Angewandte
Chemie
diazo esters 1a or 1b is nonselective because of the flexibility
of the anion conformation. This stereochemical process is in
THF at À108C was highly efficient and stereoselective to
afford the anti-a-hydroxy-b-amino esters 10a–c.[18,19] Pd/C-
catalyzed hydrogenation of the a-ketoesters 9a–c, on the
other hand, gave the syn-a-hydroxy-b-amino esters 11a–c,[20]
respectively, also with high yields and selectivities
(Scheme 4).[18,19b]
contrast with the addition of the enolates of acyl oxazolidi-
[5,16]
=
=
nones to C O or C N bonds,
where complexation is
usually responsible for the high stereoselectivities. Interest-
ingly, the reaction of aromatic aldehydes with 1d under
similar conditions gave rather poor diastereoselectivities and
low yields.
In summary, this study is the first example of the highly
diastereoselective nucleophilic addition of the anion derived
=
The utility of the addition products 3 was demonstrated by
the concise synthesis of syn- and anti-a-hydroxy-b-amino acid
derivatives. Thus, the chiral oxazolidinone auxiliary was
removed by addition of lithium methoxide in THF to give
the chiral methyl a-diazoesters 7a–g,k–m, and 8 (Table 3).[17]
from a-diazocarbonyl compounds to a C N bond. This
reaction can be successfully applied to the synthesis of both
anti- and syn-a-hydroxy-b-amino acid derivatives. Since the
diazo group has diverse reactivity, it should be possible to
apply the addition products obtained by this reaction to other
organic syntheses.
Table 3: Removal of the chiral oxazolidinone auxiliary.
Received: May 20, 2004
Revised: July 27, 2004
Keywords: amino acids · chiral auxiliaries · diastereoselectivity ·
.
diazo compounds · nucleophilic addition
Entry
R
Product
ee [%][a]
Yield [%][b]
[1] For recent reviews, see: a) T. Ye, M. A. McKervey, Chem. Rev.
1994, 94, 1091; b) A. Padwa, D. J. Austin, Angew. Chem. 1994,
106, 1881; Angew. Chem. Int. Ed. Engl. 1994, 33, 1797; c) M. P.
Doyle, M. A. McKervey, T. Ye, Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds, Wiley, New York,
1998; d) A. Padwa, J. Organomet. Chem. 2001, 617–618, 3;
e) M. P. Doyle, D. C. Forbes, Chem. Rev. 1998, 98, 911;
f) H. M. L. Davies, E. G. Antoulinakis, J. Organomet. Chem.
2001, 617–618, 47; g) D. J. Timmons, M. P. Doyle, J. Organomet.
Chem. 2001, 617–618, 98; h) D. M. Hodgson, F. Y. T. M. Pierard,
P. A. Stupple, Chem. Soc. Rev. 2001, 30, 50.
1
2
3
4
5
7
8
9
C6H5
7a
7b
7c
7d
7e
7 f
7g
7k
7l
90
>99
92
95
85
91
90
83
88
65
67
58
83
66
78
69
73
77
56
60
p-PhC6H4
p-ClC6H4
p-FC6H4
p-MeOC6H4
m-CNC6H4
m-BrC6H4
=
À
C6H5CH CH
2-(5-bromo)thienyl
2-furyl
10
11
12
7m
8
>99
87
nPr
[2] For a review, see: M. Regitz, Synthesis 1972, 351.
[3] a) U. Schöllkopf, H. Frasnelli, D. Hoppe, Angew. Chem. 1970, 82,
291; Angew. Chem. Int. Ed. Engl. 1970, 9, 300; b) U. Schöllkopf,
B. Bµnhidai, H. Frasnelli, R. Meyer, H. Beckhaus, Liebigs Ann.
Chem. 1974, 1767; c) R. Pellicciari, B. Natalini, J. Chem. Soc.
Perkin Trans. 1 1977, 1822; d) R. Pellicciari, B. Natalini, B. M.
Sadeghpour, M. Marinozzi, J. P. Snyder, B. L. Williamson, J. T.
Kuethe, A. Padwa, J. Am. Chem. Soc. 1996, 118, 1; e) C. J.
Moody, R. J. Taylor, Tetrahedron Lett. 1987, 28, 5351; f) E.
Wenkert, C. A. McPherson, J. Am. Chem. Soc. 1972, 94, 8084;
g) T. L. Burkoth, Tetrahedron Lett. 1969, 10, 5049; h) N. F.
Woolsey, M. H. Khalil, J. Org. Chem. 1972, 37, 2405; i) N.
Jiang, J. Wang, Tetrahedron Lett. 2002, 43, 1285; j) W. Yao, J.
Wang, Org. Lett. 2003, 5, 1527.
[a] ee value determined by chiral HPLC (see Supporting Information for
details). [b] Total yield.
The diazo groups of 7a–c were subsequently oxidized with
dimethyldioxirane (DMD) to give a-ketoesters 9a–c, respec-
tively (Scheme 4). Reduction of the oxo group with NaBH4 in
[4] a) N. Jiang, Z. Qu, J. Wang, Org. Lett. 2001, 3, 2989; b) N. Jiang,
Z. Ma, Z. Qu, X. Xing, L. Xie, J. Wang, J. Org. Chem. 2003, 68,
893.
[5] a) D. A. Evans, J. Bartoli, T. L. Shih, J. Am. Chem. Soc. 1981,
103, 2127; b) for a review, see: D. J. Ager, I. Prakash, D. R.
Schaad, Chem. Rev. 1996, 96, 835.
[6] For recent reviews on the synthesis of b-amino acid derivatives,
see: a) S. Abele, D. Seebach, Eur. J. Org. Chem. 2000, 1; b) M.
Liu, M. P. Sibi, Tetrahedron 2002, 58, 7991; c) J.-A. Ma, Angew.
Chem. 2003, 115, 4426; Angew. Chem. Int. Ed. 2003, 42, 4290.
[7] a) N. Haddad, N. Galili, Tetrahedron: Asymmetry 1997, 8, 3367;
b) Y. Landais, D. Planchenault, Tetrahedron 1997, 53, 2855;
c) M. P. Doyle, R. L. Dorow, J. W. Terpstra, R. A. Rodenhouse,
J. Org. Chem. 1985, 50, 1663; d) N-(diazoacetyl)oxazolidinone
1d can be easily prepared from the reaction of (S)-(À)-4-benzyl-
2-oxazolidinone with triphosgene, followed by treatment with
diazomethane, or by deprotonation of (S)-(À)-4-benzyl-2-oxa-
Scheme 4. Synthesis of both anti- and syn-a-hydroxy-b-amino acid
derivatives from chiral methyl a-diazoesters 7a–c.
Angew. Chem. Int. Ed. 2004, 43, 5977 –5980
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