Catalytic asymmetric synthesis of a nitrogen analogue of dialkyl tartrate by direct mannich reaction under phase-transfer conditions

Article abstract of DOI:10.1021/ol049215u

(Equation Presented) Phase-transfer-catalyzed direct Mannich reaction of glycinate Schiff base 3 with α-imino ester 4 has been accomplished with high enantioselectivity by the utilization of N-spiro C₂-symmetric chiral quaternary ammonium bromi

Full text of DOI:10.1021/ol049215u

ORGANIC
LETTERS
2004
Vol. 6, No. 14
2397-2399
Catalytic Asymmetric Synthesis of a
Nitrogen Analogue of Dialkyl Tartrate by
Direct Mannich Reaction under
Phase-Transfer Conditions
Takashi Ooi, Minoru Kameda, Jun-ichi Fujii, and Keiji Maruoka*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity,
Sakyo, Kyoto 606-8502, Japan
maruoka@kuchem.kyoto-u.ac.jp
Received April 28, 2004
ABSTRACT
Phase-transfer-catalyzed direct Mannich reaction of glycinate Schiff base 3 with r-imino ester 4 has been accomplished with high enantioselectivity
by the utilization of N-spiro C -symmetric chiral quaternary ammonium bromide 2 as a catalyst. This methodology enables the catalytic asymmetric
2
synthesis of differentially protected 3-aminoaspartate, a nitrogen analogue of dialkyl tartrate. The product (syn-5) was converted into a precursor
(6) of streptolidine lactam.
Natural and unnatural tartaric acids and their derivatives are
undoubtedly one of the most familiar and readily available
chiral molecular units, and during the past few decades, we
have witnessed a dramatic increase in their fruitful applica-
tions, resulting in valuable contributions particularly in
modern asymmetric synthesis.1 Surprisingly, however, the
corresponding nitrogen analogues 1, 3-aminoaspartates, have
received little attention despite their potential utility as
C2-symmetric chiral ligands for the design of new chemo-
therapeutic agents2 as well as asymmetric catalysts.3 Asym-
metric syntheses of 1, using stoichiometric amounts of chiral
sources, have been reported.4 The recently disclosed Mannich
protocol using chiral Lewis acids from the Jørgensen
group5 and Yudin’s stereoselective alkylation strategy with
the Pd(OAc)2/BINAP system6 are the only examples of
catalytic methods for the preparation of 1. In this letter, we
report catalytic asymmetric synthesis of nitrogen analogues
of dialkyl tartrate by the highly enantioselective direct
Mannich reaction of glycine derivative 3 with R-imino ester
4 under phase-transfer conditions (Scheme 1). The usefulness
of this new method has been demonstrated in its application
to the concise stereoselective construction of a precursor of
Streptolidine lactam, taking full advantage of a differentially
protected tartrate nitrogen analogue.
(1) For representative reviews, see: (a) Johnson, R. A.; Sharpless, K.
B. In Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley-
VCH: New York, 2000; Chapter 6A, p 231. (b) Seebach, D.; Beck, A. K.;
Heckel, A. Angew. Chem., Int. Ed. 2001, 40, 92.
(2) Reviews: (a) Sundquist, W. I.; Lippard, S. J. Coord. Chem. ReV.
1990, 100, 293. (b) Lucet, D.; Le Gall, T.; Mioskowski, C. Angew. Chem.,
Int. Ed. 1998, 37, 2581. See also: (c) Hunt, S. In Chemistry and
Biochemistry of the Amino Acids; Barret, G. C., Ed.; Chapman and Hall:
London, 1985; Chapter 4.
(4) (a) Ferna´ndez-Meg´ıa, E.; Paz, M. M.; Sardina, F. J. J. Org. Chem.
1994, 59, 7643. (b) Alvarez-Ibarra, C.; Csa´ky¨, A. G.; Colmenero, B.;
Quiroga, M. L. J. Org. Chem. 1997, 62, 2478.
(5) Bernardi, L.; Gothelf, A. S.; Hazell, R. G.; Jørgensen, K. A. J. Org.
Chem. 2003, 68, 2583.
(3) Review: Togni, A.; Venanzi, L. M. Angew. Chem., Int. Ed. Engl.
1994, 33, 497.
(6) Chen, Y.; Yudin, A. K. Tetrahedron Lett. 2003, 44, 4865.
10.1021/ol049215u CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/16/2004

