Study of an unexpected rearrangement of the α-phenyl pyrane derivatives prepared via hetero-Diels-Alder reaction of acyclic vinyl allenes and aldehydes

Article abstract of DOI:10.1021/jo8010107

(Chemical Equation Presented) The Lewis acid catalyzed hetero-Diels-Alder reaction between acyclic vinyl allenes and aldehydes as heterodienophiles was studied. This reaction allows for the preparation of pyrane derivatives in good yields, high facial and regioselectivity and moderate endolexo ratio. When benzaldehyde was used as the heterodienophile, rearranged products were obtained depending on the reaction conditions. DFT calculations were used to study the rearrangement, concluding that it is a highly selective ionic process, driven by the stability of the rearranged products.

Full text of DOI:10.1021/jo8010107

Study of an Unexpected Rearrangement of the r-Phenyl Pyrane
Derivatives Prepared via Hetero-Diels-Alder Reaction of Acyclic
Vinyl Allenes and Aldehydes
Juan M. Ruiz, David Rega´s, Mar´ıa M. Afonso, and J. Antonio Palenzuela*
Instituto UniVersitario de Bio-Orga´nica “Antonio Gonza´lez”, Departamento de Qu´ımica Orga´nica,
UniVersidad de La Laguna, 38206 La Laguna, Tenerife, Spain
jpalenz@ull.es
ReceiVed May 9, 2008
The Lewis acid catalyzed hetero-Diels-Alder reaction between acyclic vinyl allenes and aldehydes as
heterodienophiles was studied. This reaction allows for the preparation of pyrane derivatives in good
yields, high facial and regioselectivity and moderate endo/exo ratio. When benzaldehyde was used as the
heterodienophile, rearranged products were obtained depending on the reaction conditions. DFT calculations
were used to study the rearrangement, concluding that it is a highly selective ionic process, driven by the
stability of the rearranged products.
SCHEME 1
Introduction
Vinylallenes have been used as dienes in Diels-Alder
reactions for many years in both the inter- and intramolecular
versions of the reaction.1 The special structural features of
the allene moiety introduces interesting differences with the
cycloaddition reaction of standard dienes, especially in the
regio- and face-selectivity of the reaction.2 In a study using
cyclohexenyl-allenes (semicyclic vinyl allenes), Krause and
co-workers3 concluded that the selectivity in this type of
compounds is due to the steric interaction of the incoming
dienophile with the substituents on the vinyl allene, following
a model first proposed by Reich and co-workers.4 Theoretical
calculations at the ab initio level have also been carried out
for the Diels-Alder reaction of vinyl allenes and acrolein,5
showing that the substitution pattern on the vinyl allene
affects the regioselectivity of the process. The same study
concluded that the reaction is a concerted asynchronous
process. Other theoretical studies indicates that the presence
of the allene lowers the activation energy of the reaction when
compared to the nonallenic case,6 making them more reactive
than similarly substituted dienes.
Recently, we presented our work on the use of semicyclic
vinyl allenes as dienes in the hetero-Diels-Alder reaction with
aldehydes acting as heterodienophiles.7 The reaction with
imines8 and the intramolecular version of those reactions9 were
also studied. For the reaction with aldehydes (Scheme 1), it was
observed that alkyl-substituted vinyl allenes showed a reactivity
similar to that of dienes substituted by strong activating groups
(alkoxy or silyloxy).
(6) Ferreiro, M. L.; Rodr´ıguez-Otero, J.; Cabaleiro-Largo, E. M. Struct. Chem.
2004, 15, 323.
(7) Rega´s, D.; Ruiz, J. M.; Afonso, M. M.; Palenzuela, J. A. J. Org. Chem.
2006, 71, 9153.
(1) Murakami, M.; Matsuda, T. In Modern Allene Chemistry; Krause, N.,
Hashmi, A. S. K., Eds.;Wiley-VCH: Weinheim, Germany, 2004; Vol. 2, pp 727-
815.
(2) Bertrand, M; Grimaldi, J.; Waegell, B Bull. Soc. Chim. Fr. 1971, 962.
(3) Koop, U.; Handke, G.; Krause, N. Liebigs Ann. Chem. 1996, 1478.
(4) Reich, H. J.; Eisenhart, E. K.; Whipple, W. L.; Kelly, M. J. J. Am. Chem.
Soc. 1988, 110, 6432.
(8) Rega´s, D.; Afonso, M. M.; Rodr´ıguez, M. L.; Palenzuela, J. A. J. Org.
Chem. 2003, 68, 7845.
(9) (a) Rega´s, D.; Ruiz, J. M.; Afonso, M. M.; Galindo, A.; Palenzuela, J. A.
Tetrahedron Lett. 2003, 44, 8471. (b) Rega´s, D.; Afonso, M. M.; Palenzuela,
J. A. Synthesis 2004, 757.
(5) Wright, J. B.; Pranata, J. THEOCHEM 1999, 460, 67.
7246 J. Org. Chem. 2008, 73, 7246–7254
10.1021/jo8010107 CCC: $40.75 2008 American Chemical Society
Published on Web 08/16/2008

SCHEME 3
FIGURE 1. General structure of the vinyl allenes used in this work.
SCHEME 2
When vinyl allene 13 was reacted with benzaldehyde, which
was the most reactive aldehyde for the reaction with the
semicyclic compounds,7 under the reaction conditions previously
used, that is, addition of 1 equiv of BF3 ·Et2O to the aldehyde
in ethyl ether at 0 °C, after 15 min addition of the vinyl allene
and stirring at room temperature for 24 h, a mixture of two
compounds was obtained in a 69:31 ratio and moderate yield
(64%). The two compounds were identified spectroscopically14
as the cycloadducts cis- and trans-17, coming respectively from
an endo (major) and exo (minor) approach of the aldehyde to
the dienic portion of the vinyl allene, through the less hindered
face and with total regioselectivity (Scheme 3).
The reaction of vinyl allenes 14 and 15 with benzaldehyde
under the same reaction conditions was similar, yielding 56%
of 18 and 54% of 19 in 70:30 and 79:21 cis:trans mixtures,
respectively.
The moderate yields are due mainly to the low stability of
the vinyl allenes under the reaction conditions. This behavior
is parallel to that of the semicyclic vinyl allenes, showing the
same regio- and face-selectivity and similar yields.7
When the same reaction was carried out using vinyl allene
16, substituted by a tert-butyl and a methyl group on the allenic
portion of the molecule, in a substitution pattern that was not
reactive in the semicyclic systems with aldehydes, a mixture
of two compounds was again obtained after 72 h. The study of
their structure revealed that one of them, which could not be
isolated pure, corresponds to the cis cycloadduct 20, but the
other compound (21) presented some anomalous shifts in the
1H NMR spectrum. Thus, the vinylic proton of the exocyclic
double bond, which was expected at around 5 ppm as a quartet,
showed up as a singlet at 6.6 ppm, and the proton geminal to
both the oxygen and the phenyl group was expected at 5.1 ppm
as a singlet but instead appears at 4.5 ppm as a quartet. Those
changes indicated that 21 was not the trans isomer of 20. After
a complete spectroscopic study it was concluded that the
structure of this compound has suffered a rearrangement, with
the phenyl group and the vinylic methyl group on the exocyclic
double bond exchanging places. Also, the relative stereochem-
istry of the two positions adjacent to the oxygen was deduced
as being trans (Scheme 4).
In the same work, computational studies using Density
Functional Theory showed that the reaction with BF3-complexed
aldehydes is a pericyclic, highly asynchronous process that
proceeds through a polar transition state.
Pursuing our interest in understanding the effect of the allene
moiety in pericyclic reactions, we decided to prepare acyclic
vinyl allenes with different alkyl groups as substituents on the
dienic portion of the molecule and compare their reactivity as
dienes in the hetero-Diels-Alder reaction with that of the
semicyclic analogs. In this paper, we present the results of that
study together with the calculations carried out to explain the
unexpected rearrangement observed in some cases during the
reaction.
