An efficient CuI-promoted synthesis of tri- and tetrasubstituted alkenes using organozinc species

Article abstract of DOI:10.1055/s-2006-926299

An efficient method for the synthesis of multifunctionalized alkenes has been developed. In the presence of 5 mol% CuI as catalyst, organozinc species CF₃COOZnEt, CF₃COOZnMe and CF₃COOZnPh reacted with α,β-acetylenic keton

Full text of DOI:10.1055/s-2006-926299

6
66
PAPER
An Efficient CuI-Promoted Synthesis of Tri- and Tetrasubstituted Alkenes
Using Organozinc Species
E
S
fficient
C
uI-
P
o
romoted Sy
n
g
i- And Tetra-substi
Xt uted Alkenes ue,* Lin He, Yong-Kang Liu, Kai-Zhen Han, Qing-Xiang Guo
Department of Chemistry, University of Science and Technology of China, Hefei 230026, P. R. of China
Fax +86(551)3606689; E-mail: xuesong@ustc.edu.cn
Received 27 July 2005; revised 9 September 2005
via the reaction of a,b-acetylenic ketones with dicyclo-
hexylborane.11
Abstract: An efficient method for the synthesis of multifunctional-
ized alkenes has been developed. In the presence of 5 mol% CuI as
catalyst, organozinc species CF COOZnEt, CF COOZnMe and Although organozinc reagents have been widely used in
3
3
CF COOZnPh reacted with a,b-acetylenic ketones and aldehydes in
12,13
3
the conjugate addition to a,b-acetylenic esters,
reac-
one pot providing trisubstituted alkenes in high yields with stereo-
selectivity. The reaction with b-substituted-a,b-acetylenic ketones
gave tetrasubstituted alkenes in good yields with Z-isomers as the
major products.
tion with a,b-acetylenic ketones has not been reported so
far. In continuation of our interest in exploring the reac-
1
4
tivity and behavior of organozinc species CF CO ZnR
3
2
with electrophiles,15 we found that organozinc species
CF CO ZnEt, which can be readily prepared by stirring
Key words: organozinc species, a,b-acetylenic ketones, aldehydes,
multifunctionalized alkenes, CuI
3
2
ZnEt with CF CO H in dichloromethane at 0 °C for 30
2
3
2
minutes, can react with a,b-acetylenic ketones and alde-
hydes in one pot to afford the unusual b-branched Morita–
Bayllis–Hillman adducts with stereoselectivity in excel-
Stereoselective synthesis of tri- and tetrasubstituted al-
1
–4
kenes is an attractive goal to organic chemists. Among
many approaches the Baylis–Hillman reaction, also
known as Morita–Baylis–Hillman reaction (MBH), is a
typical method for the synthesis of multifunctionalized
16
lent yields in the absence of any catalyst. Unfortunately,
when organozinc species CF COOZnPh (which formed
3
from diphenylzinc and CF COOH) was used to this reac-
3
tion, instead of CF CO ZnEt, the yields decreased dra-
5
3
2
alkenes. However, this reaction suffers from very slow
matically. For example, the reaction of CF COOZnPh
6
3
reaction rates which limit the scope of substrates. In order
with 3-butyn-2-one and 4-chlorobenzaldehyde provide
the corresponding adduct in only 29% yield after stirring
to overcome the limitations of the original MBH reaction,
alternative methods to accelerate the reaction rate, such as
change in catalyst, irradiation with microwaves, reaction
under high pressure, and reaction in ionic liquids, have
for 15 hours. The organozinc species CF COOZnPh has a
3
lower reactivity than CF CO ZnEt in the 1,4-Michael type
3
2
addition to a,b-acetylenic ketones, which made the forma-
tion of b-substituted allenolate zinc intermediate difficult
and resulted in a lower yield. Since copper(I) reagents can
5
been developed.
In 1983, Marino and coworkers developed the stereospe-
cific synthesis of olefins via coupling substituted (a-carb- catalyze the 1,4-addition of organozincs to a,b-unsaturat-
1
7
ethoxyvinyl) cuprate reagents with ketones; however, a ed ketones efficiently, we chose CuI as a catalyst for our
mixture of isomers was obtained when aldehydes were reaction system. Fortunately, we found that 5 mol% CuI
7
used as the electrophilic acceptors. Later on, Li and co- could promote the conjugate addition efficiently and af-
workers reported an approach for diastereosynthesis of ford the desired products in good to excellent yields with
tetrasubstituted alkenes via coupling organocupraes with stereoselectivity. Therefore, we modified this reaction
chiral b-substituted a,b-acetylenic esters followed by ad- system by addition catalytic amount of CuI, and herein,
dition of aldehydes in the presence of Et AlCl leading to
a mixture of Z- and E-isomers. Subsequently, they suc-
2
we report these results.
8
Through an effort to optimize the reaction conditions,
such as temperature, solvents, and the amount of catalyst,
we found that the reaction performed in dichloromethane
at room temperature in the presence of 5 mol% CuI gave
the best results. This new procedure represented in
Scheme 1 with results summarized in Table 1.
cessfully extended this strategy to enatiopure p-toluene-
sulfinimines as electrophiles and obtained the desired
9
Baylis–Hillman-type adducts. Recently, a general syn-
thesis of b-substituted Baylis–Hillman adducts by cou-
pling vinyl aluminum species with various electrophiles
such as aldehydes, fluoroketones, a-keto esters, a-acyl cy-
10
anides, and a,b-acetylenic ketones was reported. In the
same year, Kabalka and coworkers successfully synthe-
sized stereodefined functionalized trisubstituted olefins
OH
O
O
CF3COOZnR
CuI (5 mol%)
R1
R2
2
R1
R CHO
CH2CI2, r.t.
H
R
1
2
3
SYNTHESIS 2006, No. 4, pp 0666–0674
x
x
.
x
x
.2
0
0
6
Scheme 1
Advanced online publication: 11.01.2006
DOI: 10.1055/s-2006-926299; Art ID: F13005SS
Georg Thieme Verlag Stuttgart · New York
©

PAPER
Efficient CuI-Promoted Synthesis of Tri- and Tetrasubstituted Alkenes
667
From the parallel experiments (Table 1, entries 1, 2, 4, 6, non-aromatic a,b-acetylenic ketones can be employed as
, 10, 12–14, 18, and 19), we easily found that the pres- Michael-type acceptors. Aromatic a,b-acetylenic ketones
9
ence of CuI (5 mol%) could improve the reaction yields submitted to this reaction, instead of 3-butyn-2-one, in-
dramatically. For example, 84% yield of 3a was obtained creased yields significantly (Table 1, entry 2 vs. 5 and en-
when the reaction was carried out under the catalyst CuI. try 3 vs. 6), which can be ascribed to the higher reactivity
In comparison, a 29% yield was obtained in the absence of aromatic a,b-acetylenic ketones than that of aliphatic
of CuI. Meanwhile, either alkylzinc species a,b-acetylenic ketones. The substituents on the benzene
CF COOZnMe, CF COOZnEt or arylzinc species ring of aromatic a,b-acetylenic ketones seem to have no
3
3
CF COOZnPh could be used as nucleophilic reagent in obvious effect on the yields in the presence of CuI as cat-
3
the reaction. After careful analysis of the results shown in alyst. On the other hand, when alkylzinc species
Table 1, we found that all sorts of aromatic aldehydes CF COOZnMe and CF COOZnEt were employed in the
3
3
were suitable electrophilic acceptors in the reaction. The reaction, the aromatic aldehydes with an electron-with-
reactivity of aromatic aldehydes had an effect on the reac- drawing group or an electron-donating group on the ben-
tion yields when arylzinc species CF COOZnPh was used zene ring gave high reaction yields (Table 1, entries 9–
3
in the reaction. As shown in Table 1, when the benzene 22). Interestingly, the stereochemistry of the b-branched
ring of arylaldehyde has an electron-withdrawing group, Baylis–Hillman adducts 3 was determined to be Z config-
1
the desired product was formed in a better yield. Other- uration for all cases. H NMR analyses of the crude prod-
wise, the desired product was obtained in a lower yield if ucts indicated that no formation of the corresponding E-
an electron-donating group was present on the benzene isomers occurred in the reactions, where organozinc spe-
ring of arylaldehyde. At the same time, both aromatic and cies CF COOZnEt and CF COOZnPh were employed.
