Synthesis of a novel type of chiral bisphosphine ligand (NORPHOS-7-NEt2) with an amino group for neighboring participation in asymmetric allylic alkylation

Article abstract of DOI:10.1055/s-1998-1578

A new chiral bisphosphine ligand, NORPHOS-T-NEt₂, with an amino group has been prepared. It has been applied to the Pd-catalyzed asymmetric allylic alkylation of rac-(E)-diphenyl-2-propenyl pivalate upon using (25,3S,7R)-NORPHOS-7-NEt₂ (1) (M-Chirality) having an amino group on the ligand, the same absolute configuration product was obtained as compared to using (2R,3R)-NORPHOS (P-Chirality). This result clearly indicated the possibility of the interaction of the amino group on the ligand with the incoming nucleophile.

Full text of DOI:10.1055/s-1998-1578

January 1998
SYNLETT
45
Synthesis of a Novel Type of Chiral Bisphosphine Ligand (NORPHOS-7-NEt ) with an Amino
2
1
Group for Neighboring Participation in Asymmetric Allylic Alkylation
Issei Achiwa, Akira Yamazaki, and Kazuo Achiwa*
School of Pharmaceutical Science, University of Shizuoka, 52-1 Yada, Shizuoka 422, Japan
Received 6 October 1997
Abstract: A new chiral bisphosphine ligand, NORPHOS-7-NEt , with
2
an amino group has been prepared. It has been applied to the Pd-
catalyzed asymmetric allylic alkylation of rac-(E)-diphenyl-2-propenyl
pivalate upon using (2S,3S,7R)-NORPHOS-7-NEt (1) (M-Chirality)
2
having an amino group on the ligand, the same absolute configuration
product was obtained as compared to using (2R,3R)-NORPHOS (P-
Chirality). This result clearly indicated the possibility of the interaction
of the amino group on the ligand with the incoming nucleophile.
Recently we synthesized a novel type of chiral bisphosphine ligand
2
3
BHMP-7-X and NORPHOS-7-X with a carboxyl group which was
found to be efficient for palladium-catalyzed asymmetric allylic
2
4
5
3
alkylation, amination, cyclization and asymmetric hydrogenation by
interaction of a carboxyl group on the phosphine ligand with the
incoming nucleophile and the substrate.
6
Figure 1
In connection of this work, we planned to introduce an amino group as a
7
hetero-functional group on NORPHOS. The synthetic route to the
optically active bisphosphine ligand (S,S)-NORPHOS-7-NEt ((S,S)-1)
2
is shown in Scheme 1.
Synthesis of (2S,3S)-7 was carried out according to the methods in our
3
previous work and the following etherification of (S,S)-7 with N,N-
Scheme 1
diethyl chloroacetamide gave (S,S)-8 in 81% yield. Reduction of (S,S)-8
with diborane at 80 °C gave (S,S)-9 in 70% yield. Final reduction of the
phosphine oxide 9 was achieved by heating with HSiCl -NEt in
3
3
toluene under an atomosphere of argon followed by treatment with 30%
8
NaOH aq. to give (S,S)-NORPHOS-7-NEt ((S,S)-1) in 68% yield.
2
Asymmetric allylic substitution reaction of 1,3-diphenyl-2-propenyl
pivalate 10 (0.5 mmol) with the nucleophile produced by mixing
dimethyl malonate, N,O-bis(trimethylsilyl)acetamide (BSA), and
lithium acetate as a catalyst was carried out at room temperature for 48
hr using a palladium complex generated in situ from a chiral ligand
9
(0.05 mmol) and [Pd(π-C H )Cl] (0.0125 mmol) as catalyst. The
3
5
2
results are summarized in the Table.
The Pd-catalyzed asymmetric allylic alkylation of 10 with (S,S)-1 (M-
10
Chirality) gave (R)-11 of the same absolute configuration as the
product (R)-11 obtained with (R,R)-NORPHOS (P-Chirality). This
result clearly indicates the interaction of the amino group on the ligand
with the incoming nucleophile and the importance of the neighboring
11,12
participation in enantioselection of asymmetric allylic alkylation.
Another explanation that the NORPHOS-7-NEt ligand forms an
2
13
aminophosphine-Pd complex to catalyze the asymmetric allylic
alkylation with high optical yield may be unreasonable, because of the

46
LETTERS
SYNLETT
conformational flexibility of the eight-membered aminophosphine-Pd
complex and also the lack of the asymmetric environment near the
amino group.
Asymmetry, 7, 403 (1996).
(6) T. Hayashi, N. Kawamura, and Y. Ito, J. Am. Chem. Soc.,
109,7876 (1987), T. Hayashi, M. Sawamura, and Y. Ito,
Tetrahedron, 48, 1999 (1992), M. Sawamura, and Y. Ito, Chem.
Rev., 92, 857 (1992) and the references cited therein.
In summary, a new bisphosphine ligand, (2S,3S,7R)-NORPHOS-7-
NEt ((S,S)-1) having an amino group as a neighboring participating
2
group was synthesized and found to be efficient for palladium complex-
catalyzed asymmetric allylic alkylation.
(7) H. Brunner, W. Pieronczyk, B. Schonhammer, K. Steng, L.
Bernal, and J. Korp, Chem. Ber., 114, 1137 (1981).
24
(8) (2S,3S,7R)-1: [α]
+9.0 (c 1.57, CHCl ).
3
D
Acknowledgement
(9) B. M. Trost, and D. L. Van Vranken, Chem. Rev., 96, 395 (1996)
This work was partly supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Japan.
and the references cited therein.
(10) S. Sakuraba, T. Morimoto, and K. Achiwa, Tetrahedron:
Asymmetry, 2, 597 (1991).
(11) T. Hayashi, A. Yamamoto, T. Hagihara, and Y. Ito, Tetrahedron
Lett., 27, 191 (1986). (R)-(S)-BPPF-X (P-Chirality) having diol as
a neighboring participation group gave (S)-11 in 48%ee yield.
References and Notes
(1) Asymmetric Reactions Catalyzed by Chiral Metal Complexes.
LXXIX.
(12) BHMP-7X having a carboxyl group as a neighboring participating
group was found to be efficient for asymmetric allylic amination
of 10 to give (R)-amino-compounds in high optical yield by
(2) A. Yamazaki, T. Morimoto, and K. Achiwa, Tetrahedron:
Asymmetry, 4, 2287 (1993).
3-5
interaction of the carboxylate group and the amino group.
(3) A. Yamazaki, I. Achiwa, K. Horikawa, M. Tsurubo, and K.
(13) Efficient aminophosphine ligands form five- or six-membered Pd
complexes and have the asymmetric environment near the amino
Achiwa, Synlett, 455 (1997).
(4) A. Yamazaki, and K. Achiwa, Tetrahedron: Asymmetry, 6, 51
9
group. ( P. van Matt, and A. Pfaltz, Angew. Chem., Int. Ed. Engl.,
(1995).
32, 566 (1993), J. Sprinz, M. Kiefer, G. Helmchen, and M.
Reggelin, Tetrahedron Lett., 35, 1523 (1994), H. Kubota, and K.
Koga, Tetrahedron Lett., 35, 6689 (1994)).
(5) A. Yamazaki, and K. Achiwa, Tetrahedron: Asymmetry, 6, 1021
(1995), A. Yamazaki, I. Achiwa, and K. Achiwa, Tetrahedron: