Synthesis of (Z)-1-aza-1,3-enynes by the cross-coupling of terminal alkynes with isocyanides catalyzed by rare-earth metal complexes

Article abstract of DOI:10.1002/anie.200804306

(Chemical Equation Presented) Rare reactivity: A binuclear catalyst intermediate leads to the Z-selective cross-coupling of terminal alkynes with isocyanides to exclusively yield the (Z)-1-aza-1,3-enyne products for the first time (see scheme).

Full text of DOI:10.1002/anie.200804306

Communications
DOI: 10.1002/anie.200804306
Homogeneous Catalysis
Synthesis of (Z)-1-Aza-1,3-enynes by the Cross-Coupling of Terminal
Alkynes with Isocyanides Catalyzed by Rare-Earth Metal Complexes**
Wen-Xiong Zhang, Masayoshi Nishiura, and Zhaomin Hou*
À
The 1,1-insertion of isocyanides into the C H bond of
terminal alkynes is a straightforward, atom economical
Z enynes.[4c,5] They also worked for the catalytic addition of
À
À
À
terminal alkyne C H, amine N H, and phosphine P H bonds
to carbodiimides to give the corresponding propiolami-
dines,[4a,6a] guanidines,[4a,6b,c] and phosphaguanidines,[4a,6d,e]
respectively. We report herein that such half-sandwich rare-
earth metal complexes can also serve as excellent catalysts for
the cross-coupling of isocyanides with terminal alkynes to
give an unprecedented selective formation of (Z)-1-aza-1,3-
enynes. Mechanistic aspects of this catalytic process are also
described.
ꢀ
=
route to conjugated 1-aza-1,3-enynes (RC C-CH NR’),
which are compounds that are bifunctional (a basic nitrogen
=
ꢀ
center found in the C N bond and a C C bond) and are
useful synthons in organic synthesis.[1–3] However, very few
catalysts are known to promote the catalytic coupling reaction
of isocyanides with terminal alkynes,[1] whereas stoichiometric
insertion of isocyanides into a metal–acetylide bond is well
documented.[2] In 2004, Eisen and co-workers reported the
first catalytic coupling of isocyanides with terminal alkynes
catalyzed by actinide metallocene complexes, which afforded
the corresponding (E)-1-aza-1,3-enynes as a major product
together with alkyne oligomerization products and double-
insertion products.[1a,d] Takaki and co-workers found that rare-
earth silylamides, such as [Ln{N(SiMe3)2}3] (Ln = Y, La, Sm,
Yb), could also catalyze the cross-coupling of isocyanides with
terminal alkynes in the presence of amine additives to yield a
mixture of E and Z isomers of 1-aza-1,3-enynes.[1b,c] As far as
we are aware, selective formation of (Z)-1-aza-1,3-enynes in
the reaction of terminal alkynes with isocyanides has not been
reported previously. The search for new catalysts for the
efficient and selective cross-coupling reaction of terminal
alkynes and isocyanides is therefore of interest and impor-
tance.