3
3
Table 1 Reaction of a,b-Acetylenic Ketones with CF COOZnR and Aldehydes in the Presence of CuI (5 mol%)
3
Entry
R
R1
R2
Time (h)
15
15
15
10
10
10
10
10
5
Product yield (%)a
3a, 84 (29)b
3b, 49 (9)b
3c, 68
1
2
3
4
5
6
7
8
9
C H
Me
Me
Me
4-ClC H
6
5
5
5
5
5
5
5
5
6
4
C H
4-MeOC H
6
6
4
4
C H
C H
5
6
6
C H
C H
4-ClC H
4
3d, 91 (54)b
3e, 66
6
6
5
5
5
6
C H
C H
4-MeOC H
6
6
6
C H
C H
C H
3f, 80 (50)b
3g, 94
6
6
6
5
5
C H
4-ClC H
C H
6
6
4
6
C H
4-MeOC H
4-ClC H
3h, 96
6
6
4
6
4
Et
Me
Me
C H
C H
3i, 93 (88)b
3j, 93 (86)b
3k, 89
6
5
10
11
12
13
14
15
16
18
19
20
21
22
Et
4-MeOC H
5
6
4
4
Et
3-MeOC H
10
10
15
15
15
15
10
10
10
10
10
6
5
6
Et
4-MeOC H
C H
3l, 85 (77)b
3m, 94(67)b
3n, 88 (45)b
3o, 90
6
4
6
5
5
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
C H
C H
6
4-MeOC H
6
4
4
3-MeOC H
6
1-naphthyl
C H
3p, 89
3q, 91 (76)b
3r, 82 (55)b
3s, 92
6
5
5
6
5
C H
4-MeOC H
6
6
4
4-ClC H
C H
5
6
4
4
6
4-ClC H
4-MeC H
3t, 93
6
6
4
4
4-MeOC H
4-MeC H
3u, 89
6
4
6
a
Yields after purification by column chromatography.
Yields in parentheses were obtained in the absence of CuI.
b
Synthesis 2006, No. 4, 666–674 © Thieme Stuttgart · New York

6
68
S. Xue et al.
PAPER
But it should be noted that a small amount of the E-isomer To explain the results obtained, we propose a mechanism
(
Z/E > 20:1) was detected when CF COOZnMe was used depicted in Scheme 3, which is derived from the cyclic
3
1
7
18
in this reaction.
transition state model proposed by Noyori and Kishi.
RCu was generated by metathesis of organozinc species
CF COOZnR and CuI. The combination of CF COOZnR
This mild methodology could also be extended to b-sub-
stituted a,b-acetylenic ketones as the conjugate addition
acceptors (Scheme 2). The results are summarized in
Table 2.
3
3
and
RCu
gave
the
mixed-metal
complex
(
CF COOZnR)(RCu) 6, which might have high capability
3
of transferring the R group from the metal to the b-posi-
tion of acetylenic ketone. The initial reaction step in-
volves the 1,4-conjugate addition of complex 6 to a,b-
acetylenic ketone to form an active zinc-allenolate inter-
mediate 7. Formation of this intermediate is accelerated
by the coordination of the Lewis acid zinc atom to carbon-
yl oxygen of acetylenic ketones, whereas the complex 6
has a stronger Lewis acid character in comparison to the
The reactions were carried out under similar conditions as
described above and afforded tetrasubstituted alkenes
with a mixture of Z- and E-isomers in good yields. For ex-
ample, exposure of CF COOZnMe to 1-phenylhex-2-yn-
3
1
-one and benzaldehyde in the presence of 5 mol% CuI
provided 74% yield of (Z)-5a and 17% yield of (E)-5a in
a combined yield of 91%. Under the same conditions, p-
tolualdehyde gave the corresponding tetrasubstituted al-
kenes 5b in a combined yield of 88%, while (Z)-5b was
isolated in 68% yield along with 20% yield of (E)-5b.
independent organozinc species CF COOZnR. At the
3
same time, R group in the complex 6 is endowed with high
transfer capability, further accelerating the formation of
intermediate 7. Copper complex promoted the formation
of intermediate 7 and improved reaction yields efficiently.
However, more complex clusters may be present in the re-
action system, and full understanding of the reaction re-
quires further studies.
When organozinc species CF COOZnEt was used, the re-
3
action proceeded smoothly and provided good yields in
the presence of CuI. However, what troubled us most in
this reaction is that Z- and E-isomers were very difficult to
separate by column chromatography. Similarly, the pres-
ence of CuI is very important to the reaction. For example,
In the second reaction step, the aldehyde carbonyl coordi-
nates with zinc atom, which serves to orient the carbonyl
group of aldehyde for attack on the allenolate. Therefore,
treatment of CF COOZnEt with 1-phenylhex-2-yn-1-one
3
and benzaldehyde in the absence of CuI provided tetra-
substituted alkenes 5c in 50% yield, but with 5 mol% CuI,
the yield of 5c increased to 85% (Table 2, entry 3). This
can be ascribed to the steric hindrance of the substitution
group at the b-position of acetylenic ketones, which made
the conjugate addition difficult and lowered the yields.
The presence of CuI accelerated the conjugate addition of
2
the steric interaction between aldehyde R group and the
3
substitute groups R and R at b-position of the allenolate
dominates the stereochemistry of this reaction. The alde-
hyde attacks the allenolate mainly from the less hindered
side of the allenoate 7 to provide Z-isomer as the main
product.
CF COOZnEt to b-substituted a,b-acetylenic ketones and
3
improved the reaction yields significantly.
For R3 = H (Table 1), when oranozinc species
CF COOZnPh and CF COOZnEt were used in this reac-
3
3
OH
O
tion, the aldehyde attacked the allenolate from the less
hindered side of the allenolate 7 to provide the sole Z-iso-
mer (R = Ph, Et). However, when R was methyl group,
which has a smaller bulk, the aldehyde could attack the al-
lenolate from either side of it and gave a mixture of Z- and
E-isomers with a Z/E ratio of > 20:1. On the other hand,
when a b-substituted acetylenic ketone was employed, a
CF3COOZnR
CuI (5 mol%)
O
R1
2
R2
R1
R CHO
+
CH2CI2, r.t.
R3
R
R3
4
2
5
Scheme 2
Table 2 Reaction of b-Substituted a,b-Acetylenic Ketones with CF COOZnR and Aldehydes in the Presence of CuI (5 mol%)
3
Entry
R
R1
R3
R2
Time (h)
Product
5a
Yield (%)a
91 (74)c
88
Z/E
1
2
3
4
5
Me
Me
Et
C H
C H
C H
20
20
15
15
15
15
4:1
6
5
5
5
5
5
3
7
7
7
7
5
7
6
5
C H
C H
4-CH C H
4
5b
3:1
6
3
3
6
C H
C H
C H
5
5c
85 (54)c
90
1.2:1b
1.3:1b
3:1b
6
3
6
Et
C H
C H
4-MeOC H
5d
6
3
6
4
4
Et
C H
C H
C H
5
5e
85
6
6
6
6
Et
Me
C H
4-MeOC H
5f
82
1.2:1b
3
6
a
Yields after purification by column chromatography.
Z/E selectivity was determined by H NMR analysis.
The reaction was carried out in the absence of CuI.
b
c
1
Synthesis 2006, No. 4, 666–674 © Thieme Stuttgart · New York

PAPER
Efficient CuI-Promoted Synthesis of Tri- and Tetrasubstituted Alkenes
669
double substituted intermedinate b,b¢-substituted allenol- consumption of the starting aldehyde. The reaction was quenched
by sat. aq NH Cl and extracted with Et O (10 × 3 mL). The com-
ate was formed. The aldehyde reacted with allenolate
from either side since the steric divergence of the two
sides decrease, so that a mixture of Z- and E-isomers with
moderate to low ratio was formed as summarized in
Table 2.
4
2
bined organic extracts were washed with brine, dried over MgSO
4
and concentrated under reduced pressure to an oily residue. The de-
sired product was isolated by silica gel chromatography with PE–
EtOAc (10:1–5:1).
