Direct mono-insertion of isocyanides into terminal alkynes catalyzed by rare-earth silylamides

Article abstract of DOI:10.1039/b414302g

Rare-earth silylamide complexes, Ln[N(SiMe₃)₂] ₃ (Ln = Y, La, Sm, Yb), effectively catalyzed the coupling reaction of isocyanides with both aliphatic and aromatic terminal alkynes under mild conditions. The Royal Society o

Full text of DOI:10.1039/b414302g

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COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Direct mono-insertion of isocyanides into terminal alkynes catalyzed by
rare-earth silylamides{
Kimihiro Komeyama,* Daisuke Sasayama, Tomonori Kawabata, Katsuomi Takehira and Ken Takaki
Received (in Cambridge, UK) 17th September 2004, Accepted 26th October 2004
First published as an Advance Article on the web 13th December 2004
DOI: 10.1039/b414302g
Rare-earth silylamide complexes, Ln[N(SiMe
3
)
2
]
3
(Ln 5 Y, La,
increased to 76% with amylamine (entry 3). Tertiary amines like
triethylamine showed no obvious effect (entry 4). By screening the
catalyst, it became apparent that the lager metals, Sm and La, gave
the better yield of 3ad (entries 3, and 5–7).
Sm, Yb), effectively catalyzed the coupling reaction of
isocyanides with both aliphatic and aromatic terminal alkynes
under mild conditions.
A selection of various terminal alkynes 1a–h and isocyanides
The insertion reaction of carbon–carbon unsaturated compounds
into various transition metal–carbon bonds is one of the most
powerful methods for carbon chain construction, and it has been
widely utilized as a key step in organic synthesis. This process was
also used in the lanthanide-catalyzed transformation of alkynes
and alkenes: for example, cyclization/hydrosilylation and oligo-
2a–e was investigated using Sm(btsa) (10 mol%) and amylamine
3
(20 mol%) in cyclohexane at room temperature (Table 2). The
reaction of oct-1-yne (1a) with tert-butyl isocyanide (2a) did not
commenced under the present conditions (entry 1). At elevated
temperature (65 uC), the isocyanide 2a was completely changed to
oligomers, though the alkyne 1a was mostly remained. Phenyl
isocyanide (2b) gave similar results (entry 2). These results implied
that the insertion of isocyanide 2 into the metal–carbon bond of
the iminoyl intermediate took place faster than its competitive
protonation. In fact, it is clear that with the aromatic isocyanides
having bulkier substituents at o-position, the selectivity of 3 was
1
merization. In addition, one-carbon elongation using carbon
monoxide and isocyanides has been recognized as an important
tool in the formation of carbonyl and iminoyl functions, which
2
lead to multi-functionalized alcohols and amines. The reaction is
3,4
mainly promoted by late transition metals. However, there has
been no precedent for the catalytic direct mono-insertion of
isocyanides into terminal alkynes. Very recently, Eisen et al.
reported the insertion of tert-butyl isocyanide into terminal alkynes
5
catalyzed by actinides. With respect to rare-earth complexes, their
unique reactions with carbon monoxide and useful synthetic
reaction, though stoichiometric, via isocyanide insertion into Ln-
6,7
carbon bond have been reported.
In our previous work, rare-earth silylamide, Ln(btsa)3
btsa 5 N(SiMe ], was found to catalyze the dimerization of
aliphatic and aromatic terminal alkynes, leading to 1,3-enynes with
[
3 2
)
8,9
high regio- and stereoselectivities. During the investigation, we
also found that a coupling reaction of terminal alkynes and
isocyanides took place effectively in the presence of the silylamide
catalysts and amine additives (Scheme 1). In this Communication,
we would like to disclose these results.
When oct-1-yne (1a) was treated with equimolar amounts of
2
-mesityl isocyanide (2d) in the presence of Sm(btsa)
3
(10 mol%)
Scheme 1 Catalytic coupling of terminal alkynes and isocyanides.
TBS 5 tert-butyl dimethyl silyl.
