Cyclic allene intermediates in intramolecular dehydro Diels-Alder reactions: Labeling and theoretical cycloaromatization studies

Article abstract of DOI:10.1021/jo0265380

A comprehensive theoretical and experimental investigation of dehydro Diels-Alder reactions examining the evolution of the cyclic allene intermediates under conditions for intramolecular and ionic and radical intermolecular cycloaromatization processes is

Full text of DOI:10.1021/jo0265380

Cyclic Allen e In ter m ed ia tes in In tr a m olecu la r Deh yd r o
Diels-Ald er Rea ction s: La belin g a n d Th eor etica l
Cycloa r om a tiza tion Stu d ies†
David Rodr´ıguez, Armando Navarro-Va´zquez, Luis Castedo, Domingo Dom´ınguez,* and
Carlos Saa´*
Departamento de Quı´mica Orga´nica y Unidad Asociada al CSIC, Facultad de Qu´ımica, Universidad de
Santiago de Compostela, 15782 Santiago de Compostela, Spain
qocsaa@usc.es
Received October 8, 2002
A comprehensive theoretical and experimental investigation of dehydro Diels-Alder reactions
examining the evolution of the cyclic allene intermediates under conditions for intramolecular and
ionic and radical intermolecular cycloaromatization processes is reported. Theoretical calculations
showed that the most favored intramolecular path for cycloaromatization of 1,2,4-cyclohexatriene
4 and its benzoannulated derivative 14, strained cyclic allenes, consists of a pair of successive [1,2]
H shifts rather than a [1,5] shift. Cycloaromatization of cyclic allenes may follow both inter- and
intramolecular pathways, depending on the experimental conditions (use of protic or aprotic
solvents). For synthetic purposes, the best procedure is to use a protic solvent to promote the ionic
intermolecular route, the fastest and highest yielding. When the reaction is carried out in CCl4,
intermolecular radical addition of chlorine to the cyclic allene competes with intramolecular
aromatization paths. Theoretical calculations predict a low barrier for the reaction of cyclic allenes
with carbon tetrachloride, and that the cyclic allenes act as nucleophiles in this reaction.
In tr od u ction
and which normally evolve to aromatic products by
isomerization. For the reaction of diarylacetylenes 15b,c
in the presence of MeOH(D) as proton source, deuterium
experiments have recently demonstrated that this isomer-
ization takes place by means of an intermolecular ionic
mechanism rather than an intramolecular hydrogen shift
(Scheme 2).10
These experimental results can be explained in terms
of the bonding in the putative intermediates. Specifically,
we have shown that the allene moiety of cyclic allenes
The intramolecular dehydro Diels-Alder reactions
(intramolecular [4+2] cycloadditions) of alkynes with
certain enynes have long been known1 and are well-
documented.2 During the past decade considerable effort
has gone into generalizing this cyclization to other
enynes3 and arylacetylenes (arenynes)4 so as to harness
it for the synthesis of polycyclic aromatic compounds. For
example, the intramolecular [4+2] cycloadditions of 1a -d
give the tetracyclic nuclei of benzo[b]fluorenes 2a -d 5 and
benzo[a]fluorene 3d ,6 which belong to classes of natural
compounds that exhibit interesting biological activity
(Scheme 1).7
(5) (a) Schmittel, M.; Strittmatter, M.; Schenk, W. A.; Hagel, M. Z.
Naturforscher 1998, 53b, 1015-1020. (b) Rodr´ıguez, D.; Navarro, A.;
Castedo, L.; Dom´ınguez, D.; Saa´, C. Org. Lett. 2000, 2, 1497-1500. (c)
Rodr´ıguez, D.; Castedo, L.; Dom´ınguez, D.; Saa´, C. Tetrahedron Lett.
1999, 40, 7701-7704. For synthesis of benzo[b]fluorenes by intramo-
lecular [4+2] cycloaddition of alkynes to allenes, see: Frutos, O.;
Echavarren, A. M. Tetrahedron Lett. 1997, 38, 7941-7942.
(6) Atienza, C.; Mateo, C.; de Frutos, OÄ .; Echavarren, A. M. Org.
Lett. 2001, 3, 153-155.
(7) (a) Gould, S. J . Chem. Rev. 1997, 97, 2499-2510. (b) Gould, S.
J .; Melville, C. R.; Cone, M. C.; Chen, J .; Carney, J . R. J . Org. Chem.
1997, 62, 320-324. (c) Protean, P. J .; Li, Y.; Chen, J .; Thomas
Williamson, R.; Gould, S. J .; Laufer, R. S.; Dmitrienko, G. I. J . Am.
Chem. Soc. 2000, 122, 8325-8326 and references therein.
(8) For a review of the reactivity and structure of cyclic allenes,
see: J ohnson, R. P. Chem. Rev. 1989, 89, 1111-1124.
(9) (a) Roth, W. R.; Hopf, H.; Horn, C. Chem. Ber. 1994, 127, 1765-
1779. (b) Hopf, H.; Berger, H.; Zimmermann, G.; Nu¨chter, U.; J ones,
P. G.; Dix, I. Angew. Chem., Int. Ed. Engl. 1997, 36, 1187-1190. (c)
Ferna´ndez-Zertuche, M.; Herna´ndez-Lamoneda, R.; Ram´ırez-Sol´ıs, A.
J . J . Org. Chem. 2000, 65, 5207-5211. (d) Prall, M.; Kru¨ger, A.;
Schreiner, P. R.; Hopf, H. Chem. Eur. J . 2001, 7, 4386-4394.