(
Z)-3-[(4-Chlorophenyl)(hydroxy)methyl]-4-phenylbut-3-en-2-
In summary, an efficient and mild method to synthesize
tri- and tetrasubstituted alkenes has been developed. Com-
one (3a)
Prepared according to general procedure 1 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow oil (84%).
pared to the only CF CO ZnR based system, this new pro-
3
2
cedure can be subjected to more substrates and increase
the reaction yields dramatically.
IR (neat): 3430, 2964, 1682, 1597, 1491, 1409, 1361, 1261, 1187,
1
–1
091, 1015, 866, 802, 754, 699 cm .
1
H NMR (300 MHz, CDCl ): d = 7.23–7.29 (m, 7 H), 7.10–7.16 (m,
3
CF3CO2ZnR + CuI
CF3CO2ZnR + RCu
CF3CO2ZnI + RCu
2
H), 6.85 (br s, 1 H), 5.45 (br s, 1 H), 3.28 (s, 1 H), 1.74 (s, 3 H).
1
3
(CF3CO2ZnR) (RCu)
C NMR (75 MHz, CDCl ): d = 207.9, 144.6, 139.7, 135.3, 133.7,
3
1
33.0, 128.9, 128.8, 128.7, 127.9, 75.6, 31.6.
6
+
HRMS (EI): m/z [M ] calcd for C H O Cl: 286.0761; found:
1
7
15
2
2
86.0761.
RCu
CF3CO2ZnR
(
Z)-3-[(4-Methoxyphenyl)(hydroxy)methyl]-4-phenylbut-3-en-
-one (3b)
2
CF3CO2Zn
O
Prepared according to general procedure 1 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow oil (49%).
O
R1
R1
6
R
R3
IR (neat): 3472, 1683, 1609, 1506, 1365, 1244, 1226, 1192, 1172,
1074, 1018, 922, 838, 822, 749 cm .
R3
–1
4
7
1
H NMR (300 MHz, CDCl ): d = 7.15–7.28 (m, 7 H), 6.82 (d, J =
3
2
8.8 Hz, 2 H), 5.47 (d, J = 5.3 Hz, 1 H), 3.74 (s, 3 H), 2.85 (d, J = 5.3
R CHO
Hz, 1 H), 1.74 (s, 3 H).
OH
R
O
CF3CO2
Zn
13
C NMR (75 MHz, CDCl ): d = 208.5, 159.4, 145.6, 135.6, 133.5,
R1
3
H
R2
R1
H O+
131.3, 128.7, 128.6, 127.9, 114.0, 75.5, 55.3, 31.6.
3
O
+
R3
HRMS (EI): m/z [M ] calcd for C H O : 282.1256; found:
282.1274.
R3
18 18
3
O
R2
R
5
(
Z)-2-[Hydroxy(phenyl)methyl]-1-phenylbut-2-en-1-one (3c)
Scheme 3 A plausible mechanism of the reaction in the presence of
CuI
Prepared according to general procedure 1 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow oil (68%).
IR (neat): 3439, 3061, 3029, 2917, 1650, 1595, 1578, 1449, 1384,
–
1
1
363, 1244, 1070, 1020, 913, 700 cm .
All reactions were conducted under nitrogen atmosphere in oven-
dried glassware with magnetic stirring. Dichloromethane was dried
and freshly distilled from calcium hydride under nitrogen atmo-
sphere. Diethyl ether and THF were dried and distilled from sodium
and benzophenone under nitrogen protection. Diethylzinc, dimeth-
ylzinc and diphenylzinc were purchased from Aldrich, 3-butyn-2-
one was purchased from Lancaster, aldehydes were purified by dis-
tillation or recrystallization prior to use. Petroleum ether (PE) used
had the boiling range of 60–90 °C.
1
H NMR (300 MHz, CDCl ): d = 7.68 (d, J = 7.3 Hz, 2 H), 7.18–
3
7
.35 (m, 9 H), 5.77 (s, 1 H), 2.60 (s, 1 H), 1.72 (s, 3 H).
13C NMR (75 MHz, CDCl
129.6, 129.3, 128.6, 128.4, 127.6, 126.5, 76.3, 33.2.
): d = 200.2, 141.6, 140.6, 137.7, 133.4,
3
+
HRMS (EI): m/z [M ] calcd for C H O : 252.1152; found:
2
1
7
16
2
52.1150.
(
Z)-2-[(4-Chlorophenyl)(hydroxy)methyl]-1,3-diphenylprop-2-
1H NMR (300 MHz) and 13C NMR (75 MHz) spectra were mea-
sured with a Bruker AC 300 spectrometer using TMS as an internal
standard. HRMS data were obtained with a Micromass GCT TOF
mass spectrometer. IR spectra were recorded on a Perkin-Elmer
FT210 spectrophotometer. Chromatographic purification was per-
formed on silica gel (100–200 mesh) and analytical TLC on silica
gel 60-F254 was detected by fluorescence.
en-1-one (3d)
Prepared according to general procedure 1 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow solid (91%);
mp 121.0–122.0 °C.
IR (KBr): 3371, 2868, 1642, 1592, 1489, 1448, 1370, 1264, 1238,
–1
1
085, 1031, 1013, 829, 697, 683 cm .
1
H NMR (300 MHz, CDCl ): d = 7.56 (d, J = 7.7 Hz, 2 H), 7.32 (d,
3
J = 8.2 Hz, 2 H), 7.16–7.29 (m, 3 H), 7.10 (m, 2 H), 6.99 (m, 5 H),
Reaction of a,b-Acetylenic Ketones with CF CO ZnPh and Al-
3
2
6
.92 (s, 1 H), 5.63 (d, J = 5.2 Hz, 1 H), 3.17 (d, J = 5.2 Hz, 1 H).
dehydes in the Presence of CuI (Table 1); General Procedure 1
1
3
In the presence of CuI (0.025 mmol, 4.7 mg), to a solution of Ph Zn
C NMR (75 MHz, CDCl ): d = 200.4, 141.6, 139.7, 136.0, 134.7,
2
3
(
165 mg, 0.75 mmol) in CH Cl (2 mL) at 0 °C was slowly added
133.7, 133.5, 132.6, 129.5, 129.1, 128.7, 128.4, 128.3, 128.2, 128.0,
76.2.
2
2
dropwise CF COOH (58 mL, 0.75 mmol) via syringe under N . Af-
3
2
ter stirring for 60 min at r.t., aldehyde (0.5 mmol) was added fol-
lowed by addition of the acetylenic ketone (0.75 mmol). The
mixture was stirred for 10–15 h at r.t. until TLC indicated complete
+
HRMS (EI): m/z [M ] calcd for C H O Cl: 348.0917; found:
2
2
17
2
3
48.0898.
Synthesis 2006, No. 4, 666–674 © Thieme Stuttgart · New York

6
70
S. Xue et al.
PAPER
HRMS (EI): m/z [M ] calcd for C H O Cl: 378.1023; found:
+
(
Z)-2-[Hydroxy(4-methoxyphenyl)methyl]-1,3-diphenylprop-2-
2
3
19
3
en-1-one (3e)
378.1019.
Prepared according to general procedure 1 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); yellow solid (66%); mp
Reaction of a,b-Acetylenic Ketones with CF CO ZnEt and Al-
dehydes in the Presence of CuI (Table 1 and Table 2); General
Procedure 2
3
2
9
6.5–97.5 °C.
IR (KBr): 3372, 2952, 2832, 1643, 1592, 1512, 1448, 1369, 1249,
–
1
In the presence of CuI (0.025 mmol, 4.7 mg), to a solution of Et
2
Zn
1
174, 1036, 959, 828, 757, 696, 686 cm .
(
77 mL, 0.75 mmol) in CH Cl (2 mL) at 0 °C was slowly added
2
2
1
H NMR (300 MHz, CDCl ): d = 7.59 (d, J = 7.3 Hz, 2 H), 7.28 (m,
H), 7.10 (m, 2 H), 6.95–7.05 (m, 5 H), 6.89 (s, 1 H), 6.78 (d, J =
.6 Hz, 2 H), 5.62 (d, J = 4.4 Hz, 1 H), 3.70 (s, 3 H), 2.91 (d, J = 4.4
3
dropwise CF COOH (58 mL, 0.75 mmol) via syringe under N . Af-
3
2
3
8
ter stirring for 30 min at 0 °C, aldehyde (0.5 mmol) was added, and
then the acetylenic ketone (0.75 mmol) was added. The mixture was
stirred for 5–15 h at r.t. until TLC indicated complete consumption
of the starting aldehyde. The reaction was quenched by sat. aq
Hz, 1 H).
