The first regioselective hydroformylation of acetylenic thiophenes catalyzed by a zwitterionic rhodium complex and triphenyl phosphite

Article abstract of DOI:10.1021/jo9912653

The hydroformylation of acetylenic thiophenes is readily accomplished by using the zwitterionic rhodium catalyst (η⁶-C₆H₅BPh₃)^-Rh⁺(1,5-COD) and triphenyl phosphite in the presence of CO and H₂. This catalytic system affords, as the major product, the *β-unsaturated aldehyde with the aldehyde and thiophene attached to the same olefin carbon atom. Assistance of sulfur from the heterocycle provides excellent regioselectivity and yields when the acetylenic unit is a propargyl ether or ester, phenylacetylene, or an enyne.

Full text of DOI:10.1021/jo9912653

9640
J . Org. Chem. 1999, 64, 9640-9645
Th e F ir st Regioselective Hyd r ofor m yla tion of Acetylen ic
Th iop h en es Ca ta lyzed by a Zw itter ion ic Rh od iu m Com p lex a n d
Tr ip h en yl P h osp h ite
Bernard G. Van den Hoven and Howard Alper*
Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Ontario, Canada K1N 6N5
Received August 9, 1999
The hydroformylation of acetylenic thiophenes is readily accomplished by using the zwitterionic
rhodium catalyst (η6-C6H5BPh3)-Rh+(1,5-COD) and triphenyl phosphite in the presence of CO and
H2. This catalytic system affords, as the major product, the R,â-unsaturated aldehyde with the
aldehyde and thiophene attached to the same olefin carbon atom. Assistance of sulfur from the
heterocycle provides excellent regioselectivity and yields when the acetylenic unit is a propargyl
ether or ester, phenylacetylene, or an enyne.
In tr od u ction
by Buchwald and co-workers in 1995,9 and by Hidai and
co-workers in 1997,10 demonstrate that the hydroformy-
lation of acetylenes can be readily accomplished in high
regioselectivity and yields. Recently, we described the
hydroformylation of conjugated enynes in which a cata-
lytic system comprising the zwitterionic rhodium complex
1 and triphenyl phosphite were utilized with CO and H2
to form R,â-unsaturated aldehydes in excellent regiose-
lectivity and moderate to good yields.11
The coordinating ability of sulfur-containing com-
pounds to reactive sites of metal complexes has long been
a limiting factor toward the catalysis of sulfur-containing
materials.1 Catalysis in the presence of sulfur has been
of considerable interest for many years due to applica-
tions in organic chemistry,2 the pharmaceutical3 and
polymer4 industries.
In past years, we have shown how catalysis may be
used for the selective aerobic oxidation of sulfides,5
carbonylation of thiazolidines,6 and thiocarbonylation of
propargylic alcohols, allenes, allylic alcohols, and enynes
with thiols and carbon monoxide, affording unsaturated
thioesters and dithioesters.7 Hydroformylation of a va-
riety of alkenes including vinyl sulfones and sulfoxides
was readily catalyzed by the zwitterionic rhodium com-
plex (η6-C6H5BPh3)-Rh+(1,5-COD) (1).8 To our knowledge,
the hydroformylation of a triple bond to form an R,â-
unsaturated aldehyde in the presence of sulfur has not
been accomplished.
Acetylenic thiophenes and other acetylenic sulfur-
containing heterocycles occur naturally in plants,12 and
may be readily prepared by the Pd/CuI coupling of
haloheterocycles with terminal alkynes.13 Over the past
few years, increased attention has been given to sulfur-
containing heterocycles which contain substituted un-
saturated groups.14 Hydroformylation of an acetylenic
unit in these heterocycles would result in the formation
of either a branched or linear R,â-unsaturated aldehyde
with a thiophene conjugating unit. These novel materials
would have the potential to be applied in further modi-
fications to new functionalities, or transformations in-
(7) (a) Xiao, W.-J .; Alper, H. J . Org. Chem. 1997, 62, 3422. (b) Xiao,
W.-J .; Vasapollo, G.; Alper, H. J . Org. Chem. 1998, 63, 2609. (c) Xiao,
W.-J ..; Alper, H. J . Org. Chem. 1998, 63, 7939. (d) Xiao, W.-J .;
Vasapollo, G.; Alper, H. J . Org. Chem. 1999, 64, 2080.