(10) Keto-enol isomerization of 3-hydroxy-1,2,4-cyclohexatriene to
cyclohexa-2,5-dien-1-one through intramolecular proton transfer has
recently been studied at the MP2(fc)/6-31G** level. The computed
barrier to this process was only 6.7 kcal/mol, which suggests that the
trapping of hydrogens in cyclic allenes made available by protic
solvents may be a fast reaction. See ref 9c.
The intermediates in these reactions are 1,2,4-cyclo-
hexatrienes, strained cyclic allenes8 that are also ob-
served in the electrocyclization of 1,3-hexadien-5-ynes9
† This paper is dedicated to the late Prof. Antonio Gonza´lez
Gonza´lez.
(1) Michael, A.; Bucher, J . E. Chem. Ber. 1895, 28, 2511-2512.
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Daoust, K. J .; Bradley, A. Z.; DiRico, K. J .; J ohnson, R. P. J . Am. Chem.
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10.1021/jo0265380 CCC: $25.00 © 2003 American Chemical Society
Published on Web 02/07/2003
1938
J . Org. Chem. 2003, 68, 1938-1946

Intramolecular Dehydro Diels-Alder Reactions
SCHEME 1
SCHEME 2
In the course of this work Hopf/Schreiner12 have
reported an excellent computational study about isomer-
ization of 1,2,4-cyclohexatriene to benzene at BLYP and
coupled-cluster BCCD(T) levels. They conclude that the
most favored intramolecular path consists of a pair of
successive [1,2] H shifts rather than a [1,5] shift.
Here we present the results of a comparable DFT/
B3LYP computational study corroborating previous con-
clusions and the results of isotopic labeling experiments
on the relative importance of intra- and intermolecular
paths under protic, aprotic, and radical-generating condi-
tions.
F IGURE 1. Reactivity of cyclic allenes.
can be regarded as featuring a bond between an sp2-like
orbital on the central carbon and an allyl π orbital (Figure
1),5b which allows the products and transition states of
both intermolecular ionic and intermolecular radical
reactions to benefit from allylic stabilization. This bond-
ing may make the thermally allowed [1,5] hydrogen shift,
sometimes postulated as an intramolecular pathway,
significantly different from standard [1,5] H shifts.11 To
fully understand the intramolecular and ionic and radical
intermolecular cycloaromatization processes of cyclic
allenes we have undertaken a comprehensive investiga-
tion of the dehydro Diels-Alder reaction.
Com p u ta tion a l Meth od ology
All structures were optimized by DFT methods, using the
B3LYP13,14 functional as implemented in Gaussian 9815 in
conjunction with the 6-31G*16 basis set. Whether stationary
(12) (a) See ref 9d, see also comments in ref 56 of this work. (b) For
several post-HF calculations, see: Anakinov, V. P. J . Phys. Org. Chem.
2001, 14, 109-121.
(13) Becke, A. D. J . Chem. Phys. 1993, 98, 5648-5652.
(14) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785-789.
(11) For computational studies of the [1,5] H shift, see: J iao, H.;
Schleyer, P. v. R. J . Chem. Soc., Faraday Trans. 1994, 90, 1559-1567.
J . Org. Chem, Vol. 68, No. 5, 2003 1939

Rodr´ıguez et al.
TABLE 1. Rela tive En er gies (∆H0K, k ca l/m ol) of th e Sp ecies P oten tia lly In volved in Isom er iza tion of Cycloh exa tr ien e
(4) a n d Ison a p h th a len e (14) a t th e B3LYP a n d CCSD(T) Levels
4 (1A)
4i (1A)
4ii (3A)
5
6
7i (1A)
7ii(3A)
8
9
13
14
15
16
B3LYP
CCSD(T)
0.0
2.2
4.6
49.6
48.0
27.8
31.9
5.8
2.2
11.2
61.6
-81.4
-75.5
0.0
0.0
17.9
23.9
-101.5
-91.7
points were minima or first-order saddle points was deter-
mined by analytical computation of vibrational frequencies.
The minima connected via the saddle points detected were
identified by visualization of the normal mode associated with
the imaginary frequency. Zero-point vibrational energies were
scaled by a factor of 0.9804.17
tensors at the B3LYP/6-311+G**/B3LYP/6-31G* level, using
the GIAO28 method.
For intermolecular reactions with carbon tetrachloride,
energies were computed by single-point calculations at the
B3LYP/6-311+G**16 level to minimize the impact of basis set
superposition error. The role of the solvent was taken into
account by single-point B3LYP/6-311+G** calculations on the
B3LYP/6-31G* structures, using the Polarized Continuum
model (PCM)29 of Tomasi and co-workers.
For high and low open-shell species an unrestricted formal-
ism was used in the DFT calculations. When a restricted
solution was obtained for species that include some biradical
character, the stability of the determinant was confirmed by
Charges and Wiberg30 bond indices were calculated by
NBO31 analysis of the B3LYP density.
using the algorithm implemented in Gaussian 98.18 In recent
9d,19,20
studies
it has been proven that the use of the hybrid
B3LYP functional in combination with unrestricted determi-
nant can provide good activation and reaction energies in
processes involving open-shell singlets, with a low computa-
tional cost.