1
3
C NMR (75 MHz, CDCl ): d = 200.5, 159.3, 142.6, 136.2, 135.1,
3
NH Cl and extracted with Et O (10 × 3 mL). The combined organic
1
7
33.2, 133.1, 131.4, 129.5, 129.0, 128.2, 128.1, 128.0, 127.9, 113.9,
6.2, 55.2.
4
2
extracts were washed with brine, dried over MgSO and concentrat-
4
ed under reduced pressure to an oily residue. The desired product
was isolated by silica gel chromatography with PE–EtOAc (5:1–
+
HRMS (EI): m/z [M ] calcd for C H O : 344.1412; found:
2
3
20
3
3
44.1429.
1
0:1).
(
(
Z)-2-[Hydroxy(phenyl)methyl]-1,3-diphenylprop-2-en-1-one
3f)
(
Z)-3-[Hydroxy(phenyl)methyl]hex-3-en-2-one (3i)
Prepared according to general procedure 2 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow oil (93%).
Prepared according to general procedure 1 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); yellow solid (80%); mp
7
IR (neat): 3428, 2968, 1956, 1682, 1493, 1453, 1372, 1212, 1021,
7
8.0–79.5 °C.
–
1
65, 702 cm .
IR (KBr): 3379, 3059, 2867, 1642, 1592, 1494, 1448, 1373, 1262,
1
1
–
1
H NMR (300 MHz, CDCl ): d = 7.20–7.30 (m, 5 H), 5.83 (dt, J =
3
237, 1034, 1022, 957, 758, 724, 697 cm .
1
.0, 7.6 Hz, 1 H), 5.37 (d, J = 5.5 Hz, 1 H), 2.83 (d, J = 5.5 Hz, 1
1
H NMR (300 MHz, CDCl ): d = 7.58 (d, J = 8.4 Hz, 2 H), 7.38 (d,
3
H), 2.25 (dq, J = 7.5, 7.6 Hz, 2 H), 2.16 (s, 3 H), 1.06 (t, J = 7.5 Hz,
3
J = 8.7 Hz, 2 H), 7.25 (m, 3 H), 7.16 (m, 1 H), 7.08 (m, 2 H), 7.00
H).
(m, 5 H), 6.91 (s, 1 H), 5.67 (d, J = 5.1 Hz, 1 H), 3.06 (d, J = 5.1 Hz,
1
3
C NMR (75 MHz, CDCl ): d = 204.58, 142.79, 141.84, 139.39,
1
1
H).
3
1
28.47, 127.67, 126.44, 75.63, 31.72, 22.92, 13.96.
3
C NMR (75 MHz, CDCl ): d = 200.5, 142.2, 141.0, 136.2, 135.0,
3
+
HRMS (EI): m/z [M ] calcd for C H O : 204.1150; found:
2
1
33.2, 131.9, 129.5, 129.0, 128.5, 128.2, 128.1, 127.9, 126.6, 76.7.
13 16
2
04.1142.
+
HRMS (EI): m/z [M ] calcd for C H O : 314.1307; found:
2
2
18
2
3
14.1297.
(
Z)-3-[Hydroxy(4-methoxyphenyl)methyl]hex-3-en-2-one (3j)
Prepared according to general procedure 2 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow oil (93%).
(
Z)-1-(4-Chlorophenyl)-2-[hydroxy(phenyl)methyl]-3-phenyl-
prop-2-en-1-one (3g)
Prepared according to general procedure 1 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); yellow solid (94%); mp
1
IR (neat): 3435, 2966, 2838, 1683, 1611, 1585, 1512, 1249, 1174,
–
1
1
033, 837 cm .
17.0–119.0 °C.
1
H NMR (300 MHz, CDCl ): d = 7.18 (d, J = 8.5 Hz, 2 H), 6.80 (d,
3
J = 8.5 Hz, 2 H), 5.80 (t, J = 7.5 Hz, 1 H), 5.32 (d, J = 4.9 Hz, 1 H),
3.72 (s, 3 H), 2.75 (d, J = 4.9 Hz, 1 H), 2.22 (dq, J = 7.5, 7.5 Hz, 2
H), 2.10 (s, 3 H), 0.99 (t, J = 7.5 Hz, 3 H).
IR (KBr): 3467, 3058, 3030, 2963, 1669, 1586, 1570, 1492, 1454,
–
1
1
399, 1228, 1169, 1087, 1014, 972, 843, 783, 697 cm .
1
H NMR (300 MHz, CDCl ): d = 7.49 (d, J = 8.5 Hz, 2 H), 7.35 (d,
3
1
3
C NMR (75 MHz, CDCl ): d = 204.6, 159.2, 142.9, 138.6, 133.9,
J = 7.1 Hz, 2 H), 7.19–7.27 (m, 3 H), 6.93–7.05 (m, 7 H), 6.93 (s, 1
H), 5.67 (d, J = 4.8 Hz, 1 H), 3.00 (d, J = 4.8 Hz, 1 H).
3
1
27.8, 113.9, 75.1, 55.3, 31.6, 22.8, 14.0.
+
1
3
HRMS (CI): m/z [MH ] calcd for C H O : 235.1334; found:
C NMR (75 MHz, CDCl ): d = 199.3, 141.8, 140.9, 139.7, 134.8,
14 18
3
3
2
35.1336.
1
7
34.6, 132.2, 130.8, 129.1, 128.7, 128.6, 128.4, 128.3, 128.2, 126.6,
6.9.
(
1
Z)-2-[Hydroxy(3-methoxyphenyl)methyl]-1-phenylpent-2-en-
-one (3k)
+
HRMS (EI): m/z [M ] calcd for C H O Cl: 348.0917; found:
2
2
17
2
3
48.0911.
Prepared according to general procedure 2 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow oil (89%).
(
Z)-1-(4-Methoxyphenyl)-2-[hydroxy(4-chlorophenyl)methyl]-
-phenylprop-2-en-1-one (3h)
IR (neat): 3462, 2966, 1657, 1597, 1487, 1450, 1368, 1317, 1259,
3
–
1
1
158, 1040, 958, 876, 786 cm .
Prepared according to general procedure 1 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); yellow oil (96%).
1
H NMR (300 MHz, CDCl ): d = 7.75 (d, J = 8.4 Hz, 2 H), 7.51 (m,
3
1
H), 7.38 (m, 2 H), 7.22 (m, 1 H), 6.94 (m, 2 H), 6.75 (m, 1 H), 5.90
(t, J = 7.8 Hz, 1 H), 5.51 (d, J = 5.3 Hz, 1 H), 3.75 (s, 3 H), 3.18 (d,
J = 5.3 Hz, 1 H), 1.83 (dq, J = 7.4, 7.8 Hz, 2 H), 0.88 (t, J = 7.4 Hz,
IR (KBr): 3436, 3025, 2964, 1644, 1596, 1571, 1508, 1490, 1421,
1
–
1
247, 1167, 1089, 1029, 957, 833, 757, 695 cm .
1
H NMR (300 MHz, CDCl ): d = 7.55 (d, J = 8.9 Hz, 2 H), 7.30 (d,
3
3
H).
J = 8.4 Hz, 2 H), 7.20 (d, J = 8.4 Hz, 2 H), 7.02 (m, 5 H), 6.85 (s, 1
H), 6.58 (d, J = 8.9 Hz, 2 H), 5.58 (d, J = 5.1 Hz, 1 H), 3.88 (s, 3 H),
1
3
C NMR (75 MHz, CDCl ): d = 200.2, 159.8, 143.4, 140.6, 137.9,
3
1
2
36.6, 133.5, 129.5, 129.4, 128.6, 118.9, 113.4, 111.9, 76.6, 55.3,
3.4, 13.6.
3
1
.34 (d, J = 5.1 Hz, 1 H).
