Consecutive reactions of vinylic phosphonium salts with Grignard reagents catalyzed by CuBr-Ag2CO3 or CuBr-H2O

Full text of DOI:10.1021/jo960899w

J . Org. Chem. 1996, 61, 8659-8661
8659
Ta ble 1. Ca ta lyzed Sequ en tia l Ad d ition s
Con secu tive Rea ction s of Vin ylic
P h osp h on iu m Sa lts w ith Gr ign a r d
Rea gen ts Ca ta lyzed by Cu Br -Ag2CO3 or
Cu Br -H2O
yield of
run
R1
C6H5
C6H5
C6H5
C6H5
R2
additivea
4 (%)b
1
2
3
4
5
6
4-(CH3)2NC6H4 CuBr
4-(CH3)2NC6H4 Ag2CO3
4-(CH3)2NC6H4 CuBr-Na2CO3
4-(CH3)2NC6H4 CuBr-Ag2CO3
25
0
20
73
20
73
Yanchang Shen* and J iangzhao Yao
4-CH3C6H4 4-CH3OC6H4
4-CH3C6H4 4-CH3OC6H4
CuBr
CuBr-Ag2CO3
Shanghai Institute of Organic Chemistry, Academia Sinica,
354 Fenglin Lu, Shanghai 200032, China
a
b
All additives were dried before use. Isolated yields.
Received May 15, 1996
Ta ble 2. Rea ction s of Gr ign a r d Rea gen ts w ith 1
F ollow ed by Ad d ition of 3 Ca ta lyzed by Cu Br -Ag2CO3
In recent years sequential transformations have at-
tracted much interest because they provide a simple and
efficient entry to complex compounds by including two
or more transformations in a single operation to increase
the complexity of a substrate starting from commercially
available relatively simple precursors.1 In our laboratory
consecutive reactions of phosphonium salts have been
developed as a general synthetic approach for polyfunc-
tionalized fluoroalkenes,2 fluoro enynes,3 fluoro dienes,4
and fluoro epoxides5 which would be difficult to prepare
otherwise.
The chemistry of vinylic phosphonium salts has at-
tracted considerable interest since the â-addition of
nucleophiles to the vinyl group is a convenient and
synthetically useful reaction for the formation of new
alkylidenephosphoranes which can be utilized as syn-
thetic reagents, particularly for the synthesis of hetero-
cyclic compounds.6
The reactions of vinyltriphenylphosphonium salts with
alkyllithium and Grignard reagents have been reported,
but both reactions proceed in poor yields.7 It thus
appears that as a synthetic method, the ability of the
addition of organolithium and Grignard reagents to
vinylic phosphonium salts to produce results is strictly
limited. This limitation may be due to the basicity of
those reagents.
compd
R1
R2
yield (%)a (E):(Z)b
4a
4a c
4b
4c
4d
4e
4f
4g
4h
4i
C6H5
C6H5
C6H5CH2
C6H5
4-CH3OC6H4 4-CH3OC6H4
4-CH3C6H4
C6H5CH2
4-(CH3)2NC6H4
4-(CH3)2NC6H4
4-(CH3)2NC6H4
4-CH3OC6H4
73
80
60
88
81
73
73
46
88
83
75
80
100:0
100:0
100:0
94:6
93:7
92:8
4-CH3OC6H4
4-CH3OC6H4
92:8
4-CH3OC6H4 C6H5CHdCH
55:45
50:50
33:67
18:82
88:12
C6H5
C6H5
C6H5
C2H5
4-FC6H4
c-C6H11
4-NO2C6H4
4-CH3OC6H4
4j
4k c
a
b
Isolated yields. The ratios of (E)- and (Z)-isomers were
estimated on the basis of NMR data. c The reaction was catalyzed
by CuBr-H2O.
The reaction of PhMgBr with vinyltriphenylphospho-
nium bromide in the presence of CuBr was successful,
but the yield was low (25%) when either a catalytic or
equivalent amount of CuBr was used.
