Synthesis of octahydroquinolines through the Lewis acid catalyzed reaction of vinyl allenes and imines

Article abstract of DOI:10.1021/jo034480z

The reaction of vinyl allenes with imines under Lewis acid catalysis has been explored. Vinyl allenes in which the allenic portion of the molecule is tri- or tetrasubstituted gave octahydroquinoline derivatives as single isomers together with a minor comp

Full text of DOI:10.1021/jo034480z

Syn th esis of Octa h yd r oqu in olin es th r ou gh th e Lew is Acid
Ca ta lyzed Rea ction of Vin yl Allen es a n d Im in es
David Rega´s, Mar´ıa M. Afonso, Mat´ıas L. Rodr´ıguez, 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 April 15, 2003
The reaction of vinyl allenes with imines under Lewis acid catalysis has been explored. Vinyl allenes
in which the allenic portion of the molecule is tri- or tetrasubstituted gave octahydroquinoline
derivatives as single isomers together with a minor compound formed by an ene reaction of the
imine with the allene. Compounds in which the allene is 1,3-disubstituted do not react under the
conditions assayed.
In tr od u ction
by steric interactions between the incoming dienophile
and the out-of-plane substituents on the vinyl allene.
Also, Krause and co-workers concluded,6c based on semi-
empirical calculations on the parent 1,2,4-pentatriene,
that the regioselectivity is controlled by steric factors,
since the HOMO coefficients for the carbon atoms at the
extreme of the dienic portion of the molecule are similar
in size. Theoretical calculations at the ab initio level have
also been carried out for the Diels-Alder reaction of vinyl
allenes and acrolein,7 showing that when the parent
system is considered, no regioselectivity is expected.
However, in the methyl-substituted vinyl allene (3-
methyl-1,2,4-hexatriene), the electron-donating ability of
the methyl groups results in one of the regioisomers being
favored. The same study concluded that the reaction is
a concerted asynchronous process. Recently,8 we have
found that 1-cyclohexenyl allenes, which were shown to
display high selectivity in Diels-Alder reactions by
Krause and co-workers,6c can also act as dienes in hetero-
Diels-Alder reactions with aldehydes under Lewis acid
catalysis, showing reactivity similar to that displayed by
dienes activated by one silyloxy group,9 that is, good facial
and regioselectivity and moderate endo/exo selectivity,
the yields being good for this reaction (36-70%).
Vinyl allenes have been described as taking part in
different types of pericyclic reactions, and it has been
observed that in several of those reactions the presence
of the allene moiety facilitates the reaction when com-
pared with similar dienic systems. For instance, in [1,5]
hydrogen sigmatropic shifts, the energy of activation for
the reaction is 8-12 kcal/mol lower in vinyl allenes than
in similar dienes.1 In 4e- electrocyclizations, the presence
of the allene shifts the equilibrium position from the open
form in dienes2 to an almost equimolecular mixture of
the open and closed form in vinyl allenes.3 In diallenes,
the closed form (3,4-bis(alkylidene)cyclobutene) predomi-
nates.4 In cycloaddition chemistry, vinyl allenes have
been used in the intra- and intermolecular versions of
the Diels-Alder reactions. The intramolecular reaction
allows for the preparation of polycyclic compounds with
high selectivity,5 and in the intermolecular case, the
Diels-Alder reaction has been studied with carbon
dienophiles,6 the conclusion of those studies being that
both facial and endo/exo selectivity are largely governed
(1) (a) Barrack, S. A.; Okamura, W. H. J . Org. Chem. 1986, 51, 3201.
(b) Skattebøl, L. Tetrahedron 1969, 25, 4933. (c) Heimgartner, H.;
Zsindely, J .; Hansen, H.-J .; Schmid, H. Helv. Chim. Acta 1973, 56,
2924. (d) J ensen, F. J . Am. Chem. Soc. 1995, 117, 7487.
(2) Durst, T.; Breau, L. Cyclobutene Ring Opening Reactions in
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: Oxford, UK, 1991; Vol. 5, pp 675-697.
(3) (a) Gil-Av, E.; Herling, J . Tetrahedron Lett. 1967, 1. (b) Pasto,
D. J .; Kong, W. J . Org. Chem. 1989, 54, 4028. (c) Murakami, M.; Amii,
H.; Itami, K.; Ito, Y. Angew. Chem., Int. Ed. Engl. 1995, 34, 1476.
(4) (a) Pasto, D. J .; Yang, S.-H. J . Org. Chem. 1989, 54, 3544. (b)
Hopf, H. Angew. Chem., Int. Ed. Engl. 1970, 9, 732. (c) Hopf, H.;
Lenich, F. T. Chem. Ber. 1973, 106, 3461.
Interest in the stereoselective preparation of nitrogen-
containing heterocyclic compounds prompted us to in-
vestigate the feasibility of using the equivalent reaction
with imines as heterodienophiles,10 which should allow
for the preparation of substituted octahydroquinoline
derivatives.
(5) (a) Okamura, W. H.; Curtin, M. L. Synlett 1990, 1. (b) Gibbs, R.
A.; Okamura, W. H. J . Am. Chem. Soc. 1988, 110, 4062. (c) Gibbs, R.
A.; Bartels, K.; Lee, R. W. K.; Okamura, W. H. J . Am. Chem. Soc. 1989,
111, 3717. (d) Reich, H. J .; Eisenhart, E. K. J . Org. Chem. 1984, 49,
5282. (e) Reich, H. J .; Eisenhart, E. K.; Olson, R. E.; Kelly, M. J . J .
Am. Chem. Soc. 1986, 108, 7791. (f) Deutsch, E. A.; Snider, B. B.
Tetrahedron Lett. 1983, 24, 3701. (g) Deutsch, E. A.; Snider, B. B. J .
Org. Chem. 1982, 47, 2682.
(6) (a) Reich, H. J .; Eisenhart, E. K.; Whipple, W. L.; Kelly, M. J . J .
Am. Chem. Soc. 1988, 110, 6432. (b) Spino, C.; Thibault, C.; Gingras,
S. J . Org. Chem. 1998, 63, 5283. (c) Koop, U.; Handke, G.; Krause, N.
Liebigs Ann. 1996, 1487.
(7) Wright, J . B.; Pranata, J . THEOCHEM 1999, 460, 67.
(8) Rega´s, D.; Afonso, M. M.; Galindo, A.; Palenzuela, J . A. Tetra-
hedron Lett. 2000, 41, 6781.
(9) Mujica, M. T.; Afonso, M. M.; Galindo, A.; Palenzuela, J . A. J .
Org. Chem. 1998, 63, 9728.
(10) Imines have been used as heterodienophiles in inter- and
intramolecular Diels-Alder reactions. The reaction conditions depend
on the nature of the substituents on the imine. Simple, neutral imines
need the presence of Lewis acids to react with electron-rich dienes.
For leading references, see: Weinreb, S. M. Heterodienophile Additions
to Dienes in Comprehensive Organic Synthesis; Trost, B. M., Fleming,
I., Eds.; Pergamon Press: Oxford, UK, 1991; Vol. 5, pp 401-449.
10.1021/jo034480z CCC: $25.00 © 2003 American Chemical Society
Published on Web 09/12/2003
J . Org. Chem. 2003, 68, 7845-7852
7845

Rega´s et al.
SCHEME 1 a
F IGURE 1. Observed NOEs for compound 14.
SCHEME 2
The reactivity of several of the vinyl allenes prepared
was compared with the literature data for similar
compounds6c using maleic anhydride as dienophile. Four
vinyl allenes (4, 10, 11, and 12) with diverse substituents
on the allene were chosen to check whether electronic or
steric factors preclude those molecules from acting as
dienes.
The reactions were carried out in dry toluene at room
temperature using 1 equiv of maleic anhydride. After 24-
48 h and removal of solvent, a white solid, which was
identified as a single cycloadduct to the limits of detection
of the NMR, was obtained in each case in high yield
(Scheme 2). The structure of the cycloadducts was
established on the basis of spectroscopic data,17 and the
relative stereochemistry was deduced from NOE experi-
ments (NOESY or GOESY18) as shown in Figure 1 for
one representative example.
a
Key: (a) MeMgBr, CuI, LiBr, 0 °C; (b) EtMgBr, CuBr‚Me2S,
-60 °C; (c) t-BuLi, CuCN, -78 °C.