Results and Discussion
Experimental Studies. Figure 1 shows the general structure
of the vinyl allenes used in this work. In these acyclic systems,
which have been used before in Diels-Alder reactions but not
with aldehydes,3,4,10 the non-allenic double bond lacks one of
the substituents existing in the semicyclic ones, and the two
remaining substituents on the diene (R1 and R2) would act
cooperatively as activating groups. The lack of the ring could
also result in a more conformationally flexible molecule.
We started by preparing vinyl allenes 13-16 according to
the synthetic pathway shown in Scheme 2.11 Starting from the
corresponding unsaturated ketones,12 the propargyl alcohols 5-8
were prepared by the addition of lithium acetilyde and then
transformed into the benzoates 9-12, which were in turn
converted into the vinyl allenes 13-16 by the SN2′ addition of
the methyl cuprate formed from methyl magnesium bromide
and cuprous iodide.13
This behavior could be attributed to the fact that, 16 being
the least reactive vinyl allene, longer reaction times were
needed for the reaction to progress, and thus it was considered
(10) (a) Spino, C.; Thibault, C.; Gingras, S. J. Org. Chem. 1998, 63, 5283.
(b) Yoshida, K.; Grieco, P. Chem. Lett. 1985, 155.
(11) All compounds described in this work were prepared in racemic form.
(12) Compounds 1-4 were prepared as described for 3 in Mujica, M. T.;
Afonso, M. M.; Galindo, A.; Palenzuela, J. A Tetrahedron 1996, 52, 2167.
(13) Jansen, A.; Krause, N. Inorg. Chim. Acta 2006, 359, 1761.
(14) All new compounds were identified by a combination of spectroscopic
techniques, including 1D and 2D NMR spectroscopy. The relative stereochemistry
was deduced from roesy or goesy experiments.
J. Org. Chem. Vol. 73, No. 18, 2008 7247

Ruiz et al.
SCHEME 4
SCHEME 7
SCHEME 5
SCHEME 8
SCHEME 9
SCHEME 6
was considerably slower. Thus, only 50% of cis-18 was
converted into trans-23 after 4 days, and for trans-18, 7 days
at refluxing CH2Cl2 were needed to achieve a similar transfor-
mation into cis-23. Alkyl-substituted cis-17 was more reactive,
giving the rearranged trans-24 after 2 days at room temperature
in a 69% conversion (Scheme 7).
that those somewhat stronger reaction conditions could have
facilitated the rearrangement. For that reason, it was decided
to repeat the reaction with the other vinyl allenes under forced
reaction conditions. This way it was observed, when using
15 as the vinyl allene, benzaldehyde as the heterodienophile,
and longer reaction times, that after the two expected
cycloadducts were formed, two new compounds started to
appear, and their concentration increased in time at the
expense of the cycloadducts. Those compounds were isolated,
and their structures were studied by NMR spectroscopy. The
data obtained was again quite similar to that of the cycload-
ducts, but with some of the proton NMR signals presenting
anomalous shifts similar to those described for compound
21. After completing the studies, the new compounds were
identified as cis- and trans-22 (Scheme 5). It is interesting
to note that the cis:trans ratio of the new compounds was
inverted with respect to that of the cycloadducts first obtained
from the reaction. Thus, at shorter reaction times the cis:
trans ratio of the cycloadducts (cis-19 and trans-19) was
79:21, and when longer reaction times were allowed, the
rearranged compounds cis-22 and trans-22 were formed in
a 16:84 ratio.
In order to determine the origin of the rearranged products,
the cycloaducts cis- and trans-19 were subjected independently
to a treatment with BF3 ·Et2O in ethyl ether. It was found that
each cycloadduct was transformed exclusively into one of the
new compounds. More specifically, the cycloadduct cis-19 was
completely transformed after 12 h into trans-22, whereas trans-
19 was converted into cis-22 in a slower process, completed
only after 72 h (Scheme 6). The possibility of equilibrium was
ruled out by subjecting the rearranged products to the same
reaction conditions without any change being observed.
With the cycloadducts cis-18 and trans-18 coming from vinyl
allene 14, the situation was similar, although the rearrangement
This behavior was never observed for the semicyclic vinyl
allenes, even under stronger reaction conditions.7
For the rearrangement to occur, the bond between the oxygen
in the cycle and the carbon atom substituted by the phenyl group
(the former aldehyde double bond) must be cleaved in a
heterolytic fashion and a new bond between the oxygen and
the carbon substituted by the methyl group (the former extreme
of the allene) must be formed (Scheme 8). Those two steps must
proceed rapidly, since the rearrangement seems to be highly
stereoselective.
In order to check the importance of the phenyl group in the
rearrangement, the reaction of vinyl allene 14 and propional-
dehyde was studied. Under the same conditions as before, two
compounds were isolated and characterized as the cycloadducts
cis-25 and trans-25 obtained in a 60% yield and 60:40 cis:trans
ratio (Scheme 9). Those new compounds were treated with
BF3 ·Et2O without observing any transformation other than
decomposition when the treatment was continued for a long
time.
Thus it seems clear that the rearrangement takes place only
when the substituents on the cycle (double bond and phenyl
group) are able to stabilize the incipient positive charge being
formed as the oxygen-carbon bond starts to break, under
stronger reaction conditions, usually longer reaction time.15
A similar situation, in which a doubly activated oxygen-
carbon bond breaks under Lewis acid catalysis, was described
by Porco, Schaus, and co-workers when using glycal-derived
scaffolds.16The outcome of that reaction was different to the
one described in this work because of the different arrangement
of the reacting groups on the molecule.
7248 J. Org. Chem. Vol. 73, No. 18, 2008

Computational Studies. In order to study the mechanism
of this rearrangement, computer calculations were undertaken
on model compounds 26 (cis) and 27 (trans), in which the side
chain was replaced by a methyl group in order to facilitate the
computation, and since the reaction takes place in the presence
of BF3 ·Et2O, the effect of this Lewis acid was simulated by
including BF3 coordinated to the oxygen atom in the structures.
The method chosen was the density functional theory (DFT)17
using the MPW1K functional18 with the 6-31G+(d,p) basis set,19
which has been shown to give accurate reaction barriers.20 The
use of other more commonly used functionals such as B3LYP
did not allow us to locate all stationary points. All calculations
were conducted using the Gaussian 03 suite of programs.21 The
solvent (ethyl ether) was simulated by the PCM method.22 All
energies reported include unscaled zero point energy corrections.
All stationary points were characterized by a frequency analysis.
Due to the cyclohexenic structure of the compounds in study,
the possibility of different conformations existing in solution
was taken into account, and thus, a full conformational search
using molecular mechanics was undertaken.23 All conformers
found were then optimized using DFT calculations, and only
two important conformers were found for each of the
cycloadduct-BF3 complexes, the ones in which the phenyl
group was pseudoaxial (26 Ph-ax and 27 Ph-ax) being
considerably lower in energy than the ones in which that group
presented a pseudoequatorial disposition (26 Ph-eq and 27 Ph-
eq) (figure 2). This effect must be due to the presence of the
Lewis acid, since in the noncomplexed compounds the lower
energy isomers present the phenyl group in an pseudoequatorial
disposition.
FIGURE 2. Model compounds 26 and 27 and the two lowest energy
conformations found for each one. Relative energies are in kcal/mol
and were computed at the PCM/MPW1K/6-31+G(d,p) level, using ethyl
ether as solvent and including ZPE corrections.
SCHEME 10
Initially, to study the transformation, an AM124 semiempirical
study of the rearrangement was conducted by stepwise elonga-
tion of the C2-O1 bond of the two optimized conformers of
(15) Following the reviewers’ suggestion, the reaction of vinyl allene 15 and
4-nitrobenzaldehyde was also studied. The electron-withdrawing group should
inhibit the rearrangement because the cationic intermediate would not be
stabilized by the phenyl group. The reaction yielded the expected cycloadducts
in a 88% yield and 83:17 cis:trans ratio. Those compounds did not suffer the
rearrangement under the conditions in which cis-19 and trans-19 were
transformed into cis-22 and trans-22, providing additional support to the proposed
mechanism (see Supporting Information for experimental details).
