Samarium diiodide-mediated intermolecular coupling of organic halides with cyclic imides

Article abstract of DOI:10.1016/S0040-4039(00)02148-1

SmI₂-mediated couplings between a variety of organic halides and cyclic imides have been performed giving either hydroxylactams from N-methylsuccinimide and N-methylphthalimide or δ-ketoamides from N-methylglutarimide. In the latter case, ring opening occurs during hydrolysis. Couplings of imides with alkyl halides require a catalytic amount of NiI₂.

Full text of DOI:10.1016/S0040-4039(00)02148-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 879–881
Samarium diiodide-mediated intermolecular coupling of organic
halides with cyclic imides
Sorin Farcas and Jean-Louis Namy*
Laboratoire de Catalyse Mole´culaire, associe´ au CNRS, ICMO, Bat 420, Universite´ Paris-Sud, 91405 Orsay, France
Received 20 October 2000; accepted 21 November 2000
Abstract—SmI2-mediated couplings between a variety of organic halides and cyclic imides have been performed giving either
hydroxylactams from N-methylsuccinimide and N-methylphthalimide or d-ketoamides from N-methylglutarimide. In the latter
case, ring opening occurs during hydrolysis. Couplings of imides with alkyl halides require a catalytic amount of NiI2. © 2001
Elsevier Science Ltd. All rights reserved.
Intramolecular as well as intermolecular couplings of
organic halides with carbonyl compounds, mediated by
samarium(II) derivatives, have been widely investi-
gated.1 However, few studies have been devoted to
coupling with imides. To the best of our knowledge,
only intramolecular Barbier-type reactions with N-
(iodoalkyl)succinimides and N-(iodoalkyl)phthalimides
have been reported.2,3 These reactions are slow (2–3 h
1) 1.25 equiv; n-C7H15
I
2.5 equiv. SmI2; (1 mol % NiI2)
20°C; 10 min
n-C7H15
OH
O
O
1
N
2) HCl 0.1 M
CH3
isolated yield: 90%
O
O
N
CH3
1) idem
n-C6H13
2) HCl 0.5 M
N
2
CH3
isolated yield: 92%
Scheme 1.
OH
H
SmI2
N
O
O
N
1) 2 SmI2/RX
O
CH3
R
SmI2
SmI2
CH3
R
R
R
O
O
N
O
2) H3O+
R
(not detected)
O
CH3
OSmI2
O
O
O
O
2 SmI2
RX
I2Sm
I2Sm
R
R
O
R
O
Scheme 2.
Keywords: samarium diiodide; imides; nickel diiodide; organic halides; coupling reactions.
* Corresponding author. Tel.: +33-1-69-15-4743; fax: +33-1-69-15-4680; e-mail: jelonamy@icmo.u-psud.fr
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02148-1

880
S. Farcas, J.-L. Namy / Tetrahedron Letters 42 (2001) 879–881
at 0°C), they require a catalyst (Fe(DBM)3) and afford,
in most cases, the dehydration products (enamides) in
moderate to good yields.
The results concerning N-methylsuccinimide are gath-
ered in Table 1.
Hydrolysis has been achieved with 0.5 M HCl. In every
case only dehydration products have been isolated.
Reformatsky-type reactions have been performed with
an a-halogenoester (entry 5) and a-halogenoamides
(entries 6 and 7), giving polyfunctionalized compounds
in good yields. For these reactions and the one involv-
ing benzyl bromide (entry 4), nickel diiodide is not
necessary. Reactivity of the SmI2 (NiI2 catalytic)/RX
system differs from those of organomagnesium and
organolithium. With these reagents, proton abstraction
and subsequent dimerization are always observed.7
Interestingly, less basic organocerium reagents (RMgX/
CeCl3) give selective nucleophilic substitution, but
afford amidoketones in moderate yields.8
We wish to report some results concerning intermolecu-
lar Barbier-type and Reformatsky-type reactions medi-
ated by samarium diiodide with N-methylsuccinimide,
N-methylphthalimide and N-methylglutarimide. We
found that samarium diiodide in the presence of a
catalytic amount of nickel diiodide (1 mol% with
respect to SmI2) mediates a fast coupling reaction
between N-methylsuccinimide and 1-iodoheptane to
give an hydroxylactam 1. Whether dehydration takes
place or not depends on the hydrolysis conditions.
Thus, quenching with 0.5 M HCl instead of 0.1 M HCl
leads to the formation of an alkylene pyrrolidinone 2
(Scheme 1).
No reaction occurs without NiI2, exemplifying again
the beneficial effect of this additive.4 Besides, by using
an excess of the reagents (SmI2: 5 equiv.; 1-iodohep-
tane: 2.5 equiv.) and with a longer reaction time (3 h),
the same products are obtained, showing that only one
carbonyl group is reactive. In addition, contrary to the
result obtained in a Barbier-type reaction with succinic
anhydride,5 the ring opening is never observed. This
difference might be ascribed to a weaker affinity of
samarium for nitrogen than for oxygen (Scheme 2).
In another set of experiments, Barbier-type reactions
have been carried out with N-methylphthalimide in the
presence of the SmI2 (NiI2 catalytic) system, giving
hydroxylactams in good yields with short reaction times
(Scheme 3).
In contrast with N-methylsuccinimide, dehydration
does not occur even if hydrolysis is achieved with HCl
1 M.
Table 1. Coupling reactions with N-methylsuccinimide
1) 2.5 equiv. SmI2; (1 mol % NiI2)
THF; 20°C; 10 min
R
RCH2X
+
O
O
O
N
N
2) HCl 0.5 M
1.25 equiv.
CH3
CH3
Entrya
R
X
Isolated yield (%)
1
2
3
n-C3H7
n-C6H13
I
I
I
Br
Br
Cl
Cl
95
92
89
81
85
55
70
n-C11H23
C6H5
CH3OCO
C6H5NHCO
(C6H5)2NCO
4b
5b
6b
7b
a In a Schlenk tube under argon, to 25 mL of a 0.1 M solution of SmI2 in THF (2.5 mmol) were successively added a solution of NiI2 (2.5×10−3
mmol) in THF (2.5 mL), and a mixture of an organic halide (1.25 mmol) and N-methylsuccinimide (1 mmol) in THF (10 mL) at 20°C. After
10 min stirring, the reaction mixture was quenched with HCl (0.5 M). After the usual work-up,6 the crude material was purified by flash
chromatography on silica gel.
b Without NiI2.
O
O
1) 2.5 equiv. SmI2; (1 mol % NiI2)
THF; 20°C; 10 min
RI
1.25 equiv.
+
N CH3
N CH3
2) HCl 1 M
R
O
HO
R = C2H5 ; isolated yield = 79%
R = n-C4H9 ; isolated yield = 82%
R = n-C7H15 ; isolated yield = 68%
Scheme 3.