Octahydroquinolines have been prepared through
hetero-Diels-Alder reactions between acetylcyclohexene
trimethylsilyl enol ethers and imines,11 the proportion
of endo/exo isomers depending on the reaction conditions.
Thus, under kinetic control an almost 1:1 ratio of the two
isomers is formed, whereas under thermodynamic condi-
tions the exo is favored. This has been explained as a
Diels-Alder-retro-Diels-Alder equilibrium process.
In this paper, we present the results of our studies on
the selectivity of the hetero-Diels-Alder reaction of vinyl
allenes with imines leading to octahydroquinolines.
Resu lts a n d Discu ssion
For the reaction of 4, 10, and 12, the structure and
relative stereochemistry of the products obtained indicate
a highly selective process in which the dienophile ap-
proaches the diene through the less hindered face, that
is, the one opposite to the substituent at the terminus of
the allene, as deduced from the geometry of the exocyclic
double bond in the cycloadduct. For compound 17, the
lower yield obtained may be the result of the increased
difficulty encountered by the vinyl allene in attaining the
required s-cis conformation needed for the reaction to
proceed. The cis disposition of the hydrogen atoms at the
ring junctions in all cycloadducts is indicative of an endo
approach of the maleic anhydride to the vinyl allene.
These results indicate that the vinyl allenes prepared in
this work are at least as reactive as the similar ones
described previously in the literature.6c
Once the pericyclic reactivity of the vinyl allenes was
checked, we turned our attention to their reaction with
imines. We first explored the reactivity of 9 since it gave
good results in our previous work with aldehydes.8 Using
imine 18 and different Lewis acids in CH2Cl2 at room
temperature (Table 1), we found that only one cyclo-
adduct was formed (19), together in some cases with a
For this work, six vinyl allenes (4, 8-12) were prepared
in racemic form using literature procedures for allene
formation starting from the corresponding propargyl alco-
hols.12 Thus, vinyl allene 413 was prepared in a 55% yield
following Myers’s procedure14 using o-nitrobenzene-
sulfonylhydrazine (NBSH) and starting from propargyl
alcohol 1. Compounds 8-1215 were obtained in good
yields (60-75%) by SN2′ displacement reactions of ben-
zoates 5-7 obtained from the corresponding propargyl
alcohols 1-3 (Scheme 1).16
(11) (a) Veyrat, C.; Wartski, L.; Seyden-Penne, J . Tetrahedron Lett.
1986, 27, 2981. (b) Le Coz, L.; Veyrat-Martin, C.; Wartski, L.; Seyden-
Penne, J .; Bois, C.; Philoche-Levisalles, M. J . Org. Chem. 1990, 55,
4870. (c) Paugam, R.; Valenciennes, E.; Le Coz-Bardol, L.; Garde, J .-
C.; Wartski, L.; Lance, M.; Nierlich, M. Tetrahedron: Asymmetry 2000,
11, 2509.
(12) The propargyl alcohols were prepared by the addition of the
lithium acetylide of 1-ethynylcyclohexene to the corresponding alde-
hyde or ketone in tetrahydrofuran at low temperature.
(13) The preparation of this vinyl allene by other methods has been
reported: (a) Konoike, T.; Araki, Y. Tetrahedron Lett. 1992, 33, 5093.
(b) Bardouy, R.; Delbecq, F.; Gore, J . Tetrahedron Lett. 1979, 937.
(14) Myers, A. G.; Zheng, B. J . Am. Chem. Soc. 1996, 118, 4492.
(15) The preparation of vinyl allene 8 has been reported previ-
ously: Baudouy, R.; Delbecq, F.; Gore, J . Tetrahedron 1980, 36, 189.
Also see ref 13b.
(17) The spectroscopic data recorded for most of the new compounds
prepared in this work include mono- (1H, 13C) and bidimensional
(COSY, HSQC, HMBC) NMR experiments.
(18) Stonehouse, J .; Adell, P.; Keeler, J .; Shaka, A. J . J . Am. Chem.
Soc. 1994, 116, 6037.
(16) (a) Erdik, E. Tetrahedron 1984, 40, 641. (b) Westmijze, H.;
Meijer, J .; Bos, H. J . T.; Vermeer, P. Recl. Trav. Chim. Pays-Bas 1976,
95, 299. (c) Lipshutz, B. H. Synthesis 1987, 325. (d) Lipshutz, B. H.;
Sengupta, S. Org. React. N.Y. 1992, 41, 135.
7846 J . Org. Chem., Vol. 68, No. 20, 2003

Synthesis of Octahydroquinolines
TABLE 1
Once the reactivity of 9 was established, we carried
out the reaction with the remainder of the vinyl allenes
using imines 18, 21, and 22 as dienophiles and BF3‚Et2O
as Lewis acid in CH2Cl2 as solvent. Vinyl allene 4, the
only one in which R1 is a hydrogen atom, did not react
under those conditions or any others assayed, yielding
only decomposition products under forced reaction condi-
tions. The results obtained with the other vinyl allenes
and imines prepared in this work are summarized in
Table 2.
It was observed that vinyl allenes 8-12 reacted to yield
cyclization compounds as the main product, alone or as
a mixture with the compounds derived from the ene
reaction. The structure of all bicyclic compounds follows
the same pattern found for 19, and the structure of the
minor ones was deduced from the spectroscopic analysis
of several of the compounds obtained in these reactions.
We still needed to unambiguously establish the relative
configuration of the chiral centers adjacent to the nitro-
gen atom (H-2 and H-8a) in the bicyclic compounds, and
thus, a great effort was made in order to crystallize any
of the octahydroquinolines obtained in order to confirm
the structure by X-ray diffraction methods. Finally, we
were successful in obtaining suitable crystals of com-
pound 29. Figure 3 shows a computer-generated perspec-
tive view22 of the final X-ray model of 29,23 clearly
indicating a cis relationship between the methine hydro-
gens.
The absence of NOE can be explained by the con-
formation adopted by 29, in which both hydrogens H-2
and H-8a are quite apart, assuming a similar confor-
mation in solution. The remainder of the bicyclic com-
pounds are also assumed to be cis because of the
similarity of their spectroscopical data with those of 29.
This result indicates an endo approach of the dienophile
to the dienic portion of the vinyl allene with the benzyl
group on the nitrogen occupying the exo position in the
transition state, assuming that the imine is in the E
configuration, as depicted in Scheme 3 for a pericyclic
mechanism.
In most entries in Table 2, some vinyl allene was re-
covered unaltered and the application of heat resulted
in the decomposition of several of the examples shown.
From Table 2, it can be observed that the qualitative
rate of the reactions is influenced by the size of the
substituents on the allene. Thus, for trisubstituted
systems, the change of a methyl group in 8 to an ethyl
group in 9 results in a longer reaction time, but the
reaction proceeds at room temperature. When the ethyl
group is replaced by a tert-butyl (12), the reaction is
slower and requires heating to yield the cycloadduct. This
is likely due to the increased difficulty in the diene
attaining the s-cis conformation required for the reaction
to take place, as observed in the reaction of this vinyl
allene with maleic anhydride. Comparing vinyl allene 8
(R2 ) Me) with 10 (R2 ) Ph), it can be observed that the
change of substituent on the extreme of the allene also
results in slower reactions, whereas when the allene is
tetrasubstituted (11), the reaction is even slower since
Lewis acid
time (d)
19 (%)
20 (%)
BF3‚Et2O
AlCl3
TiCl4
4
1.5
3
67
55
49
48
-
-
8
Et2AlCl
5
9
F IGURE 2. Observed NOEs for compound 19.
minor compound (20) resulting from an ene reaction
between the allene and the imine. The best results were
obtained using BF3‚Et2O, since only the cycloadduct 19
was obtained in 67% yield. AlCl3 also gave exclusively
compound 19, although in lower yield. The use of diethyl
ether as solvent also gave similar results, but the reaction
was considerably slower. Other Lewis acids (SnCl4 or
ZnCl2) resulted in no reaction.
The structure of 19 was established on the basis of its
spectroscopic data.17 The geometry of the exocyclic double
bond, deduced from NOE experiments (Figure 2), indi-
cates that the approach of the imine takes place exclu-
sively through the face of the diene opposite to the methyl
group on the terminus of the allene, in a manner similar
to that found for the reaction with maleic anhydride or
with aldehydes.8
The regiochemistry is also consistent with that exhib-
ited in the reaction of aldehydes with this vinyl allene,
in which the carbon atom of the imine double bond
attaches to the central carbon of the allene.
