Catalytic, enantioselective propargyl- and allenylation reactions of α-imino ester

Article abstract of DOI:10.1246/cl.2002.298

Catalytic, enantioselective propargyl- and allenylation reactions of α-imino ester have been achieved by means of the [Cu(MeCN)₄]ClO₄/(R)-tol-BINAP catalyst to afford the corresponding propargyl- and allenyl-substituted α-amino acid

Full text of DOI:10.1246/cl.2002.298

298
Chemistry Letters 2002
Catalytic, Enantioselective Propargyl- and Allenylation Reactions of ꢀ-Imino Ester
Hirotaka Kagoshima, Tetsumaru Uzawa, and Takahiko Akiyamaꢀ
Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588
(Received December 21, 2001; CL-011284)
Table 1. Effect of catalysts in the reaction of 1 with 2aa
Catalytic, enantioselective propargyl- and allenylation reac-
tions of ꢀ-imino ester have been achieved by means of the
[Cu(MeCN)4]ClO4/(R)-tol-BINAP catalyst to afford the corre-
sponding propargyl- and allenyl-substituted ꢀ-amino acid
derivatives, respectively, in good yields with good enantiomeric
excesses.
Chiral Lewis acid-catalyzed, enantioselective addition reac-
tions of imines with carbon nucleophiles provide a powerful
method for the synthesis of a variety of optically active nitrogen
compounds.1 When the reaction was carried out with ꢀ-imino
esters as imine substrates, optically active ꢀ-amino acid
derivatives could be obtained. Catalytic, enantioselective addi-
tion reactions of ꢀ-imino esters with carbon nucleophiles have
been recently reported.2{6 In addition to the above reactions, we
anticipated that the catalytic, enantioselective addition reactions
of ꢀ-imino esters with allenyl- and propargyl organometallics
would provide a useful route for the synthesis of optically active
propargyl- and allenyl-substituted ꢀ-amino acid derivatives,
respectively. These compounds have been prepared by using a
stoichiometric amount of chiral sources7 or by enzymatic
resolution8 so far, and the catalytic, enantioselective propargyl-
and allenylation reactions of imines have not been achieved yet
irrespective of potential utility of the resultant products: They are
(1) known to exhibit interesting biological activities9 and (2)
expected to be important synthetic intermediates for the synthesis
of a number of unnatural ꢀ-amino acid derivatives because the
2 and 3). In addition, the reaction using a Cu(OTf)2/(R)-tol-
BINAP combination proceeded with a comparable enantiomeric
excess though the yield of the product became lower (entry 4). In
the presence of [Cu(MeCN)4]ClO4/(R)-tol-BINAP catalyst,
better yield was obtained when a slightly excess amount of 1
was employed (entry 5). Lowering the reaction temperature to
À30 ꢁC further improved the enantiomeric excess to 86% (entry
6).
The absolute configuration of 3a was unambiguously
determined to be S by conversion of both 3a and commercially
available (S)-2-aminopentanoic acid (5) into a common inter-
mediate 6 as shown in Scheme 1.
carbon-carbon
multiple
bonds
can
be
readily
functionalized.7d,9b,10 In this paper, we report the first catalytic,
enantioselective propargyl- and allenylation reactions of ꢀ-imino
ester with allenyl- and propargyltins, which afford optically
active propargyl- and allenyl-substituted ꢀ-amino acid deriva-
tives, respectively.11
We have initially investigated the reaction of ꢀ-imino ester 1
with allenyltributyltin (2a) under the various conditions to
examine the effect of catalysts on yields and enantiomeric
excesses (Table 1). We have chosen the copper/chiral diphos-
phine catalysts since they have shown to be the most promising
for the enantioselective reactions using ꢀ-imino esters.2b,c,3{6 In
the presence of the chiral Lewis acid catalyst (1 mol%) prepared
from [Cu(MeCN)4]ClO4 and (R)-tol-BINAP12 in ether at room
temperature, 1 (1.0equiv) smoothly reacted with 2a (1.1 equiv) to
give a mixture of the two regioisomers, 3a and 4a, in 78% yield
(entry 1). The reaction proceeded with SE20 manner, and the
regioselectivity was quite high (3a : 4a ¼ >97 : <3). The
enantiomeric excess of the major product 3a was 80%. Choice
of the Lewis acid and chiral diphosphine ligand combination is
crucial in order to obtain both good yields and enantiomeric
excesses. For example, use of the chiral Lewis acid catalysts
prepared from [Cu(MeCN)4]ClO4 and either (R)-BINAP12 or
(R,R)-DIOP12 resulted in inferior enantiomeric excesses (entries
Scheme 1. Determination of the absolute configuration of 3a.
