Scandium-catalyzed carbon-carbon bond-forming reactions of 3-sulfanyl-and 3-selanylpropargyl alcohols

Article abstract of DOI:10.1021/ol801533p

(Chemical Equation Presented) The scandium-catalyzed substitution reactions of the phenylsulfanyl and phenylselanyl propargyl alcohols 3a-i and 7a-h regioselectively proceeded to give the propargylated compounds 4 and 8 in high yields.

Full text of DOI:10.1021/ol801533p

ORGANIC
LETTERS
2008
Vol. 10, No. 19
4251-4254
Scandium-Catalyzed Carbon-Carbon
Bond-Forming Reactions of 3-Sulfanyl-
and 3-Selanylpropargyl Alcohols
Mitsuhiro Yoshimatsu,* Tokutaro Otani, Saki Matsuda, Teruhisa Yamamoto, and
Arisa Sawa
Department of Chemistry, Faculty of Education, Gifu UniVersity,
1-1 Yanagido, Gifu 501-1193, Japan
yoshimae@gifu-u.ac.jp
Received July 22, 2008
ABSTRACT
The scandium-catalyzed substitution reactions of the phenylsulfanyl and phenylselanyl propargyl alcohols 3a-i and 7a-h regioselectively
proceeded to give the propargylated compounds 4 and 8 in high yields.
The acid-mediated propargylations of the corresponding
alcohols have been extensively investigated using the
alkyne-Co2(CO)6 complex, which can be regarded as a
reliable tool for cationic C-C bond formations (Nicholas
reaction).1 Many chemists interested in organic synthesis
use a wide variety of these complexes; however, they
could never avoid the complicated addition and elimination
process of the cobalt hexacarbonyl group despite the
significant progress made in this area.2 Recently, the
transition-metal-catalyzed propargylic substitutions using
Ru,3 Ir,4 Rh,5 Cu,6 Ti,7 Re,8 Pt,9 and Pd10 were also
investigated as the alternative routes of the Nicholas
reaction; however, the usable propargylic reagents were
unfortunately strictly limited to each nucleophile.3 Al-
though the free propargylic cation could be considered
as the alkynyl-substituted carbenium ions, their reactivity
with nucleophiles is dependent on the kind of substituents
(3) Ru: (a) Nishibayashi, Y.; Inada, Y.; Yoshikawa, M.; Hidai, M.;
Uemura, S. Angew. Chem., Int. Ed. 2003, 42, 1495. (b) Nishibayashi, Y;
Wakiji, I.; Hidai, M. J. Am. Chem. Soc. 2000, 122, 11019. (c) Nishibayashi,
Y.; Yoshikawa, M.; Inada, Y.; Hidai, M.; Uemura, S. J. Am. Chem. Soc.
2002, 124, 11846. (d) Inada, Y.; Nishibayashi, Y.; Hidai, M.; Uemura, S.
J. Am. Chem. Soc. 2002, 124, 15172. (e) Nishibayashi, Y.; Inada, Y.; Hidai,
M.; Uemura, S. J. Am. Chem. Soc. 2002, 124, 7900. (f) Nishibayashi, Y.;
Wakiji, I.; Ishii, Y.; Uemura, S.; Hidai, M. J. Am. Chem. Soc. 2001, 123,
3393. (g) Touchard, D.; Haquette, P.; Daridor, A.; Toupet, L.; Dixneuf,
P. H. J. Am. Chem. Soc. 1994, 116, 11157. (h) Nishibayashi, Y.; Milton,
M. D.; Inada, Y.; Yoshikawa, M.; Wakiji, I.; Hidai, M.; Uemura, S. Chem.
Eur. J. 2005, 11, 1433. (i) Inada, M.; Yoshikawa, M. D.; Milton, M. D.;
Nishibayashi, Y.; Uemura, S. Eur. J. Org. Chem. 2006, 881. (i) Chen, C.-
T. Coord. Chem. ReV. 1999, 190.
(4) Ir: Matsuda, I.; Komori, K.; Itoh, K. J. Am. Chem. Soc. 2002, 124,
9072.
(1) (a) Nicholas, K. M. Acc. Chem. Res. 1987, 20, 207, and references
therein. (b) Caffyn, A. J. M.; Nicholas, K. M. In ComprehensiVe Organo-
metallic Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G.,
Pergamon: New York, 1995; 12, Chapter 7.1. (c) Caffyn, A. J. M.; Nicholas,
K. M. J. Am. Chem. Soc. 1993, 115, 6438.
(5) Rh: (a) Werner, H. Chem. Commun. 1997, 903. (b) Evans, P. A.;
Lawler, M. J. Angew. Chem., Int. Ed. 2006, 45, 4970.
(6) Cu: (a) Yadav, J. S.; Reddy, B. V. S.; Rao, T. S.; Rao, K. V. R.
Tetrahedron Lett. 2008, 49, 614. (b) Detz, R. J.; Delville, M. M. E.;
Hiemstra, H.; Maarseveen, J. H. Angew. Chem., Int. Ed. 2008, 47, 3777.
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Int. Ed. 2008, 47, 3781.
(2) (a) Pauson, P. L. Organometallics in Organic Synthesis. Aspects of
a Modern Interdisciplinary Field; de Meijere, A., Dieck, H. T., Eds.;
Springer: Berlin, 1988; 233. (b) Mukai, C.; Nagami, K.; Hanaoka, M.
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M. J. Org. Chem. 1993, 58, 2946. (d) Mukai, C.; Ikeda, Y.; Sugimoto, Y.;
Hanaoka, M. Tetrahedron Lett. 1994, 35, 2179. (e) Tanaka, S.; Isobe, M.
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10.1021/ol801533p CCC: $40.75
Published on Web 09/03/2008
2008 American Chemical Society

