Hetero Diels-Alder reaction of vinyl allenes and aldehydes. An experimental and computational study

Article abstract of DOI:10.1021/jo061582r

(Chemical Equation Presented) The hetero Diels-Alder reaction of vinyl allenes and aldehydes in the presence of a Lewis acid has been studied both experimentally and theoretically. Differently substituted vinyl allenes and aldehydes were used to obtain in

Full text of DOI:10.1021/jo061582r

Hetero Diels-Alder Reaction of Vinyl Allenes and Aldehydes.
An Experimental and Computational Study
David Rega´s, Juan M. Ruiz, 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 July 31, 2006
The hetero Diels-Alder reaction of vinyl allenes and aldehydes in the presence of a Lewis acid has been
studied both experimentally and theoretically. Differently substituted vinyl allenes and aldehydes were
used to obtain information on the structural requirements of the reaction. Theoretical calculations using
the density functional theory indicate that the reaction proceeds through a highly asynchronous polar
transition state.
Introduction
following a model first proposed by Reich and co-workers.5 A
recent study indicates that the presence of the allene causes the
lowering of the activation energy of the reaction when compared
to the nonallenic case,6 making them more reactive than
similarly substituted dienes.
Vinyl allenes have been used as dienes in Diels-Alder
reactions for many years in both the inter- and the intramolecular
versions of the reaction.1 The presence of the sp carbon, which
implies out-of plane substituents on the extreme of the allene,
introduces interesting differences with the cycloaddition reaction
of standard dienes, especially in the regio- and facial selectivity
of the reaction. For the parent system, 1,2,4-pentatriene, an 80:
20 mixture of regioisomers, was obtained in the reaction with
methyl vinyl ketone.2 Depending on the position of the alkyl
substituents on the allene, the ratio can change, favoring one
of the two regioisomers. Theoretical calculations at the ab initio
level have also been carried out for the Diels-Alder reaction
of vinyl allenes and acrolein,3 showing that, when the parent
system is considered, no regioselectivity is expected. However,
in the methyl substituted vinyl allenes, the electron-donating
ability of the methyl group results in one of the regioisomers
being favored. The same study concluded that the reaction is a
concerted asynchronous process. In a study using cyclohexenyl-
allenes, Krause and co-workers4 concluded that the selectivity
in this type of compound is due to the steric interaction of the
incoming dienophile with the substituents on the vinyl allene,
Recently,7 we found that 1-cyclohexenyl allenes, similar to
those which were shown to display high selectivity in Diels-
Alder reactions by Krause and co-workers,4 can also act as
dienes in hetero Diels-Alder reactions with aldehydes under
Lewis acid catalysis. The reactivity was similar to that displayed
by dienes activated by one silyloxy group,8 that is, good facial
and regioselectivity and moderate endo/exo selectivity, with the
yields being moderate to good for this reaction (36-70%). Later,
we found that the same reaction works with imines as hetero-
dienophiles,9 although some structural limitations to the reaction,
as well as some selectivity problems arising from competing
reactions, were observed. Furthermore, the intramolecular
version of this reaction has also been explored with both
aldehydes10 and imines11 as heterodienophiles.
(5) Reich, H, J.; Eisenhart, E. K.; Whipple, W. L.; Kelly, M. J. J. Am.
Chem. Soc. 1988, 110, 6432.
(6) Ferreiro, M. L.; Rodr´ıguez-Otero, J.; Cabaleiro-Lago, E. M. Struct.
Chem. 2004, 15, 323.
(7) Rega´s, D.; Afonso, M. M.; Galindo, A.; Palenzuela, J. A. Tetrahedron
Lett. 2000, 41, 6781.
(8) Mujica, M. T.; Afonso, M. M.; Galindo, A.; Palenzuela, J. A. J. Org.
Chem. 1998, 63, 9728.
(9) Rega´s, D.; Afonso, M. M.; Rodr´ıguez, M. L.; Palenzuela, J. A. J.
Org. Chem. 2003, 68, 7845.
(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) Wright, J. B.; Pranata, J. THEOCHEM 1999, 460, 67.
(4) Koop, U.; Handke, G.; Krause, N. Liebigs Ann. Chem. 1996, 1478.
(10) Rega´s, D.; Ruiz, J. M.; Afonso, M. M.; Galindo, A.; Palenzuela, J.
A. Tetrahedron Lett. 2003, 44, 8471.
10.1021/jo061582r CCC: $33.50 © 2006 American Chemical Society
Published on Web 10/26/2006
J. Org. Chem. 2006, 71, 9153-9164
9153

Rega´s et al.
In this paper, we present the full account of our work using
aldehydes as heterodienophiles, with different vinyl allenes as
dienes, as well as a theoretical study of the reaction carried out
using the density functional theory, intending to shed light on
the mechanism of the process.
Computational Methods
FIGURE 1. General structure of the vinyl allenes used in this work.
All the calculations reported in this paper have been
performed within the density functional theory,12 using the
hybrid functional B3LYP13 and the standard basis set 6-31G-
(d,p) as implemented in the Gaussian 9814 suite of programs,
which has been shown to be a satisfactory level for the study
of the hetero Diels-Alder reaction.15
SCHEME 1
Activation energies and reaction energies were computed at
the same level, including zero-point vibrational energy (ZPVE)
corrections, which were not scaled. No basis-set superposition
error corrections were applied.
The synchronicities16 of the studied reactions were quantified
using a previously described approach17 using Wiberg bond
indices18 and evaluated using the natural bond orbital (NBO)
method.19 Donor-acceptor interactions have also been computed
using the NBO method using second-order perturbation energy.
SCHEME 2
Results and Discussion
Experimental Studies. For this work, vinyl allenes with
different substitution patterns were chosen following the general
structure shown in Figure 1, the substituents being either
hydrogen atoms or alkyl (Me, Et, t-Bu) or phenyl groups.20
Those vinyl allenes were prepared either from the propargyl
alcohols obtained from the addition of (cyclohexenylethynyl)-
lithium to carbonyl compounds or from the corresponding
benzoates as shown in Scheme 1.
(11) Rega´s, D.; Afonso, M. M.; Palenzuela, J. A. Synthesis 2004, 757.
(12) Parr, R. G.; Yang, W. Density-Functional Theory of Atoms and
Molecules; Oxford University Press: New York, 1989.
(13) (a) Kohn, W.; Becke, A. D.; Parr, R. G. J. Phys. Chem. 1996, 100,
12 974. (b) Becke, A. D. J. Chem. Soc. 1993, 98, 5648. (c) Becke, A. D.
Phys. ReV. 1988, 38, 3098.
(14) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.;
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.; Gonzalez, C.; Challacombe, M.; Gill, P. M.
W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon,
M.; Replogle, E. S.; Pople, J. A. Gaussian 98, revision A.6; Gaussian,
Inc.: Pittsburgh, PA, 1998.
(15) Guner, V.; Khuong, K. S.; Leach, A. G.; Lee, P. S.; Bartberger, M.
D.; Houk, K. N. J. Phys. Chem. A 2003, 107, 11445.
(16) Borden, W. T.; Loncharich, R. J.; Houk, K. N. Annu. ReV. Phys.
Chem. 1988, 39, 213.
(17) (a) Moyano, A.; Perica´s, M. A.; Valent´ı, E. J. Org. Chem 1989,
54, 573. (b) Lecea, B.; Arrieta, A.; Roa, G.; Ugalde, J. M.; Coss´ıo, F. P. J.
Am. Chem. Soc. 1994, 116, 9613. (c) Lecea, B.; Arrieta, A.; Lo´pez, X.;
Ugalde, J. M.; Coss´ıo, F. P. J. Am. Chem. Soc. 1995, 117, 12314. (d) Coss´ıo,
F. P.; Morao, I.; Jiao, H.; Schleyer, P. v. R. J. Am. Chem. Soc. 1999, 121,
6737.
We started by attempting the synthesis of the vinyl allenes,
unsubstituted at the inner position of the allene (R1 ) H), using
Myers and Zheng’s protocol.21 Thus, when the known propargyl
alcohol 122 was treated with PPh3, diethylazodicarboxylate
(DEAD), and o-nitrobenzene sulfonylhydrazine (NBSH) in THF
at -15 °C, a single compound was isolated in a 16% yield.
Spectroscopic studies, however, indicated that the compound
obtained was not the desired vinyl allene 2 but the diazine 3
resulting from the cycloaddition of 2 and DEAD (Scheme 2).
Reducing the amount of DEAD or lowering the temperature
of the reaction did not allow us to isolate any allenic compound,
since it apparently reacted as soon as it was formed. This
behavior indicates that 2, although not useful for our purposes,
could act as a diene. The preparation of this vinyl allene has
been reported previously using other procedures,22 but in light
of the results obtained with other vinyl allenes as described
below, we decided not to pursue its preparation.
When Myers’s protocol was applied to 4,7 the corresponding
vinyl allene 59 was obtained in a 55% yield as a nonpolar oily
compound, without a trace of the cycloaddition products
(Scheme 3). The vinyl allene 5, after purification, reacted with
DEAD in ether to give the diazine 6 (60%) as a 1:1 mixture of
E and Z isomers on the exocyclic double bond.
(18) Wiberg, K. B. Tetrahedron 1968, 24, 1083.
(19) (a) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Chem. ReV. 1988, 88,
899. (b) Reed, A. E.; Weinstock, R. B.; Weinhold, F. J. Chem. Phys. 1985,
83, 735.
(20) All compounds described in this work were prepared in racemic
form.
(21) Myers, A. G.; Zheng, B. J. Am. Chem. Soc. 1996, 118, 4492.
(22) Baudouy, R.; Delbecq, F.; Gore, J. Tetrahedron 1980, 36, 189.
9154 J. Org. Chem., Vol. 71, No. 24, 2006