Under the optimized conditions, catalytic, enantioselective
propargylation reactions using allenyltin reagents were carried
out (Table 2).13 It was found that the nature of the substituents on
the tin atom slightly affected both yields and enantiomeric
excesses. When allenyltriphenyltin (2b) was subjected to the
reaction, a mixture of 3a and 4a was produced in 38% yield, and
the enantiomeric excess of 3a was 77% (entry 2). Electron-
withdrawing group significantly decreased the nucleophilicity of
allenyltin 2, thus the reaction using 2c did not proceed completely
(entry 3).
We have anticipated that in place of allenyltins, propargyltins
would react with 1 to produce corresponding allenyl-substituted
amino ester in a fashion of SE20. Then, we have focused on
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
299
Table 2. Catalytic, enantioselective propargyl- and allenylation reactionsa
Massy-Westropp, and P. Razzino, Tetrahedron, 51, 4183 (1995). c) K.
Tanaka, M. Ahn, Y. Watanabe, and K. Fuji, Tetrahedron: Asymmetry, 7,
1771 (1996). d) S. Collet, P. Bauchat, R. Danion-Bougot, and D.
Danion, Tetrahedron: Asymmetry, 9, 2121 (1998). e) N. J. Church and
D. W. Young, J. Chem. Soc., Perkin Trans. 1, 1998, 1475.
J. P. Scannell, D. L. Pruess, T. C. Demny, F. Weiss, T. Williams, and A.
Stempel, J. Antibiot., 24, 239 (1971). O. Leukart, M. Caviezel, A.
Eberle, E. Escher, A. Tun-Kyi, and R. Schwyzer, Helv. Chim. Acta, 59,
2181 (1976).
a) C. Walsh, Tetrahedron, 38, 871 (1982). b) E. M. Wallace, J. A.
Moliterni, M. A. Moskal, A. D. Neubert, N. Marcopulos, L. B. Stamford,
A. J. Trapani, P. Savage, M. Chou, and A. Y. Jeng, J. Med. Chem., 41,
1513 (1998).
development of allenylation of 1 with propargyltins. The reaction
of methyl-substituted propargyltin 2d afforded a mixture of 3c
and 4c in 95% yield with a high regioselectivity (3c : 4c ¼ 5 : 95,
entry 4). Unfortunately, the enantiomeric excess of the major
product 4c was moderate (61% ee). When the reaction of phenyl-
substituted propargyltin 2e was carried out, 4d was obtained in a
moderate yield with high enantiomeric excess (25%, 97% ee,
entry 5). Gratifyingly, both yield and enantiomeric excess were
greatly improved when trimethylsilyl-substituted propargyltin 2f
was used. The corresponding allenyl-substituted amine 4e was
obtained in 93% ee (entry 6).
8
9
In summary, we have developed catalytic, enantioselective
propargyl- and allenylation reactions of ꢀ-imino ester in the
presence of [Cu(MeCN)4]ClO4/(R)-tol-BINAP catalyst. The
present reaction provides a new methodology for the synthesis
of optically active ꢀ-amino acid derivatives.
10G. T. Crisp and T. A. Robertson, Tetrahedron, 48, 3239 (1992). L. B.
Wolf, K. C. M. F. Tjen, F. P. J. T. Rutjes, H. Hiemstra, and H. E.
Schoemaker, Tetrahedron Lett., 39, 5081 (1998).
11 Catalytic, enantioselective propargyl- and allenylation reactions of
aldehydes have been reported: G. E. Keck, D. Krishnamurthy, and X.
