Coupling reactions of ortho-substituted halobenzenes with alkynes. The synthesis of phenylacetylenes and symmetrical or unsymmetrical 1,2-diphenylacetylenes

Article abstract of DOI:10.1135/cccc19990649

The Pd- or Pd/Cu-catalyzed coupling reactions of halobenzenes bearing the methyl, hydroxymethyl, acetoxymethyl, methoxycarbonyl, or both methoxy and 4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl groups in the ortho-position with gaseous or metallated acetylene, (trialkylsilyl)acetylenes, and arylacetylenes have been systematically studied. Various functionalized aryl- or diarylacetylenes have been synthesized in good to excellent yields. Whereas additional fluoro, nitro, or methoxy group attached to the benzene ring does not interfere in the coupling reactions, the presence of a methoxycarbonyl requires a careful optimization of reaction conditions to achieve moderate yields.

Full text of DOI:10.1135/cccc19990649

Coupling Reactions of Halobenzenes
649
COUPLING REACTIONS OF ortho-SUBSTITUTED HALOBENZENES
WITH ALKYNES. THE SYNTHESIS OF PHENYLACETYLENES AND
SYMMETRICAL OR UNSYMMETRICAL 1,2-DIPHENYLACETYLENES
1,
2,
3
4
Irena G. STARÁ *, Ivo STARÝ *, Adrian KOLLÁROVIČ , Filip TEPLÝ ,
5
David ŠAMAN and Pavel FIEDLER
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic,
Flemingovo n. 2, 166 10 Prague 6, Czech Republic; e-mail: 1 stara@uochb.cas.cz, 2 stary@uochb.cas.cz,
3
4
adrian@uochb.cas.cz, fteply@prfdec.natur.cuni.cz, 5 saman@uochb.cas.cz
Received March 12, 1999
Accepted April 18, 1999
Th e Pd- or Pd/Cu-catalyzed couplin g reaction s of h aloben zen es bearin g th e m eth yl,
h ydroxym eth yl, acetoxym eth yl, m eth oxycarbon yl, or both m eth oxy an d 4,4-dim eth yl-
4,5-dih ydro-1,3-oxazol-2-yl groups in th e ortho-position with gaseous or m etallated acety-
len e, (trialkylsilyl)acetylen es, an d arylacetylen es h ave been system atically studied. Various
fun ction alized aryl- or diarylacetylen es h ave been syn th esized in good to excellen t yields.
Wh ereas addition al fluoro, n itro, or m eth oxy group attach ed to th e ben zen e rin g does n ot
in terfere in th e couplin g reaction s, th e presen ce of a m eth oxycarbon yl requires a careful op-
tim ization of reaction con dition s to ach ieve m oderate yields.
Key w ord s: Haloben zen es; Ph en ylacetylen es; Diph en ylacetylen es; Cross-couplin g reaction s;
Palladium catalysis; Aren es; Alkyn es.
Arylacetylen es are both versatile syn th etic in term ediates an d fun ction al
buildin g blocks of a wide use1. As a result of en orm ous developm en t of
m odern organ om etallic syn th etic tools in th e last two decades, cross-
couplin g reaction s of aryl h alides or triflates with alkyn es un der palla-
dium (0 or II) catalysis an d copper(I) co-catalysis h ave dom in ated in th e
preparation of aryl- an d 1,2-diarylacetylen e derivatives2. Th e un ique posi-
tion of th e couplin g m eth odology stem s from th e m ild reaction con dition s
used, h igh toleran ce to various fun ction al groups, an d broad variability of
th e experim en tal setup allowin g a careful tun in g of reaction con dition s to
ach ieve usually good preparative yields.
In con n ection with our in terest in th e developm en t of n ovel strategies
for th e syn th esis of h elically ch iral m olecules3, we required a gen eral an d
efficien t route to various ortho-fun ction alized arylacetylen es. Alth ough
pleth ora of ph en yl- an d n aph th ylacetylen es h as been described in litera-
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

650
Stará et al.:
ture, on ly little atten tion h as been paid to a system atic study of couplin g
acetylen es with aryl h alides bearin g various groups in th e ortho-position .
Recen tly, we h ave disclosed a report on th e syn th esis of 2-fun ction alized
1-eth yn yln aph th alen e derivatives4. In th is paper, we describe a study on
th e couplin g reaction of 2-substituted h aloben zen es with gaseous or
m etallated acetylen e as well as term in al alkyn es un der Pd or Pd/Cu cataly-
sis.
RESULTS AND DISCUSSION
Coupling Reactions of 2-Halobenzoates with Gaseous or Metallated Acetylene
On treatm en t of 2-brom oben zoate 1a with gaseous acetylen e un der
Pd(PPh 3)2Cl2/CuI catalysis in piperidin e4, th e educt was con sum ed but n o
expected bis-coupled product 2 was detected (Sch em e 1; Table I, en try 1).
Om ittin g th e copper(I) co-catalyst, gen erally used to prom ote th e cou-
plin g1,2, th e desired reaction took place but th e product 2 was isolated in an
un satisfactory yield (Table I, en try 2). Wh en brom in e in 1a was replaced by
iodin e an d Pd(PPh 3)4 was used as th e catalyst, ben zoate 1b afforded th e
diarylacetylen e 2 in an acceptable yield (52%; Table I, en try 3).
H
H
(g)
COOMe
COOMe
X
or
Bu Sn
3
SnBu
3
PdL (cat)
n
MeOOC
2
1a, X = Br
1b, X = I
CuI (cat)
SCHEME 1
In order to com pare th e efficien cy of an altern ative syn th etic m eth odol-
ogy, we turn ed our atten tion to th e cross-couplin g reaction between aryl
h alides an d alkyn ylstan n an es5. On treatm en t of iodoben zoate 1b with
bis(tributylstan n yl)acetylen e un der Pd(PPh 3)2Cl2 catalysis, th e diaryl-
acetylen e 2 was obtain ed in th e best yield ach ieved (56%; Table I, en try 4).
Th e use of Pd(PPh 3)4 in stead of Pd(PPh 3)2Cl2 led to a lower yield of 2 (Table I,
en try 5) in con trast to couplin g h aloben zoates with gaseous acetylen e, vide
supra. Th e Pd(PPh 3)4-catalyzed reaction of iodoben zoate 1b with alkyn yl-
zin c reagen t6 ClZn –C≡C–Zn Cl did n ot afford th e coupled product 2.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Coupling Reactions of Halobenzenes
651
Coupling Reactions of Halobenzenes with Gaseous Acetylene
Th e h aloben zen es 3–7 bearin g a m eth yl or h ydroxym eth yl group in th e
ortho-position h ave been foun d to un dergo sm ooth ly th e Pd-catalyzed cou-
plin g reaction with gaseous acetylen e to provide th e correspon din g
diarylacetylen es 8–12 in h igh yields (76–99%; Table II, en tries 1, 3–8). In all
cases, a positive effect of th e CuI co-catalyst on preparative yields was ob-
served bein g m ost pron oun ced in th e couplin g reaction s of th e
brom on itroben zen e 4 (Table II, cf. en tries 2 an d 3). In terestin gly, th e reac-
tion course of th e Pd/Cu-catalyzed couplin gs of h aloben zen es with acety-
len e was alm ost in varian t to th e presen ce or absen ce of an addition al
3-n itro, 3-m eth oxycarbon yl, an d 4-m eth oxyl group.
TABLE I
Couplin g reaction s of 2-brom o- or 2-iodoben zoate with gaseous or m etallated acetylen e.
Tun in g reaction con dition s
b
Acetylen ea
equivalen t
PdLn
CuI
Con d. Yieldc of 2d
En try Educt
Solven t
m ole % m ole %
°C; h
%
NH
1
2
3
1a
1a
1b
HC≡CH (g)
HC≡CH (g)
HC≡CH (g)
A, 5
A, 5
5
0
0
80; 6
0e
NH
NH
80; 4
80; 3
18
B, 2.5
52
4
5
1b
1b
Bu3Sn –C≡C–Sn Bu3
A, 5
B, 5
0
0
THF
THF
50; 18
50; 18
56f
20f
0.55
Bu3Sn –C≡C–Sn Bu3
0.55
a
Th e reaction con ducted un der atm osph eric pressure of gaseous acetylen e un less n oted oth er-
b
c
wise (stan n ylated acetylen e reacted un der argon ); A: Pd(PPh 3)2Cl2, B: Pd(PPh 3)4; isolated;
d
e
f
see ref.8; th e startin g m aterial con sum ed, a com plex m ixture of products form ed; yield
calculated from GC an alysis of th e reaction m ixture with an in tern al stan dard.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

652
Coupling Reactions of Halobenzenes with (Trialkylsilyl)acetylenes
Stará et al.:
Th e ortho-substituted h aloben zen es 1a, 1b, 6a, 6b, 13–17 were treated with
(trialkylsilyl)acetylen es un der th e Pd(PPh 3)4 catalysis in th e absen ce of CuI
(ref.4) to furn ish th e silyl-protected arylacetylen es 18, 20–23, 25, an d 27
(Table III). Alth ough good preparative yields were m ostly attain ed (up to
99%), it was n ecessary to fin d out th e best reactin g (trialkylsilyl)acetylen e
by trial an d error.
TABLE II
Couplin g reaction s of 2-substituted h aloben zen es with gaseous acetylen e
a
PdLn
CuI
Con d.b
°C; h
Yieldc
%
En try
Educt
Product
m ole % m ole %
1
3
1.5
3
80; 0.25
8d
96
I
2
3
4
5
6
4
4
5
5
0
10
0
80; 4
9
9
9
78
76
98
Br
O
N
NO
2
2
O N
2
80; 2.5
80; 0.75
80; 0.5
r.t.; 1
I
5
10
10
MeOOC
COOMe
MeOOC
5
5
1
10
2
10
HO
OH
OH
I
6b
11d 94
HO
OH
OH
I
7
8
7
7
5
5
0
r.t.; 1
12
12
80
99
MeO
MeO
OMe
10
80; 0.1
a
b
Pd(PPh 3)4; th e reaction con ducted in piperidin e un der atm osph eric pressure of gaseous
acetylen e; isolated; see ref.4.
c
d
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Coupling Reactions of Halobenzenes
653
TABLE III
Couplin g reaction s of 2-substituted h aloben zen es with (trialkylsilyl)acetylen es
b
Acetylen ea
PdLn
Con d.c
°C; h
Yieldd
%
En try
Educt
Product
equivalen t m ole %
OH
OH
Br
1
6a
A, 2.2
5
80; 6
18ae
54
TMS
OH
19
14
TMS
OH
TMS
2
3
6b
6b
A, 2.2
B, 1.2
5
5
50; 20
80; 13
18a
19
46
25
I
OH
18b
20
97
86
99
73
28
63
6
TIPS
OH
Br
OH
4
5
6
7
8
13
14
15
15
1a
B, 1.2
B, 1.2
A, 2.2
B, 1.2
A, 2.2
2.5
5
80; 20
F
F
TIPS
TIPS
OH
Br
OH
80; 22
80; 1f
21
F
F
OAc
OAc
5
22a
22b
23ag
24
TMS
TIPS
I
MeOOC
MeOOC
OAc
5
80; 1f
MeOOC
COOMe
Br
COOMe
5
80; 6
TMS
O
N
TMS
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

654
Stará et al.:
TABLE III
(Continued)
b
Acetylen ea
PdLn
Con d.c
°C; h
Yieldd
%
En try
Educt
Product
equivalen t m ole %
COOMe
9
1b
1b
A, 2.2
B, 1.2
5
5
80; 2
23a
24
49
<5
I
COOMe
10
80; 13
23b
44
42
8
TIPS
COOMe
COOMe
Br
11
16
A, 2.2
5
80; 4
25
26
MeO
TMS
MeO
COOMe
TMS
MeO
TMS
N
N
O
O
I
12
17
A, 2.2
10
80; 6
27
27
TMS
OMe
OMe
O
OMe
28h
22
N
a
b
c
d
A: Me3Si–C≡CH, B: iPr3Si–C≡CH; Pd(PPh 3)4; th e reaction con ducted in piperidin e; iso-
lated; see ref.9; th e reaction con ducted in diisopropylam in e; see refs10,17
;
see ref.11
.
e
f
g
h
Regardless of th e h alogen atom iden tity, couplin g of (trim eth ylsilyl)acet-
ylen e with both th e ben zyl alcoh ols 6a an d 6b afforded th e eth yn yl deriva-
tive 18a in m oderate yields alon g with th e side product 19 arisen from 18a
by a subsequen t carbopalladation (Table III, en tries 1 an d 2). By con trast,
th e use of (triisopropylsilyl)acetylen e led exclusively to th e form ation of
th e eth yn yl derivative 18b in n early quan titative yield (Table III, en try 3).
