One-Pot, Large-Scale Synthesis of Nickel(II)
Complexes Derived from
2-[N-(r-Picolyl)amino]benzophenone (PABP) and
r- or â-Amino Acids
Guanghui Deng,† Jiang Wang,† Yu Zhou,†,‡
Hualiang Jiang,†,§ and Hong Liu*,†
Drug DiscoVery and Design Centre, State Key Laboratory of
Drug Research, Shanghai Institute of Materia Medica, Graduate
School of the Chinese Academy of Sciences, Shanghai Institutes
for Biological Sciences, Chinese Academy of Sciences, 555
Zuchongzhi Road, Shanghai 201203, China, School of
Pharmaceutical Engineering, Shenyang Pharmaceutical
UniVersity, Shenyang, Liaoning 110016, China, and School of
Pharmacy, East China UniVersity of Science and Technology,
Shanghai 200237, China
FIGURE 1. Ni(II) complexes derived from PABP and R- or â-amino
acids.
tailor-made approach for preparing various nonproteingenic
amino acids, in particular, structurally complex and sterically
constrained derivatives.4 The Ni(II) complex of glycine Schiff’s
base GlyNi(II)PABP (1a, Figure 1), which emerged as a new
type of efficient and highly reactive achiral nucleophilic glycine
equivalent,5 has several unique features. The Ni(II) complex
1a is achiral nucleophilic glycine equivalent to offer a stere-
ochemically reliable and efficient homologation via alkyl halide
alkylation and Michael addition reaction.5a,c Furthermore, the
nucleophilic glycine equivalent 1a features attractive physico-
chemical characteristics such as high stability in strong bases,
high crystallinity, convenient purification, and megatemperature
tolerance.6 The preparation of 1a and practical synthesis of
various R-amino acids with 1a are well-documented by Be-
lokon’s group5a,6b,7 and Soloshonok’s group5d,6a,d,8 (Scheme 1).
However, Belokon’s route, which employed excess SOCl2 for
the ligand 3 preparation, not only led to incomplete transforma-
tion and generally low chemical yields but also led to laborious
purification prior to its use for Ni(II) complex formation.2a,9
Soloshonok’s procedure although improved the overall yield
(up to 93%),5d,9 but requires inconvenient inert atmosphere
ReceiVed May 26, 2007
A
one-pot, large-scale procedure for preparing the
Belokon-Soloshonok nucleophilic glycine equivalent 2-[N-
(R-picolyl)amino]benzophenone (PABP) derived Ni(II) com-
plex [GlyNi(II)PABP] is described. It has been accomplished
by using isobutyl chloroformate to form PABP and then
NaH/KOH as mixed bases to afford the corresponding
complexes in a one-pot manner (up to an overall yield of
98%). The potential of this method for preparation of
â-amino acids derivatives, such as â-AlaNi(II)PABP and
â-PheNi(II)PABP, has been demonstrated. The structure of
â-AlaNi(II)PABP is characterized by single-crystal X-ray
diffraction.
(2) (a) Belokon, Y. N.; Bespalova, N. B.; Churkina, T. D.; Cisarova, I.;
Ezernitskaya, M. G.; Harutyunyan, S. R.; Hrdina, R.; Kagan, H. B.;
Kocovsky, P.; Kochetkov, K. A.; Larionov, O. V; Lyssenko, K. A.; North,
M.; Polasek, M.; Peregudov, A. S.; Prisyazhnyuk V. V.; Vyskocil S. J.
Am. Chem. Soc. 2003, 125, 12860-12871. (b) Soloshonok, V. A.; Cai, C.;
Yamada, T.; Ueki, H.; Ohfune, Y.; Hruby, V. J. J. Am. Chem. Soc. 2005,
127, 15296-15303. (c) Soloshonok, V. A.; Yamada, T.; Ueki, H.; Moore,
A. M.; Cook, T. K.; Arbogast, K. L.; Soloshonok, A. V.; Martin, C. H.;
Ohfune, Y. Tetrahedron 2006, 62, 6412-6419.