Reaction of Vinyl Allenes and Aldehydes
SCHEME 3
SCHEME 5
SCHEME 6 a
SCHEME 4
a (a) MeMgBr, CuI, LiBr, 0 °C; (b) EtMgBr, CuBr‚Me2S, -60 °C; (c)
t-BuLi, CuCN, -78 °C.
1) were not reactive toward the hetero Diels-Alder reaction
with aldehydes, and no further experiments with this type of
compounds were made.
Those results indicate that this vinyl allene, although less
reactive than 2 toward DEAD, was a good diene. However,
when we assayed its reactivity toward aldehydes using BF3‚
Et2O as a Lewis acid, the results were quite different. Thus,
with propionaldehyde, a compound was isolated in a low yield
(10%) showing a 1H NMR spectrum consistent with the
incorporation of two molecules of aldehyde and one molecule
of vinyl allene. After further studies, the compound was
identified as the dioxane 9, the result of a Prins-type reaction
between the terminal double bond of the allene and the aldehyde
(Scheme 4). Increasing the amount of aldehyde allowed us to
increase the yield, but only up to 15%.
We then turned our attention to the alkyl substituted vinyl
allenes, some of which had been prepared in our previous work
from the SN2′ reaction of a suitable cuprate onto a propargyl
benzoate.9 The reagents and the yields are shown in Scheme 6.
All vinyl allenes prepared, with the exception of 20 which
lacks substituents at the end of the allene moiety, showed good
reactivity when maleic anhydride was used as the dienophile,
indicating that they are at least as reactive in the Diels-Alder
reaction as the vinyl allenes previously published.4
When we tried the hetero Diels-Alder reaction of those vinyl
allenes with aldehydes and BF3‚Et2O as the Lewis acid, the
reaction proceeded in all cases except for vinyl allenes 20 and
23, which did not give any compounds under the conditions
tried, and 24, which only reacted with benzaldehyde. Table 1
shows the results obtained.
All compounds obtained present the same geometry on the
exocyclic double bond and are the result of a complete facial
selectivity, with the approach of the dienophile through the less
hindered face of the vinyl allene, the one opposite to the
orthogonal group on the extreme of the allene. The regiochem-
istry of the approach is also high and the same in all examples
studied, with the new bonds formed between the central bond
of the allene and the carbonyl carbon atom and between the
terminal carbon of the dienic system and the carbonyl oxygen.
The endo/exo selectivity, however, is not very high, with
mixtures of compounds with a cis (coming from the endo
approach) and a trans (coming from the exo approach) relative
This type of Prins reaction has usually been carried out in
aqueous media using protic acids, but examples of Lewis acid
catalysis are known.23
Using isobutyraldehyde instead of propionaldehyde, a similar
compound (10) was obtained in a 22% yield. No compound
coming from a hetero Diels-Alder reaction was observed. The
relative stereochemistry of 9 and 10 was established by GOESY
experiments.24
When we applied Myers’s protocol to propargyl alcohol 11,9
a mixture of vinyl allene 12 (10%) and diazine 13 (15%) was
obtained (Scheme 5). A slightly better yield of 12 (24%), without
contamination with diazine, was obtained using LiAlH4/AlCl3
as the reagents.25 However, its reaction with propionaldehyde
gave only decomposition under all conditions tested.
From these results, it became clear that the vinyl allenes
unsubstituted at the inner position of the allene (R1 ) H, Figure
(23) Snider, B. N. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 2, pp 527-561.
(24) Stonehouse, J.; Adell, P.; Keeler, J.; Shaka, A. J. J. Am. Chem.
Soc. 1994, 116, 6037.
(25) Shen, G. Y.; Tapia, R.; Okamura, W. H. J. Am. Chem. Soc. 1987,
109, 7499.
J. Org. Chem, Vol. 71, No. 24, 2006 9155

Rega´s et al.
TABLE 1. Reaction of Vinyl Allenes with Aldehydes in the
SCHEME 7
Presence of BF3‚Et2Oa
entry vinyl allene aldehyde compound (% yield) cis:trans ratio
1
2
3
4
5
6
7
8
9
10
11
12
13
18
18
18
19
19
19
21
21
21
22
22
22
24
7
8
25
7
8
25
7
8
25
7
8
25
25
26 (63)
27 (26)
28 (76)
29 (49)
30 (24)
31 (74)
32 (70)
33 (60)
34 (62)
35 (54)
36 (36)
37 (40)
38 (39)
46:54
0:100
49:51
52:48
57:43
53:47
70:30
74:26
64:36
73:27
66:34
75:25
0:100
by a phenyl and gives slightly lower yields but similar selectivity
(about 70:30 cis:trans). The least reactive is 20 which does not
give any product under the conditions used in this work.
As a conclusion concerning the substitution patterns and the
reactivity, it can be said that in order to react with aldehydes,
the vinyl allenes need to have substituents at the R1 position
which must not exert too much steric hindrance. The allene
terminus must be monosubstituted, and alkyl groups seem to
be slightly more reactive than phenyl groups.
Computational Studies. These experimental results do not
allow us to draw any conclusions regarding the mechanism of
the Lewis acid-catalyzed reaction between vinyl allenes and
aldehydes, which could range from a highly asynchronous
pericyclic process to an ionic one. Also, a number of questions
remain unanswered such as the role of the substituents on the
inner carbon of the allene moiety or the difference in endo/exo
selectivity when such a substituent changes from a methyl to
an ethyl group.
a The stereochemistry of the products was deduced from NMR data
(GOESY experiments). The cis:trans ratio was obtained by integration of
the H NMR spectra of the crude reaction mixtures.
1
stereochemistry of the hydrogen atoms of the positions adjacent
to the oxygen being obtained, in most cases. No explanation
has been found for the lack of reactivity of 20, which has two
hydrogen atoms at the end of the allene moiety, although it may
be due to decomposition under the reaction conditions since it
resulted in the most acid-sensitive vinyl allene prepared, and
no product could be isolated from any of the reactions tried.
Compound 23, substituted with a tert-butyl group on the allene,
also presents low reactivity, which may be due to the difficulty
in attaining the necessary s-cis conformation because of steric
hindrance.11
Analyzing the results presented in Table 1, it can be observed
that, with trisubstituted allenes, the endo/exo selectivity is higher
for the ethyl substituted compounds, and thus the cis:trans ratio
changes from endo isomers as a major compound when R1 is
Et (vinyl allenes 21, 22) to an almost 1:1 mixture of endo and
exo isomers when R1 is Me (using vinyl allene 19) or even to
exo isomers as the favored isomer with vinyl allene 18 and
isobutyraldehyde. Since both alkyl groups exert a similar
electronic and steric effect on the diene in Diels-Alder
reactions,26 we have attributed this behavior to the stability
problems observed for the cycloadducts, stability being espe-
cially low for the cis compounds when R1 is Me. When the
allene is tetrasubstituted (24), only the trans compound is
obtained, which may be explained by the slow reaction caused
by the difficulties on the approach of the heterodienophile to
either face of the diene because of the presence of the two
orthogonal methyl groups. The longer reaction times may
facilitate the decomposition mainly of the less stable cis
cycloadduct.
For those reasons, it was decided to undertake a computational
study of this reaction.
In order to better understand the reaction, we decided to first
carry out the study of the uncatalyzed process in order to obtain
information on the reactivity of the two systems, the vinyl allene
and the aldehyde.
The computations were carried out using simplified models
in order to reduce the computational cost. Thus, instead of
cyclohexenyl allenes 5 or 18, we chose as models vinyl allenes
A and B, in which the cyclohexene ring is replaced by a 1,2-
dimethylethene moiety, and the only difference between them
is the substituent R1 (Scheme 7). Acetaldehyde was selected as
a model for the dienophile.
Only one regiochemistry was studied since preliminary
calculations indicated that the one found experimentally was
much lower in energy than the opposite one at any of the
computational levels tried. Furthermore, the dienic system in
the s-cis conformation of the vinyl allene presents two distinct
faces because of the presence of the out-of-plane methyl group
on the extreme of the allene moiety, and the published
calculations4 indicated, as mentioned before, that the approach
of the dienophile is controlled by steric factors and should take
place by the face opposite to the orthogonal alkyl group. Taking
If we compare the reactivity of the ethyl substituted vinyl
allenes then it can be seen that the most reactive is 21, which
bears a methyl group and a hydrogen atom at the end of the
allene. Next comes 22 in which the methyl group is replaced
(26) Robiette, R.; Marchand-Brynaert, J.; Peeters, D. J. Org. Chem. 2002,
67, 6823.
9156 J. Org. Chem., Vol. 71, No. 24, 2006

Reaction of Vinyl Allenes and Aldehydes
FIGURE 2. Calculated structures of the transition states and reaction profiles for the reactions of vinyl allenes A and B with acetaldehyde. Relevant
distances are in Å, and activation energies, reaction energies, and Gibbs activation energies at 298 K are in kcal/mol.
all of this into account, we started by modeling the reaction
coordinates and calculating all stationary points involved at the
B3LYP/6-31G(d,p) level for the reactions depicted in Scheme
7. There are two possible transition states for each reaction
which correspond to the endo (TSAN and TSBN for the reactions
of A and B, respectively) and exo (TSAX and TSBX) approaches
of the dienophile to the dienic part of the vinyl allene, and thus
two cycloadducts are possible for each process. Scheme 7 shows
the reactions studied, the naming convention, and the arbitrary
numbering scheme used in this part of the discussion.
The transition states coming from the endo approach of the
dienophile (TSAN and TSBN) lead to products in which the
hydrogen atoms at the positions adjacent to the oxygen are cis
(PAN and PBN), whereas those coming from the exo approach
(TSAX and TSBX) produce trans compounds (PAX and PBX).
Frontier molecular orbital analysis indicates that these reactions
are controlled by the vinyl allenes HOMO aldehyde LUMO
interactions and also indicates that the reaction of B should be
favored.27 Figure 2 depicts the profiles for the reactions of vinyl
allenes A and B with acetaldehyde, calculated at the B3LYP/
6-31G(d,p) level together with their activation energies, Gibbs
activation energy at 298 K, reaction energies, and bond-forming
distances. The reactions are calculated to be exothermic, with
the cis product coming from the endo approach of the dienophile
being the more stable in both cases.
found are similar to those calculated for the reaction of butadiene
and acetaldehyde.28 The structure of the transition states studied
and the transition vector motion along the reaction coordinates
for all cases are consistent with a concerted Diels-Alder
cycloaddition. In addition, no intermediate corresponding to a
stepwise intermediate could be found after performing intrinsic
reaction coordinate (IRC) calculations. Only the starting com-
pounds and the cycloadducts were found on either side of the
transition state along the reaction coordinate. Studying the
geometry of the different transition states, we observed the
expected changes in going from reactants to transition state,
such as the shortening of the participating single bond of the
vinyl allene and the lengthening of the carbonyl double bond
and of the two double bonds of the dienic portion of the vinyl-
allene. The difference in the bond-forming distances in the
transition states indicates asynchronous processes, which were
studied using the relative variation of the Wiberg bond index
at the transition state (δâi), which was calculated for each bond
involved in the reaction using the NBO method. The results
are presented in Table 2. The average variation of the bond
orders at the transition state (δâav) indicates that in all the
reactions studied, the transition state occurs before the midpoint
in the reaction coordinate; the transition states for the reaction
of the alkyl-substituted vinyl allene B (0.41) were attained
slightly earlier than the corresponding ones for the hydrogen-
substituted vinyl allene A (0.42). The same values were found
for the endo and exo approaches. Examination of the individual
variation of the bond order for each bond involved in the
reaction (δâi) indicates that the bond between the carbonyl
oxygen, O7, and the extreme of the diene, C5, presents the
smaller change for each reaction, whereas the C2-C3 allenic
double bond presents the larger one. This is consistent with the
different bond-forming distances calculated at the transition
From Figure 2, it can be observed that the transition states
arising from the reaction of vinyl allene A (TSAN and TSAX
)
present higher activation energy and Gibbs activation energy
than those coming from the alkyl-substituted vinyl allene B
(TSBN and TSBX). The endo approach is the more favorable
one in both of these cases. The observed activation energies
(27) The B3LYP/6-31.G(d,p) HOMO/LUMO energies (eV) are: s-trans
A (-5.67/-0.16); s-trans B (-5.64/-0.13); s-trans CR (-5.70/0.16); s-trans
Câ (-5.65/0.10); acetaldehyde (-6.94/-0.60); BF3-acetaldehyde complex
(-9.22/-2.41); and s-trans D (-5.72/-0.18).
(28) (a) Park, Y. S.; Lee, B.-S.; Lee, I. New J. Chem. 1999, 23, 707. (b)
McCarrick, M. A.; Wu, Y.-D.; Houk, K. N. J. Org. Chem. 1993, 58, 3330.
J. Org. Chem, Vol. 71, No. 24, 2006 9157

Rega´s et al.
TABLE 2. Relative Wiberg Bond Index Variation at the
Transition State for Each Bond Involved (δâi), Average Bond Order
Variation at the Transition State (δâav), and Synchronicities (sy) for
Each Transition State Calculateda
SCHEME 8
δBi
transition
state
O7-C6 C6-C2 C2-C3 C3-C4 C4-C5 C5-O7 δâav sy
TSAN
TSAX
TSBN
TSBX
0.44
0.43
0.45
0.45
0.44
0.41
0.46
0.43
0.57
0.54
0.57
0.56
0.39
0.41
0.35
0.37
0.40
0.44
0.37
0.40
0.26 0.42 0.91
0.29 0.42 0.93
0.24 0.41 0.87
0.26 0.41 0.90
a The arbitrary numbering presented in Scheme 7 is used.
TABLE 3. Second-Order Perturbation Energies for the
Interaction between Donor and Acceptor π Orbitals at the
Transition States of the Studied Reactionsa
donor
acceptor
TSAN
TSAX
TSBN
TSBX
π2-3
π6-7
π4-5
π2-3
π6-7
π4-5
π1-2
π6-7
π*6-7
π*2-3
π*2-3
π*4-5
π*4-5
π*6-7
π*6-7
π*1-2
54.93
9.37
26.89
11.41
5.60
3.99
5.00
2.20
38.07
6.45
27.14
12.41
6.95
7.38
6.12
1.91
63.80
10.02
26.55
10.07
5.02
2.94
5.39
2.40
59.35
8.82
28.29
10.18
6.25
4.09
4.43
1.99
a Energies are in kcal/mol and are stabilizing (i.e., negative). The arbitrary
numbering presented in Scheme 7 is used.
states and is consistent with the formation of the bond between
C2-C6 being the more advanced of the two new bonds formed
in the reaction. Those results give global asynchronicities of
0.91 for the endo and 0.93 for the exo approaches for the case
of vinyl allene A, which may be described as slightly asyn-
chronous, with smaller values for vinyl allene B (0.87 for the
endo approach and 0.90 for the exo one), which indicates a
higher degree of asynchronicity.
BF3 was selected as the model and included in the calculations.
The Lewis acid-acetaldehyde complex was modeled as trans,
since both the computational results and the experimental data30
indicated that this is the preferred disposition. Scheme 8 shows
the reaction under study and the naming convention used.
Figure 3 depicts the profiles for the reactions of vinyl allenes
A and B with acetaldehyde catalyzed by boron trifluoride and
calculated at the B3LYP/6-31G(d,p) level together with their
activation energies, reaction energies, Gibbs activation energies
at 298 K, and bond-forming distances. As with the uncatalyzed
processes, no intermediate corresponding to a stepwise inter-
mediate could be found after performing IRC calculations. The
reactions are also calculated to be exothermic with the cis
product, coming from the endo approach of the dienophile, being
the more stable in both cases.
The NBO analysis also gives some insight into the electronic
nature of the transition states of the reactions under study. Table
3 shows the interaction energy between the donor and the
acceptor π orbitals for the systems involved in the reaction.
The expected interaction of π and π* orbitals for a pericyclic
process can be observed in Table 3, although in a nonsym-
metrical distribution. Thus, the stronger donation goes from the
allenic C2-C3 double bond (π2-3) to the antibonding orbital
of the carbonyl group (π*6-7) and is more important for the
alkyl-substituted systems (TSBN and TSBX). The second one is
the interaction between the two double bonds of the dienic
system (π4-5 to π*2-3) which is similar in magnitude in all cases
studied, whereas the interaction for the carbonyl double bond
and the π*4-5 is much smaller. As a result of these interactions,
a charge transfer, calculated using a natural population analysis,
from the vinyl allenes to the aldehyde takes place at the
transition state which is larger for TSBN and TSBX (0.221 e for
both) than for TSAN (0.204 e) and TSAX (0.183 e). Another
interesting feature found is the interaction between the terminal
allenic double bond π1-2, orthogonal to the diene in the starting
compounds, and the carbonyl group, which is of the same
magnitude as those on the bond-forming interaction between
the carbonyl group and the C4-C5 double bond. This is
probably due to the distortion of the allene at the transition state,
which allows for some overlap of the two orbitals.
Also, the transition states arising from the reaction of vinyl
allene A with the acetaldehyde-BF3 complex (cTSAN and
cTSAX) present activation energies similar to those calculated
27b
for butadiene and formaldehyde catalyzed by BH3 but are
higher than those coming from the alkyl-substituted vinyl allene
B (cTSBN and cTSBX). The difference between the two systems
is now larger than in the uncatalyzed case. This is in agreement
with the experimental observation that the alkyl-substituted vinyl
allenes react with aldehydes in the presence of a Lewis acid,
whereas the unsubstituted ones do not react under the same
conditions. Looking at the difference in energy between the endo
and the exo approaches in each case, it can be observed that
the presence of the Lewis acid is especially significant for the
All these data indicate that the studied reactions are pericyclic,
(29) The analysis of the Mulliken charges at the transition states also
follows the same pattern. See Supporting Information for a discussion.
(30) Reetz, M. T.; Hu¨llmann, M.; Massa, W.; Berger, S.; Rademacher,
P.; Heymanns, P. J. Am. Chem. Soc. 1986, 108, 2405.
slightly asynchronous processes.29
The next step in the calculations was to add a Lewis acid in
order to compare them with the experimental results obtained.
9158 J. Org. Chem., Vol. 71, No. 24, 2006

Reaction of Vinyl Allenes and Aldehydes
FIGURE 3. Calculated reaction profiles for the reactions of vinyl allenes A and B with BF3-complexed acetaldehyde. Relevant distances are in
Å, and activation energies, Gibbs activation energies at 298 K, and reaction energies are in kcal/mol.
reactions of B, since the endo-exo difference is only 0.5
kcal/mol, indicating that a mixture of cycloadducts should be
expected in this case. The Gibbs activation energy differences
also follow the same trend. This is in contrast with the
experimental data since the methyl-substituted vinyl allenes gave
either 1:1 ratios or even the cycloadduct coming from the exo
approach as the only product.
disposition is â and the interaction with the incoming hetero-
dienophile is minimized. Thus, the â disposition must be the
reacting one. The reaction profile calculated for this more favor-
able approach is quite similar to that of the reaction of B. The
main difference is the higher stability of the trans cycloadduct;
however, the activation energies are of similar magnitude, and
therefore, the expected endo/exo ratio should also be similar.
Thus, from these calculations, it can be concluded that the
difference in selectivity of the reactions with the alkyl-substituted
vinyl allenes is not due to structural reasons but to the
experimentally observed lower stability of the cis compounds
coming from the endo approach, especially those in which the
substituent at the R1 position is a methyl group.
The geometry of the transition states is also different from
that of the uncatalyzed cases, the bond-forming distances now
being larger and the differences among them greater, the largest
being the one between the carbonyl oxygen and the end of
the diene (O7-C5). This indicates a higher degree of asyn-
chronicity for the catalyzed processes. The study of the syn-
chronicity of the reactions is presented in Table 4. The average
variation of the bond index at the transition state (δâav) indicates
that all reactions studied occur earlier in the reaction coordi-
nate than in the uncatalyzed cases, with the transition states for
the reaction of the alkyl-substituted vinyl allenes B and C
(0.28-0.29) occurring earlier than the corresponding ones for
the hydrogen-substituted vinyl allene A (0.32-0.33). Slightly
larger values were found for the exo approaches. Examination
of the individual variation of the bond index for each bond
involved in the reaction (δâi) shows values similar to those
found for the uncatalyzed process for the bonds involved in
the formation of the C2-C6 bond (C2-C3, C2-C6, and
C6-O7), whereas the remainder of the bonds show smaller
values. Those results give global asynchronicities of 0.78 for
the endo and 0.77 for the exo approaches for the case of vinyl
allene A, which may be described as highly asynchronous, and
The ethyl-substituted vinyl allenes gave experimental
endo/exo ratios close to 70:30, and it was also observed that
these compounds were more stable than the methyl-substituted
ones. The cis cycloadducts were also more prone to decomposi-
tion than the trans ones, and thus the difference in endo/exo
ratios was attributed to the decomposition of the cis isomer.
However, the possibility of other effects taking place could not
be ruled out, and thus the reaction of the ethyl-substituted vinyl
allene was studied using C as the model. For this vinyl allene
the conformation of the ethyl group must be taken into account
since two possible dispositions of the ethyl group can be
described for the reacting s-cis conformation of vinyl allene C;
one in which the terminal methyl of the ethyl group and the
methyl on the extreme of the allene are syn relative to the plane
defined by the diene, and another in which those two methyl
groups are anti. Thus, there are two different starting points for
this reaction, related by the rotation of the ethyl group. The
more stable of the two conformers of the vinyl allene is the
anti one, probably because of the nonbonded interaction of the
two out-of-plane methyl groups in the syn conformer. However,
in the transition states, the situation is reversed since the main
interaction is that of the ethyl group with the incoming hetero-
dienophile which is highly destabilizing. The results of this study
are shown in Figure 4. The effect of the conformation of the
ethyl group is clear from the comparison of the two reaction
profiles. When the rotamer with the R disposition of the methyl
group is considered, the transition states are higher in energy,
and the bond-forming distances are also larger than when the
J. Org. Chem, Vol. 71, No. 24, 2006 9159

