Regio- And stereoselective cross-coupling of tert-propargyl alcohols with bis(trimethylsilyl)acetylene and its utilization in constructing a fluorescent donor - Acceptor system

Article abstract of DOI:10.1021/ol070799k

1,1-Disubstituted 3-aryl-2-propyn-1-ols undergo regio- and stereoselective cross-coupling on treatment with bis(trimethylsilyl)acetylene in the presence of a rhodium catalyst via cleavage of C(sp)-C(sp³) and C(sp)-Si bonds to produce the corres

Full text of DOI:10.1021/ol070799k

ORGANIC
LETTERS
2007
Vol. 9, No. 11
2231-2233
Regio- and Stereoselective
Cross-Coupling of tert-Propargyl
Alcohols with
Bis(trimethylsilyl)acetylene and Its
Utilization in Constructing a Fluorescent
Donor−
Acceptor System†
Akinobu Horita, Hayato Tsurugi, Atsushi Funayama, Tetsuya Satoh, and
Masahiro Miura*
Department of Applied Chemistry, Faculty of Engineering, Osaka UniVersity, Suita,
Osaka 565-0871, Japan
miura@chem.eng.osaka-u.ac.jp
Received April 4, 2007
ABSTRACT
1,1-Disubstituted 3-aryl-2-propyn-1-ols undergo regio- and stereoselective cross-coupling on treatment with bis(trimethylsilyl)acetylene in the
presence of a rhodium catalyst via cleavage of C(sp) Si bonds to produce the corresponding 2-hydroxymethyl-(E)-enynes.
C(sp3) and C(sp)
The subsequent desilylative Sonogashira coupling followed by base-promoted cyclization affords fluorescent dihydrofuran derivatives.
−
−
The catalytic synthesis of π-conjugated enyne compounds
has attracted considerable interest, due to the presence of
the skeleton in natural products and their utility as versatile
building blocks in organic synthesis.1 While a variety of
enynes can now be prepared by the dimerization of alkynes,
the selective cross-coupling of two different alkynes is, in
general, still difficult owing to the fact that the formation of
regio- and stereoisomers as well as homodimers is possible,
and thus a major challenge.2,3 Among the rare, leading
examples of the cross-coupling is the palladium-catalyzed
reaction of terminal alkynes with internal ones having an
electron-withdrawing group.2 As in this instance, a key
alkynylmetal intermediate generated by C(sp)-H bond
activation of a terminal alkyne is usually involved in such a
reaction.
Meanwhile, various unique and useful catalytic processes
involving C-C bond cleavage via â-carbon elimination in
metal alcoholate intermediates have recently been developed.4
In the course of our work on the transformations,5 we found
that in the presence of a rhodium catalyst, γ-arylated tert-
propargyl alcohols, i.e., ketone-masked aryl acetylenes 1,
† This paper is dedicated to the heartfelt memory of the late Professor
Yoshihiko Ito of Kyoto and Doshisha Universities.
(3) (a) Akita, M.; Yasuda, H.; Nakamura, A. Bull. Chem. Soc. Jpn. 1984,
57, 480. (b) Yi, C. S.; Liu, N. Organometallics 1998, 17, 3158. (c) Lucking,
U.; Pfaltz, A. Synlett 2000, 1261. (d) Wang, J.; Kapon, M.; Berthet, J. C.;
Ephritikhine, M.; Eisen, M. S. Inorg. Chim. Acta 2002, 334, 183. (e) Chen,
L.; Li, C.-J. Tetrahedron Lett. 2004, 45, 2771. (f) Hirabayashi, T.; Sakaguchi,
S.; Ishii, Y. AdV. Synth. Catal. 2005, 347, 872. (g) Katayama, H.; Yari, H.;
Tanaka, M.; Ozawa, F. Chem. Commun. 2005, 4336.
(1) (a) Trost, B. M. Angew. Chem., Int. Ed. 1995, 34, 259. (b) Tsuji, J.
