M. Benaglia et al. / Tetrahedron Letters 45 (2004) 8705–8708
8707
1%mol, 9 was obtained after purification in 77% yield
and 61% ee (entries 10 and 11).
efficient bis-imine-based chiral ligands make the present
methodology very attractive.
In other experiments the methodology was then
extended to differently substituted imines (Fig. 2).
Acknowledgements
The catalytic system worked with imines modified both
at the N-residue or at the C-residue, affording products
10–13 in yields from fair to excellent, and enantioselec-
tivities up to 55% (Table 2).
This work was supported by MIUR (Progetto Nazio-
nale Stereoselezione in Sintesi Organica. Metodologie
ed Applicazioni) and C.I.N.M.P.I.S. (Consorzio Inter-
universitario Nazionale Metodologie e Processi Innova-
tivi di Sintesi).
It is worth mentioning that the copper(I) complex of
ligand 3 was able to catalyze also the addition of alkyl
acetylenes derivatives to imines. Indeed, the reaction be-
tween imine 8 and 1-hexyne afforded the corresponding
propargyl amine 14 with 73% yield and 71% ee. Analo-
gously the addition of 1-decyne to imine 8 gave 15 in
References and notes
1
2
3
. Review: Comprehensive Asymmetric Catalysis; Jacobsen,
E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin,
1999; Vols. I–III.
. For a review of asymmetric synthesis of propargylamines,
see: Blanchet, J.; Bonin, M.; Micouin, L. Org. Prep.
Proced. Int. 2002, 34, 459.
. Reviews: (a) Pu, L.; Yu, H. B. Chem. Rev. 2001, 101, 757;
(b) Frantz, D. E.; Fassler, R.; Tomooka, C. S.; Carreira,
E. M. Acc. Chem. Res. 2000, 33, 373.
1
9
9
1% yield and 73% ee. Also for alkyl acetylene addi-
tion the reaction promoted by only 5%mol of catalyst
afforded product 15 in very good yield (81%) and with-
out appreciable loss of enantioselectivity (71%, entry 8
vs entry 9).
In summary, we have developed a new, asymmetric cat-
alyst to promote phenyl and alkyl acetylene derivatives
addition to imines. A very simple experimental proce-
dure at room temperature allowed to obtain optically
active propargyl amines in very good yields and enantio-
selectivity up to 81%. The chiral bis-imine ligands are
readily prepared in very high yields from commercially
available materials.
4. For addition of organometallic reagents to chiral imines
see: (a) Bloch, R. Chem. Rev. 1998, 98, 1407; (b) Enders,
D.; Reinhold, U. Tetrahedron: Asymmetry 1997, 8, 1895.
See also: (c) Huffman, M. A.; Yasuda, N.; DeCamp, A. E.;
Grabowski, E. J. J. J. Org. Chem. 1995, 60, 1590; (d)
Frantz, D. E.; Fassler, R.; Oetiker, J.; Carreira, E. M.
Angew. Chem., Int. Ed. 2002, 41, 3054; (e) Frantz, D. E.;
Fassler, R.; Carreira, E. M. J. Am. Chem. Soc. 1999, 121,
1
1245, and references cited therein.
5
. For a few selected examples of interesting methodologies
affording racemic compounds see also: (a) Fischer, C.;
Carreira, E. M. Org. Lett. 2001, 3, 4319; (b) Fischer, C.;
Carreira, E. M. Org. Lett. 2004, 6, 1497; (c) Wei, C.; Li,
Z.; Li, C. J. Org. Lett. 2003, 5, 4473.
We believe that the extremely simple methodology and
the mild reaction conditions, as well as the possibility
of a modular approach for developing new and more
6
. (a) Koradin, C.; Polborn, K.; Knochel, P. Angew. Chem.,
Int. Ed. 2002, 41, 2535; (b) Gommermann, N.; Koradin,
C.; Polborn, K.; Knochel, P. Angew. Chem., Int. Ed. 2003,
42, 5763.
X
X
R
Ligand / Cu(OTf)
HN
N
R
H
7. (a) Traverse, J. F.; Hoveyda, A. H.; Snapper, M. L. Org.
Lett. 2003, 5, 3273. See also: (b) Akullian, L. C.;
Hoveyda, A. H.; Snapper, M. L. Angew. Chem., Int. Ed.
2003, 42, 4244.
Y
Y
1
0-15
8
9
. Wie, C.; Li, C. J. J. Am. Chem. Soc. 2002, 124, 5638.
. Puglisi, A.; Benaglia, M.; Annunziata, R.; Bologna, A.
Tetrahedron Lett. 2003, 44, 2947.
Figure 2. Cu(I) promoted addition of phenyl and alkyl acetylene of
differently substituted imines.
1
0. Suga, H.; Kakehi, A.; Ito, S.; Ibata, T.; Fudo, T.;
Watanabe, Y.; Kinoshita, Y. Bull. Chem. Soc. Jpn. 2003,
Table 2. Enantioselective addition of phenyl and alkyl acetylene to
differently substituted imines
7
6, 189.
1
1. (a) Sanders, C. J.; Gillespie, K. M.; Bell, D.; Scott, P. J.
Am. Chem. Soc. 2000, 122, 7132; (b) Sanders, C. J.;
Gillespie, K. M.; Scott, P. Tetrahedron: Asymmetry 2001,
a
Product Yield Ee
b
Entry Ligand
R
X
Y
H
(
%)
(%)
1
2, 1055.
1
2
3
4
5
6
7
8
9
3
3
3
4
4
3
3
3
3
Ph
Ph
Ph
Ph
Ph
Ph
OMe
H
10
77
55
98
75
53
37
73
91
81
45
41
25
55
27
n.d.
71
73
71
1
2. Binaphthyl diamine is available in both enantiomeric
forms and it costs about three times less than pyridyl-bis-
oxazolines employed by Li and 20 times less than Quinap
used by Knochel. Products 1, 2, 3, 4, 5 were obtained in
OMe 11
H
Cl
H
12
10
OMe
H
OMe 11
9
8%, 85% 91%, 98%, 77% yields, respectively.
H
Tos
H
13
14
15
15
1
3. Vogtle, F.; Thomessen, R.; Steckhan, E.; Schumacher, K.
Tetrahedron Lett. 1985, 26, 2077. Product 6 was obtained
in 97% yield.
4. Reetz, M. T.; Haderlein, G.; Angermund, K. J. Am. Chem.
Soc. 2000, 122, 996. Following the reported procedure, in
our hands, product 7 was obtained in 51% yield after
chromatographic purification.
C
C
C
4
8
8
H
H
H
9
H
17
17
H
H
c
H
H
1
a
b
c
Yields determined after chromatographic purification.
Enantiomeric excess determined by HPLC (Chiracel OD).
Reaction run with 5%mol of catalyst.