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Coupling Reactions of Halobenzenes
655
Sim ilarly, th e 4- an d 3-fluoroben zyl alcoh ols 13 an d 14 provided clean ly
th e fluorin ated aryl acetylen es 20 an d 21 in excellen t yields (Table III, en -
tries 4 an d 5). Con sequen tly, th e presen ce of th e bulky triisopropylsilyl
group slowed down th e couplin g but, at th e sam e tim e, it disallowed th e
un desirable addition of an organ opalladium species on th e triple bon d. By
con trast, th e couplin g of th e 3-m eth oxycarbon yl derivative 15 with
(trim eth ylsilyl)acetylen e produced th e arylacetylen e 22a in a good yield
wh ereas th e use of (triisopropylsilyl)acetylen e resulted in a low yield of 22b
(Table III, cf. en tries 6 an d 7).
Th e couplin g reaction s of th e 2-h aloben zoates 1a, 1b , an d 16 with
(trim eth ylsilyl)- an d (triisopropylsilyl)acetylen e displayed a dim in ish ed
ability of h aloben zen es bearin g an ester group in th e ortho-position to pro-
duce correspon din g eth yn ylated derivatives. On treatm en t with
(trim eth ylsilyl)acetylen e, all th e h aloben zoates 1a, 1b, an d 16 provided th e
arylacetylen es 23a an d 25 in m od erate yield s (Table III, en tries 8, 9,
and 11). Moreover, two side products were detected: the am ide 24 (Table III,
en tries 8 an d 9) an d th e en yn e 26 (Table III, en try 11)17. Application of
(triisopropylsilyl)acetylen e did n ot im prove th e yield of couplin g (Table III,
en try 10).
TABLE IV
Deprotection of silylated ph en ylacetylen es
TBAFa Con d.b
Yieldc
%
En try
Educt
Product
equiv.
m in
OH
OH
F
TIPS
1
20
1.7
15
29
30
31
99
85
99
F
OH
OH
TIPS
2
3
21
1.4
1.3
5
F
F
OAc
OAc
TMS
22a
30
MeOOC
MeOOC
a
b
c
1.0 M Bu4NF in THF; room tem perature; isolated.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

656
Stará et al.:
(Trim eth ylsilyl)acetylen e reacted with th e 2,6-disubstituted iodoben zen e
17 to give th e arylacetylen e 27 in a low yield alon g with th e deh alogen ated
product 28 (Table III, en try 12). It reveals th at th e reaction of
(trim eth ylsilyl)acetylen e with an arylpalladium (II) in term ediate form ed
from 17 com petes with its proton olysis.
TABLE V
Couplin g reaction s of ortho-substitued h aloben zen es with ph en ylacetylen es
b
PdLn
Con d.c
h
Yieldd
%
En try
Educt
Acetylen ea
Product
m ole %
OH
OH
OH
1
6b
6b
6b
15
29
30
31
31
5
10
5
5
2
32
33
34
35
72
99
65
11
F
I
OH
F
OH
OH
OH
2
3
4
F
F
OAc
OH
1e
OAc
MeOOC
MeOOC
MeOOC
OAc
I
OAc
5
1e
OAc
MeOOC
MeOOC
a
b
c
Equim olar am oun ts of h aloben zen e an d arylacetylen e reacted; Pd(PPh 3)4; th e reaction
d
e
con ducted at 80 °C in piperidin e un less n oted oth erwise; isolated; th e reaction con ducted
in diisopropylam in e.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Coupling Reactions of Halobenzenes
657
Coupling Reactions of Halobenzenes with Phenylacetylenes
Deprotection of th e silylated arylacetylen es 20, 21, an d 22a proceeded
sm ooth ly in th e presen ce of tetrabutylam m on ium fluoride to afford th e ter-
m in al acetylen es 29–31 in h igh yields (Table IV, en tries 1–3). Th ese com -
poun ds were furth er used in th e Pd-catalyzed couplin g reaction s with
ortho-substituted h aloben zen es, vide infra.
Th e yields of th e couplin gs were stron gly in fluen ced by com bin ation of
th e reaction partn ers. Wh ereas th e Pd-catalyzed reaction of th e aryl-
acetylen es 29–31 with 2-iodoben zyl alcoh ol 6b furn ish ed th e cross-coupled
diarylacetylen es 32–34 in good to excellen t yields (Table V, en tries 1–3),
th e reaction between 15 an d 31 led to th e h om o-coupled product 35 in a
very low yield7 (Table V, en try 4).
CONCLUSION
In th e Pd- or Pd/Cu-catalyzed couplin g reaction of gaseous acetylen e,
bis(tributylstan n yl)acetylen e, (trialkylsilyl)acetylen es, an d arylacetylen es
with h aloben zen es bearin g th e m eth yl, h ydroxym eth yl, acetoxym eth yl,
an d m eth oxycarbon yl group in th e ortho-position , th e target aryl- or
diarylacetylen es can be syn th esized in good to excellen t yields. However,
wh en couplin g m eth oxycarbon yl derivatives, a careful optim ization of th e
reaction con dition s is required to get even m oderate yields. Th e presen ce of
addition al substituen ts such as fluoro, n itro, an d m eth oxy does n ot in ter-
fere with th e couplin g reaction .
EXPERIMENTAL
Gen eral
Meltin g poin ts were determ in ed on a Kofler h ot-stage apparatus an d are un corrected.
1H NMR spectra were m easured at 500 or 200 MHz, 13C NMR spectra at 125 MHz, in CDCl3
with TMS as an in tern al stan dard or in aceton e-d6 (referen ced to aceton e). 19F NMR spectra
were m easured at 470.32 MHz in CDCl3 or in aceton e-d6 with CFCl3 as an in tern al stan dard.
Ch em ical sh ifts are given in δ-scale, couplin g con stan ts J in Hz. For n um berin g of th e skele-
ton see Fig. 1. IR spectra were m easured in CHCl3, CCl4, an d in KBr pellets (in cm –1). EI MS
spectra were determ in ed at an ion izin g voltage 70 eV. FAB MS spectra were m easured usin g
the thioglycerol–glycerol m atrix and m ethanol as a solvent. HR MS spectra were obtained by the
EI or FAB technique. GC MS analyses were carried out on a DB-5 column (0.25 × 30 m × 0.25 µm),
EI MS spectra of separated com poun ds were m easured at an ion izin g voltage 70 eV. All reac-
tion s were perform ed in Sch len k or double-n ecked flasks equipped with rubber septa an d
con n ected via rubber tubin gs to a stan dard vacuum /argon lin e. All ch em icals were reagen t
grade m aterials. Tetrah ydrofuran was fresh ly distilled from sodium –ben zoph en on e un der n i-
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

658
Stará et al.:
trogen ; diisopropylam in e an d piperidin e were distilled from calcium h ydride un der argon
an d degassed by th ree freeze-pum p-th aw cycles before use, dim eth ylform am ide was distilled
from calcium h ydride un der reduced pressure an d stored over 4Å m olecular sieves. Th e reac-
tion s with gaseous acetylen e un der atm osph eric pressure were perform ed in a vessel con -
n ected to a rubber balloon filled with acetylen e directly from a cylin der16
.
1
3
2'
6
3'
4'
5
1'
2
6'
4
5'
Substituent
1-CH OH
2
2'-CH OH
2
4'-F
32
33
34
1-CH OH
2
2'-CH OH
2
5'-F
1-CH OAc 4-COOMe
2
2'-CH OH
2
3
5
2
2'
3'
4'
4
1'
1
6'
5'
6
Substituent
2-COOMe
2'-COOMe
2
3
2
2
3
4
4
1
1
5
5
6
6
Substituent
2-Me
5-NO
2-Me
2-CH OH
5-NO
9
2
2
4-OMe
2-CH OH 4-OMe
2
12
2
5
4
2
4'
2'
5'
1'
6'
6
3
3'
1
Substituent
4-Me
1'-COOMe
1-COOMe
1-COOMe
4'-Me
10
35
4-CH OAc 1'-COOMe 4'-CH OAc
2 2
FIG. 1
Num berin g of diarylacetylen e skeleton s as utilized in 1H an d 13C NMR spectra sign al assign -
m en ts
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Coupling Reactions of Halobenzenes
659
Bis(tributylstan n yl)acetylen e, (trim eth ylsilyl)- an d (triisopropylsilyl)acetylen e (Aldrich )
were used as received. Th e startin g h aloben zen es were purch ased from Aldrich (3, 4, 6a,
3-iodo-4-m eth ylben zoic acid, 1-brom o-4-fluoro-2-m eth ylben zen e, 2-brom o-4-fluoro-1-m eth yl-
ben zen e), Acros Ch im ica (1a, 6b), an d Avocado (1b) or prepared accordin g to th e literature
procedures4 (7, 16). Th e n ovel or m odified syn th eses of startin g h aloben zen es 5 (ref.12), 13,
14, 15, and 17 or acetylenes 29, 30, and 31 are reported below. The com pound 28 was prepared
accordin g to th e literature procedure11. TLC was perform ed on Silica gel 60 F254-coated
alum in ium sh eets (Merck) an d spots were detected by ceric sulfate–ph osph om olybdic
acid–sulfuric acid solution . Flash ch rom atograph y was perform ed on Silpearl silica gel
(Kavalier Votice, Czech Republic) or Silica gel 60 (0.040–0.063 m m or <0.063 m m , Merck).
Sem ipreparative HPLC was carried out on a silica gel colum n (Partisil M9, Wh atm an 10/50,
500 m m × 10 m m ; sam ple in jection s on a 10–20 m g scale) usin g a refractom etric detector.
Gen eral Procedure for th e Couplin g Reaction of Haloben zen es 1b, 3–5, 6b, an d 7
with Gaseous Acetylen e
Method A). A Sch len k flask was ch arged with h aloben zen e (5.0 m m ol), Pd(PPh 3)4 (2.5–10
m ole %), stoppered with a rubber septum , an d flush ed with argon . Piperidin e (10 m l) was
added an d th e m ixture was briefly h eated at 40–50 °C un der stirrin g to get a clear solution .
Th en a rubber balloon filled with acetylen e was attach ed to th e side arm an d th e flask was
purged of rem ain in g argon usin g a n eedle in troduced th rough th e septum over th e surface
of th e reaction m edium . Th e m ixture was stirred un der atm osph eric pressure of acetylen e at
am bien t tem perature or 80 °C for 0.75–4 h un til th e educt disappeared (m on itored by TLC).
Th e precipitate was filtered off an d wash ed with petroleum eth er (2 × 5 m l). Th e com bin ed
fraction s were evaporated to dryn ess in vacuo (at <50 °C) an d th e residue was ch rom ato-
graph ed on silica gel to obtain th e product.
Method B). It differs from th e m eth od A) in th e presen ce of CuI (2–10 m ole %).
Procedure for th e Couplin g Reaction of Haloben zen e 1b
with Bis(tributylstan n yl)acetylen e
Method C). A Sch len k flask was ch arged with h aloben zen e 1b (0.20 m m ol), Pd(PPh 3)2Cl2
(5 m ole %), stoppered with a rubber septum , an d flush ed with argon . THF (5 m l) was added
an d th e m ixture was stirred at room tem perature for 5 m in . Th en bis(tributylstan n yl)acety-
len e (60 µl, 0.114 m m ol, 1.1 equivalen t) was added with a syrin ge an d th e m ixture was
stirred at 50 °C for 18 h un til th e edduct disappeared (m on itored by TLC or GC). Th e solu-
tion was evaporated to dryn ess in vacuo (at <50 °C) an d th e residue was ch rom atograph ed
on silica gel to obtain th e product.
