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
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