Stereoselective Construction of Tetrasubstituted Exocyclic Alkenes from the -Cycloaddition of Vinylallenes

Full text of DOI:10.1021/jo980482l

J . Org. Chem. 1998, 63, 5283-5287
5283
Ster eoselective Con str u ction of
Tetr a su bstitu ted Exocyclic Alk en es fr om
th e [4 + 2]-Cycloa d d ition of Vin yla llen es
Claude Spino,* Carl Thibault, and St e´ phane Gingras
Universit e´ de Sherbrooke, D e´ partement de Chimie, 2500
Boul. Universit e´ , Sherbrooke, Qc, J 1K 2R1, Canada
Received March 13, 1998
In the course of our synthetic studies on quassinoids1
we required the stereoselective preparation of a tetra-
substituted exocyclic double bond of the type shown as
1 2
structure 1 (eq 1, R , R
, X * H).2 Starting from the
F igu r e 1. Exocyclic alkene geometries resulting from the two
approaches on the vinylallenes.
Sch em e 1
corresponding 2-X-2-cyclohexen-1-one 2, a wide range of
methods were examined to no avail, including Wittig
olefination, aldol condensation/elimination, McMurray
coupling, addition of 2-propenyllithium followed by Clais-
en rearrangement or S 2′ displacements. Most of them
N
either gave back starting material or decomposition
products. Yet, we could prepare trisubstituted analogues
3
in high yields. Possibly the steric congestion experi-
Sch em e 2
enced by the four substituents on this rather planar
π-system was to blame. The stereoselective construction
of tetrasubstituted exocyclic double bonds in general
remains a challenge in organic synthesis. We herein
disclose preliminary results on the [4 + 2]-cycloaddition
of vinylallenes as a stereoselective route to tetrasubsti-
tuted exocyclic alkenes including very strained ones that
are difficult to prepare by other methods.
Reich and co-workers reported vinylallene cycloaddi-
tions that led to trisubstituted exocyclic alkenes with
excellent stereoselectivity.3 The geometry of the alkenes
was consistent with an approach of the dienophile from
the least hindered face of the diene (I‡ in Figure 1).
Others have reported on the use of intramolecular Diels-
,4
Alder cycloadditions of vinylallenes for natural product
synthesis.5
-8
To the best of our knowledge, no report of
intermolecular [4 + 2]-cycloaddition of vinylallenes to
form unsymmetrically tetrasubstituted exocyclic double
bonds has appeared in the literature.
We prepared vinylallenes 5a ,b and 8b,c,d as depicted
in Schemes 1 and 2.9 Compounds 4a -d were obtained
from the addition of the appropriate alkynylmetal to
crotonaldehyde. The resulting alcohols 4a and 4b were
directly acetylated (Scheme 1) while alcohols 4b-d were
oxidized and reacted with the anion of 1,3-dithiane prior
to acetylation to give acetates 7b-d, respectively (Scheme
2). Displacement of each acetate with dialkylcuprates
under strictly defined conditions led to vinylallenes 5 or
*
Corresponding author. Tel: (819)-821-7087. Fax: (819)-821-8017.
E-mail: cspino@courrier.usherb.ca.
1) For a review on the synthesis of quassinoids, see: Kawada, K.;
Kim, M.; Watt, D. S. Org. Prepr. Proc. Int. 1989, 21, 521.
2) Spino, C.; Liu, G.; Tu, N.; Girard, S. J . Org. Chem. 1994, 59,
596.
3) Reich, H. J .; Eisenhart, E. K.; Whipple, W. L.; Kelly, M. J . J .
Am. Chem. Soc. 1988, 110, 6432 and references therein.
4) For a review on vinylallenes, see: Egenburg, I. Z. Russ. Chem.
Rev. 1978, 47, 470.
(
(
5
8
, respectively, with no or small amounts of byproducts
(
3
,10
from addition on the double bond.
Table 1 summarizes
(
the results of the cycloaddition of each vinylallene with
(
(
(
(
5) Okamura, W. H.; Curtin, M. L. Synlett 1990, 1.
6) Reich, H. J .; Eisenhart, E. K. J . Org. Chem. 1984, 49, 5282.
7) Keck, G. E.; Kachensky, D. F. J . Org. Chem. 1986, 51, 2487.
8) Deutsch, E. A.; Snider, B. B. J . Org. Chem. 1982, 47, 2682.
(9) All new compounds gave satisfactory NMR and mass spectral
data.
(10) Macdonald, T.; Reagan, D. R. J . Org. Chem. 1980, 45, 4740.
S0022-3263(98)00482-4 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/01/1998

5
284 J . Org. Chem., Vol. 63, No. 15, 1998
Ta ble 1. [4 + 2]-Cycloa d d ition s of Vin yla llen es 5 a n d 8 in Tolu en e w ith Va r iou s Dien op h iles
Notes
a
See text for acronyms. Isolated yield, unoptimized. c cf Figure 1. Ratio based on integration of signals in NMR or GC spectra of
b
d
e
crude product. 15 was a 2:1 mixture of isomers. 40 °C in CH2Cl2 + Me2AlCl.
various dienophiles. The reported yields are for isolated
material, and though the maleic anhydride adducts could
not be purified by chromatography, the crude material
was of acceptable purity for identification. In the other
cases, the isomers could be separated by chromatography
and their structures were secured by spectral methods.