Further experiments showed that the reaction pro-
ceeded more efficiently in the presence of a catalytic
amount of CuBr-Ag2CO3.
Resu lts a n d Discu ssion
We report that the consecutive reactions between
Grignard reagents, vinylic phosphonium salts, and then
aldehydes are catalyzed by CuBr-Ag2CO3 or CuBr-H2O.
The reaction of a phenyl Grignard reagent with vinyl-
triphenylphosphonium bromide gave a red ylide solution.
After addition of an aldehyde, triphenylphosphine but no
alkene was obtained. The Grignard reagent acts as a
The results are summarized in Table 1.
A variety of Grignard reagents and aldehydes could
be used in this reaction. The results are summarized in
Table 2.
Attempts to use alkyl Grignard reagents in this reac-
tion failed. However, we found that either alkyl or aryl
Grignard reagents did react with 1-propenyltriphenylphos-
phonium bromide in the presence of CuBr-H2O. The
results are summarized in Table 3.
base rather than a nucleophile under these conditions.
(1) (a) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. Engl. 1993,
32, 131. (b) Padwa, A.; Curtis, E. A.; Sandanayaka, V. P. J . Org. Chem.
1996, 61, 73.
(2) Shen, Y.-C.; Qiu, W.-M. Tetrahedron Lett. 1987, 28, 449.
(3) Shen, Y.-C.; Qiu, W.-M. J . Chem. Soc., Chem. Commun. 1987,
703.
(4) Shen, Y.-C.; Qiu, W.-M. Tetrahedron Lett. 1987, 28, 4283.
(5) (a) Shen, Y.-C.; Liao, Q.-M.; Qiu, W.-M. J . Chem. Soc., Chem.
Commun. 1988, 1309. (b) Shen, Y.-C.; Liao, Q.-M.; Qiu, W.-M. J . Chem.
Soc., Perkin Trans. 1 1990, 695.
(6) (a) Zbiral, E. In Organophosphorus Reagents in Organic Syn-
thesis; Cadogan, J . I. G., Ed.; Academic Press: London, 1979. (b)
Seyferth, D.; Fogel, J ., J . Organomet. Chem. 1966, 6, 205. (c) Linder-
man, R. J .; Meyers, A. I. Tetrahedron Lett. 1983, 24, 3043.
(7) Haubrich, A.; Klaveren, M. V.; Koten, G. V.; Handke, G.; Krause,
N. J . Org. Chem. 1993, 58, 5849 and references cited therein.
Similarly either alkyl or aryl Grignard reagents reacts
with vinyltriphenylphosphonium bromide in the presence
of CuBr-H2O. The results are summarized in Table 2
(4a c and 4k ).
The effect of additives as well as reaction time and
temperature has been investigated. The results are
summarized in Tables 3 and 4. It is obvious that the
S0022-3263(96)00899-7 CCC: $12.00 © 1996 American Chemical Society

8660 J . Org. Chem., Vol. 61, No. 24, 1996
Notes
Ta ble 3. Rea ction s of Gr ign a r d Rea gen ts w ith 5
Ta ble 5
F ollow ed by Ad d ition of 3 Ca ta lyzed by Cu Br -H2O
run
nucleophile
yield (%)
(E):(Z)
compd
R1
R2
yield (%)a
(E):(Z)b
1
2
Ph2CuLi
PhMgBr
60
90
45:55
100:0
6a
6b
6c
6d
6e
6f
6g
6h
6h c
6h d
6i
C6H5
4-(CH3)2NC6H4
4-(CH3)2NC6H4
4-(CH3)2NC6H4
4-FC6H4
piperyl
4-FC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
90
75
70
90
94
87
82
82
68
10
84
100:0
100:0
100:0
60:40
55:45
40:60
33:67
30:70
18:82
10:90
14:86
n-C4H9
C6H5CH2
n-C4H9
C6H5CH2
C6H5CH2
C6H5
n-C4H9
n-C4H9
n-C4H9
C6H5
rate and yield of the reaction. However, excessive water
could react with the Grignard reagent leading to de-
creased yields (Table 4, run 3).