The relationship between the two hydrogens at the
positions adjacent to the nitrogen atom could not be
established at this point, although the absence of NOE
between them led us to think at first that they were
disposed in trans. However, the observed NOE between
both methine hydrogens and the benzylic methylene
protons and the fact that the lack of NOE is not valid
evidence of a stereochemical relationship cast some
doubts on the relative configuration of those two cen-
ters.19
The structure of 20 was difficult to establish at this
point because the H NMR spectrum at room tempera-
1
ture showed a complex mixture of conformers, which
could be partially clarified by heating at 75 °C in C6D6.20
Thus, 20 was assigned the structure shown by compari-
son with the minor compounds obtained in the other
similar reactions described later in this work.21
(19) We thank one of the reviewers for helpful discussions in regard
to this problem.
(20) The conformational behavior of this compound also precluded
obtaining a satisfactory 13C NMR spectrum. See the Supporting
Information for copies of the NMR spectra.
(21) The geometry of the double bonds in the ene compounds was
assigned on the basis of the ROESY spectra of compounds 33-36.
(22) Spek, A. L. PLATON92, University of Utrecht, The Nether-
lands, 1992.
(23) See the Supporting Information for the X-ray data.
J . Org. Chem, Vol. 68, No. 20, 2003 7847

Rega´s et al.
TABLE 2. Rea ction of Vin yl Allen es a n d Im in es u n d er Lew is Acid Ca ta lysisa ,b
entry
vinyl allene
imine
T (°C)
time (d)
23-32 (%)
33-41 (%)
% recovered allenec
1
2
3
4
5
6
7
8
9
8
8
9
10
10
10
11
11
11
12
18
21
21
18
21
22
18
21
22
18
rt
rt
rt
rt
rt
1.5
1.5
3
4
4
3
3
5
5
23 (54)
24 (43)
25 (39)
26 (71)
27 (61)
28 (57)
29 (67)
30 (37)
31 (41)
32 (34)
33 (11)
34 (7)
35 (4)
36 (5)
37 (12)
38 (3)
39 (6)
40 (2)
41 (7)
-
-
20
24
13
15
5
rt
40
40
40
40
-
15
23
25
10
5
a
b
Only one enantiomer shown. All reactions were carried out using BF3‚Et2O in CH2Cl2. c A dash indicates no recovered vinyl allene.
The rest of the mass balance results from decomposition.
SCHEME 3
F IGURE 3. Computer-generated view of the X-ray structure
of 29.
heating is again required to obtain reaction products.
These results, especially the latter, can be explained by
the increased difficulty of the imine to approach the
dienic portion of the vinyl allene.
chemistry is due to steric reasons as proposed in the
previously cited works. However, the high selectivity
shown by the reaction, in which only one cyclization
product was obtained, and especially the geometry of the
exocyclic double bond seem to point to a pericyclic
mechanism.
In conclusion, we have found that vinyl allenes in
which the allene portion of the molecule is tri- or
tetrasubstituted react with imines in the presence of
Lewis acids to afford octahydroquinoline derivatives with
high facial, regio-, and endo selectivities. This results in
compounds with cis stereochemistry at the two positions
adjacent to the nitrogen atom as the major products.
Depending on the Lewis acid used, minor compounds
resulting from an ene reaction are also obtained.
The experimental data obtained did not allow us to
confirm the mechanism of the reaction, which may be
either an asynchronous concerted reaction or a cationic
stepwise process. Thus, the fact that vinyl allene 4 (R1
) H) did not react, whereas with an alkyl group at the
R1 position cyclization products were obtained, may
indicate that an electron-donating group is needed at that
position to activate the reaction by raising the energy of
the HOMO of the diene. This activation may also be
responsible for the regiochemistry shown by the reaction,
as described for the reaction of vinyl allenes and ac-
roleine.7 An alternative explanation could be that the
group at R1 stabilizes the positive charge formed at that
position in a stepwise mechanism and that the regio-
7848 J . Org. Chem., Vol. 68, No. 20, 2003

Synthesis of Octahydroquinolines
44), 147 (88), 133 (14), 119 (100); HRMS (EI) m/z calcd for
C12H18 162.1408, found 162.1394.
Exp er im en ta l Section
(()-1-Bu ta -1,2-d ien ylcycloh exen e (4). 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 (2.65 g, 17.7 mmol) in THF (7 mL). After
10 min, 2-nitrobenzenesulfonylhydrazine (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 (hexanes) af-
forded vinyl allene 4 (1.3 g, 55%) as a colorless oil: 1H NMR
(400 MHz, CDCl3) δ 5.77 (m, 1H), 5.63 (s, 1H), 5.32 (m, 1H),
2.09 (m, 2H), 2.02 (m, 2H), 1.68 (dd, J ) 3.2, 7.0 Hz, 3H), 1.60
(m, 4H); 13C NMR (100 MHz, CDCl3) δ 204.9, 132.4, 125.3,
97.0, 88.5, 25.7, 25.6, 22.5, 22.4, 14.6.
(()-1-(1-Meth ylbu ta -1,2-d ien yl)cycloh exen e (8). To a
stirred suspension of LiBr (1.2 g, 13.9 mmol) and CuI (2.6 g,
13.9 mmol) in THF (25 mL) at 0 °C was slowly added a solution
of MeMgBr 2.8 M in diethyl ether (4.95 mL, 13.9 mmol). After
the mixture was stirred for 15 min, a solution of benzoate 5
(585 mg, 2.3 mmol) in THF (40 mL) was added via cannula.
The reaction mixture was allowed to warm to rt overnight,
and then a saturated solution of NH4Cl (50 mL) was added
and the reaction was extracted with diethyl ether (4 × 50 mL).
After drying (Na2SO4), concentration, and flash column chro-
matography (hexanes), vinyl allene 8 was obtained (218 mg,
64%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 5.66 (s,
1H), 5.21 (bs, 1H), 2.10 (m, 4H), 1.82 (s, 3H), 1.65 (d, J ) 7.0
Hz, 3H), 1.60 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 204.8,
134.0, 122.1, 101.9, 86.4, 27.0, 25.9, 22.9, 22.4, 16.3, 14.9; IR
(CHCl3) 2900, 1935, 1680, 1640 cm-1; MS(EI) m/z 148 (M+,
27), 133 (50), 119 (29), 105 (100); HRMS (EI) m/z calcd for
(()-1-(1-ter t-Bu tylbu ta -1,2-d ien yl)cycloh exen e (12). To
a stirred solution of CuCN (354 mg, 3.95 mmol) in diethyl ether
(20 mL) at -78 °C was slowly added a solution of t-BuLi 1.7
M in pentane (4.6 mL, 7.9 mmol). After 5 min, the reaction
mixture was warmed to 0 °C, and after 15 min it was cooled
again to -78 °C and a solution of benzoate 5 (500 mg, 1.97
mmol) in diethyl ether (10 mL) was then slowly added. The
reaction mixture was stirred for 1 h and allowed to warm to 0
°C. After 1 h, water (50 mL) was added, and the mixture was
extracted with diethyl ether (3 × 30 mL). After drying and
concentration of the organic layer, the crude reaction mixture
was purified by flash column chromatography (hexanes) yield-
ing vinyl allene 12 (269 mg, 72%) as a colorless oil: 1H NMR
(400 MHz, CDCl3) δ 5.60 (s, 1H), 5.06 (q, J ) 6.8 Hz, 1H), 2.08
(m, 4H), 1.66 (d, J ) 6.8 Hz, 3H), 1.58 (m, 4H), 1.09 (s, 9H);
13C NMR (100 MHz, CDCl3) δ 202.1, 134.1, 124.6, 116.6, 85.5,
33.8, 30.7, 30.2, 25.5, 23.1, 22.0, 14.9; IR (CHCl3) 2850, 1940
cm-1; MS(EI) m/z 190 (M+, 20), 175 (60), 147 (14), 133 (31);
HRMS (EI) m/z calcd for C14H22 190.1721, found 190.1709.
Gen er a l Exp er im en ta l P r oced u r e for th e Rea ction of
Vin yl Allen es w ith Ma leic An h yd r id e. To a stirred solution
of the vinyl allene in toluene (0.3 M) at rt under argon
atmosphere was added maleic anhydride (1 equiv). After 24-
36 h, the solvent was removed, and after filtration through a
short pad of silica gel the product was obtained as a white
solid.