Rega´s et al.
FIGURE 4. Calculated reaction profiles for the reactions of vinyl allene C with BF3-complexed acetaldehyde in the two conformations of the ethyl
group. Relevant distances are in Å, and activation energies, Gibbs activation energies, and reaction energies are in kcal/mol.
TABLE 4. Bond Order Variation at the Transition State for Each
Bond Involved (δâi), Average Bond Order Variation at the
Transition State (δâav), and Synchronicities (sy) for Each Transition
State Calculated for the Catalyzed Reactionsa
The natural population analysis performed using the NBO
method indicates that the net charge transfer in the transition
state from the vinyl allene to the heterodienophile is quite similar
in all cases, being 0.34 and 0.36 e for the endo and exo
approaches of vinyl allene A, 0.32 and 0.33 e for B, and 0.32
and 0.34 e for the corresponding endo and exo approaches of
the vinyl allene C to the aldehyde-BF3 complex, which is much
larger that those found for the uncatalyzed reactions. All these
data also reinforce the idea that the reaction of vinyl allenes
and aldehydes under BF3 catalysis occurs through a highly polar
transition state somewhat zwitterionic in character, similar to a
nucleophilic attack by the central carbon of the allene on the
carbonyl group in the early stages of the process.
δBi
transition
state
O7-C6 C6-C2 C2-C3 C3-C4 C4-C5 C5-O7 δâav sy
cTSAN
cTSAX
cTSBN
cTSBX
cTSCN
cTSCX
cTSDN
cTSDX
0.43
0.46
0.39
0.42
0.40
0.42
0.36
0.39
0.38
0.39
0.34
0.35
0.34
0.35
0.33
0.35
0.51
0.54
0.46
0.49
0.47
0.47
0.47
0.49
0.27
0.28
0.21
0.21
0.22
0.21
0.23
0.22
0.27
0.27
0.22
0.22
0.22
0.22
0.23
0.23
0.08 0.32 0.78
0.07 0.33 0.77
0.06 0.28 0.75
0.05 0.28 0.74
0.06 0.28 0.75
0.05 0.29 0.74
0.06 0.28 0.77
0.05 0.29 0.75
a The arbitrary numbering presented in Scheme 8 is used.
Another observation made during the experimental work was
the lack of reactivity of vinyl allene 20, which bears no
substituents at the terminal allene carbon, toward dienophiles.
Only decomposition was obtained in all reactions assayed. This
could be due to the high lability of the vinyl allene which
decomposes under the reaction conditions as indicated above
or be due to the importance of the substituents at the terminal
carbon of the allene. Computational studies identical to those
described above, using D as the model, were carried out, and it
was found that the HOMO of D is lower in energy than any of
the others calculated,27 which does not correlate with the
activation energies found (Figure 5).
even smaller values for vinyl allenes B and C (0.75 for the endo
approach and 0.74 for the exo one).
The second-order perturbation analysis performed on the
transition states is quite different from the one performed in
the uncatalyzed reactions. Thus, the C2-C3 double bond (π2-3
)
is not found in the NBO analysis. Instead, two p orbitals of
similar energy are located on those atoms and labeled LP(C2)
and LP*(C3), and the donation from LP(C2) to the antibonding
orbital of the carbonyl double bond π*6-7 is precisely the most
important one in all catalyzed cases studied. The high value of
this donation contrasts with the smaller ones found for the
interactions of the carbonyl π orbitals and the C4-C5 double
bond, and this difference agrees with the higher asynchronicity
found in this catalyzed process. The interaction of the C1-C2
double bond of the allene and the carbonyl group is smaller
than in the uncatalyzed process, probably because of the earlier
transition state in which the distortion of the allene is not large
enough to allow a good interaction between the corresponding
orbitals.
The energies of activation are midway between those found
for the reactions of A and B, and in this case, the endo transition
state (cTSDN) is slightly higher than the exo one (cTSDX),
although for Gibbs activation energies this situation is reversed,
and the values are closer to those found for the reaction of B.
Both approaches, endo and exo, present early transition states
with bond-forming distances similar to those calculated for
cTSBX and cTSBN and low synchronicities (Table 4). The net
9160 J. Org. Chem., Vol. 71, No. 24, 2006

Reaction of Vinyl Allenes and Aldehydes
TABLE 5. Second-Order Perturbation Energies for the Interaction between Donor and Acceptor π Orbitals at the Transition States of the
Studied Catalyzed Reactionsa
donor
acceptor
cTSAN
cTSAX
cTSBN
cTSBX
cTSCN
cTSCX
cTSDN
cTSDX
LP(C2)
π6-7
π*6-7
195.08
11.01
194.49
10.63
159.05
8.30
51.58
27.81
0.29
152.93
6.71
51.23
27.77
0.20
163.14
8.51
50.85
27.97
0.29
0.50
1.07
154.82
6.68
51.00
28.25
0.20
145.83
8.03
53.66
27.80
0.28
0.50
0.74
151.29
6.95
52.30
28.01
0.20
0.55
0.35
LP(C2)b
LP*(C3)b
π*4-5
π4-5
LP*(C3)b
π6-7
29.30
0.35
0.59
1.13
0.59
π*4-5
π4-5
π*6-7
0.54
0.56
π1-2
π*6-7
0.47
0.37
0.96
0.52
π6-7
π*1-2
0.28
0.58
0.25
0.41
0.30
a The arbitrary numbering presented in Scheme 8 is used. Energies are in kcal/mol and are stabilizing (i.e., negative). No entry indicates a value lower
than the threshold of 0.5 kcal used by the program. b The orbitals denoted, LP(C2) and LP*(C3), are semi-occupied.
Experimental Section
(()-Diethyl-3-methylene-6,7,8,8a-tetrahydrocinnoline-1,2-
(3H,5H)-dicarboxylate (3). To a suspension of PPh3 (5.6 g, 21.3
mmol) and DEAD (3.2 mL, 20.3 mmol) in THF (43 mL) at -15
°C was slowly added a solution of propargyl alcohol 1 (2.41 g,
17.7 mmol) in THF (7 mL). After 10 min, 2-nitrobenzenesulfo-
nylhydrazine (4.6 g, 21.2 mmol) in THF (25 mL) was added via
cannula. The reaction mixture was allowed to warm to rt and was
stirred for 7 h. Then it was poured over pentane (50 mL), and the
organic layer was washed with cold water (5 × 150 mL), dried
(Na2SO4), and concentrated. Flash column chromatography (8:2
hexane/EtOAc) afforded 820 mg of compound 3 (2.8 mmol,
1
16%): amorphous orange solid; H NMR (400 MHz, CDCl3, 330
K) δ 5.80 (s, 1H), 5.21 (s, 1H), 4.88 (s, 1H), 4.51 (bs, 1H), 4.17
(m, 4H), 2.30 (m, 1H), 2.10 (m, 2H), 1.84 (m, 2H), 1.54-1.46 (m,
3H), 1.25 (m, 6H); 13C NMR (100 MHz, CDCl3, 330 K) δ 154.2,
153.2, 141.6, 137.4, 116.3, 105.6, 62.1, 34.1, 31.9, 28.0, 25.0, 14.3,
14.2; IR (CHCl3) 1700 cm-1; MS (EI) m/z 294 (M+, 17), 221 (39),
193 (11), 177 (8), 149 (100). HRMS (EI) m/z: calcd for
C15H22N2O4, 294.1579; found, 294.1587.
(()-(3-Cyclohexenylpropa-1,2-dienyl)benzene (12). To a stirred
suspension of LiAlH4 (815 mg, 21.4 mmol) and AlCl3 (959 mg,
7.19 mmol) in diethyl ether (30 mL) at -15 °C under argon was
slowly added a solution of propargyl alcohol 11 (2.28 g, 10.74
FIGURE 5. Calculated reaction profiles for the reactions of vinyl allene
D with BF3-complexed acetaldehyde. Relevant distances are in Å, and
activation energies, Gibbs activation energies, and reaction energies
are in kcal/mol.
mmol) in diethyl ether (5 mL). The reaction mixture was allowed
to warm to rt and stirred for 18 h. Then it was quenched by the
successive addition of H2O (1.8 mL), 10% NaOH (1.8 mL), and
H2O (5.3 mL) at 0 °C. The reaction mixture was diluted with ether,
filtered through Celite, and concentrated. Purification of the residue
by column chromatography (hexane) gave 12 (509 mg, 24%) as a
charge transfers from the vinyl allene to the BF3-acetaldehyde
complex in both approaches (0.31 e for the endo and 0.34 e for
the exo) are also similar to those found for B, and the second-
order perturbation analysis is also quite similar in both cases
(Table 5). All these data seem to indicate that D should be some-
what less reactive than vinyl allene B in a catalyzed reaction,
but they do not clarify if the lack of results found experimentally
is due to the higher activation energy or to its lability. These
studies also indicate that the presence of the substituents at the
terminal position of the allene is not as important for the success
of the reaction as the ones at the inner carbon of the allene.
1
colorless oil. H NMR (400 MHz, CDCl3) δ 7.4-7.17 (m, 5H),
6.39 (d, J ) 6.2 Hz, 1H), 6.25 (d, J ) 6.4 Hz, 1H), 5.77 (bs, 1H),
2.2-1.99 (m, 4H), 1.77-1.54 (m, 4H); IR (CHCl3) 2900, 1940,
1585, 1488 cm-1; MS (EI) m/z 196 (M+, 89), 181 (21), 138 (98).
HRMS (EI) m/z: calcd for C15H16, 196.1252; found, 196.1375.
(()-(E)-Diethyl-3-benzylidene-6,7,8,8a-tetrahydrocinnoline-
1,2(3H,5H)-dicarboxylate (13). We used a procedure identical to
that described for the preparation of 3 from 1 to afford a mixture
of vinyl allene 12 (241 mg, 10%) and the title compound 13 (690
mg, 15%) as an amorphous orange solid from the propargyl alcohol
11 (2.6 g, 12.3 mmol); 1H NMR (400 MHz, CDCl3, 330 K) δ 7.76
(m, 2H), 7.24-7.14 (m, 3H), 6.69 (s, 1H), 6.27 (bs, 1H), 6.18 (bs,
1H), 4.13 (m, 2H), 3.96 (m, 2H), 2.18 (m, 2H), 1.93 (m, 2H), 1.51-
1.42 (m, 4H), 1.08 (t, J ) 7.03 Hz, 3H), 0.97 (m, 3H); 13C NMR
(100 MHz, CDCl3, 330 K) δ 155.4, 137.4, 135.0, 128.4, 128.1,
127.6, 127.4, 120.6, 88.9, 82.2, 62.4, 61.2, 55.2, 29.1, 25.4, 22.2,
21.4, 14.0, 13.9; MS (EI) m/z 370 (M+, 0.19), 341 (0.34), 282
(0.85), 196 (17), 195 (100). HRMS (EI) m/z: calcd for C21H26N2O4,
370.1892; found, 370.1892.
Conclusions
In conclusion, we have studied the reaction of vinyl allenes
with aldehydes under Lewis acid catalysis and have found that
the substitution pattern on the allene is important for its success.
The regio- and facial selectivity are high, but an endo/exo
mixture is obtained in most cases. The mechanism of the
reaction was studied computationally using density functional
theory, concluding that in the uncatalyzed case, the reaction is
pericyclic, but when BF3 is included as a Lewis acid, the reaction
takes place through a highly polar transition state. Endo/exo
mixtures are expected in all cases studied.
(()-(E)-Diethyl-3-ethylidene-6,7,8,8a-tetrahydrocinnoline-1,2-
(3H,5H)-dicarboxylate (6) and (Z)-Diethyl-3-ethylidene-6,7,8,-
8a-tetrahydrocinnoline-1,2(3H,5H)-dicarboxylate (6). To a stirred
solution of vinyl allene 5 (150 mg, 1.13 mmol) in diethyl ether (4
mL) at -78 °C was slowly added DEAD (0.18 mL, 1.13 mmol).
J. Org. Chem, Vol. 71, No. 24, 2006 9161

