A novel Sc(OTf)3-catalyzed prop-2-ynylation and penta-2,4-diynylation of soft nucleophiles

Article abstract of DOI:10.1055/s-2001-18099

The prop-2-ynylation and penta-2,4-diynylation of soft nucleophiles catalyzed by Sc(OTf)₃ from prop-2-ynal diethyl acetals 1a-e, and penta-2,4-diynal diethyl acetals 1g-i gave the alkylated and arylated products 2a-i, 3g, 4g,h, 6a-c in good to high yields.

Full text of DOI:10.1055/s-2001-18099

LETTER
1799
A Novel Sc(OTf)3-Catalyzed Prop-2-ynylation and Penta-2,4-diynylation of
Soft Nucleophiles
A
N
ovel Sc(OTf)3-Catialyzed
t
Prop-2
s
-
ynylation
u
and Penta-2
h
, 4-diynylatio
i
n
ro Yoshimatsu,* Masako Kuribayashi, Tomoko Koike
Department of Chemistry, Faculty of Education, Gifu University, Yanagido, Gifu 501-1193, Japan
Fax +81(58)2932207; E-mail: yoshimae@cc.gifu-u.ac.jp
Received 13 August 2001
O
Abstract: The prop-2-ynylation and penta-2,4-diynylation of soft
nucleophiles catalyzed by Sc(OTf)3 from prop-2-ynal diethyl ace-
tals 1a–e, and penta-2,4-diynal diethyl acetals 1g–i gave the alkylat-
ed and arylated products 2a–i, 3g, 4g,h, 6a–c in good to high yields.
Ph
R1R2N
7 (62%)
Key words: scandium triflate, C-C bond formation, prop-2-ynyl
COPh
cation, propargyl cation
8a (R1=R2=Et) (27%)
8b (R1=nBu;R2=H) (88%)
i
ii
EtO
O
Cationic prop-2-ynylation has been a difficult process be-
cause of the low ability of the alkynyl group to stabilize
the cations.1 In the 1970s, the novel Nicholas reaction us-
PhS
iii
COPh
Ph
9 (4E:4Z=72:28)
(65%)
+
2a
ing (prop-2-ynyl)Co2(CO)6 complexes, which are syn-
iv
PhSe
thons for the prop-2-ynyl cations, was discovered. This
chemistry has provided new C-C bond formations,2 which
are utilized for the syntheses of both heterocycles3,4,5 and
biologically active compounds,6 and the well-known
[2+2+2] cycloaddition (Pauson–Khand reaction).7 The ki-
netics of the dicobalt-coordinated prop-2-ynyl cations
have also been studied along with their electrophilicities
due to the substituents on the cations.1 However, this nov-
el method has some limitations: 1) the dicobalt octacarbo-
nyl is hard to handle because of its toxicity and air
sensitivity,8 2) the process involves some inconvenience
in as much as the precursors have to be produced by the
addition of dicobalt octacarbonyl to the acetylenes and the
prop-2-ynylated products were obtained through the oxi-
dative demetalation of dicobalt hexacarbonyl from the
complexes.
v
COPh
10 (4E:4Z=83:17)
(72%)
PhSe
Ph
O
11 (22%)
Scheme Reagents: i) Et2NLi/–78 °C; ii) R1R2NLi/0 °C; iii) PhSNa/
EtOH; iv) (PhSe)2/NaBH4; v) (PhSe)2/NaH/0 °C
further investigate the scope of this chemistry, we next ex-
plored the catalytic prop-2-ynylation of soft nucleophiles
without the stabilizing effect of the -phenylseleno or
phenylthio group. If the cationic prop-2-ynylation catalyt-
ically proceeds without the dicobalt octacarbonyl or stabi-
lization by the selenium or sulfur functional groups, this
method will prove to be novel and more convenient. We
now report the general prop-2-ynylation of soft nucleo-
philes using Sc(OTf)3 having a weak Lewis acidity and
high catalytic activity15 and our further investigation of
the penta-2,4-diynylation of the nucleophiles.
Acetals have been reported to be a good acceptor for
the soft nucleophiles such as the allyltrimethylsilane,9 the
silyl enol ether10,11 and TMSCN.12 The relative reactivities
of the , -unsaturated acetals are higher than that of the
other acetals.13 However, that of the 2-alkynal acetals
have not been discussed. There has been a few examples
of the 2-alkynal acetals used in the Lewis acid catalyzed
reactions with the soft nucleophiles;12 however, the reac-
tions of prop-2-ynal acetal 1a with the silyl enol ether
gave unsatisfactory results. We have previously reported
a novel -(phenylseleno)- or -(phenylthio)-substituted
prop-2-ynylation of nucleophiles.14 The -phenylseleno
or phenylthio groups effectively stabilized the prop-2-
ynyl cations and the regioselective prop-2-ynylation with
