In situ manganese dioxide alcohol oxidation-Wittig reactions: Preparation of bifunctional dienyl building blocks

Full text of DOI:10.1021/jo9913558

6
16
J . Org. Chem. 2000, 65, 616-620
In Situ Ma n ga n ese Dioxid e Alcoh ol
Sch em e 1
Oxid a tion -Wittig Rea ction s: P r ep a r a tion
of Bifu n ction a l Dien yl Bu ild in g Block s
Xudong Wei* and Richard J . K. Taylor*
enoate 4, prepared in this way, has been employed as a
precursor to the lower side of the chain of the manumycin
antibiotics.6
Department of Chemistry, University of York,
Heslington, York YO10 5DD, U.K.
Received August 25, 1999
The original investigation illustrated in Scheme 1 was
carried out on an isomeric mixture of bromopropenols 3
There is continuing interest in the preparation of
7
(E: Z ) 3:1). Herein we describe the extension of this
functionalized building blocks for the stereocontrolled
methodology to isomerically pure 3-bromopropenols 3E
and 3Z, illustrate that the bromopropenol geometry is
retained, explore the range of Wittig reagents that can
be utilized in this procedure, and apply the methodology
in natural product synthesis. Scheme 2 illustrates the
procedures used to prepare 3E and 3Z and their further
elaboration.
1
,2
preparation of alkenes and dienes. In principle, the
-halopropenals 1 and 2 would seem to be ideal bifunc-
3
tional precursors to alkenes and dienes via aldehyde
elaboration/cross coupling. However, numerous reports3
in the literature refer to the difficulties encountered in
the isolation of 3-chloro- and 3-bromopropenal, their
rapid decomposition at room temperature, their sensitiv-
ity to light, and the fact that they have a severe irritant
effect on the mucous membranes of the eyes and nose.
These problems have undoubtedly limited the applica-
tions of halopropenals in synthesis. It should be noted,
however, that Meyer, Marek, and Normant have devel-
oped conditions for the preparation of 2E- and 2Z-
iodopropenal and demonstrated that these compounds
are more stable than the corresponding chlorides or
bromides (they can be stored in solution in the refrigera-
Thus, ethyl propiolate 5a was readily converted into
8
a
the Z-bromoacrylate 6, and propriolic acid 5b into
E-bromoacylate 7,8b using published stereoselective pro-
cedures (Scheme 2). Reduction with lithium aluminum
9
hydride then gave the requisite 3-bromopropenols 3Z
and 3E in good overall yield as pure stereoisomers. These
compounds were then subjected to the in situ alcohol
oxidation-Wittig conditions using (carboethoxymeth-
ylene)triphenylphosphorane. As shown in Scheme 2 and
Table 1, in both cases the bromodienoates 4 were
obtained in good yield and with complete retention of the
preexisting alkene geometry.
tor for several weeks), although they retain lachrymatory
properties.4
A range of related stabilized Wittig reagents were also
explored (Table 1). In all cases the products were
obtained with faithful retention of the original alkenyl
geometry but as isomers about the newly formed double
bonds. These E: Z ratios were generally in the expected
ranges with the E-isomers predominating. A notable
exception involved the reaction of 3Z with (cyanometh-
ylene)triphenylphosphorane; in this reaction the Z ,Z-
product 13Z,Z predominated (13Z,Z:13E,Z was ca.5:2).
Reaction of 3E with (cyanomethylene)triphenylphos-
phorane, however, gave a mixture of 13E,E and 13Z,E
in which the E,E-isomer predominated as expected.
Further studies are proceeding to rationalize the former
result and to apply the unexpected observation.
We have recently described an in situ manganese
dioxide alcohol oxidation-Wittig procedure and demon-
strated its utility for the elaboration of 3-bromopropen-
-ol 3 as shown in Scheme 1. This procedure avoids the
need to isolate the intermediate bromopropenals 1 and
and produces the bromodienoate 4 directly. Bromodi-
5
1
2
(
1) For recent references in this area, see: Castet-Caillabet, D.;
Ramondenc, Y.; Pl e´ , G.; Duhamel, L. Tetrahedron 1999, 55, 7583-
588. Crousse, B.; Mladenova, M.; Ducept, P.; Alami, M.; Linstrumelle,
7
G. Tetrahedron 1999, 55, 4353-4368. Brasseur, D.; Rezaei, H.; Fuxa,
A.; Alexakis, A.; Mangeney, P.; Marek, I.; Normant, J .-F. Tetrahedron
Lett. 1998, 39, 4821-4824. Raeppel, S.; Toussaint, D.; Suffert, J .
Synlett 1998, 537-539. Takacs, J . M.; J aber, M. R.; Clement, F.;
Walters, C. J . Org. Chem. 1998, 63, 6757-6760. Wang, Z.; Lu, X.; Lei,
A.; Zhang, Z. J . Org. Chem. 1998, 63, 3806-3807. Lipshutz, B. H.;
Ullman, B.; Lindsley, C.; Pecchi, S.; Buzard, D. J .; Dickson, D. J . Org.
Chem. 1998, 63, 6092-6093. Lipshutz, B. H.; Lindsley, C. J . Am. Chem.