The geometry of all exocyclic alkenes were inferred from
X-ray single-crystal analyses on the major component of
exocyclic double bond twists by more than 20° to alleviate
steric repulsion between the four substituents. Adducts
13 and 14 are all strained systems difficult to obtain by
other methods.
TCE gave higher ratios of isomers than maleic anhy-
dride, a result consistent with the endo approach of the
latter, exposing the smaller hydrogens to the substituents
on the allene (Figure 1, c ) d ) CN vs H). Less reactive
dienophiles, such as methyl acrylate (MAcr), methyl vinyl
ketone (MVK), and phenyl vinyl sulfone were slow to
react at room temperature, but heating the vinylallenes
for extended periods of time resulted in significant
decomposition (except for 8c). However, dimethylalumi-
num chloride catalyzed the cycloaddition with MAcr and
MVK (entries 5). It was evident that two regioisomers
11 and 12 had formed in these cycloadditions, in contrast
1
4b, 14c, and 14d .
Trisubstituted alkenes 9a and 10a were obtained with
high selectivity, in line with results published by Reich.3
Vinylallenes 5b and 8b bearing a methyl and a straight
n-alkyl chain reacted at room temperature in toluene in
5
days with tetracyanoethylene (TCE) or maleic anhy-
dride (MA) to give good yields of separable isomers
entries 2, 4 and 6, 9). Those gave moderate but accept-
(
1
1-13
able ratios of geometric isomers considering the small
steric difference between a methyl and a simple n-alkyl
chain. Vinylallenes 8c and 8d substituted with either a
trimethylsilyl or a branched alkyl chain gave high yields
and excellent ratios of geometric isomers (entries 7, 8 and
with what has been reported in simpler systems.
In
the case of MVK, we could identify the four isomers by
1
H NMR and they consisted of a 1:1 ratio of the two
regioisomers 11 and 12 each as the expected 3:1 mixture
of geometrical double bond isomers.
1
0, 11). The silyl-substituted allene required refluxing
Curiously, the reaction of vinylallene 5b with TCE
yielded the [2 + 2]-cycloadduct 15 along with the [4 +
2]-cycloadduct 10b. The structures of the two separable
isomers of 15 were ascertained by NMR spectroscopy and
toluene for complete reaction. Vinylsilanes can be trans-
formed into a host of vinylic functionalities and this route
may indirectly lead to a large number of exocyclic alkenyl
products in a highly stereoselective manner. We are
currently undertaking these transformations. The X-ray
analysis shows compound 14c to be highly strained and
its synthesis is noteworthy. In the crystal form, its
(
(
(
11) Bertrand, M.; Grimaldi, J .; Waegell, B. Bull. Soc. Fr. 1971, 962.
12) Yoshida, K.; Grieco, P. Chem. Lett. 1985, 155.
13) For a case of regioselectivity similar to ours see Santelli, M.;
El Abed, D.; J ellal, A. J . Org. Chem. 1986, 51, 1199.

Notes
J . Org. Chem., Vol. 63, No. 15, 1998 5285
mass spectrometry. We did not observe any [2 + 2]-cy-
magnesium sulfate, and filtered. Evaporation of the solvent in
vacuo was followed by a Kugelrohr distillation (0.1 Torr, 80 °C)
to yield 1-heptyn-3-ol (1.59 g, 44%) as a colorless oil. H NMR
cloadduct in the other reactions. Though the thermal [2
1
+
2]-cycloaddition of allenes is well-known, it is remark-
(
CDCl
3
): δ 4.36 (dt, 1H, J ) 6.6, 1.6 Hz), 2.45 (d, 1H, J ) 2.2
1
4
able that this one occurs at room temperature. Alter-
natively, this could be indicative of a biradical mechanism
in this case.
Hz), 1.95 (s, 1H), 1.76-1.68 (m, 2H), 1.49-1.29 (m, 4H), 0.91 (t,
-1
3
H, J ) 7.1 Hz). IR (neat, cm ): 3550-3070 (bw), 3303 (ms).
MS (m/ z, intensity): 111 (M-1, 5), 79 (60), 70 (50), 55 (100), 41
50). Exact mass calcd for C 11O: 111.0810. Found: 111.0808.
A round-bottomed flask was charged with dichloromethane
30 mL), 1-heptyn-3-ol (1.36 g, 12.4 mmol), and dimethoxymethane
6.5 mL, 73.5 mmol) under nitrogen. The solution was cooled
to 0 °C and was allowed to stir for 10 min. Then 100 mg of
(
7
H
(
(
P
1
2
O
5
was added while the reaction stirred vigorously. Every
0 min, 100 mg of P was added until the reaction was
2
O
5
completed, as monitored by TLC. The mixture was then
carefully added to 100 mL of an ice-cold saturated solution of
aqueous sodium bicarbonate and the gummy residue remaining
in the flask was also carefully washed with that same solution.
