Access to functionalized imidazolidin-2-one derivatives by Iron-catalyzed oxyamination of alkenes

Article abstract of DOI:10.1002/chem.201802190

Functionalized imidazolidin-2-one were prepared by using an iron-catalyzed alkene oxyamination reaction. Hy-droxylamine derivatives were used in this atom-economical process, and the addition of an external oxidant was not required. The conditions developed were shown to be efficient for mono-, di-, and trisubstituted double bonds, and a large scope of diamino alcohol precursors were delivered in good yields with good diastereoselectivities. The mechanistic pathway was studied and appears to involve both a fused aziridine and a carbocationic species.

Full text of DOI:10.1002/chem.201802190

A Journal of
Accepted Article
Title: Access to functionalized imidazolidin-2-one derivatives by iron-
catalyzed oxyamination of alkenes
Authors: Anne-Doriane Manick, Sidonie Aubert, Boubacar Yalcouye,
Thierry Prangé, Farouk Berhal, and Guillaume Prestat
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To be cited as: Chem. Eur. J. 10.1002/chem.201802190
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Access to functionalized imidazolidin-2-one derivatives by iron-
catalyzed oxyamination of alkenes
Anne-Doriane Manick,[a] Sidonie Aubert,[a] Boubacar Yalcouye,[a] Thierry Prangé,[b] Farouk Berhal*[a]
and Guillaume Prestat*[a]
Abstract: Functionalized imidazolidin-2-one were prepared using an
iron catalyzed alkene oxyamination reaction. This atom-economical
process is using hydroxylamine derivatives without addition of any
external oxidant. The conditions developed are efficient on mono-,
di- and tri-substituted double bonds leading to good yields and
diastereoselectivities and allow the access to a large scope of
diaminoalcohol precursors. Mechanistic pathway was studied and
appeared to involve both a fused aziridine and a carbocationic
species.
Vicinal amino-oxygenation of alkenes has become a
powerful reaction for the access of amino-alcohol moieties in a
single step from olefins.[8] Since the pioneer work reported by
Sharpless for asymmetric amino-hydroxylation of alkenes,[9]
great progresses have been made in intramolecular or
intermolecular versions, using various metals such as Os,[10]
Rh,[11] Pd,[12] Pt,[13] Cu,[14] Fe,[15] Au,[16] or Ag.[17] The group of
Hao Xu reported recently an iron-catalyzed intramolecular
amino-oxygenation
of
alkenes
using
hydroxylamine
derivatives.[18] This original approach fits in perfectly with the
field of sustainable chemistry as a totally atom-economic
process in which all the atoms of the substrate are conserved on
the product using an environmentally benign metal catalyst.
Moreover, the process is also step-economical as cyclization
and formation of carbon-nitrogen and carbon-oxygen bonds
occurred in a single step. Despite the great potential of this
reaction, only the synthesis of oxazolidinone compounds has
been reported to date. In order to get a broader scope, we
describe herein the iron-catalyzed intramolecular amino-
oxygenation of allyl-benzoyloxy urea derivatives for the
synthesis of 4-methylene-oxy-functionalized imidazolidin-2-one
products as 1,2,3-diaminoalcohol precursors.
Introduction
Imidazolidinone scaffolds are important building blocks
found in many biologically active drugs and natural products.
The vitamin B7 and the marine sponge alkaloid Agelastatin[1]
(antitumor activity) as well as the angiotensin-converting-
enzyme inhibitor Imidapril (treatment of chronic heart failure) are
some representative examples of this class of compounds
(Figure 1).[2] Furthermore, 4-methylene-oxy-functionalized
imidazolidin-2-one are important precursors of 1,2,3-diamino-
alcohol derivatives and are used as versatile intermediates for
the preparation of pharmaceuticals or bioactive products such as
Tamiflu (influenza A/B treatment)[3] and Balanol (potent protein
kinase A and B inhibitor, Figure 1).[4] The classical routes for the
synthesis of diamino-alcohol moieties involve multistep
processes with several protection and deprotection reactions,
consuming a large amount of resources. During the last decades,
the concept of sustainable chemistry has emerged with the idea
of minimizing negative environmental impacts of chemical
processes.[5] Thus, the development of atom- and step-
economical methodologies is, today more than ever, an
essential scientific and societal concern.[6] In this context,
following our research program dedicated to the development of
domino reactions and hetero-functionalization of alkenes,[7] we
became interested in the preparation of 1,4-disubstituted
imidazolidin-2-one scaffolds via an atom-economical approach.