for 24 h at room temperature in cyclohexane, the coupling
product, 1-(2-mesitylimino)non-2-yne (3ad), was obtained in only
1
0% yield as a mixture of syn and anti isomers. The alkyne was
Table 1 Effect of amines and catalysts for the coupling reaction of 1a
with 2d
recovered in 48%, but most of the isocyanide 2d was consumed to
provide oligomeric products. We therefore focused our attention
on inhibiting the oligomerization of isocyanide by amine additives
that altered the catalyst activities and served as a proton source in
a
Yield (%) Recovery (%)
a
Entry Catalyst
Additive (mol%) 3ad
1a
2d
8
the dimerization of terminal alkynes. These results are summar-
1
2
3
4
5
6
7
Sm(btsa)
Sm(btsa)
Sm(btsa)
Sm(btsa)
3
3
3
3
None
PhNH (25)
2
10
7
76
9
38
35
62
48
66
16
52
59
36
15
11
67
0
32
28
17
tr
ized in Table 1. Addition of aniline caused a low conversion of 1a
and 2d (entry 2), whereas yield of the product 3ad drastically
C
Et
5
H
11NH
N (25)
11NH
2
(20)
3
Yb(btsa)
Y(btsa)3
3
C
5
H
2
(20)
{ Electronic supplementary information (ESI) available: Details of the
procedure and spectral data for the products in Table 2. See http://
5 11 2
C H NH (20)
5 11 2
La(btsa)3 C H NH (20)
www.rsc.org/suppdata/cc/b4/b414302g/
*kkome@hiroshima-u.ac.jp
a
Determined by GC.
6
34 | Chem. Commun., 2005, 634–636
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Table 2 Examples for the coupling of alkynes (1) and isocyanides (2)
catalyzed by Sm(btsa) in the presence of amylamine
3
a
Entry
Alkyne
Isocyanide
Time/h
Product
Yield (%)
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1b
1c
1d
1e
1f
2a
2b
2c
2d
2e
2e
2e
2e
2e
2e
2e
2e
1
20
5
9
9
9
9
6
24
6
6
3aa
3ab
3ac
3ad
3ae
3be
3ce
3de
3ee
3fe
0
0
53
76
88
86
94
88
95
95
85
93
Scheme 3 Plausible reaction mechanism of mono-insertion of isocyanide
into terminal alkynes.
10
11
12
1g
1h
9
6
3ge
3he
absence of the amine additive, multiple insertion of 2 to B in
preference to its protonation with 1 (path b) would result in
oligomerization.
a
Determined by GC and H NMR.
In summary, we have demonstrated that readily available rare-
earth silylamide complexes are able to catalyze mono-insertion of
isocyanides into terminal alkynes. This reaction proceeds in high
yield and compatibility with various aromatic and aliphatic
terminal alkynes in the presence of amine additives.{
higher due to the inhibition of the oligomerization (entries 2–5).
Thus, the product 3ae was obtained in 88% yield, using 2,6-
diisopropylphenyl isocyanide (2e).
Compatibility of the present reaction was tested in the screening
of various terminal alkynes for the coupling reaction with 2e
Kimihiro Komeyama,* Daisuke Sasayama, Tomonori Kawabata,
Katsuomi Takehira and Ken Takaki
(Table 2, entries 6–12). 3,3-Dimethylbut-1-yne (1b) provided the
corresponding aldimine 3be in high yield (entry 6). Interestingly,
the presence of tertiary amino group did not appear to alter the
yield and product selectivity (entry 7), whereas TBS-protected
propargyl alcohol 1d required a longer period to complete the
reaction (entry 8). However, the corresponding alkynes containing
primary amino group and TMS-protected alcohol moiety could
not be used, because no reaction took place under the similar
conditions. Aromatic alkynes were more reactive than aliphatic
ones in general (entries 5 vs. 9). Electron-donating substituents
such as p-methoxyphenylacetylene (1f) led to slightly increase yield
Department of Chemistry and Chemical Engineering, Graduate School
of Engineering, Hiroshima University, Kagamiyama,
Higashi-Hiroshima, 739-8527, Japan.
E-mail: kkome@hiroshima-u.ac.jp; Fax: +81 82 424 5494;
Tel: +81 82 424 7738
Notes and references
{
Representative experimental procedure: All reactions were carried out
under Ar atmosphere. A solution of 1a (99 mL, 0.67 mmol), 2e (125 mg,
.67 mmol), and amylamine (15.4 mL, 0.134 mmol) in cyclohexane (0.7 mL)
was added into Sm(btsa) (42 mg, 0.067 mmol). After 9 h of stirring at
0
3
(
95%), as compared to electron-withdrawing substituents of 1g