Rega´s et al.
The reaction mixture was allowed to warm to rt and was stirred
for 5 h. Then it was diluted with pentane (10 mL), poured over
cold water, and extracted with diethyl ether (4 × 15 mL). After
drying (Na2SO4), concentration, and flash chromatography (8:2
hexane/EtOAc), an E:Z mixture of (1:1) compound 6 was obtained
(209 mg, 0.68 mmol, 60%) as an amorphous orange solid. (E-6):
1H NMR (300 MHz, CDCl3) δ 6.11 (s, 1H), 5.63 (bs, 1H), 4.48
(bs, 1H), 4.26-4.00 (m, 4H), 2.40-2.26 (m, 1H), 2.20-1.98 (m,
2H), 1.90-1.68 (m, 1H), 1.78 (d, J ) 7.7 Hz, 3H), 1.67-1.36 (m,
4H), 1.25 (t, J ) 7.0 Hz, 6H); IR (CHCl3) 1700 cm-1; MS (EI)
m/z 308 (M+, 19), 293 (49), 249 (8), 235 (78), 221 (36), 163 (100).
HRMS (EI) m/z: calcd for C16H24N2O4, 308.1736; found, 308.1693.
(Z-6): 1H NMR (400 MHz, CDCl3, 328 K) δ 5.81 (s, 1H), 5.26
(q, J ) 7.07 Hz, 1H), 4.43 (bs, 1H), 4.25-4.10 (m, 4H), 2.30-
2.22 (m, 1H), 2.13-2.02 (m, 2H), 1.86-1.75 (m, 2H), 1.72 (d, J
) 7.7 Hz, 3H), 1.55-1.40 (m, 3H), 1.25 (t, J ) 7.0 Hz, 3H), 1.24
(t, J ) 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 155.4, 154.4,
138.5, 132.6, 119.3, 117.0, 62.3, 62.1, 57.9, 34.4, 32.7, 28.1, 25.4,
14.5, 13.5; IR (CHCl3) 1700 cm-1; MS (EI) m/z 308 (M+, 21),
293 (36), 249 (6), 235 (51), 221 (32), 163 (100). HRMS (EI) m/z:
calcd for C16H24N2O4, 308.1736; found, 308.1669.
the vinyl allene (1.0 equiv). The reaction mixture was stirred at
room temperature (12-48 h), triethylamine (2.5 equiv) and water
were added, and the reaction mixture was extracted with diethyl
ether. Drying (MgSO4) and concentration afforded crude products.
Flash column chromatography on silica gel (98:2 hexane/EtOAc)
gave the products in the yields indicated.
(2R*,4R*,6R*,Z)-5-(Cyclohexenylmethylene)-2,4-diethyl-6-
methyl-1,3-dioxane (9). We followed the general procedure for
the reaction of vinyl allenes with aldehydes described above. Vinyl
allene 5 (100 mg, 0.75 mmol), propionaldehyde 7 (0.08 mL, 1.12
mmol), and BF3‚Et2O (1.1 equiv), after 12 h, provided compound
9 (28 mg, 15%) as an amorphous solid: 1H NMR (400 MHz,
CDCl3) δ 5.70 (s, 1H), 5.50 (s, 1H), 4.93 (t, J ) 5.3 Hz, 1H), 4.75
(dd, J ) 10.8, 4.1 Hz, 1H), 4.46 (q, J ) 6.2 Hz, 1H), 2.22
(m, 1H), 2.05 (m, 4H), 1.66-1.53 (m, 6H), 1.50-1.43 (m, 1H),
1.35 (d, J ) 6.2 Hz, 3H), 1.02-0.92 (m, 6H); 13C NMR (100
MHz, CDCl3) δ 136.8, 133.7, 126.6, 125.6, 95.9, 74.8, 71.1, 29.1,
28.2, 25.5, 24.4, 22.7, 22.0, 17.6, 10.2, 8.7; IR (CHCl3) 1590, 1445
cm-1; MS (EI) m/z 250 (M+, 1), 221 (3), 205 (2), 192 (39), 175
(22). HRMS (EI) m/z: calcd for C16H26O2, 250.1932; found,
250.1943.
3-Cyclohexenylprop-2-ynyl-benzoate (14). To a stirred solution
of 1 (4.8 g, 35.0 mmol) in THF (200 mL) at -78 °C under argon
was added dropwise n-BuLi (21.8 mL, 1.6 M in hexanes, 35 mmol).
The reaction mixture was kept at this temperature for 40 min and
was stirred further for 5 min at 0 °C. The reaction mixture was
then cooled to -78 °C, benzoyl chloride (4.4 mL, 38.5 mmol) was
added, and the reaction mixture was allowed to reach room
temperature. The mixture was stirred for 3 h, and a saturated
aqueous ammonium chloride solution was added. The mixture was
then extracted with diethyl ether. The combined organic layers were
washed with a saturated aqueous sodium chloride solution, dried
(MgSO4), and concentrated. Flash column chromatography (97:3
hexane/EtOAc) afforded 5.88 g of compound 14 (24.5 mmol,
70%): yellow oil; 1H NMR (400 MHz, CDCl3) δ 8.07 (d, J ) 7.9
Hz, 2H), 7.57 (t, J ) 7.0 Hz, 1H), 7.45-7.41 (m, 2H), 6.17 (bs,
1H), 5.04 (s, 2H), 2.12-2.08 (m, 4H), 1.63-1.56 (m, 4H); 13C
NMR (100 MHz, CDCl3) δ 165.9, 136.3, 133.1, 129.7, 129.6, 128.3,
119.8, 88.4, 80.2, 53.4, 28.8, 25.5, 22.1, 21.3; IR (CHCl3) 2900,
(2R*,4R*,6R*,Z)-5-(Cyclohexenylmethylene)-2,4-diisopropyl-
6-methyl-1,3-dioxane (10). We followed the general procedure for
the reaction of vinyl allenes with aldehydes described above. Vinyl
allene 5 (100 mg, 0.75 mmol), isobutyraldehyde 8 (0.10 mL, 1.12
mmol), and BF3‚Et2O (1.1 equiv), after 20 h, provided compound
10 (46 mg, 22%) as an amorphous solid: 1H NMR (400 MHz,
CDCl3) δ 5.80 (s, 1H), 5.67 (bs, 1H), 4.65 (d, J ) 6.0 Hz, 1H),
4.52 (d, J ) 10.7 Hz, 1H), 4.38 (q, J ) 6.1 Hz, 1H), 2.35 (m, 1H),
2.06 (m, 2H), 1.74-1.53 (m, 4H), 1.32 (d, J ) 6.2 Hz, 3H), 1.02
(d, J ) 6.4 Hz, 3H), 0.94 (m, 3H), 0.93 (m, 6H), 0.76 (d, J ) 6.8
Hz, 3H); MS (EI) m/z 278 (M+, 0.7), 277 (8), 251 (5), 199 (53),
127 (87), 98 (87), 98 (96), 83 (92), 57 (100). HRMS (EI) m/z:
calcd for C18H30O2, 278.2246; found, 278.2229.
Reaction of Vinyl Allene 18 and Propionaldehyde 7. Following
the general procedure, vinyl allene 18 (100 mg, 0.68 mmol),
propionaldehyde 7 (0.07 mL, 1.02 mmol), and BF3‚Et2O (1.1 equiv),
after 24 h, provided compounds 26 (88 mg, cis/trans 46:54,
63%), which were isolated after flash chromatography and HPLC
as pale yellow oils. (2S*,8aR*,E)-3-Ethylidene-4-methyl-2-phen-
2200, 1700, 1590 cm-1
.
1
1-(Penta-1,2-dien-3-yl)cyclohex-1-ene (20). Following the pro-
cedure previously described,9 the propargyl benzoate 14 (2.0 g, 8.33
mmol) was converted into the title compound 20 (757 mg, 61%)
as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 5.72 (bs, 1H),
4.93 (bs, 2H), 2.20-2.11 (m, 6H), 1.70-1.56 (m, 4H), 1.06 (t, J
yl-3,5,6,7,8,8a-hexahydro-2H-chromene (cis-26). H NMR (400
MHz, C6D6) δ 5.41 (q, J ) 7.2 Hz, 1H), 4.10 (m, 1H), 3.81 (bs,
1H), 2.66 (d, J ) 14.4 Hz, 1H), 2.25-2.22 (m, 1H), 1.99 (s, 3H),
1.84-1.79 (m, 4H), 1.65-1.45 (m, 4H), 1.33-1.08 (m, 6H);
13C NMR (100 MHz, C6D6) δ 138.5, 137.3, 123.3, 116.3, 77.6,
77.4, 35.3, 27.5, 27.2, 25.0, 24.6, 17.4, 15.4, 10.7; IR (CHCl3)
1440, 1370 cm-1. (2R*,8aR*,E)-3-Ethylidene-4-methyl-2-phenyl-
) 9.8 Hz, 3H); IR (CHCl3) 2900, 1925 cm-1
.
(()-(3-Cyclohexenylpenta-1,2-dienyl)benzene (22). Following
the procedure previously described,9 the propargyl benzoate 16 (2.3
g, 7.27 mmol) was converted into the title compound 22 (1.23 g,
75%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.34-7.16
(m, 5H), 6.40 (bs, 1H), 5.85 (bs, 1H), 2.38-2.06 (m, 6H), 1.68-
1.56 (m, 4H), 1.10 (t, J ) 9.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 205.9, 135.6, 132.6, 128.5, 126.6, 126.4, 122.8, 113.6, 98.0, 27.3,
26.0, 22.9, 22.5, 21.9, 12.5; IR (CHCl3) 2900, 1915, 1585, 1480
cm-1; MS (EI) m/z 224 (M+, 90), 209 (17), 195 (53), 181 (20),
165 (98). HRMS (EI) m/z: calcd for C17H20, 224.1565; found,
224.1569.
1
3,5,6,7,8,8a-hexahydro-2H-chromene (trans-26). H NMR (400
MHz, C6D6) δ 5.22 (q, J ) 7.3 Hz, 1H), 4.09 (d, J ) 13.8 Hz,
2H), 2.68-2.65 (m, 1H), 2.21 (m, 1H), 1.97 (s, 3H), 1.88-1.82
(m, 1H), 1.78 (d, J ) 7.3 Hz, 3H), 1.67-1.51 (m, 4H), 1.32-1.15
(m, 3H), 1.06 (t, J ) 7.4 Hz, 3H); 13C NMR (100 MHz, C6D6) δ
137.4, 137.0, 120.5, 119.3, 80.8, 71.5, 35.2, 27.5, 27.3, 24.8, 24.6,
17.0, 15.1, 10.7; IR (CHCl3) 1450, 1370 cm-1
.
Reaction of Vinyl Allene 18 and Isobutyraldehyde 8. Fol-
lowing the general procedure, vinyl allene 18 (100 mg, 0.68 mmol),
isobutyraldehyde 8 (0.09 mL, 1.02 mmol), and BF3‚Et2O (1.1
equiv), after 48 h, provided compound 27 (38 mg, 26%) as a pale
yellow oil. (2R*,8aR*,E)-3-Ethylidene-2-isopropyl-4-methyl-
1-(5-Methylhexa-3,4-dien-3-yl)cyclohex-1-ene (24). Following
the procedure previously described,9 the propargyl benzoate 17 (1.23
g, 4.6 mmol) was converted into the title compound 24 (522 mg,
64%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 5.67 (bs,
1H), 2.13 (m, 4H), 2.04 (m, 2H), 1.71 (s, 6H), 1.65-1.55 (m, 4H),
0.99 (t, J ) 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 201.0,
134.2, 120.9, 107.1, 97.9, 27.3, 25.8, 23.0, 22.5, 21.8, 20.7, 12.4;
1
3,5,6,7,8,8a-hexahydro-2H-chromene (trans-27). H NMR (400
MHz, C6D6) δ 5.20 (q, J ) 7.2 Hz, 1H), 4.05 (m, 1H), 3.67 (d, J
) 10.0 Hz, 1H), 2.64 (d, J ) 13.6 Hz, 1H), 2.21 (m, 1H), 2.04 (m,
1H), 1.96 (s, 3H), 1.78 (d, J ) 7.2 Hz, 3H), 1.66-1.51 (m, 4H),
1.33-1.07 (m, 2H), 1.24 (d, J ) 6.4 Hz, 3H), 0.87 (d, J ) 6.5 Hz,
3H); 13C NMR (100 MHz, C6D6) δ 137.4, 136.5, 120.4, 86.2, 71.6,
35.5, 27.5, 27.5, 24.6, 20.0, 19.7, 17.1, 15.1; IR (CHCl3) 1440,
1370 cm-1; MS (EI) m/z 220 (M+, 21), 205 (13), 177 (42), 159
(8), 149 (86). HRMS (EI) m/z: calcd for C15H24O, 220.1827; found,
220.1834.
IR (CHCl3) 2900, 1940, 1600 cm-1
.
General Experimental Procedure for the Reaction of Vinyl
Allenes and Aldehydes. To a stirred solution of the aldehyde (1.5
equiv) and boron trifluoride etherate (1.1 equiv) in diethyl ether
(0.15 M) at 0 °C under N2 atmosphere was added, after 15 min,
9162 J. Org. Chem., Vol. 71, No. 24, 2006