(8) (a) Totland, K.; Alper, H. J . Org. Chem. 1993, 58, 3326. (b) Alper,
H.; Zhou, J . Q. J . Org. Chem. 1992, 57, 3729. (c) Amer, I.; Alper, H. J .
Am. Chem. Soc. 1990, 112, 3674. (d) Lee, C. W.; Alper, H. J . Org. Chem.
1995, 60, 499.
New advances have been recently reported for the
hydroformylation of internal acetylenes. Results obtained
(9) J ohnson, J . R.; Cuny, G. D.; Buchwald, S. L. Angew. Chem., Int.
Ed. Engl. 1995, 34, 1760.
(10) Ishii, Y.; Miyashita, K.; Kamita, K.; Hidai, M. J . Am. Chem.
Soc. 1997, 119, 6448.
(1) (a) Dubois, M. R. Chem. Rev. 1989, 89, 1. (b) Hegedus, L. L.;
McCabe, R. W. In Catalyst Poisoning; Marcel Dekker: New York, 1984.
(c) Hutton, A. T. In Comprehensive Coordination Chemistry; Wilkinson,
G., Gillard, R. D., McCleverty, J . A., Eds.; Pergamon: Oxford, 1984;
Vol. 5, p 1151.
(2) (a) J oule, J . A.; Mills, K.; Smith, G. F. Heterocyclic Chemistry,
3rd ed.; Chapman and Hall: London, 1995. (b) Meyers, A. I. In
Heterocycles in Organic Chemistry; Taylor, E. C., Weissberger, A., Eds.;
J ohn Wiley and Sons: New York, 1974. (c) Paquette, L. A. Principles
of Modern Heterocyclic Chemistry, W. A. Benjamin Inc.: New York,
1968.
(3) (a) Krohn, K., Kirst, H. A., Maag, H., Eds. Antibiotics and
Antivirial Compounds; VCH Publishers Inc.: New York, 1993. (b)
Lednicer, D.; Mitscher, L. A. Organic Chemistry of Drug Synthesis;
J ohn Wiley and Sons: New York, 1977.
(4) (a) Choi, W.; Sanda, F.; Endo, T. J . Polym. Sci., Part A: Polym.
Chem. 1998, 36, 1189. (b) Ng, S. C.; Chan, H. S. O.; Wong, P. M. L.;
Tan, K. L.; Tanb, B. T. G. Polymer 1998, 39, 4963. (c) Longridge, J . J .;
Rawson, J . M. Polyhedron 1998, 17, 1871.
(11) Van den Hoven, B. G.; Alper, H. J . Org. Chem. 1999, 64, 3964.
(12) Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V. Comprehensive
Heterocyclic Chemistry II; Pergamon: Oxford, 1996; Vol. 2, p 679.
(13) (a) Carpita, A.; Lezzi, A.; Rossi, R.; Marchetti, F.; Merlino, S.
Tetrahedron 1985, 41, 621. (b) Rossi, R.; Carpita, A.; Lezzi, A.
Tetrahedron 1984, 40, 2773. (c) Sakamoto, T.; Shiraiwa, M.; Kondo,
Y.; Yamanaka, H. Synthesis 1983, 312. (d) Ames, D. E.; Bull, D.;
Takundwa, C. Synthesis 1981, 364. (e) D’Auria, M.; De Mico, A.;
D’Onofrio, F.; Piancatelli, G. J . Org. Chem. 1987, 52, 5243.