The aqueous layer was separated and extracted three times with
diethyl ether. The organic layers were combined then washed
with brine, dried over anhydrous magnesium sulfate, filtered,
and evaporated under reduced pressure to yield a yellow oil. The
oil was purified by Kugelrohr distillation (0.1 Torr, 90 °C) to
This preliminary study reveals the potential of the
intermolecular Diels-Alder reaction of vinylallenes to
selectively construct tetrasubstituted exocyclic double
bonds on six-membered rings. Highly strained molecules
can be prepared in this way. Further expansion and
applications of this methodology are in progress and will
be reported in due course.
yield 3-methoxymethoxy-1-heptyne (1.00 g, 53%) as a colorless
1
oil. H NMR (CDCl
)
1
3
): δ 4.94 (d, 1H, J ) 6.8 Hz), 4.59 (d, 1H, J
6.8 Hz), 4.31 (td, 1H, J ) 6.6, 2.0 Hz), 3.38 (s, 3H), 2.40 (d,
H, J ) 2.1 Hz), 1.79-1.71 (m, 2H), 1.51-1.30 (m, 4H), 0.92 (t,
3H, J ) 7.2 Hz). IR (neat, cm ): 3303 (ms), 1035 (s). MS (m/
z, intensity): 155 (M - 1, 1), 111 (10), 99 (100), 55 (20), 45 (100).
Exact mass calcd for C H O : 155.1072. Found: 155.1075.
Exp er im en ta l Section
-
1
Reactions were performed under a dry nitrogen atmosphere
with oven-dried glassware unless otherwise stated. Diethyl
ether, hexanes, and tetrahydrofuran were distilled over sodium-
benzophenone. Dichloromethane and triethylamine were dis-
tilled over calcium hydride. Flash chromatography was done
using Merck Kieselgel silica gel 60 (230-400 mesh A. S. T. M.)
Concentration of organic solutions implies evaporation on a
rotary evaporator followed by pumping under reduce pressure
9
15
2
3-Methoxymethoxy-1-heptyne (1.00 g, 6.4 mmol) was dissolved
in tetrahydrofuran (3 mL) and cooled to -78 °C. A solution of
n-butyllithium (3.2 mL, 2 M in pentane, 6.4 mmol) was then
added dropwise. The mixture was stirred for 0.5 h at -78 °C
and then crotonaldehyde (0.45 mL, 5.4 mmol) was slowly added.
The mixture was stirred for 1.5 h and quenched with saturated
aqueous ammonium chloride. The aqueous layer was separated
and extracted three times with diethyl ether. The organic layers
were combined, washed with water then with brine, dried over
anhydrous magnesium sulfate, and filtered. Evaporation of the
solvent in vacuo gave 4d (1.22 g, 100%) as a slightly yellow oil
(0.5 mmHg).
(
E)-3-Hyd r oxy-4-h exen -1-yn e (4a ). Crotonaldehyde (4.14
mL, 50 mmol) was added to a solution of ethynylmagnesium
bromide (100 mL, 50.0 mmol, 0.5 M/THF) at -78 °C. After 2 h
of stirring, the mixture was poured into a solution of saturated
ammonium chloride and extracted twice with diethyl ether. The
combined organic layers were washed with water and brine,
dried over magnesium sulfate, and concentrated. The crude
product 4a was obtained in 76% yield as a colorless oil. 1H NMR
1
3
used directly for the next reaction. H NMR (CDCl , 300 MHz):
δ 5.87 (dq, 1H, J ) 15.1, 7.0 Hz), 5.61 (bdd, 1H, J ) 15.1, 6.3
Hz), 4.93 (d, 1H, J ) 6.8 Hz), 4.85 (d, 1H, J ) 6.3 Hz), 4.58 (d,
1H, J ) 6.8 Hz), 4.37 (t, 1H, J ) 6.3 Hz), 3.37 (s, 3H), 1.8-1.7
(
4
1
CDCl
3
, 300 MHz): δ 1.73 (d, 3H, J ) 6.5 Hz), 2.12 (bd, 1H, J )
.8 Hz), 2.56 (d, 1H, J ) 1.6 Hz), 4.82 (m, 1H), 5.59-5.66 (dm,
(m, 3H), 1.72 (d, 3H, J ) 7.0 Hz), 1.50-1.30 (m, 4H), 0.92 (t,
3
H, J ) 15.5 Hz), 5.92 (dq, 1H, J ) 15.5, 6.5 Hz). IR (CHCl ,
3H, J ) 7.1 Hz). IR (neat, cm-1): 3550-3100 (mb), 1036 (s).
-
1
cm ): 3594-3306 (bs), 3017 (m). LRMS (m/z (relative inten-
sity)): 96 (M , 10), 81 (100), 67 (20), 53 (80). Exact mass calcd
MS (m/ z, intensity): 181 (M - C H O, 4), 164 (5), 122 (70), 107
2
5
+
(100), 95 (20), 79 (45). Exact mass calcd for C11
Found: 181.1233.
