Indium-mediated barbier reactions of azides: A facile synthesis of N-allylamine derivatives

Article abstract of DOI:10.1081/SCC-120006459

N-Allylic amines are conveniently prepared in high yields by the reaction of azides with allylindium reagents in the presence of sodium iodide in DMF at ambient temperature.

Full text of DOI:10.1081/SCC-120006459

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INDIUM-MEDIATED BARBIER REACTIONS OF AZIDES: A
FACILE SYNTHESIS OF N-ALLYLAMINE DERIVATIVES
J. S. Yadav a , Ch. Madhuri a , B. V. S. Reddy a , G. S. Kiran Kumar Reddy a & G. Sabitha a
a Organic Chemistry Division-1 , Indian Institute of Chemical Technology , Hyderabad,
500007, India
Published online: 18 Oct 2011.
To cite this article: J. S. Yadav , Ch. Madhuri , B. V. S. Reddy , G. S. Kiran Kumar Reddy & G. Sabitha (2002) INDIUM-
MEDIATED BARBIER REACTIONS OF AZIDES: A FACILE SYNTHESIS OF N-ALLYLAMINE DERIVATIVES, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:18, 2771-2777, DOI: 10.1081/
SCC-120006459
To link to this article: http://dx.doi.org/10.1081/SCC-120006459
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 18, pp. 2771–2777, 2002
INDIUM-MEDIATED BARBIER
REACTIONS OF AZIDES: A FACILE
SYNTHESIS OF N-ALLYLAMINE
DERIVATIVES
*
J. S. Yadav, Ch. Madhuri, B. V. S. Reddy,
G. S. Kiran Kumar Reddy, and G. Sabitha
Organic Chemistry Division-1 Indian Institute of
Chemical Technology, Hyderabad-500007, India
ABSTRACT
N-Allylic amines are conveniently prepared in high yields by
the reaction of azides with allylindium reagents in the pres-
ence of sodium iodide in DMF at ambient temperature.
Key Words: Indium reagents; Allylation; Azides; Allylamines
Organometallic reactions have found wide applications in organic syn-
thesis.[1] In particular, organoindium reagents[2] have attracted much
attention due to their compatibility with many organic functional groups
(e.g., R–OH, CO2R), stability and reactivity even in aqueous media.
Further, indium mediated reactions exhibit a low nucleophilicity thus per-
mitting chemoselective transformations of groups of similar reactivity.
Allylindium reagents, generated in situ from allyl halides and indium
*Corresponding author. E-mail: yadav@iict.ap.nic.in
2771
DOI: 10.1081/SCC-120006459
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2772
YADAV ET AL.
metal, react with various electrophiles[3,4] such as carbonyl compounds,
C¼N unsaturated systems, C–C multiple bonds, acyl halides, gem-diacetates
and epoxides to generate homoallyl products. Aqueous solvents have
proved to be most effective for indium-mediated reactions[5] and in certain
cases significant regio-, diastereo- and even enantioselectivities have been
achieved. Although, indium has been used extensively in carbonyl addition
reactions it has not been used in the Barbier allylation reactions of azides.
N-Allylamines are useful precursors for amino-Claisen rearrangement 6 and
are generally prepared by reaction of allylbromide with primary amines in
the presence of base. However, inspite of their potential utility, most of these
procedures suffer from the formation of a mixture of products containing
mono- and di-allylated products and also incompatibility with base sensitive
substrates. The problems associated with these procedures can be overcome
by the use of indium metal for this transformation.
In continuation of our work on the applications of metals such as
indium, magnesium, and zinc for various transformations,[7] we report here
a novel and practical method for the preparation of N-allylamines through
the indium-mediated allylation of azides. The treatment of phenyl azide with
indium metal and methyl 2-(bromomethyl) acrylate in the presence of NaI in
DMF gave exclusively mono-allylated ester in 80% yield (Scheme 1).
Similarly, several aromatic and aliphatic azides were reacted with
methyl 2-(bromomethyl) acrylate and indium metal in DMF to afford the
corresponding mono-allylaminoester derivatives in excellent yields. Further,
the reactons of azides with allylindium bromide in the presence of NaI
resulted in the formation of mono-N-allylamines in high yields with only
a trace amount of corresponding N,N-diallylamine which was easily sepa-
rated by column chromatography. The reactions proceeded smoothly at
ambient temperature to give the products in high yields in a short reaction
time. Unlike many zinc or tin promoted reactions that use acid catalyst, heat
or sonication for inducing the reaction, this procedure does not require any
stringent conditions or anhydrous solvent. Even though, this reaction pro-
ceeded smoothly in commercial DMF (containing 0.2% water) the reaction
in water alone was not successful. The results as summarized in Table 1
Scheme 1.