(16) Yeager, A. R.; Min, G. K., Jr.; Schaus, S. E. Org. Lett. 2006, 8, 5065.
(17) Parr, R. G.; Yang, W. Density-Functional Theory of Atoms and
Molecules; Oxford: New York, 1989.
(18) Lynch, B. J.; Fast, P. L.; Harris, M.; Truhlar, D. G. J. Phys. Chem. A
2000, 104, 4811.
(19) Hehre, W. J.; Radom, L.; Schleyer, P. v.R.; Pople, J. A. Ab Initio
Molecular Orbital Theory; Wiley: New York, 1986; pp 76-87, and references
therein.
(20) (a) Ess, D. H.; Houk, K. N. J. Phys. Chem. A 2005, 109, 9542. (b)
Lynch, B. J.; Truhlar, D. G. J. Phys. Chem. A 2001, 105, 2936.
(21) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, Jr., J. A.; Vreven, T.; Kudin, K. N.;
Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci,
B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada,
M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.;
Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian,
H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.;
Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski,
J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg,
J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.;
Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.;
Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.;
Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill,
P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A.
Gaussian 03, ReVision C.02; Gaussian, Inc.: Wallingford, CT, 2004.
(22) (a) Miertus, S.; Scrocco, E.; Tomasi, J. Chem. Phys. 1981, 55, 117. (b)
Cossi, M.; Scalmani, G.; Rega, N.; Barone, V. J. Chem. Phys. 2002, 117, 43.
(c) Cammi, R.; Mennucci, B.; Tomasi, J. J. Phys. Chem. A 2000, 104, 5631.
(23) PCMODEL, V7.0; Serena Software: Bloomington, IN.
each cycloadduct. It was observed that, in the four cases, the
energy increases steadily as the molecular geometry changed
by rotation around the C3-C4 bond. At a certain point there is
a sharp decrease in the energy as the intermediate structures
collapses into the final products (see Supporting Information).
The final products found in this study differ from the starting
compounds in either the relative stereochemistry of the sub-
stituents at the positions adjacent to the oxygen atom (28 and
30) or in the geometry of the exocyclic double bond (29 and
31) (Scheme 10). Interestingly, the two lower energy conformers
for each cycloadduct give raise to compounds with the
experimentally observed stereochemistry, those in which the
exocyclic double bond does not change its geometry (28 and
30).
(24) Dewar, M. J. S.; Zoebisch, E. G.; Healy, E. F.; Stewart, J. J. P. J. Am.
Chem. Soc. 1985, 107, 3902.
J. Org. Chem. Vol. 73, No. 18, 2008 7249

Ruiz et al.
FIGURE 3. Energy profile for the rearrangement of 26 Ph-ax showing the structures of the stationary points and the relevant distances. Relative
energies are in kcal/mol, calculated at the PCM/MPW1K/6-31+G(d,p) level including ZPE corrections. Bond distances are in angstroms.
In order to study in detail the mechanism of the rearrange-
ment, we choose the cis cycloadduct 26 in its lower energy
conformation, the one in which the phenyl group is pseudoaxial
(26 Ph-ax), and calculated its reaction profile at the DFT level.
This profile is presented in Figure 3 together with the structures
of the transition states found and the relevant distances and
relative energies.
The geometry of the first transition state (TS1) corresponds
to the breaking of the C2-O1 bond and is located 20.49 kcal/
mol higher in energy than the starting compound. The inter-
mediate (I) is only 0.86 kcal/mol more stable that TS1, and the
length of the bonds being broken and formed is quite similar
and midway between those of the transition states and of the
starting and final compounds. The geometry of the second
transition state (TS2) corresponds to the formation of the new
C1′-O1 bond and is located at a slightly lower energy level
than TS1. The final product (28) is 2.71 kcal/mol more stable
than the starting one, due probably to the conjugation of the
phenyl ring to the dienic system present in the molecule. The
nature of the compounds involved in the reaction was also
FIGURE 4. More relevant electron donations (in kcal/mol) for each
studied using the second order perturbation analysis of the Fock
stationary point on the reaction profile, found by a second order
matrix using NBO calculations.25 The more relevant interactions
perturbation analysis of the Fock matrix using NBO calculations.
are summarized in Figure 4.
In the initial compound only the conjugation of the two
double bonds (donation from the π orbital of one double bond
to the π* of the other) and the strong donation from the
oxygen lone pairs to the boron atom of the Lewis acid present
values above average, the later one being present in all
structures studied. In the first transition state (TS1), the
incipient positive charge being formed at C2 is stabilized by
donation from the π orbital of the allylic double bond, the π
system of the phenyl group, and one lone pair of the oxygen
atom. The interaction between the two double bonds dimin-
ishes as the C3-C4 bond rotates and the π systems become
orthogonal. In the intermediate (I) the situation is similar,
but no donation from the oxygen atom to the cationic center
is observed. In the second transition state (TS2), the donation
now goes from the π system of the phenyl group to the π*
orbital of the allylic double bond and from the π orbital of
this double bond to the other end of the allylic system, the
C1′ carbon to which the oxygen is getting attached. Again, a
(25) (a) Foster, J. P.; Weinhold, F. J. Am. Chem. Soc. 1980, 102, 7211. (b)
Reed, A. E.; Weinhold, F. J. Chem. Phys. 1985, 83, 1736. (c) Reed, A. E.;
Weinstock, R. B.; Weinhold, F. J. Chem. Phys. 1985, 83, 735. (d) Reed, A. E.;
Curtiss, L. A.; Weinhold, F. Chem. ReV. 1988, 88, 899.
7250 J. Org. Chem. Vol. 73, No. 18, 2008

NMR (100 MHz, CDCl3) δ 138.3 (s), 134.4 (d), 128.4 (d), 128.2
(d), 127.7 (d), 127.6 (d), 85.1 (s), 73.8 (d), 72.8 (t), 71.7 (s), 69.4
(t), 35.4 (t), 32.3 (t), 8.7 (q); MS (EI) m/z 244 (M+, 0.52), 226
(24), 197 (40), 171 (26), 91 (100); HRMS (EI) m/z calcd for
C16H20O2 244.1463, found 244.1457.
(E)-3-tert-Butylnon-4-en-1-yn-3-ol (8). Following the general
procedure using 2.32 g of 4 (13.78 mmol), propargyl alcohol 8
was obtained in 90% yield as a colorless oil. 1H NMR (400 MHz,
CDCl3) δ 5.98 (dt, J ) 6.4, 15.4 Hz, 1H), 5.60 (d, J ) 15.4 Hz,
1H), 2.53 (s, 1H), 2.08 (q, J ) 6.4 Hz, 2H), 1.97 (brs, 1H),
1.40-1.24 (m, 4H), 1.01 (s, 9H), 0.89 (t, J ) 6.7 Hz, 3H); 13C
NMR (75 MHz, CDCl3) δ 132.7 (d), 129.9 (d), 85.3 (s), 76.9 (s),
73.3 (d), 38.4 (s), 31.7 (t), 31.3 (t), 25.0 (q), 22.2 (t), 13.8 (q); MS
(EI) m/z 194 (M+, 0.5), 179 (8), 137 (63), 81 (100); HRMS (EI)
m/z calcd for C13H22O 194.1670, found 194.1632.
donation from the oxygen atom to the deficient center
appears. Finally, in the rearranged product the phenyl group
contributes to the conjugation of the dienic system, making
this the thermodynamically most stable structure.
This sequence of events explains the importance of the phenyl
group (or presumably any group that can stabilize the positive
charge) in the rearrangement, since it helps the stabilization not
only of the final product but also of the transition states.
