C O M M U N I C A T I O N S
Table 2. Catalytic Enantioselective Strecker Reaction of
Detailed mechanistic studies and further applications of this
methodology to the synthesis of biologically active compounds are
ongoing.
Ketoiminesa
Acknowledgment. Financial support was provided by RFTF
of the Japan Society for the Promotion of Science and PRESTO of
the Japan Science and Technology Corporation.
Supporting Information Available: Experimental procedures and
characterization of the products. This material is available free of charge
References
(1) (a) Iyer, M. S.; Gigstad, K. M.; Namdev, N. D.; Lipton, M. J. Am. Chem.
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E. N. AdV. Synth. Catal. 2001, 343, 197. (f) Ishitani, H.; Komiyama, S.;
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Komiyama, S.; Hasegawa, Y.; Kobayashi, S. J. Am. Chem. Soc. 2000,
122, 762. (h) Krueger, C. A.; Kuntz, K. W.; Dzierba, C. D.; Wirschun,
W. G.; Gleason, J. D.; Snapper, M. L.; Hoveyda, A. H. J. Am. Chem.
Soc. 1999, 121, 4284. (i) Porter, J. R.; Wirschun, W. G.; Kuntz, K. W.;
Snapper, M. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 2657. (j)
Josephsohn, N. S.; Kuntz, K. W.; Snapper, M. L.; Hoveyda, A. H. J. Am.
Chem. Soc. 2001, 123, 11594. (k) Corey, E. J.; Grogan, M. J. Org. Lett.
1999, 1, 157. (l) Takamura, M.; Hamashima, Y.; Usuda, H.; Kanai, M.;
Shibasaki, M. Angew. Chem., Int. Ed. 2000, 39, 1650. (m) Takamura,
M.; Hamashima, Y.; Usuda, H.; Kanai, M.; Shibasaki, M. Chem. Pharm.
Bull. 2000, 48, 1586. (n) Yet, L. Angew. Chem., Int. Ed. 2001, 40, 875.
(2) (a) Vachal, P.; Jacobsen, E. N. Org. Lett. 2000, 2, 867. (b) Vachal, P.;
Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 10012.
(3) Chavarot, M.; Byrne, J. J.; Chavant, P. Y.; Valle´e, Y. Tetrahedron:
Asymmetry 2001, 12, 1147.
(4) For reviews, see: (a) Ohfune, Y.; Harikawa, M. J. Synth. Org. Chem.
1997, 55, 982. (b) Cativiela, C.; Diaz-de-Villegas, M. D. Tetrahedron:
Asymmetry 1998, 9, 3517.
(5) Catalytic asymmetric alkylation is another powerful methodology for
disubstituted R-amino acid synthesis. For recent examples, see: (a) Ooi,
T.; Takeuchi, M.; Kameda, M.; Maruoka, K. J. Am. Chem. Soc. 2000,
122, 5228. (b) Trost, B. M.; Dogra, K. J. Am. Chem. Soc. 2002, 124,
7256.
(6) Yabu, K.; Masumoto, S.; Yamasaki, S.; Hamashima, Y.; Kanai, M.; Du,
W.; Curran, D. P.; Shibasaki, M. J. Am. Chem. Soc. 2001, 123, 9908.
(7) (a) Masumoto, S.; Yabu, K.; Kanai, M.; Shibasaki, M. Tetrahedron Lett.
2002, 43, 2919. (b) Yabu, K.; Masumoto, S.; Kanai, M.; Curran, D. P.;
Shibasaki, M. Tetrahedron Lett. 2002, 43, 2923. Chiral ligands 1 and 3
can be synthesized through 12 steps from triacetyl-D-glucose (ca. 20%
overall yield, not optimized), and are commercially available from Junsei
Chemical Co., Ltd. (Fax: +81-3-3270-5461).
a For a representative procedure, see ref 11. b Isolated yield is after
conversion to the corresponding oxazolidone, unless otherwise noted.
c Isolated yield was determined after purification of 5 by column chroma-
tography. d Determined by chiral HPLC after appropriate conversions. See
the Supporting Information for details. e The absolute configuration was
determined to be (S). f CH3CH2CN/CH2Cl2 ) 4/1 was used as the solvent.
g Ee decreased using 10 mol % of catalyst.
Scheme 1. Conversion of the Products
(8) For the beneficial effects of protic additives on catalytic enantioselective
Strecker reaction of aldoimines, see refs 1h, 1j, 1l, and 1m.
(9) Krzyzanowska, B.; Stec, W. J. Synthesis 1982, 270. For a recent example
of catatlytic enantioselective reaction (hydrogenation) using N-diphen-
ylphosphinoyl ketoimines, see; Spindler, F.; Blaser, H.-U. AdV. Synth.
Catal. 2001, 343, 68.
(10) The product appeared to be silylated 5 in the reaction mixture. The silyl
ether was hydrolyzed during the aqueous workup.
(11) Representative procedure: A solution of Gd(OiPr)3 (0.2 M in THF, 37.5
µL, 0.0075 mmol, purchased from Kojundo Chemical Laboratory Co.,
Ltd. Fax: +81-492-84-1351) was added to a solution of ligand 3 (7.5
mg, 0.015 mmol) in 0.15 mL of THF in an ice bath. The mixture was
stirred for 30 min at 45 °C, and then the solvent was evaporated. After
drying the resulting pre-catalyst under vacuum (∼5 mmHg) for 1 h,
substrate 4a (96 mg, 0.3 mmol) was added as a solid in one portion.
Propionitrile (0.1 mL) and TMSCN (60 µL, 0.45 mmol) were added to
the mixture at -40 °C to start the reaction.
(12) On the basis of the NMR studies, imines 4 appear to exist in a very fast
equilibrium between E and Z isomers. See the Supporting Information
for details.
(13) Formylation was necessary for further conversion of the N-benzyl-protected
aminonitriles to the deprotected amino acid derivatives, due to their lability.
See ref 2.
(14) The crude mixture after workup contains product 5, ligand 3, and the
silylated ligand. The ligand was recoverable after acid hydrolysis in 83%
yield.
also be converted to the saturated derivative 8i (Scheme 1). This
procedure might supplement the moderate enantioselectivity from
primary alkyl-substituted ketoimines.
In conclusion, we achieved a catalytic enantioselective Strecker
reaction with broad substrate generality using N-diphenylphosphi-
noyl ketoimines as substrates. The products could easily be
converted to disubstituted R-amino acids and their derivatives.
JA034980+
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