Gen eral Procedure for th e Couplin g Reaction of Haloben zen es 1a, 1b, 6a, 6b, an d 15–17
with (Trim eth ylsilyl)acetylen e
Method D). A glass pressure tube with gas in let was ch arged with h aloben zen e (1.0 m m ol)
an d Pd(PPh 3)4 (5–10 m ole %). Th e tube was stoppered with a rubber septum an d flush ed
with argon . Piperidin e (or diisopropylam in e; 3 m l) was added an d th e m ixture was briefly
h eated un der stirrin g at 40–50 °C to get a clear solution . After coolin g to room tem perature,
(trim eth ylsilyl)acetylen e (310 µl, 2.2 equivalen t) was added. Th e septum was replaced in a
stream of argon by a n eedle valve wh ich was tigh tly closed. Th e reaction m ixture was stirred
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

660
Stará et al.:
at 50 or 80 °C for 1–20 h un til th e educt disappeared (m on itored by TLC). Th e precipitate
was filtered off an d wash ed with petroleum eth er (2 × 2 m l). Th e com bin ed fraction s were
evaporated to dryn ess in vacuo (at <50 °C) an d th e residue was ch rom atograph ed on silica
gel to obtain th e product.
Gen eral Procedure for th e Couplin g Reaction of Haloben zen es 1b, 6b, an d 13–15
with (Triisopropylsilyl)acetylen e
Method E). A Sch len k flask was ch arged with h aloben zen e (1.0 m m ol), Pd(PPh 3)4 (2.5–5
m ole %), an d flush ed with argon . Piperidin e (or diisopropylam in e; 3 m l) was added an d th e
m ixture was briefly h eated un der stirrin g at 40–50 °C to get
a clear solution .
(Triisopropylsilyl)acetylen e (270 µl, 1.2 equivalen t) was added an d th e reaction m ixture was
stirred at 80 °C for 1–22 h un til th e educt disappeared (m on itored by TLC). Th e precipitate
was filtered off an d wash ed with petroleum eth er (2 × 2 m l). Th e com bin ed fraction s were
evaporated to dryn ess in vacuo (at <50 °C) an d th e residue was ch rom atograph ed on silica
gel to obtain th e product.
Gen eral Procedure for th e Couplin g Reaction of Haloben zen es 6b an d 15
with Arylacetylen es 29–31
Method F). A Sch len k flask was ch arged with h aloben zen e (1.0 m m ol), Pd(PPh 3)4 (5–10
m ole %), an d flush ed with argon . Piperidin e (or diisopropylam in e; 2 m l) was added an d th e
m ixture was briefly h eated un der stirrin g at 40–50 °C to get a clear solution . Arylacetylen e
(1.0 m m ol) in piperidin e (or diisopropylam in e; 1 m l) was added an d th e reaction m ixture
was stirred at 80 °C for 1–5 h un til th e educt disappeared (m on itored by TLC). Th e precipi-
tate was filtered off an d wash ed with petroleum eth er (2 × 2 m l). Th e com bin ed fraction s
were evaporated to dryn ess in vacuo (at <50 °C) an d th e residue was ch rom atograph ed on sil-
ica gel to obtain th e product.
Gen eral Procedure for Desilylation of Haloben zen es 20, 21, an d 22a
Method G). A solution of trim eth ylsilyl or triisopropylsilyl derivative (0.30 m m ol) in dry
THF (3 m l) un der argon was treated with tetrabutylam m on ium fluoride (1 M stock solution
in THF, 1.3–1.7 equivalen t) at room tem perature for 5–30 m in wh ile stirred. Th e reaction
m ixture was evaporated in vacuo to dryn ess an d th e residue was ch rom atograph ed on silica
gel to get th e product.
Dim eth yl 2,2′-Eth yn ediyldiben zoate8 (2)
Method A). Com poun d 1b (2.0 g, 7.63 m m ol), Pd(PPh 3)4 (220 m g, 0.19 m m ol, 2.5 m ole %),
piperidin e (25 m l), gaseous acetylen e, 80 °C, 3 h . Flash ch rom atograph y on silica gel (petro-
leum eth er–eth er–aceton e 85 : 5 : 10) afforded 2 (583 m g, 52%). M.p. an d IR in accord with
th e literature data8. 1H NMR (500 MHz, CDCl3): 3.96 (s, 6 H, 2 × CH3); 7.40 (dt, 2 H, J = 7.7,
7.7, 1.4, 5,5′-H); 7.52 (dt, 2 H, J = 7.6, 7.6, 1.5, 4,4′-H); 7.73 (dd, 2 H, J = 7.8, 1.4, 3,3′-H);
7.99 (dd, 2 H, J = 7.9, 1.5, 6,6′-H). 13C NMR (CDCl3): 52.17 (q, 2 × CH3), 93.09 (s, 2 × –C≡),
123.83 (s, C-2,2′), 128.13 (d, C-5,5′), 130.45 (d, C-6,6′), 131.74 (d, C-3,3′), 131.77 (s, C-1,1′),
134.32 (d, C-4,4′), 166.63 (s, C=O). EI MS (m/z, rel. in ten sity): 294 (M+•, 13), 279 (100), 264
(24), 248 (21), 220 (16), 132 (29), 116 (15), 102 (24), 88 (27), 75 (13), 28 (29).
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Coupling Reactions of Halobenzenes
661
Meth yl 3-Iodo-4-m eth ylben zoate12 (5)
Th e com poun d 5 was prepared accordin g to th e literature procedure13. Th ion yl ch loride
(7.50 m l, 102.82 m m ol, 4.0 equivalen t) was added dropwise to absolute m eth an ol (50 m l) at
–30 °C un der stirrin g. A solution of 3-iodo-4-m eth ylben zoic acid (6.76 g, 25.80 m m ol) in ab-
solute m eth an ol (100 m l) was dropwise added over a 1 h period. Th e reaction m ixture was
stirred at –30 °C for 30 m in , warm ed up to room tem perature, an d fin ally h eated at 40 °C
for 1 h . Volatiles were rem oved in vacuo an d th e residue was filtered th rough a sh ort colum n
of alum in a (eluted with petroleum eth er) to afford 5 (6.98 g, 98%). 1H NMR (200 MHz,
CDCl3): 2.48 (s, 3 H, CH3); 3.91 (s, 3 H, CH3O); 7.30 (d, 1 H, J = 7.9, 5-H); 7.91 (dd, 1 H, J =
7.9, 1.8, 6-H); 8.47 (d, 1 H, J = 1.8, 2-H). EI MS (m/z, rel. in ten sity): 276 (M+•, 100), 245 (80),
217 (12), 198 (4), 90 (14).
Bis(2-m eth yl-5-n itroph en yl)eth yn e (9)
Method B). Com poun d 4 (537 m g, 2.49 m m ol), Pd(PPh 3)4 (144 m g, 0.125 m m ol, 5 m ole %),
CuI (47 m g, 0.247 m m ol, 10 m ole %), piperidin e (7 m l), 80 °C, 2.5 h . Flash ch rom atograph y
on silica gel (petroleum eth er–eth er–aceton e 85 : 10 : 5) gave 9 as an am orph ous solid (287 m g,
78%). IR (CHCl3): 3 083 w, 2 959 w, 2 926 w, 1 613 w, 1 579 w, 1 525 s, 1 488 w, 1 448 w,
1 381 w, 1 351 vs, 1 304 w, 1 285 w, 1 266 w, 1 135 w, 1 074 w, 1 036 w, 906 w, 831 m , 823
m , 643 w, 445 w. 1H NMR (500 MHz, CDCl3): 2.65 (s, 6 H, 2 × CH3); 7.44 (d, 2 H, J = 8.4,
2 × 3-H); 8.13 (dd, 2 H, J = 8.4, 2.5, 2 × 4-H); 8.38 (d, 2 H, J = 2.5, 2 × 6-H). 13C NMR
(CDCl3): 21.23 (q, 2 × CH3), 91.92 (s, 2 × –C≡), 123.56 (d, 2 × C-4), 123.78 (s, 2 × C-1),
126.92 (d, 2 × C-6), 130.54 (d, 2 × C-3), 146.19 (s, 2 × C-5), 147.60 (s, 2 × C-2). EI MS (m/z,
rel. in ten sity): 296 (M+•, 100), 249 (11), 203 (50), 202 (49), 189 (27), 176 (9), 101 (6). HR EI MS:
calculated for C16H12N2O4 296.0797; foun d 296.0794.
Dim eth yl 4,4′-Dim eth yl-3,3′-eth yn ediyldiben zoate (10)
Method B). Com poun d 5 (1.23 g, 4.093 m m ol), Pd(PPh 3)4 (236 m g, 0.204 m m ol, 5 m ole %),
CuI (78 m g, 0.410 m m ol, 10 m ole %), piperidin e (5 m l), 80 °C, 0.5 h . Flash ch rom atograph y
on silica gel (petroleum eth er–eth er 85 :15) provided 10 (645 m g, 98%), m .p. 136–137 °C
(dich lorom eth an e–aceton e). IR (CHCl3): 2 954 w, 1 719 vs, 1 606 w, 1 572 w, 1 499 w, 1 457
w (sh ), 1 438 m , 1 418 w, 1 380 vw, 1 317 m , 1 297 m , 1 289 m , 1 248 s, 1 137 w, 1 103 w,
1 036 vw, 1 003 w, 915 w, 841 w. 1H NMR (500 MHz, CDCl3): 2.59 (s, 6 H, 2 × CH3); 3.93 (s,
6 H, 2 × CH3O); 7.33 (d, 2 H, J = 8.0, 5,5′-H); 7.91 (dd, 2 H, J = 8.0, 1.9, 6,6′-H); 8.19 (d, 2 H,
J = 1.9, 2,2′-H). 13C NMR (CDCl3): 21.20 (q, 2 × CH3), 52.16 (q, 2 × CH3O), 92.01 (s,
2 × –C≡), 123.35 (s, C-3,3′), 127.97 (s, C-1,1′), 129.43 (d, C-5,5′), 129.71 (d, C-6,6′), 133.17
(d, C-2,2′), 145.25 (s, C-4,4′), 166.51 (s, 2 × C=O). EI MS (m/z, rel. in ten sity): 322 (M+•, 100),
291 (29), 277 (16), 263 (11), 231 (7), 204 (36), 203 (37), 202 (26), 189 (13), 130 (31), 101
(18), 89 (11), 77 (5). HR EI MS: calculated for C20H18O4 322.1205; foun d 322.1194.
Bis(2-h ydroxym eth yl-4-m eth oxyph en yl)eth yn e (12)
Method B). Com poun d 7 (100 m g, 0.379 m m ol), Pd(PPh 3)4 (22 m g, 0.019 m m ol, 5 m ole %),
CuI (7 m g, 0.037 m m ol, 10 m ole %), piperidin e (3 m l), 80 °C, 0.1 h . Flash ch rom atograph y
on silica gel (petroleum eth er–eth er–aceton e 80 : 10 : 10 to 50 : 30 : 20) provided 12 as an oil
(56 m g, 99%). IR (KBr): 3 322 m (br), 3 251 m (br), 3 091 w, 3 052 w, 3 007 w, 2 956 w,
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662
Stará et al.:
2 936 m , 2 835 m , 1 612 s, 1 564 m , 1 500 vs, 1 463 m , 1 453 m , 1 438 m , 1 430 m , 1 363 w,
1 315 s, 1 295 vs, 1 274 s, 1 221 vs, 1 193 m , 1 158 m , 1 116 s, 1 057 s (sh ), 1 050 s, 1 034 s,
886 w, 880 m , 819 m , 808 m , 724 m , 694 m , 681 m , 541 m , 444 w. 1H NMR (500 MHz,
CDCl3): 3.92 (s, 6 H, 2 × CH3); 4.93 (brs, 4 H, 2 × CH2); 6.92 (ddt, 2 H, J = 8.5, 2.7, 0.6, 0.6,
2 × 5-H); 7.27 (dt, 2 H, J = 2.7, 1.0, 1.0, 2 × 3-H); 7.50 (d, 2 H, J = 8.5, 2 × 6-H). 13C NMR
(CDCl3): 55.61 (q, 2 × CH3), 63.13 (t, 2 × CH2), 90.92 (s, 2 × –C≡), 112.79 (d, 2 × C-3), 113.06
(d, 2 × C-5), 113.73 (s, 2 × C-1), 133.74 (d, 2 × C-6), 146.49 (s, 2 × C-2), 160.91 (s, 2 × C-4).
EI MS (m/z, rel. in ten sity): 298 (M+•, 100), 265 (45), 237 (26), 209 (22), 165 (28), 149 (30),
134 (91), 121 (19), 91 (18), 77 (16). HR EI MS: calculated for C18H18O4 298.1205; foun d
298.1157.