It has been reported that10 cuprates react with vinyl-
triphenylphosphonium bromide; the resulting phospho-
ranes react with aldehydes to give alkenes as a mixture
of (Z)- and (E)-isomers. The stereoselectivity could be
changed significantly by the addition of hexamethylphos-
phoramide (HMPA), a highly toxic cancer suspect agent.
We have repeated the cuprate method for comparsion
with our results and found that, in the case examined,
our method gave a higher yield and was more stereose-
lective as shown in Table 5.
3-NO2C6H4
a
b
Isolated yields. The ratios of (E)- and (Z)-isomers were
estimated on the basis of NMR data. c The reaction was carried
d
out at 0-70 °C for 10-30 min. The reaction was carried out at
-70 °C for 90 min.
Ta ble 4. Effect of th e Am ou n ts of Cu Br a n d Wa ter
run
compd
CuBr (mol %)
H2O (µL)
yield (%)a
1
2
3
4
5
6
7
4k
4k
4k
6g
6g
6g
6g
22
22
22
22
11
0
0
4
8
4
4
4
4
0
80
50
82
53
16
85
In conclusion, the consecutive reaction of vinylic phos-
phonium salts with a variety of Grignard reagents and
aldehydes to form substituted alkenes (R1CH2CHdCHR2
or R1CH(CH3)CHdCHR2) is catalyzed by CuBr-Ag2CO3
or CuBr-H2O. The stereoselectivity depended on the
nature of substituents in the benzene ring of the alde-
hydes. Electron-donating groups increase the (E)-
selectivity, whereas the reverse is true for electron-
withdrawing groups. We have not yet formulated a
reasonable explanation for these results. However, the
method provides a direct route to various substituted
styrenes and represents an improvement over previous
related routes.10
22b
a
b
Isolated yields. Using 22 mmol % of CuCl as catalyst.
yield decreased and the stereoselectivity improved as the
reaction temperature was decreased (Table 3, 6h , 6h ,c
and 6h d).
Although the mechanistic aspects are not clear at
present, the following parameters play important roles.
(1) Cop p er (I) Ca ta lyst. Either CuBr or CuCl could
be used in this reaction as a catalyst (Table 4).
(2) Silver Ca r bon a te. A number of coadditives, such
as Ag2CO3, LiCl, ZnCl2, CoCl2, FeCl3, MoO3, and Cp2TiCl2,
were tested, but silver carbonate was the only compound
that showed catalytic activity. When silver carbonate
was used alone, no reaction took place (Table 1, run 2).
In the case of CuBr-Na2CO3, the yields were low (Table
1, run 3). It seems that silver salts may play an
important role8 as follows.
Exp er im en ta l Section
Gen er a l. Mass spectra were obtained by chemical ionization,
and the mass spectra are reported as m/e (relative intensity).
All reactions were performed in oven-dried glassware under an
atmosphere of dry nitrogen. Solvents were removed under
reduced pressure with a rotary evaporator, and the residue was
chromatographed on a silica gel column. The ratios of (E)- and
(Z)-isomers were estimated on the basis of NMR data. The
experimental error is <5% from duplicate experiments.
Gen er a l P r oced u r e for th e P r ep a r a tion of Su bstitu ted
Alk en es 4. Grignard reagent 2 (1.5 mmol) was added dropwise
to a suspension of vinyltriphenylphosphonium bromide (1) (1.36
mmol), CuBr (0.28 mmol), and Ag2CO3 (0.04 mmol) in THF (10
mL) at -78 °C under nitrogen. After the addition of 2, the
reaction mixture was allowed to reach to -40 °C and stirred for
1 h. Then the aldehyde 3 (0.87 mmol) was added, and the
temperature was warmed to 20 °C within 4 h. After letting the
mixture stand overnight, the mixture was diluted with 30 mL
of ether, water was added, and the organic layer was separated
and dried. Removal of the solvent gave a residue which was
purified by chromatography with petroleum ether-ethyl acetate
(100:2) as the eluting solvent.
