Reaction of Yb-imine complexes with isocyanates. Novel synthesis of α-aminoacetamides

Article abstract of DOI:10.1246/cl.2002.790

Yb(II)-imine complexes, prepared from Yb metal and aromatic imines in THF and HMPA, reacted with isocyanates to give α-aminoacetamides. This method provides a novel synthetic route to α-amino-substituted acetamide derivatives.

Full text of DOI:10.1246/cl.2002.790

790
Chemistry Letters 2002
Reaction of Yb-Imine Complexes with Isocyanates. Novel Synthesis of ꢀ-Aminoacetamides
Ryoma Ueno, Kohei Yano, Yoshikazu Makioka, Yuzo Fujiwara, and Tsugio Kitamuraꢀy
Department of Applied Chemistry, Faculty of Engineering, Kyushu University, Hakozaki, Fukuoka 812-8581
yDepartment of Chemistry and Applied Chemistry, Faculty of Science and Engineering, Saga University,
Honjo-machi, Saga 840-8502
(Received May 10, 2002; CL-020405)
Yb(II)-imine complexes, prepared from Yb metal and
filtrate was analyzed by GC. Column chromatography on silica
gel afforded N-isopropyl-2,2-diphenyl-2-(phenylamino)aceta-
mide (3a)7 as crystals. The results are given in Table 1.
aromatic imines in THF and HMPA, reacted with isocyanates
to give ꢀ-aminoacetamides. This method provides a novel
synthetic route to ꢀ-amino-substituted acetamide derivatives.
Table 1. Optimization of reaction conditionsa
Organic synthesis using lanthanoid metals or reagents has
been developed extensively.1 In our study on the development of
organic synthesis using lanthanoid metals, we have found that the
reaction of Yb metal and an aromatic ketone gives a Yb-ketone
complex via two-electron transfer.2 This Yb complex reacts with
various electrophiles including carbon electrophiles, indicating a
‘‘umpoled’’ dianionic character. Similarly, Yb metal reacts with
an aromatic imine to form the corresponding Yb-imine complex.3
This Yb-imine complex has relatively strong basicity compared
with the Yb-ketone complex. Therefore, the Yb-imine complex
abstracts protons from acetone to lead to the reduced amine.4 The
Yb-imine complex also catalyzes the isomerization of terminal
alkynes to internal alkynes and the dehydrogenative coupling
reaction of terminal alkynes and hydrosilanes.5
On the other hand, the reaction forming the C–C bond is one
of important synthetic methods. However, there is only one
example that the Yb-imine complex reacts with carbon electro-
philes.6 The Yb-imine complexes prepared in situ afford ꢀ-
aminoacetic acid derivatives by the reaction with CO2. If the Yb-
imine complexes attack nucleophilically to the cumulene bond of
isocyanates, the reaction will lead to the formation of ꢀ-
aminoacetamides as shown in Scheme 1. Here we report a simple
and novel synthesis of ꢀ-aminoacetamides from imines and
isocyanates by using Yb metal.
The best result was obtained in the case requiring 3 h for the
first step (time 1) and 1 h for the second step (time 2).
Next, we examined the additives except HMPA. In the
absence of HMPA, the yield of aminoacetamide 3a was 34%.
Addition of 1,3-dimethylimidazolidin-2-one or dimethoxyethane
was not effective in the formation of 3a. Other additives such as
N,N-dimethylacetamide, N,N,N0,N0-tetramethylurea and tri-
methyl phosphate retarded the formation of 3a. As the result,
HMPA is essential for this aminoacetamide synthesis.
Scheme 1.
The synthesis of ꢀ-aminoacetamides in this study consists of
the following two steps: the preparation of the Yb-imine complex
and the reaction with an isocyanate. This one-pot synthesis can be
conducted as follows.
Yb metal (0.25 mmol) and N-(diphenylmethylene)aniline
(1a, 0.25 mmol) were placed under Ar and then THF (1.0 mL),
hexamethylphosphoramide (HMPA, 0.25 mL) and MeI (3.0 ꢁL,
an activating agent of Yb) were added successively. The solution
of the Yb-imine complex was prepared by stirring the mixture for
the time indicated in Table 1 (time 1). The reaction of the Yb-
imine complex was conducted by adding isopropyl isocyanate
(0.50 mmol) and by stirring the mixture for the time indicated in
Table 1 (time 2). The reaction mixture was quenched with H2O
(0.1 mL). The resulting precipitates were filtered off and the