Reaction of Vinyl Allenes and Aldehydes
Reaction of Vinyl Allene 18 and Benzaldehyde 25. Following
the general procedure, vinyl allene 18 (100 mg, 0.68 mmol),
benzaldehyde 25 (0.10 mL, 1.02 mmol), and BF3‚Et2O (1.1 equiv),
after 17 h, provided compounds 28 (131 mg, cis/trans 49:51,
76%), which were isolated after flash chromatography and HPLC
as pale yellow oils. (2S*,8aR*,E)-3-Ethylidene-4-methyl-2-phen-
139.0, 137.7, 129.3, 127.7, 126.4, 125.2, 120.2, 85.5, 72.1, 35.7,
27.7, 27.5, 27.4, 24.6, 19.8, 19.5, 16.8; IR (CHCl3) 1630, 1480,
1440 cm-1; MS (EI) m/z 282 (M+, 37), 239 (100), 211 (95), 184
(29), 169 (24). HRMS (EI) m/z: calcd for C20H26O, 282.1983;
found, 282.1960.
Reaction of Vinyl Allene 19 and Benzaldehyde 25. Following
the general procedure, vinyl allene 19 (100 mg, 0.48 mmol),
benzaldehyde 25 (0.07 mL, 0.72 mmol), and BF3‚Et2O (1.1 equiv),
after 24 h, provided compounds 31 (112 mg, cis/trans 53:47, 74%),
which were isolated after flash chromatography and HPLC as pale
yellow oils. (2S*,8aR*,E)-3-Benzylidene-4-methyl-2-phenyl-
3,5,6,7,8,8a-hexahydro-2H-chromene (cis-31). 1H NMR (400
MHz, C6D6) δ 7.66-7.64 (m, 2H), 7.34-7.03 (m, 8H), 6.10 (s,
1H), 5.20 (s, 1H), 4.26 (m, 1H), 2.62 (d, J ) 13.8 Hz, 1H), 2.33
(m, 1H), 1.77-1.49 (m, 4H), 1.74 (s, 3H), 1.34-1.22 (m, 2H);
13C NMR (100 MHz, C6D6) δ 140.9, 140.3, 140.2, 139.0, 129.4,
128.4, 127.7, 127.6, 126.4, 125.2, 123.3, 79.9, 78.1, 35.5, 27.8,
27.3, 24.5, 17.4; IR (CHCl3) 1720, 1590, 1480, 1440 cm-1; MS
(EI) m/z 316 (M+, 28), 225 (19), 220 (13), 219 (75), 218 (100).
HRMS (EI) m/z: calcd for C23H24O, 316.1827; found, 316.1788.
(2R*,8aR*,E)-3-Benzylidene-4-methyl-2-phenyl-3,5,6,7,8,8a-
hexahydro-2H-chromene (trans-31). 1H NMR (400 MHz, C6D6)
δ 7.65-7.63 (m, 2H), 7.34-7.11 (m, 8H), 6.35 (s, 1H), 5.48 (s,
1H), 4.06 (m, 1H), 2.44 (d, J ) 11.6 Hz, 1H), 2.27 (m, 1H), 1.78-
1
yl-3,5,6,7,8,8a-hexahydro-2H-chromene (cis-28). H NMR (400
MHz, C6D6) δ 7.62-7.20 (5H), 5.10 (s, 1H), 5.02 (q, J ) 7.3 Hz,
1H), 4.22 (m, 1H), 2.69 (d, J ) 15.2 Hz, 1H), 2.31 (m, 1H), 2.01
(s, 3H), 1.70-1.58 (m, 3H), 1.64 (d, J ) 7.1 Hz, 3H), 1.32-1.20
(m, 3H); 13C NMR (100 MHz, C6D6) δ 141.0, 139.7, 137.7, 128.3,
127.2, 123.6, 121.1, 79.9, 77.8, 35.2, 27.5, 27.2, 24.5, 17.4, 15.4.
(2R*,8aR*,E)-3-Ethylidene-4-methyl-2-phenyl-3,5,6,7,8,8a-hexahy-
dro-2H-chromene (trans-28). 1H NMR (400 MHz, C6D6) δ 7.62-
7.17 (m, 5H), 5.35 (s, 1H), 5.27 (q, J ) 7.3 Hz, 1H), 3.97 (m, 1H),
2.50 (d, J ) 13.3 Hz, 1H), 2.22 (m, 1H), 2.04 (s, 3H), 1.83 (d, J
) 7.3 Hz, 3H), 1.67-1.50 (m, 3H), 1.24-1.12 (m, 3H); 13C NMR
(100 MHz, C6D6) δ 141.2, 138.0, 135.4, 127.7, 127.5, 127.0, 122.4,
121.4, 80.0, 72.0, 34.9, 27.4, 27.1, 24.5, 17.0, 15.3; IR (CHCl3)
1590, 1480, 1440 cm-1; MS (EI) m/z 254 (M+, 36), 239 (33), 225
(21), 211 (8), 197 (7). HRMS (EI) m/z: calcd for C18H22O,
254.1670; found, 254.1652.
Reaction of Vinyl Allene 19 and Propionaldehyde 7. Following
the general procedure, vinyl allene 19 (100 mg, 0.48 mmol),
propionaldehyde 7 (0.05 mL, 0.72 mmol), and BF3‚Et2O (1.1 equiv),
after 26 h, provided compounds 29 (63 mg, cis/trans 52:48, 49%),
which were isolated after flash chromatography and HPLC as pale
yellow oils. (2S*,8aR*,E)-3-Benzylidene-2-ethyl-4-methyl-3,5,6,7,8,-
8a-hexahydro-2H-chromene (cis-29). 1H NMR (400 MHz, C6D6)
δ 7.39-7.12 (m, 5H), 6.52 (s, 1H), 4.13 (m, 1H), 3.90 (dd, J )
5.4, 7.2 Hz, 1H), 2.57 (m, 1H), 2.28 (m, 1H), 1.88 (m, 2H), 1.69
(s, 3H), 1.62-1.53 (m, 3H), 1.32-1.17 (m, 3H), 1.24 (t, J ) 7.3
Hz, 3H); 13C NMR (100 MHz, C6D6) δ 139.8, 139.5, 129.5, 127.7,
126.4, 121.1, 77.7, 77.5, 35.5, 27.6, 27.2, 24.9, 24.5, 17.2, 10.6;
IR (CHCl3) 1590, 1440 cm-1; MS (EI) m/z 268 (M+, 55.5), 253
(10), 239 (45), 225 (10), 211 (17). HRMS (EI) m/z: calcd for
C19H24O, 268.1827; found, 268.1807. (2R*,8aR*,E)-3-Benzylidene-
2-ethyl-4-methyl-3,5,6,7,8,8a-hexahydro-2H-chromene (trans-
1.62 (m, 2H), 1.76 (s, 3H), 1.50 (m, 1H), 1.24-1.15 (m, 3H); 13
C
NMR (100 MHz, C6D6) δ 140.6, 138.7, 136.7, 130.2, 129.4, 128.1,
128.0, 127.7, 127.5, 127.2, 126.7, 121.2, 79.3, 72.6, 35.0, 27.7,
27.1, 24.5, 16.9; IR (CHCl3) 1720, 1670, 1590, 1440 cm-1; MS
(EI) m/z 316 (M+, 30), 225 (24), 220 (14), 219 (75), 218 (100).
HRMS (EI) m/z: calcd for C23H24O, 316.1827; found, 316.1791.
Reaction of Vinyl Allene 21 and Propionaldehyde 7. Following