Figure 1. Imidazolidinone and diamino-alcohol in bioactive compounds.
Results and Discussion
[a]
Dr. A.-D. Manick, S. Aubert, Dr. B. Yalcouye, Dr. F. Berhal, Pr. Dr.
G. Prestat
We initiated the reaction optimization using compound 1a
as model substrate, iron(II) acetate as catalyst and acetonitrile
as solvent. The target product 2a was isolated in a poor 26 %
yield (Table 1, entry 1). A screening of potential ligands was
conducted using first a series of bidentate nitrogen-based
derivatives. The addition of 2,2’-biquinoline L1 and 2,2’-
bipyridine L2 increased the yield and product 2a was obtained in
34 % and 39 % respectively (Table 1, entries 2 and 3).
Functionalized phenanthrolines were then tested. The use of
1,10-phenanthroline L3 led to a moderate 39 % yield (Table 1,
Laboratoire de Chimie et Biochimie Pharmacologiques et
Toxicologiques, UMR CNRS 8601, Université Paris Descartes, 45
rue des Saints Pères, 75006 Paris, France.
E-mail: farouk.berhal@parisdescartes.fr,
guillaume.prestat@parisdescartes.fr
[b]
Pr. Dr. T. Prangé
Laboratoire de Cristallographie et RMN Biologiques, UMR CNRS
8015, Université Paris Descartes, 4 avenue de l’Observatoire,
75270 Paris, France.
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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entry 4) whereas the electron-rich 3,4,7,8-tetramethyl-1,10-
phenanthroline L4 induced a dramatic decrease in the reaction
efficiency (14 % yield, Table 1, entry 5). The more electron-rich
4,7-dimethoxy-1,10-phenanthroline L5 and the electron-poor
3,5,6,8-tetrabromo-1,10-phenanthroline L6 gave yields close to
that observed in the presence of ligand L3 (respectively 40 %
and 34 % yield, Table 1, entries 6 and 7). Tridentate nitrogen-
based ligands were then screened. The 2,2’:6’,2’’-terpyridine L7
gave a moderate 34 % yield whereas the pybox derivative L8
gave a poor 20 % yield (Table 1, entries 8 and 9). Finally, the
diketone-based 1,3-diphenylpropanedione ligand L9 was tested
were found almost as efficient (52 and 50 % yield respectively,
entries 5 and 6) the latter substituent was chosen for the
following studies since this moiety is easier to remove. The
addition of 2,4-dichlorobenzoic acid or the corresponding sodium
salt to the reaction mixture, as an external nucleophile, did not
increase significantly the yield (53 % vs. 50 %, Table 2, entry 6
vs. 7 and 8). Interestingly, the use of an acetate group instead of
a benzoate derivative led to a similar result (50 %, Table 2, entry
9 vs. 6). A control experiment in the absence of iron catalyst was
performed and surprisingly the target product was obtained,
although in a poor 16 % yield (Table 2, entry 10). This result
affording the target product 2a in a moderate 37 % yield (Table 1, suggests a cleavage of the N-O bond under thermic conditions
entry 10). The best yields were thus obtained with ligands L2, L3
and L5 and the 1,10-phenanthroline ligand L3 was selected to
continue the optimization.
generating reactive species, which could undergo insertion on
the double bond to afford the target compound. The substituent
on the N-2 atom was then modulated. By using the 3,4-
dimethoxybenzyl derivative, a decrease in the reaction efficiency
was observed (43 %, Table 2, entry 11). A satisfying yield was
obtained for the substrate 1i with N-2 bearing a simple hydrogen
atom (67 % yield, Table 2, entry 12). Finally, the best yields
were obtained for products 2j and 2k respectively 75 % and
76 % with N-2 bearing a methyl or an allyl moiety (entries 13 and
14).
Table 1. Screening of ligands.
entry[a]
1
ligand
---
yield (%)[b]
26
Table 2. Study of N-1 and N-2 substitution.
2
34
3
4
39
39
yield
entry[a]
1
R1
R2
substrate
product
5
6
14
40
(%)[b]
41
Bn
1a
2a
2
3
4
5
Bn
Bn
Bn
Bn
1b
1c
1d
1e
42
23
45
52
2b
2c
2d
2e
7
8
34
34
20
37
9
10
6
Bn
Bn
1f
1f
50
53
2f
2f
7[c]
[a] Reactions were carried out under Ar using 1a (1 equiv), Fe(OAc)2 (10
mol %), ligand (20 mol %), in ACN for 18 h at 70 °C. [b] Isolated yields.