(2-Brom o-5-fluoroph en yl)m eth an ol (13)
A m ixture of 1-brom o-4-fluoro-2-m eth ylben zen e (9.53 g, 50.42 m m ol), N-brom osuccin im ide
(9.66 g, 54.27 m m ol, 1.08 equivalen t), K2CO3 (100 m g), an d 2,2′-azobis(isobutyron itrile)
(100 m g) in CCl4 (100 m l) was irradiated with an IR lam p to reflux for 1 h . Th e reaction
m ixture was cooled to room tem perature, th e precipitate was filtered off, an d th e filtrate was
con cen trated in vacuo. Th e residue was ch rom atograph ed on silica gel (petroleum eth er) to
obtain 1-brom o-2-brom om eth yl-4-fluoroben zen e14 (9.13 g, 68%). 1H NMR (200 MHz,
CDCl3): 4.55 (s, 2 H, CH2); 6.92 (ddd, 1 H, J = 8.7, 7.8, 3.1, 5-H); 7.20 (dd, 1 H, J = 8.7, 3.1,
3-H); 7.54 (dd, 1 H, J = 8.7, 5.3, 6-H). EI MS (m/z, rel. in ten sity): 266 (M+•, 15), 189 (100),
187 (90), 108 (29), 91 (7).
A solution of 1-brom o-2-brom om eth yl-4-fluoroben zen e (1.80 g, 6.72 m m ol) in dioxan e
(20 m l) was added portion wise un der stirrin g to a suspen sion of CaCO3 (3.72 g, 37.17
m m ol, 5.5 equivalen t) in water (25 m l) at 100 °C. Th e m ixture was refluxed for 20 h . Th e
solven ts were rem oved in vacuo an d th e residue was triturated with dich lorom eth an e. Th e
organ ic portion was wash ed with 5% h ydroch loric acid (1 ×), saturated KHCO3 (2 ×), an d
dried over Na2SO4. Th e solution was evaporated to dryn ess an d th e residue was
ch rom atograph ed on silica gel (h exan e–eth er–aceton e 80 : 10 : 10) to provide 13 (948 m g,
69%), m .p. 88–90 °C (ch loroform ). IR (CHCl3): 3 615 m , 3 464 w (br), 3 077 vw, 3 029 vw,
2 933 w, 2 884 w, 1 606 m , 1 583 s, 1 468 vs, 1 414 m , 1 376 w, 1 268 s, 1 239 m , 1 145 s,
1 106 s, 1 052 m , 1 026 s, 950 w, 875 s, 813 s, 620 m , 590 m , 561 w, 544 w, 492 w, 443 w.
1H NMR (500 MHz, CDCl3): 2.01 (t, 1 H, J = 6.2, OH); 4.72 (dt, 2 H, J = 6.2, 0.7, 0.7, CH2);
6.89 (dddt, 1 H, J = 8.7, 7.8, 3.1, 0.7, 0.7, 4-H); 7.27 (ddt, 1 H, J = 9.2, 3.1, 0.8, 0.8, 6-H);
7.48 (dd, 1 H, J = 8.7, 5.2, 3-H). 13C NMR (CDCl3): 64.48 (t, CH2), 115.56 (dd, JC–F = 23.8,
C-6), 115.76 (d, JC–F = 2.8, C-2), 115.85 (dd, JC–F = 22.9, C-4), 133.61 (dd, JC–F = 8.2, C-3),
142.00 (d, JC–F = 7.2, C-1), 162.30 (d, JC–F = 247.7, C-5). 19F NMR (CDCl3): –114.60 (ddd, JF–H
=
9.3, 7.8, 5.1). EI MS (m/z, rel. in ten sity): 204 (M+•, 79), 187 (7), 175 (13), 125 (100), 107 (13),
97 (70), 96 (53), 95 (44), 77 (22), 75 (20). HR EI MS: calculated for C7H6BrFO 203.9586;
foun d 203.9573.
(2-Brom o-4-fluoroph en yl)m eth an ol (14)
A m ixture of 2-brom o-4-fluoro-1-m eth ylben zen e (947 m g, 5.01 m m ol), N-brom osuccin im ide
(1.02 g, 5.73 m m ol, 1.14 equivalen t), K2CO3 (50 m g), an d 2,2′-azobis(isobutyron itrile) (50 m g)
in CCl4 (20 m l) was irradiated with an IR lam p to reflux for 1 h . Th e reaction m ixture was
cooled to room tem perature, th e precipitate was filtered off, an d th e filtrate was con cen -
trated in vacuo. Th e residue was ch rom atograph ed on silica gel (petroleum eth er) to obtain
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Coupling Reactions of Halobenzenes
663
2-brom o-1-brom om eth yl-4-fluoroben zen e15 (767 m g, 57%). 1H NMR (200 MHz, CDCl3): 4.58
(s, 2 H, CH2); 7.03 (ddd, 1 H, J = 8.5, 7.9, 2.8, 5-H); 7.33 (dd, 1 H, J = 8.1, 2.8, 3-H); 7.44
(dd, 1 H, J = 8.5, 5.8, 6-H). EI MS (m/z, rel. in ten sity): 266 (M+•, 8), 189 (88), 187 (100), 108
(35), 107 (18).
A solution of 2-brom o-1-brom om eth yl-4-fluoroben zen e (476 m g, 1.78 m m ol) in dioxan e
(10 m l) was added portion wise un der stirrin g to a suspen sion of CaCO3 (925 m g, 9.24
m m ol, 5.2 equivalen t) in water (10 m l) at 100 °C. Th e m ixture was refluxed for 6 h . Th e sol-
ven ts were rem oved in vacuo an d th e residue was triturated with dich lorom eth an e. Th e or-
gan ic portion was wash ed with 5% h ydroch loric acid (1 ×), saturated KHCO3 (2 ×), an d dried
over Na2SO4. Th e solution was evaporated to dryn ess an d th e residue was ch rom atograph ed
on silica gel (h exan e–eth er–aceton e 80 : 10 : 10) to provide 14 (297 m g, 82%), m .p.
68.5–69.5 °C (ch loroform ). IR (CHCl3): 3 609 m , 3 462 w (br), 3 062 vw, 3 027 vw, 2 933 w,
2 888 w, 1 600 s, 1 590 s, 1 488 vs, 1 399 w, 1 383 w, 1 265 m , 1 230 s, 1 177 w, 1 121 w,
1 029 m , 863 s, 588 w, 564 w (br), 460 w, 445 w. 1H NMR (500 MHz, CDCl3): 1.96 (t, 1 H, J =
6.1, OH); 4.72 (d, 2 H, J = 6.1, CH2); 7.05 (ddd, 1 H, J = 8.5, 8.1, 2.5, 5-H); 7.31 (dd, 1 H, J =
8.1, 2.6, 3-H); 7.46 (ddt, 1 H, J = 8.5, 6.0, 0.7, 0.7, 6-H). 13C NMR (CDCl3): 64.41 (t, CH2),
114.65 (dd, JC–F = 21.0, C-5), 119.90 (dd, JC–F = 34.4, C-3), 122.52 (d, JC–F = 9.7, C-2), 129.94
(dd, JC–F = 8.8, C-6), 135.70 (d, JC–F = 3.4, C-1), 161.81 (d, JC–F = 250.5, C-4). 19F NMR
(CDCl3): –113.25 (dtt, JF–H = 8.1, 8.1, 6.1, 1.0, 1.0). EI MS (m/z, rel. in ten sity): 204 (M+•, 84),
187 (16), 175 (11), 125 (100), 107 (16), 97 (93), 96 (71), 95 (53), 75 (23). HR EI MS: calcu-
lated for C7H6BrFO 203.9586; foun d 203.9573.
2-Iodo-4-(m eth oxycarbon yl)ben zyl Acetate (15)
A m ixture of 5 (4.35 g, 15.76 m m ol), N-brom osuccin im ide (3.07 g, 17.25 m m ol, 1.09 equiva-
len t), K2CO3 (100 m g), an d 2,2′-azobis(isobutyron itrile) (100 m g) in CCl4 (15 m l) was irradi-
ated with an IR lam p to reflux for
1 h . Th e reaction m ixture was cooled to room
tem perature, th e precipitate was filtered off, an d th e filtrate was con cen trated in vacuo. Th e
residue was ch rom atograph ed on silica gel (petroleum eth er–eth er 95 : 5) to furn ish m eth yl
4-brom om eth yl-3-iodoben zoate (3.90 g, 70%). IR (CHCl3): 1 724 vs, 1 597 w, 1 558 m , 1 482 w,
1 437 s, 1 294 vs, 1 285 vs, 1 263 vs, 1 226 m , 1 120 s, 1 036 m , 971 m , 608 w. 1H NMR
(200 MHz, CDCl3): 3.93 (s, 3 H, CH3); 4.60 (s, 2 H, CH2); 7.54 (d, 1 H, J = 8.0, 5-H); 7.99 (dd,
1 H, J = 8.0, 1.8, 6-H); 8.51 (d, 1 H, J = 1.8, 2-H). EI MS (m/z, rel. in ten sity): 354 (M+•, 14),
275 (84), 245 (16), 229 (9), 149 (15), 117 (16), 89 (41), 63 (24), 39 (100). HR EI MS: calcu-
lated for C9H8BrIO2 353.8752; foun d 353.8752.
Meth yl 4-brom om eth yl-3-iodoben zoate (1.47 g, 4.14 m m ol) in N,N-dim eth ylform am ide
(10 m l) was treated with an h ydrous sodium acetate (840 m g, 10.24 m m ol, 2.47 equivalen t)
un der stirrin g at 80 °C for 2 h . Th e reaction m ixture was cooled to room tem perature, di-
luted with water, an d extracted with eth er (3 ×). Th e com bin ed eth ereal extracts were
wash ed with water (2 ×) an d dried over Na2SO4. Eth er was rem oved in vacuo an d th e crude
product was purified by flash ch rom atograph y on silica gel (petroleum eth er–eth er–aceton e
95 : 5 : 0 to 80 : 10 : 10) to get 15 as an oil (1.13 g, 82%). IR (CHCl3): 1 740 vs (sh ), 1 725 vs,
1 600 w, 1 560 m , 1 484 w, 1 437 s, 1 291 vs, 1 259 vs, 1 247 vs, 1 141 w, 1 119 s, 1 054 m ,
1 030 s, 971 m , 805 w, 602 w, 463 w. 1H NMR (500 MHz, CDCl3): 2.18 (s, 3 H, CH3CO2);
3.92 (s, 3 H, CH3O2C); 5.14 (brs, 2 H, CH2); 7.43 (dtt, 1 H, J = 8.0, 0.8, 0.8, 0.3, 0.3, 6-H);
8.01 (ddq, 1 H, J = 8.0, 1.7, 0.2, 0.2, 0.2, 5-H); 8.50 (brd, 1 H, J = 1.7, 3-H). 13C NMR
(CDCl3): 20.79 (q, CH3CO2), 52.40 (q, CH3O2C), 69.57 (t, CH2), 96.95 (s, C-2), 128.47 (d,
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664
Stará et al.:
C-6), 129.39 (d, C-5), 131.31 (s, C-4), 140.44 (d, C-3), 143.15 (s, C-1), 165.27 (s, CH3O2C),
170.36 (s, CH3CO2). EI MS (m/z, rel. in ten sity): 334 (M+•, 3), 303 (7), 275 (7), 207 (54), 165
(100), 147 (16), 89 (7), 43 (28). HR EI MS: calculated for C11H11IO4 333.9702; foun d
333.9703.
2-(2-Iodo-3-m eth oxyph en yl)-4,4-dim eth yl-4,5-dih ydro-1,3-oxazole (17)
A solution of 28 (ref.11) (107 m g, 0.521 m m ol) in dry THF (2 m l) un der argon was cooled to
–45 °C an d butyllith ium (1.6 M in h exan es, 500 µl, 0.80 m m ol, 1.5 equivalen t) was added.
Th e reaction m ixture was stirred at –45 °C for 1.5 h . Iodin e (215 m g, 0.847 m m ol, 1.6 equiv-
alen t) in dry THF (1 m l) was added an d th e m ixture was allowed to reach room tem perature
durin g 1.5 h . Solven ts were evaporated in vacuo an d th e residue was dissolved in dich loro-
m eth an e. Th e solution was wash ed with aqueous Na2S2O3 (5%, 1 ×), water (1 ×), dried over
Na2SO4, an d con cen trated in vacuo. Th e crude product was purified by flash ch rom atograph y
on silica gel (petroleum eth er–eth er–aceton e 80 : 10 : 10) to get 17 (100 m g, 58%), m .p.