(3a R*,9a S*,9b R*)-4(E)-E t h ylid en e-3a ,4,6,7,8,9,9a ,9b -
octa h yd r on a p h th o[1,2-c]fu r a n -1,3-d ion e (14). Following
the general procedure, vinyl allene 4 (150 mg, 1.12 mmol)
furnished, after 6 h, cycloadduct 14 (244 mg, 94%): white solid;
mp 106-108 °C; 1H NMR (400 MHz, CDCl3) δ 6.24 (s, 1H),
5.57 (q, J ) 7.1 Hz, 1H), 3.73 (d, J ) 8.6 Hz, 1H), 3.47 (t, J )
8.6 Hz, 1H), 2.58 (m, 1H), 2.39 (d, J ) 13.2 Hz, 1H), 2.09 (m,
1H), 1.94-1.84 (m, 2H), 1.83 (d, J ) 7.1 Hz, 3H), 1.47-1.30
(m, 4H); 13C NMR (100 MHz, CDCl3) δ 171.5, 171.3, 141.4,
126.2, 122.7, 115.7, 45.0, 43.9, 36.6, 36.1, 31.2, 28.3, 26.7, 13.0;
IR (CHCl3) 2880, 1855, 1770, 1700, 1435 cm-1; MS (EI) m/z
232 (M+, 54), 204 (22), 159 (100); HRMS (EI) m/z calcd for
C
11H16 148.1252, found 148.1295.
(()-1-(1-E t h ylb u t a -1,2-d ien yl)cycloh exen e (9). To a
stirred suspension of CuBr‚Me2S (9.1 g, 44.3 mmol) in THF
(150 mL) at -60 °C was added a solution of EtMgBr 3 M in
diethyl ether (14.8 mL, 44.3 mmol). After the mixture was
stirred for 1 h, a solution of benzoate 5 (1.87 g, 7.39 mmol) in
THF (50 mL) was added via cannula. The reaction mixture
was allowed to warm to rt overnight, and then a saturated
solution of NH4Cl (150 mL) was added and the reaction
extracted with diethyl ether (3 × 200 mL). After drying
(Na2SO4), concentration, and flash column chromatography
(hexanes), vinyl allene 9 was obtained (720 mg, 60%) as a
colorless oil: 1H NMR (400 MHz, CDCl3) δ 5.69 (s, 1H), 5.25
(bs, 1H), 2.15 (m, 6H), 1.68 (d, J ) 7 Hz, 3H), 1.61 (m 4H),
1.02 (t, J ) 7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 204.1,
133.3, 121.5, 108.9, 88.8, 27.3, 25.7, 22.5, 21.6, 20.1, 14.7, 12.5;
IR (CHCl3) 2880, 1930, 1700 cm-1; MS(EI) m/z 162 (M+,45),
147 (33), 133 (41), 119 (40), 103 (93), 91 (100); HRMS (EI) m/z
calcd for C12H18 162.1408, found 162.1433.
C
14H16O3 232.1099, found 232.1102.
(3a R*,9a S*,9bR*)-4(Z)-Ben zylid en e-5-m et h yl-3a ,4,6,7,
8,9,9a ,9b -oct a h yd r on a p h t h o[1,2-c]fu r a n -1,3-d ion e (15).
Following the general procedure, vinyl allene 10 (69.4 mg, 0.33
mmol) furnished, after 48 h, cycloadduct 15 (94.6 mg, 93%):
white solid; mp 111-113 °C; 1H NMR (400 MHz, CDCl3) δ
7.32-7.19 (m, 5H), 6.49 (s, 1H), 3.96 (d, J ) 9.1 Hz, 1H), 3.41
(dd, J ) 6.1, 9.1 Hz, 1H), 2.47 (bs, 1H), 2.38-2.17 (m, 3H),
1.87 (m, 2H), 1.66 (m, 2H), 1.55 (s, 3H), 1.43 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 172.0, 171.8, 139.2, 136.5, 132.4, 129.7,
128.8, 128.6, 128.1, 127.5, 52.0, 45.4, 36.9, 25.0, 24.3, 21.7, 21.3,
16.5; IR (CHCl3) 1850, 1765, 1440 cm-1; MS (EI) m/z 308 (M+,
100), 262 (96), 247 (26), 235 (36), 221 (86); HRMS (EI) m/z
calcd for C20H20O3 308.1412, found 308.1398.
(()-(3-Cycloh ex-1-en ylbu ta-1,2-dien yl)ben zen e (10). Fol-
lowing the same procedure used for the preparation of 8, and
starting with benzoate 6 (923 mg, 2.92 mmol), vinyl allene 10
was obtained (411 mg, 67%) as a colorless oil: 1H NMR (400
MHz, CDCl3) δ 7.30 (m, 3H), 7.20 (m, 2H), 6.30 (s, 1H), 5.82
(m, 1H), 2.19 (m, 3H), 2.11 (m, 1H), 1.98 (s, 3H), 1.64 (m, 4H);
13C NMR (100 MHz, CDCl3) δ 206.4, 135.4, 133.2, 128.5, 127.7,
123.3, 106.5, 95.6, 26.9, 25.9, 22.8, 22.3, 15.9; IR (CHCl3) 2875,
1920, 1590 cm-1; MS(EI) m/z 210 (M+, 100), 195 (21), 181 (20),
167 (54); HRMS (EI) m/z calcd for C16H18 210.1408, found
210.1397.
1-(1,3-Dim eth ylbu ta -1,2-d ien yl)cycloh exen e (11). Fol-
lowing the same procedure used for the preparation of 8, and
starting with benzoate 7 (2.24 g, 8.34 mmol), vinyl allene 11
was obtained (879 mg, 65%) as a colorless oil: 1H NMR (400
MHz, CDCl3) δ 5.64 (bs, 1H), 2.14 (m, 2H), 2.04 (m, 2H), 1.79
(s, 3H), 1.69 (s, 6H), 1.58 (m, 4H); 13C NMR (75 MHz, CDCl3)
δ 201.6, 134.9, 121.5, 100.2, 95.5, 26.9, 25.9, 23.0, 22.5, 20.7,
16.4; IR (CHCl3) 2945, 1950, 1450 cm-1; MS(EI) m/z 162 (M+,
(3a R*,9a S*,9b R*)-4-Isop r op ylid en e-5-m et h yl-3a ,4,6,7,
8,9,9a ,9b -oct a h yd r on a p h t h o[1,2-c]fu r a n -1,3-d ion e (16).
Following the general procedure, vinyl allene 11 (150 mg, 0.92
mmol) furnished, after 48 h, cycloadduct 16 (200 mg, 83%):
white solid; mp 123-125 °C; 1H NMR (400 MHz, CDCl3) δ 4.25
(d, J ) 9.0 Hz, 1H), 3.27 (dd, J ) 5.1, 9.0 Hz, 1H), 2.12-2.26
(m, 4H), 1.89 (s, 3H), 1.77 (s, 3H), 1.75 (s, 3H), 1.73 (m, 2H),
1.65 (m, 1H), 1.56 (m, 1H), 1.30 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 172.7, 172.3, 137.0, 131.8, 128.8, 126.4, 46.6, 46.0,
36.2, 24.5, 24.0, 23.0, 21.5, 21.1, 20.9, 18.2; IR (CHCl3) 2950,
2855, 1860, 1780 cm-1; MS (EI) m/z 260 (M+, 57), 232 (55),
217 (19), 199 (9), 187 (65), 173 (100); HRMS (EI) m/z calcd for
C
16H20O3 (M+) 260.1412, found 260.1387.
(3a R*,9a S*,9b R*)-5-ter t-Bu t yl-4(Z)-et h ylid en e-3a ,4,6,
7,8,9,9a ,9b-octa h yd r on a p h th o[1,2-c]fu r a n -1,3-d ion e (17).
Following the general procedure, vinyl allene 12 (52 mg, 0.27
mmol) furnished, after 72 h, cycloadduct 17 (59 mg, 75%):
white solid; mp 112-114 °C; 1H NMR (400 MHz, CDCl3) δ 5.46
J . Org. Chem, Vol. 68, No. 20, 2003 7849

Rega´s et al.
