Direct organo-catalytic asymmetric α-amination of aldehydes - A simple approach to optically active α-amino aldehydes, α-amino alcohols, and α-amino acids

Article abstract of DOI:10.1002/1521-3773(20020517)41:10<1790::AID-ANIE1790>3.0.CO;2-Y

L-Proline as the catalyst: The first direct asymmetric α-amination of aldehydes using L-proline as the catalyst is presented (see scheme; Pg = protecting group). This new reaction gives easy access to optically active α-amino aldehydes, α-amino alcohols, and α-amino acids from simple and easily available starting materials and catalysts. The reactions proceed in high yields and excellent enantioselectivities with as little as 2 mol % of the catalyst.

Full text of DOI:10.1002/1521-3773(20020517)41:10<1790::AID-ANIE1790>3.0.CO;2-Y

COMMUNICATIONS
Efforts are underway to access the alternate transannular
[4‡2] cycloaddition pathway leading to the hexacyclinic acid
framework, and will be reported in due course.
Direct Organo-Catalytic Asymmetric
a-Amination of Aldehydes–A Simple
Approach to Optically Active a-Amino
Aldehydes, a-Amino Alcohols, and a-Amino
Acids**
Received: March 15, 2002 [Z18907]
[1] a) H. Muramatsu, M. Miyauchi, B. Sato, S. Yoshimura, 40th Sympo-
sium on the Chemistry of Natural Products (Fukuoka, Japan), 1998,
Paper 83, p. 487; b) B. Sato, H. Muramatsu, M. Miyauchi, Y. Hori, S.
Takese, M. Mino, S. Hashimoto, H. Terano, J. Antibiot. 2000, 53, 123.
Anders B˘gevig, Karsten Juhl,
Nagaswamy Kumaragurubaran, Wei Zhuang, and
Karl Anker J˘rgensen*
Susceptible cell lines were : MCF-7(IC 50 ˆ 27ngmL À1), A549 (IC50
ˆ
À1
73ngmLÀ1), HT-29 (IC50 ˆ 7 3 ngmL ), Jurkat (IC50 ˆ 33 ngmLÀ1),
P388 (IC50 ˆ 21 ngmLÀ1), and B16 (IC50 ˆ 67ngmL À1); c) B. Sato, H.
Makajima, Y. Hori, M. Hino, S. Hashimoto, H. Terano, J. Antibiot.
2000, 53, 204; d) S. Yoshimura, B. Sato, T. Kinoshita, S. Takese, H.
Terano, J. Antibiot. 2000, 53, 615; e) S. Yoshimura, B. Sato, T.
Kinoshita, S. Takese, H. Terano, J. Antibiot. 2002, 55, C-1.
[2] R. Hˆfs, M. Walker, A. Zeeck, Angew. Chem. 2000, 39, 3400; Angew.
Chem. Int. Ed. 2000, 39, 3258.
One of the ultimate goals and challenges in chemistry is to
develop stereoselective transformations for the creation of
functionalized optically active molecules with structural
diversity from simple and easily available starting materials.
Several procedures to generate optically active molecules are
known and among these asymmetric catalysis plays an
important role.
The importance of optically active a-amino acids, a-amino
aldehydes, and a-amino alcohols, formed by asymmetric
catalysis,[1] has stimulated an enormous development in
synthetic strategies, and two different catalytic, enantioselec-
[3] a) For a review of TADA reactions, see E. Marsault, A. Toro, P.
Nowak, P. Deslongchamps, Tetrahedron 2001, 57, 4243; b) for a recent
example in synthesis, see also longithorone A: M. E. Layton, C. A.
Morales, M. D. Shair, J. Am. Chem. Soc. 2002, 124, 773; c) for the use
of a bromodiene in a TADA reaction, see W. R. Roush, K. Koyama,
M. L. Curtin, K. J. Moriarty, J. Am. Chem. Soc. 1996, 118, 7502; d) for
this type of hetero-[4‡2] cycloaddition, see K. Shin, M. Moriya, K.