3
C NMR (75 MHz, CDCl ): d = 198.8, 171.3, 163.8, 141.6, 139.7,
3
+
HRMS (CI): m/z [MH ] calcd for C H O : 296.1412; found:
1
7
34.9, 133.5, 131.9, 129.3, 129.0, 128.9, 128.6, 128.2, 128.0, 113.6,
6.4, 55.4.
19 20
3
2
96.1404.
Synthesis 2006, No. 4, 666–674 © Thieme Stuttgart · New York

PAPER
Efficient CuI-Promoted Synthesis of Tri- and Tetrasubstituted Alkenes
671
(
Z)-1-(4-Methoxyphenyl)-2-[hydroxy(phenyl)methyl]pent-2-
IR (neat): 3437, 2940, 2837, 1686, 1600, 1489, 1435, 1365, 1260,
1153, 1043, 794, 753, 700 cm .
–
1
en-1-one (3l)
Prepared according to general procedure 2 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow oil (85%).
1
H NMR (300 MHz, CDCl ): d = 7.20 (m, 1 H), 6.82 (m, 2 H), 6.75
3
(
m, 1 H), 5.96 (q, J = 7.4 Hz, 1 H), 5.35 (d, J = 5.8 Hz, 1 H), 3.74
IR (neat): 3436, 2966, 1651, 1597, 1509, 1456, 1420, 1370, 1314,
(s, 3 H), 2.89 (d, J = 5.8 Hz, 1 H), 2.15 (s, 3 H), 1.86 (d, J = 7.4 Hz,
3 H).
–
1
1
258, 1158, 1025, 954, 909, 851, 733, 701 cm .
1
13
H NMR (300 MHz, CDCl ): d = 7.73 (d, J = 6.9 Hz, 2 H), 7.37 (m,
C NMR (75 MHz, CDCl ): d = 204.3, 159.7, 144.0, 143.6, 133.3,
3
3
2
H), 7.16–7.33 (m, 3 H), 6.83 (d, J = 6.9 Hz, 2 H), 5.84 (t, J = 7.6
Hz, 1 H), 5.51 (br s, 1 H), 3.84 (s, 3 H), 3.30 (br s, 1 H), 1.85 (dq,
J = 7.4, 7.6 Hz, 2 H), 0.89 (t, J = 7.4 Hz, 3 H).
129.4, 118.7, 113.0, 111.9, 75.4, 55.2, 31.7, 15.5.
+
HRMS (EI): m/z [M ] calcd for C H O : 220.1099; found:
1
3
16
3
2
20.1092.
1
3
C NMR (75 MHz, CDCl ): d = 198.7, 164.0, 141.7, 140.8, 135.5,
3
1
31.9, 130.7, 128.4, 127.7, 126.4, 113.8, 76.8, 55.5, 23.3, 13.6.
(Z)-3-[(1-Naphthyl)(hydroxy)methyl]pent-3-en-2-one (3p)
Prepared according to general procedure 3 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow oil (89%).
+
HRMS (CI): m/z [MH ] calcd for C H O : 297.1485; found:
2
1
9
21
3
97.1484.
IR (neat): 3423, 3051, 2919, 1685, 1510, 1422, 1386, 1354, 1210,
–
1
Reaction of a,b-Acetylenic Ketones with CF CO ZnMe and Al-
1074, 1056, 987, 804, 784, 733 cm .
3
2
dehydes in the Presence of CuI (Table 1 and Table 2); General
Procedure 3
1
H NMR (300 MHz, CDCl ): d = 7.79–7.92 (m, 3 H), 7.64 (m, 1 H),
3
7
(
.40–7.51 (m, 3 H), 6.28 (br s, 1 H), 5.82 (q, J = 7.3 Hz, 1 H), 2.85
In the presence of CuI (0.025 mmol, 4.7 mg), to a solution of Me Zn
2
d, J = 4.4 Hz, 1 H), 2.32 (s, 3 H), 1.83 (d, J = 7.3 Hz, 3 H).
(
54 mL, 0.75 mmol) in CH Cl (2 mL) at 0 °C was slowly added
2 2
1
3
C NMR (75 MHz, CDCl ): d = 204.2, 143.9, 137.0, 133.7, 133.4,
dropwise CF COOH (58 mL, 0.75 mmol) via syringe under N . Af-
3
3
2
1
1
30.6, 128.8, 128.5, 126.2, 125.7, 125.4, 124.2, 123.7, 71.5, 31.3,
ter stirring for 30 min at 0 °C, aldehyde (0.5 mmol) was added, and
then the acetylenic ketone (0.75 mmol) was added. The mixture was
stirred for10–15 h at r.t. until TLC indicated complete consumption
of the starting aldehyde. The reaction was quenched by sat. aq
NH Cl and extracted with Et O (10 × 3 mL). The combined organic
5.5.
+
HRMS (EI): m/z [M ] calcd for C H O : 240.1150; found:
2
1
6
16
2
40.1148.
4
2
extracts were washed with brine, dried over MgSO and concentrat-
4
(Z)-2-[Hydroxy(phenyl)methyl]-1-phenylbut-2-en-1-one (3q)
Prepared according to general procedure 3 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow oil (91%).
ed under reduced pressure to an oily residue. The desired product
was isolated by silica gel chromatography with PE–EtOAc (5:1–
1
0:1).
IR (neat): 3439, 3061, 3029, 2917, 1650, 1595, 1578, 1449, 1384,
1
1H NMR (300 MHz, CDCl
1 H), 7.12–7.35 (m, 7 H), 5.94 (q, J = 7.7 Hz, 1 H), 5.49 (d, J = 4.7
Hz, 1 H), 3.10 (d, J = 4.7 Hz, 1 H), 1.42 (d, J = 7.7 Hz, 3 H).
13C NMR (75 MHz, CDCl
129.6, 129.3, 128.6, 128.4, 127.6, 126.5, 76.3, 15.8.
–
1
363, 1244, 1070, 1020, 913, 700 cm .
(
Z)-3-[Hydroxy(phenyl)methyl]pent-3-en-2-one (3m)
Prepared according to general procedure 3 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow oil (94%).
3
): d = 7.68 (d, J = 7.3 Hz, 2 H), 7.45 (m,
IR (neat): 3428, 2964, 2920, 1684, 1493, 1451, 1260, 1020, 806,
–
1
7
02 cm .
3
): d = 200.2, 141.6, 140.6, 137.7, 133.4,
1
H NMR (300 MHz, CDCl ): d = 7.17–7.31 (m, 5 H), 5.95 (d, J =
3
+
7
.3 Hz, 1 H), 5.39 (br s, 1 H), 2.92 (br s, 1 H), 2.15 (s, 3 H), 1.85 (d,
HRMS (EI): m/z [M – H ] calcd for C17
H
16
O
2
: 251.1072; found:
J = 7.3 Hz, 3 H).
251.1074.
1
3
C NMR (75 MHz, CDCl ): d = 204.4, 144.3, 141.8, 132.9, 128.4,
3
(
Z)-2-[Hydroxy(4-methoxyphenyl)methyl]-1-phenylbut-2-en-1-
1
27.6, 126.4, 72.9, 31.6, 15.5.
one (3r)
+
HRMS (EI): m/z [M ] calcd for C H O : 190.0994; found:
1
2
14
2
Prepared according to general procedure 3 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow oil (82%).
1
90.0971.
IR (neat): 3453, 2916, 2837, 1656, 1612, 1579, 1512, 1449, 1362,
(
(
Z)-3-[(4-Methoxyphenyl)(hydroxy)methyl]pent-3-en-2-one
3n)
–
1
1
303, 1248, 1072, 1034, 912, 837, 732 cm .
1H NMR (300 MHz, CDCl
): d = 7.70 (d, J = 7.8 Hz, 2 H), 7.44 (t,
J = 7.4 Hz, 1 H), 7.40 (t, J = 7.8 Hz, 2 H), 7.28 (t, J = 8.4 Hz, 2 H),
.84 (d, J = 8.4 Hz, 2 H), 5.98 (q, J = 7.4 Hz, 1 H), 5.45 (d, J = 4.6
Hz, 1 H), 3.70 (s, 3 H), 2.95 (d, J = 4.6 Hz, 1 H), 1.42 (d, J = 7.4 Hz,
Prepared according to general procedure 3 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow oil (88%).
3
6
IR (neat): 3436, 2935, 2838, 1685, 1611, 1511, 1249, 1174, 1033,
8
–1
35, 769 cm .
