Table 2 In-mediated reaction of 1 in aqueous media
Entry
Reagent
Product
Yield (%)a
de (%)b
1
2
3b
3c
3d
3d
3e
3e
2b
2c
2d
2d
2e
2e
91c
90
93
95
96
96
> 98
> 98
63
64
58
3
Scheme 4 Reagents and conditions: i, c-Pentyl I (40 equiv.) or ButI (10
equiv.), In (10 equiv.), H2O, 20 °C, 48 h.
4d
5
6d
59
nucleophilic tert-butyl radical worked well to give 79% yield of
the desired product 2h with 98% de. In our previous studies, the
triethylborane-induced alkyl radical addition to imine deriva-
tives is frequently plagued by the formation of an ethylated by-
product as a result of competitive addition of an ethyl radical
generated from triethylborane.5,8 It should be noted that the
indium-mediated radical reaction gave selectively the desired
alkylated products.
In addition to the previously reported asymmetric synthesis
of a-amino acids via triethylborane-induced alkyl radical
addition to glyoxylic oxime ether in organic solvent,5 the
indium-mediated allylation and alkylation method in aqueous
media disclosed a broader aspect of the utility of glyoxylic
oxime ether for the synthesis of various types of a-amino acid
derivatives.
We thank a Grant-in-aid for Scientific Research (B) from the
Ministry of Education, Culture, Sports, Science and Technol-
ogy of Japan and the Science Research Promotion Fund of the
Japan Private School Promotion Foundation for research grants.
H.M. gratefully acknowledges the financial support from
Takeda Science Foundation and The Mochida Memorial
Foundation, Japan.
a Isolated yields. b Diastereoselectivities were determined by 1H NMR
analysis. c The threo-isomer was selectively obtained. d Reactions were
carried out at 0 °C for 2 h.
for 72 h (entry 3). These selectivities are slightly better than that
obtained by triethylborane-induced radical reaction in organic
solvent at 20 °C reported by our group.5 As the best result, the
treatment with isopropyl iodide (10 equiv.) and indium (10
equiv.) in H2O gave the desired product 2f in 53% yield with
84% de, accompanied with 21% of the starting compound 1
after being stirred at 20 °C for 48 h (Table 3, entry 5). These
reactions would proceed via a tin-free radical process including
the single-electron transfer (SET) reaction from indium as
shown in our previous report.4 The product 2f could be
converted into (R)-N-Cbz-valine 4. Thus, the absolute ster-
eochemical course of the radical addition to 1 was found to be
the same as that for the allylation of 1 and triethylborane-
induced radical reaction of 1.5 Although the indium-mediated
alkylation reaction of 1 was slower than the indium-mediated
allylation reaction of 1, it is important to note that aliphatic a-
amino acids would not be readily synthesized by applying the
known reactions of organometallic reagents.7 Thus, the synthe-
sis of aliphatic a-amino acids using the radical addition to
glyoxylic imines complements the synthesis of allylic and
aromatic a-amino acids using the nucleophilic addition of
organometallic reagents to glyoxylic imines.
Notes and references
1 For a recent review, see: C. J. Li and T. H. Chan, Tetrahedron, 1999, 55,
11149. For some examples of indium-mediated reaction, see: (a) Y. Yang
and T. H. Chan, J. Am. Chem. Soc., 2000, 122, 402; (b) T. H. Chan and
Y. Yang, J. Am. Chem. Soc., 1999, 121, 3228; (c) L. A. Paquette and R.
R. Rothhaar, J. Org. Chem., 1999, 64, 217; (d) S. Woo, N. Sqires and A.
G. Fallis, Org. Lett., 1999, 1, 573; (e) G. Engstrom, M. Morelli, C.
Palomo and T. Mitzel, Tetrahedron Lett., 1999, 40, 5967; (f) T.-P. Loh
and J. R. Zhou, Tetrahedron Lett., 1999, 40, 9115.
Modest chemical yield and good diastereoselectivity were
obtained in reaction of 1 with a cyclopentyl radical in H2O after
being stirred at 20 °C for 48 h, (Scheme 4). Particularly, the
2 (a) W. Lu and T. H. Chan, J. Org. Chem., 2001, 66, 3467; (b) W. Lu and
T. H. Chan, J. Org. Chem., 2000, 65, 8589; (c) T. H. Chan and W. Lu,
Tetrahedron Lett., 1998, 39, 8605; (d) . For examples of indium-mediated
allylation of imines in organic solvents, see: R. Yanada, A. Kaieda and Y.
