, 202.1364.
NMR (CDCl3, 75 MHz, δ): 160.0 (C), 132.8 (CH), 126.9 (CH),
125.4 (CH), 122.3 (C), 115.5 (CH), 71.0 (CH), 28.1 (CH2), 25.0
(CH2), 18.8 (CH2). MS m/z (%): 242 (M+, 3), 162 (4), 143 (9),
81 (100), 80 (48), 79 (27). HRMS m/z: calcd for C13H13OF3,
242.0919; found, 242.0943.
2-(2′-Cycloh exen yl)-4-tr iflu or om eth ylp h en ol (1f). Oil.
FTIR νmax (cm-1): 3602 (OH), 3471 (OH). 1H NMR (CDCl3, 300
MHz, δ):7.37 (m, 2H), 6.86 (d, 1H, J ) 9 Hz), 6.10 (m, 1H),
5.75 (m, 2H), 3.61 (m, 1H), 2.30-1.40 (m, 6H). 13C NMR
(CDCl3, 300 MHz, δ): 156.8 (C), 131.9 (CH), 131.8 (C), 128.6
(CH), 126.8 (CH), 124.9 (C), 124.8 (CH), 120.1 (C), 116.2 (CH),
37.9 (CH), 29.7 (CH2), 24.9 (CH2), 21.2 (CH2). MS m/z (%): 242
(M+, 100), 227 (45), 223 (17), 213 (38), 199 (51), 188 (35), 175
(15), 145 (29). HRMS m/z: calcd for C13H13OF3, 242.0919;
found, 242.0917.
2-(2′-Cycloh exen yl)-4-a cetylp h en ol (1g). Solid, mp 99-
100 °C. Recrystallized from CH2Cl2/hexane. FTIR νmax (cm-1):
3600 (OH), 3458 (OH), 1680 (CdO). 1H NMR (CDCl3, 300 MHz,
δ): 7.8-7.74 (m, 2H), 6.85 (d, 1H, J ) 8 Hz), 6.15-6.06 (m,
2H), 5.86-5.80 (m, 1H), 3.61 (m, 1H), 2.55 (s, 3H), 2.20-1.50
(m, 6H). 13C NMR (CDCl3, 75 MHz, δ): 199.1 (C), 159.9 (C),
132.5 (CH), 131.0 (CH), 130.7 (C), 130.0 (C), 129.6 (CH), 129.4
(CH), 116.1 (CH), 36.8 (CH), 30.3 (CH2), 26.8 (CH3), 25.4 (CH2),
21.6 (CH2). MS m/z (%): 216 (M+, 70), 201 (100), 173 (15), 145
(16). HRMS m/z: calcd for C14H16O2, 216.1150; found, 216.1150.
Anal. Calcd for C14H16O2: C, 77.81; H, 7.46. Found: C, 77.36;
H, 7.35.
4-(2′-Cycloh exen yloxy)a cetop h en on e (3g). Solid, mp
47-49 °C. Recrystallized from CH2Cl2/hexane. FTIR νmax
(cm-1): 1684 (CdO), 1170. 1H NMR (CDCl3, 300 MHz, δ): 7.92
(d, 2H, J ) 9 Hz), 6.94 (d, 2H, J ) 9 Hz), 6.05-5.96 (m, 1H),
5.88-5.81 (m, 1H), 4.89 (m, 1H), 2.55 (s, 3H), 2.45-1.50 (m,
6H). 13C NMR (CDCl3, 75 MHz, δ): 196.6 (C), 161.8 (C), 132.8
(CH), 130.5 (CH), 129.9 (C), 125.3 (CH), 115.0 (CH), 70.8 (CH),
28.0 (CH2), 26.2 (CH3), 24.9 (CH2), 18.7 (CH2). MS m/z (%):
216 (M+, 7), 137 (100), 121 (26), 81 (85), 79 (56), 78 (26). HRMS
m/z: calcd for C14H16O2, 216.1150; found, 216.1142. Anal. Calcd
for C14H16O2: C, 77.81; H, 7.46. Found: C, 77.67; H, 7.55.
