Three-component synthesis of homoallylic carbamates

Article abstract of DOI:10.1081/SCC-200048980

Scandium inflate catalyzed three component condensation of aldehyde, benzyl carbamate, and allyltrimethylsilane to afford the corresponding N-Cbz protected homoallylic amine is described. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200048980

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Three‐Component Synthesis of
Homoallylic Carbamates
Hima Rani Kalita a & Prodeep Phukan a
a Department of Chemistry , Gauhati University ,
Guwahati, 781014, India
Published online: 28 Jul 2007.
To cite this article: Hima Rani Kalita & Prodeep Phukan (2005) Three‐Component
Synthesis of Homoallylic Carbamates, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 35:3, 475-481, DOI:
10.1081/SCC-200048980
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Synthetic Communicationsw, 35: 475–481, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200048980
Three-Component Synthesis of Homoallylic
Carbamates
Hima Rani Kalita and Prodeep Phukan
Department of Chemistry, Gauhati University, Guwahati, India
Abstract: Scandium triflate catalyzed three component condensation of aldehyde,
benzyl carbamate, and allyltrimethylsilane to afford the corresponding N-Cbz
protected homoallylic amine is described.
Keywords: Homoallylic amine, allyltrimethylsilane, scandium triflate, aldehyde,
benzylcarbamate
Nucleophilic addition of allylic organometallic to imine constitutes an
important reaction for the preparation of homoallylic amine.[1] The
homoallyl amines and derivatives are useful intermediate in natural product
synthesis.[2–4] Usually, synthesis of homoallylic amines is achieved by allyla-
tion of aldimines using allyl stannane in the presence of a Lewis acid.[5–12]
Other allylic metals such as allylgermane,[13,14] allylgalium,[15] and allylsi-
lane[16–20] were used in the presence of Lewis acid catalyst for this
synthetic protocol. Most of these methodologies are fraught with limitations
such as excess use of catalyst (or co-catalyst), moisture sensitive conditions,
and poor substrate selectivity. Although our recent process involving
iodine[21] as catalyst was efficient, substrates bearing TBDMS protecting
group could not be used.[22] In recent years, scandium trifluoromethane
sulfonate is emerging as attractive Lewis acid catalyst for various organic
transformations.[23] Herein, we wish to report the synthesis of N-Cbz
protected homoallyl amine using scandium triflate as a catalyst (Scheme 1).
Received in India October 6, 2004
Address correspondence to Prodeep Phukan, Department of Chemistry, Gauhati
University, Guwahati 781014, India. E-mail: pphukan@yahoo.com

476
H. R. Kalita and P. Phukan
Scheme 1.
The reaction of benzaldehyde, benzylcarbamate, and allyltrimethylsilane
in the presence of 5% Sc(OTf)3 in acetonitrile at ambient temperature resulted
in the formation of the homoallylic amine in high yield (Table 1). Rate
enhancement was not significant when 10 mol% of catalyst was used, while
rate of reaction was slow when 2 mol% of catalyst was used. Simultaneous
formation of homoallylic alcohol due to addition of allyltrimethylsilane
with aldehyde was not observed. Both aromatic and aliphatic aldehydes
undergo homoallylation with very good yield irrespective of the nature of
the substrate. With 4-nitrobenzaldehyde and isobutaraldehyde, yields were
relatively poor.
In conclusion, synthesis of Cbz protected homoallyl amines were achieved
using allyltrimethylsilane as allylating agent in presence of Sc(OTf)3 as catalyst.
EXPERIMENTAL
1H NMR and 13C NMR spectra were recorded in Bruker 400 MHz instrument.
Chemical shifts are given in d units relative to the tetramethylsilane (TMS)
signal as an internal reference in CDCl3. Coupling constants (J) are
reported in hertz. IR spectra were recorded in Perkin-Elmer Spectrum RXI
FT-IR spectrometer. Mass spectra were recorded on a Finnigan mass spec-
trometer using ionisation energy of 70eV and elemental analysis was
carried out in Perkin-Elmer 2400 Series II elemental analyser. Silica gel
(230–400 mesh, SRL) was used for column chromatography.
Typical procedure for the synthesis of homoallylic amine: The solution
of aldehyde (1 mmol) and Sc(OTf)3 (0.05 mmol) in benzyl carbamate (1 mmol)
and allyltrimethylsilane (1 mmol) in CH3CN (2 mL) was stirred and monitored
by TLC. The reaction mixture was diluted with ether, washed with brine, dried
(Na2SO4), and concentrated. The crude product was purified by flash chromato-
graphy on silica gel (230–400 mesh) with petroleum ether–EtOAc (10–20%)
as eluent to give the pure product (65–85%).
Spectral Data
N-Benzyloxycarbonyl-1-phenylbut-3-enylamine (4a):[24] White solid; mp.
67–688C (Lit.[24] mp (for R (þ)-enantiomer 68–698C). IR (Nujol, cm21):