17 2
H O :181.1228.
for C
E)-4-Hyd r oxy-5-h ep ten -2-yn e (4b). Propyne (1.54 mL,
7.2 mmol) was condensed into a flask containing 10 mL of dry
6 8
H O: 96.0575. Found: 96.0578.
(
(2E)-2,4,5-Deca tr ien e (5a ). Acetic anhydride (30 mL, 312
mmol) was added to a mixture of alcohol 4a (15 g, 156 mmol),
4-(dimethylamino)pyridine (3.8 g, 31.2 mmol), and triethylamine
(43 mL, 312 mmol) in 10 mL of dry dichloromethane. The
reaction mixture was stirred for 5 h and was then poured into
diethyl ether. The solution was washed with solutions of 1 N
HCl and saturated sodium bicarbonate. Each separate aqueous
layer was extracted twice with diethyl ether. The combined
organic layers were washed with brine, dried over magnesium
sulfate, filtered, and concentrated. Purification by flash chro-
matography (10% ethyl acetate/hexanes) gave 11.0 g of a
2
THF at -78 °C, and 17 mL of n-butyllithium (23.6 mmol, 1.4
M/pentane) was added slowly. After 30 min of stirring, cro-
tonaldehyde (1.5 mL, 18.1 mmol) was added by syringe. The
yellow solution was quenched after 50 min at -78 °C with a
solution of saturated ammonium chloride. The aqueous phase
was extracted twice with diethyl ether. The combined organic
layers were washed with water and brine, dried over magnesium
sulfate, filtered, and concentrated to give 100% crude yield of
1
alcohol 4b. H NMR (CDCl
3
, 300 MHz): δ 1.70 (d, 3H, J ) 6.6
Hz), 1.85 (d, 3H, J ) 2.1 Hz), 1.98 (bd, 1H, J ) 4.3 Hz), 4.76 (m,
colorless oil (52%).
1
3
H NMR (CDCl , 300 MHz): δ 1.74 (d, 3H,
1
H), 5.59 (bdd, 1H, J ) 15.1, 6.2 Hz), 5.84 (dq, 1H, J ) 15.1, 6.6
J ) 6.6 Hz), 2.06 (s, 3H), 2.55 (d, 1H, J ) 2.2 Hz), 5.55 (dm, 1H,
-1
Hz). IR (CHCl , cm ): 3596-3436, 3018. LRMS (m/z (relative
3
J ) 15.6 Hz), 5.80 (bd, 1H, J ) 6.5 Hz), 6.01 (dq, 1H, J ) 15.6,
+
-1
intensity)): 110 (M , 10), 95 (100), 67 (50), 40 (50). Exact mass
calcd for C 10O: 110.0732. Found: 110.0736.
E)-7-Meth oxym eth oxy-2-u n d ecen -5-yn -4-ol (4d ). Valer-
6.6 Hz). IR (CHCl , cm ): 3307, 3027, 1736. LRMS (m/z
3
7
H
(relative intensity)): 123 ((M - CH3
(100). Exact mass calcd for C H O : 123.0446. Found: 123.0448.
+
), 10), 95 (25), 77 (80), 43
(
7
7
2
aldehyde (3.33 mL, 31.3 mmol) was slowly added to a solution
of ethynylmagnesium bromide (67 mL of 0.5M in THF, 33.5
mmol) at -78 °C. The mixture was stirred for 45 min at -78
A flask containing copper iodide (1.70 g, 9.0 mmol), lithium
iodide (1.20 g, 9.0 mmol), and 20 mL of dry tetrahydrofuran was
cooled to -30 °C. A solution of n-butyllithium (11.5 mL, 17.9
mmol, 1.55 M in hexanes) was slowly added. The solution was
left at -30 °C for 3 h. A solution of (E)-3-acetoxy-4-hexen-1-
yne (1.03 g, 7.5 mmol) in 5 mL of dry THF was added. The
mixture was stirred for 30 min at -30 °C and 1 h at 0 °C. The
solution was then poured into a solution of saturated ammonium
chloride. The aqueous layer was extracted three times with
pentane. The combined organic layers were washed with water
°
C and then quenched with saturated aqueous ammonium
chloride. The aqueous layer was separated then extracted three
times with diethyl ether. The organic layers were combined and
washed with water then with brine, dried over anhydrous
(14) Landor, S. R.; Hopf, H.; J acobs, T. L. The Chemistry of Allenes,
Reactions; Academic Press: London, 1982; Vol. 2.