102–103 °C (petroleum eth er–eth er–aceton e). IR (CHCl3): 3 075 w, 2 840 m , 1 665 s, 1 587 s,
1 567 s, 1 467 vs, 1 443 m , 1 424 vs, 1 386 m , 1 367 s, 1 353 s, 1 318 vs, 1 282 s, 1 264 vs,
1 187 s, 1 175 m , 1 127 s, 1 094 m , 1 045 vs, 967 s, 523 w, 431 w. 1H NMR (500 MHz,
CDCl3): 1.43 (s, 6 H, 2 × CH3); 3.90 (s, 3 H, CH3O); 4.15 (s, 2 H, CH2); 6.87 (dd, 1 H, J = 8.2,
1.5, 4-H); 7.12 (dd, 1 H, J = 7.6, 1.5, 6-H); 7.32 (dd, 1 H, J = 8.2, 7.6, 5-H). 13C NMR (CDCl3):
28.19 (q, 2 × CH3), 56.72 (q, CH3O), 68.16 (s, CH3C), 79.50 (t, CH2), 87.94 (s, C-2), 112.30
(d, C-4), 122.83 (d, C-6), 129.22 (d, C-5), 136.77 (s, C-1), 158.56 (s, C=N), 163.24 (s, C-3). EI
MS (m/z, rel. in ten sity): 331 (M+•, 100), 316 (59), 301 (31), 288 (6), 260 (24), 245 (7), 161
(12). HR EI MS: calculated for C12H14INO2 331.0069; foun d 330.9792; calculated for
C
11H11INO2 (M – CH3) 315.9835; foun d 315.9770.
[2-(2-Trim eth ylsilyleth yn -1-yl)ph en yl]m eth an ol9 (18a)
Method D). Com poun d 6a (100 m g, 0.535 m m ol), trim eth ylsilylacetylen e (165 µl, 1.168
m m ol, 2.2 equivalen t), Pd(PPh 3)4 (31 m g, 0.027 m m ol, 5 m ole %), piperidin e (2 m l), 80 °C,
6 h . Flash ch rom atograph y on silica gel (petroleum eth er–eth er–aceton e 80 : 10 : 10) af-
forded a m ixture of 18a an d 19 (4 : 1 accordin g to 1H NMR). Com poun ds 18a an d 19 were
separated by sem ipreparative HPLC on a silica gel colum n (petroleum eth er–aceton e 90 : 10)
to provide 18a (59 m g, 54%) an d m ore polar 19 (22 m g, 14%) as oils. IR (CHCl3): 3 608 m ,
3 070 w, 2 962 s, 2 928 m , 2 901 m , 2 876 m , 2 153 s, 1 599 w, 1 570 w, 1 482 m , 1 451 m ,
1 252 s, 1 037 m , 1 008 m , 867 vs, 844 vs, 645 m . 1H NMR (500 MHz, CDCl3): 0.27 (s, 9 H,
(CH3)3Si); 2.22 (brt, 1 H, J = 6.1, OH); 4.82 (d, 2 H, J = 6.1, CH2); 7.24 (dt, 1 H, J = 7.5, 7.5,
1.5, 4-H); 7.33 (dt, 1 H, J = 7.5, 7.5, 1.5, 5-H); 7.41 (brd, 1 H, J = 7.6, 3-H); 7.47 (dd, 1 H, J =
7.6, 1.5, 6-H). 13C NMR (CDCl3): –0.11 (q, (CH3)3Si), 64.10 (t, CH2), 99.60 (s, C≡C–Si),
102.60 (s, C≡C–Si), 121.20 (s, C-2), 127.22 (d, C-6), 127.37 (d, C-4), 128.95 (d, C-5), 132.45
(d, C-3), 143.16 (s, C-1). EI MS (m/z, rel. in ten sity): 204 (M+•, 58), 189 (27), 171 (26), 161
(13), 145 (16), 131 (50), 129 (52), 115 (31), 87 (15), 73 (69), 61 (100).
[2-(2-Triisopropylsilyleth yn -1-yl)ph en yl]m eth an ol (18b)
Method E). Com pound 6b (65 m g, 0.278 m m ol), triisopropylsilylacetylene (75 µl, 0.334 m m ol,
1.2 equivalen t), Pd(PPh 3)4 (16 m g, 0.014 m m ol, 5 m ole %), piperidin e (2 m l), 80 °C, 13 h .
Flash ch rom atograph y on silica gel (petroleum eth er–eth er 85 : 15) furn ish ed 18b (75 m g, 97%)
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Coupling Reactions of Halobenzenes
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as an oil. IR (CHCl3): 3 610 w, 3 570 w (sh ); 3 469 w (br), 3 071 w, 2 959 s, 2 944 vs, 2 925 s
(sh), 2 891 s, 2 866 vs, 2 151 m , 1 600 w, 1 570 vw, 1 481 m , 1 462 s, 1 450 m , 1 383 m,1 367 w,
1 243 w, 1 160 w (sh), 1 102 w, 1 072 w, 1 035 m, 1 011 m, 997 m, 995 w, 883 w, 852 m, 844 m,
809 w, 678 s, 663 s, 640 m, 611 w, 599 w, 538 w, 460 w. 1H NMR (500 MHz, CDCl3): 1.14 (s,
21 H, 3 × (CH3)2CH); 2.26 (brt, 1 H, J = 6.1, OH); 4.85 (d, 2 H, J = 6.1, CH2); 7.24 (dt, 1 H, J =
7.6, 7.6, 1.2, 4-H); 7.33 (dt, 1 H, J = 7.8, 7.8, 1.2, 5-H); 7.42 (brdd, 1 H, J = 7.8, 1.2, 6-H);
7.49 (dd, 1 H, J = 7.6, 1.4, 3-H). 13C NMR (CDCl3): 11.26 (d, 3 × (CH3)2CH), 18.64 (q,
3 × (CH3)2CH), 64.15 (t, CH2), 96.01 (s, C≡C–Si), 104. 41 (s, C≡C–Si), 121.52 (s, C-2), 127.11
(d, C-4), 127.32 (d, C-6), 128.78 (d, C-5), 132.75 (d, C-3), 143.08 (s, C-1). EI MS (m/z, rel.
intensity): 288 (M+•, 1), 245 (26), 203 (47), 175 (100), 161 (9), 115 (15), 75 (5), 61 (11). FAB MS
(m/z): 289 ((M + H)+), 271, 245, 229, 203, 201, 175, 159, 145, 115, 103, 87, 73, 59. HR FAB
MS: calculated for C18H29OSi (M + H) 289.1988; foun d 289.2028.
{2-[2,4-Bis(trim eth ylsilyl)but-1-en -3-yn -1-yl]ph en yl}m eth an ol (19)
For preparation , see com poun d 18a. 1H NMR (200 MHz, CDCl3) in a m ixture with 18a:
0.18 (s, 9 H, (CH3)3Si–C≡); 0.25 (s, 9 H, (CH3)3Si–C=); 4.74 (s, 2 H, CH2); 7.19–7.49 (m , 5 H,
arom . an d –CH=). EI MS from th e GC MS an alysis of a m ixture of 18a an d 19 (m/z, rel.
in ten sity): 302 (M+•, 2), 243 (6), 229 (33), 213 (6), 197 (33), 155 (6), 119 (61), 75 (36), 73 (100).
{5-Fluoro-2-[2-(triisopropylsilyl)eth yn -1-yl]ph en yl}m eth an ol (20)
Method E). Com poun d 13 (500 m g, 2.439 m m ol), triisopropylsilylacetylen e (660 µl, 2.942
m m ol, 1.2 equivalen t), Pd(PPh 3)4 (70 m g, 0.061 m m ol, 2.5 m ole %), piperidin e (8 m l), 80 °C,
20 h . Flash ch rom atograph y on silica gel (h exan e–eth er 90 : 10) gave 20 (640 m g, 86%) as
an oil. IR (CHCl3): 3 621 w, 3 568 w (sh ), 3 455 w (br), 3 076 vw, 3 046 vw, 2 959 vs, 2 945 vs ,
2 866 vs, 2 152 s, 1 607 s, 1 583 m , 1 488 vs, 1 462 s, 1 423 m , 1 383 m , 1 367 m , 1 344 w,
1 272 s, 1 245 m , 1 187 m , 1 145 s, 1 095 m , 1 034 s, 1 018 s, 996 s, 955 m , 940 m , 883 vs,
825 s (sh ), 814 s, 678 s, 661 s, 617 m , 607 m (sh ), 536 m , 491 m , 460 m , 445 m . 1H NMR
spectrum (500 MHz, CDCl3): 1.13 (brs, 21 H, 3 × (CH3)2CH); 2.17 (brs, 1 H, OH); 4.84 (brd,
2 H, J = 5.0, CH2); 6.92 (dt, 1 H, J = 8.5, 8.5, 2.7, 4-H); 7.19 (ddt, 1 H, J = 9.7, 2.7, 0.9, 0.9,
6-H); 7.45 (dd, 1 H, J = 8.4, 5.6, 3-H). 13C NMR (CDCl3): 11.25 (d, 3 × (CH3)2CH), 18.65 (q,
3 × (CH3)2CH), 63.49 (t, CH2), 95.72 (s, C≡C–Si), 103.21 (s, C≡C–Si), 113.94 (dd, JC–F = 23.9,
C-6), 114.20 (dd, JC–F = 22.9, C-4), 117.07 (d, JC–F = 2.9, C-2), 134.44 (dd, JC–F = 8.2, C-3),
145.94 (d, JC–F = 7.3, C-1), 162.77 (d, JC–F = 250.0, C-5). 19F NMR (CDCl3): –110.18 (ddd, JF–H
=
9.4, 8.6, 5.6). EI MS (m/z, rel. in ten sity): 306 (M+•, 2), 263 (10), 221 (49), 193 (100), 179 (10),
141 (7), 133 (15), 115 (7), 75 (8), 61 (7). HR EI MS: calculated for C18H27FOSi 306.1815;
foun d 306.1784.
{4-Fluoro-2-[2-(triisopropylsilyl)eth yn -1-yl]ph en yl}m eth an ol (21)
Method E). Com poun d 14 (100 m g, 0.488 m m ol), triisopropylsilylacetylen e (130 µl, 0.580
m m ol, 1.2 equivalen t), Pd(PPh 3)4 (28 m g, 0.024 m m ol, 5 m ole %), piperidin e (2 m l), 80 °C,
22 h . Flash ch rom atograph y on silica gel (h exan e–eth er 90 : 10) provided 21 (148 m g, 99%)
as an oil. IR (CHCl3): 3 610 m , 3 572 w (sh ), 3 452 w (br), 3 075 vw, 3 039 vw, 2 960 s, 2 944 s,
2 866 vs, 2 150 m , 1 608 s, 1 581 s, 1 493 s, 1 479 s, 1 463 s, 1 414 m , 1 384 m , 1 367 m ,
1 344 w, 1 268 s, 1 254 m , 1 151 s, 1 097 s, 1 072 m , 1 039 m , 1 012 s, 997 s, 959 s, 883 s,
828 m , 822 m , 679 s, 543 m , 446 m . 1H NMR (500 MHz, CDCl3): 1.14 (m , 21 H,
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3 × (CH3)2CH); 2.12 (t, 1 H, J = 6.5, OH); 4.81 (brd, 2 H, J = 6.5, CH2); 7.03 (dt, 1 H, J = 8.4,
8.4, 2.7, 5-H); 7.18 (dd, 1 H, J = 9.0, 2.7, 3-H); 7.40 (ddq, 1 H, J = 8.6, 5.8, 0.6, 0.6, 0.6, 6-H).
