Organometallic reaction in aqueous media. A samarium induced, efficient, synthesis of homoallyl hydroxylamines and hydrazides

Article abstract of DOI:10.1016/S0040-4039(01)01637-9

Samarium can be used directly for the allylation of aldonitrones and hydrazones in aqueous media in the presence of Bu₄NBr.

Full text of DOI:10.1016/S0040-4039(01)01637-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7883–7886
Organometallic reaction in aqueous media. A samarium induced,
efficient, synthesis of homoallyl hydroxylamines and hydrazides
Dhrubojyoti D. Laskar, Dipak Prajapati* and Jagir S. Sandhu
Regional Research Laboratory, Jorhat, 785006 Assam, India
Received 19 June 2001; revised 20 August 2001; accepted 30 August 2001
Abstract—Samarium can be used directly for the allylation of aldonitrones and hydrazones in aqueous media in the presence of
Bu4NBr. © 2001 Elsevier Science Ltd. All rights reserved.
Metal mediated reactions in aqueous media have
recently found considerable application in organic syn-
thesis as they offer significant advantages over conven-
tional reactions using dry organic solvents. The
addition of an allylic organometallic moiety to a carbon
framework is of particular interest and among various
metals employed for this purpose,1 samarium attracts
unique attention2 due to the distinct advantages it
offers in comparison with other metals such as Zn, Sn,
Mg, Cd and Bi. The main drawbacks of these metals
are long reaction times and only reactive halides are
found to be effective. The use of samarium3 is also
rapidly increasing because of its advantages (availabil-
ity, solubility and cost) over the widely-used single-elec-
tron transfer reagent, samarium diiodide. Yanada2c has
studied extensively various reactions mediated by
samarium in conjunction with different types of Lewis
acids. We have also studied4 a facile coupling of keto-
cyanides to 1,2-diketones by this metal in the presence
of a catalytic amount of iodine. Kagan et al. have
demonstrated5 and favorably compared the samarium
diiodide-mediated Barbier reaction of aldehydes and
ketones with other available methods. This method
using samarium diiodide is good, but the commercially-
available reagent is expensive, and is also moisture- and
air-sensitive. As an alternative, this reagent can be
prepared in situ in an inert atmosphere under very
stringent conditions. In a very recent report6 for the
Barbier type allylation of ketones in the presence of
samarium metal, the authors observed the formation of
unexpected reductive coupled products (diols) instead
of the allylated products. In continuation of our ongo-
ing programme on metal mediated organic transforma-
tions,7 we report herein the first example of samarium
mediated allylation of aldonitrones and hydrazones
under aqueous conditions using tetrabutylammonium
bromide (TBAB) as an additive (Scheme 1).
The 1,3-dipolar cycloaddition reactions of nitrones
have been studied extensively, but nitrones also
undergo several other reactions which are far less well
known. Addition of organomagnesium or organo-
lithium reagents to aldonitrones provides N,N-disubsti-
tuted hydroxylamines8 which can be reduced to
secondary amines. These hydroxylamines are syntheti-
cally valuable intermediates9 and can be generated
through the allylation of aldonitrones which act as
good electrophiles for organometallic additions.10
Examples of organometallic additions to ketonitrones
have also been reported,11 albeit in cases limited to
cyclic nitrones. We have found that various
Scheme 1.
Keywords: samarium; homoallyl hydrazides; aldonitrones; hydrazones; homoallyl hydroxylamines.
* Corresponding author. Fax: +91 376 370011, +91 376 370116; e-mail: drrljt@csir.res.in
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01637-9

7884
D. D. Laskar et al. / Tetrahedron Letters 42 (2001) 7883–7886
Table 1. Samarium mediated allylation of aldonitrones 1 and hydrazones 4

