LETTER
Oxidative Functionalisation of SuperQuat Enamides
1661
lit.,20 [a]20D –36 (c 1.0, EtOH)} in 93% yield after purifi-
cation and in > 98% ee.21 Although similar reduction of
(4S,1¢R,2¢S)-15 (>98% d.e.) with NaBH4 led to low isolat-
ed yields of the required diol 18, treatment with LiAlH4 al-
References
(1) (a) Adam, W.; Peters, E.-M.; Peters, K.; von Schnering, H.
G.; Voerckel, V. Chem. Ber. 1992, 125, 1263. (b) Adam,
W.; Ahrweiler, M.; Paulini, K.; Reissig, H.-U.; Voerckel, V.
Chem. Ber. 1992, 125, 2719.
(2) (a) Barton, D. H. R.; Motherwell, W. B.; Zard, S. Z. J. Chem.
Soc., Chem. Commun. 1981, 774. (b) Zhang, X.; Foote, C.
S. J. Am. Chem. Soc. 1993, 115, 8867. (c) Adam, W.;
Ahrweiler, M.; Sauter, M.; Schmiedeskamp, B. Tetrahedron
Lett. 1993, 34, 5247. (d) Adam, W.; Ahrweiler, M.; Peters,
K.; Schmiedeskamp, B. J. Org. Chem. 1994, 59, 2733.
(e) Adam, W.; Reinhardt, D. J. Chem. Soc., Perkin Trans. 2
1994, 1503.
(3) Baldwin, J. E.; O’Neil, I. A. Tetrahedron Lett. 1990, 31,
2047.
(4) Baldwin, J. E.; Aldous, D. J.; Chan, C.; Harwood, L. M.;
O’Neil, I. A.; Peach, J. M. Synlett 1989, 9; and references
contained therein.
lowed the direct isolation of diol 18 in 56% yield {[a]25
D
+15.2 (c 0.90, CHCl3), lit. ent-18; [a]22 –11.0 (c 1.00,
D
CHCl3)22]; (78% yield as the bis-acetate derivative)23 and
in > 96% ee.24 Treatment of (3¢,3¢-dimethylbut-1¢-enyl)-
13 with MCPBA gave syn-(4S,1¢R,2¢S)-16 in > 96% de,
but this ester was not amenable to recrystallisation and
proved extremely labile, fragmenting to a complex mix-
ture of products upon attempted purification by chroma-
tography. As a result, direct reduction of the crude
reaction mixture with LiAlH4 allowed the direct isolation
of diol 19 in 51% yield (65% yield as the bis-acetate)23
and in > 96% ee (Scheme 4).24
(5) (a) Bach, J.; Bull, S. D.; Davies, S. G.; Nicholson, R. L.;
Sanganee, H. J.; Smith, A. D. Tetrahedron Lett. 1999, 40,
6677. (b) Bull, S. D.; Davies, S. G.; Nicholson, R. L.; Smith,
A. D. Tetrahedron: Asymmetry 2000, 11, 3475. (c) Davies,
S. G.; Nicholson, R. L.; Smith, A. D. Synlett 2002, 1637.
(d) Bach, J.; Bull, S. D.; Davies, S. G.; Nicholson, R. L.;
Sanganee, H. J.; Smith, A. D. Org. Biomol. Chem. 2003,
2001. (e) For a related approach see: Gaul, C.; Scharer, K.;
Seebach, D. J. Org. Chem. 2001, 66, 3059.
(6) (a) Xiong, H.; Hsung, R. P.; Berry, C. R.; Rameshkumar, C.
J. Am. Chem. Soc. 2001, 123, 7174. (b) Rameshkumar, C.;
Xiong, H.; Tracey, M. R.; Berry, C. R.; Yao, L. J.; Hsung, R.
P. J. Org. Chem. 2002, 67, 1339.
(7) (a) Adam, W.; Bosio, S. G.; Wolff, B. T. Org. Lett. 2003, 5,
819. (b) Xiong, H.; Hsung, R. P.; Shen, L.; Hahn, J. M.
Tetrahedron Lett. 2002, 43, 4449. (c) For earlier studies
regarding the epoxidation of an achiral enamide see: Adam,
W.; Reinhardt, D.; Reissig, H.-U.; Paulini, K. Tetrahedron
1995, 45, 12257. (d) For a related protocol see: Adam, W.;
Bosio, S. G.; Turro, N. J. J. Am. Chem. Soc. 2002, 124, 8814.