Resu lts a n d Discu ssion
In t r a m olecu la r Isom er iza t ion : Com p u t a t ion a l
Stu d ies. The structure of 1,2,4-cyclohexatriene has
previously been computed at semiempirical,32 DFT,9d,19a,33
MP2,12b and MRCI34 levels. These studies predict the
chiral singlet ground-state structure 4.35 The reaction is
highly exothermic, the reaction enthalpy ∆H0K being
-81.4 kcal/mol at the B3LYP level and -75.5 kcal/mol
by CCSD(T) (Table 1).36
The [1,5] hydrogen shift path from 4 to 13 passes
through the transition structure 5 (Scheme 3, path a),
in which the reactive termini are brought together by a
highly distorted geometry with a C6-C1-C2 bond angle
of 94° (Figure 2). This transition structure shows some
degree of asynchrony, as the C2-H distance, 1.377 Å, is
appreciably shorter than C6-H (1.469 Å). Since C1 lies
far from the plane defined by the other carbons, there is
no aromatic stabilization and the barrier is very high,
49.6 kcal/mol at the B3LYP/6-31G* level and 48.0 kcal/
mol by CCSD(T) calculations,37 making it unlikely that
this is the path followed in cyclohexatriene aromatization.
The alternative aromatization pathway b involves two
[1,2] hydrogen shifts (Scheme 3). The first leads to the
cyclohexa-2,4-dienylidene σ-π diradical 7 via transition
For structures of closed-shell nature, further single-point
calculations were performed at the CCSD(T)21 level (single-
reference coupled clusters methods are unreliable for molecules
with strong biradical character; this is alleviated in ref 9d by
the use of BCCD(T)22 method). All coupled-cluster calculations
used an RHF determinant as reference. For species 7, further
multireference calculations were performed at the MCQDPT223
level, using the PC-GAMESS24 version of the GAMESS-US25
package. All these coupled-cluster and multireference calcula-
tions used a cc-pVDZ basis set26 and the frozen core ap-
proximation. Nucleus-Independent Chemical Shifts (NICS)27
were determined by computation of the isotropic shielding
(15) 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.; Baboul, A. G.; 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.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.;
J ohnson, B.; Chen, W.; Wong, M. W.; Andres, J . L.; Gonza´lez, C.; Head-
Gordon, M.; Replogle, E. S.; Pople, J . A. Gaussian 98, Revision A.7;
Gaussian, Inc.: Pittsburgh, PA, 1998.
(16) Hehre, W.; Radom, L.; Schleyer, P. v. R.; Pople, J . A. Ab Initio
Molecular Orbital Theory; Wiley: New York, 1986.
(17) Wong, M. W. Chem. Phys. Lett. 1996, 256, 391-399.
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9047-9052.
(19) (a) Bettinger, H. F.; Schreiner, P. R.; Schaefer, H. F., III;
Schleyer, P. v. R. J . Am. Chem. Soc. 1998, 120, 5741-5744. (b)
Schreiner, P. R.; Prall, M. J . Am. Chem. Soc. 1999, 121, 8615-8617.
(20) For a clear treatment of this problem see: Gra¨fenstein, J .;
Hjerpe, A. M.; Kraka, E.; Cremer, D. J . Phys. Chem. A 2000, 104,
1748-1761.
(21) Pople, J . A.; Head-Gordon, M.; Raghavachari, K. J . Chem. Phys.
1987, 87, 5968-5975.
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index.html.
(25) Schmidt, M. W.; Baldridge, K. K.; Boatz, J . A.; Elbert, S. T.;
Gordon, M. S.; J ensen, J . H.; Koseki, S.; Matsunaga, N.; Nguyen, K.
A.; Su, S. J .; Windus, T. L.; Dupuis, M.; Montgomery, J . A. J . Comput.
Chem. 1993, 14, 1347.
(26) Davidson, E. R. Chem. Phys. Lett. 1996, 260, 514-517. For CC
calculations orbitals were expressed as spherical harmonics whereas
a Cartesian expression was used in MCQDTP2 calculations.
(27) Schleyer, P. v. R.; Maerker, C.; Dransfeld, A.; J iao, H.; Hommes,
N. J . R. v. E. J . Am. Chem. Soc. 1996, 118, 6317-6318.
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112, 8251-8260.
(29) Miertus, S.; Scrocco, E.; Tomasi Chem. Phys. 1981, 55, 117-
129.
(30) Wiberg, K. Tetrahedron 1968, 24, 1083-1096.
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899-926.
(32) J anoschek, R. Angew. Chem., Int. Ed. Engl. 1992, 31, 476-
478. These were MCSCF calculations with two electrons in two orbitals.
(33) Freeman, P. K.; Pugh, J . K. J . Org. Chem. 1999, 64, 3947-
3953.
(34) Engels, B.; Schoneboom, J . C.; Munster, H. F.; Groetsch, S.;
Christl, M. J . Am. Chem. Soc. 2002, 124, 287-297.
(35) Structure 4 undergoes racemization through the Cs singlet
diradical transition structure 4i, which we have computed to be 2.2
kcal/mol above 4 (the triplet Cs structure 4ii is a minimum in the triplet
surface and lies 4.6 kcal/mol above 4). This value is very close to the
AM1 value obtained by J anoschek32 (2.0 kcal/mol) and also quite close
to the BLYP value obtained by Schreiner (5.9 kcal/mol). All these
values suggest that racemization of 4 is a very fast process (Scheme
3). However, post-HF methods such as BCCD(T) (ref 9d) and CASPT2
and MRCI (ref 34) indicate a higher value of about 10 kcal/mol.