8[d]
9
Bn
Bn
Bn
1f
53
50
16
2f
Me
1g
1f
2g
2f
The nature of solvent and catalyst as well as the effect of
additives were then studied. No improvement was observed by
using other classical polar and non-polar solvents or other iron
complexes (see Supporting Information). The effect of the
temperature on the reaction course was also investigated. A
slight increase in the yield and a cleaner reaction were observed
at 100 °C (41 % yield, Table 2, entry 1). Having in hand the
optimized reaction conditions in terms of catalyst, solvent and
temperature (iron(II)-acetate, 1,10-phenanthroline, ACN, 100 °C),
we turned our attention to the effects of the N-1 and N-2
substitution. First, the benzoyl moiety on the N-1 atom was
modulated. Different electron-rich and electron-poor aryl groups
were evaluated leading to yields between 23 and 52 % (Table 2,
entries 1-6). While 2,4,6-trimethyl- and 2,4-dichloro-benzoyl
10[e]
11
12
13
14
3,4-diMeO-Bn
1h
1i
43
67
75
76
2h
2i
H
Me
Allyl
1j
2j
1k
2k
[a] Reactions were carried out under Ar using substrate 1 (1 equiv), Fe(OAc)2
(10 mol %), phenanthroline (20 mol %), in ACN for 18 h at 100 °C. [b] Isolated
yields. [c] 1 equiv of 2,4-dichlorobenzoic acid was added. [d] 1 equiv of 2,4-
dichlorobenzoic acid sodium salt was added. [e] Without iron at 100 °C.
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To study the scope of this transformation special attention
was paid to disubstituted alkenes which represent a challenge
for oxyamination reactions catalyzed by other metals.[7e,19] We
began our investigations by replacing the reactive allyl
appendage by a cinnamyl group (Table 3).
Substrate 3a was thus submitted to the reaction conditions.
Gratifyingly, excellent diastereoselectivity and good yield were
observed for the phenyl-substituted product 4a (96:4 dr, 74%
yield, Table 3, entry 1). The impact of the substitution on N-1
and N-2 atoms on the reaction outcome with cinnamyl
substrates was also explored. Switching from the 2,4-
dichlorobenzoyl to a simple benzoyl on N-1 did not impact the
yield of the reaction and only a slight decrease of the dr, from
96:4 to 92:8, was obtained for 4b vs 4a (Table 3, entry 2 vs 1).
As previously observed (Table 2), replacing the methyl on N-2
by a benzyl group induced a significant drop in the yield. Indeed,
compounds 4c and 4d were isolated in 55 % and 47 % yield
respectively still in high dr (Table 3, entries 3 and 4 vs 1 and 2).
These results clearly demonstrated that the diastereoselectivity
is poorly influenced by the N-1 and N-2 substitution, while the
yield is dramatically affected. Disubstituted E-alkenes bearing
electron-donating and electron-withdrawing styryl groups were
then evaluated (Table 3). The electron-deficient substrates 3e
and 3f reacted smoothly affording 2-nitrophenyl 4e and 4-
chlorophenyl 4f products in a good 94:6 dr and moderate to
good yields, 45 % from the sterically demanding substrate 3e
and 76 % from 3f (Table 3, entries 5 and 6). On the contrary, the
electron-rich products 3-methylphenyl 4g, 4-methylphenyl 4h, 4-
methoxyphenyl 4i and 2-methoxyphenyl 4j were isolated in good
yields (from 61 % to 76 %) but in moderate to poor dr (from
38:62 to 12:88, Table 3, entries 7-10). These results highlighted
the influence of the electronic effects of the styryl moiety on the
selectivity of the transformation and could suggest different
mechanistic pathways for electron deficient and electron rich
alkenes.