5
286 J . Org. Chem., Vol. 63, No. 15, 1998
Notes
and brine, dried over magnesium sulfate, filtered, and concen-
trated. Purification by flash chromatography (1% ethyl acetate/
pentane) gave the allene 5a as a colorless oil (694 mg, 68%). H
4.0 Hz), 2.97 (ddt, 2H, J ) 15.5, 11.8, 2.6 Hz), 4.66 (s, 1H), 5.78
1
3
3
(m, 2H). C NMR (CDCl , 75 MHz): δ 14.1 (q), 18.3 (q), 19.2
1
(q), 22.5 (t), 25.6 (t), 27.1 (t), 31.6 (t), 2 × 31.8 (t), 34.2 (t), 48.0
NMR (CDCl
3
, 300 MHz): δ 0.9 (m, 3H), 1.20-1.40 (m, 4H), 1.74
(d), 104.3 (s), 105.3 (s), 125.0 (d), 126.4 (d), 202.7 (s). IR (CHCl ,
3
+
-
1
(
6
dd, 3H, J ) 6.6, 2.1 Hz), 1.95-2.05 (m, 2H), 5.37 (q, 1H, J )
cm ): 2928, 1794. LRMS (m/z (relative intensity)): 282 (M ,
1
3
.6 Hz), 5.60 (dq, 1H, J ) 14.1, 6.6 Hz), 5.7-5.9 (m, 2H).
C
7), 267 (10), 211 (50), 119 (100). Exact mass calcd for C16
282.1476. Found: 282.1482.
26 2
H S :
NMR (CDCl
3
, 75 MHz): δ 14.1 (q), 18.1 (q), 22.7 (t), 28.6 (t), 31.3
-
1
(t), 92.2 (d), 126.6 (d), 127.2 (d), 206.1 (s). IR (CHCl
3
, cm ):
Gen er a l P r oced u r e for th e Cycloa d d ition of Vin yla l-
len es. To a round-bottomed flask under nitrogen were added
the allene, the dienophile, and dry toluene. The mixture was
stirred for several hours or days at room temperature or reflux.
The solvent was then evaporated and purified as stated.
Cycloa d d u ct 9a . Allene 5a (84.9 mg, 0.62 mmol) and maleic
anhydride (61.1 mg, 0.62 mmol) in 1.5 mL of dry toluene for 7
days at room temperature as described in the general procedure
+
2
1
960, 2931, 1698. LRMS (m/z (relative intensity)): 136 (M , 4),
27 (10), 108 (50), 94 (90), 79 (100). Exact mass calcd for
C
10
H
16: 136.1252. Found: 136.1247.
(
E)-5-Hep ten -2-yn -4-on e (6b). The alcohol 4b (500 mg, 4.5
mmol) was dissolved in 45 mL of dry dichloromethane. The
mixture was cooled to 0 °C, and molecular sieves (1 g) were
added. After 5 min of stirring, pyridinium chlorochromate (1.47
g, 6.81 mmol) was added portionwise and the mixture was
stirred overnight. Activated charcoal was added and filtered
through Celite. Celite was added to the filtrate and stirred for
1
gave 139 mg of crude cycloaddition products 9a (96%). H NMR
(CDCl , 300 MHz): δ 0.89 (t, 3H, J ) 7.3 Hz), 1.26 (d, 3H, J )
3
7.7 Hz), 1.22-1.44 (m, 4H), 2.19 (q, 2H, J ) 7.3 Hz), 2.72 (m,
1H), 3.37 (dd, 1H, J ) 17.9, 9.0 Hz), 3.84 (d, 1H, J ) 9.0), 5.77-
5
min. The mixture was filtered over a pad of silica, activated
1
3
charcoal, and Celite, yielding 384 mg (79%) of a colorless oil (6b).
5.85 (m, 2H), 6.44 (d, 1H, J ) 9.3 Hz).
3
C NMR (CDCl , 75
1
H NMR (CDCl
3
, 300 MHz): δ 1.95 (d, 3H, J ) 6.5 Hz), 2.03 (s,
MHz): δ 13.9 (q), 17.4 (q), 22.2 (t), 27.4 (t), 28.7 (d), 31.3 (t), 45.0
(d), 45.2 (d), 65.8 (s), 122.2 (s), 123.6 (d), 132.1 (d), 134.2 (d),
171.6 (s). IR (CHCl , cm ): 3030, 2959, 1852, 1782. LRMS
3
(m/z (relative intensity)): 234 (M , 10), 206 (15), 161 (20), 119
3
H), 6.13 (dd, 1H, J ) 15.0, 2.7 Hz), 7.16 (dq, 1H, J ) 15.0, 6.5
-
1
-1
Hz). IR (CHCl
3
, cm ): 3018, 1646, 1623. LRMS (m/z (relative
+
+
intensity)): 110 (M , 12), 95 (100), 67 (50), 40 (50). Exact mass
calcd for C 10O: 110.0732. Found: 110.0736.
E)-4-Acetoxy-4-(1,3-dith ian -2-yl)-5-h epten -2-yn e (7b). 1,3-
7
H
(30), 105 (100), 91 (90). Exact mass calcd for C14
Found: 234.1261.
18 3
H O : 234.1256.
(
Dithiane (642 mg, 5.3 mmol) was dissolved in 25 mL of THF
and this solution was cooled to -40 °C. A solution of n-
butyllithium (2.8 mL, 5.6 mmol, 2 M/pentane) was added slowly.