13C NMR (CDCl3): 11.24 (d, 3 × (CH3)2CH), 18.64 (q, 3 × (CH3)2CH), 63.46 (t, CH2), 97.27 (s,
C≡C–Si), 103.07 (s, C≡C–Si), 115.91 (dd, JC–F = 21.1, C-5), 119.25 (dd, JC–F = 22.9, C-3),
123.21 (d, JC–F = 9.2, C-2), 128.95 (dd, JC–F = 8.7, C-6), 138.99 (d, JC–F = 3.0, C-1), 161.54 (d,
JC–F = 246.8, C-4). 19F NMR (CDCl3): –115.54 (dddt, JF–H = 9.0, 8.3, 5.7, 0.8, 0.8). EI MS (m/z,
rel. in ten sity): 306 (M+•, 1), 263 (25), 221 (29), 193 (100), 179 (9), 141 (9), 131 (18), 103
(14), 75 (19), 61 (12). HR EI MS: calculated for C15H20FOSi (M – C3H7) 263.1267; foun d
263.1211.
4-Meth oxycarbon yl-2-[2-(trim eth ylsilyl)eth yn -1-yl]ben zyl Acetate (22a)
Method D). Com poun d 15 (100 m g, 0.299 m m ol), trim eth ylsilylacetylen e (95 µl, 0.672 m m ol,
2.2 equivalen t), Pd(PPh 3)4 (17 m g, 0.015 m m ol, 5 m ole %), diisopropylam in e (2 m l), 80 °C,
1 h . Flash ch rom atograph y on silica gel (petroleum eth er–eth er 90 : 10) provided 22a (66 mg,
73 %) as an oil. IR (CHCl3): 2 900 w, 2 157 w, 1 763 s, 1 745 m (sh), 1 610 w, 1 570 w , 1 491 w,
1 438 m , 1 410 w, 1 380 m , 1 362 w, 1 300 s, 1 290 s (sh ), 1 252 s, 1 097 m , 1 043 w, 1 030 w ,
991 w, 980 w (sh ), 921 w, 854 s, 847 s, 701 w, 647 w. 1H NMR (500 MHz, CDCl3): 0.26 (s, 9 H,
(CH3)3Si); 2.16 (s, 3 H, CH3CO2); 3.92 (s, 3 H, CH3O2C); 5.30 (s, 2 H, CH2); 7.44 (brd, 1 H, J =
8.3, 6-H); 7.97 (dd, 1 H, J = 8.3, 2.0, 5-H); 8.14 (d, 1 H, J = 2.0, 3-H). 13C NMR (CDCl3): 0.19
(q, (CH3)3Si), 20.82 (q, CH3CO2), 52.30 (q, CH3O2C), 64.13 (t, CH2), 100.82 (s, C≡C–Si),
101.10 (s, C≡C–Si), 122.46 (s, C-2), 127.54 (d, C-6), 129.55 (d, C-5), 129.77 (s, C-4), 133.63
(d, C-3), 142.60 (s, C-1), 166.09 (s, CH3O2C), 170.54 (s, CH3CO2). EI MS (m/z, rel. in ten sity):
304 (M+•, 47), 289 (100), 273 (13), 261 (27), 247 (64), 232 (20), 215 (15), 187 (11), 157 (21),
128 (18), 91 (19), 73 (25), 59 (12). HR EI MS: calculated for C16H20O4Si 304.1131; foun d
304.1118.
4-Meth oxycarbon yl-2-[2-(triisopropylsilyl)eth yn -1-yl]ben zyl Acetate (22b)
Method E). Com poun d 15 (85 m g, 0.254 m m ol), triisopropylsilylacetylen e (70 µl,
0.312 m m ol, 1.2 equivalen t), Pd(PPh 3)4 (15 m g, 0.013 m m ol, 5 m ole %), diisopropylam in e
(2 m l), 80 °C, 1 h. Flash chrom atography on silica gel (petroleum ether–ether 90 : 10) gave 22b
(14 m g, 28%) as an oil. IR (CHCl3): 2 945 vs, 2 893 s, 2 866 s, 2 155 w, 1 746 vs (sh ), 1 723 vs,
1 609 w, 1 570 w, 1 494 w, 1 462 s, 1 438 s, 1 410 m , 1 381 s, 1 362 m , 1 292 vs, 1 250 vs,
1 232 vs, 1 137 m (sh ), 1 124 s, 1 097 s, 1 045 s, 1 029 s, 996 s, 965 w (br, sh ), 920 s, 901 m ,
883 s, 845 w, 679 s, 665 m , 605 w. 1H NMR (500 MHz, CDCl3): 1.14 (m , 21 H,
3 × (CH3)2CH); 2.14 (s, 3 H, CH3CO2); 3.93 (s, 3 H, CH3O2C); 5.33 (brs, 2 H, CH2); 7.46 (dq,
1 H, J = 8.1, 0.6, 0.6, 0.6, 6-H); 7.97 (dd, 1 H, J = 8.1, 1.7, 5-H); 8.14 (brd, 1 H, J = 1.7, 3-H).
13C NMR (CDCl3): 11.25 (d, 3 × (CH3)2CH), 18.64 (q, 3 × (CH3)2CH), 20.83 (q, CH3CO2),
52.29 (q, CH3O2C), 64.33 (t, CH2), 97.66 (s, C≡C–Si), 102.69 (s, C≡C–Si), 122.88 (s, C-2),
127.6 7 (d, C-6), 129.40 (d, C-5), 129.81 (s, C-4), 133.74 (d, C-3), 142.51 (s, C-1), 166.14 (s,
CH3O2C), 170.51 (s, CH3CO2). EI MS (m/z, rel. in ten sity): 388 (M+•, 0.5), 334 (5), 303 (9),
275 (8), 207 (62), 165 (100), 147 (15), 89 (8). HR EI MS: calculated for C19H25O4Si
(M – C3H7) 345.1522; foun d 345.1519.
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Coupling Reactions of Halobenzenes
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Meth yl 2-[2-(Trim eth ylsilyl)eth yn -1-yl]ben zoate10,18 (23a)
Method D). Com pound 1a (100 m g, 0.465 m m ol), trim ethylsilylacetylene (145 µl, 1.026 m m ol,
2.2 equivalen t), Pd(PPh 3)4 (27 m g, 0.023 m m ol, 5 m ole %), piperidin e (2 m l), 80 °C, 6 h .
Flash ch rom atograph y on silica gel (petroleum eth er–eth er–aceton e 80 : 10 : 10) yielded 23a
(68 m g, 63%) an d m ore polar 24 (8 m g, 6%) as oils. IR (CCl4): 3 070 w, 3 023 w, 2 995 w,
2 900 m , 2 160 m , 1 738 vs, 1 722 vs, 1 597 m , 1 568 m , 1 483 s, 1 447 s, 1 434 s, 1 408 w,
1 297 vs, 1 272 s, 1 250 vs, 1 191 m , 1 163 m , 870 vs, 844 vs, 700 s, 643 m . 1H NMR (500
MHz, CDCl3): 0.28 (s, 9 H, (CH3)3Si); 3.92 (s, 3 H, CH3O2C); 7.36 (dt, 1 H, J = 7.7, 7.7, 1.5,
5-H); 7.44 (dt, 1 H, J = 7.6, 7.6, 1.4, 4-H); 7.58 (dd, 1 H, J = 7.7, 1.4, 3-H); 7.90 (dd, 1 H, J =
7.8, 1.5, 6-H). 13C NMR (CDCl3): –0.16 (q, (CH3)3Si), 51.95 (q, CH3O2C), 99.65 (s, C≡C–Si),
103.26 (s, C≡C–Si), 123.18 (s, C-2), 128.16 (d, C-5), 130.24 (d, C-6), 131.46 (d, C-3), 132.57
(s, C-1), 134.51 (d, C-4), 166.90 (s, CH3O2C). EI MS (m/z, rel. in ten sity): 232 (M+•, 13), 217
(39), 201 (5), 187 (100), 158 (27), 143 (34), 129 (15), 115 (18), 101 (16), 93 (15), 86 (14), 79
(11), 59 (5).
Meth yl 2-[2-(Triisopropylsilyl)eth yn -1-yl]ben zoate (23b)
Method E). Com poun d 1b (160 m g, 0.611 m m ol), triisopropylsilylacetylen e (165 µl, 0.736
m m ol, 1.2 equivalen t), Pd(PPh 3)4 (35 m g, 0.030 m m ol, 5 m ole %), piperidin e (2 m l), 80 °C,
13 h . Flash ch rom atograph y on silica gel (petroleum eth er–eth er 97 : 3) gave 23b (84 m g,
44%) as an oil. IR (CHCl3): 3 070 w, 2 960 vs (sh ), 2 945 vs, 2 930 s (sh ), 2 892 s, 2 866 vs,
2 156 m , 1 728 vs, 1 714 vs, 1 596 m , 1 568 m , 1 482 s, 1 463 s, 1 447 s, 1 434 s, 1 383 m ,
1 367 w, 1 300 vs, 1 276 s, 1 254 s, 1 191 m , 1 163 w, 1 130 s, 1 081 s, 1 068 w (sh ), 1 043 m ,
996 m , 965 m , 883 s, 858 m , 847 s, 809 m , 701 m , 679 vs, 660 s, 636 s, 545 w, 463 w.
1H NMR (500 MHz, CDCl3): 1.15 (s, 21 H, 3 × (CH3)2CH); 3.91 (s, 3 H, CH3O2C); 7.35 (dt,
1 H, J = 7.6, 7.6, 1.2, 4-H); 7.43 (dt, 1 H, J = 7.6, 7.6, 1.5, 5-H); 7.59 (ddd, 1 H, J = 7.8, 1.7,
0.5, 3-H); 7.88 (ddd, 1 H, J = 7.8, 1.5, 0.5, 6-H). 13C NMR (CDCl3): 11.33 (d, 3 × (CH3)2CH),
18.63 (q, 3 × (CH3)2CH), 52.13 (q, CH3O2C), 96.31 (s, C≡C–Si), 105.13 (s, C≡C–Si), 123.42 (s,
C-1), 127.98 (d, C-5), 130.17 (d, C-6), 131.33 (d, C-3), 132.64 (s, C-2), 134.93 (d, C-4),
167.19 (s, CH3O2C). EI MS (m/z, rel. in ten sity): 316 (M+•, 1), 273 (100), 243 (29), 231 (7),
201 (20), 173 (19), 129 (11), 59 (9). FAB MS (m/z): 317 ((M + H)+), 285, 279, 273, 243, 215,
197, 185, 173, 155, 145, 129, 113, 93, 73, 59. HR FAB MS: calculated for C19H29O2Si (M + H)
317.1937; foun d 317.1963.
1-[Piperidin -1-yl)am in o]carbon yl-2-[(trim eth ylsilyl)eth yn yl]ben zen e (24)
For preparation , see 23a. 1H NMR (200 MHz, CDCl3): 0.23 (s, 9 H, (CH3)3Si); 1.35–1.78 (m ,
6 H, NCH2CH2CH2CH2CH2); 3.11–3.28 (m , 2 H, NCH2CH2CH2CH2CH2); 3.69–3.80 (m , 2 H,
NCH2CH2CH2CH2CH2); 7.24–7.76 (m , 4 H, arom .).
Meth yl 5-Meth oxy-2-[2-(trim eth ylsilyl)eth yn -1-yl]ben zoate (25)
Method D). Com poun d 16 (100 m g, 0.408 m m ol), trim eth ylsilylacetylen e (125 µl, 0.884
m m ol, 2.2 equivalen t), Pd(PPh 3)4 (24 m g, 0.021 m m ol, 5 m ole %), piperidin e (2 m l), 80 °C,
4 h . Flash ch rom atograph y on silica gel (petroleum eth er–eth er 90 : 10) yielded 25 (45 m g,
42%) an d m ore lipoph ilic 26 (12 m g, 8%) as oils. IR (CHCl3): 3 083 w, 2 901 m , 2 841 m ,
2 155 s, 1 715 s (br), 1 604 s, 1 560 m , 1 495 vs, 1 465 s, 1 446 s, 1 437 s, 1 421 m , 1 415 m ,
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1 322 vs, 1 293 vs, 1 250 vs, 1 183 m , 1 138 m , 1 079 s, 1 036 s, 899 m , 859 vs, 844 vs, 825 s,
700 w, 637 m , 573 m . 1H NMR (500 MHz, CDCl3): 0.26 (s, 9 H, (CH3)3Si); 3.84 (s, 3 H,
CH3O); 3.92 (s, 3 H, CH3O2C); 6.97 (dd, 1 H, J = 8.6, 2.8, 4-H); 7.41 (d, 1 H, J = 2.8, 6-H);
7.50 (d, 1 H, J = 8.6, 3-H). 13C NMR (CDCl3): 0.24 (q, (CH3)3Si), 52.32 (q, CH3O2C), 55.77
(q, CH3O), 97.76 (s, C≡C–Si), 103.59 (s, C≡C–Si), 115.01 (d, C-6), 115.63 (s, C-2), 118.33 (d,
C-4), 134.21 (s, C-1), 136.16 (d, C-3), 159.46 (s, C-5), 167.03 (s, CH3O2C). EI MS (m/z, rel.
in ten sity): 262 (M+•, 51), 247 (24), 231 (7), 217 (100), 202 (6), 173 (7), 116 (5). HR EI MS:
calculated for C14H18O3Si 262.1025; foun d 262.0980.