Three-Component Synthesis of Homoallylic Carbamates
477
Table 1. Synthesis of Cbz protected homoallyl amine
Entry
a
Aldehyde (1)
Time (h)
2
Producta(4)
Yieldb (%)
83
b
c
d
3
78
83
85
3.5
2.5
e
5
67
f
3.5
4
78
78
g
h
i
4.5
4.5
80
65
aAll productsare characterizedbyIR, NMR, mass spectroscopy and elemental analysis.
bIsolated yield after chromatographic purification.
3056, 1714, 1423, 1262, 739. 1H NMR (400 MHz, CDCl3): 7.36–7.24
(m, 5H), 7.24–7.13 (m, 5H), 5.67–5.50 (m,1H), 5.10-4.94 (m 5H), 4.81–
4.65 (m, 1H), 2.55–2.37 (m, 2H); 13C NMR (100 MHz, CDCl3): 155.6,
141.9, 136.4, 133.7, 128.5, 128.4, 128.1, 127.3, 126.2, 118.4, 66.7, 54.4,
41.0. MS (m/z, % rel. intensity): 240 (31), 196 (28), 129 (3), 107 (9), 104
(14), 91 (100), 77 (11), 65 (8).

478
H. R. Kalita and P. Phukan
N-Benzyloxycarbonyl-1-(4-bromophenyl) but-3-enylamine (4b): White
solid; mp 87–888C. IR (Nujol, cm21): 3055, 1714, 1598, 1418, 1266, 748. 1H
NMR (400 MHz, CDCl3): 7.44 (d, J ¼ 8.1 Hz, 2H), 7.40–7.25 (m, 5H), 7.13
(d, J ¼ 7.7 Hz, 2H), 5.72–5.54 (m, 1H), 5.22–4.96 (m, 5H), 4.82–4.65
(m, 1H), 2.60–2.36 (m, 2H). 13C NMR (100 MHz, CDCl3): 155.6, 141.0,
136.2, 133.2, 131.6, 128.5, 128.2, 127.9, 121.1, 118.9, 66.9, 53.9, 40.8. MS
(m/z, % rel. intensity): 320 (8), 274 (10), 253 (6) 185 (36), 105 (34), 91
(100), 77 (41), 65 (6). Anal. Calcd for C18H18BrNO2: C, 60.01; H, 5.03; N,
3.89. Found: C, 59.97; H, 5.07; N, 3.84.
N-Benzyloxycarbonyl-1-(4-methoxyphenyl)but-3-enylamine (4c): White
solid; mp 70–718C (Lit.[24] mp (for S-(2)-enantiomer 67–688C). IR (Nujol,
1
cm21): 3055, 1719, 1506, 1427, 1266, 739. H NMR (400 MHz, CDCl3):
7.41–7.29 (m, 5H), 7.19 (d, J ¼ 7.8 Hz, 2H), 6.86 (d, J ¼ 8.6 Hz, 2H),
5.77–5.58 (m, 1H), 5.20–5.00 (m, 5H), 4.80–4.70 (m, 1H), 3.79 (s, 3H),
2.60–2.54 (m, 2H). 13C NMR (100 MHz, CDCl3): 158.7, 155.6, 136.4,
133.9, 128.4, 128.0, 127.3, 118.2, 113.8, 86.7, 55.2, 53.9, 40.9. MS (m/z,
