reducing agents (NaBH4, NaCNBH3, BH3‚Et3N) did not meet
with much success and yielded only intractable reaction
mixtures from which the desired NH-spiropyrrolidinyloxin-
dole could not be isolated. Interestingly, 3a underwent
smooth reduction with sodium borohydride in acetic acid to
afford a single product (65%) which was characterized as
N′-ethyspiropyrrolidinyoxindole 6a on the basis of its spectral
data (Scheme 2).20 Similarly the N-methylspiropyrrolinylox-
indole 3b also gave the corresponding N′-ethyl derivative
6b in 63% yield under identical conditions. The products
6a-b are apparently formed by further reduction of the
initially formed N′-acetylated intermediates under these
reaction conditions.21 These observations led us to the idea
of accomplishing with reductive dethiomethylation-N-
methylation of 3 to either 4 or 5 in one-pot operation. After
much experimentation, these two objectives were readily
Scheme 2
achieved by treatment of 3a with Raney Nickel (W2) in
refluxing methanol (8 h) yielding a single product which
surprisingly was found to be the desired dl-coerulescine 4
1
obtained in 80% yield. The H and 13C NMR data and the
mp (113-115 °C, lit.9 112-113 °C) of the synthetic
coerulescine was found to be identical with the reported
data.10 A similar reductive dethiomethylation-N-alkylation
when performed on the corresponding 5-methoxyspiropyr-
rolinyloxindole 3c by subjecting it to Raney Ni (W2)
treatment in refluxing methanol afforded the (()-horsfiline
5 as a single product (75%), mp 151-152 °C (lit.7 151-
(20) The structures of all new compounds was confirmed with the help
of spectral and analytical data. 3-[(1-Aziridino)(methylthio)methylene]-
2-oxindole 2a. Light yellow crystals (chloroform-hexane); mp 109-110
°C; yield 65%. IR (KBr): 3051, 2928, 1675, 1606 cm-1 1H NMR (400
.
MHz, CDCl3): δ 2.58 (brs, 3H), 2.67 (brs, 2H), 2.68 (brs, 2H), 6.91 (d, J
) 7.6 Hz, 1H), 7.03 (dt, J ) 1, 7.6 Hz, 1H), 7.15 (dt, J ) 1, 7.6 Hz, 1H),
7.78 (d, J ) 7.6 Hz, 1H), 8.50 (brs, 1H, exchangeable with D2O). 13C NMR
(100 MHz, CDCl3): δ 15.61, 34.67, 35.75, 109.02, 121.08, 122.33, 122.75,
122.92, 125.67, 137.65, 167.77, 169.23. 5-Methoxy-3-[(1-aziridino)-
(methylthio)methylene]-2-oxindole 2c. Light yellow crystalline solids
(chloroform-hexane); mp 85-86 °C; yield 66%. IR (KBr): 3169, 2932,
1701, 1600 cm-1. 1H NMR (400 MHz, CDCl3): δ 2.56 (brs, 4H), 2.59 (s,
3H), 3.81 (s, 3H), 6.66 (dd, J ) 2.4, 8.6 Hz, 1H), 6.82 (d, J ) 8.6 Hz, 1H),
7.01 (d, J ) 2.4 Hz, 1H), 8.79 (brs, 1H, exchangeable with D2O).
1-Methylthio-2-oxospiro(3H-indole-3,3′-1-pyrroline) 3a. Yellow crystals
(chloroform-hexane); mp 145 °C; yield 70%. IR (KBr): 2213, 1616, 1436,
1
153 °C), with superimposable H and 13C NMR spectra.7
This concomitant reductive dethiomethylation-N-methyla-
tion of 2-methylthiopyrroline under Raney Ni/methanol
condition is quite unexpected, although examples of the
formation of N-ethyl products during the reduction of imines
and nitriles with Raney Ni in ethanol are known in the
literature.22 Thus, in an another experiment, when 3a was
reduced with W2 Raney Ni in refluxing ethanol, workup of
the reaction mixture yielded the N′-ethyl product 6a, which
was found to be identical with the product obtained earlier
by NaBH4/AcOH reduction of 3a. Reductive methylation of
3c with either sodium cyanoborohydride/HCHO or with
HCHO/HCO2H also afforded the (()-horsfiline 5 in 55%
and 30% yields, respectively.
1
1383 cm-1. H NMR (400 MHz, CDCl3): δ 2.34 (ddd, J ) 4.9, 7.9, 14.0
Hz, 1H), 2.35 (s, 3H), 2.69 (ddd, J ) 4.9, 7.9, 14.0 Hz, 1H), 4.11 (ddd, J
) 4.9, 7.9, 14.0 Hz, 1H), 4.20 (ddd, J ) 4.9, 7.9, 14.0 Hz, 1H), 6.89 (d, J
) 7.8 Hz, 1H), 6.99 (t, J ) 7.6 Hz, 1H), 7.05 (d, J ) 7.6 Hz, 1H), 7.19 (t,
J ) 7.8 Hz, 1H), 8.75 (brs 1H, exchangeable with D2O). 13C NMR (100
MHz, CDCl3): δ 13.76, 37.37, 60.54, 66.81, 110.29, 123.14, 123.55, 129.08,
130.08, 141.14, 171.14, 178.12. MS (m/z, %): 232 (M+, 11.5), 231 (80.5),
158 (100). Anal. Calcd for C12H12N2OS (232.17): C, 62.07; H, 5.16; N,
12.06. Found: C, 62.15; H, 5.47; N, 12.21. 5-Methoxy-1′-methylthio-2-
oxospiro(3H-indole-3,3′-1-pyrroline) 3c. Light yellow crystals (chloroform-
hexane); mp 120-121 °C; yield 68%. IR (KBr): 2993, 1795, 1540 cm-1
.