Ogasawara, Tetrahedron Lett. 1998, 39, 3765; e) S. Takano, S. Satoh, K.
Ogasawara, J. Chem. Soc. Chem. Commun. 1988, 59; f) S. Takano, S.
Satoh, K. Ogasawara, K. Aoe, Heterocycles 1990, 30, 583; g) M.
Yamauchi, S. Katayama, O. Baba, T. Watanabe, J. Chem. Soc. Chem.
Commun. 1983, 281.
À
À
tive approaches are attractive: the C C and the C N bond-
forming reactions. The catalytic enantioselective C C bond-
forming reactions include the addition to imines, such as the
Strecker[2] and Mannich[3] reactions.
À
À
The catalytic, enantioselective, direct C N bond-forming
reaction using aldehydes and a nitrogen source, such as
azodicarboxylates, would constitute one of the simplest
procedures for the construction of a stereogenic carbon
center attached to a nitrogen atom (Scheme 1). Recently, we
presented the first direct, enantioselective a-amination of
2-keto esters catalyzed by chiral copper(ii) bisoxazoline
complexes.[4, 5] This development led to a simple synthetic
approach to optically active syn-b-amino-a-hydroxy esters.
[4] Sorensen and co-workers have recently completed a synthesis of
FR182877 through an approach that is closely related to the route
described in this Communication: D. A. Vosburg, C. D. Vanderwal,
E. J. Sorenson, J. Am. Chem. Soc. 2002, ASAP.
[5] I. Ohtani, T. Kusumi, Y. Kashman, H. Kakisawa, J. Am. Chem. Soc.
1991, 113, 4092. See also ref. [1d] for analytical data on the Mosher
esters of FR182877.
[6] J. R. Gage, D. A. Evans, Org. Synth. 1990, 68, 7 7 .
[7] H. Ishiwata, H. Sone, H. Kigoshi, K. Yamada, J. Org. Chem. 1994, 59,
4712.
[8] D. B. Dess, J. C. Martin, J. Am. Chem. Soc. 1991, 113, 7277.
[9] E. J. Corey, P. L. Fuchs, Tetrahedron Lett. 1972, 3769.
[10] M. A. Brodney, J. P. O×Leary, J. A. Hansen, R. J. Giguere, Synth.
Commun. 1995, 25, 521.
[11] S.-i. Kiyooka, H. Kuroda, Y. Shimasaki, Tetrahedron Lett. 1986, 27, 3009.
[12] A. Arase, M. Hoshi, A. Mijin, K. Nishi, Syn. Commun. 1995, 25, 1957.
[13] a) For a review, see N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457;
b) for the use of TlOH, see J. Uenishi, J. M. Beau, R. W. Armstrong, Y.
Kishi, J. Am. Chem. Soc. 1987, 109, 4756; c) for the use of TlOEt, see
S. A. Frank, H. Chen, R. K. Kunz, M. J. Schnaderbeck, W. R. Roush,
Org. Lett. 2000, 2, 2691; d) for the use of Tl2CO3, see I. E. Marko, F.
Murphy, S. Dolan, Tetrahedron Lett. 1996, 37, 2507; e) for the first
Suzuki coupling with vinyldibromide, see W. R. Roush, R. Riva, J.
Org. Chem. 1988, 53, 710.
[14] C. R. Holmquist, E. J. Roskamp, J. Org. Chem. 1989, 54, 3258.
[15] S. Higashibayashi, K. Shinko, T. Ishizu, K. Hashimoto, H. Shirahama,
M. Nakata, Synlett 2000, 1306.
Scheme 1. Pg ˆ protecting group.
[16] For a Cs2CO3-mediated macrocarbocyclization, see S. Phoenix, E.
Bourque, P. Deslongchamps, Org. Lett. 2000, 2, 4149.
[17] L. Ouellet, P. Langlois, P. Deslongchamps, Synlett 1997, 689, and
references therein.
[18] a) C. D. Vanderwal, D. A. Vosberg, S. Weiler, E. J. Sorensen, Org.