(q, J ) 6.9 Hz, 1H), 3.78 (d, J ) 9.0 Hz, 1H), 3.20 (dd, J ) 5.1,
9.0 Hz, 1H), 2.70 (dd, J ) 3.9, 9.3 Hz, 1H), 2.19 (m, 1H), 2.09
(m, 1H), 1.96 (m, 1H), 1.85 (m, 2H), 1.67 (d, J ) 6.9 Hz, 3H),
1.64 (m, 1H), 1.40 (m, 2H), 1.15 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 172.1, 171.9, 140.3, 139.6, 125.9, 53.3, 45.3, 39.9, 33.8,
30.5, 25.0, 25.0, 22.3, 19.7, 17.2; IR (CHCl3) 2900, 2825, 1845,
1760, 1455 cm-1; MS (EI) m/z 288 (M+, 38), 260 (19), 245 (33),
159 (100); HRMS (EI) m/z calcd for C18H24O3 (M+) 288.1725,
found 288.1736.
Gen er a l Exp er im en ta l P r oced u r e for th e Rea ction of
Vin yl Allen es w ith Im in es. Vinyl allene (1.0 equiv) was
added to a stirred solution of the imine (1-2 equiv) and boron
trifluoride etherate (1.1-1.2 equiv) in CH2Cl2 (0.1 M) at 0 °C.
The reaction mixture was stirred at room temperature or
refluxed for 36 h to 5 days, and then TEA (2.4 equiv) and water
(10 mL) were added and the reaction mixture was extracted
with CH2Cl2. Drying (MgSO4) and concentration afforded crude
products. Flash column chromatography on silica gel (hexanes/
EtOAc) gave the products in the yields indicated.
Rea ction of Vin yl Allen e 9 w ith Im in e 18. Following the
general procedure, vinyl allene 9 (133 mg, 0.82 mmol), imine
18 (240 mg, 1.23 mmol), and BF3‚Et2O (1.2 equiv), after 4 days
at rt and flash chromatography (97:3 hexanes/EtOAc), pro-
vided octahydroquinoline 19 (196 mg, 67%). When TiCl4 was
used as Lewis acid, 19 was obtained in a 49% yield together
with triene 20 (8%).
(2R*,8a S*)-1-Ben zyl-4-eth yl-3(E)-eth ylid en e-2-p h en yl-
1,2,3,5,6,7,8,8a -octa h yd r oqu in olin e (19): oily; white solid;
1H NMR (400 MHz, CDCl3) δ 7.53-7.51 (m, 2H), 7.42-7.33
(m, 4H), 7.27-7.14 (m, 4H), 5.18 (q, J ) 7.39 Hz, 1H), 4.06 (s,
1H), 3.85 (d, J ) 13.4 Hz, 1H), 3.74 (d, J ) 13.4 Hz, 1H), 2.82-
2.76 (m, 2H), 2.66-2.55 (m, 2H), 1.99 (d, J ) 7.38 Hz, 3H),
1.66-1.53 (m, 2H), 1.43-1.42 (m, 1H), 1.20 (t, J ) 7.47 Hz,
3H), 1.10-1.07 (m, 1H), 0.90-0.80 (m, 2H), 0.64-0.60 (m, 1H);
13C NMR (100 MHz, CDCl3) δ 144.9, 141.2, 137.8, 132.2, 129.4,
129.1, 128.5, 128.4, 127.6, 127.2, 126.4, 122.9, 68.6, 64.2, 62.1,
36.0, 30.3, 27.5, 27.2, 23.0, 15.7, 15.3; IR (CHCl3) 2900, 1590,
1485, 1440 cm-1; MS (EI) m/z 357 (M+, 27), 328 (100), 280 (21),
91 (60); HRMS (EI) m/z calcd for C26H31N 357.2456, found
357.2402.
1.47 (m, 4H), 1.54 (d, J ) 6.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 148.0, 143.9, 142.9, 141.1, 134.9, 129.1, 128.7, 128.3,
128.3, 128.1, 127.5, 127.2, 123.0, 111.6, 67.0, 52.1, 26.2, 25.8,
23.2, 22.5, 14.9; IR (CHCl3) 2800, 1625, 1585, 1485, 1445; MS
(EI) m/z 343 (M+, 3), 307 (29), 289 (14), 154 (100), 136 (41);
HRMS (EI) m/z calcd for C25H29N 343.2300, found 343.2309.
Rea ction of Vin yl Allen e 8 w ith Im in e 21. Following the
general procedure, vinyl allene 8 (150 mg, 1.01 mmol), imine
21 (249 mg, 1.57 mmol), and BF3‚Et2O (1.2 equiv), after 1.5
days at rt and flash chromatography (97:3 hexanes/EtOAc),
provided octahydroquinoline 24 (134 mg, 43%) and triene 34
(22 mg, 7%) together with unreacted 8 (20 mg).
(2R*,8aS*)-1-Ben zyl-3(E)-eth yliden e-2-isopr opyl-4-m eth -
yl-1,2,3,5,6,7,8,8a -octa h yd r oqu in olin e (24): colorless oil; 1H
NMR (400 MHz, CDCl3) δ 7.42-7.21 (m, 5H), 4.97 (q, J ) 7.16
Hz, 1H), 3.59 (s, 2H), 2.85-2.81 (m, 1H), 2.71-2.68 (m, 1H),
2.21 (d, J ) 10.5 Hz, 1H), 1.99 (s, 3H), 1.93-1.68 (m, 5H),
1.82 (d, J ) 7.16 Hz, 3H), 1.53-1.49 (m, 1H), 1.27-1.16 (m,
2H), 0.98 (d, J ) 6.5 Hz, 3H), 0.68 (d, J ) 6.6 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 141.5, 136.5, 136.0, 129.6, 128.3,
126.9, 122.2, 119.3, 74.6, 62.9, 62.8, 37.1, 29.7, 29.6, 27.0, 26.7,
21.7, 20.5, 18.2, 15.6; IR (CHCl3) 2850, 1585, 1480, 1435 cm-1
;
MS (EI) m/z 309 (M+, 0.2), 289 (10), 266 (100), 154 (94), 137
(50); HRMS (EI) m/z calcd for
C22H31N 309.2456, found
309.2536.
(()-Ben zyl-[2-(1-cycloh ex-1-en ylvin yl)-1-isop r op ylbu t-
2(E)-en yl]a m in e (34): colorless oil; 1H NMR (400 MHz,
CDCl3) δ 7.37-7.21 (m, 5H), 5.80 (s, 1H), 5.60 (q, J ) 6.6 Hz,
1H), 5.18 (s, 1H), 4.65 (s, 1H), 3.87 (d, J ) 13.2 Hz, 1H), 3.57
(d, J ) 13.2 Hz, 1H), 2.82 (d, J ) 4.6 Hz, 1H) 2.21-2.07 (m,
4H), 1.82-1.77 (m, 1H), 1.69-1.52 (m, 5H), 1.63 (d, J ) 6.7
Hz, 3H), 0.93 (d, J ) 6.8 Hz, 3H), 0.83 (d, J ) 6.8 Hz, 3H); 13
C
NMR (100 MHz, CDCl3) δ 149.1, 141.9, 141.0, 135.7, 128.6,
127.0, 126.9, 121.9, 111.2, 68.3, 52.0, 29.3, 26.2, 26.1, 23.3, 22.6,
21.2, 17.5, 14.9; MS (EI) m/z 309 (M+, 8), 307 (28), 289 (19),
266 (21), 154 (100), 136 (66); HRMS (EI) m/z calcd for C22H31
N
309.2456, found 309.2547.
Rea ction of Vin yl Allen e 9 w ith Im in e 21. Following the
general procedure, vinyl allene 9 (100 mg, 0.61 mmol), imine
21 (148 mg, 0.92 mmol), and BF3‚Et2O (1.1 equiv), after 3 days
at rt and flash chromatography (97:3 hexanes/EtOAc), pro-
vided octahydroquinoline 25 (78 mg, 39%) and triene 35 (8
mg, 4%), together with unreacted 9 (24 mg).