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N-ALLYLAMINE DERIVATIVES
2773
Table 1. Preparation of N-Allylamines Through Allylation of Azides
Azide
(1)
Producta
(2)
Reaction
Time (h)
Yieldb
(%)
Entry
a
Allyl Bromide
1.5
2.0
1.0
80
85
87
b
c
d
2.5
81
e
f
3.0
2.5
84
80
g
h
i
3.5
3.0
2.5
75
89
80
j
2.0
1.5
90c
88c
k
l
2.5
73c
(continued)

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2774
YADAV ET AL.
Table 1. Continued
Producta
Azide
(1)
Reaction
Time (h)
Yieldb
(%)
Entry
m
Allyl Bromide
(2)
3.0
85c
n
2.5
84
o
p
3.0
2.0
70c
80
1
aAll products were characterised by H NMR, IR and Mass spectra.
bIsolated yields after purification.
c5–8% di-allylated products were isolated.
clearly reveal the scope and generality of the reaction with respect to various
alkyl and aryl azides. The formation of mono-N-allylamines may be attrib-
uted to the addition of allylindium reagent to the azide with successive loss
of N2 followed by proton capture during the work-up. The reactions were
clean, high yielding and completed with in 1–3.5 h. Among various metals
such as samarium, yttrium, zinc and bismuth studied for this transformation
indium was found to be effective in terms of selectivity and conversion.
In summary, we have described a novel and convenient procedure for
the preparation of mono-N-allylamines through the indium mediated
Barbier allylation of azides. The procedure offers several advantages includ-
ing high yields of products, short reaction times, cleaner reaction profiles,
greater selectivity, simple experimental/product isolation procedures which
makes it a useful and attractive strategy for the synthesis of mono-N-allyl
amines.
EXPERIMENTAL
General Procedure
A mixture of azide (5 mmol), allylbromide or methyl 2-(bromomethyl)
acrylate (7.5 mmol), indium powder (7.5 mmol) and sodium iodide (7.5 mmol)
in DMF (15 mL) was stirred at room temperature for an appropriate time

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N-ALLYLAMINE DERIVATIVES
2775
(Table 1). After completion of the reaction as indicated by TLC, the reaction
mixture was quenched with saturated ammonium chloride (15 mL) and
extracted with diethyl ether (2 Â 15 mL). Evaporation of the solvent followed
by purification on silica gel (Merck, 100–200 mesh, ethyl acetate–hexane,
0.5–9.5) gave pure mono-N-allylamine.
1
Spectral data for products: 2a: H NMR (CDCl3) ꢀ : 3.80 (s, 3H), 4.03
(s, 2H), 5.80 (s, 1H), 6.25 (s, 1H), 6.58 (d, 2H, J ¼ 7.8 Hz), 6.65 (t, 1H,
J ¼ 7.7 Hz), 7.18 (t, 2H, J ¼ 7.8 Hz). EIMS: m/z: 191 Mþ, 158, 130, 106,
77, 41. IR (KBr): ꢁ 3415, 2950, 1602, 1505, 1437, 1299, 1153, 952, 812, 750.
1
2b: H NMR (CDCl3) ꢀ: 2.25 (s, 3H), 3.80 (s, 3H) 4.15 (s, 2H), 5.55
(s, 1H), 6.25 (s, 1H), 6.30 (m, 1H), 6.50 (m, 1H), 7.05 (m, 1H). EIMS: m/z:
283 Mþ, 253, 224, 198, 172, 144, 117, 77. IR (KBr): ꢁ 3405, 2932, 1617, 1515,
1444, 1233, 1139, 1024, 769.
1
2c: H NMR (CDCl3) ꢀ: 3.70 (s, 3H), 3.80 (s, 3H), 4.18 (s, 2H), 5.80
(s, 1H), 6.23 (s, 1H), 6.23 (s, 1H), 6.70 (d, 2H, J ¼ 8.0 Hz), 6.75 (d, 2H,
J ¼ 8.0 Hz). EIMS: m/z: 221 Mþ, 205, 188, 174, 149, 136, 120, 77, 41.
IR (KBr): ꢁ 3410, 2937, 1620, 1517, 1450, 1237, 1144, 1030, 775.
1
2d: H NMR (CDCl3) ꢀ: 3.80 (s, 3H), 4.15 (s, 2H), 5.60 (s, 1H), 6.25
(s, 1H), 6.50 (dd, 1H, J ¼ 8.0 and 2.7Hz), 6.55 (d, 1H, J ¼ 2.7Hz), 6.65
(d, 1H, J ¼ 8.0 Hz), 7.05 (t, 1H, J ¼ 8.0 Hz). EIMS: 225 Mþ, 210, 193,
166, 140, 115, 99, 76. IR (KBr): ꢁ 3420, 2945, 1608, 1515, 1435, 1295,
1148, 957, 820, 760. IR (KBr): ꢁ 3418, 2953, 1605, 1515, 1440, 1296, 1157,
960, 815, 758.
2e: 1H NMR (CDCl3) ꢀ: 2.23 (s, 3H), 3.75 (brs, NH), 3.83 (s, 3H), 4.18
(s, 2H), 5.80 (s, 1H), 6.28 (s, 1H), 6.58 (d, 1H, J ¼ 8.0 Hz), 6.70 (t, 1H,
J ¼ 7.8 Hz), 7.10–7.18 (m, 2H). EIMS: m/z: 205 Mþ, 190, 173, 144, 124,
120, 106, 91, 77, 65, 39. IR (KBr): ꢁ 3420, 2968, 1616, 1520, 1450, 1295,
1157, 965, 825, 770.
1
2f: H NMR (CDCl3) ꢀ: 3.80 (s, 3H), 3.83 (s, 3H), 4.03 (s, 2H), 4.65
(brs, NH), 5.80 (s, 1H), 6.30 (s, 1H), 6.40 (s, 1H), 6.58 (d, 1H, J ¼ 7.8 Hz),
6.20 (d, 1H, J ¼ 8.0 Hz). EIMS: m/z: 255 Mþ, 224, 180, 154, 126, 99, 78, 39.
IR (KBr): ꢁ 3425, 2960, 1607, 1525, 1438, 1298, 1155, 960, 820, 760.
1
2g: H NMR (CDCl3) ꢀ: 3.83 (s, 3H), 4.25 (s, 2H), 5.85 (s, 1H), 6.35
(s, 1H), 6.58 (d, 1H, J ¼ 7.8 Hz), 7.25 (d, 1H, J ¼ 8.0 Hz) 7.30 (d, 1H,
J ¼ 8.0 Hz), 7.43–7.50 (m, 2H), 7.80–7.87 (m, 2H). EIMS: m/z: 241 Mþ,
209, 180, 154, 127, 115, 79, 41. IR (KBr): ꢁ 3418, 2965, 1605, 1510, 1450,
1299, 1163, 950, 820, 765.
2h: 1H NMR (CDCl3) ꢀ: 3.79 (s, 6H), 3.83 (s, 3H), 3.98 (s, 2H),
5.80 (s, 1H), 6.18 (d, 1H, J ¼ 7.8 Hz), 6.20 (d, 1H, J ¼ 1.8 Hz), 6.28
(s, 1H), 6.68 (d, 1H, J ¼ 7.8 Hz). EIMS: m/z: 251 Mþ, 235, 203, 153,
138, 110, 79, 41. IR (KBr): ꢁ 3415, 2950, 1602, 1505, 1437, 1299, 1153,
952, 812, 753.