Com p u ta tion a l Meth od s. To evaluate the energies of the
intermediates and transition states in the excited singlet (S1)
state, the PES at the triplet (T1) excited state was first studied.
Then, the optimized triplet geometries were assumed to be the
same as in S1, and hence, they were used to obtain the S1
energies.
Density-functional theory19 calculations have been carried
out using the B3LYP or UB3LYP20 methods, together with the
standard 6-31G* basis set.21 The geometry optimizations of
singlet (S0) or triplet (T1) states were carried out using the
Berny analytical gradient optimization method.22 For mini-
mized triplet states, the UB3LYP wave functions showed
nonspin contamination ( s2 ≈ 2.0). Energies for the excited
singlet (S1) states were evaluated by configuration interaction
calculations including only single electronic excitations (CIS).23
All calculations were carried out with the Gaussian 98 suite
of programs.24
2-(1-Meth oxy-5-h exen yl)ph en ol (2a). Oil. FTIR νmax (cm-1):
3378 (OH), 1244. 1H NMR (CDCl3, 300 MHz, δ): 7.94 (s, 1H),
7.24-7.14 (m, 1H), 6.96-6.78 (m, 3H), 5.84-5.68 (m, 1H), 5.04
(m, 2H), 4.25 (t, 1H, J ) 7 Hz), 3.39 (s, 3H), 2.10-1.30 (m,
6H). 13C NMR (CDCl3, 75 MHz, δ): 155.3 (C), 138.4 (CH), 129.0
(CH), 128.4 (CH), 124.9 (C), 119.6 (CH), 116.8 (CH), 114.8
(CH2), 86.0 (CH), 57.3 (CH3), 35.4 (CH2), 33.1 (CH2), 25.1 (CH2).
MS m/z (%): 206 (M+, 25), 174 (57), 159 (17), 146 (20), 137
(100), 133 (60), 131 (25), 120 (25), 107 (16). HRMS m/z: calcd
for C13H18O2, 206.1307; found, 206.1354.
Ackn owledgm en t. Financial support from the Span-
ish MCYT (Grants BQU2001-2725 and BQU2002-
01032), the Generalitat Valenciana (Grant GV01-272),
and the Fundacio´n J ose´ y Ana Royo (fellowship to
E.A.L.) is gratefully acknowledged.
2-(1-Meth oxy-7-octen yl)ph en ol (2d). Oil. FTIR νmax (cm-1):
3377 (OH), 1243. 1H NMR (CDCl3, 300 MHz, δ): 7.92 (s, 1H),
7.20-7.12 (m, 1H), 6.94-6.76 (m, 3H), 5.84-5.68 (m, 1H),
5.00-4.86 (m, 2H), 4.21 (t, 1H, J ) 7 Hz), 3.36 (s, 3H), 2.06-
1.16 (m, 10H). 13C NMR (CDCl3, 75 MHz, δ): 138.4 (CH), 128.9
(CH), 128.4 (CH), 124.5 (C), 119.6 (CH), 116.8 (CH), 114.3
(CH2), 86.1 (CH), 57.2 (CH3), 35.9 (CH2), 33.6 (CH2), 28.8 (CH2),
28.7 (CH2), 25.6 (CH2). MS m/z (%): 234 (M+, 18), 202 (10),
137 (100), 133 (29), 120 (41), 107 (43). HRMS m/z: calcd for
Su p p or tin g In for m a tion Ava ila ble: General experimen-
1
tal procedures and H and 13C NMR spectra of compounds 1d ,
1f, 1g, 2a , 2d , 2e, 2f, 3f, and 3g. This material is available
free of charge via the Internet at http://pubs.acs.org.
C
15H22O2, 234.1620; found, 234.1630.
4-Met h oxy-2-(1-m et h oxy-5-h exen yl)p h en ol (2e). Oil.