85%) in the same position (entries 10 vs. 11). Although acetalated
formyl groups have been known to usually disturb the rare-earth-
room temperature, the reaction mixture was quenched with distilled water
and ether. Yield of 3ae was measured by gas chromatography with
dimethyl terephthalate as an internal standard. After extraction with ether,
the combined organic layer was washed with brine, dried over anhydrous
(
1b
catalyzed reaction because of its strong acidity, the present
silylamide catalyst could notably perform the coupling reaction of
Na
(250 uC/10 mmHg) gave 1-(2,6-diisopropylphenylimino)non-2-yne (3ae)
117 mg, 59%) as a yellow oil mixture of the syn and anti-isomers (65/35).
2 4
SO , and evaporated in vacuo. Kugelrohr distillation of the mixture
22
(
1
h to give 3he in 93% yield (entry 12).
The reaction of hex-1-yne with 2e was carried out using
stoichiometric amounts of Sm(btsa) without the amine additives
in order to get information about the reaction mechanism (Scheme
). Quenching of the reaction mixture with D O gave a mixture of
+
1
3
MS m/z (70 eV) 297 (M , 36), 282 (100), 212 (35). H NMR (CDCl ) anti
isomer: d 0.91 (3H, t, J 5 7.0 Hz), 1.01–1.49 (18 H, m), 1.61–1.69 (2H, m),
2.46 (2H, dt, J 5 1.5, 7.2 Hz), 2.92 (2H, sept, J 5 6.9 Hz), 7.03–7.14 (3H,
m), 7.40 (1H, t, J 5 1.5 Hz); syn isomer (assignable peaks only): d 0.84 (3H,
t, J 5 7.2 Hz), 1.01–1.49 (18 H, m), 2.14 (2H, dt, J 5 1.4, 6.9 Hz), 2.82 (2H,
3
2
2
1
3
sept, J 5 6.9 Hz), 7.03–7.14 (3H, m), 7.84 (1H, t, J 5 1.4 Hz). C NMR
CDCl ) anti isomer: d 14.01, 19.5, 22.5, 23.5, 27.71, 27.86, 28.0, 31.3, 78.9,
97.0, 123.0, 124.6, 137.5, 147.1, 148.6. syn isomer: d 14.05, 19.0, 22.4, 23.3,
7.67, 27.84, 28.7, 31.2, 76.5, 100.3, 122.7, 124.1, 136.3, 145.2, 147.3. Anal.
oligomers, from which the compound 4, derived from the alkyne
and three molecules of 2e, was isolated in 10% yield as the least
molecular weight fraction. The iminoyl proton of 4 was found to
be deuterated in 92%.
(
3
2
Calcd for C21H31N: C, 84.79; H, 10.50; N, 4.71. Found: C, 84.89; H, 10.62;
N, 4.49.
Based on the results described above, a reaction process would
be explained as depicted in Scheme 3. 1,1-Insertion of the
isocyanide 2 to rare-earth alkynide A, generated from alkyne 1
1
For the review: (a) Lanthanides: Chemistry and Use in Organic Synthesis,
ed. S. Kobayashi, Springer, Berlin, 1999; (b) G. A. Molander and
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terminal alkynes: (c) H. J. Heeres and J. H. Teuben, Organometallics,
8
and the amide species, would yield a key iminoyl intermediate B.
Then, predominant protonation of B with the amine additive
could afford the product 3 and rare-earth amide (path a). In the
1991, 10, 1980; (d) M. Nishiura, Z. Hou, Y. Wakatsuki, T. Yamaki and
T. Miyamoto, J. Am. Chem. Soc., 2003, 125, 1184; (e) C. G. J. Tazelaar,
S. Bambirra, D. Leusen, A. Meetsma, B. Hessen and J. H. Teuben,
Organometallics, 2004, 23, 936.
2
3
Recent report on synthetic utilities of iminoyl alkynes: (a) I. Hachiya,
K. Ogura and M. Shimizu, Synthesis, 2004, 1349; (b) H. Dube,
N. Gommermann and P. Knochel, Synthesis, 2004, 2015.
For insertion of isocyanides under stoichiometric conditions, Ti: (a)
E. Klei and J. H. Teuben, J. Organomet. Chem., 1980, 188, 97; Zr: (b)
G. S. Bristow, P. B. Hitchcock and M. F. Lappert, J. Chem. Soc., Chem.
Commun., 1982, 462; Nb: (c) A. H. Klazinga and J. H. Teuben,
Scheme 2 Labelling of the stoichiometric reaction of hex-1-yne with 2e.
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Chem. Commun., 2005, 634–636 | 635

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4
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9
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2
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2
2
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6
36 | Chem. Commun., 2005, 634–636
This journal is ß The Royal Society of Chemistry 2005