(36) The apparent discrepancy between experimental and theoretical
reaction enthalpies has recently been resolved; see ref 34.
(37) The QCISD(T)/6-311G** barriers to [1,5] H shifts in 1,3-
cyclopentadiene and 1,3-pentadiene at 0 K are 29.7 and 40.0 kcal/mol,
respectively. See ref 12.
1940 J . Org. Chem., Vol. 68, No. 5, 2003

Intramolecular Dehydro Diels-Alder Reactions
F IGURE 2. Geometrical parameters and bond orders (italics) of all computed species. For 7, values for the singlet state 7i are
followed by values for the triplet state 7ii.
SCHEME 3. Rea ction P a th w a ys for In tr a m olecu la r Isom er iza tion of 1,2,4-Cycloh exa tr ien e 4 to Ben zen e
structure 6. Schleyer and co-workers,19,38 who studied this
species at the B3LYP/TZ2P//B3LYP/DZP level as a pos-
sible intermediate in the topoisomerization of benzene,
concluded that, unlike the Cs structure between 4 and
ent-4, it has as a triplet ground-state structure; Hopf/
Schreiner’s9d BLYP calculations afforded a biradical
singlet ground state (albeit with a very small singlet-
triplet gap); and single-configuration BCCD(T) calcula-
tions predicted a zwitterionic structure. According to our
B3LYP calculations the triplet state 7ii is located 2.2
kcal/mol above 4 and 3.6 kcal/mol below the singlet state
7i, a triplet-singlet gap even larger than that obtained
by Schleyer, 2.9 kcal/mol; the preference for the triplet
state at this computational level appears to be due to its
strong delocalization of the π system endowing C2 with
both σ and π spin density (Scheme 4) and thereby
reducing electronic repulsion relative to the singlet state
7i, in which C2 only has σ density. Multireference
MCQDPT2(6,6) calculations on the geometry of 7ii
nevertheless afforded a singlet ground state lying 3.9
kcal/mol below the triplet state (and 31.9 kcal/mol below
the most stable zwitterionic state), implying that, as
J . Org. Chem, Vol. 68, No. 5, 2003 1941

Rodr´ıguez et al.
SCHEME 4. Reson a n t Str u ctu r es a n d Sp in
Den sity Rep r esen ta tion of Dir a d ica l 7 (3A Sta te)
SCHEME 5
Hopf/Schreiner found, the true intermediate structure
must also be in a singlet state. Note that the C3-C4-
C5-C6 angle of 19° in the C1 B3LYP singlet structure
7i suggests a degree of σ-π coupling. In both 7i and 7ii
the C2-C3 and C5-C6 bonds are shorter than C3-C4
and C4-C5 because the former have double-bond char-
acter in two resonant structures and the latter in only
one.
In the singlet surface the transition structure 6 pre-
sents a barrier of 27.8 kcal/mol to the process 4 f 7. This
is much lower than that for the [1,5] H shift. In 6, the
carbon skeleton is nearly planar (the C2-C3-C4-C5
dihedral angle is only 6°), which allows more efficient π
overlapping than in 5.
The second [1,2] hydrogen shift in path b, 7 f 8 f 13,
involves overcoming a barrier of only 5.4 kcal/mol from
singlet 7i. Transition structure 8, in which the migrating
hydrogen lies over the C1-C2 bond, is stabilized by
conjugation beginning to extend to the sixth carbon atom.
In keeping with this the geometry of 8 indicates an early
transition, having C1-H and C2-H bond lengths of 1.196
and 1.464 Å, respectively.
Another possible path from 4 to singlet 7i consists of
a [1,2] hydrogen shift between C1 and C2 via transition
structure 9 (path c, Scheme 3). However, this process
involves overcoming a barrier of 62.8 kcal/mol. Due to
the late attainment of the transition structure it has a
strong biradical character, so much so that the unre-
stricted Kohn-Sham determinant fails to exhibit spatial
spin-symmetry ( S2 ) 0.863).
F IGURE 3. NICS at selected points in the vicinity of
transition structures 6 and 15.
means that intramolecular isomerization might well
compete with intermolecular ionic or radical processes
in the naphthalenic systems we have studied experimen-
tally (Scheme 2).
All attempts to optimize a naphthalenic biradical
analogue of 7 led to naphthalene (16), the biradical
proving to be an inflection point rather than a minimum
of the potential surface. The whole isomerization process
14 f 16 has an enthalpy of -101.5 kcal/mol. As in the
parent system, the transition state 15 possesses a closed-
shell character and a nearly planar geometry. Ten
electrons contribute to the π system, and two occupy an
sp2-like orbital, centered on C2, lying in the molecular
plane. The aromatic character of 15 is corroborated, as
in 6, by the bond lengths being more uniform than in
the starting structure; the fact that C1-C6 is shortened
to 1.486 Å in 6, but elongated to 1.530 Å in 15, is in
keeping with their numbers of ring delocalized electrons,
six and ten, respectively. The aromatic character is also
indicated by the moderately negative NICS27 calculated
for the ring centers and for points 1.0 Å above and
beneath them (see Figure 3).40 At the same level, NICS
of -8.0 and -10.2 ppm were obtained for points 0.0 and
1.0 Å above the center of the benzene molecule, and
values of -8.6 and -10.6 ppm for the naphthalene
molecule.