Transition Metal Reagents and Catalysts; Wiley: Chichester, UK, 2000.
(2) (a) Trost, B. M.; Chan, C.; Ruhter, G. J. Am. Chem. Soc. 1987, 109,
3486. (b) Trost, B. M.; Harms, A. E. Tetrahedron Lett. 1996, 37, 3971. (c)
Trost, B. M.; Sorum, M. T.; Chan, C.; Harms, A. E.; Ruhter, G. J. Am.
Chem. Soc. 1997, 119, 698.
10.1021/ol070799k CCC: $37.00
© 2007 American Chemical Society
Published on Web 05/04/2007

efficiently undergo homocoupling with liberation of a ketone
molecule through C(sp)-C(sp3) bond cleavage to regio- and
stereoselectively produce 1,4-diaryl-2-hydroxymethyl-(E)-
enynes 2 (Scheme 1, a).5e Notably, the products readily
Table 1. Rhodium-Catalyzed Reaction of tert-Propargyl
Alcohols with Bis(trimethylsilyl)acetylenea
Scheme 1
entry
X
R
ligand time (h)
4, % yieldb
2, % yieldb
1
OH Ph dppb
OH Ph dppb
2
4
4
4
9
8
4
8
2
4
4
64e
16
trace
16
trace
3
8
20
6
trace
31
trace
2c
99 (98)e
cyclize in the presence of a base to form dihydrofuran
derivatives, some of which exhibit strong fluorescence in
the solid state. During the examination of cross-coupling
using 1, we have observed that the propargyl alcohols
selectively react with bis(trimethylsilyl)acetylene (3) via
activation of one of the C(sp)-Si bonds to afford the
corresponding 1-aryl-4-trimethylsilyl-(E)-enynes 4 (Scheme
1, b). The silyl function has also been subjected to further
structural elaboration to lead to a donor-acceptor (D-A)
π-conjugated system on the dihydrofuran scaffold.
When a mixture of 1,1,3-triphenyl-2-propyn-1-ol (1ap)
(0.5 mmol) was treated with 3 (3 mmol) in the presence of
[(cod)Rh(OH)]2/dppb (4 mol %) in refluxing toluene for 2
h, 2-[(E)-benzylidene]-4-trimethylsilyl-1,1-diphenyl-3-butyn-
1-ol (4ap) was produced along with the homocoupling
product 2ap in 64% and 16% yields (calculated as 2[product]/
[1a], see below), respectively (entry 1 in Table 1). Addition
of 1ap in a slow manner through a cannula to keep the
concentration of 1ap low could successfully suppress the
formation of 2ap to allow the almost exclusive formation
of 4ap (entry 2). Analysis of the reaction mixture by GC-
MS confirmed the formation of 1-phenyl-2-(trimethylsilyl)-
acetylene and benzophenone in quantitative yields (0.5 equiv)
as the byproducts, which may provide important mechanistic
information. Decreasing the amount of 3 to 1.0 mmol still
gave 76% of 4ap (entry 3). The reaction was found to be
sensitive to the variation of ligand. The use of dppp or dppe
in place of dppb reduced the yield of 4ap and induced the
formation of its (Z)-isomer in a small, but considerable
amount (entries 4 and 5). The reaction without any phosphine
ligand was sluggish (entries 7 and 8). The use of [(cod)-
3c,f OH Ph dppb
76e
4c
5c
6c
7c
8c
9c
OH Ph dppp
OH Ph dppe
OH Ph PPh3
OH Ph
76 (71) (96:4)g
64 (57) (89:11)g
d
43 (37)e
32
Cl
Cl
Ph
Ph dppb
6
60
10
11c
OH Me dppb
OH Me dppb
62e
89 (88)e
a Reaction conditions: [Rh]:[ligand]:[1]:[3] ) 0.02:0.02:0.5:3.0 (in
mmol), in refluxing toluene (4 mL) under N2. b GC yield based on the half
amount of 1 used. Value in parentheses indicates isolated yield. c Toluene
solution of 1 (2 mL, 0.25 mM) was added over 2 h. d PPh3 (0.04 mmol)
was used. e Exclusively (E)-isomer. f [3] ) 1.0 mmol. g E/Z ratio.