D. D. Laskar et al. / Tetrahedron Letters 42 (2001) 7883–7886
7885
Scheme 2.
aldonitrones and hydrazones derived from aromatic
aldehydes undergo allylation when reacted with a stoi-
chiometric quantity of the allylsamarium reagent gener-
ated in situ in a Bu4NBr–DMF–H2O system at room
temperature.
aldehyde was successfully allylated. Usually, the nitro
group is sensitive to reduction by metals and can not be
allylated under Barbier conditions.8 In this sense, the use
of TBAB as an activating agent is superior to the use of
Al, Fe or NaBH4 reported previously.9 Also, allyl iodide
was found to be as reactive as allyl bromide, but the
reactivity of allyl chloride was found to be much less.
Furthermore, the reaction is not equally effective when
aliphatic aldonitrone 1g or aliphatic hydrazone 4f were
used as substrate. The reaction takes 11–12 h in 55–61%
yields only (Table 1). Further, increasing the reaction time
gave no significant improvement on the yield and resulted
indecompositionofproduct. Interestingly, whenthesame
experiment was performed with ketone (acetophenone)
derived nitrone or hydrazone, the reaction did not yield
any allylated product and the starting materials were
recovered, after stirring at room temperature for 18–20
h. Moreover, the reaction failed to produce any desired
product when THF–H2O (3:1) or THF was used as
solvent. This indicated that the nature of the solvent is
important in the formation of the product in the samar-
ium-induced allylation reaction. Although, the detailed
mechanism of the reaction is not clear, it is likely that
Bu4NBr effects the generation of an active organosamar-
ium reagent.
In a typical procedure, a suspension of samarium powder
(1.5 g, 10 mmol), allylbromide (1.2 g, 10 mmol) and TBAB
(0.322 g, 1 mmol) was taken in 15 ml DMF–H2O (2:1)
in a 150 ml round bottom flask and the mixture stirred
at room temperature until all the metal dissolved to form
a clear solution. To the reaction mixture was then added
a solution of aldonitrone 1a (1.97 g, 10 mmol) in DMF.
The resulting mixture was stirred for 1.5 h at room
temperature. After completion (monitored by tlc) the
reaction was quenched with dil. HCl and poured into
ice-cold water, followed by extraction with ether (3×20
ml). The combined ether extract were washed with brine,
dried over anhydrous sodium sulphate and the residue
obtained thereafter on evaporation of the solvent was
subjected to column chromatography using ethyl acetate–
hexane 1:5 as eluent to afford the pure product 3a in 85%
yield. Similarly, other aldonitrones and hydrazones12
werereacted, seeTable1. Thereactionsaregenerallyclean
and no trace of an N-allylated product could be detected
in the NMR spectra of the crude products. All products
were characterized by infrared and 1H NMR spec-
troscopy, and by comparison with authentic samples
(Scheme 2).
In conclusion, this simple and easily reproducible tech-
nique using samarium under aqueous conditions affords
various homoallyl hydrazides and homoallyl hydroxyl-
amines of potentially high synthetic utility in excellent
yields and without the formation of any undesirable side
products.
The effect of Bu4NBr was found to be remarkable,
virtually no allylation occurring in its absence. We tried
a number of alkaline metal salts to activate the metal like
NaBr, KBr, MgBr2 and KCl in aqueous media in place
of Bu4NBr, but found these to be ineffective giving no
reaction. However, a 1 M concentration of NH4Cl was
found to quite effective in activating the samarium to give
a good yield of the corresponding homoallylic hydroxyl-
amines and hydrazides. Roughly 0.1 equivalent of
Bu4NBr was found to be sufficient for these reactions and
the use of a large excess did not result in higher yields
or better reaction rates. We thus use Bu4NBr as the
standard additive to activate commercial samarium metal
and examined its reaction with a number of aldonitrones
and hydrazones. The results are summarised in Table 1.
These results reveal the generality of this methodology
in terms of structural variations of the nitrone moiety and
in each case homoallylic hydroxylamines were isolated in
excellent yields within 1.5–2 h (entries 1–7). Furthermore,
electron-donating or -withdrawing groups on the aro-
matic ring did not seen to affect the reaction significantly
either in the yield of the product or the rate of the reaction.
Moreover, nitro functions were not reduced under the
reaction conditions. Thus the nitrone from 3-nitrobenz-
Acknowledgements
One of us (D.D.L.) thanks Council of Scientific and
Industrial Research (CSIR), New Delhi for the award of
a senior research fellowship to him.
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