Chen, Tetrahedron Lett., 35, 8323 (1994). C.-M. Yu, S.-K. Yoon, H.-S.
Choi, and K. Baek, Chem. Commun., 1997, 763. C.-M. Yu, S.-K. Yoon,
K. Baek, and J.-Y. Lee, Angew. Chem., Int. Ed., 37, 2392 (1998). S. E.
Denmark and T. Wynn, J. Am. Chem. Soc., 123, 6199 (2001). D. A.
Evans, Z. K. Sweeney, T. Rovis, and J. S. Tedrow, J. Am. Chem. Soc.,
123, 12095 (2001).
Dedicated to Professor Teruaki Mukaiyama on the occasion
of his 75th birthday.
References and Notes
12 ðRÞ-tol-BINAP ¼ ðRÞ-2,20-bis(di-p-tolylphosphino)-1,10-binaphthyl;
ðRÞ-BINAP ¼ ðRÞ-2,20-bis(diphenylphosphino)-1,10-binaphthyl;ðR; RÞ-
DIOP ¼ ðR; RÞ-2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenyl-
phosphino)-butane.
1
2
S. Kobayashi and H. Ishitani, Chem. Rev., 99, 1069 (1999).
Mannich reactions: a) E. Hagiwara, A. Fujii, and M. Sodeoka, J. Am.
Chem. Soc., 120, 2474 (1998). b) D. Ferraris, B. Young, T. Dudding, and
T. Lectka, J. Am. Chem. Soc., 120, 4548 (1998). c) D. Ferraris, B.
Young, C. Cox, W. J. Drury, III, T. Dudding, and T. Lectka, J. Org.
Chem., 63, 6090 (1998). d) K. Juhl, N. Gathergood, and K. A. Jꢀrgensen,
Angew. Chem., Int. Ed., 40, 2995 (2001).
Ene reactions: W. J. Drury, III, D. Ferraris, C. Cox, B. Young, and T.
Lectka, J. Am. Chem. Soc., 120, 11006 (1998). S. Yao, X. Fang, and K.
A. Jꢀrgensen, Chem. Commun., 1998, 2547.
Allylation reactions: X. Fang, M. Johannsen, S. Yao, N. Gathergood, R.
G. Hazell, and K. A. Jꢀrgensen, J. Org. Chem., 64, 4844 (1999).
Cycloaddition reactions: S. Yao, S. Saaby, R. G. Hazell, and K. A.
Jꢀrgensen, Chem. Eur. J., 6, 2435 (2000).
Other alkylation reactions: a) M. Johannsen, Chem. Commun., 1999,
2233. b) N. Nishiwaki, K. R. Knudsen, K. V. Gothelf, and K. A.
Jꢀrgensen, Angew. Chem., Int. Ed., 40, 2992 (2001).
13 A typical experimental procedure for entry 1 of Table 2: The catalyst
was prepared by treating [Cu(MeCN)4]ClO4 (0.65 mg, 2.0 ꢁmol) and
(R)-tol-BINAP (1.49 mg, 2.2 ꢁmol) in ether (1 mL) and stirring at room
temperature for 0.5 h. To this mixture was added 1 (102 mg, 0.40 mmol)
in ether (0.5 mL), and the resultant mixture was cooled to À30 ꢁC. To
this mixture was added 2a (66 mg, 0.20 mmol). After being stirred for
5 h at this temperature, the reaction was quenched with 10% aqueous
KF. The aqueous layer was extracted with ether, and the combined
organic layers were washed with brine and dried over Na2SO4. After
filtration and concentration, the residue was purified by column
chromatography (SiO2, eluent: hexane to hexane/EtOAc ¼ 5=1) to
give the mixture of 3a and 4a (57 mg, 96%, 3a : 4a ¼ 97 : 3). The
enantiomeric excess of 3a was determined to be 86% by HPLC analysis
using Chiralpak AD column (hexane/iPrOH ¼ 5=1).
3
4
5
6
7
a) S. Ikegami, H. Uchiyama, T. Hayama, T. Katsuki, and M.
Yamaguchi, Tetrahedron, 44, 5333 (1988). b) D. P. G. Hamon, R. A.