(14) (a) Boivin, J .; Huppe, S.; Zard, S. Z. Tetrahedron Lett. 1996,
37, 8735. (b) Degl’Innocenti, A.; Funicello, M.; Scafato, P.; Spagnolo,
P. Tetrahedron Lett. 1997, 38, 2171. (c) Varney, M. D.; Romines, W.
H.; Palmer, C. L. PCT Int. Appl. WO 9,640,674, 1996. (d) Tanaka, H.;
Fukuzumi, K.; Togawa, T.; Banno, K.; Ushiro, T.; Morii, M.; Nakatani,
T. PCT Int. Appl. WO 9,633,195, 1996. (e) Chan, M. F.; Raju, B. G.;
Kois, A.; Verner, E. J .; Wu, C.; Castillo, R. S.; Yalamoori, V.; Balaji,
V. N. US Patent 5,594,021, 1997. (f) Labadie, S. S. Synth. Commun.
1998, 28, 2531.
(5) Aldea, R.; Alper, H. J . Org. Chem. 1995, 60, 8365.
(6) Khumtaveeporn, K.; Alper, H. J . Am. Chem. Soc. 1994, 116, 5662.
10.1021/jo9912653 CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/02/1999

Hydroformylation of Acetylenic Thiophenes
J . Org. Chem., Vol. 64, No. 26, 1999 9641
volving cyclization15 or addition reactions,16 ultimately
assisting in the preparation of drugs17 and pesticides.18
We now describe the use of catalytic quantities of 1,
in the presence of triphenyl phosphite, CO, and H2, to
attain the hydroformylation of both simple and function-
alized acetylenic thiophenes in good to excellent conver-
sions, selectivities, and yields.
F igu r e 1. Rhodium coordination to an enyne prior to hydro-
formylation.
Resu lts a n d Discu ssion
The hydroformylation of conjugated enynes was per-
formed using the zwitterionic rhodium complex 1 and
triphenyl phosphite, 3-6 mmols of enyne, and 12 atm of
synthesis gas at 60 °C for 36-48 h (eq 1). Under these
conditions branched formyl dienes were obtained in 50-
55% yields.11
F igu r e 2. Thiophene coordination to a rhodium complex.
In 1997, a theoretical study on the binding of thiophenes
to transition metals noted two possible modes of com-
plexation to rhodium (Figure 2).19 The η1 complex (15
kcal/mol) was appreciably lower in binding energy than
the η2 complex (30 kcal/mol). This study suggested the
possibility of a sulfur assisted hydroformylation of acetyl-
enic thiophenes. In many studies,20 including our own
work on the hydroformylation of enynes, it was observed
that when there is both a double bond and a triple bond
present within a molecule, the triple bond is more
reactive. This is consistent with the binding energy for
rhodium-triple bond coordination being lower than the
binding energy for the metal coordinating to a double
bond. One could infer that the η1 binding energy to the
thiophene sulfur would be similar to that for a triple bond
to rhodium. Having both of these functionalities adjacent
to each other would result in a beneficial arrangement
for the rhodium-catalyzed hydroformylation of the triple
bond.
During this investigation an interesting substrate was
examined to gain insight into the mechanism of the
reaction. The hydroformylation of 1-(3-methoxyprop-1-
ynyl)cyclohexene resulted in two formyl dienes with a
branched-to-linear ratio of 2:1 (eq 2).
It was observed during our study on the hydroformyl-
ation of enynes that triphenyl phosphite is less active as
a ligand than the functionalized bisphosphite ligand used
by Buchwald and co-workers.9 By controlling the substi-
tution within the aromatic phosphite structure, the
kinetics of the reaction can be readily controlled. It may
be desirable in some cases to use a less active catalytic
system to attain a product when the substrate is more
active.
It was conceivable that a dual interaction between the
catalyst and substrate could occur prior to hydroformyl-
ation (Figure 1). The strength of this initial interaction
may govern the resulting regioselectivity.
(15) (a) Li, Y.; Thiemann, T.; Sawada, T.; Mataka, S.; Tashiro, M.
