Copper-catalyzed cross-coupling of 1-iodoalkynes with organostannanes

Article abstract of DOI:10.1055/s-1998-6087

Copper-catalyzed cross-coupling of 1-iodoalkynes with organostannanes was readily achieved in the presence of CuI (10 mol%) in DMF at room temperature for 6 hours by adding 1-iodoalkynes slowly to organostannanes.

Full text of DOI:10.1055/s-1998-6087

SYNTHESIS
Short Papers
1252
Copper-Catalyzed Cross-Coupling of 1-Iodoalkynes with Organostannanes
Suk-Ku Kang,* Won-Yeob Kim, Xianghua Jiao
Department of Chemistry, Sung Kyun Kwan University, Natural Science Campus, Suwon 440-746, Korea
Fax +82(331)290-7079; E-mail: skkang@chem.skku.ac.kr
Received 5 January 1998; revised 23 February 1998
Abstract: Copper-catalyzed cross-coupling of 1-iodoalkynes with
the presence of CuI (10 mol%) in DMF at room tempera-
ture, the homocoupled products of bisphenylacetylene,
bisfuran, and the cross-coupled product 3b were formed
in the ratio of 2:1:1. We assumed that 1-iodo-2-phenyl-
acetylene (1a) is the reactive species which undergoes ho-
mocoupling. Finally, by adding 1a slowly to organostan-
nanes 2b via syringe pump we could get the cross-coupled
product 3b as the major product. Thus, it is crucial to add
1-iodoalkynes slowly via a syringe pump to reduce homo-
coupling. The results of copper-catalyzed cross-coupling
of 1-iodoalkynes with organostannanes are summarized
in the Table. 1-Iodo-2-phenylacetylene (1a) was slowly
added via a syringe pump to organostannane 2a in DMF
at room temperature for 6 hours to afford the cross-cou-
pled product 3a9 in 71% yield (entry 1, Table). The reac-
tion of 1a with 2-furylstannane 2b proceeded smoothly to
give 2-furyl-substituted alkyne 3b in 75% yield by adding
1a slowly (entry 2). In considering the mechanistic expla-
nation, it is presumed that the slow addition of 1-iodo-
alkynes prevents the homocoupling of 1-iodoalkynes. As
indirect evidence when the same reaction was conducted
by the slow addition of organostannane 2b to 1a, the ho-
mocoupled product of 1a was produced in ~25% yield
along with 50% yield of the cross-coupled product 3b and
bisfuran (~25%). Accordingly, the iodoalkyne 1a was
subjected to coupling with 2-thienylstannane 2c to give
the product 3c10 in 77% yield (entry 3). This coupling
method was applied to alkenyl-, alkynyl-, and allylstan-
nanes (entries 4–6). Thus, the iodoalkyne 1a underwent
facile cross coupling in the presence of CuI (10 mol%)
with (E)-β-styrylstannane 2d, 1-phenylethynylstannane
2e, and allylstannane 2f to afford the coupled products
3d,11 3e, and 3f in 76, 80, and 90% yields, respectively
(entries 4–6). For the alkyl-substituted 1-iodoalkyne 1b,
the reaction under the typical conditions with 2a gave the
phenyl-substituted alkyne 3g in 88% yield (entry 7).
Treatment of 1b with alkenylstannane 2d and alkynyl-
stannane 2e under the same conditions provided the cou-
pled product 3h and 3i in 71 and 76% yields, respectively
(entries 8 and 9). When 1-iodoalkyn-3-ol 1c was reacted
with 2a and 2b, the coupled products 3j and 3k were
readily obtained (entries 10 and 11). Finally, 1-iodoalkyn-
3-ene 1d was smoothly coupled with the alkenylstannane
2d to afford the yndiene compound 3l in 82% yield (entry
12).
organostannanes was readily achieved in the presence of CuI
(10 mol%) in DMF at room temperature for 6 hours by adding
1-iodoalkynes slowly to organostannanes.
Key words: copper-catalyzed cross-coupling, 1-iodoalkynes,
organostannanes, 1-substituted acetylenes
The conjugated enyne moiety is an important structural
unit in a number of natural products. The enynes have
been generally prepared by the coupling reactions of ter-
minal alkynes with aryl or vinyl halides, which is known
as the Sonogashira reaction.1 The synthesis of enynes can
be also accomplished using haloalkynes with aryl and alk-
enyl copper compounds.2
The palladium-catalyzed cross-coupling (Stille reaction)3
of organic electrophiles such as vinyl halides or triflates
with organostannanes has become an extremely powerful
tool in organic synthesis. The cross-coupling of vinyl io-
dides or vinyl triflates with alkynylstannanes to obtain
enynes in the presence of palladium catalyst has been re-
ported.4 However, the cross-coupling of haloalkynes with
organostannanes to synthesize enynes has rarely been re-
ported.5 In 1990, Liebeskind et al.6 reported the first ex-
ample of the palladium-catalyzed cross-coupling of 1-
iodohexyne with cyclobutenylorganostannane. Recently,
palladium-catalyzed cross-coupling of 1-iodoalkynes
with (E)-α-selanylvinylstannanes was reported by Huang
et al.7 In connection with our programs to utilize copper
as a catalyst for cross-coupling,8 we have investigated the
copper iodide catalyzed cross-coupling of 1-iodoalkynes
with organostannanes. Here we report copper(I) iodide
catalyzed cross-coupling of 1-iodoalkynes with aryl-, alk-
enyl-, alkynyl-, and allylstannanes.
Initially, we examined the copper-catalyzed cross-cou-
pling of 1-iodo-2-phenylacetylene (1a) and 2-furylstan-
nane 2b to determine the optimum reaction conditions. A
series of experiments were performed. Of the catalysts
tested CuI (10 mol%) was the most suitable and better
than PdCl2 in NMP at room temperature. As solvents
among NMP, DMF, THF, THF/NMP (1: 1), and 1,4-diox-
ane, NMP and DMF were preferable. The addition of ad-
ditives to reduce homocoupling, such as LiCl and NaCl,
did not improve the yields of the cross-coupled products,
even if the addition of KCl and CsCl increased the yields
of the cross-coupled products with limited success. With-
out additives when the above reaction was conducted in
Reagent grade commercially available reagents and solvents were
used. DMF was freshly distilled from CaH2 prior to use. 1-Io-
doalkynes 2a, 2b, and 2c were prepared12 from the corresponding 1-
alkynes and BuLi followed by iodination with molecular iodine. The
1-iodoalkyne 2b was prepared13 from the corresponding 1-alkyne by
treatment with NIS and AgNO3.