Table 3. Exploration of the scope for styryl derivatives.
yield
entry[a]
substrate
major product
anti:syn[c]
96:4
(%)[b]
1
74
2
3
4
75
55
47
92:8
92:8
94:6
5
45
94:6
To explore more deeply the scope, we then focused on
diversely functionalized olefins (Table 4). Good yields and
moderate dr were obtained for the crotyl, propyl and prenyl
derivatives 4k, 4l and 4m (71 %, 75 % and 72 % yield
respectively, Table 4, entries 1-3). The styryl product 4n, which
can be seen as an interesting scaffold for post-functionalization,
was isolated in a moderate 47 % yield and a poor 60:40 dr
(Table 4, entry 4). The methallyl substrate 3o led to product 4o
in a good 68 % yield unlike the phenyl analogue 4p, which was
isolated in a poor 34 % yield (Table 4, entries 5 and 6). The yield
of this latter compound could be increased to 56 % by changing
the 2,4-dichlorobenzoyl group on N-1 to a simple benzoyl
derivative (Table 4, entry 7 vs 6). The vinyl benzyl compound 3r
also underwent the transformation and gave product 4r in
moderate yield and dr (50 %, 70:30, Table 4, entry 8). Finally,
the cyclohexyl substrate 3s led to a unique diastereoisomer with
a moderate 41 % yield which highlighted the impact of the
conformation on the diastereoselectivity (Table 4, entry 9).
6
7
76
76
76
75
61
94:6
80:20
70:30
12:88
38:62
8
9
10
[a] Reactions were carried out under Ar using substrate (1 equiv), Fe(OAc)2 (10
mol %), phenanthroline (20 mol %), in ACN for 18 h at 100 °C. [b] Isolated
yields. [c] dr determined by 1H NMR on the crude mixture.
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Table 4. Exploration of the reaction scope.
yield
entry[a]
substrate
major product
anti:syn[c]
60:40
(%)[b]
1
71
Figure 2. Single crystal X-Ray analysis for compounds 4a and 4i.
2
3
75
72
80:20
---
Finally, our reaction conditions were applied on a 1 gram
scale experiment (3.3 mmol) using substrate 1j, which afforded
compound 2j in 74 % yield as expected. To demonstrate the
easy access to interesting building blocks from the
functionalized imidazolidinone products synthesized, the
cleavage of the protective groups was carried out on compound
2j. The ester moiety was easily removed in the presence of
potassium carbonate with an excellent 91 % yield. Furthermore,
the urea was cleaved using an aqueous 3 M HCl solution to
afford the diamino-alcohol salt 6 in a quantitative yield (Scheme
1).
4
47
60:40
5
6
68
34
---
---
7
56
---
Scheme 1. Deprotection reactions.
8
9
50
41
70:30
>98:2
Regarding the mechanism of this transformation, the group
of Hao Xu proposed an iron nitrenoid as key intermediate, which
one could undergo either an olefin aziridination or a direct
oxyamination reaction through carbo-radical species.[18] The
authors emphasized that the rate of aziridination versus
oxyamination depends on the counterion and ligand
combinations. In order to postulate a mechanism applicable to
our conditions, we conducted various control experiments. First,
substrate 1a was submitted to our reaction conditions
decreasing the temperature from 100 °C to rt. This allowed the
isolation of the aziridine 7 in 40 % yield.[21] The pure aziridine
was next submitted to the oxyamination reaction conditions in
the presence of 1 equivalent of benzoic acid. The expected
product 2a was isolated in 39 % yield (Scheme 2-a). Similarly,
the E-styryl substrate 3d afforded at rt the corresponding
aziridine 8 which was isolated with a moderate 43 % yield as the
single trans-isomer.[21] The pure aziridine 8 was then subjected
to the reaction conditions in the presence of 1 equivalent of
benzoic acid and the compound 4d was obtained in a good
77 % yield and excellent 96:4 dr (Scheme 2-a). These
experiments demonstrated that the aziridines 7 and 8 can be
[a] Reactions were carried out under Ar using substrate (1 equiv), Fe(OAc)2 (10
mol %), phenanthroline (20 mol %), in ACN for 18 h at 100 °C. [b] Isolated
yields. [c] dr determined by 1H NMR on the crude mixture.
The stereochemistry was assigned using single crystal X-
Ray diffraction for compounds 4a, 4i, 4k, 4l and 4s and NMR
correlations were used for the other products (Figure 2).[20] The
major stereoisomer comes from a global anti-addition except,
surprisingly, for the methoxy derivatives 4i and 4j.
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opened in the reaction conditions and are possible intermediates
in this transformation. We then conducted a one pot procedure
involving independently substrates 1a and 3d. The reaction was
launched at room temperature and after observation of the
aziridine intermediate (based on TLC analysis), the solution was
heated at 100 °C without addition of any additive. The
oxyamination products 2a and 4d were isolated in respectively
45 % and 53 % yield (94:6 dr for 4d, Scheme 2-b). These results
are similar to the ones obtained under the standard conditions
(see Table 2, entry 1 and Table 3, entry 4). Therefore, we
hypothesized that for these substrates the reaction proceeded
through an aziridination followed by a SN2 type opening route
although the intermediate aziridine was not detected under
these conditions.