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2776
YADAV ET AL.
2i: 1H NMR (CDCl3) ꢀ: 3.80 (s, 3H), 4.08 (s, 2H), 4.70 (brs, NH), 5.85
(s, 1H), 6.28 (s, 1H), 6.45 (d, 1H, J ¼ 8.0 Hz), 7.02 (d, 1H, J ¼ 8.0 Hz) 7.25
(d, 1H, J ¼ 2.0 Hz). EIMS: m/z: 260 Mþ, 228, 198, 174, 133, 111, 75, 55.
IR (KBr): ꢁ 3418, 2965, 1605, 1510, 1450, 1299, 1163, 950, 820, 765.
2k: 1H NMR (CDCl3) ꢀ: 2.30 (s, 3H), 3.85 (m, 2H), 5.25–5.35 (m, 2H),
5.95 (m, 1H), 6.80 (d, 2H, J ¼ 8.0 Hz), 7.35 (d, 2H, J ¼ 8.0 Hz). IR (KBr):
ꢁ 3425, 2960, 1607, 1525, 1438, 1298, 1155, 960, 820, 760.
1
2n: H NMR (CDCl3) ꢀ: 3.30 (s, 2H), 3.60 (s, 3H), 3.78 (s, 2H), 5.98
(s, 1H), 6.28 (s, 1H), 7.25–7.38 (m, 5H). EIMS: m/z: 205 Mþ, 179, 141, 116,
107, 91, 69, 41. IR (KBr): ꢁ 3415, 2950, 1602, 1505, 1437, 1299, 1153, 952,
812, 753.
1
2p: H NMR (CDCl3) ꢀ: 3.80 (m, 2H), 5.20 (d, 1H, J ¼ 10.8 Hz), 5.30
(d, 1H, J ¼ 16.8 Hz), 5.90 (m, 1H), 6.45–6.55 (m, 2H), 6.60 (m, 1H), 7.05
(m, 1H). IR (KBr): ꢁ 3410, 2960, 1615, 1510, 1440, 1305, 1160, 965, 826, 760.
ACKNOWLEDGMENTS
Ch M, BVS & GSKKR thank CSIR, New Delhi for the award of
fellowships.
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Received in the UK May 31, 2001