Soc. 1997, 119, 4555-4556.
The utility of the products from the in situ alcohol
oxidation-Wittig sequence has been illustrated by the
synthesis of a simple natural product10 and its stereo-
isomer (Scheme 3). Adduct 11E,E was reduced with
(6) Alcaraz, L.; Macdonald, G.; Ragot, J .; Lewis, N. J .; Taylor, R. J .
K. Tetrahedron 1999, 55, 3707-3716. See also: Macdonald, G.; Alcaraz,
L.; Wei, X.; Lewis, N. J .; Taylor, R. J . K. Tetrahedron 1998, 54, 9823-
9836.
(7) J ung, M. E.; Light, L. A. Tetrahedron Lett. 1982, 23, 3851-3854.
Delorme, D.; Girard, Y.; Rokach, J . J . Org. Chem. 1989, 54, 3635-
3640.
(8) (a) Ma, S.; Lu, X. Chem. Commun. 1990, 1643-1644; Org. Synth.
1993, 72, 112-115. (b) J ust, G.; Ouellet, R. Can. J . Chem. 1976, 54,
2925-2934.
(9) MacInnes, I.; Schorstein, D. E.; Suckling; C. J .; Wrigglesworth,
R. J . Chem. Soc., Perkin Trans. 1 1981, 1103-1108.
(10) Bohlmann, F.; Kleine, K.-M.; Arndt, C. Chem. Ber. 1966, 99,
1642-1647.
(11) For a recent review, see: Sonogashira, K. In Metal-catalyzed
Cross-coupling Reactions; Diederich, F., Stang, P. J ., Eds.; Wiley-
VCH: Berlin, 1998; pp 203-229.
(2) For recent reviews on two directional synthesis/bifunctional
reagents, see: Ross, C. S.; Schreiber, S. L. Acc. Chem. Res. 1994, 27,
9
-17. Magnusson, S. R. Tetrahedron 1995, 51, 2167-2213.
3) Protopopova, T. V.; Skoldinov, A. P. Zh. Obshch. Khim. 1958,
9, 945-948. Patel, B. A.; Kim, J .-I.; Bender, D. D.; Kao, L.-C.; Heck,
(
2
R. F. J . Org. Chem. 1981, 46, 1061-1067. Meyers, A. I.; Babiak, K.
A.; Campbell, A. L.; Comins, D. L.; Fleming, M. P.; Henning, R.;
Heuschmann, M.; Hudspeth, J . P.; Kane, J . M.; Reider, P. J .; Roland,
D. M.; Shimizu, K.; Tomioka, K.; Walkup, R. D. J . Am. Chem. Soc.
1
1
983, 105, 5015-5024. Grabowski, E. J . J .; Autrey, R. L. Tetrahedron
969, 25, 4315-4330.
(4) Meyer, C.; Marek, I.; Normant, J .-F. Synlett 1993, 386-388. See
also: Raeppel, S.; Toussaint, D.; Suffert, J . Synlett 1998, 537-539.
5) Wei, X.; Taylor, R. J . K. Tetrahedron Lett. 1998, 39, 3815-3818.
See also: Blackburn, L.; Wei, X.; Taylor, R. J . K. Chem. Commun. 1999,
337-1338.
(
1
1
0.1021/jo9913558 CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/31/1999

Notes
J . Org. Chem., Vol. 65, No. 2, 2000 617
Sch em e 2
Sch em e 3
sodium borohydride to give bromodienol 15E,E, which
ICN silica gel (32-63) or Matrex silica gel 60 (70-200) using
the eluant specified. Petroleum ether is the fraction with bp 40-
60 °C and was redistilled before use. Diethyl ether was distilled
from sodium-benzophenone ketyl immediately before use.
Water is distilled water. Except where specified, all reagents
were purchased from commercial sources and were used without
further purification.
1
1
underwent efficient Sonogashira coupling with 2-eth-
ynylthiophene12 to complete the first reported synthesis
of 9-(2-thienyl)-nona-4E,6E-dien-8-yn-3-ol (16), isolated
from the roots of Anthemis saguramica Sosn. The same
sequence was followed using the isomeric dienone 11E,Z
to give the natural product isomer 17 in high yield.
It should also be noted that the bromodienoates 4E,E
and 4E,Z have been employed as key intermediates in
the total syntheses of AF- and AK-toxins by Crombie et
al.,13 with Stille coupling being employed to elaborate the
vinyl bromide unit.