Lett. 1999, 1, 645; b) C. D. Vanderwal, D. A. Vosberg, E. J. Sorensen,
Org. Lett. 2001, 3, 4307.
[19] M. Gray, I. P. Andrews, D. F. Hook, J. Kitteringham, M. Voyle,
Tetrahedron Lett. 2000, 41, 6237.
[20] E. D. Laganis, B. L. Chenard, Tetrahedron Lett. 1984, 25, 5831.
[21] T. Mukaiyama, M. Usui, K. Saigo, Chem. Lett. 1976, 49.
[22] A sample of natural FR182877 was not available for direct compar-
ison.
[*] Prof. Dr. K. A. J˘rgensen, Dr. A. B˘gevig, Dr. K. Juhl,
Dr. N. Kumaragurubaran, W. Zhuang
Center for Catalysis
Department of Chemistry
Aarhus University
8000 Aarhus C (Denmark)
Fax : (‡45)8919-6199
E-mail: kaj@chem.au.dk
[**] This work was made possible by a grant from The Danish National
Research Foundation.
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
1790
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1433-7851/02/4110-1790 $ 20.00+.50/0
Angew. Chem. Int. Ed. 2002, 41, No. 10

COMMUNICATIONS
Herein we present the first catalytic, enantioselective,
direct a-amination of aldehydes, that is, the successful and
unprecedented use of unmodified aldehydes for the stereo-
yield and 90% ee (Table 1, entry 10). The direct a-amination
of 1a was also investigated for the azodicarboxylates 2b, c
(Table 1, entries 11 and 12) to introduce more useful N-
protecting groups (see below).
selective creation of C N bonds using l-proline[3c,d, 6, 7] as the
À
catalyst (Scheme 1). These reactions give an easy and simple
access to many classes of optically active molecules with high
structural diversity. The molecules include a-amino alde-
hydes, a-amino alcohols, and a-amino acids, all key chiral
elements in many natural products as well as in medicinal
chemistry.
Further attractive features of the l-proline-catalyzed direct
a-amination reactions are: 1) the neat reaction proceeds
smoothly in, for example, propanal with only a slight decrease
in enantioselectivity,[8] and 2) the reaction can also be
performed in gram scale with the same high yield and
enantioselectivity (e.g. propanal reacts with DEAD (10 mmol
scale) to give the a-aminated product 3a in 98% yield and
92% ee).
The results for the direct a-amination of some representa-
tive aldehydes 1a, b with different azodicarboxylates 2a
c
catalyzed by l-proline [Eq. (1)] under various reaction
conditions are presented in Table 1.
The enantiomeric excesses of the products formed by the
direct a-amination of aldehydes decrease slowly because of
the acidity of the a-position next to the carbonyl group. This
problem can easily be solved by the in situ reduction of the
aldehyde group of the a-aminated aldehydes. This approach
leads to a simple, catalytic, enantioselective procedure for the
formation of valuable a-amino alcohols [Eq. (2)]. To simplify
the isolation and analytical procedures the a-amino alcohols
were converted into the N-amino oxazolidinones 4. The
results are presented in Table 2.