3
H).
1
H NMR (300 MHz, CDCl ): d = 7.26 (d, J = 8.6 Hz, 2 H), 6.88 (d,
3
13
C NMR (75 MHz, CDCl ): d = 200.3, 159.1, 142.7, 137.7, 133.8,
3
J = 8.6 Hz, 2 H), 6.01 (q, J = 7.3 Hz, 1 H), 5.42 (br s, 1 H), 3.80 (s,
1
33.4, 129.3, 129.2, 128.7, 127.8, 113.8, 75.9, 55.3, 15.8.
3
1
H), 2.77 (br s, 1 H), 2.22 (s, 3 H), 1.91 (d, J = 7.3 Hz, 3 H).
+
3
HRMS (EI): m/z [M ] calcd for C18
H
18
O
3
: 282.1256; found:
C NMR (75 MHz, CDCl ): d = 204.3, 159.0, 144.5, 133.9, 132.0,
3
2
82.1261.
1
27.8, 113.7, 74.7, 55.2, 31.4, 15.3.
+
HRMS (EI): m/z [M ] calcd for C H O : 220.1099; found:
1
3
16
3
(Z)-1-(4-Chlorophenyl)-2-[(hydroxy)phenylmethyl]but-2-en-1-
one (3s)
2
20.1080.
Prepared according to general procedure 3 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow oil (92%).
(
(
Z)-3-[(3-Methoxyphenyl)(hydroxy)methyl]pent-3-en-2-one
3o)
IR (neat): 3446, 3030, 2918, 1707, 1660, 1587, 1487, 1452, 1401,
Prepared according to general procedure 3 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow oil (90%).
–
1
1
248, 1172, 1090, 1012, 912, 849 cm .
Synthesis 2006, No. 4, 666–674 © Thieme Stuttgart · New York

6
72
S. Xue et al.
PAPER
1
1
H NMR (300 MHz, CDCl ): d = 7.62 (d, J = 8.6 Hz, 2 H), 7.10–
H NMR (300 MHz, CDCl ): d = 7.57 (d, J = 7.7 Hz, 2 H), 7.37 (m,
3
3
7
2
.30 (m, 7 H), 5.95 (q, J = 7.2 Hz, 1 H), 5.49 (d, J = 5.1 Hz, 1 H),
.95 (d, J = 5.1 Hz, 1 H), 1.43 (d, J = 7.2 Hz, 3 H).
1 H), 7.19–7.29 (m, 4 H), 7.06–7.16 (m, 3 H), 5.80 (d, J = 7.2 Hz, 1
H), 3.59 (d, J = 7.2 Hz, 1 H), 1.90 (s, 3 H), 1.72 (m, 2 H), 1.12–1.35
(m, 2 H), 0.58 (t, J = 7.3 Hz, 3 H).
1
3
C NMR (75 MHz, CDCl ): d = 198.8, 142.3, 141.4, 139.9, 135.9,
3
1
3
1
30.7, 129.3, 128.9, 128.4, 127.8, 126.3, 74.1, 14.6.
C NMR (75 MHz, CDCl ): d = 201.5, 142.5, 140.3, 138.3, 136.1,
3
+
133.0, 129.2, 128.3, 128.2, 127.2, 126.0, 71.3, 36.4, 25.3, 21.5,
4.4.
HRMS (EI): m/z [M ] calcd for C H O Cl: 286.0761; found:
2
1
7
15
2
1
86.0764.
+
HRMS (EI): m/z [M ] calcd for C H O : 294.1620; found:
2
0
22
2
(
Z)-1-(4-Chlorophenyl)-2-[(4-methylphenyl)(hydroxy)methyl]-
294.1628.
but-2-en-1-one (3t)
Prepared according to general procedure 3 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow solid (93%);
(Z)-2-[Hydroxy(4-methylphenyl)methyl]-3-methyl-1-phenyl-
hex-2-en-1-one (5b)
8
2.0–83.0 °C.
Prepared according to general procedure 3 and purified by chroma-
tography on silica gel (PE–EtOAc, 15:1–20:1); light yellow oil
(88%) with (Z)-5b (68%) and (E)-5b (20%).
IR (neat): 3432, 2919, 1660, 1585, 1439, 1400, 1251, 1089, 1010,
9
–
1
21, 824, 749 cm .
1
H NMR (300 MHz, CDCl ): d = 7.63 (d, J = 8.6 Hz, 2 H), 7.30 (d,
3
(Z)-5b
J = 8.6 Hz, 2 H), 7.16 (d, J = 8.1 Hz, 2 H), 7.05 (d, J = 8.1 Hz, 2 H),
5
Hz, 1 H), 2.24 (s, 3 H), 1.40 (d, J = 7.2 Hz, 3 H).
1
IR (neat): 3432, 2919, 1660, 1585, 1439, 1400, 1251, 1089, 1010,
.93 (q, J = 7.2 Hz, 1 H), 5.46 (d, J = 5.1 Hz, 1 H), 2.84 (d, J = 5.1
–1
9
21 cm .
1
H NMR (300 MHz, CDCl ): d = 7.62 (d, J = 7.7 Hz, 2 H), 7.42 (m,
3
3
C NMR (75 MHz, CDCl ): d = 198.8, 142.5, 139.8, 138.5, 137.5,
3
1 H), 7.27 (m, 2 H), 7.18 (d, J = 7.9 Hz, 2 H), 6.97 (d, J = 7.9 Hz, 2
H), 5.75 (d, J = 7.2 Hz, 1 H), 3.30 (d, J = 7.2 Hz, 1 H), 2.33 (s, 3 H),
1.87 (s, 3 H), 1.74 (t, J = 7.5 Hz, 2 H), 1.28 (m, 2 H), 0.58 (t, J = 7.5
Hz, 3 H).
1
36.0, 130.7, 129.2, 129.1, 129.0, 126.4, 76.0, 21.2, 15.8.
+
HRMS (EI): m/z [M ] calcd for C H O Cl: 300.0917; found:
3
1
8
17
2
00.0912.
1
3
C NMR (75 MHz, CDCl ): d = 201.9, 141.1, 139.6, 138.3, 136.8,
3
(
Z)-1-(4-Methoxyphenyl)-2-[(4-methylphenyl)(hydroxy)meth-
1
2
35.9, 133.2, 129.4, 128.9, 128.5, 125.9, 72.4, 36.4, 21.7, 21.7,
1.1, 14.5.
yl]but-2-en-1-one (3u)
Prepared according to general procedure 3 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1); light yellow oil (89%).
+
HRMS (EI): m/z [M ] calcd for C H O : 308.1776; found:
2
1
24
2
3
08.1769.
IR (neat): 3445, 2919, 1651, 1597, 1509, 1443, 1420, 1364, 1312,
1
–
1
253, 1170, 1030, 912, 826 cm .
(
E)-5b
1
IR (neat): 3434, 2919, 1710, 1596, 1439, 1408, 1251, 1085, 1015,
H NMR (300 MHz, CDCl ): d = 7.70 (d, J = 8.6 Hz, 2 H), 7.19 (d,
3
–
1
9
27 cm .
J = 7.9 Hz, 2 H), 7.03 (d, J = 7.9 Hz, 2 H), 6.80 (d, J = 8.6 Hz, 2 H),
5
3
.87 (q, J = 7.2 Hz, 1 H), 5.42 (d, J = 5.3 Hz, 1 H), 3.78 (s, 3 H),
.15 (d, J = 5.3 Hz, 1 H), 2.22 (s, 3 H), 1.42 (d, J = 7.2 Hz, 3 H).
1
H NMR (300 MHz, CDCl ): d = 7.60 (d, J = 7.2 Hz, 2 H), 7.38 (m,
3
1
H), 7.27 (m, 2 H), 7.19 (m, 2 H), 6.95 (d, J = 8.0 Hz, 2 H), 5.77
1
3
(d, J = 7.6 Hz, 1 H), 3.57 (d, J = 7.6 Hz, 1 H), 2.30 (m, 2 H), 2.16
C NMR (75 MHz, CDCl ): d = 198.7, 163.9, 142.6, 138.7, 137.1,
3
(s, 3 H), 1.58 (s, 3 H), 1.60 (m, 2 H), 0.96 (t, J = 7.3 Hz, 3 H).
