5710
S. P. Kolis et al. / Tetrahedron Letters 44 (2003) 5707–5710
12. Black, D. S. C.; Craig, D. C.; Kumar, N. J. Chem. Soc.,
Chem. Commun. 1989, 425–426.
(900 mL) is added dropwise over a period of 90 min. The
biphasic solution is stirred at room temperature until
HPLC indicates that no starting material remains. The
mixture is transferred to a separatory funnel with the aid
of 4-L CH2Cl2 and 4-L DI H2O, and the organic layer is
separated. The organic layer is washed with 2×4 L satd
NaHCO3(aq) and 2×4 L satd NaCl(aq). The organic layer
is separated, dried (Na2SO4) and filtered through a pad of
SiO2 to provide 9a (140.4 g, 88%) as a brown oil. 1H
NMR (d6-DMSO, 400 MHz) l 7.73 (dd, J=1.2 Hz, 8.1
Hz, 1H), 7.43 (dd, J=0.9 Hz, 7.5 Hz, 1H), 7.13 (t, J=7.5
Hz, 1H), 7.04 (d, J=3 Hz, 1H), 6.81 (s, 1H), 6.55 (d,
J=3.0 Hz, 1H), 4.21–4.37 (m, 2H), 4.09 (s, 3H), 1.33 (t,
J=6.9 Hz, 3H); 13C NMR (CDCl3, 75 MHz) l 152.6,
132.6, 130.8, 123.8, 123.3, 118.8, 116.7, 114.2, 101.1, 65.3,
64.5, 35.8, 13.8; IR (KBr, cm−1): 3022, 2985, 1758, 1372,
1342, 1332, 1250, 1153, 1021; anal calcd for C14H14N2O3:
C, 62.78; H, 5.85; N, 8.13. Found: C, 62.68; H, 5.68; N,
8.10; mass spectrum: molecular ion: m/z=344.0; base
peak: m/z=344.0; Preparation of 10a: Cyanocarbonate
9a (139 g, 404 mmol) is dissolved in EtOAc (5.1 L) and
10% Pd–C (35 g) is added. The slurry is hydrogenated at
50°C and 50 psi H2. When HPLC indicates that 9a has
been consumed, the reaction mixture is cooled to rt and
is filtered through Hyflo. The solvent is removed in vacuo
and the product 10a (93 g, 85%) is isolated as a yellow
13. Black, D. S. C.; Bowyer, M. C.; Kumar, N.; Mitchell, P.
S. R. J. Chem. Soc., Chem. Commun. 1993, 819–821.
14. Kanagawa, H.; Kanzawa, A.; Kadoya, M.; Naito, T.;
Nanasawa, M. Bull. Chem. Soc. Jpn. 1983, 56, 762–765.
15. Kobayashi, S.; Tsuchiya, Y.; Mukaiyama, T. Chem. Lett.
1991, 537–540.
16. Kurauchi, M.; Imamoto, T.; Yokoyama, M. Tetrahedron
Lett. 1981, 22, 4985–4986.
17. Scholl, M.; Lim, C.-K.; Fu, G. C. J. Org. Chem. 1985, 60,
6229–6231.
18. van Leusen, A. M.; Oomkes, P. G. Synth. Commun. 1980,
10, 399–403.
19. Yokoyama, M.; Ohteki, H.; Karauchi, M.; Hoshi, K.;
Yanagisawa, E.; Suzuki, A.; Imamoto, T. J. Chem. Soc.,
Perkin Trans. 1 1984, 2635–2640.
20. Yoneda, R.; Harusawa, S.; Kurihara, T. Tetrahedron
Lett. 1989, 30, 3681–3684.
21. Harusawa, S.; Yoneda, R.; Kurihara, T.; Hamada, Y.;
Shiori, T. Chem. Pharm. Bull. 1983, 31, 2932–2935.
22. Mico, I.; Najera, C. Tetrahedron 1993, 49, 4327–4332.
23. Lithium cyanide is not commercially available, and the
majority of procedures require its use to implement
cyanophosphonations. The reason for this is unclear.
24. 1.1 equiv. of LDA was used for compound 5 where
R=H.
1
solid. H NMR (CDCl3, 400 MHz) l 7.57 (d, J=5.2 Hz,
1H), 7.54 (dd, J=9.6 Hz, 2.4 Hz, 1H), 7.21–7.29 (m, 2H),
6.58 (d, J=4.8 Hz, 1H), 4.32 (s, 2H), 1.65 (s, 9H); 13C
NMR (d6-DMSO, 75 MHz) l 149.1, 132.5, 132.3, 128.7,
126.7, 123.4, 121.3, 118.9, 117.8, 107.5, 84.2, 27.5, 23.5;
IR (KBr, cm−1): 3010, 2984, 2936, 2255, 1746, 1425, 1732,
1337, 1259, 1154, 1102, 1024, 1014; HRMS calculated for
C15H16N2O2: 256.1212; Found: 256.1212.
25. Kurihara, T.; Fujimoto, T.; Harusawa, S.; Yoneda, R.
Synthesis 1987, 397–399.
26. Au, A. T. Synth. Commun. 1984, 14, 743–748.
27. The experimental procedure for a large-scale preparation
is as follows: Preparation of 9a: 7-formyl-1-tert-butoxy-
carbonyl indole (7a) (114 g, 465 mmol) is dissolved in
CH2Cl2 (900 mL) and Bu4NCl H2O (6.6 g, 24 mmol) and
ethyl chloroformate (46 mL, 481 mmol) are added. The
solution is stirred, and NaCN (47.2 g, 963 mmol) in water
28. Alternative reducing agents were not examined to effect
this chemistry.