Conclusions
In conclusion, we have found that acyclic vinyl allenes can
react with aldehydes in the presence of BF3 ·Et2O in a way
similar to the one found for the semicyclic systems used by us
previously, yielding pyrane derivatives. When benzaldehyde is
used as heterodienophile, the cycloadducts can suffer a selective
rearrangement through an ionic mechanism in which the
stabilized allylic cation formed by the breaking of the
oxygen-carbon bond, induced by the presence of the Lewis
acid, rotates and is quickly trapped by the same oxygen atom
at the other end of the allylic system. The driving force of the
process being the thermodynamic stabilization obtained as a
result of the conjugation of the double bonds with the phenyl
group. The phenyl group also helps by stabilizing the transition
states.
General Procedure for Preparation of Benzoates 9-12. To a
stirred solution of the propargyl alcohol (5 - 8) (1 equiv) in THF
(70 mL) at -78 °C under argon was added dropwise n-BuLi (1.6
M in hexanes, 1.1 equiv). The reaction mixture was kept at this
temperature for 30 min and stirred for a further 5 min at 0 °C. It
was then cooled to -78 °C, benzoyl chloride (1.1 equiv) was added,
and the reaction mixture was allowed to reach room temperature.
The mixture was stirred for 3 h, and saturated aqueous NH4Cl
solution was added. The mixture was then extracted with diethyl
ether, and the combined organic layers were washed with a saturated
aqueous NaCl solution, dried (MgSO4), concentrated and purified
by column chromatography affording the corresponding benzoates
(9 -12).
(E)-3-Methylundec-4-en-1-yn-3-yl Benzoate (9). Following the
general procedure, 5 (1.3 g, 7.21 mmol) was converted into 9 in
Experimental Section
1
78% yield, obtained as a yellow oil. H NMR (400 MHz, CDCl3)
General Procedure for Preparation of Propargyl Alcohols
5-8. To a solution of acetylene (3 equiv) in THF at -78 °C was
added dropwise n-BuLi (1.6 M in hexane, 2.5 equiv), and the
mixture was stirred for 30 min. Then, a solution of the R,ꢀ-
unsaturated ketone (1 equiv) in THF was added. The reaction
mixture was allowed to warm to room temperature for 2 h. Then
it was quenched with aqueous saturated solution of NH4Cl and
extracted with ether. The combined organic extracts were washed
with brine, dried (Na2SO4), concentrated and purified by column
chromatography to give the propargyl alcohols 5-8.
δ 8.03-8.01 (m, 2H), 7.55-7.40 (m, 3H), 6.13 (dt, J ) 6.9, 15.4
Hz, 1H), 5.74 (d, J ) 15.4 Hz, 1H), 2.71 (s, 1H), 2.10 (q, J ) 7.2
Hz, 2H), 1.85 (s, 3H), 1.43-1.27 (m, 8H), 0.87 (t, J ) 6.7 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 164.5 (s), 137.0 (s), 133.2
(d), 132.8 (d), 130.8 (s), 130.1 (d), 129.6 (d), 128.2 (d), 82.8 (s),
74.7 (d), 73.9 (s), 31.9 (t), 31.6 (t), 28.9 (q), 28.8 (t), 28.8 (t), 22.6
(t), 14.1 (q); MS (EI) m/z 284 (M+, 3), 213 (4), 197 (15), 105 (100);
HRMS (EI) m/z calcd for C19H24O2 284.1776, found 284.1768
(E)-7-(tert-Butyldiphenylsilyloxy)-3-methylhept-4-en-1-yn-3-yl Ben-
zoate (10). Following the general procedure, 6 (3.25 g, 8.59 mmol)
was converted into 10 in 85% yield, obtained as a colorless oil. IR
(CHCl3) 3300, 2900, 1720, 1450 cm-1; 1H NMR (400 MHz, CDCl3)
δ 8.06-8.03 (m, 2H), 7.71-7.69 (m, 4H), 7.57-7.54 (m, 1H),
7.45-7.37 (m, 8H), 6.25 (dt, J ) 6.9, 15.4 Hz, 1H), 5.87 (d, J )
15.4 Hz, 1H), 3.78 (t, J ) 6.3 Hz, 2H), 2.73 (s, 1H), 2.40 (m, 2H),
1.89 (s, 3H), 1.07 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 164.9
(s), 136.0 (d), 134.3 (s), 133.3 (d), 132.5 (d), 131.2 (s), 130.1 (d),
128.7 (d), 128.1 (d), 83.1 (s), 75.3 (d), 74.9 (s), 63.5 (t), 35.7 (t),
29.1 (q), 27.3 (q), 19.6 (s); MS (EI) m/z 482 (M+, 0.2), 425 (0.6),
303 (29), 225 (60), 199 (100); HRMS (EI) m/z calcd for C31H34O3Si
482.2277, found 482.2269.
(E)-7-(Benzyloxy)-3-ethylhept-4-en-1-yn-3-yl Benzoate (11).
Following the general procedure, 7 (1.5 g, 6.88 mmol) was
converted into 11 in 54% yield as a colorless oil. IR (CHCl3) 3300,
2900, 2100, 1780, 1710, 1600 cm-1; 1H NMR (400 MHz, CDCl3)
δ 8.03-8.01 (m, 2H), 7.57-7.53 (m, 1H), 7.44-7.40 (m, 2H),
7.33-7.25 (m, 5H), 6.17 (dt, J ) 6.9, 15.5 Hz, 1H), 5.70 (d, J )
15.5 Hz, 1H), 4.52 (s, 3H), 3.56 (t, J ) 6.8 Hz, 2H), 2.73 (s, 1H),
2.48-2.42 (m, 2H), 2.21-2.15 (m, 1H), 2.01-1.95 (m, 1H), 1.09
(t, J ) 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 164.4 (s),
138.4 (s), 132.9 (d), 130.9 (d), 130.2 (s), 129.6 (d), 128.3 (d), 127.6
(d), 127.5 (d), 81.3 (s), 78.4 (s), 75.9 (d), 72.9 (t), 69.5 (t), 34.4
(t), 32.5 (t), 8.4 (q); MS (EI) m/z 348 (M+, 0.5), 135 (12), 120 (9),
105 (100); HRMS (EI) m/z calcd for C23H24O3 348.1725, found
348.1759.
(E)-3-Methyl-undec-4-en-1-yn-3-ol (5). Following the general
procedure using R,ꢀ-unsaturated ketone 1 (1.44 g, 9.33 mmol), the
propargyl alcohol 5 was obtained in 98% yield as a colorless oil.
1
IR (CHCl3) 3300, 2900, 2100 cm-1; H NMR (400 MHz, CDCl3)
δ 5.97 (dt, J ) 6.9, 15.3 Hz, 1H), 5.56 (d, J ) 15.3 Hz, 1H), 2.54
(s, 1H), 2.23 (brs, 1H), 2.03 (q, J ) 6.9 Hz, 2H), 1.54 (s, 3H),
1.38-1.26 (m, 8H), 0.86 (t, J ) 6.7 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ133.4 (d), 131.0 (d), 86.5 (s), 72.5 (d), 67.8 (s), 31.8 (t),
31.6 (t), 30.3 (q), 28.9 (t), 28.8 (t), 22.6 (t), 14.1 (q); HRMS (EI)
m/z calcd for C12H20O 180.1514, found 180.1516.
(E)-7-(tert-Butyldiphenylsilyloxy)-3-methylhept-4-en-1-yn-3-ol
(6). Following the general procedure using 3.25 g of 2 (9.20 mmol),
propargyl alcohol 6 was obtained in 84% yield as a colorless oil.
1
IR (CHCl3) 3600, 3400, 2900 cm-1; H NMR (400 MHz, CDCl3)
δ 7.69-7.68 (m, 4H), 7.45-7.26 (m, 6H), 6.04 (dt, J ) 6.9, 15.4
Hz, 1H), 5.65 (d, J ) 15.4 Hz, 1H), 3.74 (t, J ) 6.4 Hz, 2H), 2.55
(s, 1H), 2.33 (q, J ) 6.6 Hz, 2H), 1.56 (s, 3H), 1.07 (s, 9H); 13C
NMR (75 MHz, CDCl3) δ 135.6 (d), 135.4 (d), 133.9 (s), 129.6
(d), 127.6 (d), 86.3 (s), 72.6 (s), 67.8 (s), 63.2 (t), 35.1 (t), 30.2
(q), 26.9 (q), 19.2 (s); MS (EI) m/z 321 (M+ - tBu, 10), 303 (6),
229 (17), 199 (100); HRMS (EI) m/z calcd for C20H21O2Si (M+
tBu) 321.1311, found 321.1262.