As a control experiment, a 1:1 mixture of cyclohexyl
isocyanide and phenylacetylene in [D6]benzene was stirred at
room temperature or 908C for 12 hours, but no coupling
product was observed.[7] In contrast, in the presence of a small
amount of a half-sandwich rare-earth metal alkyl complex, a
rapid cross-coupling reaction took place at room temperature
to give the corresponding (Z)-1-aza-1,3-enyne product 2a
(Table 1). Benzene or toluene seemed to be better as solvents
relative to THF (Table 1, entries 2–4). Among the rare-earth
Table 1: Rare-earth-metal-catalyzed monoinsertion of cyclohexyl isocya-
nide into phenylacetylene.[a]
We recently found that half-sandwich rare-earth metal
alkyl complexes bearing a silylene-linked cyclopentadienyla-
mido ligand[4] served as efficient catalysts for the catalytic
dimerization of terminal alkynes to give the corresponding
[*] Prof. Dr. W.-X. Zhang, Dr. M. Nishiura, Prof. Dr. Z. Hou
Organometallic Chemistry Laboratory, RIKEN (Advanced Science
Institute), Hirosawa 2-1, Wako, Saitama 351-0198 (Japan)
Fax: (+81)48-4624665
Entry
Cat.(Ln, mol%)
Solvent
t [h]
Yield of 2a [%][b]
E-mail: houz@riken.jp
1
2
3
4
5
6
7
8
0
[D6]benzene
[D6]benzene
[D8]THF
12
0.5
4
0.5
2
0
80
41
79
>99
98
80
79
48
42
0
1a (Y, 2)
1a (Y, 2)
1a (Y, 2)
1a (Y, 1)
1a (Y, 0.5)
1b (Y, 2)
1c (Y, 2)
1d (Yb, 2)
1e (Lu, 2)
1 f (Sc, 2)
1g (Y, 2)
1h (Sm, 2)
1i (Nd, 2)
1j (La, 2)
Prof. Dr. W.-X. Zhang
Beijing National Laboratory for Molecular Sciences (BNLMS) and
College of Chemistry, Peking University, Beijing 100871 (China)
[D8]toluene
[D6]benzene
[D6]benzene
[D6]benzene
[D6]benzene
[D6]benzene
[D6]benzene
[D6]benzene
[D6]benzene
[D6]benzene
[D6]benzene
[D6]benzene
[**] This work was partly supported by a Grant-in-Aid for Scientific
Research on Priority Areas (No. 18065020, “Chemistry of Concerto
Catalysis”) from the Ministry of Education, Culture, Sports, Science,
and Technology of Japan, a Grant-in-Aid for Scientific Research (A;
No. 18205010) from Japan Society for the Promotion of Science,
and the National Natural Science Foundation of China (Nos.
20702003, 20521202).
5
0.5
0.5
0.5
0.5
2
0.5
0.5
0.5
0.5
9
10
11
12
13
14
15
80
66
64
50
Supporting information for this article is available (experimental
details, X-ray crystallographic data, and scanned NMR spectra of all
new products) on the WWW under http://dx.doi.org/10.1002/anie.
200804306. CCDC 699801 and CCDC 699802 contain the supple-
mentary crystallographic data for 2q and 3, respectively. These data
can be obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[a] Conditions: phenylacetylene (0.50 mmol), cyclohexyl isocyanide
(0.50 mmol). [b] Conversion determined by 1H NMR analysis.
Cy =cyclohexyl.
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complexes surveyed, the yttrium complexes (e.g., 1a,g)
showed the highest activity for this reaction (Table 1, entries 2
and 9–15), whereas the scandium complex (1 f) was not
effective under the same conditions (Table 1, entry 11). The
yttrium trimethylsilylmethyl complex 1a showed the same
activity as that of the aminobenzyl analogue 1g (Table 1,
entries 2 and 12), suggesting that the activity of the present
catalyst system is not significantly affected by the initial alkyl
group. Thus, in the presence of 1 mol% of 1a in [D6]benzene
at room temperature, the reaction of phenylacetylene with
cyclohexyl isocyanide quantitatively yielded cross-coupling
product 2a within 2 hours (Table 1, entry 5). Formation of a
phenylacetylene homodimerization product[5] or double-
insertion products[1a,d] was not observed.
entries 4–8). Thiophenyl-, cyclohexenyl-, and alkyl-substi-
tuted alkynes were also used (Table 2, entries 10–13). An
À
aliphatic C Cl bond also survived the reaction conditions
(Table 2, entry 14).