J . Org. Chem. 1997, 62, 7926. (b) Katritzky, A. R.; Serdyuk, L.; Xie,
L.; Ghiviriga, I. J . Org. Chem. 1997, 62, 6215. (c) Hoerndler, C.;
Hansen, H. J . Helv. Chim. Acta 1997, 80, 2520. (d) Kaye, P. T.; Molema,
W. E. Chem. Commun. 1998, 2479. (e) Cossy, J .; Rakotoarisoa, H.;
Kahn, P.; Desmurs, J .-R. Tetrahedron Lett. 1998, 39, 9671. (f) J ones,
R. C. F.; Patel, P.; Hirst, S. C.; Smallridge, M. J . Tetrahedron 1998,
54, 6191. (g) Ho¨ppe, H. A., Lloyd-J ones, G. C.; Murray, M.; Peakman,
T. M.; Walsh, K. E. Angew. Chem., Int. Ed. Engl. 1998, 37, 1545.
(16) (a) Boldi, A. M.; J ohnson, C. R.; Eissa, H. O. Tetrahedron Lett.
1999, 40, 619. (b) Lu, T.-J .; Cheng, S.-M.; Sheu, L.-J . J . Org. Chem.
1998, 63, 2738. (c) Shiraishi, H.; Nishitani, T.; Sakaguchi, S.; Ishii, Y.
J . Org. Chem. 1998, 63, 6234. (d) Yoshimatsu, M.; Oguri, K.; Ikeda,
K.; Gotoh, S. J . Org. Chem. 1998, 63, 4475.
Acetylenic thiophenes may be readily prepared by the
direct coupling of halo-substituted thiophenes (-Br and
-I) with terminal alkynes in the presence of tetrakis-
(triphenylphoshine)palladium, CuI, and base (eq 3).13
(17) (a) Chang, C.-T.; Chen, K.-M.; Liu, W.-H.; Lin, F.-I.; Wu, R.-T.,
U.S. Patent 5,602,170, 1997. (b) Chang, C.-T.; Chen, K.-M.; Liu, W.-
H.; Lin, F.-I.; Wu, R.-T. U.S. Patent 5,747,525, 1998. (c) Ebermann,
R.; Alth, G.; Kreitner, M.; Kubin, A. J . Photochem. Photobiol., B 1996,
36, 95. (d) Wierzbicky, M.; Sauveur, F.; Bonnet, J .; Tordjman, C. Fr.
Demande FR 2,752,576, 1998. (e) Asari, T.; Okamoto, S.; Kono, S.
J apanese Patent 10,316, 673, 1998.
(18) (a) Walter, H. PCT Int. Appl. WO 9,733,890, 1997. (b) Morita,
K.; Murabayashi, A., J apanese Patent 09,095,482, 1997. (c) Kanehira,
K.; Tagawa, H.; Shiono, M. J apanese Patent 09,104,682, 1997. (d)
Fischer, R.; Dumas, J .; Bretschneider, T.; Gallenkamp, B.; Lieb, F.;
Wernthaler, K.; Erdelen, C.; Wachendorff-Neumann, U.; Mencke, N.;
Turberg, A. Ger. Offen DE 19,527,190, 1996. (e) Theobald, H.; Harries,
V.; Kardorff, U.; Baeuerle, P.; Goetz, G. PCT Int. Appl. WO 9,314,079,
1993.
The acetylenic unit may have functionalities including
alkyl, propargyl ether, alcohol, or ester, phenylacetylene,
and enyne. Yields ranging from 65% to 90% were
obtained in these reactions (Table 1).
(19) Sargent, A. L.; Titus, E. P. Organometallics 1998, 17, 65.
(20) (a) Doyama, K.; J oh, T.; Takahashi, S. Tetrahedron Lett. 1996,
27, 4497. (b) Doyama, K.; J oh, T.; Shiohara, T.; Takahashi, S. Bull.
Chem. Soc. J pn. 1988, 61, 4353. (c) Campi, E. M.; J ackson, W. R. Aust.
J . Chem. 1989, 42, 471.

9642 J . Org. Chem., Vol. 64, No. 26, 1999
Ta ble 1. P r ep a r a tion of Acetylen ic Th iop h en esa
Van den Hoven and Alper
a
Reaction conditions: heterocycle (2), 20 mmol; alkyne (3), 25-30 mmol; Pd(PPh3)4, 0.2 mmol; CuI, 0.5 mmol; PhH, 50 mL; Et3N, 15
mL; room temperature, 24 h. The product was isolated by Kugelrohr distillation. c The ester was prepared by esterification of 4f, and
b
isolated by silica gel column chromatography using pentane/ether (90:10). CH2Cl2 instead of PhH, reflux, 5 days. e Reflux. f The product
d
was isolated via preparative HPLC size exclusion chromatography using CHCl3 as the eluant.