Summing up, as Hopf/Schreiner found,9d the [1,5]
hydrogen shift ought not to be an operative pathway for
the isomerization of 1,2,4-cyclohexatriene to benzene,
which may, however, take place through a path of much
lower energy consisting of two consecutive [1,2] hydrogen
shifts, the rate-limiting first shift leading to cyclohexa-
2,4-ylidene as intermediate. Benzoannulation signifi-
cantly favors this intramolecular pathway due to exten-
sion of the conjugation system of the first transition
structure.
Hopf/Schreiner9d considered a fourth mechanism (path
d, Scheme 3) in which the 1,1-biradical 11 is formed via
the transition structure 10 (33 kcal/mol above 4) and
yields benzene 13 upon [1,4] hydrogen migration via
transition structure 12. However, the barrier to this
second step is 48 kcal/mol, which clearly rules out this
reaction path.
Effect of Ben zoa n n u la tion . Benzo[f]annulation39 of
4 to isonaphthalene 14 lowers the barrier to the first [1,2]
hydrogen shift of path b (Scheme 5) by nearly 10 kcal/
mol (∆H ) 17.9 kcal/mol; see Table 1). This difference in
activation enthalpy must be attributed to conjugation in
transition state 15 being more extensive than in 6, and
Exp er im en ta l Resu lts: Isotop ic La belin g. To com-
pare the intermolecular ionic path with the intramolecu-
lar path we studied the thermal behavior of deuterated
ynone 1a -d5 in the presence and absence of a proton
source. Compound 1a -d5 was prepared following the
(38) The transition structures 6 and 8 were also computed in ref
19, with geometric results very close to ours.
(39) Hopf/Schreiner found that benzo[c]annulation of cyclohexatriene
increased the barrier to aromatization via path b; see ref 9d.
(40) Calculations for this set of points minimizes the effects of σ
bonds on NICS.
1942 J . Org. Chem., Vol. 68, No. 5, 2003

Intramolecular Dehydro Diels-Alder Reactions
SCHEME 6
SCHEME 8
150 °C afforded two silylated products with similar TLC
retention factors. Treatment of a THF solution of the
reaction mixture with TBAF for 5 min allowed separation
of a 59% yield of the expected desilylated benzo[b]flu-
orenone 2a (70% as 2a -d5) from a 23% yield of the re-
arranged silylated benzo[c]fluorenone 1944 (60% as 19-
d5, 40% as 19-d4). It is worth noting that 19, unlike 2b,
failed to desilylate under mild conditions.45
SCHEME 7
Rearranged aromatic products like those from dehy-
dro Diels-Alder reactions such as 19 have also been
obtained from other TMS-ethynyl-substituted starting
compounds.6,46 In the present case, rearrangement will
have involved production of the 1,2-dehydro[10]annulene
21a by opening of the initial cyclic allene intermediate
20, isomerization of 21a to 21b, [1,6]-electrocyclization
of 21b to a second cyclic allene 22, and aromatization of
the latter to the rearranged benzo[c]fluorenone 19 (Scheme
9).
Finally, we compared the intermolecular radical path
with the intramolecular path by studying the thermal
behavior of ynone 1b in CCl4.47 Heating a 127 mM CCl4
solution of 1b for 10 h in a sealed tube at 150 °C afforded
both a fraction containing products of the intramolecular
path (a 6.5:1 mixture of benzo[b]- and benzo[c]fluorenones
2b and 1944 in 41% combined yield) and a fraction
containing a 32% yield of the product of the intermolecu-
lar path, the 5-chlorobenzo[b]fluorenone 23 (Scheme 10).
Remarkably, not only did the two cycloaromatization
pathways compete, but the ratio of the linear to the
rearranged product of the intramolecular path, 6.5:1, was
higher than under nonradical conditions (2.5:1, Scheme
8).
sequence depicted in Scheme 6: Sonogashira coupling of
arylacetylene 1741 with iodobenzene-d5 gave a 76% yield
of the diarylacetylenic alcohol 18, which quantitative
oxidation to ketone 1b -d5 and subsequent desilylation
with Borax42 transformed into the desired deuterated
ynone 1a -d5 in 85% yield.
Heating a solution of 1a -d5 in 90:10 (v/v) toluene/MeOH
for 10 h in a sealed tube at 150 °C gave benzo[b]fluor-
enone 2a -d4 in 72% yield with no accompanying 2a -d5
(Scheme 7); similarly, when a 90:10 mixture of toluene/
MeOD was used, benzo[b]fluorenone 2a -d5 was obtained
with no 2a -d4. Heating a dry, deoxygenated 25 mM
solution of 1a -d5 in benzene for 10 h in a sealed tube at
150 °C gave a 50% yield of benzo[b]fluorenone 2a , 60%
as 2a -d5 and 40% as 2a -d4 (Scheme 7).43 The appearance
of 2a -d4 is attributed to an ionic intermolecular path
involving adventitious proton sources.
(44) Thermolysis of 1b followed by desilylation gave a 61% yield of
2a and 28% yield of 19 (nondeuterated), this latter confirmed by X-ray
analysis. Rodr´ıguez, D.; Navarro-Va´zquez, A.; Castedo, L.; Dom´ınguez,
D.; Saa´, C. Tetrahedron Lett. 2002, 43, 2717-2720.
(45) Toyota, M.; Terashima, S. Tetrahedron Lett. 1989, 30, 829-
832.
Due to a certain instability of ynone 1a -d5, we decided
also to evaluate the thermal behavior of the stable
silylated ynone 1b-d5 (Scheme 8). Surprisingly, heating
a benzene solution of 1b-d5 for 10 h in a sealed tube at
(46) Rodr´ıguez, D.; Navarro-Va´zquez, A.; Castedo, L.; Dom´ınguez,
D.; Saa´, C. J . Am. Chem. Soc. 2001, 123, 9178-9179.