at the R- and γ-positions.11 Furthermore, the acid- or
Lewis acid-mediated propargylations should involve both
the ꢀ-eliminations and the Meyer-Schuster rearrange-
ments.1a,12 After extensive studies of the Lewis acid
catalyzed propargylation of the alcohols, we found a new
versatile propargylation using alcohols bearing sulfur and
selenium functional groups matched by the scandium-
nitromethane catalytic system. We preliminarily exhibited
the scandium-catalyzed Friedel-Crafts reactions of both
propargyl alcohols 1 and 3a with 2-methylthiophene in
Scheme 1. The reaction of 1 with 2-methylthiophene in the
portant role in the regioselective propargylations. We now
report a direct C-C bond formation of the sulfanyl- and
selanyl-substituted propargyl alcohol catalyzed scandium
triflate and the novel transformations using the products.
First, we chose to begin our study with the phenylsulfanyl
propargyl alcohol bearing the electron-donating anisyl group
3b and 2-methylthiophene in the presence of 5 mol % of
Lewis acids (Table 1). Screening of various Lewis acids (e.g.,
Table 1. Discovering Reaction Conditions for Scandium-
Catalyzed 2-Methylthienylationa, b
Scheme 1. Scandium-Catalyzed Friedel-Crafts Reactions
% yields
run
condition
4ba
3b
1
2
3
4
5
6
7
8
9
BF3·Et2O (10 mol %), MeNO2, 0 °C, 10 min
TMSOTf (10 mol %), MeNO2, 0 °C, 10 min
TiCl4 (5 mol %), MeNO2, rt, 0.5 h
Yb(OTf)3 (5 mol %), MeNO2, rt, 1.5 h
Hf(OTf)4 (5 mol %), MeNO2, 0 °C, 10 min
La(OTf)3 (5 mol %), MeNO2, rt, 1 h
SnCl4 (8 mol %), MeNO2, 0 °C, 10 min
Sc(OTf)3 (5 mol %), MeNO2, 0 °C, 10 min
Sc(OTf)3 (5 mol %), CH2Cl2, rt, 1 h
Sc(OTf)3 (5 mol %), THF, rt, 4 h
68
65
34
50
80
30
61
91
66
32
100
0
33
20
42
0
63
35
0
0
65
10
11
Sc(OTf)3 (5 mol %), DMF, rt, 72 h
a All reactions of 3b (0.18 mmol) with 2-methylthiophene (0.54 mmol)
were carried out in the presence of scandium triflate (0.009 mmol) in MeNO2
(0.50 mL). b Isolated yield of 4ba.
presence of 5 mol % of Sc(OTf)3 at room temperature
proceeded to give a mixture of both the 2-phenylpropynylated
thiophene and 3-substituted isomer 2 in 25% yield, ac-
companied by 1 (75%). The reaction of 3a regioselectively
provided 5-methyl-2-[1′-phenyl-3′-(phenylsulfanyl)prop-2-
ynyl]thiophene (4aa) in quantitative yield. It was proved that
the γ-sulfanyl functional group effectively played an im-
Yb(OTf)3, La(OTf)3, BF3·Et2O) as well as the solvent (e.g.,
dichloromethane, 1,2-dichloroethane, DMF, and THF) found
the best combination of both the Lewis acids and the solvents
to be scandium triflate-nitromethane. Furthermore, the
product 4ba was surprisingly obtained as a single regioiso-
mer, 5-methyl-2-[1-(p-anisyl)-3-(phenylsulfanyl)prop-2-ynyl]th-
iophene, in 91% yield (entry 8). The substitution pattern of
4ba was determined as the 2,5-substituted product based on
the coupling constant of the 1H NMR spectrum, shown at δ