% rel. intensity): 270 (40), 226 (54), 162 (6), 134 (6), 107 (2), 91 (100), 77
(2), 65 (4). Anal. Calcd for C19H21NO3: C, 73.29; H, 6.80; N, 4.50. Found:
C, 73.25; H, 6.82; N, 4.54.
N-Benzyloxycarbonyl-1-(3-chlorophenyl)but-3-enylamine (4d): White
solid; mp 62–638C. IR (Nujol, cm21): 3055, 1714, 1506, 1266, 739, 702.
1H NMR (400 MHz, CDCl3): 7.41–7.17 (m, 8H), 7.12 (d, J ¼ 6.3 Hz, 1H),
5.72–5.51 (m, 1H), 5.21–4.93 (m 5H), 4.82–4.68 (m, 1H), 2.59–2.36
(m, 2H); 13C NMR (100 MHz, CDCl3): 155.6, 136.2, 134.4, 133.1, 129.8,
128.5, 128.2, 127.5, 126.3, 124.5, 119.0, 66.9, 53.9, 40.9. MS (m/z, %
rel. intensity): 274 (12), 230(18), 166 (5),141 (67), 113 (25), 91 (100), 77
(42), 65 (5). Anal. Calcd for C18H18ClNO2: C, 68.46; H, 5.74; N, 4.43.
Found: C, 68.42; H, 5.69; N, 4.48.
N-Benzyloxycarbonyl-1-(4-nitrophenyl)but-3-enylamine (4e): White
solid; mp 88–898C. IR (Nujol, cm21): 3047, 2307, 1719, 1516, 1266, 739.
1H NMR (400 MHz, CDCl3): 8.1 (d, J ¼ 7.8 Hz, 2H), 7.50–6.92 (m, 7H),
5.65–5.45 (m, 1H), 5.23–4.91 (m, 5H), 4.86–4.72 (m, 1H), 2.56–2.30
(m, 2H). 13C NMR (100 MHz, CDCl3): 155.5, 149.6, 147.1, 132.4, 128.5,
128.3, 128.2, 127.0, 123.8, 119.7, 67.7, 54.1, 40.7. MS (m/z, %
rel. intensity): 285 (6), 241 (13), 191 (2), 177 (2), 152 (16), 108 (4), 91
(100), 77 (4), 65 (4). Anal. Calcd. for C18H18N2O4: C, 66.25; H, 5.56; N,
8.58. Found: 66.29; H, 5.51; N, 8.63.
N-Benzyloxycarbonyl-1-benzylbut-3-enylamine (4f): White solid; mp
1
86–878C. IR (Nujol, cm21): 3065, 1701, 1520, 1446, 1252, 1040, 744. H
NMR (400 MHz, CDCl3): 7.52–7.07 (m, 10H), 5.88–5.70 (m, 1H), 5.17-
5.00 (m, 4H), 4.65 (d, J ¼ 6.8 Hz, 1H), 4.06–3.88 (m, 1H), 2.91–2.68
(m, 2H), 2.36–2.23 (m, 1H), 2.21 ¼ 2.04 (m, 1H). 13C NMR (100 MHz,
CDCl3): 155.7, 137.8, 136.6, 134.1, 129.4, 128.5 128.4, 128.0, 128.0,
126.4, 118.2, 66.5, 51.6, 40.4, 38.1. MS (m/z, % rel. intensity): 254 (4),