(()-Ben zyl-(3-cycloh ex-1-en yl-2(E)-eth yliden e-1-ph en yl-
p en t-3(E)-en yl)a m in e (20): colorless oil; 1H NMR (400 MHz,
C6D6, 348 K) δ 7.48-7.16 (m, 10H), 6.05 (bs, 1H), 5.77 (bs,
1H), 5.64 (bs, 1H), 4.33 (s, 1H), 3.80 (d, J ) 13.5 Hz, 1H), 3.68
(d, J ) 13.5 Hz, 1H), 2.17 (bs, 2H), 2.05 (bs, 2H), 1.75-1.36
(2R*,8a S*)-1-Ben zyl-4-eth yl-3(E)-eth ylid en e-2-isop r o-
p yl-1,2,3,5,6,7,8,8a -octa h yd r oqu in olin e (25): colorless oil;
1H NMR (400 MHz, CDCl3) δ 7.41-7.23 (m, 5H), 4.97 (q, J )
7.2 Hz, 1H), 3.58 (s, 2H), 2.85-2.81 (m, 1H), 2.69-2.67 (m,
1H), 2.51-2.39 (m, 2H), 2.20-2.17 (m, 1H), 1.90-1.84 (m, 1H),
1.82 (d, J ) 7.2 Hz, 3H), 1.81-1.69 (m, 4H), 1.55-1.51 (m,
1H), 1.28-1.12 (m, 2H), 1.05-0.99 (m, 6H), 0.71 (d, J ) 6.5
Hz, 3H); 13C NMR (75 MHz, CDCl3) δ141.1, 135.4, 134.5, 129.1,
129.0, 127.8, 126.4, 119.0, 74.6, 62.6, 62.4, 36.7, 29.5, 28.9, 26.9,
26.7, 22.7, 21.1, 20.1, 15.0, 14.7; IR (CHCl3) 2900, 1595, 1485,
1445 cm-1; MS (EI) m/z 323 (M+, 5.6), 307 (14.6), 280 (100),
154 (28), 136 (22); HRMS (EI) m/z calcd for C23H33N 323.2613,
found 323.2651.
(m, 5H), 1.58 (bs, 6H); IR (CHCl3) 2900, 1600, 1485, 1440 cm-1
;
MS (EI) m/z 357 (M+, 45), 307 (38), 251 (31), 196 (62), 154
(79); HRMS (EI) m/z calcd for
C26H31N 357.2456, found
357.2550.
Rea ction of Vin yl Allen e 8 w ith Im in e 18. Following the
general procedure, vinyl allene 8 (150 mg, 1.01 mmol), imine
18 (300 mg, 1.52 mmol), and BF3‚Et2O (1.2 equiv), after 1.5
days at rt and flash chromatography (97:3 hexanes/EtOAc),
provided octahydroquinoline 23 (187 mg, 54%) and triene 33
(32 mg, 11%).
(2R*,8a S*)-1-Ben zyl-3(E)-eth ylid en e-4-m eth yl-2-p h en -
yl-1,2,3,5,6,7,8,8a-octah ydr oqu in olin e (23): oily, white solid;
1H NMR (400 MHz, CDCl3) δ 7.54-7.13 (m, 10H), 5.19 (q, J )
7.26 Hz, 1H), 4.07 (s, 1H), 3.86 (d, J ) 13.4 Hz, 1H), 3.75 (d,
J ) 13.4 Hz, 1H), 2.82-2.74 (m, 2H), 2.17 (s, 3H), 1.98 (d, J )
7.25 Hz, 3H), 1.64-1.42 (m, 4H), 1.11-1.07 (m, 1H), 0.81-
0.77 (m, 1H), 0.6-0.56 (m, 1H); 13C NMR (100 MHz, CDCl3) δ
144.8, 141.2, 137.8, 133.9, 129.4, 129.1, 128.6, 127.6, 127.2,
126.5, 122.8, 121.8, 68.3, 64.1, 62.3, 36.0, 30.3, 27.1, 26.8, 18.1,
16.0; IR (CHCl3) 2900, 1595, 1495, 1445 cm-1; MS (EI) m/z
343 (M+, 39), 328 (95), 314 (16), 266 (77), 91 (100); HRMS (EI)
m/z calcd for C25H29N 343.2300, found 343.2265.
(()-Ben zyl(3-cycloh ex-1-en yl-2(E)-eth ylid en e-1-isop r o-
p ylp en t-3(E)-en yl)a m in e (35): colorless oil; 1H NMR (400
MHz, CDCl3, 330K): δ 7.38-7.19 (m, 10H), 5.76 (m, 1H), 5.60
(m, 2H), 3.93 (d, J ) 13.2 Hz, 1H), 3.61 (d, J ) 13.2 Hz, 1H),
2.92 (s, 1H), 2.17 (m, 1H), 2.03 (m, 2H), 1.76, (m, 1H), 1.59
(m, 6H), 0.96 (d, J ) 6.8 Hz, 3H), 0.82 (d, J ) 6.8 Hz, 3H); IR
(CHCl3) 2900, 1710, 1595, 1485, 1440 cm-1; MS (EI) m/z 323
(M+, 12), 307 (23), 280 (81), 154 (100), 136 (44); HRMS (EI)
m/z calcd for C23H33N 323.2613, found 323.2676.
Rea ction of Vin yl Allen e 10 w ith Im in e 18. Following
the general procedure, vinyl allene 10 (75 mg, 0.36 mmol),
imine 18 (103 mg, 0.53 mmol), and BF3‚Et2O (1.2 equiv), after
4 days at rt and flash chromatography (97:3 hexanes/EtOAc),
provided octahydroquinoline 26 (103 mg, 71%) and triene 36
(7 mg, 5%) together with unreacted 10 (10 mg).
(()-Ben zyl[2-(1-cycloh ex-1-en ylvin yl)-1-ph en ylbu t-2(E)-
1
en yl]a m in e (33): colorless oil; H NMR (400 MHz, CDCl3) δ
7.33-7.20 (m, 10H), 5.69-5.63 (m, 2H), 5.10 (s, 1H), 4.51 (s,
1H), 4.19 (s, 1H), 3.73 (d, J ) 13.48 Hz, 1H), 3.64 (d, J ) 13.48
Hz, 1H), 2.35 (brs, 1H), 2.10 (brs, 2H), 1.97 (brs, 2H), 1.64-
7850 J . Org. Chem., Vol. 68, No. 20, 2003

Synthesis of Octahydroquinolines
(2R*,8aS*)-1-Ben zyl-3(E)-ben zyliden e-4-m eth yl-2-ph en -
yl-1,2,3,5,6,7,8,8a-octah ydr oqu in olin e (26): oily, white solid;
1H NMR (400 MHz, CDCl3) δ 7.58-7.20 (m, 15H), 6.26 (s, 1H),
4.33 (s, 1H), 4.04 (d, J ) 13.3 Hz, 1H), 3.91 (d, J ) 13.3 Hz,
1H), 2.97 (m, 1H), 2.75 (m, 1H), 1.79 (s, 3H), 1.77-0.67 (m,
7H); 13C NMR (100 MHz, CDCl3) δ 144.1, 140.8, 139.9, 139.4,
136.2, 129.6, 129.1, 129.1, 128.7, 128.2, 127.8, 127.4, 127.2,
126.8, 126.8, 121.9, 67.8, 64.2, 62.5, 36.0, 30.4, 27.0, 26.5, 18.1;
IR (CHCl3) 2850, 1720, 1590, 1480, 1440 cm-1; MS (EI) m/z
405 (M+, 73), 390 (100), 376 (10), 328 (77), 314 (11); HRMS
(EI) m/z calcd for C30H31N 405.2456, found 405.2452.
(()-Ben zyl(2(E)-ben zyliden e-3-cycloh ex-1-en yl-1-ph en yl-
bu t-3-en yl)a m in e (36): colorless oil; 1H NMR (400 MHz,
CDCl3) δ 7.40-7.12 (m, 15 H), 6.84 (s, 1H), 5.78 (s, 1H), 5.06
(s, 1H), 4.49 (s, 1H), 4.31 (s, 1H), 3.79 (AB system, J ) 13.3
Hz, 2H), 2.16 (m, 2H), 1.94 (m, 2H), 1.63 (m, 2H), 1.5 (m, 2H);
13C NMR (100 MHz, CDCl3) 148.5, 137.5, 134.3, 129.8, 129.2,
128.8, 128.6, 128.4, 128.3, 127.5, 127.3, 127.1, 127.0, 112.0,
68.3, 52.2, 26.2, 25.8, 23.2, 22.5; MS (EI) m/z 405 (M+, 80),
1H), 3.19 (t, J ) 5.7 Hz, 1H), 2.21 (m, 2H), 2.01 (m, 2H), 1.85-
1.50 (m, 6H), 1.26 (m, 8H), 0.89 (t, J ) 6.7 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 148.5, 142.9, 141.0, 137.3, 134.3, 128.7,
128.3, 128.1, 127.9, 127.9, 126.7, 126.4, 110.7, 64.2, 51.2, 34.2,
31.9, 29.4, 26.2, 25.8, 25.7, 22.9, 22.7, 21.5, 14.1; IR (CHCl3)
3300, 2800, 1930, 1865, 1790, 1725 cm-1; MS (EI) m/z 413 (M+,
22), 328 (79), 306 (17), 91 (100); HRMS (EI) m/z calcd for
C
30H39N 413.3082, found 413.3063.