-
(E)-7-(Benzyloxy)-3-ethylhept-4-en-1-yn-3-ol (7). Following the
general procedure using 1.5 g of 3 (6.88 mmol), propargyl alcohol
7 was obtained in 63% yield as a colorless oil. IR (CHCl3) 3400,
1
2900, 2100 cm-1; H NMR (400 MHz, CDCl3) δ 7.35-7.26 (m,
5H), 6.03 (dt, J ) 5.2, 15.4 Hz, 1H), 5.58 (d, J ) 15.4 Hz, 1H),
4.52 (s, 2H), 3.53 (t, J ) 6.7 Hz, 2H), 2.57 (s, 1H), 2.40 (q, J )
6.7 Hz, 2H), 1.81-1.66 (m, 2H), 0.99 (t, J ) 7.4 Hz, 3H); 13C
(E)-3-tert-Butylnon-4-en-1-yn-3-yl Benzoate (12). Following
the general procedure, 8 (2.4 g, 12.35 mmol) was converted into
12 in 62% yield as a colorless oil. IR (CHCl3) 3300, 2900, 1725,
J. Org. Chem. Vol. 73, No. 18, 2008 7251

Ruiz et al.
1
1600, 1450 cm-1; H NMR (300 MHz, CDCl3) δ 8.04-8.02 (m,
stirred at room temperature for 12-24 h. Then, TEA (2.5 equiv)
was added, and the mixture was poured on iced water, extracted
with ether, dried over MgSO4 concentrated and purified by column
chromatography to give the cycloadducts as a cis:trans mixture that
was separated by HPLC.
2H), 7.57-7.26 (m, 3H), 6.09 (dt, J ) 6.8, 15.5 Hz, 1H), 5.50 (d,
J ) 15.5 Hz, 1H), 2.71 (s, 1H), 2.21 - 2.07 (m, 2H),1.46 - 1.30
(m, 4H), 1.17 (s, 9H), 0.90 (t, J ) 6.9 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 164.1 (s), 135.1 (d), 132.7 (d), 131.3 (s), 129.5
(d), 128.3 (d), 126.2 (d), 83.3 (s), 80.7 (s), 76.4 (d), 39.7 (s), 31.8
(t), 31.2 (t), 25.2 (q), 22.2 (t), 13.9 (q); MS (EI) m/z 298 (M+, 3),
242 (4), 193 (30), 105 (100); HRMS (EI) m/z calcd for C20H26O2
298.1933, found 298.1899.
General Procedure for Preparation of Vinyl Allenes 13-16. To
a suspension of LiBr (6 equiv) and CuI (6 equiv) in THF at 0 °C
under argon was slowly added MeMgBr (6 equiv). After 15 min
the corresponding benzoate (9 - 12) (1 equiv) in THF was added,
and the reaction was allowed to reach room temperature and was
stirred for 8 h. After cooling at -20 °C, 50 mL of a saturated
aqueous solution of NH4Cl were added, and the reaction was
extracted with diethyl ether, washed with saturated aqueous
solutions of NaHCO3 and NaCl, dried over Na2SO4, concentrated
and purified by column chromatography (n-hexane) to give the
corresponding vinyl allene (13-16).
(E)-4-Methyl-dodeca-2,3,5-triene (13). Following the general
procedure, 9 (1.6 g, 5.62 mmol) was converted into 13 in 53%
yield, obtained as a colorless oil. IR (CHCl3) 1940, 1440 cm-1; 1H
NMR (400 MHz, CDCl3) δ 5.97 (d, J ) 15.6 Hz, 1H), 5.50 (dt, J
) 6.9, 15.5 Hz, 1H), 5.16-5.13 (m, 1H), 2.09 (q, J ) 6.9 Hz,
2H), 1.72 (s, 3H), 1.65 (d, J ) 3.3 Hz, 3H), 1.40-1.26 (m, 8H),
0.89 (t, J ) 6.3 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 206.8 (s),
129.1 (d), 128.7 (d), 100.5 (s), 84.6 (d), 32.9 (t), 31.9 (t), 29.6 (t),
28.9 (t), 22.6 (t), 15.6 (q), 14.5 (q), 14.0 (q); HRMS (EI) m/z calcd
for C13H22 178.1721, found 178.1750.
cis- and trans-17. Using 13 (150 mg, 0.84 mmol) as the vinyl
allene and following the general procedure, a 69:31 mixture of cis
and trans 17 was obtained in 64% yield. (2R*,6S*,E)-3-Ethylidene-
6-hexyl-4-methyl-2-phenyl-3,6-dihydro-2H-pyran (cis-17): pale
yellow oil. IR (CHCl3) 2900, 1600, 1450 cm-1; 1H NMR (400 MHz,
C6D6) δ 7.56-7.54 (m, 2H), 7.32-7.19 (m, 3H), 5.50 (s, 1H), 5.11
(s, 1H), 5.02 (m, 1H), 4.43 (brs, 1H), 2.08 (s, 3H), 1.79-1.56 (m,
4H), 1.64 (d, J ) 7.5 Hz, 3H), 1.41-1.29 (m, 6H), 0.95 (t, J ) 6.8
Hz, 3H); 13C NMR (100 MHz, C6D6) δ 141.3 (s), 138.2 (s), 132.4
(s), 130.5 (d), 128.3 (d), 127.9 (d), 127.3 (d), 122.8 (d), 81.3 (d),
75.8 (d), 36.1 (t), 31.9 (t), 29.6 (t), 25.3 (t), 23.3 (q), 22.7 (t), 14.8
(q), 14.0 (q); MS (EI) m/z 284 (M+, 2.9), 269 (2), 208 (12), 193
(14), 189 (12), 105 (100); HRMS (EI) m/z calcd for C20H28O
284.2140, found 284.2138. (2S*,6S*,E)-3-Ethylidene-6-hexyl-4-
methyl-2-phenyl-3,6-dihydro-2H-pyran (trans-17): pale yellow
oil. IR (CHCl3) 2900, 1590, 1440 cm-1; 1H NMR (400 MHz, C6D6)
δ 7.61-7.59 (m, 2H), 7.35-7.19 (m, 3H), 5.41 (s, 1H), 5.26 (s,
1H), 5.24 (m, 1H), 4.07 (brs, 1H), 2.07 (s, 3H), 1.80 (d, J ) 7.3
Hz, 3H), 1.76-1.72 (m, 1H), 1.67-1.51 (m, 3H), 1.37-1.27 (m,
6H), 0.96 (t, J ) 6.8 Hz, 3H); 13C NMR (100 MHz, C6D6) δ 141.1
(s), 133.5 (s), 130.6 (d), 130.2 (s), 129.2 (d), 126.6 (d), 123.5 (d),
80.5 (d), 69.6 (d), 35.4 (t), 31.9 (t), 29.4 (t), 25.3 (t), 23.7 (q), 22.7
(t), 14.7 (q), 14.0 (q); MS (EI) m/z 284 (M+, 11), 255 (12), 199
(30), 196 (11), 181 (12), 156 (100); HRMS (EI) m/z calcd for
C20H28O 284.2140, found 284.2133.
(E)-tert-Butyl(5-methylocta-3,5,6-trienyloxy)diphenylsilane (14).