the general procedure, vinyl allene 21 (100 mg, 0.62 mmol),
propionaldehyde 7 (0.07 mL, 0.93 mmol), and BF3‚Et2O (1.1 equiv),
after 48 h, provided compounds 32 (96 mg, cis/trans 70:30, 70%),
which were isolated after flash chromatography and HPLC as pale
yellow oils. (2S*,8aR*,E)-2,4-Diethyl-3-ethylidene-3,5,6,7,8,8a-
1
hexahydro-2H-chromene (cis-32). H NMR (400 MHz, C6D6) δ
5.41 (q, J ) 7.4 Hz, 1H), 4.10 (dd, J ) 4.9, 11.3 Hz, 1H), 3.79 (t,
J ) 6.3 Hz, 1H), 2.67 (m, 1H), 2.49-2.45 (m, 2H), 2.22 (m, 1H),
1.81 (d, J ) 7.5 Hz, 3H), 1.65-1.54 (m, 4H), 1.38-1.19 (m, 4H),
1.20 (t, J ) 7.5 Hz, 3H), 1.10 (t, J ) 7.2 Hz, 3H); 13C NMR (100
MHz, C6D6) δ 137.4, 136.6, 129.9, 116.0, 78.3, 77.3, 35.5, 27.5,
27.3, 25.1, 24.6, 22.3, 14.8, 14.2, 10.7. (2R*,8aR*,E)-2,4-Diethyl-
3-ethylidene-3,5,6,7,8,8a-hexahydro-2H-chromene (trans-32). 1H
NMR (400 MHz, C6D6) δ 5.21 (q, J ) 7.4 Hz, 1H), 4.08 (m, 2H),
2.66 (d, J ) 13.9 Hz, 1H), 2.45 (c, J ) 7.4 Hz, 2H), 1.85-1.77
(m, 3H), 1.78 (d, J ) 7.4 Hz, 3H), 1.67-1.51 (m, 4H), 1.33-1.08
(m, 2H), 1.05 (t, J ) 7.4 Hz, 6H); 13C NMR (100 MHz, C6D6) δ
137.1, 135.5, 119.0, 81.5, 71.6, 35.3, 27.7, 27.2, 24.7, 21.8, 14.6,
14.2, 10.7; IR (CHCl3) 2900, 1500, 1425 cm-1; MS (EI) m/z 220
(M+, 15), 191 (100), 177 (5), 163 (16). HRMS (EI) m/z: calcd for
C15H24O, 220.1827; found, 220.1833.
1
29). H NMR (400 MHz, C6D6) δ 7.33-7.12 (m, 5H), 6.32 (s,
1H), 4.21 (t, J ) 7.2 Hz, 1H), 4.12 (m, 1H), 2.58 (d, J ) 13.8 Hz,
1H), 2.23 (m, 1H), 1.86 (m, 1H), 1.65 (m, 4H), 1.67 (s, 3H), 1.52
(m, 1H), 1.33-1.17 (m, 2H), 1.10 (t, J ) 7.4 Hz, 3H); 13C NMR
(100 MHz, C6D6) δ 139.7, 139.1, 138.6, 129.3, 127.7, 126.4, 124.0,
120.3, 79.8, 72.1, 35.2, 27.7, 27.3, 24.6, 24.5, 16.9, 10.6; IR (CHCl3)
1630, 1585, 1480, 1440 cm-1; MS (EI) m/z 268 (M+, 49), 253
(13), 239 (50), 225 (10.5), 211 (36). HRMS (EI) m/z: calcd for
C19H24O, 268.1827; found, 268.1818.
Reaction of Vinyl Allene 19 and Isobutyraldehyde 8. Fol-
lowing the general procedure, vinyl allene 19 (100 mg, 0.48 mmol),
isobutyraldehyde 8 (0.06 mL, 0.72 mmol), and BF3‚Et2O (1.1
equiv), after 26 h, provided compounds 30 (32 mg, cis/trans 57:
43, 24%), which were isolated after flash chromatography and
HPLC as pale yellow oils. (2S*,8aR*,E)-3-Benzylidene-2-isopro-
Reaction of Vinyl Allene 21 and Isobutyraldehyde 8. Fol-
lowing the general procedure, vinyl allene 21 (100 mg, 0.62 mmol),
isobutyraldehyde 8 (0.08 mL, 0.93 mmol), and BF3‚Et2O (1.1
equiv), after 22 h, provided compounds 33 (87 mg, cis/trans 74:
26, 60%), which were isolated after flash chromatography and
HPLC as pale yellow oils. (2S*,8aR*,E)-4-Ethyl-3-ethylidene-2-
isopropyl-3,5,6,7,8,8a-hexahydro-2H-chromene (cis-33). 1H NMR
(400 MHz, C6D6) δ 5.38 (q, J ) 7.3 Hz, 1H), 4.10 (dd, J ) 5.1,
11.2 Hz, 1H), 3.66 (d, J ) 7.07 Hz, 1H), 2.67 (d, J ) 15.8 Hz,
1H), 2.48-2.44 (m, 2H), 2.16-2.11 (m, 2H), 1.80 (d, J ) 7.3 Hz,
3H), 1.62-1.54 (m, 4H), 1.30 (d, J ) 6.56 Hz, 3H), 1.27-0.97
(m, 2H), 1.08 (d, J ) 6.8 Hz, 6H); 13C NMR (100 MHz, C6D6) δ
137.1, 135.6, 130.0, 117.6, 83.4, 76.3, 35.5, 29.2, 27.4, 27.0,
1
pyl-4-methyl-3,5,6,7,8,8a-hexahydro-2H-chromene (cis-30). H
NMR (400 MHz, C6D6) δ 7.37-7.11 (m, 5H), 6.49 (s, 1H), 4.15
(m, 1H), 3.81 (d, J ) 6.3 Hz, 1H), 2.58 (d, J ) 15.6 Hz, 1H), 2.24
(m, 2H), 1.68 (s, 3H), 1.65-1.57 (m, 3H), 1.31 (d, J ) 6.6 Hz,
3H), 1.29-1.19 (m, 3H), 1.16 (d, J ) 6.6 Hz, 3H); 13C NMR (100
MHz, C6D6) δ 139.5, 139.3, 138.4, 129.4, 127.7, 126.4, 123.4,
122.4, 82.1, 76.7, 35.4, 29.1, 27.6, 26.7, 24.4, 20.8, 17.8, 17.2; IR
(CHCl3) 1590, 1440 cm-1; MS (EI) m/z 282 (M+, 32), 253 (11),
239 (89), 225 (16), 211 (88). HRMS (EI) m/z: calcd for C20H26O,
282.1983; found, 282.1960. (2R*,8aR*,E)-3-Benzylidene-2-iso-
propyl-4-methyl-3,5,6,7,8,8a-hexahydro-2H-chromene (trans-
1
30). H NMR (400 MHz, C6D6) δ 7.35-7.11 (m, 5H), 6.30 (s,
1H), 4.09 (m, 1H), 3.82 (d, J ) 10.1 Hz, 1H), 2.57 (d, J ) 135.6
Hz, 1H), 2.27 (m, 1H), 2.07 (m, 1H), 1.70-1.60 (m, 3H), 1.66 (s,
3H), 1.52 (m, 1H), 1.34-1.17 (m, 2H), 1.26 (d, J ) 6.5 Hz, 3H),
0.93 (d, J ) 6.6 Hz, 3H); 13C NMR (100 MHz, C6D6) δ 140.1,
24.6, 22.4, 20.7, 18.3, 14.9, 14.3; IR (CHCl3) 1585, 1440 cm-1
.
(2R*,8aR*,E)-4-Ethyl-3-ethylidene-2-isopropyl-3,5,6,7,8,8a-hexahy-
1
dro-2H-chromene (trans-33). H NMR (400 MHz, C6D6) δ 5.21
(q, J ) 7.4 Hz, 1H), 4.05 (dd, J ) 4.7, 11.2 Hz, 1H), 3.66 (d, J )
J. Org. Chem, Vol. 71, No. 24, 2006 9163