Rea ction of Vin yl Allen e 11 w ith Im in e 18. Following
the general procedure, vinyl allene 11 (125 mg, 0.77 mmol),
imine 18 (225 mg, 1.15 mmol), and BF3‚Et2O (1.1 equiv), after
3 days at 40 °C and flash chromatography (97:3 hexanes/
EtOAc), provided octahydroquinoline 29 (184 mg, 67%) and
triene 39 (16 mg, 6%).
(2R*,8aS*)-1-Ben zyl-3-isopr opyliden e-4-m eth yl-2-ph en -
yl-1,2,3,5,6,7,8,8a -octa h yd r oqu in olin e (29): white crystals;
1
mp 125-127 °C; H NMR (400 MHz, CDCl3) δ 7.53-7.14 (m,
10H), 4.60 (s, 1H), 3.77 (m, 2H), 2.77 (d, J ) 11.7 Hz, 1H),
2.68 (d, J ) 13.9 Hz, 1H), 2.07 (s, 3H), 1.99 (s, 3H), 1.60 (m,
2H), 1.55 (s, 3H), 1.45 (m, 2H), 1.09 (m, 1H), 0.75 (m, 1H),
0.66 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 143.8, 141.0, 136.2,
129.1, 128.9, 128.7, 128.1, 127.7, 127.2, 126.7, 126.0, 122.1,
63.1, 62.0, 61.2, 35.8, 29.9, 26.5, 26.0, 23.5, 21.5, 19.4; IR
(CHCl3) 3050, 3025, 3000, 2900, 2800, 1940, 1855, 1790, 1730,
1590 cm-1; MS (EI) m/z 357 (M+, 44), 342 (100), 280 (20);
HRMS (EI) m/z calcd for C26H31N 357.2456, found 357.2458.
(()-Ben zyl[2-(1-cyclohex-1-en ylvin yl)-3-m eth yl-1-ph en yl-
bu t-2-en yl]a m in e (39): colorless oil; 1H NMR (400 MHz,
CDCl3, 328K) δ 7.34-7.12 (m, 10H), 5.36 (bs, 1H), 5.09 (s, 1H),
4.86 (s, 1H), 3.73 (AB system, J ) 13.4 Hz, 2H), 2.06 (m, 1H),
1.92 (s, 3H), 1.86 (m, 3H), 1.71 (m, 2H), 1.62 (s, 3H), 1.38 (m,
4H); 13C NMR (100 MHz, CDCl3) δ 147.9, 142.7, 140.8, 135.4,
130.0, 128.2, 128.1, 127.5, 127.5, 127.4, 126.7, 126.1, 111.0,
61.3, 51.3, 25.6, 25.1, 22.9, 22.7, 21.9, 19.7; IR (CHCl3) 3000,
2900, 2750, 1725, 1580 cm-1; MS (EI) m/z 357 (M+, 48), 266
(16), 250 (28), 25 (31), 196 (72), 981 (100); HRMS (EI) m/z calcd
for C26H31N 357.2456, found 357.2445.
299 (63), 196 (62), 91 (100); HRMS (EI) m/z calcd for C30H31
N
405.2456, found 405.2495.
Rea ction of Vin yl Allen e 10 w ith Im in e 21. Following
the general procedure, vinyl allene 10 (152 mg, 0.72 mmol),
imine 21 (173 mg, 1.07 mmol), and BF3‚Et2O (1.2 equiv), after
4 days at rt and flash chromatography (97:3 hexanes/EtOAc),
provided octahydroquinoline 27 (162 mg, 61%) and triene 37
(32 mg, 12%) together with unreacted 10 (23 mg).
(2R*,8a S*)-1-Ben zyl-3(E)-b en zylid en e-2-isop r op yl-4-
m eth yl-1,2,3,5,6,7,8,8a -octa h yd r oqu in olin e (27): colorless
oil; 1H NMR (400 MHz, CDCl3) δ 7.73-7.18 (m, 10H), 6.00 (s,
1H), 3.71 (m, 2H), 2.82 (m, 2H), 2.45 (d, J ) 10.5 Hz, 1H),
2.02 (bs, 1H), 1.75 (m, 2H), 1.71 (m, 2H), 1.64 (s, 3H), 1.54
(dq, J ) 3.3, 12.6 Hz, 1H), 1.26 (m, 1H), 1.14 (m, 1H), 1.02 (d,
J ) 6.4 Hz, 3H), 0.75 (d, J ) 6.6 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ 140.7, 139.0, 138.5, 137.5, 129.2, 128.9, 127.9, 127.7,
126.6, 125.9, 123.7, 121.9, 73.8, 62.5, 62.3, 36.4, 29.4, 28.9, 26.4,
26.1, 21.0, 19.9, 17.5; IR (CHCl3) 2925, 2850, 1630, 1595 cm-1
;
MS (EI) m/z 371 (M+, 1), 329 (27), 328 (100); HRMS (EI) m/z
calcd for C27H33N 371.2613, found 371.2609.
Rea ction of Vin yl Allen e 11 w ith Im in e 21. Following
the general procedure, vinyl allene 11 (125 mg, 0.77 mmol),
imine 21 (187 mg, 1.16 mmol), and BF3‚Et2O (1.2 equiv), after
5 days at 40 °C and flash chromatography (97:3 hexanes/
EtOAc), provided octahydroquinoline 30 (93 mg, 37%) and
triene 40 (5 mg, 2%) together with unreacted 11 (19 mg).
(2R*,8a S*)-1-Ben zyl-2-isop r op yl-3-isop r op ylid en e-4-
m eth yl-1,2,3,5,6,7,8,8a -octa h yd r oqu in olin e (30): colorless
oil; 1H NMR (400 MHz, CDCl3) δ 7.40-7.19 (m, 5H), 3.53 (AB
system, J ) 13.7 Hz, 2H), 2.90 (d, J ) 10.5 Hz, 1H), 2.77 (d,
J ) 13.7 Hz, 1H), 2.66 (d, J ) 10.9 Hz, 1H), 1.90-1.62 (m,
5H), 1.92 (s, 3H), 1.82 (s, 3H), 1.62 (s, 3H), 1.45 (m, 1H), 1.16
(()-Ben zyl-(2(E)-ben zylid en e-3-cycloh ex-1-en yl-1-iso-
p r op ylbu t-3-en yl)a m in e (37): colorless oil; 1H NMR (400
MHz, CDCl3) δ 7.40-7.12 (m, 10H), 6.60 (s, 1H), 5.92 (s, 1H),
5.18 (s, 1H), 4.76 (s, 1H), 3.96 (d, J ) 13.2 Hz, 1H), 3.64 (d, J
) 13.2 Hz, 1H), 3.05 (d, J ) 3.7 Hz, 1H), 2.26 (m, 1H), 2.15
(m, 1H), 1.98 (m, 2H), 1.70-1.50 (m, 6H), 1.00 (d, J ) 6.8 Hz,
3H), 0.88 (d, J ) 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
149.5, 138.0, 134.8, 129.1, 128.7, 128.3, 128.1, 127.2, 126.9,
126.7, 124.3, 111.7, 69.1, 52.0, 30.1, 29.7, 26.2, 23.3, 22.5, 21.7,
16.4; IR (CHCl3) 2900, 2850, 1710 cm-1; MS (EI) m/z 371 (M+,
10), 328 (6), 307 (30), 289 (10), 154 (100); HRMS (EI) m/z calcd
for C27H33N 371.2613, found 371.2541.
Rea ction of Vin yl Allen e 10 w ith Im in e 22. Following
the general procedure, vinyl allene 10 (124 mg, 0.59 mmol),
imine 22 (288 mg, 1.42 mmol), and BF3‚Et2O (1.2 equiv), after
3 days at rt and flash chromatography (97:3 hexanes/EtOAc),
provided octahydroquinoline 28 (139 mg, 57%) and triene 38
(7 mg, 3%) together with unreacted 10 (6 mg).