3-Br om o-2Z-p r op en ol (3Z). A solution of ethyl 3-bromo-2Z-
propenoate 68a (2.69 g, 15 mmol) in dry diethyl ether (8 mL)
was added dropwise to a stirred mixture of LiAlH
mmol) in dry diethyl ether (30 mL) under a N atmosphere at 0
C. The mixture was stirred at 0 °C for 1 h and then quenched
4
(380 mg, 10
2
°
at 0 °C by addition of water (0.4 mL), 15% NaOH (0.4 mL), and
more water (1.2 mL), followed by filtration. The mixture was
diluted with diethyl ether (50 mL), washed with saturated
NaHCO (15 mL), and dried over Na SO . Evaporation of the
3 2 4
solvent in vacuo gave the title compound 3Z (1.76 g, 86%), which
In summary, we have utilized bromopropenols 3E and
3
Z in the in situ oxidation-stabilized Wittig sequence
and demonstrated that the reactions proceed easily and
efficiently, obviating the need to isolate the intermediate
aldehydes. We have also shown that the preexisting
alkene geometry is retained and that this procedure
therefore produces a range of bifunctional diene building
blocks that have potential in natural product synthesis.
was used directly in the next step without any further purifica-
tion: colorless oil, R
H NMR (270 MHz, CDCl ) δ 1.70 (s, 1H), 4.32 (dd, J ) 5.8, 1.4,
f
0.31 (1:1 petroleum ether-diethyl ether);
1
3
13
2
H), 6.28 (dt, J ) 7.3, 1.4, 1H), 6.37 (dt, J ) 7.3, 5.8, 1H);
C
NMR (67.9 MHz, CDCl
3
) δ 60.8, 108.8, 133.9; IR (film) νmax 3340
-
1
+
cm ; MS (EI) m/z 137, 135 (M - 1); HRMS (EI) m/z 134.9448
7
9
(calcd for C
3 4
H BrO 134.9446, 1.9 ppm error).
3
-Br om o-2E-p r op en ol (3E). A solution of 3-bromo-2E-pro-
Exp er im en ta l Section
8
b
penoic acid 7 (1.51 g, 10 mmol) in dry diethyl ether (8 mL)
was added dropwise to a stirred mixture of LiAlH (380 mg, 10
mmol) in dry diethyl ether (30 mL) under a N atmosphere at 0
°C. The mixture was stirred at 0 °C for 2 h and then quenched
at 0 °C by addition of water (0.4 mL), 15% NaOH (0.4 mL), and
more water (1.2 mL), followed by filtration. Workup as above
gave the title compound 3E (952 mg, 70%), which was used
Gen er a l Dir ection s. Elemental analyses were carried out
at the University of Newcastle. Chromatography is medium-
pressure flash column chromatography and was performed using
4
2
(
12) Beny, J .-P.; Dhawan, S. N.; Kagan, J .; Sundlass, S. J . Org.
Chem. 1982, 47, 2201-2204.
13) Crombie, L.; Horsham, M. A.; J arrett, S. R. M. J . Chem. Soc.,
Perkin Trans. 1 1991, 1511-1524.
(
directly in the next step without any further purification:
colorless oil, R
1
f
0.31 (1:1 petroleum ether-diethyl ether);
H

6
18 J . Org. Chem., Vol. 65, No. 2, 2000
Ta ble 1. In Situ Oxid a tion -Wittig Rea ction of 3-Br om o-2E- a n d -2Z-p r op en ol (3E a n d 3Z)
Notes
a
A mixture of byproducts, which probably contained 9Z,Z, was isolated. b TLC analysis indicated the presence of trace amounts of
what is believed to be the isomeric compounds 11Z,Z and 11E,E, but they were too volatile to be isolated.

Notes
J . Org. Chem., Vol. 65, No. 2, 2000 619
NMR (270 MHz, CDCl
3
) δ 1.80 (s, 1H), 4.11-4.14 (m, 2H), 6.35-
) δ 62.9, 107.8, 136.5;
3 3
CDCl ) δ 2.27 (s, 3H, CH ), 6.23 (dt, J ) 11.5, 1.0, 1H, H-3),
1
3
6
.39 (m, 2H); C NMR (67.9 MHz, CDCl
3
6.62 (dt, J ) 7.3, 1.0, 1H, H-6), 6.78 (ddd, J ) 11.5, 10.8, 1.0,
-
1
+
13
IR (film) νmax 3352 cm ; MS (EI) m/z 137, 135 (M - 1); HRMS
1H, H-4), 7.97 (ddd, J ) 10.8, 7.3, 1.0, 1H, H-5); C NMR (67.9
7
9
(EI) m/z 134.9449 (calcd for C
3
H
4
BrO 134.9446, 2.4 ppm error).
MHz, CDCl
3
) δ 32.2, 118.8, 127.9, 129.5, 136.3, 199.4; IR (film)
-
1
+
Syn th esis of Br om od ien es by in Situ Oxid a tion -Wittig
Rea ction s. Gen er a l P r oced u r e. A mixture of 3-bromo-2-
propenol 3E or 3Z (41 mg, 0.3 mmol), Wittig reagent (0.36 mmol,
ν
max 1685 cm ; MS (EI) m/z 176, 174 (M ); HRMS (EI) m/z
7
9
173.9688 (calcd for C
6
H
7
BrO 173.9680, 4.5 ppm error).
7-Br om oh epta-4E,6Z-dien -3-on e (11E,Z): colorless oil (63%),
1
1
.2 equiv) and manganese dioxide (261 mg, 10 equiv) in dry
R 0.42 (1:1 petroleum ether-diethyl ether); H NMR (270 MHz,
f
dichloromethane (9 mL) was stirred for 1-2 days and monitored
by TLC (1:1 diethyl ether-petroleum ether) until the starting
material was no longer detectable. The manganese dioxide was
removed by suction through a pad of Celite, which was then
washed with additional dichloromethane (10 mL). The solution
was concentrated to about 1 mL and loaded to a silica gel
column. Elution with diethyl ether-petroleum ether gave the
pure product. The reactions of 3E and 3Z with (carboethoxy-
methylene)triphenylphosphorane have also been carried out on
a 300 mg scale in comparable yield.