Propanal 1a reacts with diethyl azodicarboxylate (DEAD)
2a catalyzed by l-proline at room temperature under ambient
conditions in CH2Cl2 and the a-aminated product 3a is
formed in 93% yield and with 92% ee (Table 1, entry 1). The
procedure for the isolation of the a-aminated product is
remarkable: addition of H2O and extraction with Et2O
followed by evaporation of the excess aldehyde and the
solvent gives pure 3a. At 08C the enantioselectivity of the
reaction is not significantly improved (93% ee). However, the
reaction also proceeds with lower catalyst loadings (Table 1,
entries 2 4) and a highly enantioselective reaction takes
place using only 2 mol% of l-proline as the catalyst. Avariety
of other solvents can also be applied with success for the
catalytic, enantioselective, direct a-amination reaction (Ta-
ble 1, entries 5 9). Butanal 1b is a-aminated, in good yield,
and high enantioselectivity using DEAD 2a to give 3b in 77%
The various aldehydes 1a f all react with azodicarbox-
ylates affording the a-aminated aldehydes in high yields and
enantioselectivities in the presence of l-proline (10 mol%) as
the catalyst. Further transformations give the N-amino
oxazolidinones 4. The results given in Table 2, entries 1 and
Table 1. Catalytic, enantioselective, direct a-amination of aldehydes 1a, b using the azodicarboxylates 2a c catalyzed by l-proline under various reaction
conditions.[a]
Entry
Aldehyde
Azodicarboxylate
Solvent
Cat. Load [%]
Reaction time [min]
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
9
R1 ˆ Me (1a)
R1 ˆ Me (1a)
R1 ˆ Me (1a)
R1 ˆ Me (1a)
R1 ˆ Me (1a)
R1 ˆ Me (1a)
R1 ˆ Me (1a)
R1 ˆ Me (1a)
R1 ˆ Me (1a)
R1 ˆ Et (1b)
R1 ˆ Me (1a)
R1 ˆ Me (1a)
R2 ˆ Et (2a)
R2 ˆ Et (2a)
R2 ˆ Et (2a)
R2 ˆ Et (2a)
R2 ˆ Et (2a)
R2 ˆ Et (2a)
R2 ˆ Et (2a)
R2 ˆ Et (2a)
R2 ˆ Et (2a)
R2 ˆ Et (2a)
R2 ˆ iPr (2b)
R2 ˆ tBu (2c)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
ClCH2CH2Cl
MeCN
EtOAc
toluene
dioxane
CH2Cl2
CH2Cl2
CH2Cl2
50
20
5
45
55
105
300
120
30
300
450
50
120
105
205
3a 93
3a 82
3a 87 91
3a 92
3a 87 89
3a 7 0
3a 7 7
3a 81
3a 86
3b 7 7
3c 91
3d 99
92
92
2
84
50
50
50
50
50
10
10
10
91
81
86
68
90
88
89
10
11
12
[a] Experimental conditions: l-proline was added to a stirred solution of the azodicarboxylate (1.0 mmol) and aldehyde (1.5 mmol) in the solvent (3 mL) at
room temperature. The reaction mixture was quenched with H2O (5 mL), extracted with Et2O, and dried over anhydrous Na2SO4. The solvent and the excess
aldehyde were removed by evaporation (see Supporting Information). [b] Yield of isolated product. [c] Enantiomeric excesses determined by GC using a
chiral Chrompack CP Chiralsil-Dex Cb column.
Angew. Chem. Int. Ed. 2002, 41, No. 10
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COMMUNICATIONS
Table 2. Catalytic, enantioselective, direct a-amination of aldehydes 1a
f
aldehyde 3e (>90% yield). Oxidation of the aldehyde by
KMnO4 to the carboxylic acid and esterification followed by
hydrolysis of the Boc groups (Boc ˆ tert-butoxycarbonyl),
reduction, and finally a N-Boc protection gives the N-Boc-
protected valine methyl ester 6 [Eq. (4); TMS ˆ trimethylsilyl,
TFA ˆ trifluoroacetic acid, DMAP ˆ 4-dimethylaminopyri-
dine] maintaining the enantiomeric excess obtained in the
enantioselective amination step (90% ee). The absolute
configuration of the chiral carbon center in 6 was assigned
as R.[11]
with azodicarboxylates 2a, d catalyzed by l-proline (10 mol%) at room
temperature in CH2Cl2 [Eq. (2)].[a]
Entry
Aldehyde
Azodicarboxylate
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
R1 ˆ Me (1a)
R1 ˆ Et (1b)
R1 ˆ iPr (1c)
R1 ˆ tBu (1d)
R1 ˆ allyl (1e)
R1 ˆ Bn (1 f)
R1 ˆ iPr (1c)
R2 ˆ Et (2a)
R2 ˆ Et (2a)
R2 ˆ Et (2a)
R2 ˆ Et (2a)
R2 ˆ Et (2a)
R2 ˆ Et (2a)
R2 ˆ Bn (2d)
4a 67 93
4b 7 7
4c 83
4d 57 91
4e 92
95
93
93
89
91
4 f 68
4g 7 0
[a] Experimental conditions: l-proline (11.5 mg, 0.10 mmol) was suspend-
ed in CH2Cl2 (2.5 mL) followed by the addition of the aldehyde
(1.50 mmol) and the azodicarboxylate (1.00 mmol). The reaction mixture
was stirred at room temperature until the yellow color of the azodicarbox-
ylate disappeared. MeOH (2.5 mL) was added followed by careful addition
of NaBH4 (50 mg). After 20 min, NaOH (0.5n, 2.5 mL) was added and after
2 h the organic solvents were removed in vacuo. The aqueous phase was
diluted and extracted with EtOAc and the organic phase dried over
anhydrous MgSO4 and concentrated in vacuo to give pure N-amino
oxazolidinones (see Supporting Information). [b] Yield of isolated product.