(2R*,8a S*)-1-Ben zyl-3(E)-ben zylid en e-2-h exyl-4-m eth -
yl-1,2,3,5,6,7,8,8a -octa h yd r oqu in olin e (28): colorless oil; 1H
NMR (400 MHz, CDCl3) δ 7.43-7.18 (m, 10H), 6.06 (s, 1H),
3.74 (AB system, J ) 13.7 Hz, 2H), 2.98 (t, J ) 7.5 Hz, 2H),
2.84 (m, 1H), 1.96 (m, 1H), 1.76 (m, 3H), 1.61 (s, 3H), 1.25 (m,
10H), 0.90 (t, J ) 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
140.7, 139.1, 137.3, 129.0, 128.8, 127.7, 126.6, 126.0, 123.6,
121.3, 66.4, 62.1, 61.8, 36.5, 34.2, 31.9, 30.9, 29.6, 29.3, 26.9,
26.5, 26.3, 22.7, 17.7, 14.1; IR (CHCl3) 2800, 1940, 1870, 1790,
1720 cm-1; MS (EI) m/z 413 (M+, 3), 398 (2), 328 (100); HRMS
(EI) m/z calcd for C30H39N 413.3082, found 413.3076.
(m, 2H), 1.00 (d, J ) 6.6 Hz, 3 H), 0.66 (d, J ) 6.6 Hz, 3H); 13
C
NMR (75 MHz, CDCl3) δ 141.4, 134.4, 132.0, 129.0, 127.7,
126.4, 124.0, 122.8, 66.5, 62.1, 61.9, 36.4, 29.5, 29.3, 26.4, 26.1,
23.1, 21.5, 20.1, 20.1, 19.5; IR (CHCl3) 2850, 1935, 1860, 1795,
1730 cm-1; MS (EI) m/z 323 (M+, 2), 280 (100), 246 (2); HRMS
(EI) m/z calcd for C23H33N 323.2613, found 323.2596.
(()-Ben zyl[2-(1-cycloh ex-1-en ylvin yl)-1-isop r op yl-3-
m et h ylb u t -2-en yl]a m in e (40): colorless oil; 1H NMR (400
MHz, CDCl3) δ 7.49-7.21 (m, 5H), 5.81 (s, 1H), 5.22 (s, 1H),
4.64 (s, 1H), 3.74 (d, J ) 13.1 Hz, 1H), 3.52 (d, J ) 13.1 Hz,
1H), 3.07 (d, J ) 8.9 Hz, 1H), 2.19 (bs, 2H), 2.06 (bs, 2H), 1.71
(s, 3H), 1.66 (s, 3H), 1.53 (m, 5H), 0.98 (d, J ) 6.6 Hz, 3H),
0.81 (d, J ) 6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 148.6,
128.2, 128.0, 127.6, 126.6, 126.0, 114.6, 64.5, 52.4, 31.6, 29.7,
25.8, 23.2, 23.0, 22.2, 20.9, 20.2, 19.9.
Rea ction of Vin yl Allen e 11 w ith Im in e 22. Following
the general procedure, vinyl allene 11 (125 mg, 0.77 mmol),
imine 22 (373 mg, 1.84 mmol), and BF3‚Et2O (1.2 equiv), after
5 days at 40 °C and flash chromatography (97:3 hexanes/
EtOAc), provided octahydroquinoline 31 (115 mg, 41%) and
triene 41 (20 mg, 7%) together with unreacted 11 (29 mg).
(2R*,8a S*)-1-Ben zyl-2-h exyl-3-isop r op ylid en e-4-m eth -
yl-1,2,3,5,6,7,8,8a -octa h yd r oqu in olin e (31): colorless oil; 1H
(()-Ben zyl[1-(1(E)-ben zylid en e-2-cycloh ex-1-en yla llyl)-
h ep tyl]a m in e (38): colorless oil; 1H NMR (300 MHz, CDCl3)
δ 7.43-7.13 (m, 10H), 6.55 (s, 1H), 5.93 (s, 1H), 5.23 (s, 1H),
4.81 (s, 1H), 3.90 (d, J ) 13.2 Hz, 1H), 3.70 (d, J ) 13.2 Hz,
J . Org. Chem, Vol. 68, No. 20, 2003 7851

Rega´s et al.
NMR (400 MHz, CDCl3) δ 7.40-7.20 (m, 5H), 3.58 (s, 2H), 3.40
(dd, J ) 7.0, 7.8 Hz, 1H), 2.80 (d, J ) 16.3 Hz, 1H), 2.68 (d, J
) 9.9 Hz, 1H), 1.92 (s, 3H), 1.83 (s, 3H), 1.66 (m, 3H), 1.60 (s,
(2R*,8aS*)-1-Ben zyl-4-ter t-bu tyl-3(E)-eth yliden e-2-ph en -
yl-1,2,3,5,6,7,8,8a -octa h yd r oqu in olin e (32): colorless oil; 1H
NMR (400 MHz, CDCl3, 330 K) δ 7.32-7.10 (m, 10H), 5.27
(bs, 1H), 4.19 (s, 1H), 3.84 (d, J ) 14.3 Hz, 1H), 3.68 (d, J )
14.3 Hz, 1H), 2.76 (m, 1H), 2.62 (m, 1H), 2.27 (m, 1H), 1.80
(m, 1H), 1.68 (d, J ) 6.89 Hz, 3H), 1.64-1.47 (m, 4H), 0.92 (s,
9H); 13C NMR (100 MHz, CDCl3, 330 K) δ 145.1, 141.0, 140.1,
138.6, 129.1, 128.6, 128.4, 127.6, 127.0, 126.2, 125.7, 119.3,
72.0, 62.1, 59.8, 34.2, 30.1, 17.2; IR (CHCl3) 2900, 1590, 1485,
1440 cm-1; MS (EI) m/z 385 (M+, 1.4), 307 (22), 289 (10), 154
(100), 136 (50); HRMS (EI) m/z calcd for C28H35N 385.2769,
found 385.2692.
3H), 1.47 (m, 4H), 1.25 (m, 10H), 0.87 (t, J ) 7.0 Hz, 3H); 13
C
NMR (100 MHz, CDCl3) δ 141.3, 134.2, 132.6, 128.7, 127.8,
126.4, 124.1, 122.2, 61.4, 61.4, 59.1, 36.5, 34.2, 31.9, 29.6, 29.5,
26.5, 26.5, 26.3, 23.3, 22.7, 21.4, 19.5, 14.1; IR (CHCl3) 2900,
1720, 1680 cm-1; MS (EI) m/z 365 (M+, 3), 350 (5), 280 (100);
HRMS (EI) m/z calcd for C26H39N 365.3082, found 365.3084.
(()-Ben zyl[1-[1-(1-cycloh ex-1-en ylvin yl)-2-m eth ylp r o-
1
p en yl]h ep tyl]a m in e (41): colorless oil; H NMR (300 MHz,
CDCl3) δ 7.35-7.21 (m, 5H), 5.77 (bs, 1H), 5.22 (s, 1H), 4.61
(s, 1H), 3.74 (d, J ) 13.3 Hz, 1H), 3.58 (d, J ) 13.3 Hz, 1H),
3.51 (t, J ) 6.2 Hz, 1H), 2.30-2.23 (m, 4H), 1.71 (s, 3H), 1.64
(s, 3H), 1.65-1.45 (m, 4H), 1.23 (m, 10H), 0.85 (t, J ) 7.0 Hz,
3H); 13C NMR (75 MHz, CDCl3, 330 K) δ 148.3, 144.1, 141.3,
136.0, 129.9, 128.6, 128.0, 126.9, 128.5, 110.7, 57.7, 51.5, 35.3,
32.0, 29.5, 27.1, 25.7, 25.6, 23.0, 23.0, 22.7, 22.2, 19.4, 14.1.
Ack n ow led gm en t. This work was supported in part
by Grant No. BQU2001-3184 (MCYT, Spain) and Grant
No. 1FD97-0747-C04-01 (FEDER, EU). D.R. thanks the
MEC (Spain) for a fellowship.
Su p p or tin g In for m a tion Ava ila ble: General experimen-
tal procedures and NMR spectra for all new compounds and
ORTEP drawing and X-ray data for compound 29. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Rea ction of Vin yl Allen e 12 w ith Im in e 18. Following
the general procedure, vinyl allene 12 (215 mg 1.1 mmol),
imine 18 (330 mg, 1.69 mmol), and BF3‚Et2O (1.1 equiv), after
5 days at 40 °C and flash chromatography (97:3 hexanes/
EtOAc), provided octahydroquinoline 32 (148 mg, 34%) to-
gether with unreacted 12 (54 mg).
J O034480Z
7852 J . Org. Chem., Vol. 68, No. 20, 2003