CDCl ) δ 1.14 (t, J ) 7.3, 3H, CH ), 2.66 (q, J ) 7.3, 2H, CH ),
3
3
2
6.33 (dt, J ) 15.8, 0.7, 1H, H-4), 6.62 (dt, J ) 7.3, 0.7, 1H, H-7),
6.78 (ddd, J ) 10.5, 7.3, 0.7, 1H, H-6), 7.46 (ddd, J ) 15.8, 10.5,
0.7, 1H, H-5); 13C NMR (67.9 MHz, CDCl ) δ 8.1, 33.6, 117.1,
3
-
1
131.2, 132.8, 136.4, 201.0; IR (film) ν
max
1691 cm ; MS (EI) m/z
+
79
190, 188 (M ); HRMS (EI) m/z 187.9841 (calcd for C H BrO
7
9
187.9837, 2.3 ppm error).
-P h en yl-5-br om op en ta -2E,4Z-d ien -2-on e (12E,Z): white
solid, mp 69-70 °C (60%), R 0.38 (1:1 petroleum ether-diethyl
ether); H NMR (270 MHz, CDCl ) δ 6.69 (dt, J ) 7.3, 0.8, 1H,
1
f
1
3
(
a ) F r om 3-Br om o-2Z-p r op en ol. Eth yl 5-br om op en ta -
E,4Z-d ien oa te (4E,Z): colorless oil (68%), R 0.60 (2:1 petro-
leum ether-diethyl ether); H NMR (270 MHz, CDCl ) δ 1.32
), 6.08 (dt, J )
5.5, 0.7, 1H, H-2), 6.59 (dt, J ) 7.3, 0.7, 1H, H-5), 6.78 (ddd, J
H-5), 6.92 (ddd, J ) 10.8, 7.3, 0.8, 1H, H-4), 7.15 (dt, J ) 15.4,
2
f
0
0
.8, 1H, H-2), 7.45-7.63 (m, 3H, ArH), 7.72 (ddd, J ) 15.4, 10.8,
1
13
3
.8, 1H, H-3), 7.92-8.00 (m, 2H, ArH); C NMR (67.9 MHz,
(
1
t, J ) 7.0, 3H, CH
3
), 4.24 (q, J ) 7.0, 2H, CH
2
3
CDCl ) δ 117.9, 128.5, 128.7, 128.8, 131.3, 133.0, 137.7, 138.8,
1
HRMS (CI) m/z (MNH
-1
+
90.8; IR (solid film) νmax 1656 cm ; MS (EI) m/z 238, 236 (M );
79
)
10.6, 7.3, 0.7, 1H, H-4), 7.59 (ddd, J ) 15.5, 10.6, 0.7, 1H,
+
4
) 254.0184 (calcd for C11H13 BrNO
1
3
H-3); C NMR (67.9 MHz, CDCl
3
) δ 14.2, 60.6, 116.5, 125.2,
2
54.0181, 1.2 ppm error). Anal. calcd for C11
9
H BrO: C, 55.72;
-
1
1
2
30.6, 138.8, 166.4; IR (film) νmax 1713 cm ; MS (EI) m/z 206,
79
H, 3.83. Found: C, 55.49; H, 3.89. The NMR data were consistent
+
04 (M ); HRMS (EI) m/z 203.9790 (calcd for C
7
H
9
BrO
2
14
with those published.
-P h en yl-5-br om op en ta -2Z,4Z-d ien -2-on e (12Z,Z): white
solid, mp 74-75 °C (6%), R 0.46 (1:1 petroleum ether-diethyl
ether); H NMR (270 MHz, CDCl ) δ 6.66 (dt, J ) 7.5, 1.1, 1H,
H-5), 6.96 (dt, J ) 11.5, 1.1, 1H, H-2), 7.07 (ddd, J ) 11.5, 10.5,
2
03.9786, 2.2 ppm error). The NMR data were consistent with
1
1
3
those published.
f
Eth yl 5-br om op en ta -2Z,4Z-d ien oa te (4Z,Z): colorless oil
1
3
1
(
16%), R
MHz, CDCl
CH ), 5.89 (d, J ) 11.4, 1H, H-2), 6.61 (d, J ) 7.3, 1H, H-5),
.95 (dd, J ) 11.4, 10.9, 1H, H-3), 7.99 (dd, J ) 10.9, 7.3, 1H,
f
0.64 (2:1 petroleum ether-diethyl ether); H NMR (270
3
) δ 1.30 (t, J ) 7.0, 3H, CH ), 4.20 (q, J ) 7.0, 2H,
3
1
.1, 1H, H-3), 7.45-7.62 (m, 3H, ArH), 7.92-7.99 (m, 3H, ArH,
2
H-4). This compound readily isomerized to 9E,Z and further
6
characterization was not possible.
