Indium mediated allylation of C=N compounds in aqueous media

Article abstract of DOI:10.1016/S0040-4039(00)01676-2

Allylindium adds to a variety of tosyl and aryl hydrazones derived from aromatic aldehydes and ketones at ambient temperature in a DMF-H₂O solvent system to afford homoallylic tosyl hydrazides and homoallylic hydrazines, respectively. Homoallylic hydroxylamines were isolated via addition of allylindium to aldonitrones. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01676-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9311–9314
Indium mediated allylation of CꢀN compounds in aqueous
media
H. M. Sampath Kumar,* S. Anjaneyulu, E. Jagan Reddy and J. S. Yadav
Organic Division-I, Indian Institute of Chemical Technology,† Hyderabad-7, India
Received 21 December 1999; revised 8 June 2000; accepted 27 September 2000
Abstract
Allylindium adds to a variety of tosyl and aryl hydrazones derived from aromatic aldehydes and
ketones at ambient temperature in a DMF–H2O solvent system to afford homoallylic tosyl hydrazides and
homoallylic hydrazines, respectively. Homoallylic hydroxylamines were isolated via addition of
allylindium to aldonitrones. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: hydrazones; nitrones; allylindium.
Organometallic reactions in aqueous media have recently found considerable application in
organic synthesis as they offer significant advantages over conventional reactions using dry
organic solvents. The metal mediated addition of an allylic moiety into a carbon framework is
of particular interest and among various metals employed for this purpose,1 indium attracts
unique attention2 due to the distinct advantages it offers in comparison with other metals such
as Zn, Mg and Sn. CꢁN unsaturated compounds are good electrophiles3 capable of reacting with
organometallic compounds and allyl-indium reagents have been successfully added to various
CꢁN unsaturated groups such as imines and nitriles, to generate a host of compounds bearing
the homoallylic group. In continuation of our efforts for convenient metal mediated organic
transformations,4 we report here indium mediated allylation of CꢀN systems that have not been
studied so far, such as tosyl and aryl hydrazones and aldonitrones in a DMF–water system.
An allylindium reagent generated in situ readily undergoes addition to the ‘CꢀN’ bond of
tosyl hydrazones in a DMF–H2O system at ambient temperature (Scheme 1).
Moderate to high yields of homoallylic tosyl hydrazides were isolated after 7–13 h of reaction.
The product formation was ascertained by TLC monitoring and the product isolation was
achieved by quenching the reaction with aqueous ammonium chloride solution followed by
solvent extraction. The reactions are generally clean and no trace of N-allylated product could
* Corresponding author.
† IICT Communication No. 4289.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01676-2

9312
Scheme 1.
1
be detected in the H NMR spectra of the crude products. However, purification wherever
necessary was performed by flash chromatography. On the basis of the good results obtained
with sulfonyl hydrazones it seemed logical to investigate the possibility of extending this
methodology to simple aryl substituted hydrazones, which gave unsymmetric homoallylic
hydrazines in good yields. These results are summarised in Table 1, which clearly indicate that
the present strategy becomes a general allylation protocol for a variety of tosyl and aryl
hydrazones derived from different aldehydes and ketones.8a‡
Table 1
Reaction of allylindium reagent with aryl and tosyl hydrazonesa
Entry
Ar
R
Ar1
Reactionb time (h)
Yieldc,d (%)
a
b
c
d
e
f
g
h
i
C6H5
H
H
H
H
H
H
H
C6H5
CH3
H
SO2C6H4CH3
SO2C6H4CH3
SO2C6H4CH3
SO2C6H4CH3
SO2C6H4CH3
SO2C6H4CH3
SO2C6H4CH3
SO2C6H4CH3
SO2C6H4CH3
C6H5
8
10
9
11
10
12
13
7
89
83
82
80
80
75
77
77
90
85
88
4-CH3C6H4
4-CH3OC6H4
4-NO2C6H4
3,4-(OCH2O)C6H3
4-ClC6H4
3,4-Cl2C6H3
C6H5
C6H5
C6H5
4-CH3OC6H4
8
8
10
j
k
H
C6H5
a Prepared by standard literature methods.4
b Reactions carried out at room temperature (25°C).
1
c All products were characterised by H NMR and Mass spectrometry.
d Yields of the product after chromatography.
Homoallylic hydroxylamines are synthetically valuable intermediates5 which can be generated
through the allylation of aldonitrones which also act as good electrophiles for organometallic
additions.6 Even though this reaction has been reported using metals such as Zn, Mg and Sn in
dry organic solvents, the same has not been investigated under aqueous conditions. We found
that various aldonitrones derived from aromatic aldehydes undergo allylation when reacted with
a stoichiometric quantity of the allylindium reagent (generated in situ) in a DMF–H2O system
at ambient temperature (Scheme 2).8b
‡ One limitation of the present methodology is that the reaction does not work with aliphatic hydrazones, as these
do not work under these reaction conditions.