RhCl]2 in place of the hydroxyl complex together with dppb
was less effective (entry 9). The reaction of 2-methyl-4-
phenyl-3-butyn-2-ol (1am) proceeded similarly (entries 10
and 11).
The cross-coupling reactions of various 3-(4-substituted
phenyl)-1,1-diphenyl-2-propyn-1-ols 1bp-1fp with the di-
silylacetylene 3 in the double scale of entry 2 in Table 1
gave the corresponding products 4bp-4fp with good isolated
yields irrespective of the nature of the 4-substituents (Scheme
2).
Scheme 2
(4) (a) Satoh, T.; Miura, M. Top. Organomet. Chem. 2005, 14, 1. (b)
Murakami, M.; Ito, Y. Top. Organomet. Chem. 1999, 3, 97. (c) Rybtchinski,
B.; Milstein, D. Angew. Chem., Int. Ed. 1999, 38, 870. (d) Mitsudo, T.;
Kondo, T. Synlett 2001, 309. (e) Perthuisot, C.; Edelbach, B. L.; Zubris,
D. L.; Simhai, N.; Iverson, C. N.; Mu¨ller, C.; Satoh, T.; Jones, W. D. J.
Mol. Catal. A: Chem. 2002, 189, 157. (f) Jun, C.-H.; Moon, C. W.; Lee,
D.-Y. Chem. Eur. J. 2002, 8, 2423. (g) Catellani, M. Synlett 2003, 298. (h)
Nishimura, T.; Araki, H.; Maeda, Y.; Uemura, S. Org. Lett. 2003, 5, 2997.
(i) Nishimura, T.; Uemura, S. Synlett 2004, 201. (j) Murakami, M.; Makino,
M.; Ashida, S.; Matsuda, T. Bull. Chem. Soc. Jpn. 2006, 79, 1315.
(5) (a) Terao, Y.; Wakui, H.; Satoh, T.; Miura, M.; Nomura, M. J. Am.
Chem. Soc. 2001, 123, 10407. (b) Terao, Y.; Wakui, H.; Nomoto, N.; Satoh,
T.; Miura, M.; Nomura, M. J. Org. Chem. 2003, 68, 5236. (c) Terao, Y.;
Nomoto, N.; Satoh, T.; Miura, M.; Nomura, M. J. Org. Chem. 2004, 69,
6942. (d) Wakui, H.; Kawasaki, S.; Satoh, T.; Miura, M.; Nomura, M. J.
Am. Chem. Soc. 2004, 126, 8658. (e) Funayama, A.; Satoh, T.; Miura, M.
J. Am. Chem. Soc. 2005, 127, 15354.
A plausible mechanism for the formation of the enyne 4
is illustrated in Scheme 3, in which neutral ligands are
omitted. The first step involves the reaction of 1 with
hydroxyrhodium(I) species to form rhodium alcoholate A
and the successive â-carbon elimination with liberation of
benzophenone or acetone gives arylalkynylrhodium B. Then,
the alkynyl exchange between B and 3 takes place to from
2232
Org. Lett., Vol. 9, No. 11, 2007

Scheme 3
Scheme 4
fluorescence in a range of 492-589 nm (see Figure S2 in
the Supporting Information). Notably, 6cp-CN showed a
relatively strong emission compared to a typical green
emitter, tris(8-hydroxyquinolino)aluminum (Alq3), by a factor
of 1.6. Dihydrofurans 6bp-CN and 6cp-CN, both of which
possess an electron-donating group at R1 and an electron-
withdrawing group at R2, showed strong fluorescence in
solution (Φ ) 0.76 and 0.53 in dioxane, respectively). This
contrasts with the fact that each of the other compounds 6dp-
NMe2, 6dp-OMe, 6ep-NMe2, and 6fp-NMe2 as well as the
homocoupling product 2ap shows only a weak emission in
solution. Furthermore, 6bp-CN showed a large positive
solvatochromism of fluorescence (λmax ) 508 nm in hexane;
539 nm in dioxane; 594 nm in MeCN), suggesting a strong
intramolecular charge-transfer character in the excited state,
while the chromism of 6cp-CN was very small (see Figure
S3 in the Supporting Information). These results indicate that
the electronic nature of R1 and R2 strongly affects not only
the fluorescent wavelength but also the efficiency in both
solid and solution.