The mixture was stirred for 2 h at -40 °C and was allowed to
reach -20 °C. The mixture was immediately cooled back to -78
Cycloa d d u ct 10b a n d 15. Allene 5b (100 mg, 0.67 mmol)
and tetracyanoethylene (85 mg, 0.67 mmol) in 1.5 mL of dry
toluene for 5 days at room temperature as described in the
general procedure gave after flash chromatography (7% ethyl
acetate/hexanes) 58 mg of [4 + 2]-cycloaddition products 10b
(25%) and 70 mg of [2+ 2]-cycloaddition products 15 (30%).
°
C and the ketone 6b (550 mg, 5.1 mmol) in 5 mL of THF was
-
1
added. The reaction was stirred overnight at -60 °C. The
mixture was poured into water and was extracted three times
with chloroform. The combined organic layers were washed
twice with water, once with a solution of 7% potassium hydrox-
ide, once with water, dried over anhydrous magnesium sulfate,
filtered, and concentrated. The residue was purified by flash
Cycloadducts 10b: IR (CHCl
1379. LRMS (m/z (relative intensity)): 278 (M , 70), 222 (100),
18 4
195 (50), 182 (75), 167 (45). Exact mass calcd for C17H N :
3
, cm ): 2932, 2338, 1601, 1461,
+
1
3
278.1531. Found: 278.1523. Ma jor : H NMR (CDCl , 300
MHz): δ 0.94 (t, 3H, J ) 7.2 Hz), 1.32-1.52 (m, 4H), 1.61 (d,
3H, J ) 7.6 Hz), 2.29 (s, 3H), 2.29-2.41 (m, 2H), 3.21 (q, 1H, J
chromatography (7% ethyl acetate/hexanes) to give 7b (884 mg,
) 7.0 Hz), 5.54 (dd, 1H, J ) 10.4, 1.5 Hz), 6.62 (dd, 1H, J )
1
13
7
1
(
6%). H NMR (CDCl
3
, 300 MHz): δ 1.76 (d, 3H, J ) 6.6 Hz),
3
10.4, 2.6 Hz). C NMR (CDCl , 75 MHz): δ 13.8 (q), 17.5 (q),
.92 (s, 3H), 1.96-2.08 (m, 2H), 2.69-2.79 (m, 2H), 3.06-3.17
22.2 (q), 22.5 (t), 30.2 (t), 35.9 (t) and (d), 42.1 (s), 48.5 (s), 109.4
(s), 109.7 (s), 109.9 (s), 111.2 (s), 115.7 (s), 123.9 (d), 124.6 (d),
m, 3H), 3.95 (s, 1H), 5.63 (bd, 1H, J ) 16.0 Hz), 6.15 (dq, 1H,
-
1
150.5 (s). Min or : 1H NMR (CDCl
J ) 15.6, 6.6 Hz). IR (CHCl
3
, cm ): 3582-3482, 3018. LRMS
3
, 300 MHz): δ 0.98 (t, 3H, J
+
(
m/z (relative intensity)): 228 (M , 5), 154 (7), 119 (110), 91 (75).
) 7.0 Hz), 1.40-1.70 (m, 4H), 1.61 (d, 3H, J ) 6.7 Hz), 2.02 (s,
3H), 2.38-2.50 (m, 1H), 2.65-2.77 (m, 1H), 3.15-3.27 (m, 1H),
5.55 (dd, 1H, J ) 10.0, 1.5 Hz), 6.61 (dd, 1H, J ) 10.0, 2.3 Hz).
2
Exact mass calcd for C11H16OS : 228.0643. Found: 228.0641.
Acetic anhydride (80 mL, 0.848 mmol) was added to a mixture
of alcohol (97 mg, 0.424 mmol), 4-(dimethylamino)pyridine (10
mg, 0.0848 mmol), and triethylamine (120 mL, 0.848 mmol) in
1
3
3
C NMR (CDCl , 75 MHz): δ 13.7 (q), 17.4 (q), 20.2 (q), 22.9 (t),
29.1 (t), 36.0 (d), 36.6 (t), 66.0 (s), 78 (s), 109.5 (s), 110.0 (s),
111.2 (s), 111.7 (s), 115.2 (s), 124.4 (d), 124.7 (d), 150.5 (s).