1
31.8, 130.6, 129.0, 128.5, 126.4, 113.9, 76.4, 55.5, 21.1, 15.7.
1
3
+
C NMR (75 MHz, CDCl ): d = 201.5, 141.9, 138.8, 138.3, 137.1,
HRMS (EI): m/z [M ] calcd for C H O : 296.1412; found:
2
3
1
9
20
3
1
2
36.9, 134.0, 130.8, 129.1, 128.7, 126.5, 71.6, 36.2, 23.2, 22.7,
2.5, 14.9.
96.1408.
2
-[Hydroxy(phenyl)methyl]-3-methyl-1-phenylhex-2-en-1-one
+
HRMS (EI): m/z [M ] calcd for C H O : 308.1776; found:
2
1
24
2
(
5a)
3
08.1766.
Prepared according to general procedure 3 and purified by chroma-
tography on silica gel (PE–EtOAc, 20:1–25:1); light yellow oil
2
-[Hydroxy(phenyl)methyl]-3-ethyl-1-phenylhex-2-en-1-one
(
91%) with (Z)-5a (74%) and (E)-5a (17%).
(5c)
Prepared according to general procedure 2 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1–20:1) to give a light yellow
oil as a mixture of (Z)-5c and (E)-5c (1.2:1, 85%).
1
(
Z)-5a
IR (neat): 3452, 1662, 1640, 1596, 1580, 1493, 1449, 1380, 1318,
1
–
1
234, 1175, 1026, 952 cm .
H NMR (300 MHz, CDCl ; major isomer): d = 7.58 (m, 2 H), 7.48
3
1
H NMR (300 MHz, CDCl ): d = 7.57 (d, J = 7.7 Hz, 2 H), 7.19–
3
(m, 1 H), 7.19–7.28 (m, 4 H), 7.13 (m, 3 H), 5.78 (d, J = 7.3 Hz, 1
H), 3.48 (d, J = 7.3 Hz, 1 H), 2.18–2.32 (m, 2 H), 1.75–1.81 (m, 2
H), 1.50 (m, 2 H), 1.13 (t, J = 7.3 Hz, 3 H), 0.56 (t, J = 7.3 Hz, 3 H).
1
7
.38 (m, 5 H), 7.03–7.12 (m, 3 H), 5.81 (d, J = 7.6 Hz, 1 H), 3.72
d, J = 7.6 Hz, 1 H), 2.27–2.34 (m, 2 H), 1.50–1.61 (m, 2 H), 1.46
s, 3 H), 0.97 (t, J = 7.3 Hz, 3 H).
(
(
1
H NMR (300 MHz, CDCl ; minor isomer): d = 7.58 (m, 2 H), 7.48
3
3
C NMR (75 MHz, CDCl ): d = 200.8, 141.5, 140.1, 137.1, 134.7,
3
(m, 1 H), 7.19–7.28 (m, 4 H), 7.13 (m, 3 H), 5.38 (d, J = 7.3 Hz, 1
H), 3.50 (d, J = 7.3 Hz, 1 H), 2.18–2.32 (m, 2 H), 1.75–1.81 (m, 2
H), 1.50 (m, 2 H), 0.98 (t, J = 7.4 Hz, 3 H), 0.78 (t, J = 7.4 Hz, 3 H).
13
1
1
32.1, 128.2, 127.4, 127.1, 126.1, 124.8, 72.6, 38.8, 20.9, 17.8,
3.8.
+
HRMS (EI): m/z [M ] calcd for C H O : 294.1620; found:
2
2
0
22
2
C NMR (75 MHz, CDCl ): d = 200.77, 200.69, 145.1, 144.8,
3
94.1625.
1
1
3
41.37, 141.32, 137.28, 137.13, 134.4, 132.04, 131.99, 128.2,
28.1, 127.3, 127.2, 127.1, 126.4, 126.1, 124.9, 71.31, 71.27, 34.9,
1.6, 26.2, 23.1, 21.1, 20.3, 13.5, 12.9, 12.4, 11.5.
+
(
E)-5a
IR (neat): 3451, 3061, 1717, 1661, 1596, 1579, 1493, 1449, 1379,
–
1
HRMS (EI): m/z [M ] calcd for C21H O : 308.1776; found:
24 2
1
317, 1241, 1175, 1075, 953 cm .
3
08.1769.
Synthesis 2006, No. 4, 666–674 © Thieme Stuttgart · New York

PAPER
Efficient CuI-Promoted Synthesis of Tri- and Tetrasubstituted Alkenes
673
2
-[Hydroxy(4-methoxyphenyl)methyl]-3-ethyl-1-phenylhex-2-
Acknowledgment
en-1-one (5d)
We thank the National Natural Science Foundation of China (No.
0202009) and the Natural Science Foundation of Anhui province
No. 050460302) for financial support.
Prepared according to general procedure 2 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1 –15:1) to give a light yel-
low oil as a mixture of (Z)-5d and (E)-5d (1.3:1, 90%).
1
2
(
H NMR (300 MHz, CDCl ; minor isomer): d = 7.62 (m, 2 H), 7.39
3
(
m, 1 H), 7.19–7.28 (m, 4 H), 6.68 (d, J = 8.7 Hz, 2 H), 5.73 (d, J =
References
7
1
7
1
.2 Hz, 1 H), 3.65 (s, 3 H), 3.28 (d, J = 7.2 Hz, 1 H), 2.26 (m, 2 H),
.79 (m, 2 H), 1.50 (m, 2 H), 1.12 (t, J = 7.5 Hz, 3 H), 0.57 (t, J =
.3 Hz, 3 H).
(
1) Lee, V. J. In Comprehensive Organic Synthesis, Vol. 4;
Trost, B. M.; Fleming, I., Eds.; Pergamon: Oxford, 1991,
1
39–168.
2) Wori, M.; Kuroda, S.; Dekura, F. J. Am. Chem. Soc. 1999,
21, 5591.
3) (a) Denmark, S. E.; Choi, J. Y. J. Am. Chem. Soc. 1999, 121,
821. (b) Maezaki, N.; Sawamoto, H.; Yoshigami, R.;
Suzuki, T.; Tanaka, T. Org. Lett. 2003, 5, 1345.
H NMR (300 MHz, CDCl ; minor isomer): d = 7.62 (m, 2 H), 7.39
3
(
(
(
(
m, 1 H), 7.19–7.28 (m, 4 H), 6.68 (dd, J = 1.9, 8.7 Hz, 2 H), 5.73
d, J = 7.2 Hz, 1 H), 3.65 (s, 3 H), 3.26 (d, J = 7.2 Hz, 1 H), 2.26 (m,
1
2
H), 1.79 (m, 2 H), 1.50 (m, 2 H), 0.93 (t, J = 7.3 Hz, 3 H), 0.80 (t,
5
J = 7.4 Hz, 3 H).
1
3
C NMR (75 MHz, CDCl ): d = 201.8, 201.7, 158.8, 145.5, 145.2,
(4) (a) Trost, B. M.; Pinkerton, A. B. J. Am. Chem. Soc. 1999,
121, 1988. (b) Trost, B. M.; Pinkerton, A. B. Angew. Chem.
Int. Ed. 2000, 39, 360.
(5) Reviews for the Morita–Baylis–Hillman reaction:
(a) Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44,
3
1
1
2
38.4, 138.3, 135.8, 134.8, 134.7, 133.1, 133.0, 129.34, 129.26,
28.3, 127.48, 127.44, 113.8, 113.6, 72.09, 72.06, 55.2, 35.8, 32.6,
7.2, 24.1, 22.2, 21.4, 14.5, 14.0, 13.3, 12.6.
+
HRMS (EI): m/z [M ] calcd for C H O : 338.1882; found:
2
2
26
3
4653. (b) Basavaiah, D.; Darma, R. P.; Hyma, R. S.
3
38.1875.
Tetrahedron 1996, 52, 8001. (c) Langer, P. Angew. Chem.
Int. Ed. 2000, 39, 3049. (d) Basavaiah, D.; Rao, A. J.;
Satyanarayana, T. Chem. Rev. 2003, 103, 811. (e) Kataoka,
T.; Kinoshita, H. Eur. J. Org. Chem. 2005, 45.