In the case of cyclohexyl isocyanide reacting with terminal
alkynes with a strongly electron-donating substituent, such as
4-methoxyphenylacetylene, yttrium complex 1a was less
efficient and afforded the coupling product 2o in only 22%
yield after 24 hours (Table 3, entry 1). The larger lanthanum
Table 3: Catalytic monoinsertion of isocyanides into aromatic terminal
alkynes bearing strongly electron-donating substituents.[a]
Table 2 summarizes some representative results of the
reactions between various terminal alkynes and isocyanides
catalyzed by yttrium complex 1a. A wide range of aromatic
Entry
R
Cat.
t [h]
Product
(Yield [%])[b]
Table 2: Catalytic monoinsertion of isocyanides into terminal alkynes.[a]
1
2
1a
1j
24
12
2o (22)
2o (97)
3
1j
12
2p (98)
Entry
R
R’
Product
(Yield [%])[b]
1
2
3
Cy
2a (98)
2b (95)
2c (95)
4
1j
12
2q (95)
tBu
Cy
5
6
1a
1j
24
12
2r (50)
2r (95)
4
Cy
2d (96)
5
6
Cy
Cy
2e (95)
2 f (95)
[a] Conditions: terminal alkynes (2.02 mmol), cyclohexyl isocyanide
(2.00 mmol), cat. (0.04 mmol), benzene (5 mL). [b] Yield of isolated
product.
7
8
9
Cy
Cy
Cy
2g (94)
2h (93)
2i (98)
complex 1j, however, showed much higher activity for this
reaction, and 2o was isolated in 97% yield after 12 hours by
using the same reaction conditions (Table 3, entry 2). These
results are in sharp contrast with what was observed for the
reaction of phenylacetylene with cyclohexyl isocyanide (see
Table 1, entries 2, 12, and 15), indicating that the effect of the
size of the metal ion on the catalytic activity could depend on
the substrates. Carbazolyl-substituted phenylacetylene[5b] and
pyridylacetylene were also added to cyclohexyl isocyanide
using lanthanum complex 1j to give the corresponding 1-aza-
1,3-enyne products 2q and 2r, respectively, in high yields
(Table 3, entries 4 and 6).
10
11
Cy
Cy
2j (95)
2k (94)
À
12
13
14
CH3(CH2)4
Cy
Cy
Cy
2l (95)
2m (96)
2n (93)
À
tBu
À
Cl(CH2)3
The 1H and 13C NMR spectra of the 1-aza-1,3-enyne
products 2a–r showed one set of signals, which was assigned
to the Z isomer. In the case of 2q, single crystals suitable for
X-ray crystallographic analysis were obtained, and an X-ray
diffraction study revealed that the solid structure of 2q adopts
a Z configuration in which the Cy group is placed cis to the
[a] Conditions: terminal alkynes (2.02 mmol), isocyanides (2.00 mmol),
1a (0.02 mmol), benzene (5 mL). [b] Yield of isolated product.
terminal alkynes could be used as the nucleophiles and
À
À
À
À
aromatic C F, C Cl, C Br, and C I bonds survived the
catalytic conditions to selectively yield the corresponding
=
acetylenic moiety around the C N bond (Figure 1). The
halogen-substituted
1-aza-1,3-enynes
2d–h
(Table 2,
Z products obtained were stable at room temperature, but
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Figure 1. ORTEP drawing of 2q with 30% probability thermal ellip-
Figure 2. ORTEP drawing of 3 with 30% probability thermal ellipsoids.
Hydrogen atoms have been omitted for clarity. Selected bond lengths
[ꢀ] and angles [8]: Y1–C1 2.558(4), Y1–C1’ 2.488(4), C1–C2 1.219(5),
C1-Y1-C1’ 78.99(14), Y1-C1-Y1’ 101.01(14). Symmetry operation
denoted ’=Àx+1, Ày, Àz+1.
soids. Hydrogen atoms, except that on the C1 atom, have been
omitted for clarity. Selected bond length [ꢀ] and angles [8]: C1–N1
1.273(8), C2–C3 1.173(9), C1–C2 1.457(10), C1-N1-C30 116.4(9),
C2-C1-N1 127.8(9).
could isomerize at high temperatures to give a mixture of the
Z/E isomers. Upon heating 2a at 1008C for 12 hours in
[D6]benzene in a closed NMR tube, the formation of a 5:13
mixture of the Z/E isomers was observed.[1d,8] The selective
formation of (Z)-1-aza-1,3-enynes in the present reaction is in
contrast with what was previously observed for other catalyst
systems, in which the E isomers were the main product[1a,d] or
a mixture of the E/Z isomers were obtained.[1b,c] To the best of
our knowledge, this is the first example of regio- and
stereoselective 1:1 cross-coupling between a terminal alkyne
and isocyanide to exclusively give the (Z)-1-aza-1,3-enyne.
