Decarboxylative 1,4-Addition of Malonic Acid Half-Thioester
and (CH3)3SiCl, and cyclization proceeded during work-up
to afford (S)-rolipram in 83% yield.
Keywords: asymmetric catalysis · asymmetric synthesis ·
drug design · enantioselectivity · Schiff bases
The results of the control experiments shown in Table 3
suggest that both Ni and La metal centers are essential for
[1] T. Fukuyama, H. Tokuyama, Aldrichimica Acta 2004, 37, 87.
Table 3. Negative control experiments.
2852; b) D. Magdziak, G. Lalic, H. M. Lee, K. C. Fortner, A. D.
works from other group, see: d) S. Orlandi, M. Benaglia, F. Cozzi,
boxylative 1,4-addition of b-keto acids to nitroalkenes, see: b) D. A.
[5] For related catalytic asymmetric decarboxylative Mannich-type reac-
tion of MAHTs, see: a) A. Ricci, D. Pettersen, L. Bernardi, F. Fini,
349, 1037; For related works with cyanocarboxylic acids as donors,
Entry
M1[a]
M2[a]
6 [x mol%]
Yield[b] [%]
ee [%]
1
2
3
4
Ni
Ni
–
–
–
0
13
14
22
29
25
23
2
20
20
20
La
La
ACHTUNGTRENNUNG
A
La
N
1
[a] NiACHTUNGTRENNUNG(OAc)2 and LaACHTUNGTRENNUNG(O-iPr)3 were used as metal sources. [b] Conversion
yield was determined by H NMR analysis
1
high enantioselectivity and reactivity. Ni alone resulted in
poor reactivity and selectivity (entries 1–2). Because the re-
activity and selectivity were similarly poor in entries 1 and
2, we assumed that the phosphine oxide additive would co-
ordinate to the La metal center rather than Ni under the op-
timized reaction conditions (Table 1, entry 11).[17] When per-
forming the reaction with La alone in the absence of Ni,
poor enantioselectivity was observed both in the La/2d=1:1
and 2:1 systems (entries 3–4). Thus, the Ni metal center is
also important for high enantioselectivity. To gain insight
into the reaction pathway, MAHT 3 was treated with
5 mol% of Ni/La/2d/6=1:1:1:2 in the absence of nitroal-
kene. After 24 h at room temperature, only 3.6% of the de-
carboxylated adduct was observed and >95% of unreacted
MAHT was recovered. The results suggested that the pres-
ent system would proceed via 1,4-addition of MAHT to ni-
troalkenes, followed by decarboxylation from the 1,4-adduct
as observed in Shairꢁs Cu-catalyzed aldol reaction of
MAHTs.[3] Further mechanistic studies to clarify the func-
tions of the two metal centers, as well as the precise reaction
mechanism, are ongoing.
[6] A review on stereoselective synthesis of g-amino acids: M. OrdꢂÇez,
C. Cativiela, Tetrahedron: Asymmetry 2007, 18, 3.
[7] A review on asymmetric 1,4-addition to nitroalkenes: a) O. M.
eral reviews on asymmetric 1,4-addition to electron-deficient al-
kenes with metal catalysis: b) J. Christoffers, G. Koripelly, A.
ing examples of metal-catalyzed highly enantioselective 1,4-addition
to nitroalkenes using nucleophiles other than MAHTs, such as 1,3-
dicarbonyl compounds, under proton transfer conditions, see d) J. Ji,
D. M. Barnes, J. Zhang, S. A. King, S. J. Wittenberger, H. E. Morton,
Yang, X. Zhou, L. Lin, L. Chang, X. Liu, X. Feng, Angew. Chem.
M. Furutachi, Z. Chen, H. Mitsunuma, S. Matsunaga, M. Shibasaki,
j) A. Nakamura, S. Lectard, D. Hashizume, Y. Hamashima, M. So-
[8] R. Schmiechen, R. Horowski, D. Palenschat. G. Paschelke, H. Wach-
tel, W. Kehr, U. S. Patent 4012495, 1975.
[9] For a review on bimetallic Schiff base catalysts: R. M. Haak, S. J.
In summary, we developed a new heterobimetallic Ni/La-
salan complex for catalytic asymmetric decarboxylative 1,4-
addition of a malonic acid half-thioester to nitroalkenes.
The previously reported dinucleating Schiff bases 1 did not
afford satisfactory results and a new dinucleating salan-type
ligand 2d was essential to achieve high enantioselectivity
and good reactivity. Further applications of the dinucleating
salan-type ligands to other reactions for which original dinu-
cleating Schiff bases 1 are not suitable, are ongoing.
[10] For heterobimetallic Schiff base catalysts containing rare earth
metals, see: a) S. Handa, V. Gnanadesikan, S. Matsunaga, M. Shiba-
[11] For selected examples of related bifunctional bimetallic Schiff base
complexes in asymmetric catalysis, see: a) V. Annamalai, E. F. Di-
2126; c) W. Li, S. S. Thakur, S.-W. Chen, C.-K. Shin, R. B. Kawthe-
Acknowledgements
This work was supported by Grant-in-Aid for Scientific Research (S) (for
M.S.), Takeda Science Foundation, and for Encouragements for Young
Scientists (A) (for S.M.) from JSPS and MEXT.
Chem. Asian J. 2010, 5, 2351 – 2354
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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