SYNTHESIS
September 1998
1253
Table 1. Copper-Catalyzed Cross-Coupling of 1-Iodoalkynes with Orgnaostannanesa
Entry
1-Iodoalkynes
PhC≡CI 1a
1a
Organostannanes
Products
Yield (%)b
1
2
PhSnBu3 2a
71
75
3
4
5
1a
1a
1a
77
76
80
6
1a
90
7
8
n-BuC≡CI 1b
2a
2d
88
71
1b
9
1b
2e
2a
76
72
10
Ph(HCOH)C≡CI 1c
11
12
1c
2b
2d
76
82
1d
a Reaction conditions: 1-iodoalkynes (1 equiv), organostannanes (1 equiv), CuI (10 mol %), DMF, r.t., 6 h.
b The isolated yields.
IR (neat): ν = 3058, 3022, 2954, 1600, 1381, 1215, 909, 735 cm–1.
MS (EI): m/z (%) = 185 (11), 184 (100), 152 (13), 139 (30), 126 (9),
74 (11), 63 (11).
Copper-Catalyzed Cross-Coupling of Organostannanes with 1-
Iodoalkynes; 2-(2-Phenylethynyl)furan (3b);Typical Procedure:
To
a stirred solution of 2-(tributylstannyl)furan (100 mg,
0.280 mmol), CuI (5.3 mg, 0.028 mmol) in DMF (3 mL) at r.t. was
slowly added the 1-iodo-2-phenylacetylene (63.9 mg, 0.280 mmol) in
DMF (3 mL) via syringe pump over 1.5 h. The mixture was stirred at
r.t. for 6 h and extracted with Et2O and washed with sat. KF (10 mL)
and then brine (10 mL). The organic layer was dried (anhyd MgSO4)
and evaporated in vacuo. The crude product was separated by column
chromatography (silica gel, hexanes, Rf 0.43) to afford 3b; yield:
35.3 mg (75%).
(E)-1,4-Diphenylbut-1-en-3-yne (3d):11
1H NMR (400 MHz, CDCl3): δ = 6.40 (d, 1H, J = 16 Hz), 7.06 (d, 1H,
J = 16 Hz), 7.33 (m, 6H), 7.38 (m, 2H), 7.62 (m, 2H).
IR (KBr): ν = 3041, 3010, 1605, 1471, 843 cm–1.
MS (EI): m/z (%) = 205 (78), 203 (100), 102 (28).
1,4-Diphenylbuta-1,3-diyne (3e):
1H NMR (400 MHz, CDCl3): δ = 7.35 (m, 6H), 7.54 (m, 4H).
IR (KBr): ν = 3104, 2158, 1594, 1477, 920 cm–1.
MS (EI): m/z (%) = 203 (16), 202 (100), 200 (23), 174 (3), 102 (22),
88 (13), 75 (6).
1H NMR (400 MHz, CDCl3): δ = 6.44 (d, 1H), 6.67 (dd, 1H), 7.37 (m,
4H), 7.54 (m, 2H).
IR (neat): ν = 3105, 3056, 2953, 1500, 1415, 1070, 918, 690, 536 cm–1.
MS (EI): m/z (%) = 169 (14), 168 (100), 140 (17), 139 (89), 114 (11),
70 (9), 63 (9).
5-Phenylpent-1-en-4-yne (3f):
1H NMR (400 MHz, CDCl3): δ = 3.22 (m, 2H). 5.19 (dt, 1H), 5.43
(dd, 1H), 5.92 (m, 1H), 7.31 (m, 3H), 7.45 (m, 2H).
IR (neat): ν = 3082, 3059, 3018, 2982, 2921, 2886, 1641, 1598, 1489,
916 cm–1.
Diphenylacetylene (3a):9
1H NMR (400 MHz, CDCl3): δ = 7.35 (m, 6H), 7.54 (m, 4H).
IR (KBr): ν = 3036, 1560, 1500, 1070, 918, 690, 536 cm–1.
MS (EI): m/z (%) = 178 (100), 176 (20), 152 (9), 89 (13), 76 (12).
MS (EI): m/z (%) = 143 (10), 142 (90), 141 (100), 115 (55), 89 (7), 63 (8).
1-Phenyl-2-(2-thienyl)acetylene (3c):10
1H NMR (400 MHz, CDCl3): δ = 7.01 (m, 1H), 7.29 (m, 2H), 7.35 (m,
3H), 7.53 (m, 2H).
1-Phenylhex-1-yne (3g):
1H NMR (400 MHz, CDCl3): δ = 0.96 (t, 3H, J = 7.3 Hz), 1.55 (m,
4H), 2.42 (t, 2H, J = 7.0 Hz), 7.34 (m, 5H).