6.54 (J ) 3.6 Hz) and 6.73 (J ) 3.6 Hz) due to the 3- and
4-thienyl hydrogens.
The scope of this reaction is shown in Table 2. The
reaction of 3b with N-methylpyrrole also gave 4bb with
complete regioselectivity (entry 1). The reaction with the silyl
enol ether exclusively provided the alkyne 4bc (entry 2).
The reactions with phenylsulfanyltrimethylsilane exclusively
gave the 1,3-bis(phenylsulfanyl)prop-1-yne 4bd in quantita-
tive yield without further addition of the phenylsulfanyl
moiety (entry 3). The p-chlorophenyl derivative also provided
the allylated 4ca and thiophene 4cb despite the electron-
poor substituent on the aromatic ring (entries 4 and 5). The
alkyl-substituted propargyl alcohols 3d,e could be used in
the reactions with nucleophiles (entries 6 and 7). Most of
the previous propargylations catalyzed by the metals are
(10) Pd: (a) Yoshida, M.; Fujita, M.; Ishii, T.; Ihara, M. J. Am. Chem.
Soc. 2003, 125, 4874. (b) Yoshida, M.; Ohsawa, Y.; Ihara, M. J. Org. Chem.
2004, 69, 1590. Bi: (c) Georgy, M.; Boucard, V.; Campagne, J.-M. J. Am.
Chem. Soc. 2005, 127, 14180. Bi: (d) Kabalka, G. W.; Yao, M.-L.; Borella,
S. J. Am. Chem. Soc. 2006, 128, 11320. (e) Zhan, Z.-P.; Yang, W.-W.;
Yang, R.-F.; Yu, J.-L.; Li, J.-P.; Liu, H.-J. Chem. Commun. 2006, 3352.
(f) Qin, H.; Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. Angew. Chem.,
Int. Ed. 2007, 46, 409. (g) Srihari, P.; Bhunia, D. C.; Sreedhar, B. P.;
Mandal, S. S.; Reddy, J. S. S.; Yadav, J. S. Tetrahedron Lett. 2007, 48,
8120. Yb: (h) Huang, W.; Wang, J.; Shen, Q.; Zhou, X. Tetrahedron 2007,
63, 11636. B: (i) Kabalka, G. W.; Yao, M.-L.; Borella, S.; Wu, Z. Org.
Lett. 2005, 7, 2865. (j) Kabalka, G. W.; Wu, Z.; Ju, Y. Org. Lett. 2004, 6,
3929. (k) Kabalka, G. W.; Yao, M.-L.; Borella, S. Org. Lett. 2006, 8, 879.
Fe: (l) Zhan, Z.-P.; Yu, J.-L.; Liu, H.-J.; Cui, Y.-Y.; Yang, R.-F.; Yang,
W.-Z.; Li, Jun.-P. J. Org. Chem. 2006, 71, 8298.
(11) (a) Olah, G. A.; Spear, R. J.; Westerman, P. W.; Denis, J.-M. J. Am.
Chem. Soc. 1974, 96, 5855. (b) Prakash, G. K. S.; Krishnamurthy, V. V.;
Olah, G. A.; Farnum, D. G. J. Am. Chem. Soc. 1985, 107, 3928. (c)
Krishnamurthy, V. V.; Prakash, G. K. S.; Iyer, P. S.; Olah, G. A. J. Am.
Chem. Soc. 1986, 108, 1575. (d) Olah, G. A.; Krishnamurthy, V. V.;
Prakash, G. K. S. J. Org. Chem. 1990, 55, 6060. (e) Mayr, H.; Bauml, E.
Tetrahedron Lett. 1983, 24, 357–360. (f) Mayr, H.; Halberstadt-Kausch,
I. K. Chem. Ber. 1982, 115, 3479.
(12) (a) Swaminathan, S.; Narayanan, K. V. Chem. ReV. 1971, 71, 429.
(b) Edens, M.; Boerner, D.; Chase, C. R.; Nass, D.; Schiavelli, M. D. J.
Org. Chem. 1977, 42, 3403. (c) Yoshimatsu, M.; Naito, M.; Kawahigashi,
M.; Shimizu, H.; Kataoka, T. J. Org. Chem. 1995, 60, 4798. (d) Ishikawa,
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.
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Org. Lett., Vol. 10, No. 19, 2008