1
3
H-4); C NMR (67.9 MHz, CDCl
3
) δ 14.2, 60.3, 117.3, 121.3,
5
-Br om op en ta -2Z,4Z-d ien on itr ile (13Z,Z): white solid, mp
-
1
1
2
2
28.5, 138.2, 165.9 ppm; IR (film) νmax 1710, cm ; MS (EI) m/z
1
3
3-34 °C (50%), R
NMR (270 MHz, CDCl
dd, J ) 7.0, 1.5, H-5), 7.13-7.28 (m, 2H, H-3, H-4); C NMR
67.9 MHz, CDCl ) δ 101.1, 115.8, 118.8, 128.7, 143.9; IR (solid
film) νmax 2216 cm ; MS (EI) m/z 159, 157 (M ); HRMS (EI)
m/z 156.9533 (calcd for C
f
0.48 (1:1 petroleum ether-diethyl ether); H
+
79
06, 204 (M ); HRMS (EI) m/z 203.9786 (calcd for C
7 9 2
H BrO
3
) δ 5.49 (dd, J ) 11.4, 1.5, 1H, H-2), 6.75
03.9786, 0.1 ppm error). Anal. Calcd for C BrO : C, 41.00;
7
H
9
2
13
(
(
H, 4.42. Found: C, 40.63; H, 4.49.
ter t-Bu tyl 5-br om op en ta -2E,4Z-d ien oa te (8E,Z): colorless
3
-1
+
1
oil (75%), R
f
0.63 (1:1 petroleum ether-diethyl ether); H NMR
79
5
H
4
BrN 156.9527, 3.9 ppm error).
t
(
1
7
270 MHz, CDCl
3
) δ 1.51 (s, 9H, Bu), 6.01 (dt, J ) 15.4, 0.7,
H, H-2), 6.54 (dt, J ) 7.2, 0.7, 1H, H-5), 6.75 (ddd, J ) 10.8,
.2, 0.7, 1H, H-4), 7.51 (ddd, J ) 15.4, 10.8, 0.7, 1H, H-3); 13
) δ 28.1, 80.8, 115.8, 127.1, 130.7, 137.9,
5
-Br om op en ta -2E,4Z-d ien on itr ile (13E,Z): white solid, mp
1
3
1-32 °C (18%), R
NMR (270 MHz, CDCl
f
0.30 (1:1 petroleum ether-diethyl ether); H
) δ 5.58 (d, J ) 15.9, 1H, H-2), 6.67 (d, J
C
3
NMR (67.9 MHz, CDCl
1
3
)
7.3, 1H, H-5), 6.77 (dd, J ) 10.3, 7.3, 1H, H-4), 7.37 (dd, J )
-
1
+
4
65.7; IR (film) νmax 1710 cm ; MS (CI) m/z 252, 250 (MNH
);
13
1
1
1
1
3
5.9, 10.3, 1H, H-3); C NMR (67.9 MHz, CDCl ) δ 102.7, 117.5,
7
9
HRMS (CI) m/z 250.0444 (calcd for C
9
H
17 BrNO
2
250.0443, 0.6
-1
18.1, 130.0, 145.1; IR (solid film) νmax 2216 cm ; MS (EI) m/z
ppm error).
+
79
59, 157 (M ); HRMS (EI) m/z 156.9527 (calcd for C
5
H
4
BrN
ter t-Bu tyl 5-br om op en ta -2Z,4Z-d ien oa te (8Z,Z): colorless
56.9527, 0 ppm error).
1
oil (15%), R
f
0.67 (1:1 petroleum ether-diethyl ether); H NMR
4
-Br om o-1,1-bip h en ylen ebu ta -3Z-d ien e (14): yellow solid,
mp 84-86 °C (35%), R 0.45 (1:1 petroleum ether-diethyl ether);
H NMR (270 MHz, CDCl ) δ 6.67 (dd, J ) 7.3, 1.4, 1H, H-4),
.25-7.46 (m, 5H, Ar-H, H-3), 7.65-7.86 (m, 5H, ArH, H-2);
t
(
1
1
270 MHz, CDCl
3
) δ 1.49 (s, 9H, Bu), 5.81 (dt, J ) 11.6, 1.0,
H, H-2), 6.56 (dt, J ) 7.3, 1.0, 1H, H-5), 6.87 (ddd, J ) 11.6,
0.8, 1.0, 1H, H-3), 7.97 (ddd, J ) 10.8, 7.3, 1.0, 1H, H-4); 13
) δ 28.2, 80.9, 116.6, 123.3, 128.5, 137.2,
f
1
3
C
7
NMR (67.9 MHz, CDCl
1
3
1
3
3
C NMR (67.9 MHz, CDCl ) δ 115.0, 119.7, 120.1, 120.7, 120.9,
-
1
+
4
65.4; IR (film) νmax 1710 cm ; MS (CI) m/z 252, 250 (MNH
);
1
1
25.2, 127.1, 127.2, 128.5, 128.6, 128.7, 136.8, 138.2, 139.2, 139.3,
41.4; MS (EI) m/z 284, 282 (M ); HRMS (EI) m/z 282.0032 (calcd
7
9
HRMS (CI) m/z 250.0443 (calcd for C H17 BrNO 250.0443, 0
9 2
+
ppm error).