Table 5. Study of the influence of the alkene geometry.
yield
entry[a]
substrate
major product
anti:syn[c]
40:60
(%)[b]
1
76
66
50
49
2
3
4
55:45
60:40
75:25
[a] Reactions were carried out under Ar using substrate (1 equiv), Fe(OAc)2 (10
mol %), phenanthroline (20 mol %), in ACN for 18 h at 100 °C. [b] Isolated
yields. [c] dr determined by 1H NMR on the crude mixture.
The Z-styryl substrate 3d’ was thus submitted to our
reaction conditions at rt. To our great surprise, the trans-
aziridine 8 was then isolated as the sole product.[21] Yields and
stereochemistry of the aziridine isolated were thus equivalent
starting from either Z or E substrates demonstrating thereby a
stereo-convergent formation of the aziridine at rt (Scheme 3 vs
Scheme 2). This result clearly ruled out an aziridination/opening
mechanism for the Z-substrates under our standard conditions
(100°C).
Scheme 2. Mechanistic study.
To gain more insights on the mechanism, the influence of
the alkene’s geometry was also investigated. Compound 3a’, Z-
isomer of 3a, was submitted to the reaction conditions and
afforded the expected products in a similar yield (76 %, Table 5,
entry 1) with a lower dr (40:60 vs 96:4). The reaction of Z-3a’
provided as the major product the opposed isomer than the one
observed starting with the E isomer 3a. The Z isomers 3b’, 3c’
and 3d’ were then studied. Yields were obtained between 49 %
and 66 % with dr from 55:45 to 75:25 (Table 5, entries 2-4).
Surprisingly, the diastereoselectivity of the Z-substrates were
clearly dependent of the N-1 and N-2 functional groups and
inconsistent with E-substrates (Table 5 entries 1-4 vs Table 3
entries 1-4).
Scheme 3. Aziridine formation from substrate 3d’.
Interestingly, the treatment of the Z-styryl derivative 3b’
with five equivalents of 2,4-dichlorobenzoic acid as external
nucleophile under the same reaction conditions gave a 90:10
mixture of the oxyaminated products 4a/4a’ and 4b/4b’ with
65 % yield and 45:55 dr for 4a/4a’ (Scheme 4). Analogous
results were obtained under standard conditions on substrate
3a’ (see Table 5, entry 1 vs Scheme 4) which demonstrated a
non-stereoselective outer sphere addition of the carboxylic acid
for this substrate.
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non-stereoselective manner. The scope of the reaction revealed
a rather different behavior for electron-deficient and electron-rich
styryl substrates (Table 3). While the nitro- and chloro-phenyl
compounds 3e,f led to high dr, the methyl and methoxy
analogues 3g-j constantly provided moderate dr, with opposite
isomer as major product for the methoxy derivatives (Table 3).
Considering the loss of diastereoselectivity observed with the
substrates bearing electron-donating styryl groups,
a
carbocationic intermediate was considered as plausible reactive
species for the transformation. Based on our results we
therefore propose the following mechanism.[24] Insertion of the
iron catalyst into N-O bond of substrate I generates both a
singlet nitrene iron(IV) II and a triplet nitrene iron(III) species II’
close in energy or in equilibrium.[23, 25] Two competitive pathways
can then occur (Scheme 6). Electron-neutral and electron-poor
E-substrates react according to pathway A. The nitrene species
evolves through a concerted process affording the trans-
aziridine III, which gives through a SN2 type ring opening the
anti-product IV. In pathway B, the iron nitrene II’ generates a
short-lived carbo-radical species V, which is rapidly oxidized to
the corresponding carbocationic intermediate VI. Final product
IV is then formed by direct non-stereoselective nucleophilic
addition onto the carbocation or via the trans-aziridine derivative
III. Pathway B is preferentially followed with Z-alkenes for which
steric hindrance disfavors the direct concerted aziridination and
electron-rich substrates that stabilize the intermediate
carbocation.
Scheme 4. Competitive study on compound 3b’ with 2,4-dichlorobenzoic acid
as external nucleophile.
All these observations led us to conclude that the
mechanistic pathway is likely to be substrate dependent and
influenced by the configuration of the double bond, the
temperature, as well as by conformational and electronic effects.