(47) A pending question is whether the conversion of a cyclic allene
to an aromatic ring might be bimolecular rather than unimolecular
even in the absence of proton sources other than the cyclic allene itself,
the proton at position 5 of 2a , for example, being provided by a second
molecule of the substrate. Unfortunately, no clear answer to this
question was provided by the MS spectrum of the products of the
crossover experiment we carried out to investigate this (heating a 1:5
mixture of 1b and 1b-d5 in benzene, followed by treatment with TBAF).
(41) Bru¨ckner, R. Synlett 1994, 51-53. Bru¨ckner, R. Liebigs Ann.
1996, C41, 447-456 and 457-471.
(42) Walton, D. R. M.; Waugh, F. J . Organomet. Chem. 1972, 37,
45-56.
(43) Determined by integration of the signals of the 1H NMR of the
purified product.
J . Org. Chem, Vol. 68, No. 5, 2003 1943

Rodr´ıguez et al.
SCHEME 9
SCHEME 10
To exclude contributions to the total amount of linear
benzo[b]fluorenone 2b by adventitious intermolecular
protonation, we repeated the experiment using deuter-
ated 1b-d5 as starting material. Gratifyingly, product
yields and ratios were similar to those obtained previ-
ously: a fraction containing a 10:1 mixture of benzo[b]-
fluorenone 2b (80% as 2b-d5) and benzo[c]fluorenone 19
in 38% combined yield was accompanied by a 44% yield
of the chlorinated benzo[c]fluorenone 23-d4 (Scheme 10).
The above results seem to indicate that intermolecular
radical addition of CCl4 can compete with the intramo-
lecular aromatization path leading to benzo[b]- and
benzo[c]fluorenones. To investigate this, we studied the
radical addition process computationally in the cases of
the simpler intermediates 4 and 14. PCM calculations
showed that the enthalpy barrier to chlorine abstraction
is 5.4 kcal/mol for cyclohexatriene 4 and as low as 2.9
kcal/mol for isonaphthalene 14 (Figure 4). Gas-phase
NBO charge analysis showed that in the transition states
24 and 25 total charges of respectively -0.176 and
-0.208 (-0.227 and -0.283 by the PCM calculations) are
transferred from the allene to the carbon tetrachloride
moiety, indicating the nucleophilic character of cyclic
allenes in halogen addition reactions. Due to this transfer
of charge in the transition states, solvation slightly lowers
the activation barriers, to 4.9 and 2.8 kcal/mol, respec-
tively (Figure 4).
F IGURE 4. Selected parameters of transition states 24 and
25 at the B3LYP/6-311+G**//B3LYP/6-31G* level. Light face
type, bond lengths; bold face type, NBO charges (chlorine and
CCl3 moieties). Left: gas-phase value. Right: PCM/toluene
value. Activation enthalpies: roman type, gas-phase value;
italic type, PCM/toluene value.
Interestingly, we also found that formation of a radical
pair, 26-27, is ca. 20 kcal/mol more favored than
formation of a contact ionic pair, 28-29, even when
solvation effects are taken into account (Figure 5).
In conclusion, our computational results thus show, in
agreement with the experimental findings, that the
intermolecular and therefore entropically disfavored
chlorine addition reaction can compete effectively, due
to its low enthalpic barrier (2.9 kcal/mol), with the
intramolecular aromatization pathway (∆H ) 17.9 kcal/
mol).
1944 J . Org. Chem., Vol. 68, No. 5, 2003

Intramolecular Dehydro Diels-Alder Reactions
was added an aqueous solution of Borax (5 mL, 0.01 M) and
the mixture was stirred for 2 h. After removing the volatiles
the resulting residue was solved in EtOAc (20 mL) and washed
with brine (3 × 20 mL). The organic layer was dried over
anhydrous Na2SO4 and evaporated to dryness. The crude
residue was purified by column chromatography on silica gel,
using hexane/EtOAc 9:1 as eluent, to yield 1a -d5 (150 mg, 85%)
as a colorless oil. 1a -d5 proved to be rather unstable both neat
and in solution but it could be stored at -30 °C for several
1
days. H NMR (CDCl3, 250 MHz) δ 8.19 (dd, J ) 7.8, 1.5 Hz,
1H), 7.69-7.65 (m, 1H), 7.57 (td, J ) 7.6, 1.5 Hz, 1H), 7.49-
7.42 (m, 1H), 3.44 (s, 1H); EI-MS m/z 235 (M+, 100), 207 (62),
204 (19).
Gen er a l P r oced u r e for Th er m a l Cycliza tion s. A solu-
tion of the ynone in dried and degassed solvent (concentration
from 25 to 130 mM) was placed in a sealed tube and heated
overnight at 150 °C in a silicon oil bath. After evaporation of
the solvent, the crude material was purified by column
chromatography on silica gel, using hexane/EtOAc as eluent.
F IGUR E 5. Reaction enthalpies (kcal/mol) at the B3LYP/
6-311+G** level calculated for the formation of contact radical
and ionic pairs from cyclic allenes and carbon tetrachloride
(gas-phase values, with PCM/toluene values in parentheses).