2
-[Hydroxy(phenyl)methyl]-1,3-diphenylpent-2-en-1-one (5e)
Prepared according to general procedure 2 and purified by chroma-
tography on silica gel (PE–EtOAc, 10:1–15:1) to give a light yellow
oil as a mixture of (Z)-5e and (E)-5e (3:1, 85%).
1
(
6) (a) Ciganek, E. Org. React. (N.Y.) 1997, 51, 201. (b) Roth,
F.; Gygax, P.; Frater, G. Tetrahedron Lett. 1992, 48, 6371.
(c) Drewes, S. E.; Njamela, O. L.; Emslie, N. D.; Ramesar,
N.; Field, J. S. Synth. Commun. 1993, 23, 2807.
H NMR (300 MHz, CDCl ; major isomer): d = 7.47 (d, J = 7.2 Hz,
3
2
H), 7.11–7.37 (m, 13 H), 5.46 (d, J = 7.0 Hz, 1 H), 3.72 (d, J = 7.0
Hz, 1 H), 2.18 (m, 2 H), 0.71 (t, J = 7.4 Hz, 3 H).
(
7) Marino, J. P.; Linderman, R. J. J. Org. Chem. 1983, 48,
1
4621.
H NMR (300 MHz, CDCl ; minor isomer): d = 7.39 (d, J = 7.1 Hz,
3
(
8) (a) Wei, H. X.; Willis, S.; Li, G. Tetrahedron Lett. 1998, 39,
2
H), 6.95–7.37 (m, 13 H), 6.02 (d, J = 7.0 Hz, 1 H), 4.45 (d, J = 7.0
8203. (b) Wei, H. X.; Willis, S.; Li, G. Synth. Commun.
Hz, 1 H), 2.67 (m, 2 H), 1.05 (t, J = 7.4 Hz, 3 H).
1
999, 29, 2959.
1
3
C NMR (75 MHz, CDCl ): d = 201.4, 200.0, 147.5, 145.4, 140.8,
3
(
9) (a) Wei, H. X.; Hook, J. D.; Fitzgerald, K. A.; Li, G.
Tetrahedron: Asymmetry 1999, 10, 661. (b) Li, G.; Wei, H.
X.; Whittlesey, B. R.; Bartrice, N. N. J. Org. Chem. 1999,
1
1
3
38.1, 132.3, 130.8, 128.3, 128.0, 127.9, 127.6, 127.5, 127.30,
27.25, 127.0, 126.8, 126.6, 126.3, 126.1, 124.8, 124.7, 72.4, 71.7,
0.8, 28.8, 12.0, 10.9.
64, 1061. (c) Li, G.; Wei, H. X.; Hook, J. D. Tetrahedron
+
HRMS (EI): m/z [M ] calcd for C H O : 342.1620; found:
Lett. 1999, 40, 4611. (d) Li, G.; Kim, S. H.; Wei, H. X.
Tetrahedron 2000, 56, 719.
2
4
22
2
3
42.1629.
(
10) (a) Ramachandran, P. V.; Reddy, M. V. R.; Rudd, M. T.;
4
-Ethyl-3-[hydroxy(4-methoxyphenyl)methyl]hept-3-en-2-one
Alaniz, J. R. Tetrahedron Lett. 1998, 39, 8791.
(
5f)
(b) Ramachandran, P. V.; Ram Reddy, M. V.; Rudd, M. T.
Tetrahedron Lett. 1999, 40, 627. (c) Ramachandran, P. V.;
Ram Reddy, M. V.; Rudd, M. T. Chem. Commun. 1999,
1979. (d) Li, G.; Wei, H. X.; Willis, S. Tetrahedron Lett.
1998, 39, 4607. (e) Chen, D.; Timmons, C.; Liu, J. Y.;
Hendley, A.; Li, G. Eur. J. Org. Chem. 2004, 3330.
11) Yu, S.; Li, N. S.; Kabalka, G. W. J. Org. Chem. 1999, 64,
Prepared according to general procedure 2 and purified by chroma-
tography on silica gel (PE–EtOAc, 15:1–10:1) to give a light yellow
oil as a mixture of (Z)-5f and (E)-5f (1.2:1, 82%).
1
H NMR (300 MHz, CDCl ; major isomer): d = 7.30 (d, J = 8.0 Hz,
3
2
H), 6.79 (d, J = 8.0 Hz, 2 H), 5.60 (d, J = 7.1 Hz, 1 H), 3.72 (s, 3
(
(
H), 3.08 (d, J = 7.1 Hz, 1 H), 2.05–2.18 (m, 4 H), 2.01 (s, 3 H), 1.45
5822.
(
m, 2 H), 0.99–1.06 (m, 3 H), 0.83–0.92 (m, 3 H).
12) For conjugate addition of zinc-copper reagents to acetylenic
1
H NMR (300 MHz, CDCl ; minor isomer): d = 7.30 (d, J = 8.0 Hz,
3
esters, see: (a) Knochel, P.; Singer, R. D. Chem. Rev. 1993,
2
H), 6.79 (d, J = 8.0 Hz, 2 H), 5.58 (d, J = 7.0 Hz, 1 H), 3.80 (s, 3
93, 2177. (b) Knoess, H. P.; Furlong, M. T.; Rozema, M. J.;
H), 3.00 (d, J = 7.0 Hz, 1 H), 2.05–2.18 (m, 4 H), 2.01 (s, 3 H), 1.45
Knochel, P. J. Org. Chem. 1991, 56, 5974. (c) Jubert, C.;
Knochel, P. J. Org. Chem. 1992, 57, 5425.
(
m, 2 H), 0.99–1.06 (m, 3 H), 0.83–0.92 (m, 3 H).
1
3
C NMR (75 MHz, CDCl ): d = 208.19, 208.15, 157.7, 143.1,
(13) For copper-catalyzed conjugate addition of zinc reagents to
acetylenic esters, see: (a) Crimmins, M. T.; Nantermet, P. J.
Org. Chem. 1990, 55, 4235. (b) Crimmins, M. T.;
Nantermet, P.; Trotter, B. W.; Vallin, I. M.; Watson, P. S. J.
Org. Chem. 1993, 58, 1038.
3
1
5
43.0, 138.42, 138.36, 133.4, 126.2, 125.96, 125.91, 112.7, 69.7,
4.2, 34.3, 32.1, 31.7, 25.7, 23.0, 21.1, 20.8, 13.3, 13.1, 12.3, 12.2.
+
HRMS (EI): m/z [M ] calcd for C H O : 276.1725; found:
2
1
7
24
3
76.1717.
(
14) For conjugate addition of organozinc reagents to acetylenic
ketones, see: (a) Brunner, M.; Maas, G. Synthesis 1995,
957. (b) Nakamura, E.; Kuwajima, I. J. Am. Chem. Soc.
1984, 106, 3368.
Synthesis 2006, No. 4, 666–674 © Thieme Stuttgart · New York

6
74
S. Xue et al.
PAPER
(17) Kitamura, M.; Miki, T.; Noyori, R. Bull. Chem. Soc. Jpn.
(
15) (a) Xue, S.; Li, Y. L.; Han, K. Z.; Yin, W.; Wang, M.; Guo,
Q. X. Org. Lett. 2002, 4, 905. (b) Xue, S.; Han, K. Z.; He,
L.; Guo, Q. X. Synlett 2003, 870. (c) Xue, S.; He, L.; Han,
K. Z.; Zheng, X. Q.; Guo, Q. X. Carbohydr. Res. 2005, 340,
03.
16) Xue, S.; He, L.; Han, K. Z.; Liu, Y. K.; Guo, Q. X. Synlett
005, 1247.
2000, 73, 999.
(18) (a) Taniguchi, M.; Hino, T.; Kishi, Y. Tetrahedron Lett.
1986, 27, 4767. (b) Taniguchi, M.; Kobayashi, S.;
Nakagawa, M.; Hino, T.; Kishi, Y. Tetrahedron Lett. 1986,
27, 4763. (c) Kinoshita, S.; Kinoshita, H.; Iwamura, T.;
Watanabe, S.; Kataoka, T. Chem. Eur. J. 2003, 9, 1496.
3
(
2
Synthesis 2006, No. 4, 666–674 © Thieme Stuttgart · New York