Three-Component Synthesis of Homoallylic Carbamates
479
204 (19), 160 (23), 107 (8), 91 (100), 71 b(6), 65 (5). Anal. Calcd for
C19H21NO2: C, 77.26; H, 7.17; N, 4.74. Found: C, 77.19; H, 7.25; N, 4.79.
N-Benzyloxycarbonyl-1-(2-phenylethyl)but-3-enylamine (4g): White
solid; mp 50–518C. IR (Nujol, cm21): 3065, 1696, 1534, 1451, 1243, 1045,
739, 698. 1H NMR (400 MHz, CDCl3): 7.32–7.16 (m, 7H), 7.13–7.06
(m, 3H), 5.77–5.60 (m, 1H), 5.10–4.95 (m, 4H), 4.54 (d, J ¼ 7.8 Hz, 1H),
3.79–3.63 (m, 1H), 2.68–2.50 (m, 2H), 2.29–2.09 (m, 2H), 1.83–1.70
(m 1H), 1.70–1.55 (m, 1H). 13C NMR (100 MHz, CDCl3): 156.2, 141.7,
136.6, 133.9, 128.5, 128.4, 128.3, 128.1, 125.9, 118.1, 66.6, 50.5, 39.5,
36.5, 32.3. MS (m/z, % rel. intensity): 268 (22), 224 (57), 207 (6), 181
(3), 157 (2), 132 (3), 114 (11), 91 (100), 77 (3), 65 (6). Anal. Calcd for
C20H23NO2: C, 77.63; H, 7.49; N, 4.53. Found: C, 77.45; H, 7.45; N, 4.59.
N-Benzyloxycarbonyl-1-heptylbut-3-enylamine (4h): White solid. mp
1
51–528C IR (Nujol, cm21): 3055, 1710, 1511, 1432, 1261, 739. H NMR
(400 MHz, CDCl3): 7.43–7.26 (m, 5H), 5.86–5.66 n(m, 1H), 5.19–4.97
(m, 4H), 4.63–4.47 (m,1H), 3.81–3.56 (m, 1H), 2.34–1.99 (m, 2H), 1.5–
1.18 (m, 12H), 0.87 (t, J ¼ 6.31 Hz, 3H). 13C NMR (100 MHz, CDCl3):
156.0, 136.7, 134.3, 128.5, 128.0, 117.8, 66.5, 50.7, 39.4, 34.6, 31.8, 29.4,
29.2, 25.8, 22.6, 14.0. MS (m/z, % rel. intensity): 262 (9), 218 (43), 197
(94), 154 (26), 129 (16), 103 (23), 91 (100), 86 (37), 69 (75), 55 (39), 43
(80). Anal. Calcd for C19H29NO2: C, 75.21; H, 9.63; N, 4.62. Found:
C, 75.27; H, 9.55; N, 4.68.
N-Benzyloxycarbonyl-1-isopropylbut-3-enylamine (4i):[24] Colourless
1
oil. IR (Nujol, cm21): 3074, 1696, 1534, 1248, 739. H NMR (400 MHz,
CDCl3): 7.41–7.27 (m, 5H), 5.84–5.65 (m, 1H), 5.19–4.98 (m, 4H), 4.67–
4.52 (m, 1H), 3.66–3.48 (m, 1H), 2.33–2.19 (m, 1H), 2.17–2.04 (m, 1H),
1.80–1.69 (m, 1H), 0.92 (d, J ¼ 6.8 Hz, 3H), 0.88 (d, J ¼ 6.8 Hz, 3H). 13C
NMR (100 MHz, CDCl3): 156.3, 136.7, 134.7, 128.5, 128.3, 128.0, 117.4,
66.5, 55.7, 36.8, 31.4, 19.2, 17.7. MS (m/z, % rel. intensity): 206 (16), 162
(20), 107 (3), 91 (100), 77 (2), 65 (5), 43 (4). Anal. Calcd for C15H21NO2:
C, 72.84; H, 8.56; N, 5.66. Found: C, 72.80, H, 8.60, N, 5.61.
ACKNOWLEDGMENT
Financial support from DST, New Delhi, India (Grant No. SR/FTP/CSA-011/
2002) is gratefully acknowledged.
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