3
50 mL of dry dichloromethane. The reaction mixture was
-
1
stirred for 5 h and was then poured into diethyl ether. The
solution was washed with solutions of 1 N HCl and saturated
sodium bicarbonate. The separate aqueous layers were ex-
tracted twice with diethyl ether. The combined organic layers
were washed with brine, dried over magnesium sulfate, filtered,
3
Cycloadducts 15: IR (CHCl , cm ): 3029, 2959, 2300, 1698,
+
1664, 1467, 1381. LRMS (m/z (relative intensity)): 278 (M , 5),
263 (10), 222 (100), 195 (45), 157 (80), 93 (90). Exact mass calcd
1
for C17
(CDCl
H
3
18
N
4
: 278.1531. Found: 278.1526. Ma jor : H NMR
, 300 MHz): δ 0.91 (t, 3H, J ) 6.7 Hz), 1.20-1.50 (m, 4H),
1
and concentrated to yield 72% (124 mg) of crude product 7b. H
1.86 (d, 3H, J ) 6.6 Hz), 1.95 (d, 3H, J ) 2.3 Hz), 2.03 (t, 2H, J
) 6.6 Hz), 4.39 (d, 1H, J ) 8.5 Hz), 5.58-5.69 (m, 1H), 6.01 (dq,
NMR (CDCl
3
, 300 MHz): δ 1.77 (d, 3H, J ) 6.6 Hz), 1.80-1.93
1
3
(
2
1
m, 1H), 1.95 (s, 3H), 2.00-2.10 (m, 1H), 2.05 (s, 3H), 2.77-
3
1H, J ) 15.0, 6.6 Hz). C NMR (CDCl , 75 MHz): δ 13.8 (q),
.95 (m, 4H), 4.86 (s, 1H), 5.77 (bd, 1H, J ) 15.5 Hz), 6.22 (dq,
17.0 (q), 18.0 (q), 22.4 (t), 29.2 (t), 32.7 (t), 39.0 (s), 40.3 (s), 55.5
(d), 108.8 (s), 109.2 (s), 109.3 (s), 110.7 (s), 116.1 (s), 123.3 (d),
-
1
3
H, J ) 15.5, 6.6 Hz). IR (CHCl , cm ): 2982, 1739. LRMS
+
135.3 (d), 149.2 (s). Min or : 1H NMR (CDCl
(m/z (relative intensity)): 270 (M , 2), 255 (5), 210 (75), 167 (50),
3
, 300 MHz): δ 0.97
1
2
19 (100). Exact mass calcd for C13
70.0756.
H
18
O
2
S
2
: 270.0748. Found:
(t, 3H, J ) 6.7 Hz), 1.35-1.60 (m, 4H), 1.72 (s, 3H), 1.88 (d, 3H,
J ) 6.7 Hz), 2.27 (t, 2H, J ) 6.7 Hz), 4.39 (d, 1H, J ) 6.8 Hz),
1
3
(
E)-4-(1,3-Dith ia n -2-yl)-6-m eth yl-2,4,5-u n d eca tr ien e (8b).
5.60-5.70 (m, 1H), 6.01 (dq, 1H, J ) 15.0, 6.7 Hz). C NMR
To a well-stirred mixture of lithium bromide (1.08 g, 12.4 mmol)
and copper iodide (2.36 g, 12.4 mmol) in 25 mL of dry THF at 0
3
(CDCl , 75 MHz): δ 13.7 (q), 17.4 (q), 20.2 (q), 22.9 (t), 29.1 (t),
36.0 (d), 36.6 (t), 66.0 (s), 78 (s), 109.5 (s), 110.0 (s), 111.2 (s),
111.7 (s), 115.2 (s), 124.4 (d), 124.7 (d), 150.5 (s).
°C was added a solution of n-pentylmagnesium bromide (6.2 mL,
1
2.4 mmol, 2 M in diethyl ether) and the solution was stirred
Cycloa d d u ct 11 a n d 12. To a 10 mL flask under nitrogen
were added allene 5b (86.6 mg, 0.58 mmol), methyl vinyl ketone
(91µL, 1.10 mmol), a solution of dimethylaluminum chloride (219
µL, 0.22 mmol, 1 M/diethyl ether), and 3 mL of dry dichlo-
romethane. The mixture was stirred overnight at room tem-
perature. The mixture was poured in saturated sodium bicar-
bonate and was extracted three times with diethyl ether. The
combined organic layers were washed with water, dried over
anhydrous magnesium sulfate, filtered, and concentrated. Pu-
rification by flash chromatography (eluted with 10% ethyl
acetate: 90% hexanes) gives an oily mixture of 11 and 12 (41.9
for 30 min. The propargylic substrate 7b (558 mg, 2.1 mmol)
in 5 mL of THF was added via syringe. After 2 h the reaction
mixture was poured into a solution of saturated ammonium
chloride. The aqueous layer was extracted twice with diethyl
ether. The combined organic layers were dried over magnesium
sulfate, filtered, and concentrated. Purification by flash chro-
matography (5% ethyl acetate/hexanes) gave 72% (418 mg) of
8
1
b as colorless oil. H NMR (CDCl
3
, 300 MHz): δ 0.88 (t, 3H,
J ) 6.7 Hz), 1.25-1.33 (m, 4H), 1.46 (m, 2H), 1.76 (s, 3H), 1.77
(d, 3H, J ) 5.5 Hz), 1.80-2.15 (m, 4H), 2.84 (dt, 2H, J ) 15.5,

Notes
J . Org. Chem., Vol. 63, No. 15, 1998 5287
mg, 28% yield). Cycloadducts 11: IR (CHCl
3
, cm-1): 3022, 2960,
(m, 5H), 1.93 (s, 3H), 2.80-2.97 (m, 4H), 3.15 (m, 1H), 3.32 (m,
1H), 4.39 (s, 1H), 6.12 (d, 1H, J ) 4.1 Hz). 13C NMR (CDCl
, 75
1
706, 1461, 1358, 1224. LRMS (m/z (relative intensity)): 220
3
+
(
M , 5), 205 (1), 177 (5), 135 (5), 119 (10), 85 (40), 43 (100). Exact
mass calcd for C15
24O: 220.1827. Found: 220.1824. 1H NMR
CDCl , 300 MHz): δ 0.85 (d, 3H, J ) 6.8 Hz), 0.90 (t, 3H, J )
.0 Hz), 1.25-1.40 (m, 6H), 1.75 (s, 3H), 2.13 (d, 2H, J ) 7.6
Hz), 2.30 (m, 1H), 2.51 (dd, 1H, J ) 3.4, 15.8 Hz), 2.72-2.81 (m,
MHz): δ 14.0 (q), 16.1 (q), 18.5 (q), 22.4 (t), 25.0 (t), 28.2 (t),
30.9 (d), 31.4 (t), 32.4 (t), 32.8 (t), 36.8 (t), 46.2 (d), 47.4 (d), 50.0
(d), 122.7 (s), 123.3 (s), 136.6 (d), 140.2 (s), 168.9 (s), 171.4 (s).