Rega´s et al.
10.2 Hz, 1H), 2.65 (d, J ) 13.7 Hz, 1H), 2.45 (q, J ) 7.4 Hz, 2H),
2.23 (m, 1H), 2.01 (m, 1H), 1.78 (d, J ) 7.4 Hz, 3H), 1.66-1.58
(m, 3H), 1.33-1.16 (m, 3H), 1.25 (d, J ) 6.5 Hz, 3H), 1.05 (t, J
) 7.4 Hz, 3H), 0.88 (d, J ) 6.7 Hz, 3H); 13C NMR (100 MHz,
C6D6) δ 137.5, 134.7, 120.2, 86.7, 71.7, 35.6, 27.7, 27.4, 27.3, 24.7,
21.9, 19.8, 19.6, 14.7, 14.1; IR (CHCl3) 2900, 1440 cm-1; MS (EI)
m/z 234 (M+, 45), 205 (71), 191 (80), 163 (100). HRMS (EI) m/z:
calcd for C16H26O, 234.1983; found, 234.2033.
(m, 1H), 2.37-2.19 (m, 4H), 1.63-1.58 (m, 4H), 1.32 (d, J ) 6.5
Hz, 3H), 1.26-0.93 (m, 2H), 1.12 (d, J ) 6.5 Hz, 3H), 0.85 (t, J
) 7.4 Hz, 3H); MS (EI) m/z 296 (M+, 16), 295 (59), 285 (19), 267
(18), 251 (100). HRMS (EI) m/z: calcd for C21H28O, 296.2140;
found, 296.2135. (2R*,8aR*,E)-3-Benzylidene-4-ethyl-2-isopro-
pyl-3,5,6,7,8,8a-hexahydro-2H-chromene (trans-36). 1H NMR
(400 MHz, C6D6) δ 7.39-7.10 (m, 5H), 6.31 (s, 1H), 4.09 (dd, J
) 4.9, 11.2 Hz, 1H), 3.79 (d, J ) 10.3 Hz, 1H), 2.57 (d, J ) 13.6
Hz, 1H), 2.29-2.21 (m, 2H), 2.05 (m, 1H), 1.69-1.62 (m, 3H),
1.50-1.49 (m, 1H), 1.28-1.19 (m, 3H), 1.25 (d, J ) 6.5 Hz, 3H),
0.97 (d, J ) 6.6 Hz, 3H), 0.79 (t, J ) 7.4 Hz, 3H); 13C NMR (100
MHz, C6D6) δ 139.4, 139.0, 136.2, 129.1, 128.0, 127.8, 126.4,
125.3, 85.8, 72.3, 35.8, 27.7, 27.6, 27.2, 24.7, 21.5, 19.5, 19.3, 14.0;
IR (CHCl3) 1590, 1440 cm-1; MS (EI) m/z 296 (M+, 51), 267 (16),
253 (100), 235 (10), 225 (74). HRMS (EI) m/z: calcd for C21H28O,
296.2140; found, 296.2112.
Reaction of Vinyl Allene 21 and Benzaldehyde 25. Following
the general procedure, vinyl allene 21 (100 mg, 0.62 mmol),
benzaldehyde 25 (0.09 mL, 0.93 mmol), and BF3‚Et2O (1.1 equiv),
after 24 h, provided compounds 34 (103 mg, cis/trans 64 :36, 62%),
which were isolated after flash chromatography and HPLC as pale
yellow oils. (2S*,8aR*,E)-4-Ethyl-3-ethylidene-2-phenyl-3,5,6,7,8,-
8a-hexahydro-2H-chromene (cis-34). 1H NMR (400 MHz, C6D6)
δ 7.61-7.14 (m, 5H), 5.07 (s, 1H), 5.03 (q, J ) 7.6 Hz, 1H), 4.22
(dd, J ) 4.8, 11.1 Hz, 1H), 2.70 (d, J ) 14 Hz, 1H), 2.51-2.43
(m, 2H), 2.33 (m, 1H), 1.68-1.55 (m, 2H), 1.65 (d, J ) 7.4 Hz,
3H), 1.34-0.86 (m, 4H), 1.12 (t, J ) 7.4 Hz, 3H); 13C NMR (100
MHz, C6D6) δ 141.0, 138.0, 130.2, 128.3, 127.8, 127.2, 120.7, 80.5,
77.9, 35.3, 27.6, 27.4, 24.6, 22.4, 14.7, 14.4; IR (CHCl3) 1670,
1440 cm-1; MS (EI) m/z 268 (M+, 23), 253 (100), 239 (45), 225
(65). HRMS (EI) m/z: calcd for C19H24O, 268.1827; found,
268.1829. (2R*,8aR*,E)-4-Ethyl-3-ethylidene-2-phenyl-3,5,6,7,8,-
8a-hexahydro-2H-chromene (trans-34). 1H NMR (400 MHz,
C6D6) δ 7.68-7.07 (m, 5H), 5.37 (s, 1H), 5.27 (q, J ) 7.4 Hz,
1H), 4.02 (dd, J ) 11.3, 4.8 Hz, 1H), 2.56-2.48 (m, 2H), 2.27 (m,
1H), 1.87 (d, J ) 7.4 Hz, 3H), 1.70-1.52 (m, 3H), 1.24-0.96 (m,
4H), 1.16 (t, J ) 7.4 Hz, 3H); 13C NMR (100 MHz, C6D6) δ 141.2,
138.3, 133.6, 128.0, 127.3, 127.0, 122.0, 80.4, 71.9, 35.1, 27.4,
Reaction of Vinyl Allene 22 and Benzaldehyde 25. Following
the general procedure, vinyl allene 22 (100 mg, 0.45 mmol),
benzaldehyde 25 (0.07 mL, 0.67 mmol), and BF3‚Et2O (1.1 equiv),
after 24 h, provided compounds 37 (59 mg, cis/trans 75:25, 40%),
which were isolated after flash chromatography and HPLC as pale
yellow oils. (2S*,8aR*,E)-3-Benzylidene-4-ethyl-2-phenyl-3,5,6,7,8,-
8a-hexahydro-2H-chromene (cis-37). 1H NMR (400 MHz, C6D6)
δ 7.67-7.02 (m, 10H), 6.11 (s, 1H), 5.19 (s, 1H), 4.29 (dd,
J ) 4.8, 11.5 Hz, 1H), 2.64 (d, J ) 14.6 Hz, 1H), 2.39-2.35
(m, 1H), 2.28 (q, J ) 7.3 Hz, 2H), 1.79-1.57 (m, 3H), 1.63-1.20
(m, 3H), 0.90 (t, J ) 7.4 Hz, 3H); 13C NMR (100 MHz, C6D6)
δ 140.1, 139.4, 139.2, 139.0, 130.8, 129.1, 128.3, 127.9, 127.7,
127.5, 126.5, 124.9, 80.5, 78.4, 35.6, 27.6, 27.5, 24.6, 22.1,
14.2; MS (EI) m/z 330 (M+, 21), 301 (6), 239 (34), 232 (100).
HRMS (EI) m/z: calcd for C24H26O, 330.1983; found, 330.1959.
(2R*,8aR*,E)-3-Benzylidene-4-ethyl-2-phenyl-3,5,6,7,8,8a-hexahy-
dro-2H-chromene (trans-37). 1H NMR (400 MHz, C6D6) δ 7.73-
7.10 (m, 10H), 6.34 (s, 1H), 5.47 (s, 1H), 4.19 (dd, J ) 4.9, 11.4
Hz, 1H), 2.46 (d, J ) 14.3 Hz, 1H), 2.34-2.25 (m, 3H), 1.75 (m,
1H), 1.63 (m, 1H), 1.50 (m, 1H), 1.26-1.12 (m, 3H), 0.85 (t, J )
7.4 Hz, 3H); 13C NMR (100 MHz, C6D6) δ 140.5, 140.0, 138.9,
135.5, 129.1, 128.0, 127.8, 127.3, 127.2, 126.7, 126.6, 79.4, 72.9,
27.2, 24.5, 22.0, 14.7, 14.4; IR (CHCl3) 1590, 1480, 1440 cm-1
;
MS (EI) m/z 268 (M+, 36), 253 (22), 239 (66), 225 (10), 211 (17).
HRMS (EI) m/z: calcd for C19H24O, 268.1827; found, 268.1790.
Reaction of Vinyl Allene 22 and Propionaldehyde 7. Following
the general procedure, vinyl allene 22 (100 mg, 0.45 mmol),
propionaldehyde 7 (0.05 mL, 0.67 mmol), and BF3‚Et2O (1.1 equiv),
after 24 h, provided compounds 35 (69 mg, cis/trans 73:27, 54%),
which were isolated after flash chromatography and HPLC as pale
yellow oils. (2S*,8aR*,E)-3-Benzylidene-2,4-diethyl-3,5,6,7,8,8a-
35.2, 27.7, 27.4, 24.6, 21.7, 14.0; IR (CHCl3) 1590, 1440 cm-1
;
1
MS (EI) m/z 330 (M+, 25), 312 (9), 253 (17), 239 (39), 232 (100).
HRMS (EI) m/z: calcd for C24H26O, 330.1983; found, 330.1973.
hexahydro-2H-chromene (cis-35). H NMR (400 MHz, C6D6) δ
7.43-7.11 (m, 5H), 6.51 (s, 1H), 4.16 (dd, J ) 4.9, 11.1 Hz, 1H),
3.91 (t, J ) 6.4 Hz, 1H), 2.63 (d, J ) 15.6 Hz, 1H), 2.59-2.21
(m, 3H), 1.91-1.84 (m, 2H), 1.69-1.58 (m, 4H), 1.33-1.20 (m,
2H), 1.23 (t, J ) 7.3 Hz, 3H), 0.85 (t, J ) 7.4 Hz, 3H); 13C NMR
(100 MHz, C6D6) δ 139.3, 138.9, 137.9, 130.6, 129.2, 127.9, 126.4,
121.0, 78.4, 77.7, 35.7, 27.6, 27.4, 25.0, 24.6, 22.0, 14.3, 10.6; IR
(CHCl3) 1590, 1440 cm-1; MS (EI) m/z 282 (M+, 21), 267 (14),
253 (74), 239 (19), 225 (23). HRMS (EI) m/z: calcd for C20H26O,
282.1983; found, 282.2031. (2R*,8aR*,E)-3-Benzylidene-2,4-
diethyl-3,5,6,7,8,8a-hexahydro-2H-chromene (trans-35). 1H NMR
(400 MHz, C6D6) δ 7.38-7.10 (m, 5H), 6.33 (s, 1H), 4.20 (t, J )
7.2 Hz, 1H), 4.10 (dd, J ) 4.9, 11.1 Hz, 1H), 2.58 (d, J ) 13.8
Hz, 1H), 2.26-2.23 (m, 3H), 1.85 (m, 1H), 1.70-1.59 (m, 4H),
1.50-1.18 (m, 3H), 1.10 (t, J ) 7.4 Hz, 3H), 0.78 (t, J ) 7.4 Hz,
3H); 13C NMR (100 MHz, C6D6) δ 139.0, 138.9, 136.9, 129.1,
127.8, 126.5, 124.1, 80.4, 72.3, 35.4, 27.6, 27.5, 24.7, 24.2, 21.4,
14.1, 10.5; MS (EI) m/z 282 (M+, 28), 267 (6), 253 (100), 235
(11), 225 (33). HRMS (EI) m/z: calcd for C20H26O, 282.1983;
found, 282.1986.
Reaction of Vinyl Allene 24 and Benzaldehyde 25. Following
the general procedure, vinyl allene 24 (100 mg, 0.57 mmol),
benzaldehyde 25 (0.08 mL, 0.85 mmol), and BF3‚Et2O (1.1 equiv),
after 48 h, provided compound 38 (64 mg, 39%) as a pale yellow
oil. (2R*,8aR*)-4-Ethyl-2-phenyl-3-(propan-2-ylidene)-3,5,6,7,8,-
8a-hexahydro-2H-chromene (trans-38). 1H NMR (400 MHz,
C6D6) δ 7.43-7.11 (m, 5H), 6.61 (s, 1H), 4.06 (m, 1H), 2.59 (d, J
) 13.6 Hz, 1H), 2.26 (m, 2H), 2.17 (m, 1H), 1.71-1.51 (m, 4H),
1.64 (s, 3H), 1.42 (s, 3H), 1.42-1.21 (m, 2H), 0.67 (t, J ) 7.4 Hz,
3H); 13C NMR (100 MHz, C6D6) δ 142.0, 139.7, 138.8, 129.3,
127.5, 126.9, 126.5, 120.2, 75.6, 35.6, 26.8, 26.0, 24.8, 24.0, 22.5,
13.9; IR (CHCl3) 1590, 1480, 1440, 1370 cm-1; MS (EI) m/z 282
(M+, 64), 267 (31), 253 (30). HRMS (EI) m/z: calcd for C20H26O,
282.1983; found, 282.1940.
Acknowledgment. This work was supported in part by Grant
BQU2001-3184 (MEC, Spain) and a University of La Laguna
Grant for Consolidated Research Groups. D.R. thanks the MEC
(Spain) for a fellowship.
Reaction of Vinyl Allene 22 and Isobutyraldehyde 8. Fol-
lowing the general procedure, vinyl allene 22 (100 mg, 0.45 mmol),
isobutyraldehyde 8 (0.06 mL, 0.67 mmol), and BF3‚Et2O (1.1
equiv), after 26 h, provided compounds 36 (48 mg, cis/trans 66:
34, 36%), which were isolated after flash chromatography and
HPLC as a pale yellow oil. (2S*,8aR*,E)-3-Benzylidene-4-ethyl-
2-isopropyl-3,5,6,7,8,8a-hexahydro-2H-chromene (cis-36). 1H
NMR (400 MHz, C6D6) δ 7.46-7.07 (m, 5H), 6.46 (s, 1H), 4.18
(dd, J ) 4.9, 11.1 Hz, 1H), 3.76 (d, J ) 7.7 Hz, 1H), 2.64-2.60
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.
JO061582R
9164 J. Org. Chem., Vol. 71, No. 24, 2006