C O M M U N I C A T I O N S
Table 2. Substrate Scope of Oxidation of Phthalimide Protected
Scheme 1. Three Consecutive Catalytic Steps for the Asymmetric
Synthesis of ꢀ-Amino Acidsa
Allylic Aminesa
a (a) 1% [Ir(COD)Cl]2, 2% (R,R,R)-L, TBD, THF; (b) cat. B; R ) Ph
95%; (c) (i) NaBH4, MeOH; R ) Me 95%; (ii) H2NNH2, EtOH, ∆; R )
Me 90%; (d) (i) 0.5% Mn-tmtacn, Cl3CCO2H, H2O2, H2O, MeCN; R )
Me 87%; (ii) H2NNH2, EtOH, ∆; R ) Me 100%.
condensations.1 Catalytic oxidation of 2 with Mn-tmtacn12 and
subsequent deprotection with hydrazine13 gave the ꢀ-amino acid 8 in
87% yield in two steps. Reduction with 1.0 equiv of NaBH4 and
deprotection with hydrazine gave the ꢀ-amino alcohol 7 (86%).14
In summary, we have demonstrated that a catalytic Wacker-type
oxidation produces selectively aldehydes from allylic phthalimides.
This methodology is used as a key step in a new procedure for the
asymmetric synthesis of a ꢀ3-amino acid involving three consecutive
catalytic steps.
Acknowledgment. This research was supported by the Bio-
Based Sustainable Industrial Chemistry (B-BASIC) programme of
NWO-ACTS in The Netherlands (B.W.).
Supporting Information Available: Spectroscopic data for all
compounds and detailed reaction procedures. This material is available
References
a A: Pd(MeCN)2Cl(NO2) (5 mol %), CuCl2 (20 mol %), tert-BuOH,
O2; 16 h; B: PdCl2 (10 mol %), CuCl (1.0 equiv), DMF/H2O (7:1), O2;
3 d. b By 1H NMR. c Pd(MeCN)2Cl(NO2) (15 mol %), CuCl2 (60 mol
%). d 96% ee.
(1) (a) EnantioselectiVe synthesis of ꢀ-amino acids; Juaristi, E., Soloshonok,
V., Eds.; Wiley-Interscience: New York, 2005. (b) Seebach, D.; Gardiner,
J. Acc. Chem. Res. 2008, 41, 1366. (c) Cheng, R. P.; Gellman, S. H.;
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Catalyst A was used to oxidize branched amine 1k in high yield and
selectivity (Table 2, entry 3). Quartenary amine 1l required a higher
catalyst loading of A, and the aldehyde was isolated in good yield
and a selectivity of 94:6 (Table 2, entry 4). With a benzyl group in
the side chain excellent yield and selectivity were achieved using
catalyst B (Table 2, entry 5). The benzyl protected amino alcohol 1n
was oxidized in 93% yield (Table 2, entry 6). The aromatic substrate
1o as well as the heteroaromatic thienyl amine 1p gave excellent yields
and selectivities (Table 2, entries 7-8). The internal olefin 1q could
be converted selectively to the ꢀ-ketone by using catalyst A (Table 2,
entry 9). However, 2-methyl-substituted olefin 1r could not be oxidized
with any of the catalysts (Table 2, entry 10).
(2) Hinterman, L. In Transition metals for organic synthesis; Beller, M., Bolm,
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The high selectivity for the anti-Markovnikov oxidation7 to the
aldehyde with these catalysts might result from coordination of the
protecting group with the palladium catalyst.8 Additionally, an
electronic effect of the nitrogen protecting group can play a role,
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conversion to the ketones (Table 1, entries 6 and 11).
We envisioned that the new aldehyde selective oxidation allows
the asymmetric synthesis of ꢀ3-amino acids from allylic compounds
using three consecutive catalytic transformations (Scheme 1). In an
asymmetric allylic amination, allylic carbonate 6 reacted with phthal-
imide to 1o with 96% ee catalyzed by an iridium/phosphoramidite
complex (Scheme 1).9,10 The subsequent oxidation did not affect the
stereochemistry, and aldehyde 2o was obtained with 96% ee (Table
2, entry 7).11 This catalytic (asymmetric) synthesis of amino aldehydes
provides an alternative to current methods to prepare this class of
compounds, e.g., using amino acids, amino alcohols, or Mannich
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Kiers, N. L.; Feringa, B. L. Tetrahedron Lett. 1992, 33, 2403.
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J. Inorg. Chem. 2004, 1330. (b) Fairlamb, I. J. S.; Kapdi, A. R.; Lee, A. F.;
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(10) Feringa, B. L. Acc. Chem. Res. 2000, 33, 346.
(11) The ee was determined after derivatization to the diacyl acetal.
(12) This compromises a new catalytic aldehyde to acid transformation; see
also: De Boer, J. W.; Brinksma, J.; Browne, W. R.; Alsters, P. L.; Hage,
R.; Feringa, B. L. J. Am. Chem. Soc. 2005, 127, 7990.
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(14) Clive, D. L. G.; Wang, J.; Yu, M. Tetrahedron Lett. 2005, 46, 2853.
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9474 J. AM. CHEM. SOC. VOL. 131, NO. 27, 2009