silylalkynylrhodium C via activation of the C-Si bond,6
presumably by an oxidative addition-reductive elimination
sequence.7 The successive regioselective insertion of another
molecule of 1 to the rhodium-carbon bond affords vinyl-
rhodium D. Enyne 4 is formed after the geometrical
isomerization of D to E and protonolysis by 1 with
regeneration of A as in the case of the homocoupling of 1.
The geometrical isomerization may occur via a zwitterionic
form.8 The interaction of the oxygen with the metal may
intervene to stabilize E.
The synthetic utility of the cross-coupling products may
be demonstrated by the transformation of the silyl group to
various aromatic substituents and the subsequent cyclization
to produce dihydrofuran derivatives that show solid-state
luminescence.5e,9 Since π-conjugated D-A molecules are
often useful as flexible systems with respect to emission
range,10 the dihydrofuran scaffold may allow observation of
the change of optical properties depending on the different
substituents of the two aromatic rings.
In summary, we have developed a new, selective alkyne
cross-coupling reaction that proceeds via cleavage of C-C
and C-Si bonds. The reaction has enabled the construction
of a series of π-conjugated D-A systems involving a
dihydrofuran skeleton that show intriguing optical properties.
As expected, the arylation of 3 with aryl iodides by a
reported method for desilylative Sonogashira coupling,11
followed by treatment with t-BuOK gave the corresponding
dihydrofurans 6 in fair to good yields, although the conditions
were not optimized (Scheme 4). They showed solid-state
Acknowledgment. This work was supported by a Grant-
in-Aid from the Ministry of Education, Culture, Sports,
Science, and Technology, Japan. We thank Ms. Y. Miyaji
for the measurement of NMR spectra and Mr. H. Moriguchi
and Mr. H. Yamada for MS spectra (Osaka University).
(6) Transmetallation between [RhCl(CO)2]2 and acyl- and vinylsilanes:
Yamane, M.; Uera, K.; Narasaka, K. Bull. Chem. Soc. Jpn. 2005, 78, 477.
(7) (a) Fangou, K.; Lautens, M. Chem. ReV. 2003, 103, 169. (b) Mu¨ller,
J.; Tschampel, M.; Pickardt, J. J. Organomet. Chem. 1988, 355, 513.
(8) Hydrosilylation reactions by rhodium and iridium complexes involv-
ing E/Z isomarization: (a) Jun, C.-H.; Crabtree, R. H. J. Organomet. Chem.
1993, 447, 177. (b) Ojima, I.; Clos, N.; Donovan, R. J.; Ingallina, P.
Organometallics 1990, 9, 3127.
(9) Filler, R.; Piasek, E. J.; Mark, L. H. J. Org. Chem. 1961, 26, 2659.
(10) Grabowski, Z. R.; Rotkiewicz, K.; Rettig, W. Chem. ReV. 2003,
103, 3899.
(11) Matthew, J. M.; Lucas, C. K.; Julia, B. B.; Tendai, L. G.; Kami, L.
H.; Ronald, G. B.; Christphor, J. M.; Paul, A. G. Org. Lett. 2002, 4, 3199.
Supporting Information Available: Standard experi-
mental procedure and characterization data for new com-
pounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL070799K
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