The optimized conditions were employed for the reaction of
various Yb-imine complexes and isocyanates. The results are
given in Table 2. 4-Methyl and methoxy-substituted aromatic
imines (1b and 1c) reacted with isopropyl isocyanate to give the
corresponding ꢀ-aminoacetamides (3b and 3c)7 in 60 and 45%
yields, respectively. The reaction of Yb-imine complexes 2a–2c
with propyl and hexyl isocyanates proceeded smoothly to give the
corresponding aminoacetamides (3d–3g). However, the reaction
with phenyl isocyanate did not provide the aminoacetamide even
in the prolonged reaction time.
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
791
Table 2. Reaction of Yb-imine complexexs 3 with isocyanatesa
Kobayashi, Eur. J. Org. Chem., 1999, 15.
2a) Z. Hou, H. Yamazaki, Y. Fujiwara, and H. Taniguchi,
Organometallics, 11, 2711 (1992). b) Z. Hou, H. Yamazaki,
K. Kobayashi, Y. Fujiwara, and H. Taniguchi, J. Chem. Soc.,
Chem. Commun., 1992, 722.
3
4
5
Y, Makioka, Y. Taniguchi, Y. Fujiwara, K. Takaki, Z. Hou,
and Y. Wakatsuki, Organometallics, 15, 5476 (1996).
K. Takaki, Y. Tsubaki, S. Tanaka, F. Bepu, and Y. Fujiwara,
Chem. Lett., 1990, 203.
a) Y. Makioka, Y. Taniguchi, T. Kitamura, Y. Fujiwara, A.
Saiki, and K. Takaki, Bull. Soc. Chim. Fr., 134, 349 (1997). b)
Y. Makioka, A. Saiki, K. Takaki, Y. Taniguchi, T. Kitamura,
and Y. Fujiwara, Chem. Lett., 1997, 27. c) K. Takaki, M.
Kurioka, T. Kamata, K. Takehira, Y. Makioka, and Y.
Fujiwara, J. Org. Chem., 63, 9265 (1998).
6
7
K. Takaki, S. Tanaka, and Y. Fujiwara, Chem. Lett., 1991,
493.
Spectral data of representative ꢀ-aminoacetamides 3 are as
follows. 3a: mp 170–171 ꢁC; IR (KBr) ꢂmax (cmÀ1) 3382(N–
H), 1670 (C=O); 1H NMR (CDCl3) ꢃ 1.02(d, J ¼ 7 Hz, 6H),
4.07 (sept, J ¼ 7 Hz, 1H), 5.13 (br s, 1H), 6.34 (br s, 1H), 6.43
(d, J ¼ 7 Hz, 2H), 6.62 (t, J ¼ 7 Hz, 1H), 6.98 (d, J ¼ 7 Hz,
2H), 7.12–7.29 (m, 6H), 7.54 (d, J ¼ 7 Hz, 4H); 13C NMR
(CDCl3) ꢃ 22.2, 41.8, 71.1, 115.8, 118.2, 122.4, 128.1, 128.4,
128.6, 141.5, 144.6, 170.6. Found: C, 80.08; H, 7.04; N,
8.10%. Calcd for C23H24N2O: C, 80.20; H, 7.02; N, 8.13%.
3b: mp 170–171 ꢁC; IR (KBr) ꢂmax (cmÀ1) 3382(N–H), 1649
(C=O); 1H NMR (CDCl3) ꢃ 1.02(d, J ¼ 7 Hz, 6H), 2.30 (s,
3H), 4.07 (sept, J ¼ 7 Hz, 1H), 5.13 (br s, 1H), 6.34 (br s, 1H),
6.44 (d, J ¼ 7 Hz, 2H), 6.64 (t, J ¼ 7 Hz, 1H), 7.00 (t,
J ¼ 7 Hz, 2H), 7.09–7.52 (m, 9H); 13C NMR (CDCl3) ꢃ 20.4,
22.2, 41.8, 71.1, 115.8, 118.2, 127.4, 128.1, 128.4, 128.6,
128.9, 137.3, 138.5, 141.4, 144.6, 144.7, 170.8. Found: C,
80.34; H, 7.29; N, 7.76%. Calcd for C24H26N2O: C, 80.41; H,
In summary, we have found a new approach to ꢀ-
aminoacetamides by using Yb-imine complexes and isocyanates.
Although the reactivity of isocyanates to the Yb-imine complexes
is similar to that of CO2, this reaction provides a very simple and
one-pot synthesis of highly substituted ꢀ-aminoacetamides. This
simple and convenient procedure will be applied to the synthesis
of functionalized aminoacetamides in near future.
References and Notes
1
a) H. B. Kagan and J. L. Namy, ‘‘Handbook on the Physics and
Chemistry of the Rare Earths,’’ ed. by K. A. Gschneider and L.
Eyring, Elsevier, Amsterdam (1984), p 525. b) P. L. Watson
and G. W. Parshall, Acc. Chem. Res., 18, 51 (1985). c) H. B.
Kagan and J. L. Namy, Tetrahedron, 42, 6573 (1986). d) G. A.
Molander, Chem. Rev., 92, 29 (1992). e) T. Imamoto,
‘‘Organic Synthesis,’’ Academic Press, London (1994). f)
Y. Taniguchi, K. Takaki, and Y. Fujiwara, Rev. Heteroat.
Chem., 12, 163 (1995). g) G. A. Molander and C. R. Harris,
Chem. Rev., 96, 307 (1996). h) M. Shibasaki, H. Sasai, and T.
Arai, Angew. Chem., Int. Ed. Engl., 36, 1236 (1997). i) S.
7.31, N, 7.81%. 3c: mp 133–135 ꢁC; IR (KBr) ꢂmax (cmÀ1
)
3382(N–H), 1649 (C=O); 1H NMR (CDCl3) ꢃ 1.05 (d,
J ¼ 7 Hz, 6H), 3.77 (s, 3H), 4.07 (sept, J ¼ 7 Hz, 1H), 5.26
(br s, 1H), 6.38 (br s, 1H), 6.43 (d, J ¼ 7:5 Hz, 2H), 6.64 (t,
J ¼ 7:5 Hz, 1H), 6.80 (t, J ¼ 7:5 Hz, 2H), 7.00–7.52 (m, 9H);
13C NMR (CDCl3) ꢃ 22.3, 41.8, 55.2, 70.6, 113.5, 115.8,
118.1, 127.5, 128.2, 128.4, 128.6, 129.8, 133.3, 141.6, 144.6,
158.7, 170.1. Found: C, 76.80; H, 6.95; N, 7.40%. Calcd for
C24H26N2O2: C, 76.98; H, 7.00; N, 7.48%.