In principle, the hydroformylation of acetylenic thio-
phenes could afford the isomeric unsaturated aldehydes
5 and 6 (eq 4).
Our initial investigation of thiophenynes utilized the
same conditions employed for the hydroformylation of
enynes. Using 3 mmol of 2-(hex-1-ynyl)thiophene (4a ), 4
mol % 1, 16 mol % (PhO)3P, 10 mL of CH2Cl2, 6 atm of
CO, and 6 atm of H2 at 60 °C for 48 h resulted in only
70% conversion of 5a accompanied by a dark red discol-
oration of the reaction mixture. Increasing the solvent

Hydroformylation of Acetylenic Thiophenes
J . Org. Chem., Vol. 64, No. 26, 1999 9643
Ta ble 2. Hyd r ofor m yla tion of Der iva tives Con ta in in g
Alk yl Acetylen ic Un itsa
volume to 20 mL of CH2Cl2 resulted in the reaction
proceeding to completion. The reaction mixture was
yellow, and a substantial amount of 7, R ) n-C4H9, was
formed here. The amount of the latter was reduced to
less than 10% of the total yield by increasing the CO-to-
H2 ratio to 2:1. It was also necessary to increase the total
pressure to 18 atm to enable the reaction to be complete
after 48 h. When functionalized alkynylthiophenes were
used as reactants, less catalyst and shorter reaction times
were required to obtain complete conversion. Acetylenic
thiophenes containing propargyl ether or ester function-
alities required 1.5 mol % 1, 6 mol % (PhO)3P, and a
reaction time of 24 h. Substrates having a double bond
or phenyl groups were best hydroformylated with 2 mol
% 1, 8 mol % (PhO)3P, and a reaction time of 24 h. The
regioselectivity of the process is dependent, to some
extent, on the catalyst loading. The higher the catalyst
loading required, the greater the preference for 5.
The hydroformylation of 2- and 3-substituted acetylenic
alkylthiophenynes is completely regioselecive, affording
5 as the only product. For example, 5a and 5k were
obtained from 4a and 4k , respectively, with <10% of 7
as a byproduct (Table 2, entries 1 and 2). Interestingly,
the process becomes less selective using the correspond-
ing benzothiophene reactants 4m and 4n . Hydroformy-
lation of 2-(hex-1-ynyl)benzothiophene (4m ) affords two
aldehydes in 88% isolated yield, with the ratio of 5m to
6m being 5:1 (Table 2, entry 3). The hydroformylation of
the isomeric 3-(hex-1-ynyl)benzothiophene (4n ) also fa-
vored the branched aldehyde 5n , but in a 64:21 ratio of
5n to 6n (Table 2, entry 4). The influence of the fused
benzene ring may be explained by visualizing the ap-
proach of 1 toward the alkynylbenzothiophene (Figure
3). The freedom of rotation of the tetraphenylborate group
bound to the rhodium complex (via π-complexation to one
arene ring) is reduced when 1 is in close proximity to
the 2-alkynylbenzothiophene. The freedom of rotation
becomes even more constrained when 4n is used as the
substrate, thus affording 5n /6n in a lower ratio than 5m /
6m .
a
Reaction conditions: 4, 3 mmol; 1, 0.12 mmol (4%), (PhO)3P,
0.48 mmol (16%); CH2Cl2, 20 mL; CO, 12 atm; H2, 6 atm; 60 °C.
The percent conversion was determined by H NMR. c The ratio
b
1
of 5 to 6 was determined by the ratio of their aldehyde 1H NMR
d
signals. The products were isolated by silica gel column chro-
matography using a pentane:ether gradient ranging from 90:10
to 75:25 as eluant. e 7% of 7, R ) C4H9, was also formed. f 9% of
g
the saturated aldehyde was formed as well. The products were
isolated by silica gel column chromatography using a pentane
ether gradient ranging from 95:5 to 85:15 as eluant.