7
9
11
for C16H11 Br 282.0044, 4.2 ppm error). Anal. calcd for C16H -
Eth yl 2-m eth yl-5-br om open ta-2E,4Z-dien oate (9E,Z): col-
Br: C, 67.87; H, 3.92. Found: C, 67.70; H, 3.99.
b) F r om 3-Br om o-2E-p r op en ol. Eth yl 5-br om op en ta -
E,4E-d ien oa te (4E,E): colorless oil (68%), R 0.60 (1:1 petro-
leum ether-diethyl ether); H NMR (270 MHz, CDCl ) δ 1.30
t, J ) 7.2, 3H, CH ), 4.21 (q, J ) 7.2, 2H, CH ), 5.92 (d, J )
15.4, 1H, H-2), 6.72-6.90 (m, 2H, H-4, H-5), 7.17 (ddd, J ) 15.4,
9.7, 1.0, 1H, H-3); 13C NMR (67.9 MHz, CDCl
) δ 14.2, 60.6,
1
orless oil (60%), R
NMR (270 MHz, CDCl
3
6
f
0.45 (4:1 petroleum ether-diethyl ether); H
) δ 1.33 (t, J ) 7.0, 3H, CH ), 1.97 (br s,
H, 2-Me), 4.25 (q, J ) 7.0, 2H, CH ), 6.57 (d, J ) 7.3, 1H, H-5),
.94 (dd, J ) 10.9, 7.3, 1H, H-4), 7.48 (d, J ) 10.9, 1H, H-3);
(
3
3
2
f
2
1
1
3
3
C
(
3
2
NMR (67.9 MHz, CDCl
3
) δ 13.5, 14.2, 60.8, 115.5, 128.1, 131.5,
-1
+
1
32.4, 167.9; IR (film) νmax 1709 cm ; MS (EI) m/z 220, 218 (M );
7
9
3
HRMS (CI) m/z 236.0293 (calcd for C
8
H
15 BrNO
2
236.0286, 2.9
-
1
1
(
C
17.7, 122.2, 135.4, 140.9, 166.4; IR (film) νmax 1713 cm ; MS
EI) m/z 206, 204 (M ); HRMS (EI) m/z 203.9789 (calcd for
H BrO 203.9786, 1.4 ppm error). The NMR data were
7 9 2
ppm error).
+
6
-Br om oh exa -3E,5Z-d ien -2-on e (10E,Z): colorless oil (65%),
7
9
1
R
f
0.41 (1:1 petroleum ether-diethyl ether); H NMR (270 MHz,
CDCl ) δ 2.35 (s, 3H, CH ), 6.30 (d, J ) 15.8, 1H, H-3), 6.65 (d,
J ) 7.3, 1H, H-6), 6.80 (dd, J ) 10.5, 7.3, 1H, H-4), 7.43 (dd, J
1
3
consistent with those published.
3
3
Eth yl 5-br om op en ta -2Z,4E-d ien oa te (4Z,E): colorless oil
1
1
3
(10%), R
MHz, CDCl
CH ), 5.71 (ddd, J ) 11.3, 1.1, 0.7, 1H, H-2), 6.46 (td, J ) 11.3,
f
0.66 (1:1 petroleum ether-diethyl ether); H NMR (270
)
3
15.8, 10.5, 1H, H-5); C NMR (67.9 MHz, CDCl ) δ 27.2, 117.3,
1
-
3
) δ 1.31 (t, J ) 7.2, 3H, CH ), 4.20 (q, J ) 7.2, 2H,
3
1
1
1
7
31.1, 133.7, 137.5, 198.5; IR (film) νmax 1689 cm ; MS (EI) m/z
79
+
2
76, 174 (M ); HRMS (EI) m/z 173.9684 (calcd for C
73.9680, 2.1 ppm error). This compound readily isomerizes to
E,E in CDCl
-Br om oh exa -3Z,5Z-d ien -2-on e (10Z,Z): colorless oil (8%),
6 7
H BrO
0
.7, 1H, H-3), 6.80 (dt, J ) 13.5, 0.7, 1H, H-5), 8.08 (ddd, J )
3
.
6
(14) Babudri, F.; Cicciomessere, A. R.; Farinola, G. M.; Fiandanese,
V.; Marchese, G. J . Org. Chem. 1997, 32911-3298.
1
R
f
0.49 (1:1 petroleum ether-diethyl ether); H NMR (270 MHz,

6
20 J . Org. Chem., Vol. 65, No. 2, 2000
Notes
1
6
3.5, 11.3, 1.1, 1H, H-4); 13C NMR (67.9 MHz, CDCl
3
) δ 14.2,
2H, H-5, H-6); 13C NMR (67.9 MHz, CDCl
3
) δ 9.6, 29.9, 73.8,
-
1
-1
0.3, 118.4, 119.0, 133.8, 140.6, 165.8; IR (film) νmax 1712, cm
;
108.4, 125.9, 131.9, 140.2; IR (film) νmax 3353 cm ; MS (EI) m/z
+
+
79
MS (CI) m/z 224, 222 (MNH
for C
BrO
4
); HRMS (CI) m/z 222.0124 (calcd
222.0130, 2.5 ppm error). Anal. calcd for C
: C, 41.00; H, 4.42. Found: C, 40.68; H, 4.61.