Following the general procedure, 10 (1.1 g, 2.27 mmol) was
converted into 14 in 73% yield, obtained as a colorless oil. IR
cis- and trans-18. Following the general procedure, vinyl allene
14 (150 mg, 0.40 mmol) provided 18 as a 70:30 mixture in 56%
yield. tert-Butyl(2-((2R*,6S*,E)-5-ethylidene-4-methyl-6-phenyl-
5,6-dihydro-2H-pyran-2-yl)ethoxy)diphenylsilane (cis-18): pale
1
(CHCl3) 2800, 1940, 1450 cm-1; H NMR (400 MHz, CDCl3) δ
1
yellow oil; IR (CHCl3) 2900, 1630, 1585, 1425 cm-1; H NMR
7.72-7.71 (m, 4H), 7.47-7.39 (m, 6H), 6.06 (d, J ) 15.7 Hz,
1H), 5.55 (dt, J ) 7.8, 15.7 Hz, 1H), 5.18 (brs, 1H), 3.75 (t, J )
6.7 Hz, 2H), 2.41 (q, J ) 6.8 Hz, 2H), 1.80 (s, 3H), 1.68 (d, J )
6.7 Hz, 3H), 1.09 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 207.4
(s), 135.4 (d), 134.4 (s), 131.3 (d), 130.0 (d), 128.0 (d), 125.4 (d),
99.7 (s), 85.2 (d), 64.3 (t), 36.6 (t), 27.3 (q), 19.7 (s), 16.0 (q),
15.0 (q); HRMS (EI) m/z calcd for C25H32OSi 376.2222, found
376.2256.
(E)-((5-Ethylocta-3,5,6-trienyloxy)methyl)benzene (15). Fol-
lowing the general procedure, 11 (1.1 g, 3.15 mmol) was converted
into 15 in 50% yield, obtained as a volatile colorless oil. 1H NMR
(300 MHz, CDCl3) δ 7.37-7.27 (m, 5H), 6.04 (d, J ) 15.8 Hz,
1H), 5.60 (dt, J ) 6.9, 16.8 Hz, 1H), 5.30-5.28 (m, 1H), 4.52 (s,
2H), 3.53 (t, J ) 6.8 Hz, 2H), 2.44 (q, J ) 6.8 Hz, 2H), 2.17-2.08
(m, 2H), 1.69 (d, J ) 7.0 Hz, 3H), 1.05 (t, J ) 7.3 Hz, 3H); 13C
NMR (75 MHz, CDCl3) δ 206.2 (s), 138.5 (s), 130.2 (d), 128.3
(d), 127.6 (d), 127.5 (d), 124.2 (d), 106.0 (s), 87.1 (d), 72.89 (t),
70.0 (t), 33.5 (t), 21.6 (t), 14.6 (q), 12.2 (q); MS (EI) m/z 242 (M+,
50), 167 (13), 105 (13), 91 (100); HRMS (EI) m/z calcd for C17H22O
242.1670, found 242.1704.
(400 MHz, C6D6) δ 7.87-7.83 (m, 4H), 7.49-7.47 (m, 2H),
7.32-7.16 (m, 9H), 5.50 (s, 1H), 5.10 (s, 1H), 4.99 (q, J ) 7.4
Hz, 1H), 4.79 (brs, 1H), 4.12 (m, 1H), 3.95 (m, 1H), 2.05-1.97
(m, 2H), 2.03 (s, 3H), 1.59 (d, J ) 7.4 Hz, 3H), 1.25 (s, 9H); 13C
NMR (75 MHz, C6D6) δ 141.2 (s), 138.1 (s), 135.8 (d), 134.2 (s),
133.9 (s), 130.6 (d), 129.6 (d), 128.4 (d), 128.0 (d), 127.8 (d), 127.3
(d), 123.0 (d), 81.3 (d), 72.6 (d), 60.2 (t), 38.9 (t), 26.9 (q), 23.4
(q), 19.2 (s), 14.9 (q); MS (EI) m/z 482 (M+, 0.3), 425 (23), 347
(13), 209 (39), 199 (100); HRMS (EI) m/z calcd for C32H38O2Si
482.2641, found 482.2652. tert-Butyl(2-((2R*,6R*,E)-5-ethylidene-
4-methyl-6-phenyl-5,6-dihydro-2H-pyran-2-yl)ethoxy)diphenyl-
silane (trans-18): IR (CHCl3) 3400, 2900, 1720, 1585, 1460 cm-1
;
1H NMR (300 MHz, C6D6) δ 7.89-7.82 (m, 4H), 7.61-7.59 (m,
2H), 7.34-7.19 (m, 9H), 5.35 (s, 1H), 5.23 (m, 2H), 4.43 (brs,
1H), 4.13 (m, 1H), 3.92 (m, 1H), 2.01 (s, 3H), 1.96-1.90 (m, 2H),
1.77 (d, J ) 7.4 Hz, 3H), 1.24 (s, 9H); 13C NMR (75 MHz, C6D6)
δ 140.9 (s), 135.8 (d), 134.2 (s), 133.7 (s), 130.5 (d), 130.3 (s),
129.6 (d), 128.1 (d), 127.8 (d), 123.6 (d), 80.4 (d), 66.9 (d), 60.4
(t), 38.3 (t), 26.9 (q), 23.2 (q), 19.2 (s), 14.7 (q); MS (EI) m/z 482
(M+, 1), 425 (45), 347 (23), 209 (84), 199 (100); HRMS (EI) m/z
calcd for C32H38O2Si 482.2641, found 482.2605.
(E)-4-tert-Butyldeca-2,3,5-triene (16). Following the general
procedure, 12 (2.27 g, 7.6 mmol) was converted into 16 in 82%
yield, obtained as a volatile colorless oil. IR (CHCl3) 2900, 1945,
cis- and trans-19. Following the general procedure, after 24 h,
vinyl allene 15 (80 mg, 0.33 mmol) provided 19 as a 79:21 cis:
trans mixture in a 54% yield. (2R*,6S*,E)-6-(2-(Benzyloxy)ethyl)-
4-ethyl-3-ethylidene-2-phenyl-3,6-dihydro-2H-pyran (cis-19): 1H
NMR (400 MHz, C6D6) δ 7.52-7.47 (m, 2H), 7.36-7.16 (m, 8H),
5.58 (s, 1H), 5.11 (s, 1H), 5.03 (q, J ) 7.0 Hz, 1H), 4.70 (brs,
1H), 4.36 (s, 2H), 3.80-3.74 (m, 1H), 3.69-3.64 (m, 1H),
2.48-2.41 (m, 1H), 2.37-2.30 (m, 1H), 2.10-2.08 (m, 2H), 1.59
(d, J ) 7.2 Hz, 3H), 1.08 (t, J ) 7.3 Hz, 3H); 13C NMR (75 MHz,
C6D6) δ 141.3 (s), 139.2 (s), 138.7 (s), 137.2 (s), 128.4 (d), 128.3
(d), 128.2 (d), 128.0 (d), 127.8 (d), 127.5 (d), 127.4 (d), 127.2 (d),
122.3 (d), 81.5 (d), 73.2 (d), 72.7 (t), 66.8 (t), 36.5 (t), 28.4 (t),
14.8 (q), 13.2 (q); MS (EI) m/z 348 (M+, 0.8), 319 (3), 257 (14),
1
1460 cm-1; H NMR (300 MHz, CDCl3) δ 5.77 (s, 2H), 5.26 (q,
J ) 7.0 Hz, 1H), 2.10-2.07 (m, 2H), 1.68 (d, J ) 6.8 Hz, 3H),
1.38-1.30 (m, 4H), 1.06 (s, 9H), 0.90 (t, J ) 7.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 201.5 (s), 141.4 (s), 132.6 (d), 123.9
(d), 113.1 (s), 87.6 (d), 32.9 (s), 32.7 (t), 31.5 (t), 29.4 (q), 22.2
(t), 14.7 (q), 13.9 (q); MS (EI) m/z 193 (M+ + 1, 92), 192 (M+,
52), 135 (40), 57 (100); HRMS (EI) m/z calcd for C14H24 192.1878,
found 192.1821.