F igu r e 3. Approach of 1 to an alkynylbenzothiophene.
sulfur relative to the position of the triple bond. The
further the sulfur atom is from the alkyne unit, the less
its influence on the regioselectivity of the hydroformy-
lation reaction. The 1-en-3-yne derivative 4j affords a
cyclopentenone (8) as the major product (Table 4, entry
2) possibly by intramolecular cyclization of the aldehyde
5j. The minor product is the formyl diene 6j which is in
accord with our previous investigation of enynes.11
The above data demonstrate the influence of the
heterocyclic sulfur atom on the hydroformylation process.
Complex 9 may be generated for acetylenic thiophenes
containing other functionalized groups. For reactants
which also have ether and ester groups, a competing
binding for rhodium is that of the alkyne and the
functional units 10 (Figure 4). The preference for 5
relative to 6 may be due to a lower binding energy for 9
than for 10. The coupled interaction with the lowest
binding energy will become the major product, and the
Hydroformylation of propargyl ether or ester deriva-
tives of acetylenic thiophenes affords two R,â-unsaturated
aldehydes, the major product being 5 in all cases (Table
3). The ratio of 5 to 6 ranged from 2.5:1.0 to 3.3:1.0 (Table
3, entries 1-4), while acetylenic thiophene propargyl
esters were obtained in a 1.8-2.3:1.0 ratio using 4g and
4h as substrates (Table 3, entries 5 and 6).
Good regioselectivity is also observed when the acety-
lenic unit has an aryl or vinyl group. The results for the
hydroformylation of 2-(1-phenylacetylenyl)thiophene (4i)
compared to 3-(1-phenylacetylenyl)thiophene (4l) (Table
4, entries 1 and 3) follow the same trend as that observed
for 2- versus 3-alkynylbenzothiophenes (4m and 4n ),
consistent with the proposed influence of the heterocyclic

9644 J . Org. Chem., Vol. 64, No. 26, 1999
Van den Hoven and Alper
Ta ble 3. Hyd r ofor m yla tion of Th iop h en yn es Con ta in in g
P r op a r gyl Eth er a n d Ester Un itsa
Ta ble 4. Hyd r ofor m yla tion of Acetylen ic Th iop h en es
Con ta in in g Ar yl or Vin yl Gr ou p sa
a
Reaction conditions: 4, 3 mmol; 1, 0.06 mmol (2%), (PhO)3P,
0.24 mmol (8%); CH2Cl2, 20 mL; CO, 12 atm; H2, 6 atm; 60 °C, 24
b
h. The percent conversion was determined by 1H NMR. c The
ratio of 5 to 6 was determined by the ratio of the aldehyde 1H
d
NMR signals. The products were isolated by silica gel column
chromatography using a pentane:ether gradient ranging from 90:
10 to 75:25 as eluant.
F igu r e 4. Rhodium coordination prior to hydroformylation.
carbonyl species 16; (5) reaction of the rhodium complex
with hydrogen gives the R,â-unsaturated aldehyde 5, and
regenerates the hydride 11.
In conclusion, this study has demonstrated the signifi-
cant influence of a thiophene sulfur on the regioselectivity
of the hydroformylation of alkynes. Good, complete
regioselectivity was observed in these reactions. This
research has led to a greater understanding of the factors
that influence the hydroformylation process. Some of the
aldehydes formed are novel and have potential in both
pharmaceutical and agrochemical businesses.
a
Reaction conditions: 4, 3 mmol; 1, 0.045 mmol (1.5%), (PhO)3P,
0.18 mmol (6%); CH2Cl2, 20 mL; CO, 12 atm; H2, 6 atm; 60 °C, 24
b
h. The percent conversion was determined by 1H NMR. c The
ratio of 5 to 6 was determined by the ratio of the aldehyde signals
in the proton NMR. The products were isolated by silica gel
d
column chromatography using a pentane:ether gradient ranging
from 90:10 to 75:25 as eluant. e 1, 0.06 mmol; (PhO)3P, 0.24 mmol.
f The products were isolated by silica gel column chromatography
using a pentane:ether gradient ranging from 90:10 to 50:50 as
eluant.