(3) Tr a ce of Wa ter . Attempts to carry out this
reaction in DMF or CH2Cl2 failed. Although in these
solvents the solubility of the vinylic phosphonium salts
increased, the solvents themselves reacted with the
Grignard reagent9 resulting in the formation of a number
of byproducts. Thus THF was used as the solvent.
Presumably the reaction takes place at the surface of the
insoluble vinylic phosphonium salts. A trace of water
absorbed on the interface would increase the solubility
of these salts in THF. This in turn should increase the
3-P h en yl-1-(4-(N,N-d im et h yla m in o)p h en yl)-1-p r op en e
(4a ). Yield: 73%; mp 48-50 °C. IR(KCl): 1620, 1500, 1360,
960 cm-1 1H NMR (CDCl3): δ 2.95 (s, 6H), 3.52 (d, 2H, J ) 6.7
.
Hz), 6.09-6.25 (m, 1H), 6.40 (d, 1H, J ) 15.7 Hz), 6.68-7.38
(m, 9H) ppm. MS: 237 (M+, 100), 236 (37), 193 (11), and 115
(17). Anal. Calcd for C17H19N (237.34): C, 86.03; H, 8.07; N,
5.90. Found: C, 86.03; H, 8.09; N, 5.78.
Gen er a l P r oced u r e for th e P r ep a r a tion of Alk en es 6.
A suspension of 1-propenyltriphenylphosphonium bromide (5)
(1.3 mmol), CuBr (0.28 mmol), THF (10 mL), and water (4 µL)
was stirred at 0 °C under nitrogen for 5 min, and the Grignard
reagent 2 (1.6 mmol) was added dropwise. After addition of the
(8) Ishio, Y.; Nishiguchi, I.; Nakao, S.; Hirashima, T. Chem. Lett.
1981, 641.
(9) Evans, E. A.Chem. Ind. (London) 1957, 1596.
(10) J ust, G.; O’Connor, B. Tetrahedron Lett. 1985, 26, 1799.

Notes
J . Org. Chem., Vol. 61, No. 24, 1996 8661
Grignard reagent, the reaction mixture was stirred at 0-10 °C
for 0.5 h and the aldehyde 3 (0.87 mmol) was added. After the
mixture was stirred overnight, the mixture was diluted with
diethyl ether (30 mL) and water, and the organic layer was
separated and dried. Removal of the solvent gave a residue
which was purified by chromatography with petroleum ether-
ethyl acetate (100:2) as the eluting solvent.
Ack n ow led gm en t. We thank the National Natural
Science Foundation of China, the Laboratory of Orga-
nometallic Chemistry, and Academia Sinica for financial
support.
Su p p or tin g In for m a tion Ava ila ble: Characterization
and analytical data of compounds 4b-k and 6b-i (6 pages).
This material is contained in libraries on microfiche, im-
mediately 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.
3-P h en yl-1-(4-(N,N-dim eth ylam in o)ph en yl)-1-bu ten e (6a).
Yield: 90%; bp 120 °C/1 mmHg. IR(neat): 1600, 1500, 1440,
980 cm-1 1H NMR (CDCl3): δ 1.42 (d, 3H, J ) 7.0 Hz), 2.92 (s,
.
6H), 3.50-3.61 (m, 1H), 6.18 (dd, 1H, J ) 6.7, 15.8 Hz), 6.32 (d,
1H, J ) 15.8 Hz), 6.65-7.30 (m, 9H) ppm. MS: 251(M+, 100),
236 (81), 221 (7), 191 (7), 91 (8). Anal. Calcd for C18H21
N
(251.37): C, 86.01; H, 8.42; N, 5.57. Found: C, 85.84; H, 8.47;
N, 5.71.
J O960899W