(3) (a) Juaristi, E.; Delia Quintana, D.; Lamatsch, B.; Seebach, D. J.
Org. Chem. 1991, 56, 2553-2557. (b) Monique, C.; Francoise, E.; Christele
G.; Marc, R.; Jean, M. Eur. J. Org. Chem. 2000, 2459-2466.
(4) (a) Tararov, V. I.; Savel’eva, T. F.; Kuznetsov, N. Y.; Ikonnikov, N.
S.; Orlova, S. A.; Belokon, Y. N.; North, M. Tetrahedron: Asymmetry 1997,
8, 79-83. (b) Xu, P.-F.; Chen, Y.-S.; Lin, S.-I.; Lu, T.-J. J. Org. Chem.
2002, 66, 2309-2314.
(5) (a) Belokon, Y. N.; Kochetkov, K. A.; Churkina, T. D.; Ikonnikov,
N. S.; Larionov, O. V.; Harutyunyan, S. R.; Vyskocil, S.; North, M.; Kagan,
H. B. Angew. Chem., Int. Ed. 2001, 40, 1948-1951. (b) Belokon, Y. N.;
Maleev, V. I.; Saveleva, T. F.; Garbalinskaya, N. S.; Saporovskaya, M. B.;
Bakhmutov, V. I.; Belikov, V. M. IzV. Akad. Nauk SSSR, Ser. Khim. 1989,
47, 631-635. (Bull. Acad. Sci. USSR, DiV. Chem. Sci. 1989, 37, 557-
562.) (c) Soloshonok, V. A.; Cai, C.; Hruby, V. J. J. Org. Chem. 2000, 65,
6688-6696. (d) Ellis, T. K.; Martin, C. H.; Ueki, H.; Soloshonok, V. A.
Tetrahedron Lett. 2003, 44, 1063-1066.
(6) (a) Ellis, T. K.; Hochla, V. M.; Soloshonok, V. A. J. Org. Chem.
2003, 68, 4973-4976. (b) Belokon, Y. N.; Kochetkov, K. A.; Churkina, T.
D.; Ikonnikov, N. S.; Orlova, S. A.; Smirnov, V. V.; Chesnokov, A. A.
MendeleeV Commun. 1997, 137-138. (c) Belokon, Y. N.; Kochetkov, K.
A.; Churkina, T. D.; Ikonnikov, N. S.; Chesnokov, A. A.; Larionov, O. V.;
Parma`r, V. S.; Kumar, R.; Kagan, H. B. Tetrahedron: Asymmetry 1998, 9,
851-857. (d) Soloshonok, V. A.; Cai, C.; Hruby, V. J. Tetrahedron Lett.
2000, 41, 135-139.
Nonproteingenic R- or â-amino acids have attracted tremen-
dous attention recently.1 They are widely utilized for biological,
biochemical, pharmaceutical, and asymmetric chemical inves-
tigations. Among various methods available to prepare R- or
â-amino acids in the literature, homologation of R- or â-amino
acids such as glycine2 or â-alanine3 equivalents is a direct, facile,
* Address correspondence to this author. Phone: +86-21-50807042. Fax:
+86-21-50807088.
† Chinese Academy of Sciences.
‡ Shenyang Pharmaceutical University.
§ East China University of Science and Technology.
(1) (a) Chiu, H.-P.; Suzuki, Y.; Gullickson, D.; Ahmad, R.; Kokona, B.;
Fairman, R.; Cheng, R. P. J. Am. Chem. Soc. 2006, 128, 15556-15557.
(b) Katritzky, A. R.; Tao, H.; Jiang, R.; Suzuki, K.; Kirichenko, K. J. Org.
Chem. 2007, 72, 407-414.
10.1021/jo071011e CCC: $37.00 © 2007 American Chemical Society
Published on Web 10/19/2007
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J. Org. Chem. 2007, 72, 8932-8934