Therefore, the aziridination/opening route cannot be considered
as the only path leading to the oxyamination products. Based on
the mechanism proposed by Hao Xu, carbo-radical species
could be involved. Previous studies have shown that nitrenoid
intermediates can be generated by cleavage of the N-O bond
from hydroxylamine derivatives[22] and that nitrene singlet and
triplet species are close in energy and could interconvert rapidly
depending on the nature of the substrate.[23] This feature could
explain the difference of dr from one product to another. To
investigate the formation of radical species as potential
intermediates, we next introduced a radical trap and a radical
inhibitor in the reaction mixture (Scheme 5). Addition of 5
equivalents of TEMPO on compound 1j induced a decrease in
the yield and compound 2j was isolated in 56 %. However the
formation of compound 9a was not observed. Under the same
conditions compound 3a’ led to 4a/4a’ with identical yield than in
standard conditions and with a slight difference of dr (50:50 vs
40:60) but without observation of product 9b (Scheme 5-a).
Compound 3a’ was also subjected to the reaction conditions in
presence of an excess of BHT giving products 4a/4a’ in 70 %
yield and 50:50 dr (Scheme 5-b). Thus, negligible differences
were obtained by addition of radical scavengers on 1j or 3a’
compared with standard conditions, which led us to conclude
that a long-lived radical species was not involved in this
mechanism.
Scheme 6. Postulated mechanism.
Conclusions
To conclude, we developed sustainable conditions for the
atom-economical preparation of 4-methylene-oxy-functionalized
imidazolidin-2-one derivatives. Moderate to good yields with
good to excellent diastereoselectivities were obtained. This
process is efficient for mono- di- and tri-substituted alkenes,
which represent an important breakthrough in comparison with
other oxyamination processes using palladium as metal catalyst.
Several control experiments were performed to propose
competing mechanistic pathways involving both a fused aziridine
and a carbocation as potential intermediates. Studies are
currently ongoing to extend the scope of this reaction to the
formation of bigger ring size heterocycles and to better clarify
the mechanism.
Scheme 5. Study of radical inhibitors addition
Having ruled out this hypothesis, the formation of a
different reactive species needed to be envisaged to explain the
formation of the functionalized imidazolidinone products in a
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[9]
a) K. B. Sharpless, A. O. Chong, K. Oshima, J. Org. Chem. 1976, 41,
177-179; b) G. Li, H.-T. Chang, K. B. Sharpless, Angew. Chem. Int. Ed.
Engl. 1996, 35, 451-454; c) For reviews, see: H. C. Kolb, K. B.
Sharpless, In Transition Metals for Organic Synthesis; M. Beller, C.
Bolm, Eds.; Wiley: New York, 1998; Vol. 2, pp 243; d) J. A. Bodkin, M.
D. McLeod, J. Chem. Soc., Perkin Trans. 1 2002, 2733-2746.
Experimental Section
Typical procedure for iron oxyamination reaction:
In a sealed tube, 10 mol % of Fe(OAc)2 and 20 mol % of phenanthroline
were placed in ACN (C = 0.1 mol/L) under argon. The solution was
stirred 30 min at room temperature and 1.0 equiv of the desired alkene
substrate was added. The solution was stirred 18 h at 100 °C. The
reaction was then quenched with a saturated aqueous solution of
NaHCO3. The aqueous layer was extracted with DCM (3 times) and the
combined organic phases were then dried with MgSO4, filtrated and the
solvent was removed under vacuum. The crude residue was purified by
silica gel flash chromatography using pentane/EtOAc as eluent (9:1 to
0:10).
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9, 1725–1728.
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Acknowledgements
We thank the CNRS and Université Paris Descartes for financial
support and the Ministère de l’Education Nationale de
l’Enseignement Supérieur et de la Recherche for a grant (A.-D.
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Keywords: iron • alkenes • oxyamination • imidazolidinone •
aziridine
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functionalized
imidazolidin-2-one derivatives by
The iron-catalyzed intramolecular oxyamination of allyl-benzoyloxy urea derivatives
is described. This atom-economical process is using hydroxylamine derivatives
without addition of any external oxidant, affording functionalized imidazolidin-2-one
products as potential 1,2,3-diaminoalcohol precursors. Mechanistic studies
highlighted the corresponding fused aziridine as a viable intermediate to explain this
transformation.
iron-catalyzed
alkenes
oxyamination
of
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