General Procedure for Reaction of Vinyl Allenes and Benz-
aldehyde. To a solution of benzaldehyde (1.1 equiv) in dry ether
was added BF3 ·Et2O (1.1 equiv) at 0 °C under argon. After 15
min the allene (1 equiv) in ether was added, and the reaction was
7252 J. Org. Chem. Vol. 73, No. 18, 2008

195 (100); HRMS (EI) m/z calcd for C24H28O2 348.2089, found
348.2143. (2S*,6S*,E)-6-(2-(Benzyloxy)ethyl)-4-ethyl-3-ethylidene-
2-phenyl-3,6-dihydro-2H-pyran (trans-19): 1H NMR (400 MHz,
C6D6) δ 7.61-7.59 (m, 2H), 7.38-7.19 (m, 8H), 5.37 (s, 1H), 5.31
(s, 1H), 5.24 (q, J ) 7.2 Hz, 1H), 4.41 (brs, 2H), 3.82-3.76 (m,
1H), 3.66-3.62 (m, 1H), 2.53-2.47 (m, 1H), 2.33-2.27 (m, 1H),
2.02 (q, J ) 5.7 Hz, 2H), 1.75 (d, J ) 7.2 Hz, 3H), 1.07 (t, J ) 7.2
Hz, 3H); 13C NMR (75 MHz, C6D6) δ 140.9 (s), 139.3 (s), 136.1
(s), 132.8 (s), 128.5 (d), 128.2 (d), 128.0 (d), 127.8 (d), 127.5 (d),
127.2 (d), 123.3 (d), 80.8 (d), 72.8 (t), 67.5 (d), 66.8 (t), 35.8 (t),
28.5 (t), 14.8 (q), 13.2 (q); HRMS (EI) m/z calcd for C24H28O2
348.2089, found 348.2091.
after 2 d, afforded 14 mg of starting material and trans-24 (47
mg, 0.165 mmol, 69%) as a yellow oil. (2R*,6R*,E)-3-
Benzylidene-6-(2-(benzyloxy)ethyl)-2,4-dimethyl-3,6-dihydro-
1
2H-pyran (trans-24): H NMR (400 MHz, C6D6) δ 7.24-7.11
(m, 5H), 6.36 (s, 1H), 5.45 (s, 1H), 4.55 (q, J ) 6.5 Hz, 1H),
4.35 (brs, 1H), 1.79-1.63 (m, 5H), 1.66 (s, 3H), 1.45 (d, J )
6.5 Hz, 3H), 1.42-1.37 (m, 5H), 0.97 (t, J ) 6.8 Hz, 3H); 13C
NMR (75 MHz C6D6) δ 138.9 (s), 138.8 (s), 131.4 (d), 129.2
(d), 127.4 (d), 126.6 (d), 124.3 (d), 73.7 (d), 70.0 (d), 35.5 (t),
32.0 (t), 29.6 (t), 25.6 (t), 22.8 (t), 22.1 (q), 18.4 (q), 14.0 (q);
MS (FAB) m/z 284 (M+, 0.9), 200 (54), 186 (39), 171 (64), 157
(32), 129 (49), 105 (100); HRMS (EI) m/z calcd for C20H28O
284.2140, found 284.2145.
Reaction of Vinyl Allene 16 and Benzaldehyde. Following
the general procedure, using 1.5 equiv of BF3 · Et2O and after
72 h, vinyl allene 16 (154 mg, 0.8 mmol) gave 59% yield of a
52:48 mixture of cycloadduct 20, which could not be isolated
pure, and rearranged product 21. (2R*,6S*,E)-4-tert-Butyl-6-
butyl-3-ethylidene-2-phenyl-3,6-dihydro-2H-pyran (20): 1H
NMR (400 MHz, C6D6) δ 7.51-7.49 (m, 2H), 7.29-7.16 (m,
3H), 6.01 (d, J ) 3.6 Hz, 1H), 5.51 (s, 1H), 5.47 (q, J ) 7.1
Hz, 1H), 4.02 (m, 1H), 1.98-1.95 (m, 1H), 1.80-1.75 (m, 2H),
1.65 (d, J ) 7.1 Hz, 3H), 1.47-1.42 (m, 3H), 0.97 (s, 9H),
0.95-0.91 (m, 3H). (2R*,6R*,E)-3-Benzylidene-6-butyl-4-tert-
butyl-2-methyl-3,6-dihydro-2H-pyran (21): IR (CHCl3) 3300,
Rearrangement of cis-18. Following the general procedure,
cis-18 (50 mg, 0.10 mmol), using 2.5 equiv of BF3 · Et2O and
after 4 d, afforded 20 mg of starting material and trans-23 (25
mg, 0.05 mmol, 50%) as a yellow oil: (2-((2R*,6R*,E)-5-
Benzylidene-4,6-dimethyl-5,6-dihydro-2H-pyran-2-yl)ethoxy-
(tert-butyl)diphenylsilane (trans-23): 1H NMR (400 MHz,
C6D6) δ 7.88-7.85 (m, 4H), 7.32-7.06 (m, 6H), 6.30 (s, 1H),
5.38 (s, 1H), 4.65 (brs, 1H), 4.28 (q, J ) 6.4 Hz, 1H), 4.11 (m,
1H), 3.95 (m, 1H), 1.96 (m, 2H), 1.52 (s, 3H), 1.39 (d, J ) 6.4
Hz, 3H), 1.29 (s, 9H); 13C NMR (75 MHz C6D6) δ 138.8 (s),
138.6 (s), 135.8 (d), 135.7 (d), 134.2 (s), 134.1 (s), 131.3 (d),
129.6 (d), 129.3 (d), 129.2 (d), 126.6 (d), 124.3 (d), 73.3 (d),
67.1 (d), 60.6 (t), 38.2 (t), 26.9 (q), 22.1 (q), 19.2 (s), 18.3 (q);
MS (EI) m/z 482 (M+, 0.2), 425 (10), 247 (23), 199 (100); HRMS
(EI) m/z calcd for C32H38O2Si 482.2641, found 482.2638.
Rearrangement of trans-18. To a solution of trans-18 (50 mg,
0.1 mmol) in CH2Cl2 at 0 °C was added BF3 · Et2O (2.5 equiv).
The reaction mixture was refluxed for 7 d, then TEA was added,
and the solvent was removed. Column chromatography afforded
20 mg of starting material and cis-23 (25 mg, 0.05 mmol, 50%
yield) as a yellow oil; (2-((2R*,6S*,E)-5-Benzylidene-4,6-
dimethyl-5,6-dihydro-2H-pyran-2-yl)ethoxy(tert-butyl)diphe-
nylsilane (cis-23): 1H NMR (400 MHz, C6D6) δ 7.95-7.83 (m,
4H), 7.34-7.18 (m, 6H), 6.54 (s, 1H), 5.46 (s, 1H), 4.66 (brs,
1H), 4.18 (m, 2H), 4.00 (m, 1H), 2.01 (m, 2H), 1.63 (s, 3H),
1.46 (d, J ) 6.4 Hz, 3H), 1.29 (s, 9H); 13C NMR (75 MHz,
C6D6) δ 139.6 (s), 139.3 (s), 135.7 (d), 134.3 (s), 134.2 (s), 132.2
(d), 131.9 (d), 129.6 (d), 129.3 (d), 126.7 (d), 122.9 (d), 73.1
(d), 72.5 (d), 60.4 (t), 39.2 (t), 26.9 (q), 22.0 (q), 19.3 (s), 18.4
(q).