Scheme 1
Upon examining the direct Mannich reaction of the
conditions resulted in the production of 5 in 41% yield.8
Fortunately, preferential formation of the syn isomer (syn/
anti ) 74:26) was observed with 79% ee for product syn-5
(entry 2). Here, we assumed that the low chemical yield was
partly due to the instability of R-imino ester 4 under the
reaction conditions. This was overcome by conducting the
reaction at -20 °C to give Mannich adduct 5 in 73% yield
(syn/anti ) 79:21, 85% ee for syn-5) (entry 3). Switching to
catalyst 2b,7d which contains a 3,4,5-trifluorophenyl group,
further enhanced the enantioselectivity, giving 5 in 79% yield
(syn/anti ) 76:24) with 87% ee (syn isomer) (entry 4). In
contrast, catalyst 2c, with radially extended 3,3′-aromatic
substituents, significantly diminished both the chemical yield
and the enantiomeric excess (entry 5). The use of mesitylene
in place of toluene improved only the diastereoselectivity in
the reaction with 2a (entry 6). However, the solvent effect
was found to be beneficial not only for the syn selectivity
but also for the enantioselectivity under the influence of 2b,
leading to 91% ee of syn-5 (88% yield, syn/anti ) 82:18)
(entry 7).
benzophenone Schiff base of tert-butyl glycinate 3 with
R-imino ester 4 under phase-transfer conditions using chiral
quaternary ammonium bromide of type 2 as a catalyst,7 our
initial concern was about the relative configuration of the
Mannich adduct 5, since only the syn isomer is optically
active. Attempted reaction of 3 with 4 in the presence of
2a7c (2 mol %) in toluene-1% aqueous NaOH at 0 °C
showed almost no indication of product formation after
stirring for 6 h (entry 1 in Table 1). Therefore, we screened
various concentrations of aqueous NaOH and found that the
use of 17% (5 N) aqueous NaOH under otherwise similar
Table 1. Direct Catalytic Asymmetric Mannich Reaction of
Glycine Derivative 3 with R-Imino Ester 4 under Phase-Transfer
Conditionsa
The synthetic utility of the differentially protected tartaric
acid nitrogen analogue, syn-5, was highlighted by its ap-
plication to the facile asymmetric synthesis of an attractive
precursor 6 of streptolidine lactam.9 Streptolidine lactam
constitutes the core structure of streptothricine antibiotics,10
a family of potent antibiotics isolated from microbial
sources.11 As illustrated in Scheme 2, 5 (syn/anti mixture)
was initially transformed to the cyclic urea 7 with triphos-
condition
(°C, h) (syn/ anti)c (configuration)e
% yieldb
% eed
entry catalyst
solvent
toluene
1f
2
3
4
5
6
7
2a
2a
2a
2b
2c
2a
2b
0, 6
trace
0, 6
41 (74:26)
73 (79:21)
79 (76:24)
49 (80:20)
88 (82:18)
88 (82:18)
79
85
87
50
84
91
-20, 6
-20, 6
-20, 6
-20, 6
-20, 6
mesitylene
a Unless otherwise specified, the reaction (0.2 mmol scale) was carried
out with 2 equiv of 4 and 17% NaOH aqueous solution (0.6 mL) in the
presence of 2 mol % of 2 under the given reaction conditions (2 mL of
solvent). b Isolated yield. c Diastereomeric ratio was determined by 1H NMR
analysis. d Enantiopurity of syn-5, which was determined by HPLC analysis
using a chiral column (DAICEL Chiralpak AD-H) with hexane-2-propanol
as a solvent. e For the assignment of the absolute configuration of the syn
isomer, see Supporting Information. f Performed with 1% NaOH as an
aqueous base.
(7) (a) Maruoka, K.; Ooi, T. Chem. ReV. 2003, 103, 3013. See also: (b)
Ooi, T.; Doda, K.; Maruoka, K. Org. Lett. 2001, 3, 1273. (c) Ooi, T.;
Taniguchi, M.; Kameda, M.; Maruoka, K. Angew. Chem., Int. Ed. 2002,
41, 4542. (d) Ooi, T.; Kameda, M.; Maruoka, K. J. Am. Chem. Soc. 2003,
125, 5139.
(8) Representative results of the Mannich reaction of 3 with NaOH
aqueous solutions of different concentrations are as follows: 10% NaOH,
11% yield (syn/anti ) 70:30), 77% ee (syn isomer); 25% NaOH, 43% yield
(71:29), 78% ee; 50% NaOH, 81% yield (79:21), 6% ee.
2398
Org. Lett., Vol. 6, No. 14, 2004