Exp er im en ta l Section
Ma ter ia ls. 2-Iodothiophene, 3-bromothiophene, and all
terminal alkynes were purchased from commercial sources.
2-Iodobenzothiophene,21 3-iodobenzothiophene,21 and the zwit-
terionic rhodium complex (η6-C6H5BPh3)-Rh+(1,5-COD) (1)22
were prepared according to the literature methods. All solvents
were dried and distilled under N2 prior to use.
Gen er a l P r oced u r e for th e P d /Cu I Cou p lin g of Iod ot-
h iop h en e to a Ter m in a l Alk yn e. To a 100 mL round-
bottom flask purged with N2 were added triethylamine (15
mL), the terminal alkyne 3 (25-30 mmol), PhH (50 mL),
iodothiophene (2) (20 mmol), Pd(PPh3)4 (0.2 mmol), and CuI
(0.5 mmol) at room temperature for 24 h. Methanol (10 mL)
was added, the solvent was evaporated, and diethyl ether (200
higher binding energy interaction will result in attaining
the minor product.
A possible mechanism for the heterocyclic sulfur
directed hydroformylation of 2-alkynylthiophenes, shown
in Figure 5, consists of the following steps: (1) the
rhodium hydride 11 binds to the heterocycle, forming an
η1-sulfur-donor ligand complex (12); (2) the triple bond
then coordinates to the metal (note, it is conceivable that
complexation occurs in the opposite order); (3) intramo-
lecular addition of the rhodium hydride to the triple bond
of the alkynylthiophene can afford the (E)-isomer 15;
(4) CO insertion into 15 would give the acyl rhodium
(21) Gaeriner, R. J . Am. Chem. Soc. 1952, 74, 4950.
(22) Schrock, P. R.; Osborn, J . A. Inorg. Chem. 1970, 9, 2339.

Hydroformylation of Acetylenic Thiophenes
J . Org. Chem., Vol. 64, No. 26, 1999 9645
F igu r e 5. Proposed mechanism.
mL) was added to the resulting residue, leading to the
precipitation of Et3NH+I-. This mixture was filtered, washed
with 10% HCl, distilled H2O, and brine, and dried over
anhydrous MgSO4 or Na2SO4. The ether solution was decol-
orized with activated charcoal and evaporated and the result-
ing residue further purified by Kugelrohr distillation to give
4.
was placed in an oil bath at 60 °C for 24-48 h, and then
allowed to cool to room temperature. The autoclave was
depressurized, the reaction mixture filtered through Celite,
and the solvent removed by rotary evaporation. The resulting
yellow residue was purified by silica gel chromatography using
a pentane:ether gradient ranging from 90:10 to 75:25 as the
eluant to afford products 5 and 6.
2-(3-Hyd r oxyp r op -1-yn yl)th iop h en e (4f): colorless liquid;
Removal of any discoloration in 5 or 6, caused by light or
heat, was affected by preparative HPLC size exclusion chro-
matography using CHCl3 as the eluant.
1
IR ν(OH) 3332 cm-1, ν(CtC) 2222 cm-1; H NMR (200 MHz,
CDCl3) δ 7.17-7.26 (m, 2H), 6.94 (dd, 1H, J ) 6.0, 4.0 Hz).
4.48 (s, 2H), 2.19 (s, 1H); 13C NMR (200 MHz, CDCl3) δ 133.0,
128.0, 127.6, 91.8, 79.6, 52.3; EI MS (m/e) 138 [M+]; HRMS
calcd for C7H6OS [M+] 138.01394, found 138.01307.