[c] ee values determined by GC using a chiral Chrompack CP Chiralsil-Dex
Cb column or by chiral HPLC.
Based on the absolute configuration of the a-aminated
products, we propose the transition-state model 7 for the
reaction. The approach of the azodicarboxylate might be
directed by interaction of the incoming
nitrogen atom with the proton of the
carboxylic acid of the l-proline ena-
mine intermediate.
In conclusion, we have demonstrat-
ed the first organo-catalytic, direct,
asymmetric a-amination of aldehydes
2 show that the masked a-amino alcohols are obtained with
excellent enantioselectivity and that a slightly higher enan-
tioselectivity is obtained when the aldehyde is reduced to the
alcohol prior to workup. The other aldehydes 1c f are
directly a aminated in a highly enantioselective fashion with
DEAD 2a in the presence of l-proline as the catalyst to give,
after reduction and cyclization, the corresponding oxazolidi-
nones in high yields and very high enantioselectivities
(Table 2, entries 3 6, 89% to 93% ee). To expand the scope
of the reaction we also treated 1c with dibenzyl azodicarbox-
ylate 2d in the presence of l-proline (10 mol%) as the
catalyst. The N-Cbz protected (Cbz ˆ phenylmethoxycar-
bonyl) N-amino oxazolidinone 4g was isolated in 70% yield
and 91% ee (Table 2, entry 7) thus showing that a readily
removable protecting group can be introduced.
with azodicarboxylates as the nitrogen
source and l-proline as the catalyst.
The new reaction provides easy access
to optically active a-amino aldehydes, a-amino alcohols, and
a-amino acids from simple and easily available starting
materials and catalyst. Aldehydes react with azodicarboxy-
lates and the corresponding optically active a-aminated
adducts are formed in high yields and enantiomeric excesses,
with as little as 2 mol% of l-proline. It is also demonstrated
that masked a-amino alcohols are formed in high yields and
excellent enantioselectivities (up to 95% ee). Furthermore,
the formation of oxazolidinones and a-amino acids is
demonstrated. This direct a-amination reaction uses readily
available and inexpensive achiral starting materials, and can
be carried out under environmentally friendly and operation-
ally simple reaction conditions.
À
The N-protecting group and the N N bond in the N-amino
oxazolidinone 4g can be removed and cleaved, respectively.
The a-aminated product 4g is first treated with H2/(Pd/C),
followed by reaction with Zn/acetone in acetic acid to afford
oxazolidinone 5 in 31% overall yield based on 2d [Eq. (3)].
The absolute configuration of 5 has been assigned as R.[9]
Hydrolysis of the oxazolidinones at this point would give the
a-amino alcohols.[10]
Received: March 1, 2002 [Z18800]
[1] See for example a) R. M. Williams, Synthesis of Optically Active a-
Amino Acids, Pergamon, Oxford, 1989; b) R. M. Williams, J. A.