SYNTHESIS
Short Papers
1254
IR (neat): ν = 3057, 1599, 1491, 1064, 909 cm–1.
MS (EI): m/z (%) = 159 (20), 158 (30), 143 (52), 129 (30), 116 (22),
115 (100), 113 (11), 102 (9).
We acknowledge with thanks the generous financial support from
KOSEF (97-0501-02-01-3), KOSEF-OCRC, and Ministry of Educa-
tion (BSRI-97-3420).
(E)-1-Phenyloct-1-en-3-yne (3h):
1H NMR (400 MHz, CDCl3): δ = 0.96 (t, 3H, J = 7.3 Hz), 1.55 (m,
4H), 2.42 (t, 2H, J = 7.0 Hz), 6.17 (dt, 1H, J = 16 Hz), 6.88 (d, 1H, J
= 16 Hz) 7.33 (m, 5H).
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IR (neat): ν = 3062, 3010, 2932, 2872, 1486, 1463, 1404, 1104, 755,
689 cm–1.
MS (EI): m/z (%) = 184 (34), 169 (9), 155 (20), 141 (100), 115 (59),
91 (20), 77 (10), 63 (10), 51 (7).
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1-Phenylocta-1,3-diyne (3i):
1H NMR (400 MHz, CDCl3): δ = 0.96 (t, 3H), 1.55 (m, 4H), 2.42 (t,
2H), 7.34 (m, 5H).
IR (neat): ν = 3054, 2986, 2931, 1487, 1441, 1265, 738 cm–1.
MS (EI): m/z (%) = 182 (26), 165 (76), 152 (53), 139 (100), 126 (40),
115 (36), 91 (21), 63 (10).
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1996, 61, 9082.
1,3-Diphenylprop-2-yn-1-ol (3j):
1H NMR (400 MHz, CDCl3): δ = 2.36 (s, 1H), 5.70 (s, 1H), 7.33 (m,
4H), 7.42 (m, 2H), 7.49 (m, 2H), 7.63 (m, 2H).
IR (neat): ν = 3377, 3118, 3063, 2199, 1707, 1490, 1286, 1032, 758,
694 cm–1.
MS (EI): m/z (%) = 209 (11), 208 (74), 207 (100), 191 (21), 179 (67),
178 (64), 165 (29), 131 (24), 130 (39), 129 (43), 102 (41), 77 (46), 51
(15).
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874.
1-Phenyl-3-(2-thienyl)prop-2-yn-1-ol (3k):
1H NMR (400 MHz, CDCl3): δ = 2.36 (s, 1H), 5.71 (s, 1H), 6.99 (dd,
1H), 7.27 (m, 2H), 7.42 (m, 3H), 7.60 (m, 2H).
IR (neat): ν = 3300, 3055, 2986, 2189, 1637, 1450, 1266, 1030, 990,
737 cm–1.
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MS (EI): m/z (%) = 213 (11), 212 (82), 183 (77), 152 (14), 139 (21),
135 (100), 107 (16), 92 (19), 77 (67), 63 (37).
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(E,E)-1,6-Diphenylhexa-1,5-dien-3-yne (3l):
1H NMR (400 MHz, CDCl3): δ = 6.30 (d, 2H, J = 16 Hz), 7.00 (d, 2H,
J = 16 Hz), 7.37 (m, 10H).
IR (KBr): = 3063, 1807, 1550, 1500, 1069, 915, 705, 687, 524 cm–1.
MS (EI): m/z (%) = 230 (42), 229 (39), 228 (34), 215 (16), 115 (100),
101 (11).
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