imine radical 2,3 which is then subjected to the second one
electron reduction to give 3. The imine 3 is isomerized to
chromioenamine 10,1d,10 and the chromioenamine reacts with
an aldehyde to give 11.11 Hydrolysis of 11 gives the aldol
adduct 12. Metalloenamines are usually prepared by deprotona-
tion of imine derivatives with strong bases,5 however, the
procedure does not require such bases. Attempts to reduce the
amount of chromium(II) with manganese and Me3SiCl resulted
in deoximation probably due to the fast trapping of the
Table 2 Preparation of g-amino alcohols from O-acetyloximes and
aldehydesa
Run
R1
R2
Yield (%)b
syn–antic
chromium imine
3 or the chromioenamine 10 with
Me3SiCl.12
1
2
3
4
5
6
7
Me (8)
Ph
Ph
86 (16)
79d
65
71
88
70+30
82+18
69+31
69+31
42+58
53+47
54+46
8
When anti- and syn-4 were employed in the reaction, almost
the same product distributions were observed [eqn. (4)]. The
8
8
Ph(CH2)2
c-C6H11
Ph
Ph(CH2)2
c-C6H11
Ph (17)
17
17
70
71
a Reaction conditions as in typical procedure (ESI) unless otherwise stated.
b Isolated yields. c Isomer ratios were determined by isolation and/or NMR.
d The reaction was conducted without addition of NiCl2.
(4)
Notes and references
1 (a) Cr: E. J. Corey and J. E. Richman, J. Am. Chem. Soc., 1970, 92,
5276; (b) R. B. Boar, J. F. McGhie, M. Robinson, D. H. R. Barton, D.
Horwell and R. V. Stick, J. Chem. Soc., Perkin Trans. 1, 1975, 1237; (c)
Ti: G. H. Timms and E. Wildsmith, Tetrahedron Lett., 1971, 195; (d)
D. H. R. Barton and S. Z. Zard, J. Chem. Soc., Perkin Trans. 1, 1985,
2191.
2 H. Tsutsui and K. Narasaka, Chem. Lett., 1999, 45.
3 Ni: J. Boivin, A.-M. Schiano, S. Z. Zard and H. Zhang, Tetrahedron
Lett., 1999, 40, 4531; J. Boivin, E. Fouquet and S. Z. Zard, Tetrahedron
Lett., 1990, 31, 3545.
4 We thank Mr Shigeki Nakatsukasa of Kyoto University for conducting
an initial investigation of chromioenamines.
5 For metalloenamines, see: S. F. Martin, Comprehensive Organic
Synthesis, ed. B. M. Trost and I. Fleming, Pergamon, Oxford, 1991, vol.
2, ch. 1.16, p. 475.
6 The yield was improved to 92% when the mixture was quenched with
aq. NaF solution for 48 h.
major product was an aldol adduct 14 at the less hindered
carbon. This result supports the proposed Scheme 1, in which
the two reactions involve the same iminyl radical as the
intermediate.
In order to utilize the nitrogen-containing adduct 11,
reduction of 11 leading to a g-amino alcohol 13 was
examined.13 A mixture obtained from 8 and benzaldehyde was
treated with LiAlH4 (10 equiv.) at 278 °C, and the temperature
of the mixture was gradually raised to 0 °C. Quenching of the
mixture with alkaline NaF solution followed by acetylation
gave the acetylated g-amino alcohol 16 in 79% yield [eqn.
(5)].14,15 The yield was increased by addition of a catalytic
7 Among the oxime derivatives examined, O-acetyl gave the best result.
Results with the other oxime derivatives are as follows: O-
benzoyloxime, 58%; O-mesyloxime, 75%; O-tosyloxime, 47%; O-
trimethylsilyloxime, 12%.
8 Although the amounts of O-acetyloxime and chromium(II) chloride can
be reduced to 1.2 and 3.6 equiv., respectively, without affecting the
yield, the couplings required longer reaction times.
9 (a) K. Takai, M. Tagashira, T. Kuroda, K. Oshima, K. Utimoto and H.
Nozaki, J. Am. Chem. Soc., 1986, 108, 6048; (b) S. Py, C. W. Harwig,
S. Banerjee, D. L. Brown and A. G. Fallis, Tetrahedron Lett., 1998, 39,
6139.
(5)
10 (a) J. V. Braun and W. Rudolph, Ber., 1934, 67B, 269; (b) For reverse
isomerization, see: K. A. Miller, T. W. Watson, J. E. Bender IV, M. M.
Banaszak-Hall and J. F. Kampf, J. Am. Chem. Soc., 2001, 123, 982.
11 J.-E. Dubois, G. Axiotis and E. Bertounesque, Tetrahedron Lett., 1985,
26, 4371; L. Wessjohann and T. Gabriel, J. Org. Chem., 1997, 62,
3772.
12 A. Fürstner and N. Shi, J. Am. Chem. Soc., 1996, 118, 12349.
13 K. Narasaka, Y. Ukaji and S. Yamazaki, Bull. Chem. Soc. Jpn., 1986,
59, 525.
14 Because chromium(III) salts can be reduced with LiAlH4, an excess
amount of the hydride source was required to complete the reduction.
See: Y. Okude, S. Hirano, T. Hiyama and H. Nozaki, J. Am. Chem. Soc.,
1977, 99, 3179.
15 The following reducing agents were examined: i-Bu2AlH (51% yield,
syn–anti = 72+28), Na(MeOCH2CH2O)3AlH (10%, 33+67); LiEt3BH
(10%, 68+32), Li(sec-Bu)3BH (35%, 63+37).
amount of NiCl2. The results of the preparation of g-amino
alcohols from O-acetyloximes and aldehydes with CrCl2 and
NiCl2 are summarized in Table 2.
In conclusion, chromioenamines are generated by treatment
of O-acetyloximes with chromium(II) via sequential reduction
and isomerization. These react with aldehydes to obtain g-
amino alcohols after reduction with LiAlH4. The reaction
proceeds under mild conditions and does not require strong
bases such as LDA.
This work was supported by a Grant-in-Aid from the
Ministry of Education, Culture, Sports, Science and Technol-
ogy of Japan.
Chem. Commun., 2001, 1724–1725
1725