various nucleophiles took place in high yields. In order to
First, we examined the propynal diethyl acetal 1a with 1-
phenyl O-trimethylsilyl enol ether in the presence of 1
mol% of Sc(OTf)3 at room temperature for 5 hours that
produced the 3-ethoxy-4-pentynophenone 2a in 57%
yield. We examined the reactions of propynal diethyl ac-
etal 1a with the silyl enol ether in the presence of 10 mol%
of other Lewis acids such as BF3 Et2O, Me3SiOTf and
Yb(OTf)3; however, the yields of the product 2a were low.
The reactions of other propynal analogs were investigated
and these results are shown in Table 1. 2-Heptynal 1b and
3-phenylpropynal diethyl acetal 1c gave the alkylated
products 2b,c in good yields (Entries 2, 3). The propynal
Synlett 2001, No. 11, 26 10 2001. Article Identifier:
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© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1800
M. Yoshimatsu et al.
LETTER
bearing an electron-withdrawing trimethylsilyl group or
an electron-donating phenylseleno group also afforded
products (Entries 4, 5).
Table 2 Reactions of Nona-2,4-diynal Acetal 1g with Arenes Cata-
lyzed by Sc(OTf)3
1mol%
Sc(OTf)3
Ar
OEt
OEt
nBu
Table 1 Reactions of Prop-2-ynal or Penta-2,4-diynal Acetals with
soft Nucleophiles Catalyzed by Sc(OTf)3
nBu
(
)
2
(
)
2
Nucleophile
Ar
6
1g
OEt
OEt 1mol% Sc(OTf)3
Entry Arene (equiv)
Ar
Product
R
R
(% yield)
Nu
nucleophile
OEt
2a-i,3g,4g,h
1a-i
1
1,2,3-trimethoxyben- 2,3,4-trimethoxyphenyl 6a (23)
zene (3)
Entry
1
R
Nucleophile
Product (Nu)
(% yield)
2
3
furan (10)
2-furyl
6b (10)
6c (28)
OTMS
Ph
1a
H
2a (CH2COPh) (57)
N-methylpyrrole (10) 2-(1-methylpyrrolyl)
2
3
4
5
6
1b nBu
1c Ph
1d TMS
2b (CH2COPh) (91)
2c (CH2COPh) (70)
2d (CH2COPh) (77)
2e (CH2COPh) (60)
2f (CH2COPh) (39)
Et2NLi at –78 °C (Scheme) gave the conjugated
enynophenone, which is a valuable Michael acceptor, in
62% yield. The reaction with an amide below 0 °C under-
went 1,6-addition to give the 5-amino-2,4-pentadienophe-
nones 8a,b. The reactions with other nucleophiles such as
PhSNa or PhSeNa afforded 5-(phenylsulfenyl)- 9 or 5-
(phenylselenenyl)-2,4-pentadienophenone 10 in good
yield. Particularly interesting is the reaction with PhSeNa,
generated from (PhSe)2/NaH, that resulted in the furan
formation.
1e
1f
PhSe
TMS
7
8
1g
2g (CH2COPh) (86)
3g (CH2COSEt) (71)
nBu
OTMS
SEt
We are now investigating the enantioselective prop-2-
ynylation using catalytic Sc(OTf)3. These results will be
reported elsewhere.
9
10
11
TMSCN
4g (CN) (95)
PhSH
4h (SPh) (60)
Acknowledgement
1h
1i
2h (CH2COPh) (78)
OTMS
Ph
Ph
The support of part of this work by the Ministry of Education, Sci-
ence and Culture, Japan, is gratefully acknowledged.
12
2i (CH2COPh) (58)
PhSe
References and Notes
(1) Kuhn, O.; Rau, D.; Mayr, H. J. Am. Chem. Soc. 1998, 120,
900; and references therein.
Next, we examined the Sc(OTf)3-catalyzed penta-2,4-diy-
nylation with soft nucleophiles. 5-Trimethylsilylpenta-
2,4-diynal diethyl acetal 1f gave a low yield of the prod-
uct; however, the other 2,4-pentadiynal acetals afforded
3-ethoxyundeca-4,6-diynophenone 2g in high yield (En-
try 7). The other soft nucleophiles examined are shown in
Table 1 (Entries 8–10). The reaction with S-ethyl O-trim-
ethylsilyl ketene thioacetal gave the alkylated product 3g.
The nitrile 4g was also obtained in high yield. Other pen-
ta-2,4-diynynal acetals 1h,i effected the alkylation to give
the penta-2,4-diynylated ketones 2h,i. The reactions with
arenes were also examined and these results are shown in
Table 2. The 1,1-bis(aryl)nona-2,4-diynes 6a–c were ob-
tained in low yields; however, the mono-arylated nona-
2,4-diynes could not be detected.
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Synlett 2001, No. 11, 1799–1801 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
A Novel Sc(OTf)3-Catalyzed Prop-2-ynylation and Penta-2,4-diynylation
1801
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Synlett 2001, No. 11, 1799–1801 ISSN 0936-5214 © Thieme Stuttgart · New York