Table 2. Regioselective Propargylation of Nucleophiles in Scandium-Nitromethane Catalytic System
b
a All reactions of 3 and 7 (0.50-3.0 mmol) with nucleophiles were carried out in the presence of scandium triflate (0.05 equiv) in MeNO2.
Org. Lett., Vol. 10, No. 19, 2008
4253

performed using 1,3-bis(aryl)- and 1,3-bis(hetaryl)propargyl
alcohols. Our method proved to be applicable to the alkyl-
substituted propargyl alcohols. It was worth noting that in
the Friedel-Crafts reactions of the cycloalkanols 3f-h, the
cyclohexanol 3f predominantly produced 2-(1-(phenylsul-
fanylethynyl)cyclohexyl-5-methylthiophene (4f ) in 91%
yield for the scandium-catalyzed reactions without ꢀ-elim-
ination (entry 8); however, the allylation of the cyclopentanol
3g provided 1-phenylsulfanylethynylcyclopent-1-ene (5g) in
92% yield, accompanied by a small amount of the allylated
product 4ga (entry 9), while the Friedel-Crafts reaction of
3g provided 5-methyl-2-[(1′-phenylsulfanylethynyl)cyclo-
pentyl]thiophene (4gb) in satisfactory yield (entry 10).
Surprisingly, the cyclododecanol 3h gave the allenic com-
pound, 2-(phenylsulfanyl)pent-1,4-dienylidenecyclododecane
6, in 41% yield (entry 11). The different regioselectivity of
both cyclododecanol 3h might be attributed to the steric
effect; however, the details of this reaction are still unclear.
The thienyl-substituted propargyl alcohol 3i was also effec-
tive for the regioselective Friedel-Crafts propargylation
(entry 12).
We then investigated and determined the scandium-
catalyzed propargylations from the alcohols bearing the
γ-phenylselanyl group as shown in Table 2 (entries 13-25).
The propargyl alcohols 7a-c reacted with very similar
nucleophiles as that performed using the sulfur analogues
to give the corresponding adducts 8aa-8c in high to excellent
yields (entries 14-19). It was noteworthy that a complete
regioselectivity occurred for all of the Friedel-Crafts
products 8aa, 8bb, 8d, 8e, 8f, 8ha,b, 8i (entries 13, 14,
19-21, 23-25).
Scheme 2. Transformations of the Friedel-Crafts Product
selenium functional group would easily transform to a wide
variety of alkynyl compounds by the alkylations of the
corresponding acetylides. The treatment of the thiophene 4ba
with n-butyllithium and p-chlorobenzaldehyde gave the
allenyl alcohol 12 via the allenyllithium intermediate.
In summary, these results proved that the sulfur and
selenium functional groups of the propargyl alcohols would
provide two kinds of excellent regioselectivities using a novel
catalytic system; one is the regioselectivity on both the
propargyl and allenyl cation, while the other is that of the
Friedel-Crafts substitutions. Now we are investigating
further transformations of the propargyl alcohols in detail.
These results will be reported elsewhere.
Supporting Information Available: Experimental pro-
cedures, spectral data, and copies of all of the new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
Next, we extended the further transformations of the
products. Typical results are shown in Scheme 2. The
Friedel-Crafts product 4ba easily underwent C-Se bond
cleavage on the alkynyl carbon to form the terminal acetylene
11. This result shows that the propargylated products bearing
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Org. Lett., Vol. 10, No. 19, 2008