-Br om oh epta-4E,6E-dien -3-on e (11E,E): colorless oil (56%),
191, 189 (M -1); HRMS (EI) m/z 189.9986 (calcd for C
7
H
11 BrO
7
9
7
H
13 BrNO
2
7
H
9
-
189.9993, 3.7 ppm error).
2
Son oga sh ir a Cou p lin g. Gen er a l P r oced u r e. In a 5 mL
round-bottom flask under nitrogen atmosphere was placed
7-bromohepta-4,6-dien-3-ol 15 (21 mg, 0.11 mmol) in degassed
benzene (1 mL). To this solution was added pyrrolidine (0.013
mL, 11 mg, 0.154 mmol) and (Ph P) Pd (5.1 mg, 0.0044 mmol).
7
1
R
f
0.43 (1:1 petroleum ether-diethyl ether); H NMR (270 MHz,
CDCl ) δ 1.12 (t, J ) 7.3, 3H, CH ), 2.59 (q, J ) 7.3, 2H, CH ),
.22 (d, J ) 15.4, 1H, H-4), 6.81-6.90 (m, 2H, H-6, H-7), 7.06
3
3
2
6
3
4
1
3
(
ddd, J ) 15.4, 7.0, 3.0, 1H, H-5); C NMR (67.9 MHz, CDCl
3
)
The resulting solution was protected from light and stirred for
δ 8.0, 34.3, 118.1, 129.5, 135.8, 138.4, 200.6; IR (film) νmax 1682
cm ; MS (EI) m/z 190, 188 (M ); HRMS (EI) m/z 187.9829 (calcd
0.75 h. 2-Ethynylthiophene12 (13 mg, 0.12 mmol) and CuI (3.4
-1
+
mg, 0.018 mmol) were added, and the reaction was stirred
overnight. Upon completion, the solution was diluted with
diethyl ether (70 mL) and washed with aqueous NH Cl (10 mL),
7
9
for C
7 9
H BrO 187.9837, 3.9 ppm error).
5
-Br om op en ta -2E,4E-d ien on itr ile (13E,E): white solid, mp
4
1
7
2-73 °C (45%), R
f
0.45 (1:1 petroleum ether-diethyl ether); H
) δ 5.43 (br d, J ) 15.9, 1H, H-2), 6.75-
.97 (m, 3H, H-3, H-4, H-5); 13C NMR (67.9 MHz, CDCl
) δ 99.9,
water (2 × 10 mL), and brine (10 mL). Drying with Na SO ,
2
4
NMR (270 MHz, CDCl
3
removal of solvent in vacuo, and column chromatography (5:1
6
1
1
1
3
petroleum ether-diethyl ether) gave the final product.
-
1
17.4, 119.6, 134.7, 146.9; IR (film) νmax 2215 cm ; MS (EI) m/z
9
-(2-Th ien yl)-n on a -4E,6E-d ien -8-yn -3-ol (16): colorless oil
+
79
59, 157 (M ); HRMS (EI) m/z 156.9534 (calcd for C
5
H
4
BrN
1
(
88%), R
f
0.26 (1:1 petroleum ether-diethyl ether); H NMR (270
) δ 0.94 (t, J ) 7.4, 3H, CH ), 1.60 (dq, J ) 6.0, 7.4,
2
H, CH ), 1.62 (br s, 1H, OH), 4.13 (q, J ) 6.0, 1H, CHOH),
56.9527, 4.5 ppm error).
MHz, CDCl
3
3
5
-Br om op en ta -2Z,4E-d ien on itr ile (13Z,E): colorless oil
2
5
6
1
(
15%), R
MHz, CDCl
1.3, 10.8, 0.7, 1H, H-3), 6.92 (dt, J ) 13.5, 0.7, 1H, H-5), 7.24
f
0.35 (1:1 petroleum ether-diethyl ether); H NMR (270
.81 (d, J ) 14.8, 1H, H-7), 5.82 (dd, J ) 15.0, 6.0, 1H, H-4),
.32 (dd, J ) 14.8, 10.7, 1H, H-6), 6.67 (dd, J ) 15.0, 10.7, 1H,
3
) δ 5.29 (dt, J ) 10.8, 0.7, 1H, H-2), 6.74 (ddd, J )
1
(
H-5), 6.98 (dd, J ) 5.1, 3.6, 1H, H-4′), 7.19 (dd, J ) 3.6, 1.2, 1H,
H-3′), 7.24 (dd, J ) 5.1, 1.2, 1H, H-5′); C NMR (67.9 MHz,
CDCl ) δ 9.6, 30.1, 73.6, 85.3, 92.6, 111.0, 123.4, 127.1, 127.2,
1
2
4
1
3
ddd, J ) 13.5, 11.3, 0.8, 1H, H-4); C NMR (67.9 MHz, CDCl
3
)
13
-
1
δ 98.1, 116.5, 120.5, 133.5, 145.8; IR (film) νmax 2217 cm ; MS
(
3
+
EI) m/z 159, 157 (M ); HRMS (EI) m/z 156.9532 (calcd for
-1
29.5, 131.7, 138.8, 140.9; IR (film) νmax 3355 cm ; MS (EI) m/z
7
9
C
5
H
4
BrN 156.9527, 3.2 ppm error).