Con clu sion s
To sum up, the cycloaromatization of cyclic allenes may
follow both inter- and intramolecular pathways, depend-
ing on the experimental conditions. For synthetic pur-
poses, the best procedure is to use a protic solvent to
promote the ionic intermolecular route, the fastest and
highest-yielding. Theoretical calculations show that ben-
zoannulation significantly lowers the barrier to the rate-
limiting [1,2] H transfer of the intramolecular route. Our
calculations also predict a very low barrier for the
reaction of cyclohexatrienes with carbon tetrachloride,
and that cyclic allenes act as nucleophiles in this reaction.
Th er m a l Cycliza tion of 1a -d 5. A solution of 1a -d5 (70 mg,
0.30 mmol, 30 mM) in toluene (9 mL) and CH3OH (1 mL) was
heated under the general conditions. After column chroma-
tography on silica gel, using hexane/EtOAc 9:1 as eluent,
benzo[b]fluorenone 2a -d4 (50 mg, 72%) was isolated as a yellow
1
solid; H NMR (CDCl3, 250 MHz) δ 8.17 (s, 1H), 7.87 (s, 1H),
7.75 (d, J ) 7.2 Hz, 1H), 7.71 (d, J ) 7.6 Hz, 1H), 7.56 (t, J )
7.6 Hz, 1H), 7.34 (t, J ) 7.2 Hz, 1H); EI-MS m/z 234 (M+, 100),
206 (28). Similarly, when the reaction was carried out with
toluene and CH3OD as solvents, benzo[b]fluorenone 2a -d5
(70%) was obtained; 1H NMR (CDCl3, 250 MHz) δ 8.17 (s, 1H),
7.75 (d, J ) 7.2 Hz, 1H), 7.71 (d, J ) 7.6 Hz, 1H), 7.56 (t, J )
7.6 Hz, 1H), 7.34 (t, J ) 7.2 Hz, 1H); EI-MS m/z 235 (M+, 100),
207 (27). Finally, when the reaction was carried out with
benzene as solvent, a 50% yield of benzo[b]fluorenone 2a was
obtained, being 60% of the material 2a -d5 and the remaining
40% 2a -d4 as shown by integration of the singlet at 7.87 ppm
Exp er im en ta l Section
Gen er a l P r oced u r es. All reactions were carried out under
argon and solvents were purified and dried following standard
procedures. Deuterated compounds were characterized by
mass spectrometry and TLC comparison with the correspond-
ing protonated analogues.5b,43
1
of H NMR of the purified product.
Th er m a l Cycliza tion of 1b-d 5 in Ben zen e. A solution of
1b-d5 (120 mg, 0.39 mmol, 65 mM) in freshly distilled benzene
(6 mL) was heated under the general conditions. After
evaporation of the solvent, the residue was solved in THF (6
mL) and treated with TBAF (1.00 mL, 1 M in THF). After
being stirred for 2 min at room temperature, the reaction
mixture was diluted with EtOAc (30 mL) and washed with
brine (3 × 30 mL). The organic layer was dried over anhydrous
Na2SO4 and evaporated to dryness. The crude residue was
purified by column chromatography on silica gel, using hexane/
EtOAc 9.5:0.5 as eluent, to yield benzo[c]fluorenone 19-d5 (28
mg, 23%, Rf 0.50), with 60% deuterium incorporation at
position 1, as an orange solid and benzo[b]fluorenone 2a (54
mg, 59%, Rf 0.25), with 70% deuterium incorporation at
position 5. Compound 19-d5: 1H NMR (CDCl3, 250 MHz) δ 8.51
(s, 0.4 × 1H), 8.04 (d, J ) 7.6 Hz, 1H), 7.66 (d, J ) 7.6 Hz,
1H), 7.56-7.48 (m, 1H), 7.34-7.27 (m, 1H), 0.45 (s, 9H).
Th er m a l Cycliza tion of 1b in CCl4. A solution of 1b (250
mg, 0.76 mmol, 127 mM) in CCl4 (6 mL) was heated under
the general conditions. After column chromatography on silica
gel, using hexane/EtOAc 9.25:0.25 as eluent, three products
were isolated: chlorinated benzo[b]fluorenone 23 (83 mg, 32%,
Rf 0.38) as a yellow solid and fluorenones 2b and 19 as an
inseparable mixture (94 mg, 41%, Rf 0.31) in a 6.5:1 ratio.