Hendrix, Chem. Rev. 1992, 92, 889; c) M. Arend, Angew. Chem. 1999,
111, 3047; Angew. Chem. Int. Ed. 1999, 38, 2873; d) L. Yet, Angew.
Chem. 2001, 113, 900; Angew. Chem. Int. Ed. 2001, 40, 875; e) R. O.
Duthaler, Tetrahedron 1994, 50, 1539; f) S. C. Bergmeier, Tetrahedron
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1998, 120, 1207, and references therein.
[2] See for example: a) M. S. Sigman, E. N. Jacobsen, J. Am. Chem. Soc.
1998, 120, 5315; b) M. S. Sigman, P. Vachal, E. N. Jacobsen, Angew.
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Sigman, E. N. Jacobsen, J. Am. Chem. Soc. 1998, 120, 4901; d) C. A.
Krueger, K. W. Kuntz, C. D. Dzierba, W. G. Wirschun, J. D. Gleason,
A very important aspect of the direct a-amination reaction
is the easy and attractive access it gives to optically active
nonproteogenic a-amino acids. Reaction of 3-methyl butanal
(1c) with di-tert-butyl azodicarboxylate (2c) catalyzed by l-
proline (10 mol%, CH2Cl2, 4 h, RT) gives the a-hydrazino
1792
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1433-7851/02/4110-1792 $ 20.00+.50/0
Angew. Chem. Int. Ed. 2002, 41, No. 10

COMMUNICATIONS
M. L. Snapper, A. H. Hoveyda, J. Am. Chem. Soc. 1999, 121, 4284;
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Chem. Int. Ed. 1998, 37, 3186; f) H. Ishitani, S. Komiyama, Y.
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A New Trend in Phenalenyl Chemistry:
A Persistent Neutral Radical, 2,5,8-Tri-tert-
butyl-1,3-diazaphenalenyl, and the Excited
Triplet State of the Gable syn-Dimer in the
Crystal of Column Motif**
[3] Catalytic enantioselective direct Mannich reactions: a) S. Yamasaki,
T. Iida, M. Shibasaki, Tetrahedron 1999, 55, 8857; b) K. Juhl, N.
Gathergood, K. A. J˘rgensen, Angew. Chem. 2001, 113, 3083; Angew.
Yasushi Morita,* Takashi Aoki, Kozo Fukui,
Shigeaki Nakazawa, Koichi Tamaki, Shuichi Suzuki,
Akira Fuyuhiro, Kagetoshi Yamamoto, Kazunobu Sato,
Daisuke Shiomi, Akira Naito, Takeji Takui,* and
Kazuhiro Nakasuji*
¬
Chem. Int. Ed. 2001, 40, 2995; c) A. Cordova, S.-I. Watanabe, F.
Tanaka, W. Notz, C. F. Barbas III, J. Am. Chem. Soc. 2002, 124, 1842;
¬
d) A. Cordova, W. Notz, G. Zhong, J. M. Betancort, C. F. Barbas III, J.
Am. Chem. Soc. 2002, 124, 1866.
[4] K. Juhl, K. A. J˘rgensen, J. Am. Chem. Soc. 2002, 124, 2420.
[5] For an review on asymmetric a-amination reactions see J.-P. Genet, C.
Greck, D. Lavergne, Modern Amination Methods (Ed.: A. Ricci),
Wiley-VCH, Weinheim, 2000, chap. 3.
[6] D. A. Evans, S. G. Nelson, J. Am. Chem. Soc. 1997, 119, 6542.