(E)-4-P r op ion oxy-2-(2-th ien yl)-2-bu ten -1-a l (5g): color-
less liquid; IR ν1(CdO) 1737 cm-1, ν2(CdO) 1698 cm-1 1H
;
NMR (200 MHz, CDCl3) δ 9.61 (s, 1H), 7.48 (dd, 1H, J ) 5.2,
1.2 Hz), 7.16 (dd, 1H, J ) 3.6, 1.2 Hz), 7.11 (dd, 1H, J ) 4.8,
3.8 Hz), 6.65 (t, 1H, J ) 5.8 Hz) 5.12 (d, 2H, J ) 5.8 Hz), 2.40
(q, 2H, J ) 7.6 Hz), 1.17 (t, 3H, J ) 7.6 Hz); 13C NMR (200
MHz, CDCl3) δ 192.4, 174.6, 147.5, 137.0, 129.7, 129.0, 128.8,
127.5, 67.5, 28.0, 9.6; EI MS (m/e) 224 [M+]; HRMS calcd for
Gen er a l P r oced u r e for th e P r ep a r a tion of P r op a r gyl
Ester Th iop h en e Der iva tives. Triethylamine (2.8 mL, 20
mmol) was added dropwise to a stirred solution of 2-(3-
hydroxyprop-1-ynyl)thiophene (4f) (1.38 g, 10 mmol), propionic
or benzoic anhydride (12.5 mmol), and 0.12 g (1.0 mmol) of
4-(dimethylamino)pyridine in CH2Cl2 (40 mL). After 2 h the
reaction mixture was treated with CH2Cl2 (60 mL), washed
with 10% HCl, saturated NaHCO3, and brine, and then dried
over anhydrous MgSO4. The solvent was removed by rotary
evaporation. The ester was further purified by silica gel
chromatography using pentane/ether (90:10) as eluant.
2-(3-P r op ion oxyp r op -1-yn yl)th iop h en e (4g): colorless
liquid; IR ν(CtC) 2230 cm-1, ν(CdO) 1744; 1H NMR (200 MHz,
CDCl3) δ 7.20-7.27 (m, 2H), 6.94 (dd, 1H, J ) 7.2, 2.4 Hz),
4.89 (s, 2H), 2.38 (q, 2H, J ) 8.0 Hz), 1.15 (t, 3H, J ) 7.7 Hz);
13C NMR (200 MHz, CDCl3) δ 174.3, 133.6, 128.4, 127.6, 122.6,
87.9, 80.3, 53.3, 28.0, 9.6; EI MS (m/e) 194 [M+]; HRMS calcd
for C10H10O2S [M+] 194.04015, found 194.04172.
Gen er a l P r oced u r e for th e Hyd r ofor m yla tion of Con -
ju ga ted Th iop h en yn es. To a 45 mL autoclave containing a
glass liner and stirring bar were added the zwitterionic
rhodium complex 1 (0.045-0.12 mmol), triphenyl phosphite
(0.18-0.48 mmol), the conjugated thiophenyne 4 (3 mmol), and
CH2Cl2 (20 mL). The autoclave was flushed three times with
carbon monoxide and pressurized to 12 atm, and then hydro-
gen was introduced to a total pressure of 18 atm. The autoclave
C
11H12O3S [M+] 224.05072, found 224.05045.
(E)-2-Meth ylpr opion oxy-3-(2-th ien yl)-2-pr open -1-al (6g):
colorless liquid; IR ν1(CdO) 1736 cm-1, ν2(CdO) 1678 cm-1
;
1H NMR (200 MHz, CDCl3) δ 9.55 (s, 1H), 7.61 (dd, 1H, J )
5.0, 0.8 Hz), 7.62 (s, 1H), 7.45 (dd, 1H, J ) 3.8, 0.6 Hz), 7.14-
7.19 (m, 1H), 5.05 (s, 2H), 2.32 (q, 2H, J ) 7.6 Hz), 1.11 (t,
3H, J ) 7.6 Hz); 13C NMR (200 MHz, CDCl3) δ 193.1, 175.0,
146.3, 137.4, 135.5, 134.0, 132.5, 128.9, 56.7, 28.0, 9.7; EI MS
(m/e) 224 [M+]; HRMS calcd for C11H12O3S [M+] 224.05072,
found 224.05118.
Ack n ow led gm en t. We are grateful to the Natural
Sciences and Engineering Research Council of Canada
for support of this research.
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR spectra of 2c, 2d , 3e, 4a -n , 5a -n , 6b-n , and 8 and
characterization for all starting materials and products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O9912653