9313
Scheme 2.
The results summarised in Table 2 reveal the generality of this methodology in terms of
structural variations of the nitrone moiety and in each case homoallylic hydroxylamines were
isolated in good yields (75–90%) within 3–4 h of reaction time.
Table 2
Reaction of allylindium reagent with aldonitronesa
Entry
R
Reactionb time (h)
Yieldc,d (%)
a
b
c
d
e
f
C6H5
3
3
3.5
4
4
90
86
85
84
75
76
88
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
3-HOC6H4
3-NO2C6H4
3,4-(OCH2O)C6H3
3
3
g
a Prepared by standard literature methods.7
b Reactions carried out at room temperature (25°C).
1
c All products were characterised by H NMR and Mass spectrometry studies.
d Yields of the product after chromatography.
In conclusion we present in this paper a high yielding allylation procedure for tosyl/aryl
hydrazones and aldonitrones in a DMF–H2O system to generate structurally interesting homoal-
lylic nitrogen compounds.
Acknowledgements
S.A and E.J.R thank CSIR New Delhi for the award of fellowships.
References
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9333. (i) Li, C. J.; Chen, D. L.; Lu, Y. Q.; Haberman, J. X.; Mague, J. T. J. Am. Chem. Soc. 1996, 118, 4216. (j)
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1998, 39, 8605.

9314
4. (a) Cintas, P. Synlett 1995, 1087. (b) Li, C. J.; Chan, T. H. Tetrahedron 1999, 55, 11149. (c) Creary, X. Org. Synth.
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8. (a) In a typical procedure a suspension of indium powder (1.14 g, 10 mmol) and allyl bromide (1.2 g, 10 mmol)
taken in 20 ml of DMF–H2O 15:5, was stirred until the metal dissolved completely to form a clear solution. To
the allyl indium reagent generated as above, a solution of hydrazone (1a, 2.74 g, 10 mmol) in DMF (10 ml) was
added. The resulting reaction mixture was stirred for 8 h at room temperature. The reaction was then quenched
with aqueous ammonium chloride (10%, 20 ml) followed by extraction with ether (2×20 ml). The combined ether
extract was washed with brine (2×10 ml), dried over anhydrous sodium sulfate and the residue obtained after
evaporation of solvent was chromatographed on silica gel [Merck (finer than 200 mesh) EtOAc–n-hexane 1:4] to
1
afford pure product (3a) as a colourless crystalline solid. H NMR (CDCl3): l 2.15–2.30 (m, 2H), 2.40–2.50 (s,
3H), 4.00–4.10 (t, J=7.2 Hz, 1H), 5.00–5.20 (m, 2H), 5.65–5.90 (m, 1H), 7.20–7.40 (m, 5H), 7.50–7.60 (m, 2H),
7.80–7.90 (d, J=7.7 Hz, 2H), 8.60 (brs, NH). MS: m/z 316 (M+, 8%), 131 (100%), 116 (8%), 91 (80%), 77 (10%).
(b) In a typical procedure, a suspension of indium powder (1.14 g, 10 mmol) and allyl bromide (1.2 g, 10 mmol)
taken in 20 ml of DMF–H2O 15:5, was stirred until the metal dissolved completely to form a clear solution. To
the allyl indium reagent, generated as above, a solution of aldonitrone (4a, 1.97 g, 10 mmol) in DMF (10 ml) was
added. The resulting reaction mixture was stirred for 3 h at room temperature. The reaction was then quenched
with aqueous ammonium chloride (10%, 20 ml) followed by extraction with ether (2×20 ml). The combined ether
extract was washed with brine (2×10 ml), dried over anhydrous sodium sulfate and the residue obtained after
evaporation of solvent was chromatographed on silica gel [Merck (finer than 200 mesh) EtOAc–n-hexane 1:4] to
1
afford pure product (5a). H NMR (CDCl3): l 2.50–2.70 (m, 2H), 4.30–4.40 (t, J=7.2, 1H), 5.05–5.25 (m, 2H),
5.60–5.80 (m, 1H), 6.45–6.60 (d, J=8.6 Hz, 2H), 6.65–6.70 (t, J=7.2 Hz, 1H), 7.00–7.10 (t, J=7.2 Hz, 2H),
7.20–7.40 (m, 6H). MS: m/z 238 (M+, 23%), 182 (100%), 131 (61%), 104 (31%), 91 (23%), 77 (49%), 41 (13%).
.