Meth yl 2-[2,4-Bis(trim eth ylsilyl)but-1-en -3-yn -1-yl]-5-m eth oxyben zoate (26)
For preparation , see 25. IR (CHCl3): 3 083 w, 2 900 m , 2 840 m , 2 113 m , 1 716 s (br), 1 605 s,
1 580 m , 1 492 s, 1 465 s, 1 444 m , 1 435 s, 1 408 m , 1 315 s, 1 291 s, 1 250 vs, 1 232 s,
1 182 m , 1 142 m , 1 074 s, 1 038 s, 982 m , 865 vs, 845 vs, 697 m , 635 m . 1H NMR (500
MHz, CDCl3): 0.18 (s, 9 H, (CH3)3Si–C≡); 0.24 (s, 9 H, (CH3)3Si–C=); 3.86 (s, 3 H, CH3O);
3.88 (s, 3 H, CH3O2C); 7.01 (ddd, J = 8.7, 2.8, 0.6, 4-H); 7.41 (d, 1 H, J = 2.8, 6-H); 7.49 (brt,
1 H, J = 0.6, –CH=); 8.39 (d, 1 H, J = 8.7, 3-H). 13C NMR (CDCl3): –1.99 (q, (CH3)3Si–C=),
0.03 (q, (CH3)3Si–C≡), 52.13 (q, CH3O2C), 55.48 (q, CH3O), 105.10 (s, C≡C–-Si), 105.59 (s,
C≡C–Si), 114.69 (d, C-6), 117.40 (d, C-4), 123.72 (s, C-2), 130.26 (s, C-1), 131.04 (d, C-3),
131.12 (s, C=C–Si), 143.62 (d, C=C–Si), 158.87 (s, C-5), 167.57 (s, CH3O2C). EI MS (m/z, rel.
in ten sity): 360 (M+•, 100), 345 (64), 329 (30), 315 (9), 287 (36), 271 (24), 257 (18), 241 (93),
226 (6), 213 (8), 89 (41), 73 (90), 59 (22). HR EI MS: calculated for C19H28O3Si2 360.1577;
foun d 360.1530.
2-{3-Meth oxy-2-[2-(trim eth ylsilyl)eth yn -1-yl]ph en yl}-4,4-dim eth yl-4,5-dih ydrooxazole (27)
Method D). Com poun d 17 (80 m g, 0.242 m m ol), trim eth ylsilylacetylen e (75 µl, 0.531
m m ol, 2.2 equivalen t), Pd(PPh 3)4 (28 m g, 0.024 m m ol, 10 m ole %), piperidin e (2 m l), 80 °C,
6 h . Flash ch rom atograph y on silica gel (petroleum eth er–eth er–aceton e 80 : 10 : 10) fur-
n ish ed 27 (20 m g, 27%) an d m ore lipoph ilic 28 (11 m g, 22%) as oils. Com poun d 27: IR
(CHCl3): 3 073 w, 2 899 m , 2 841 m , 2 155 m , 1 657 s (br), 1 591 m , 1 571 s, 1 462 s, 1 438 s,
1 385 m , 1 366 m , 1 318 s, 1 288 s, 1 268 vs, 1 250 vs, 1 188 m , 1 176 m , 1 126 m , 1 081 m ,
1 048 vs, 900 m (sh ), 865 vs, 845 vs, 699 w, 631 w, 543 w. 1H NMR (500 MHz, CDCl3): 0.26
(s, 9 H, (CH3)3Si); 1.40 (s, 6 H, (CH3)2C); 3.89 (s, 3 H, CH3O); 4.11 (s, 2 H, CH2); 6.94 (dd,
1 H, J = 7.7, 1.9, 4-H); 7.27 (t, 1 H, J = 7.8, 5-H); 7.30 (dd, 1 H, J = 7.9, 1.9, 6-H). 13C NMR
(CDCl3): 0.03 (q, (CH3)3Si), 28.37 (q, (CH3)2C), 56.37 (q, CH3O), 67.85 (s, (CH3)2C), 79.35 (t,
CH2), 98.61 (s, C≡C–Si), 103.74 (s, C≡C–Si), 112.31 (s, C-2), 112.92 (d, C-4), 121.77 (d, C-6),
129.04 (d, C-5), 133.04 (s, C-1), 161.24 (s, C=N), 162.28 (s, C-3). EI MS (m/z, rel. in ten sity):
301 (M+•, 30), 286 (39), 270 (8), 246 (21), 228 (100), 214 (25), 184 (22), 160 (7), 73 (33). HR
EI MS: calculated for C17H23NO2Si 301.1498; foun d 301.1470.
(2-Eth yn yl-5-fluoroph en yl)m eth an ol (29)
Method G). Com poun d 20 (100 m g, 0.326 m m ol), tetrabutylam m on ium fluoride (555 µl of
1
M solution in THF, 0.555 m m ol, 1.7 equivalen t), THF (3 m l), room tem perature, 15 m in .
Flash ch rom atograph y on silica gel (h exan e–eth er–aceton e 80 : 10 : 10) yielded 29 (49 m g,
99%) as an oil. IR (CHCl3): 3 611 w, 3 413 w (br), 3 305 s, 2 960 s, 2 872 s, 2 106 w, 1 608 s,
1 585 m , 1 487 s, 1 467 m , 1 458 m , 1 424 m , 1 379 m , 1 349 w (sh), 1 277 s, 1 233 m , 1 150 m ,
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Coupling Reactions of Halobenzenes
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1 095 m , 1 036 m , 1 022 m (sh), 877 m , 824 m , 661 m , 616 m , 582 m . 1H NMR (500 MHz,
CDCl3): 2.09 (brs, 1 H, OH); 3.30 (d, 1 H, J = 0.8, HC≡); 4.83 (s, 2 H, CH2); 6.94 (dtt, 1 H, J =
8.4, 8.4, 2.7, 0.6, 0.6, 4-H); 7.21 (ddt, 1 H, J = 8.4, 2.7, 0.9, 0.9, 6-H); 7.47 (dd, 1 H, J = 8.4,
5.5, 3-H). 13C NMR (CDCl3): 63.17 (t, CH2), 80.20 (s, HC≡C), 81.74 (d, HC≡C), 114.17 (dd,
JC–F = 22.9, C-6), 114.39 (dd, JC–F = 22.9, C-4), 115.71 (d, JC–F = 4.0, C-2), 134.61 (dd, JC–F
=
8.2, C-3), 146.20 (d, JC–F = 7.3, C-1), 163.05 (d, JC–F = 250.9, C-5). 19F NMR (CDCl3): –109.61
(dt, JF–H = 8.7, 8.7, 5.6). EI MS (m/z, rel. in ten sity): 150 (M+•, 72), 133 (11), 121 (40), 101
(45), 85 (45), 71 (65), 57 (100), 43 (73). HR EI MS: calculated for C9H7FO 150.0481; foun d
150.0462.
(2-Eth yn yl-4-fluoroph en yl)m eth an ol (30)
Method G). Com poun d 21 (320 m g, 1.044 m m ol), tetrabutylam m on ium fluoride (1.50 m l
of 1 M solution in THF, 1.5 m m ol, 1.4 equivalen t), THF (4 m l), room tem perature, 5 m in .
Flash ch rom atograph y on silica gel (h exan e–eth er–aceton e 80 : 10 : 10) yielded 30 (133 m g,
85%) as an oil. IR (CHCl3): 3 609 m , 3 460 vw (br), 3 304 vs, 3 076 vw, 2 928 m , 2 883 w,
2 107 vw, 1 610 s, 1 583 vs, 1 493 vs, 1 414 w, 1 386 w, 1 344 w, 1 302 w, 1 265 s, 1 250 s,
1 195 w, 1 146 m , 1 092 m , 1 039 m , 1 009 m , 942 m , 876 s, 830 m , 661 s, 628 s, 606 w
(sh ), 541w, 457 w. 1H NMR (500 MHz, CDCl3): 2.01 (brs, 1 H, OH); 3.37 (s, 1 H, HC≡); 4.80
(brs, 2 H, CH2); 7.07 (dt, 1 H, J = 8.4, 8.4, 2.7, 5-H); 7.20 (dd, 1 H, J = 8.9, 2.7, 3-H); 7.42
(dq, 1 H, J = 8.5, 5.6, 0.6, 0.6, 0.6, 6-H). 13C NMR (CDCl3): 63.15 (t, CH2), 80.11 (d, JC–F
=
2.8, HC≡C), 82.76 (d, HC≡C), 116.46 (dd, JC–F = 21.1, C-5), 119.46 (dd, JC–F = 22.9, C-3),
121.98 (d, JC–F = 10.1, C-2), 129.24 (dd, JC–F = 9.2, C-6), 139.19 (d, JC–F = 3.7, C-1), 161.54
(d, JC–F = 247.3, C-4). 19F NMR (CDCl3): –115.13 (dt, JF–H = 8.5, 8.5, 5.6). EI MS (m/z, rel. in -
ten sity): 150 (M+•, 100), 149 (72), 133 (20), 122 (29), 121 (26), 101 (61), 95 (9), 85 (8), 57
(15), 43 (9). HR EI MS: calculated for C9H7FO 150.0481; foun d 150.0473.
2-Eth yn yl-4-(m eth yloxycarbon yl)ben zyl Acetate (31)
Method G). Com poun d 22a (410 m g, 1.347 m m ol), tetrabutylam m on ium fluoride (1.75 m l
of 1 M solution in THF, 1.75 m m ol, 1.3 equivalen t), THF (4 m l), room tem perature, 30 m in .
Flash ch rom atograph y on silica gel (petroleum eth er–eth er 90 : 10) yielded 31 (311 m g,
99%) as an oil. IR (CHCl3): 3 305 s, 1 743 vs (sh ), 1 724 vvs, 1 610 m , 1 573 w, 1 496 w,
1 438 s, 1 408 m , 1 301 vs, 1 291 vs, 1 250 vs, 1 232 vs, 1 124 s, 1 094 m , 1 046 s, 1 031 m ,
987 m , 919 w, 847 w, 807 w, 661 m , 627 m , 606 w. 1H NMR (500 MHz, CDCl3): 2.16 (s, 3 H,
CH3CO2); 3.38 (s, 1 H, HC≡); 3.93 (s, 3 H, CH3O2C); 5.33 (s, 2 H, CH2); 7.49 (dq, 1 H, J =
8.1, 0.7, 0.7, 0.7, 6-H); 8.02 (dd, 1 H, J = 8.1, 1.8, 5-H); 8.18 (brd, 1 H, J = 1.8, 3-H).
13C NMR (CDCl3): 20.80 (q, CH3CO2), 52.33 (q, CH3O2C), 63.96 (t, CH2), 79.73 (s, HC≡C),
83.23 (d, HC≡C), 121.32 (s, C-2), 127.59 (d, C-6), 129.87 (s, C-4), 129.92 (d, C-5), 133.96 (d,
C-3), 142.88 (s, C-1), 165.95 (s, CH3O2C), 170.55 (s, CH3CO2). EI MS (m/z, rel. in ten sity):
232 ( M+•, 34), 207 (11), 201 (27), 190 (100), 173 (25), 165 (16), 159 (25), 149 (26), 145 (15),
131 (70), 114 (26), 101 (16), 75 (14), 62 (18), 45 (34), 43 (88). HR EI MS: calculated for
C
13H12O4 232.0736; foun d 232.0731.