Reaction of Vinyl Allene 14 and Propionaldehyde. Following
the general procedure, vinyl allene 14 (150 mg, 0.40 mmol),
propionaldehyde (0.44 mmol), and BF3 · Et2O (1.1 equiv), after
24 h, provided compounds cis-25 (63 mg, 0.14 mmol) and trans-
25 (41 mg, 0.096 mmol) in a 60:40 ratio, and 60% yield. tert-
Butyl(2-((2R*,6S*,E)-6-ethyl-5-ethylidene-4-methyl-5,6-dihydro-
2H-pyran-2-yl)ethoxy)diphenylsilane (cis-25): IR (CHCl3)
3500, 2900, 1700, 1460, 1420 cm-1; 1H NMR (400 MHz, C6D6)
δ 7.90-7.86 (m, 4H), 7.32-7.30 (m, 6H), 5.44 (s, 1H), 5.37
(q, J ) 7.3 Hz, 1H), 4.57 (brs, 1H), 4.11 (m, 1H), 3.96 (m, 1H),
3.89 (m, 1H), 2.00 (s, 3H), 1.96 (q, J ) 6.2 Hz, 2H), 1.79 -
1.70 (m, 2H), 1.76 (d, J ) 7.3 Hz, 3H), 1.27 (s, 9H), 1.13 (t, J
) 7.3 Hz, 3H); 13C NMR (75 MHz, C6D6) δ 136.8 (s), 135.8
(d), 134.2 (s), 132.4 (s), 130.4 (d), 129.7 (d), 127.8 (d), 118.2
(d), 78.6 (d), 72.1 (d), 60.6 (t), 39.2 (t), 26.9 (q), 25.7 (t), 23.2
(q), 19.2 (s), 14.9 (q), 10.4 (q); MS (EI) m/z 434 (M+, 0.1), 377
(15), 299 (12), 199 (100), 178 (97), 161 (94); HRMS (EI) m/z
calcd for C28H38O2Si 434.2641, found 434.2603. tert-Butyl(2-
((2R*,6R*,E)-6-ethyl-5-ethylidene-4-methyl-5,6-dihydro-2H-
pyran-2-yl)ethoxy)diphenylsilane (trans-25): IR (CHCl3) 3300,
2900, 1720, 1585, 1460, 1420 cm-1; 1H NMR (300 MHz, C6D6)
δ 7.92-7.87 (m, 4H), 7.33-7.25 (m, 6H), 5.37 (s, 1H), 5.17
(q, J ) 7.3 Hz, 1H), 4.59 (brs, 1H), 4.18-4.08 (m, 2H),
4.01-3.94 (m, 1H), 1.98 (s, 3H), 1.95-1.83 (m, 3H), 1.74 (d,
J ) 7.3 Hz, 3H), 1.62-1.53 (m, 1H), 1.28 (s, 9H), 1.05 (t, J )
7.4 Hz, 3H); 13C NMR (75 MHz, C6D6) δ 135.9 (s), 135.8 (d)
2900, 1595, 1460, 1360 cm-1 1H NMR (400 MHz, C6D6) δ
;
7.39-7.10 (m, 5H), 6.52 (s, 1H), 5.87 (d, J ) 3.8 Hz, 1H), 4.41
(q, J ) 6.2 Hz, 1H), 4.35 (m, 1H), 1.81-1.60 (m, 4H), 1.44 (d,
J ) 6.1 Hz, 3H), 1.44-1.39 (m, 2H), 1.06 (s, 9H), 0.99 (t, J )
7.1 Hz, 3H); 13C NMR (75 MHz, C6D6) δ 147.8 (s), 140.0 (s),
139.4 (s), 129.5 (d), 129.2 (d), 128.1 (d), 127.1 (d), 124.8 (d),
75.4 (d), 72.1 (d), 35.6 (t), 31.5 (q), 28.0 (t), 23.0 (t), 18.2 (q),
14.1 (q); MS (EI) m/z 298 (M+, 10), 241 (12), 184 (25); HRMS
(EI) m/z calcd for C21H30O 298.2296, found 298.2176.
Reaction of Vinyl Allene 15 and Benzaldehyde under Forced
Reaction Conditions. Following the general procedure using vinyl
allene 15 (80 mg, 0.33 mmol), with 1.5 equiv of BF3 · Et2O and
after 72 h, the rearranged compounds 22 were obtained in 54%
yield as a 16:84 cis:trans mixture. (2S*,6R*,E)-3-Benzylidene-
6-(2-(benzyloxy)ethyl)-4-ethyl-2-methyl-3,6-dihydro-2H-py-
ran (cis-22): colorless oil; 1H NMR (400 MHz, C6D6) δ
7.41-7.10 (m, 10H), 6.52 (s, 1H), 5.57 (s, 1H), 4.63 (brs, 1H),
4.45 (s, 2H), 4.20 (q, J ) 6.2 Hz, 1H), 3.82-3.78 (m, 1H),
3.73-3.67 (m, 1H), 2.14-2.00 (m, 3H), 1.48 (d, J ) 6.2 Hz,
3H), 1.15-1.11 (m, 1H), 0.85 (t, J ) 7.4 Hz, 3H); 13C NMR
(75 MHz, C6D6) δ 139.3 (s), 139.0 (s), 138.7 (s), 138.4 (s), 129.8
(d), 128.8 (d), 127.9 (d), 127.6 (d), 126.8 (d), 122.4 (d), 73.6
(d), 73.0 (d), 72.8 (t), 66.7 (t), 36.7 (t), 26.8 (t), 18.5 (q), 13.1
(q); HRMS (EI) m/z calcd for C24H28O2 348.2089, found
348.2073. (2R*,6R*,E)-3-Benzylidene-6-(2-(benzyloxy)ethyl)-
4-ethyl-2-methyl-3,6-dihydro-2H-pyran (trans-22): colorless
1
oil; H NMR (400 MHz, C6D6) δ 7.42-7.09 (m, 10H), 6.34 (s,
1H), 5.50 (s, 1H), 4.61 (brs, 1H), 4.49 (q, J ) 6.5 Hz, 1H), 4.47
(s, 2H), 3.83-3.77 (m, 1H), 3.72-3.67 (m, 1H), 2.15-1.96 (m,
4H), 1.40 (d, J ) 6.5 Hz, 3H), 0.80 (t, J ) 7.4 Hz, 3H); 13C
NMR (100 Mz, C6D6) δ 139.3 (s), 138.7 (s), 137.4 (s), 135.8
(s), 129.2 (d), 129.1 (d), 128.3 (d), 128.0 (d), 127.8 (d), 127.3
(d), 126.8 (d), 124.1 (d), 74.2 (d), 72.6 (t), 67.9 (d), 66.9 (t),
36.0 (t), 26.8 (t), 18.0 (q), 13.1 (q); MS (EI) m/z 348 (M+, 0.6),
257 (10), 91 (100); HRMS (EI) m/z calcd for C24H28O2 348.2089,
found 348.2086.
General Procedure for Rearrangement of Cycloadducts. To
a solution of the cycloadduct (1 equiv) in ether at 0 °C was
added BF3 · Et2O (1.0-2.5 equiv). The reaction mixture was
allowed to warm to room temperature and was stirred until TLC
showed no further transformation. Then TEA was added, and
the solvent was removed. Column chromatography afforded the
pure compounds.
Rearrangement of cis-17. Following the general procedure,
cis-17 (68 mg, 0.24 mmol), using 1.1 equiv of BF3 · Et2O and
J. Org. Chem. Vol. 73, No. 18, 2008 7253

Ruiz et al.
134.2 (s), 134.2 (s), 129.6 (d), 127.8 (d), 127.4 (d), 120.4 (d),
80.9 (d), 66.0 (d), 60.6 (t), 38.7 (t), 26.9 (q), 25.3 (t), 23.3 (q),
19.2 (s), 14.6 (q), 10.7 (q); MS (EI) m/z 434 (M+, 0.7), 377
(13), 299 (10), 199 (97), 178 (85), 161 (100); HRMS (EI) m/z
calcd for C28H38O2Si 434.2641, found 434.2628.
Supporting Information Available: General methods,
NMR spectra for all new compounds and tables including
total energies and Cartesian coordinates for all stationary
points discussed in the text. This material is available free
of charge via the Internet at http://pubs.acs.org.
Acknowledgment. This work was supported in part by an
University of La Laguna Grant for Consolidated Research
Groups. D.R. thanks the MEC (Spain) for a fellowship.
JO8010107
7254 J. Org. Chem. Vol. 73, No. 18, 2008