S. Farcas, J.-L. Namy / Tetrahedron Letters 42 (2001) 879–881
Table 2. Coupling reactions with N-methylglutarimide
881
H
N
1) 2.5 equiv. SmI2; (1 mol % NiI2)
THF; 20°C; 10 min
R
H3C
RX
+
O
N
O
O
O
1.25 equiv.
2) HCl 0.1 M
CH3
Entrya
R
X
Isolated yield (%)
1
2
n-C4H9
I
I
I
Br
85
83
72
75
n-C7H15
n-C12H25
C6H5CH2
3
4b
a The experimental procedure is similar to the one described in footnote a in Table 1, except quenching with 0.1 M HCl.
b Without NiI2.
H
N
O
H3O+
OH
R
SmI2
H3C
O
N
O
N
R
R
O
O
CH3
CH3
H3O+
SmI2
N
2 SmI2
RX
SmI2
H
N
R
R
R
R
N
R
H3C
H3C
H3C
O
OH
O
OSmI2
O
O
(not detected)
Scheme 4.
Coupling reactions with N-methylglutarimide have
been also investigated (Table 2).
We are currently studying coupling of organic halides
with some other imides, in particular acyl lactams.
In contrast with N-methylsuccinimide, N-methylglu-
tarimide undergoes a ring opening giving, in every case,
exclusively d-ketoamides in good yields. As with N-
methylsuccinimide, the reactions of halogenoalkanes
(entries 1–3) require a catalytic amount of NiI2, but
Reformatsky-type reactions have failed, even in the
presence of NiI2. The use of an excess of the reagents (5
equiv. SmI2; 2.5 equiv. organic halide) gives the same
results (products and yields). This can be explained
assuming the ring opening occurs during the hydrolysis
(whatever conditions used: 0.1 M HCl or NaHCO3/
Rochelle’s salt9). Thus, d-ketoamides would be formed
through a tautomeric equilibrium between an hydroxy-
lactam and a d-ketoamide, which is shifted towards the
latter species in a six-membered ring, as previously
reported (Scheme 4).10
Acknowledgements
We thank the University of Paris-Sud and the CNRS
for their financial support and the Socie´te´ de Secours
des Amis des Sciences for a studentship (S.F.).
References
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621.
In conclusion, N-methylsuccinimide N-methylphthal-
imide and N-methylglutarimide are reactive in samar-
ium diiodide-mediated coupling reactions with organic
halides; with alkyl halides a catalytic amount of nickel
diiodide is required. In contrast with acid anhydrides,
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methylglutarimide it readily takes place during hydroly-
sis furnishing d-ketoamides. It turns out then that the
use of a samarium(II) mediated coupling reaction of
RX with imides can be an interesting alternative to
previously reported reactions of organomagnesium,
organolithium or organocerium.
4. Kagan, H. B.; Namy, J.-L. Topics in Organometallic
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