1H NMR (400 MHz, CDCl3): δ 2.26-2.41 (m, 1H), 2.42 (s, 3H), 2.74-
2.80 (m, 1H), 3.77 (s, 3H), 4.22-4.31 (m, 2H), 6.72 (s, 1H), 6.79 (dd, J )
2.0, 8.3 Hz, 1H), 6.88 (d, J ) 8.3 Hz, 1H), 9.42 (brs, 1H, exchangeable
with D2O). 13C NMR (100 MHz, CDCl3): δ 13.80, 37.48, 55.77, 60.63,
67.41, 110.42, 110.87, 113.72, 131.44, 134.71, 156.24, 171.29, 178.39. MS
(m/z, %): 262 (M+, 45), 189 (100.0), 174 (76.4). Anal. Calcd for C12H12N2-
OS (232.17): C, 62.07; H, 5.16; N, 12.06. Found: C, 62.22; H, 5.11; N,
12.12. 2′-Ethyl-2-oxospiro(3H-indole-3,3′-pyrrolidine) 6a. Light yellow
It was of interest to examine the synthesis of dl-
coerulescine from 2-methylthiomethyleneoxindole 7a, which
should afford the sulfur-free vinylaziridine intermediate 8a
on displacement with aziridine. However, treatment of 7a
1
viscous liquid; yield 65%. IR (Nujol): 2968, 1700, 1612, 1422 cm-1. H
Scheme 3
NMR (400 MHz, CDCl3): δ 1.08 (t, J ) 7.3 Hz, 3H), 2.02 (ddd, J ) 4.6,
8.0, 12.5 Hz, 1H), 2.32 (ddd, J ) 4.6, 8.0, 12.5 Hz, 1H), 2.56 (q, J ) 7.3
Hz, 2H), 2.71 (ddd, J ) 4.6, 8.0, 12.5 Hz, 1H), 2.8 (d, J ) 9.5 Hz, 1H),
2.87 (d, J ) 9.5 Hz, 1H), 3.03 (ddd, J ) 4.6, 8.0, 12.5 Hz, 1H) 6.80 (d, J
) 7.6 Hz, 1H), 6.97 (dt, J ) 1.2, 7.6 Hz, 1H), 7.12 (dt, J ) 1.2, 7.6 Hz,
1H), 7.35 (d, J ) 7.6 Hz, 1H), 8.15 (brs, 1H, exchangeable with D2O). 13
C
NMR (100 MHz, CDCl3): δ 13.91, 37.33, 49.68, 52.94, 54.28, 65.85,
109.31, 122.81, 123.41, 127.65, 139.89, 141.70, 182.64. MS (m/z, %): 216
(M+, 28), 71 (100). Anal. Calcd for C13H16N2O (216.12): C, 72.22; H,
7.40; N, 12.95. Found: C, 72.04; H, 7.35; N, 12.86. 3-[(2-Methylthio)-
ethylaminomethylene]-1-methyl-2-oxindole 9a. Light yellow crystals
(chloroform-hexane); mp 49-50 °C; yield 80%. IR (KBr): 2175, 1657,
1
1489, 1383 cm-1. H NMR (400 MHz, CDCl3): δ 2.15 (s, 3H), 2.74 (t, J
) 6.8 Hz, 2H), 3.33 (s, 3H), 3.75 (dt, J ) 6.8, 10.0 Hz, 2H), 6.87 (d, J )
7.2 Hz, 1H), 6.99 (t, J ) 7.2 Hz, 1H), 7.09 (t, J ) 7.2 Hz, 1H), 7.26 (d, J
) 7.2 Hz, 1H), 7.48 (d, J ) 12.4 Hz, 1H), 8.88 (brs, 1H, exchangeable
with D2O). 13C NMR (100 MHz, CDCl3): δ 15.19, 25.51, 35.54, 48.63,
95.95, 107.58, 114.98, 120.86, 123.09, 124.05, 137.87, 147.92, 169.19. MS
(m/z, %): 248 (M+, 81.6), 187 (100.0). Anal. Calcd for C13H16N2OS
(248.18): C, 62.90; H, 6.44; N, 11.28. Found: C, 62.95; H, 6.28; N, 11.17.
(21) Gribble, G. W.; Lord, P. D.: Skotnicki, J.; Dietz, E.; Eaton, J. T.;
Johnson, J. L. J. Am. Chem. Soc. 1974, 96, 7812.
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