Benzo[b]fluorenone 23: mp 169-171 °C (EtOAc-hexane); 1H
NMR (CDCl3, 250 MHz) δ 8.49 (d, J ) 7.8 Hz, 1H), 8.41 (d,
J ) 8.5 Hz, 1H), 8.39 (dd, J ) 8.0, 1.5 Hz, 1H), 7.76 (d, J )
7.6 Hz, 1H), 7.69-7.57 (m, 2H), 7.56-7.48 (m, 1H), 7.40 (t,
J ) 7.6 Hz, 1H), 0.58 (s, 9H);13C NMR/DEPT (CDCl3, 62.89
MHz) δ 193.4 (CO), 143.3 (C), 143.2 (C), 140.6 (C), 138.9 (C),
135.7 (C), 134.8 (CH), 134.5 (C), 133.6 (C), 131.5 (CH), 129.2
(CH), 128.9 (CH), 128.5 (C), 126.7 (CH), 125.2 (CH), 125.0
(CH), 123.9 (CH), 3.0 (Si(CH3)3); EI-MS m/z 338 (M+, 4), 336
(M+, 12), 323 (58), 321 (100), 293 (11), 291 (30); HRMS calcd
for C20H17OSi37Cl 338.07077, found 338.07218; HRMS calcd
1-[2-(d 5-P h en yleth yn yl)p h en yl]-3-tr im eth ylsilyl-2-p r o-
p yn -1-ol (18). To a solution of 17 (1.10 g, 4.82 mmol), PdCl2-
(PPh3)2 (68 mg, 0.10 mmol), and CuI (46 mg, 0.24 mmol) in
THF (20 mL) and Et3N (6 mL) was added iodobenzene-d5 (1.01
g, 4.82 mmol) and the mixture was stirred at room tempera-
ture for 2 h. After filtration through a Celite pad, the volatiles
were removed and the residue was solved in EtOAc (30 mL)
and washed with aqueous HCl (5%) (2 × 30 mL) and brine
(2 × 30 mL). The organic layer was dried over anhydrous Na2-
SO4 and evaporated to dryness. The crude residue was purified
by column chromatography on silica gel, using hexane/EtOAc
1
9:1 as eluent, to yield 18 (1.13 g, 76%) as a colorless oil; H
NMR (CDCl3, 250 MHz) δ 7.72 (dd, J ) 7.5, 1.5 Hz, 1H), 7.56
(dd, J ) 7.5, 1.3 Hz, 1H), 7.40 (td, J ) 7.5, 1.5 Hz, 1H), 7.33
(td, J ) 7.5, 1.3 Hz, 1H), 5.94 (d, J ) 5.6 Hz, 1H), 2.66 (d, J )
5.6 Hz, 1H), 0.18 (s, 9H); 13C NMR/DEPT (CDCl3, 62.89 MHz)
δ 141.9 (C), 132.3 (CH), 131.1 (t, J ) 25 Hz, 2 × CD), 128.8
(CH), 128.2 (CH), 128.0 (t, J ) 24 Hz, CD), 127.8 (t, J ) 24
Hz, 2 × CD), 126.6 (CH), 122.5 (C), 121.4 (C), 104.4 (C), 94.9
(C), 91.3 (C), 86.5 (C), 63.5 (CH), -0.3 (Si(CH3)3); EI-MS m/z
309 (M+, 50), 294 (72), 220 (64), 73 (100).
1-[2-(d 5-P h en yleth yn yl)p h en yl]-3-tr im eth ylsilyl-2-p r o-
p yn -1-on e (1b-d 5). To a solution of 18 (190 mg, 0.61 mmol)
in CH2Cl2 (5 mL) was added small portions of activated MnO2
until disappearance of the starting material (TLC monitoring).
After filtration through a short pad of silica, the solvent was
removed in a vacuum to afford 1b-d5 (187 mg, 99%) as a pale
yellow oil in high purity (column chromatography of 1b-d5
should be avoided due to the instability of the trimethylsilyl
1
ethynyl ketone in silica). H NMR (CDCl3, 250 MHz) δ 8.16-
8.11 (m, 1H), 7.64 (d, J ) 7.6 Hz, 1H), 7.53 (td, J ) 7.6, 1.6
Hz, 1H), 7.44 (td, J ) 7.6, 1.6 Hz, 1H), 0.25 (s, 9H); EI-MS
m/z 307 (M+, 100), 292 (97), 264 (39), 73 (18).
1-[2-(d 5-P h en yleth yn yl)p h en yl]-2-p r op yn -1-on e (1a -d 5).
To a solution of 1b-d5 (230 mg, 0.75 mmol) in MeOH (8 mL)
J . Org. Chem, Vol. 68, No. 5, 2003 1945

Rodr´ıguez et al.
for C20H17OSi35Cl 336.07372, found 336.07386. Elemental
analysis calcd (%) for C20H17OSiCl: C 71.30, H 5.09. Found:
C 71.06, H 5.12.
Ack n ow led gm en t. We thank the Direccio´n General
de Investigacio´n for financial support under Projects
PB98-0606 and BQU2002-02135, and the Centro de
Supercomputacio´n de Galicia (CESGA) for generous
allocation of computational resources. D. Rodr´ıguez also
thanks the Ministerio de Educacio´n y Ciencia for a
predoctoral grant.
Th er m a l Cycliza tion of 1b-d 5 in CCl4. A solution of 1b-
d5 (155 mg, 0.50 mmol, 100 mM) in CCl4 (5 mL) was heated
under the general conditions. After column chromatography
on silica gel, using hexane/EtOAc 9.25:0.25 as eluent, three
products were isolated: chlorinated benzo[b]fluorenone 23-d4
(76 mg, 44%, Rf 0.38) as a yellow solid and fluorenones 2b (80%
as 2b-d5) and 19 (percentage of deuteration could not be
calculated due to the low intensity of 1H signals) as an
inseparable mixture (59 mg, 38%, Rf 0.31) in a 10:1 ratio.
Benzo[b]fluorenone 23-d4: 1H NMR (CDCl3, 250 MHz) δ 8.49
(d, J ) 7.6 Hz, 1H), 7.75 (d, J ) 7.1 Hz, 1H), 7.61 (td, J ) 7.6,
1.2 Hz, 1H), 7.39 (td, J ) 7.1, 1.2 Hz, 1H), 0.58 (s, 9H); EI-MS
m/z 342 (M+, 18), 340 (M+, 56), 325 (100), 327 (36).
Su p p or tin g In for m a tion Ava ila ble: Cartesian coordi-
nates for all computed species and absolute energies and S2
values. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O0265380
1946 J . Org. Chem., Vol. 68, No. 5, 2003