To gain information on the mechanistic aspects of the
present catalytic process, a stoichiometric reaction of 1a with
1 equivalent of phenylacetylene was carried out in benzene at
room temperature, and after a reaction time of 1 minnute the
corresponding phenylacetylide complex 3 was isolated in
96% yield (Scheme 1). An X-ray crystallographic analysis
in [D6]benzene displayed a triplet at d = 138.7 ppm with JY,C
22.5 Hz for the acetylide carbon atoms, suggesting that the
acetylide bridges remain intact in solution. This structure is in
contrast to the bis(cyclopentadienyl)-ligated rare-earth or
actinide alkynide complexes which tend to form monomeric
structures.[1a,d,9] The addition of 1 equivalent of cyclohexyl
isocyanide to 3 in [D6]benzene at room temperature rapidly
gave monoinsertion product 4 (Scheme 1). Although a single
crystal of 4 suitable for X-ray crystallographic analysis was
not obtained, its 1H and 13C NMR spectra were rather
informative for the elucidation of the structure. The imine
carbon atom in 4 showed a doublet at d = 181.8 ppm with
=
J
Y,C = 6.5 Hz, and the phenylacetylide carbon atom gave a
triplet at d = 137.6 ppm with JY,C = 23.9 Hz in the 13C NMR
spectrum in [D6]benzene, suggesting that 4 still possesses a
dimeric structure. The addition of 1 equivalent of phenyl-
acetylene to 4 in [D6]benzene yielded (Z)-1-aza-1,3-enyne 2a
and regenerated phenylacetylide 3 quantitatively (Scheme 1).
On the basis of the above experimental results, a possible
catalytic cycle for the present cross-coupling reaction is
proposed in Scheme 2. The acid-base reaction between a half-
Scheme 1. Stoichiometric reactions of 1a.
showed that 3 adopts a dimeric structure, in which the two
yttrium centers are bridged by two phenylacetylides
(Figure 2). There is a crystallographic inversion center at
the center of the whole molecule. The 13C NMR spectrum of 3
Scheme 2. A possible mechanism of catalytic cross-coupling of termi-
nal alkynes with isocyanides.
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b) H. Dube, N. Gommermann, P. Knochel, Synthesis 2004, 2015 –
sandwich rare-earth alkyl and a terminal alkyne should yield a
dimeric alkynide species such as A. Coordination of an
isocynide to one of the metal centers of the dimeric alkynide
species could afford B by breaking one of the two alkynide
bridges. Attack of the terminal alkynide to the coordinated
isocynide on another metal center in binuclear species B in an
intermolecular fashion should give C, which upon abstraction
of a proton from another molecule of the alkyne would yield
the corresponding (Z)-1-aza-1,3-enyne 2 and regenerate
alkynide A. Apparently, having the coupling reaction take
place at the two metal centers in a binuclear species such as B
is the key to the selective formation of the Z-isomer product
in the present catalyst system.[1,5]
In summary, we have demonstrated that half-sandwich
rare-earth metal alkyl complexes can act as excellent catalyst
precursors for the cross-coupling of various terminal alkynes
with isocyanides, selectively affording the (Z)-1-aza-1,3-
enyne products. The unprecedented Z selectivity could arise
from formation of an alkynide-bridged binuclear catalyst
species, in which the cross-coupling reaction takes place at the
two metal centers in an intermolecular fashion.
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Received: September 1, 2008
Published online: November 5, 2008
Keywords: cross-coupling · enynes · isocyanides ·
.
rare-earth metals · sandwich complexes
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