Red u ction w ith Na BH . Gen er a l P r oced u r e. Freshly
prepared 7-bromohepta-4,6-dien-3-one 11E,E or 11E,Z (18.9 mg,
+
18 (M ); HRMS (EI) m/z 218.0774 (calcd for C13
H14OS 218.0765,
4
.1 ppm error); UV (diethyl ether) 338 (21,000), 317 (27,000) nm
10
[
lit. 338.5 (21,700), 317 (26,700) nm)]. The NMR data were
0
0
.1 mmol) was dissolved in methanol (2 mL). NaBH
4
(7.6 mg,
10
consistent with those published.
.2 mmol) was added at 0 °C, and the solution was stirred at
9
-(2-Th ien yl)-n on a -4E,6Z-d ien -8-yn -3-ol (17): colorless oil
this temperature for 1 h. Aqueous ammonium chloride (5 mL)
was added, and the resulting mixture was extracted with diethyl
ether (3 × 40 mL). The organic layers were combined and dried
with sodium sulfate. Evaporation of solvent in vacuo and flash
chromatography (4:1 petroleum ether-diethyl ether) gave the
corresponding alcohols 15E,E and 15E,Z.
1
(
87%), R
f
0.25 (1:1 petroleum ether-diethyl ether); H NMR (270
) δ 0.96 (t, J ) 7.5, 3H, CH ), 1.61 (dq, J ) 6.3, 7.5,
2
H, CH ), 1.62 (br s, 1H, OH), 4.19 (q, J ) 6.3, 1H, CHOH),
MHz, CDCl
3
3
2
5
6
7
7
9
1
.67 (d, J ) 10.8, 1H, H-7), 5.91 (dd, J ) 15.0, 6.3, 1H, H-4),
.43 (t, J ) 10.8, 1H, H-6), 6.80 (dd, J ) 15.0, 10.8, 1H, H-5),
.00 (dd, J ) 5.1, 3.6, 1H, H-4′), 7.22 (dd, J ) 3.6, 1.2, 1H, H-3′),
7
-Br om oh ep ta -4E,6E-d ien -3-ol (15E,E): colorless oil (91%),
13
3
.28 (dd, J ) 5.1, 1.2, 1H, H-5′); C NMR (67.9 MHz, CDCl ) δ
1
R
f
0.32 (1:1 petroleum ether-diethyl ether); H NMR (270 MHz,
CDCl ) δ 0.92 (t, J ) 7.0, 3H, CH ), 1.50-1.65 (m, 2H, CH ),
.62 (br s, 1H, OH), 4.07 (dq, J ) 1.0, 6.5, 1H, CHOH), 5.74 (dd,
J ) 15.3, 6.5, 1H, H-4), 6.16 (ddd, J ) 15.3, 10.6, 1.0, 1H, H-5),
.7, 30.0, 73.8, 88.9, 90.4, 109.0, 123.3, 127.1, 127.4, 127.6, 131.8,
3
3
2
-1
+
39.1, 139.8; IR (film) νmax 3360 cm ; MS (EI) m/z 218 (M );
1
HRMS (EI) m/z 218.0762 (calcd for C13
H
14OS 218.0765, 1.6 ppm
-1
error); UV (diethyl ether) 338 (21,000), 317 (27,000) cm
.
6
.32 (d, J ) 13.3, 1H, H-7), 6.72 (dd, J ) 13.3, 10.6, 1H, H-6);
1
3
3
C NMR (67.9 MHz, CDCl ) δ 9.6, 30.0, 73.5, 108.9, 127.6, 136.8,
1
-
+
Ack n ow led gm en t. We are grateful to the EPSRC
for postdoctoral support (X.W.).
1
37.1; IR (film) νmax 3350 cm ; MS (EI) m/z 191, 189 (M -1);
79
HRMS (EI) m/z 188.9921 (calcd for C
ppm error).
7
H
10 BrO 188.9915, 3.2
7
-Br om oh ep ta -4E,6Z-d ien -3-ol (15E,Z): colorless oil (95%),
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
1
R
f
0.30 (1:1 petroleum ether-diethyl ether); H NMR (270 MHz,
CDCl ) δ 0.95 (t, J ) 7.5, 3H, CH ), 1.55-1.66 (m, 2H, CH ),
.67 (br s, 1H, OH), 4.15 (q, J ) 6.5, 1H, CHOH), 5.93 (dd, J )
4.6, 6.5, 1H, H-4), 6.18 (d, J ) 6.5, 1H, H-7), 6.51-6.68 (m,
spectra of compounds 3, 4, and 8-17. This material is available
free of charge via the Internet at http://pubs.acs.org.
3
3
2
1
1
J O9913558