[7] For the use of proline and other chiral amines as catalysts see for
example, a) P. I. Dalko, L. Moisan, Angew. Chem. 2001, 113, 3840;
Phenalenyl (1) is a highly symmetric (D3h) odd alternating-
hydrocarbon p radical, found as early as 1956,[1] and it still
plays an important role as a building block for spin-mediated
molecular functions in organic molecule-based magnets,[2] and
organic metal and conducting materials.[3] Recent progress in
phenalenyl chemistry has been made in the isolation of the
radical itself in the crystalline state by employing bulky
substituents (2[4a] and perchlorophenalenyl[4b]), with the
exploration of amphoteric redox systems[5] which have
intriguing potential applications, such as organic molecular
batteries,[6] and with the synthesis of novel phenalenyls with
extended conjugation, such as compound 3.[7] 1,3-Diazaphe-
nalenyl (4) is a typical example of the isoelectronic mode of
heteroatomic modification for phenalenyl. Successful isola-
tion of 2[4] aided by the steric hindrance induced by the bulky
¬
Angew. Chem. Int. Ed. 2001, 40, 37 26; b) A. Cordova, W. Notz, C. F.
Barbas III, J. Org. Chem. 2002, 67, 301; c) K. Sakthivel, W. Notz, T.
Bui, C. F. Barbas III, J. Am. Chem. Soc. 2001, 123, 5260; d) B. List,
R. A. Lerner, C. F. Barbas III, J. Am. Chem. Soc. 2000, 122, 2395;
e) J. F. Austin, D. W. C. MacMillan, J. Am. Chem. Soc. 2002, 124, 1172;
f) A. B. Northrup, D. W. C. MacMillan, J. Am. Chem. Soc. 2002, 124,
2458; g) N. A. Paras, D. W. C. MacMillan, J. Am. Chem. Soc. 2001, 123,
4370; h) W. S. Jen, J. J. M. Wiener, D. W. C. MacMillan, J. Am. Chem.
Soc. 2000, 122, 9874; i) K. A. Ahrendt, C. J. Borths, D. W. C.
MacMillan, J. Am. Chem. Soc. 2000, 122, 4243; j) A. B˘gevig, N.
Kumaragurubaran, K. A. J˘rgensen, Chem. Commun. 2002, 620.
[8] The enantiomeric excess was 77% and full conversion was obtained
after only 2 min reaction time!
[9] Absolute configuration of 5: W. A. Kleschick, M. W. Reed, J. Bordner,
J. Org. Chem. 1987, 52, 3168.
[10] S. J. Katz, S. C. Bergmeier, Tetrahedron Lett. 2002, 43, 557.
[11] Absolute configuration of 6: M. J. Burk, J. G. Allen, J. Org. Chem.
1997, 62, 7054.
1
1
R
β
R
R
2
3
1
α
α
N
6
N
7
O
O
4
9
1
2
1
2
5
8
R
R
R
R
4 R1 = R2 = H
5 R1 = tBu, R2 = H
6 R1 = R2 = tBu
1 R1 = H
3
2 R1 = tBu
[*] Prof. Dr. Y. Morita, Prof. Dr. K. Nakasuji, T. Aoki, Dr. K. Tamaki,
S. Suzuki, Prof. Dr. A. Fuyuhiro, Prof. Dr. K. Yamamoto
Department of Chemistry, Graduate School of Science
Osaka University
Toyonaka, Osaka 560-0043 (Japan)
Fax : (‡81)6-6850-5395
E-mail: nakasuji@chem.sci.osaka-u.ac.jp
Prof. Dr. T. Takui, Dr. K. Fukui, Dr. S. Nakazawa, Prof. Dr. K. Sato,
Prof. Dr. D. Shiomi
Departments of Chemistry and Materials Science
Graduate School of Science
Osaka City University
Sumiyoshi-ku, Osaka 558-8585 (Japan)
Fax : (‡81)6-6605-3137
E-mail: takui@sci.osaka-cu.ac.jp
Prof. Dr. A. Naito
Faculty of Engineering, Yokohama National University
Hodogaya-ku, Yokohama 240-0085 (Japan)
[**] This work has been supported by Grants-in-Aid for General Scientific
Research and Scientific Research on Priority Area ™Delocalized p-
Electronic Systems (No. 297)∫ from the Ministry of Education,
Culture, Sports, Science, and Technology, Japan.
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
Angew. Chem. Int. Ed. 2002, 41, No. 10
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1433-7851/02/4110-1793 $ 20.00+.50/0
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