(8) For preliminary studies in this area see: Sanganee, H. J.
DPhil Thesis; University of Oxford: UK, 1996.
(9) Experimental procedure for the synthesis (4S,1¢E)-3-(2¢-
phenylethenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (6):
Phenylacetaldehyde (0.44 mL, 3.77 mmol) was added to
oxazolidinone (S)-5 (600 mg, 3.14 mmol) in toluene (50 mL)
and p-TSA (10 mg, 0.06 mmol) and heated under Dean–
Stark conditions for three hours before concentration in
vacuo. Purification by column chromatography [EtOAc/
petroleum ether (40–60), 1:15] gave 6 (780 mg, 85%) as
white crystals; mp 144 °C; IR (CH2Cl2) cm–1: 1752 (C=O);
[a]23D +7.8 (c 1, CH2Cl2); Found; C, 78.0; H, 6.5, N, 4.65%;
C19H19NO2 requires C, 77.8; H, 6.5, N, 4.8%; dH (400MHz,
CDCl3) 7.50–7.12 [11 H, m, ArCH and CH=C(2) ¢HPh],
5.51 [1 H, d, J = 14.5 Hz, C(1¢)H=CHPh], 4.81 [1 H, s,
C(4)H], 1.66 and 1.00 [2 × 3 H, s, C(5)Me2]; dC (125 MHz,
CDCl3) 155.2 (CO), 136.2, 135.0 (Ph:Cipso × 2), 129.3,
129.1, 128.8, 126.8, 125.6 (Ph:CH), 123.4 [C(2¢)H], 113.0
[C(1¢)H], 82.6 [C(5)], 68.1 [C(4)H], 29.2, 24.0 [C(5)Me2];
m/z (CI+, NH3) 294 (MH+).
O
O
(i)
R
O
NH
Ph
O
N
Ph
(S)-5
11, R = CH2Ph, 71%, >98% d.e.m
12, R = iPr, 77%, >98% d.e.
13, R = tBu, 99%, >98% d.e.
O
(ii)
O
93% from 14
81% from 15
84% from 16
O
NH
Ph
(iii) for 14
O
O
Ar
R
(S)-5
(iv) for 15,16
O
N
+
OH
R
HO
Ph
OH
14, R = CH2Ph, 60%, >98% d.e.
15, R = iPr, 61%, >98% d.e.
16, R = tBu, (quant), >96% d.e.
17, R = CH2Ph, 93%, >98% e.e.
18, R = Pr, 56% [78%]*, >96% e.e.
19, R = Bu, 51% [65%]*, >96% e.e.
i
t
Scheme 4 Reagents and Conditions; (i) aldehyde, p-TSA, toluene,
D; (ii) MCPBA, CHCl3, 0 °C to r.t.; (iii) NaBH4, MeOH, 0 °C to r.t.;
(iv) LiAlH4, THF, r.t. *(isolated yield of bis-acetate)
In conclusion, we have demonstrated that (E)-enamides
may be prepared stereoselectively from (S)-4-phenyl-5,5-
dimethyloxazolidin-2-one (5), which may be epoxidised
selectively upon treatment with DMDO. Alternatively,
treatment of the (E)-enamides with MCPBA generates
syn-(4S,1¢R,2¢S)-1¢-m-chlorobenzoate-2¢-hydroxy deriva-
tives, which upon reductive cleavage furnish homochiral
1,2-diols in high yields. The development of further meth-
odologies for the asymmetric functionalisation of homo-
chiral enamides are currently under investigation within
our laboratory.
(10) (a) Based upon the related protocol for the synthesis of N-
alkenyl lactams described in: Zezza, C. A.; Smith, M. B.
Synth. Commun. 1987, 17, 729. (b) For a related protocol
see: Akiba, T.; Tamura, O.; Hashimoto, M.; Kobayashi, Y.;
Katoh, T.; Nakatani, K.; Kamada, M.; Hayakawa, I.;
Terashima, S. Tetrahedron 1994, 50, 3905.
Acknowledgement
The authors wish to thank Zeneca (H. J. S.) for the award of a
CASE studentship, MECD (Spain) for a Postdoctoral Fellowship
(H. R. S.) and New College, Oxford for a Junior Research Fel-
lowship (A. D. S.).
(11) Adam, W.; Bialas, J.; Hadjiarapoglou, L. Chem. Ber. 1991,
124, 2377.
Synlett 2003, No. 11, 1659–1662 ISSN 1234-567-89 © Thieme Stuttgart · New York