{2-[2-(4-Fluoro-2-h ydroxym eth ylph en yl)eth yn -1-yl]ph en yl}m eth an ol (32)
Method F). Com poun d 6b (125 m g, 0.534 m m ol), 29 (80 m g, 0.534 m m ol, 1.0 equivalen t),
Pd(PPh 3)4 (31 m g, 0.027 m m ol, 5 m ole %), piperidin e (3 m l), 80 °C, 5 h . Flash ch rom atogra-
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670
Stará et al.:
ph y on silica gel (h exan e–eth er–aceton e 80 : 10 : 10 to 50 : 30 : 20) afforded 32 (98 m g,
72%) as an oil. IR (CHCl3): 3 628 w (sh ), 3 607 m , 3 459 w (br), 3 068 w, 1 608 m , 1 600 w,
1 583 w, 1 570 w (sh ), 1 497 vs, 1 480 w (sh ), 1 452 w, 1 424 w, 1 384 w, 1 275 m , 1 233 m ,
1 152 w, 1 102 w, 1 090 w, 1 034 m , 1 020 m (br), 948 w, 825 m . 1H NMR (500 MHz,
CDCl3): 2.45 (brs, 1 H, OH); 2.82 (brs, 1 H, OH); 4.86 (brs, 2 H, CH2Ar′); 4.87 (brs, 2 H,
CH2Ar); 7.01 (dt, 1 H, J = 8.4, 8.4, 2.7, 5′-H); 7.19 (ddt, 1 H, J = 9.2, 2.7, 0.5, 0.5, 3′-H); 7.32
(dt, 1 H, J = 7.4, 7.4, 1.5, 4-H); 7.37 (dt, 1 H, J = 7.5, 7.5, 1.5, 5-H); 7.44 (ddq, 1 H, J = 7.4,
1.4, 0.6, 0.6, 0.6, 6-H); 7.54 (dd, 1 H, J = 8.5, 5.6, 6′-H); 7.56 (ddd, 1 H, J = 7.3, 1.6, 0.6,
3-H). 13C NMR (CDCl3): 63.79 (t, CH2Ar′), 64.50 (t, CH2Ar), 90.58 (s, C≡C–Ar′), 91.25 (s,
C≡C–Ar′), 114.75 (dd, JC–F = 22.0, C-3′), 115.11 (dd, JC–F = 22.9, C-5′), 117.60 (d, JC–F = 3.2,
C-1′), 121.87 (s, C-2), 127.90 (d, C-4), 128.09 (d, C-6), 128.89 (d, C-5), 132.39 (d, C-3),
134.14 (dd, JC–F = 8.2, C-6′), 142.10 (s, C-1), 145.23 (d, JC–F = 7.8, C-2′), 162.71 (d, JC–F
=
250.9, C-4′). 19F NMR (CDCl3): –110.29 (ddd, JF–H = 9.2, 8.3, 5.6). EI MS (m/z, rel. in ten sity):
256 (M+•, 9), 238 (96), 220 (11), 209 (100), 196 (22), 189 (16), 183 (40), 137 (21), 119 (17),
109 (11), 91 (13), 77 (11), 63 (7), 51 (8). HR EI MS: calculated for C16H13FO2 256.0899;
foun d 256.0886.
{2-[2-(5-Fluoro-2-h ydroxym eth ylph en yl)eth yn -1-yl]ph en yl}m eth an ol (33)
Method F). Com poun d 6b (170 m g, 0.726 m m ol), 30 (109 m g, 0.726 m m ol, 1.0 equiva-
len t), Pd(PPh 3)4 (84 m g, 0.073 m m ol, 10 m ole %), piperidin e (3 m l), 80 °C, 2 h . Flash ch ro-
m atograph y on silica gel (h exan e–eth er–aceton e 80 : 10 : 10) afforded 33 (184 m g, 99%) as
an oil. IR (CHCl3): 3 608 m , 3 465 w (br), 3 072 w, 2 933 w, 2 882 w, 2 209 vw, 1 581 vs,
1 508 s, 1 496 vs, 1 480 w (sh ), 1 464 w, 1 418 w, 1 384 w, 1 345 vw, 1 308 m , 1 263 w,
1 199 m , 1 138 w, 1 108 w, 1 083 w, 1 011 s, 1 034 m , 950 m , 875 m , 829 m , 607 w, 538 w.
1H NMR (500 MHz, aceton e-d6): 4.94 (brd, 2 H, J = 6.3, CH2Ar); 4.97 (brd, 2 H, J = 6.3,
CH2Ar′); 7.27 (dt, 1 H, J = 8.6, 8.6, 2.7, 4′-H); 7.38 (dd, 1 H, J = 9.4, 2.7, 6′-H); 7.40 (dtt, 1 H,
J = 7.6, 7.6, 1.5, 0.7, 0.7, 5-H); 7.51 (dt, 1 H, J = 7.6, 7.6, 1.5, 4-H); 7.64 (brdd, 1 H, J = 7.6,
1.5, 6-H); 7.70 (ddt, 1 H, J = 8.6, 5.9, 0.9, 0.9, 3′-H); 7.70 (ddt, 1 H, J = 7.6, 1.5, 0.9, 0.9,
3-H). 13C NMR (aceton e-d6): 62.71 (t, CH2Ar), 63.25 (t, CH2Ar′), 91.02 (d, JC–F = 3.2,
C≡C–Ar′), 93.21 (s, C≡C–Ar′), 116.35 (dd, JC–F = 21.1, C-4′), 118.73 (dd, JC–F = 22.9, C-6′),
121.23 (s, C-2), 123.46 (d, JC–F = 9.7, C-1′), 127.63 (d, C-6), 127.73 (d, C-4), 129.69 (d, JC–F
=
8.2, C-3′), 129.84 (d, C-5), 132.78 (d, C-3), 141.03 (s, C-1), 145.02 (d, JC–F = 3.4, C-2′),
162.16 (d, JC–F = 242.7, C-5′). 19F NMR (aceton e-d6): –112.99 (tt, JF–H = 8.8, 5.4). EI MS (m/z,
rel. in ten sity): 256 (M+•, 3), 238 (100), 221 (13), 209 (65), 207 (18), 196 (16), 189 (9), 183
(25), 137 (13), 119 (13), 109 (5), 91 (9), 77 (6). HR EI MS: calculated for C16H11FO (M – H2O)
238.0794; foun d 238.0799.
2-[2-(2-Hydroxym eth ylph en yl)eth yn -1-yl]-4-(m eth oxycarbon yl)ben zyl Acetate (34)
Method F). Com poun d 6b (105 m g, 0.449 m m ol), 31 (104 m g, 0.448 m m ol, 1.0 equiva-
len t), Pd(PPh 3)4 (26 m g, 0.022 m m ol, 5 m ole %), diisopropylam in e (5 m l), 80 °C, 1 h . Flash
ch rom atograph y on silica gel (petroleum eth er–eth er–aceton e 80 : 10 : 10) afforded 34 (99 m g,
65%) as an oil. IR (CHCl3): 3 607 w, 2 954 w, 2 880 vw, 2 210 vw, 1 746 m (sh ), 1 724 vs,
1 608 w, 1 572 w, 1 497 w, 1 483 w, 1 450 w, 1 438 m , 1 413 w, 1 380 w, 1 363 w, 1 318 m ,
1 282 m , 1 255 s, 1 156 w, 1 133 w (sh ), 1 106 w, 1 043 w, 1 030 w, 1 008 w, 989 w, 916 w,
845 vw. 1H NMR (500 MHz, CDCl3): 2.15 (s, 3 H, CH3CO2); 2.51 (brs, 1 H, OH); 3.95 (s, 3 H,
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Coupling Reactions of Halobenzenes
671
CH3O2C); 4.92 (s, 2 H, CH2OH); 5.41 (brs, 2 H, CH2OAc); 7.31 (dt, 1 H, J = 7.6, 7.6, 1.5,
4′-H); 7.39 (dt, 1 H, J = 7.6, 7.6, 1.5, 5′-H); 7.51 (ddt, 1 H, J = 7.5, 1.5, 0.6, 0.6, 3′-H); 7.53
(dq, 1 H, J = 8.1, 0.6, 0.6, 0.6, 6-H); 7.57 (dd, 1 H, J = 7.7, 1.5, 6′-H); 8.01 (dd, 1 H, J = 8.1,
1.8, 5-H); 8.22 (d, 1 H, J = 1.8, 3-H). 13C NMR (CDCl3): 20.87 (q, CH3CO2), 52.37 (q,
CH3O2C), 63.84 (t, CH2OH), 64.33 (t, CH2OAc), 89.98 (s, C≡C–Ar′), 92.85 (s, C≡C–Ar′),
120.87 (s, C-1′), 122.52 (s, C-2), 127.60 (d, C-3′), 127.68 (d, C-4′), 128.07 (d, C-6), 129.27 (d,
C-5′), 129.55 (d, C-5), 130.04 (s, C-4), 132.45 (d, C-6′), 133.29 (d, C-3), 141.86 (s, C-2′),
142.49 (s, C-1), 166.06 (s, CH3O2C), 170.84 (s, CH3CO2). EI MS (m/z, rel. in ten sity): 338
(M+•, 26), 307 (12), 295 (39), 277 (100), 263 (11), 219 (59), 201 (12), 191 (53), 189 (42), 178
(17), 69 (24), 57 (26), 43 (44). HR EI MS: calculated for C20H18O5 338.1154; foun d 338.1175.
Dim eth yl 4,4′-Bis(acetoxym eth yl)-3,3′-eth yn ediyldiben zoate (35)
Method F). Com poun d 15 (144 m g, 0.431 m m ol), 31 (100 m g, 0.431 m m ol, 1.0 equiva-
len t), Pd(PPh 3)4 (25 m g, 0.022 m m ol, 5 m ole %), diisopropylam in e (5 m l), 80 °C, 1 h . Flash
ch rom atograph y on silica gel (petroleum eth er–eth er–aceton e 80 : 10 : 10) afforded 35
(20 m g, 11%) as an oil. IR (CHCl3): 2 954 w, 2 933 vw, 1 746 m (sh ), 1 724 vs, 1 608 w,
1 575 w, 1 499 vw, 1 481 w, 1 463 w, 1 457 w, 1 439 m , 1 422 w, 1 317 w, 1 293 m , 1 278 w
(sh ), 1 248 vs, 1 157 w, 1 135 w (sh ), 1 103 w, 1 046 w, 1 030 w, 994 w, 917 w, 845 vw.
1H NMR (500 MHz, CDCl3): 2.17 (s, 6 H, 2 × CH3CO2); 3.95 (s, 6 H, 2 × CH3O2C); 5.41 (s,
4 H, 2 × CH2); 7.53 (d, 2 H, J = 8.1, 5,5′-H); 8.04 (dd, 2 H, J = 8.1, 1.9, 6,6′-H); 8.23 (d, 2 H, J =
1.9, 2,2′-H). 13C NMR (CDCl3): 20.87 (q, CH3CO2), 52.40 (q, CH3O2C), 64.03 (t, CH2OAc),
91.25 (s, ≡C–), 121.92 (s, C-3,3′), 127.98 (d, C-5,5′), 129.94 (d, C-6,6′), 130.06 (s, C-1,1′),
133.57 (d, C-2,2′), 142.23 (s, C-4,4′), 165.99 (s, 2 × CH3O2C), 170.56 (s, 2 × CH3CO2). EI MS
(m/z, rel. in ten sity): 438 (M+•, 23), 407 (16), 378 (55), 363 (28), 336 (48), 321 (20), 304 (30),
277 (62), 249 (18), 218 (16), 189 (38), 59 (14), 43 (100). HR EI MS: calculated for C24H22O8
438.1315; foun d 438.1305.
The financial support by the Grant Agency of the Czech Republic (Reg. Nos 203/96/0288 and
203/99/1448) is gratefully acknowledged. We are very indebted to Dr J. Závada of this Institute for
his valuable and stimulating discussions. We also thank Dr I. Valterová of this Institute for the GC
MS analyses.
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Collect. Czech. Chem. Commun. (Vol. 64) (1999)

672
Stará et al.:
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of 15 with gaseous acetylene under Pd or Pd/Cu catalysis.
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sulfuric acid, and potassium hydroxide pellets) into the reaction mixture led to reduced
yields of coupled products.
17. During preparation of the manuscript, the efficient synthesis of 23a has been
published18. The Pd(PPh3)2Cl2/CuI-catalyzed coupling of methyl 2-bromobenzoate 1a
with (trimethylsilyl)acetylene in the presence of carefully purified triethylamine (1.5
equivalent) in THF at room temperature provided 23a in 88% yield.
18. Thorand S., Krause N.: J. Org. Chem. 1998, 63, 8551.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)