FTIR νmax (cm-1): 3400 (OH), 1270, 1240. 1H NMR (CDCl3,
300 MHz, δ): 7.50 (s, 1H), 6.82-6.71 (m, 2H), 6.50 (d, 1H,
J ) 3 Hz), 5.82-5.66 (m, 1H), 5.20-4.86 (m, 2H), 4.16 (t, 1H,
J ) 7 Hz), 3.73 (s, 3H), 3.36 (s, 3H), 2.2-1.4 (m, 6H). 13C NMR
(CDCl3, 75 MHz, δ): 153.3 (C), 149.7 (C), 138.7 (CH), 126.0
(C), 117.7 (CH), 115.2 (CH), 114.5 and 114.1 (CH and CH2),
86.2 (CH), 57.7 (CH3), 56.1 (CH3), 35.7 (CH2), 33.9 (CH2), 25.5
(CH2). MS m/z (%): 236 (M+, 22), 204 (100), 189 (12), 175 (10),
163 (74), 161 (22), 152 (18), 150 (30), 137 (24), 107 (10). HRMS
m/z: calcd for C14H20O3, 236.1412; found, 236.1431.
J O034918V
(19) (a) Parr, R. G.; Yang, W. Density Functional Theory of Atoms
and Molecules; Oxford University Press: New York, 1989. (b) Ziegler,
T. Chem. Rev. 1991, 91, 651-667.
(20) (a) Becke, A. D. J . Chem. Phys. 1993, 98, 5648-5652. (b) Lee,
C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785-789.
(21) Hehre, W. J .; Radom, L.; Schleyer, P. v. R.; Pople, J . A. Ab Initio
Molecular Orbital Theory; Wiley: New York, 1986.
(22) (a) Schlegel, H. B. J . Comput. Chem. 1982, 3, 214-218. (b)
Schlegel, H. B. Geometry Optimization on Potential Energy Surfaces,
In Modern Electronic Structure Theory; Yarkony, D. R., Ed.; World
Scientific Publishing: Singapore, 1994.
(23) Foresman, J . B.; Head-Gordon, M.; Pople, J . A.; Frisch, M. J .
J . Phys. Chem. 1992, 96, 135-149.
(24) Frisch, M. J .; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J . R.; Zakrzewski, V. G.; Montgomery, J . A.,
J r.; Stratmann, R. E.; Burant, J . C.; Dapprich, S.; Millam, J . M.;
Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J .;
Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo,
C.; Clifford, S.; Ochterski, J .; Petersson, G. A.; Ayala, P. Y.; Cui, Q.;
Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;
Foresman, J . B.; Cioslowski, J .; Ortiz, J . V.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.;
Fox, D. J .; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
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1998.
2-(1-Meth oxy-5-h exen yl)-4-tr iflu or om eth ylp h en ol (2f).
Oil. FTIR νmax (cm-1): 3346 (OH), 1329, 1126. 1H NMR (CDCl3,
300 MHz, δ): 8.39 (s, 1H), 7.45 (dd, 1H, J 1 ) 8 Hz, J 2 ) 2 Hz),
7.20 (m, 1H), 6.93 (d, 1H, J ) 8 Hz), 5.86-5.68 (m, 1H), 5.06-
4.90 (m, 2H), 4.30 (dd, 1H, J 1 ) 8 Hz, J 2 ) 6 Hz), 2.03-1.30
(m, 6H). 13C NMR (CDCl3, 75 MHz, δ): 158.3 (C), 138.1 (CH),
126.3 (CH), 125.5 (CH), 121.8 (C), 117.2 (CH), 115.0 (CH2),
85.6 (CH), 57.6 (CH3), 35.3 (CH2), 33.4 (CH2), 24.9 (CH2). MS
m/z (%): 274 (M+, 6), 242 (20), 227 (11), 205 (100), 201 (27),
188 (17), 175 (14). HRMS m/z: calcd for C14H17O2F3, 274.1181;
found, 274.1174.
1-(2′-Cycloh exen yloxy)-4-tr iflu or om eth ylben zen e (3f).
Oil. FTIR νmax (cm-1): 1165. 1H NMR (CDCl3, 300 MHz, δ):
7.53 (d, 2H, J ) 8 Hz), 6.97 (d, 2H, J ) 8 Hz), 6.06-5.98 (m,
1H), 5.90-5.80 (m, 1H), 4.85 (m, 1H), 2.26-1.56 (m, 6H). 13C
J . Org. Chem, Vol. 68, No. 25, 2003 9647