Scheme 2 a
a Reaction conditions: (a) triphosgene, Et3N, CH2Cl2, rt, 69%, 99% ee (trans-7 after a single recrystallization); (b) DIBAH, ether-
CH2Cl2, -78 °C, then Me3SiCN, -78∼0 °C, 80% (dr ) 1:1.5); (c) H2, PtO2, AcOH, rt, 90%; (d) anisaldehyde, Na2SO4, CH2Cl2, rt, then
NaBH4, EtOH, 0 °C, 71%; (e) HCO2H, 60 °C, then DPPA, Et3N, DMF, 65%; (f) (Boc)2O, Et3N, CH2Cl2, 0 °C∼rt, 98%; (g) (COCl)2,
DMSO, Et3N, CH2Cl2, -78 °C, 97%; (h) ZnBH4, ether, 0 °C, 53%.
gene, in which two diastereomers could be easily separated
by simple chromatography and a single recrystallization
provided essentially enantiopure trans-7 in 69% yield (based
on 5). The subsequent selective reduction-cyanation of the
ethyl ester moiety was achieved by the sequential treatment
of trans-7 with DIBAH and Me3SiCN in ether-CH2Cl2,
furnishing the desired cyanohydrin 8 in 80% yield as a
mixture of two diastereomers. Hydrogenation of 8 gave the
primary amine, which was protected with p-methoxybenzyl
group by reductive amination. The requisite stereoisomer of
the resulting amino alcohol 10 was then converted to 11 via
acidic hydrolysis of the tert-butyl ester with formic acid and
the consecutive intramolecular formation of amide linkage
using diphenylphosphoryl azide (DPPA) in 65% yield. It is
noted that the stereochemistry of the hydroxy-bearing carbon
of the other isomer epi-10 can be inverted, after the
introduction of a tert-butoxycarbonyl group on the amino
alcohol nitrogen, by Swern oxidation and reduction with
ZnBH4 to give 11, an appropriate candidate for similar
intramolecular condensation.
In summary, phase-transfer-catalyzed direct Mannich
reaction of a glycine donor with R-imino ester has been
accomplished with high enantioselectivity by the use of
C2-symmetric chiral quaternary ammonium bromide as a
catalyst. This methodology enables the catalytic asymmetric
synthesis of 3-aminoaspartate, a nitrogen analogue of dialkyl
tartrate. Product 5, with differentiated ester groups, was
converted into 8, a precursor of streptolidine lactam. The
present finding should stimulate further research into utiliza-
tion of this class of chiral compounds.
(9) For recent synthetic efforts using 3-aminoaspartate as a key inter-
mediate, see: (a) Ferna´ndez-Meg´ıa, E.; Sardina, F. J. Tetrahedron Lett.
1997, 38, 673. (b) Ferna´ndez-Meg´ıa, E.; Iglesias-Pintos, J. M.; Sardina, F.
J. J. Org. Chem. 1997, 62, 4770. From carbohydrates: (c) Goto, T.; Ohgi,
T. Tetrahedron Lett. 1974, 1413. (d) Kusumoto, S.; Tsuji, S.; Shiba, T.
Tetrahedron Lett. 1974, 1417. (e) Kusumoto, S.; Tsuji, S.; Shiba, T. Bull.
Chem. Soc. Jpn. 1974, 47, 2690. (f) Kusumoto, S.; Tsuji, S.; Shima, K.;
Shiba, T. Bull. Chem. Soc. Jpn. 1976, 49, 3611.
(10) For the total synthesis of streptothricine, see: Kusumoto, S.; Imaoka,
S.; Kambayashi, Y.; Shiba, T. Tetrahedron Lett. 1982, 23, 2961.
(11) (a) Carter, H. E.; Clark, R. K., Jr.; Kohn, P.; Rothrock, J. W.; Taylor,
W. R.; West, C. A.; Whitfield, G. B.; Jackson, W. G. J. Am. Chem. Soc.
1954, 76, 566. (b) Nakanishi, K.; Ito, T.; Hirata, Y. J. Am. Chem. Soc.
1954, 76, 2845. (c) Brockmann, H.; Musso, H. Chem. Ber. 1955, 88, 648.
(d) Borders, D. B.; Hausmann, W. K.; Wetzel, E. R.; Patterson, E. L.
Tetrahedron Lett. 1967, 4187. (e) Borders, D. B.; Sax, K. J.; Lancaster, J.
E.; Hausmann, W. K.; Mitscher, L. A.; Wetzel, E. R.; Patterson, E. L.
Tetrahedron 1970, 26, 3123. (f) Kawakami, Y.; Yamasaki, K.; Nakamura,
S. J. Antibiot. 1981, 34, 921. (g) Kido, Y.; Furuie, T.; Suzuki, K.; Sakamoto,
K.; Yokoyama, Y.; Ueda, M.; Kinjyo, J.; Yahara, S.; Nohara, T.; Shibata,
M. J. Antibiot. 1987, 40, 1698.
Acknowledgment. This work was partially supported by
a Grant-in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.
M.K. is grateful to the Japan Society for the Promotion of
Science for Young Scientists for a Research Fellowship.
Supporting Information Available: Detailed experi-
mental procedure as well as spectroscopic characterization
of new compounds (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
OL049215U
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