H
(
7
3
1
3
Min or : H NMR (CDCl , 300 MHz): δ same as major except,
-1
1
1
2
3
.90 (s, 3H), 6.15 (d, 1H, J ) 4.1 Hz). IR (CHCl , cm ): 2929,
2
H), 5.68 (dd, 1H, J ) 5.0, 10.0 Hz), 6.40 (d, 1H, J ) 10.0 Hz).
+
779. LRMS (m/z (relative intensity)): 380 (M , 75), 309 (30),
73 (30), 41 (100). Exact mass calcd for C20 : 380.1480.
1
3
3
C NMR (CDCl , 75 MHz): δ 14.0 (q), 15.3 (q), 18.8 (q), 22.5 (t),
28 3 2
H O S
2
1
2.7 (t), 28.5 (q), 30.9 (t), 31.1 (d), 33.5 (t), 51.2 (d), 124.5 (d),
Found: 380.1475.
26.2 (s), 130.2 (d), 133.1 (s), 210.8 (s). Cycloadducts 12: IR
-1
(
(
9
CHCl
relative intensity)): 220 (M , 7), 177 (20), 163 (20), 121 (30),
3 (60), 43 (100). Exact mass calcd for C15 24O: 220.1827.
, 300 MHz): δ 0.88
3
, cm ): 3022, 2930, 1693, 1461, 1355, 1223. LRMS (m/z
+
Ack n ow led gm en t. We acknowledge the financial
support of the Natural Sciences and Engineering Re-
search Council of Canada and the Universit e´ de Sher-
brooke. We are grateful to Marc Drouin for the X-ray
structures.
H
1
Found: 220.1830. Min or : H NMR (CDCl
3
(
1
3
t, 3H, J ) 7.0 Hz), 0.97(d, 3H, J ) 7.3 Hz), 1.20-1.40 (m, 4H),
.82 (s, 3H), 1.85-2.05 (m, 4H), 2.15 (s, 3H), 2.22-2.35 (m, 1H),
.49 (t, 1H, J ) 6.0 Hz), 5.65 (dd, 1H, J ) 10.0, 4.0 Hz), 6.48
1
(
dd, 1H, J ) 10.0, 2.0 Hz). Ma jor : H NMR (CDCl
3
, 300 MHz):
δ 0.92 (t, 3H, J ) 7.0 Hz), 0.98 (d, 3H, J ) 7.2 Hz), 1.23-1.46
Su p p or tin g In for m a tion Ava ila ble: Proton NMR spectra
for all compounds, and X-ray determinations of 14b-d (ORTEP
and tables of data), and experimental and characterization
data for compounds 4c, 5b, 6c,d , 7c,d , 8c,d , 9b, 10a , 13c,d ,
14b-d (68 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
(
(
1
m, 4H), 1.61 (s, 3H), 1.72-1.80 (m, 1H), 1.95-2.02 (m, 1H), 2.11
s, 3H), 2.15-2.31 (m, 3H), 3.41 (t, 1H, J ) 6.8 Hz), 5.63 (dd,
H, J ) 3.6, 10.2 Hz), 6.50 (dd, 1H, J ) 2.2, 10.2 Hz).
Cycloa d d u ct 13b. Allene 8b (69.6 mg, 0.25 mmol) and
maleic anhydride (24.2 mg, 0.25 mmol) in 1 mL of dry toluene
for 5 days at room temperature as described in the general
procedure gave 93.0 mg of crude cycloaddition product 13b
1
(
6
99%). Ma jor : H NMR (CDCl
3
, 300 MHz): δ 0.87 (t, 3H, J )
.3 Hz), 1.20-1.35 (m, 6H), 1.44 (d, 3H, J ) 7.5 Hz), 1.7-2.3
J O980482L