Takemoto, J. Org. Chem., 2001, 66, 7516; (e) T. Basile, A. Bocoum, D.
Savoia and A. Umani-Ronichi, J. Org. Chem., 1994, 59, 7766; (f) P.
Beuchet, N. L. Marrec and P. Mosset, Tetrahedron Lett., 1992, 33,
5959.
3 (a) H. Miyabe, M. Ueda and T. Naito, J. Org. Chem., 2000, 65, 5043; (b)
H. Miyabe, K. Fujii, T. Goto and T. Naito, Org. Lett., 2000, 2, 4071; (c)
H. Miyabe, M. Ueda and T. Naito, Chem. Commun., 2000, 2059.
4 H. Miyabe, M. Ueda, A. Nishimura and T. Naito, Org. Lett., 2002, 4,
131.
Scheme 3 Reagents and conditions: i, PriI, In, 20 °C, ii, H2, Pd(OH)2,
MeOH, 20 °C (77%); iii, CbzCl, Na2CO3, acetone–H2O, 0 °C (92%); iv, 1
N LiOH, THF, 20 °C (73%).
Table 3 In-mediated isopropyl radical addition to 1 in aqueous media
Lewis
acid
Time
(h)
Yield
(%)a
de
(%)b
5 H. Miyabe, C. Ushiro, M. Ueda, K. Yamakawa and T. Naito, J. Org.
Chem., 2000, 65, 176.
Entry
Solvent
6 (a) S. Hanessian and R.-Y. Yang, Tetrahedron Lett., 1996, 37, 5273; (b)
S. Hanessian, N. Bernstein, R.-Y. Yang and R. Maguire, Bioorg. Med.
Chem. Lett., 1999, 9, 1437; (c) S. Hanessian, P.-P. Lu, J.-Y. Sanceau, P.
Chemla, K. Gohda, R. Fonne-Pfister, L. Prade and S. W. Cowan-Jacob,
Angew. Chem., Int. Ed., 1999, 38, 3160.
7 (a) D. J. Hallett and E. J. Thomas, J. Chem. Soc., Chem. Commun., 1995,
657; (b) D. J. Hallett and E. J. Thomas, Tetrahedron: Asymmetry, 1995,
6, 2575; (c) N. A. Petasis and I. A. Zavialov, J. Am. Chem. Soc., 1997,
119, 445; (d) N. A. Petasis, A. Goodman and I. A. Zavialov, Tetrahedron,
1997, 53, 16463; (e) Y. Yamamoto, S. Nishii, K. Maruyama, T. Komatsu
and W. Ito, J. Am. Chem. Soc., 1986, 108, 7778; (f) Y. Yamamoto, W. Ito
and K. Maruyama, J. Chem. Soc., Chem. Commun., 1985, 1131.
8 (a) H. Miyabe, R. Shibata, M. Sangawa, C. Ushiro and T. Naito,
Tetrahedron, 1998, 54, 11431; (b) H. Miyabe, K. Chihiro and T. Naito,
Org. Lett., 2000, 2, 4071; (c) H. Miyabe, M. Ueda, N. Yoshioka, K.
Yamakawa and T. Naito, Tetrahedron, 2000, 56, 2413.
1c
2d
3d
4e
5f
H2O–MeOH (2+1)
H2O–MeOH (2+1)
H2O–CH2Cl2 (4+1)
H2O
H2O
H2O
None
None
None
None
None
InCl3
1
72
72
24
48
24
18 (68)
43 (12)
44 (7)
48 (21)
53 (21)
50 (25)
84
84
81
82
84
81
6g
a Isolated yields. Yields in parentheses are for the recovered starting
material 1. b Diastereoselectivities were determined by H NMR analysis.
1
c Reaction was carried out with PriI (5 3 2 equiv.) and In (7 equiv.) at 20
°C. d Reactions were carried out with PriI (10 3 3 equiv.) and In (20 equiv.)
at 20 °C. e Reaction was carried out with PriI (10 3 2 equiv.) and In (10
equiv.) at 20 °C. f Reaction was carried out with PriI (10 equiv.) and In (10
equiv.) at 20 °C. g Reaction was carried out with PriI (10 equiv.), In (10
equiv.), and InCl3 (1 equiv.) at 20 °C.
CHEM. COMMUN., 2002, 1454–1455
1455