Insertion of ethyl diazoacetate into N-H and S-H bonds catalyzed by ruthenium porphyrin complexes

Article abstract of DOI:10.1039/a704687a

Ruthenium porphyrin complexes catalyze insertion of ethyl diazoacetate into sulfur-hydrogen and nitrogen-hydrogen bonds under mild conditions and with reasonable to very good yields.

Full text of DOI:10.1039/a704687a

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Insertion of ethyl diazoacetate into N᎐H and S᎐H bonds catalyzed
by ruthenium porphyrin complexes
Erwan Galardon, Paul Le Maux and Gérard Simonneaux *
Laboratoire de Chimie Organométallique et Biologique, Associé au CNRS,
Université de Rennes 1, 35042 Rennes Cedex, France
Ruthenium porphyrin complexes catalyze insertion of
ethyl diazoacetate into sulfur–hydrogen and nitrogen–
hydrogen bonds under mild conditions and with reason-
able to very good yields.
materials. Extension of the insertion process to α-methyl-α-
diazo esters is also possible; treatment of ethyl 2-diazopro-
1
2
pionate with thiophenol, in the presence of the ruthenium
porphyrin catalyst at room temperature, afforded the corres-
ponding α-thio ethyl ester with moderate yield (71%) (solvent:
toluene, 3 h). This insertion reaction can be developed to
investigate further the possibility of diastereoselectivity in the
S᎐H insertion of ruthenium carbenoids, using chiral thiols or
The insertion of diazo compounds into heteroatom–H bonds
1
remains of considerable importance in organic synthesis. After
the pioneering work of Yates on the copper-catalyzed decomp-
osition of diazo ketones in the presence of thiophenol and
5
chiral diazo esters as substrates.
2
Having established the S᎐H insertion reactions of diazo
esters as a simple route to α-thio ethyl ester derivatives, we next
investigated the corresponding reactions of N᎐H insertion. The
aniline, little work was done in this area until Paulissen et al.
3
discovered the high catalytic activity of rhodium() acetate.
While the intramolecular version of the insertion has found the
widest use in synthesis, with notably a new approach to bicyclic
II
,10
complex Ru (TMP)CO,† in catalytic amounts, reacts with
ethyl diazoacetate in the presence of alkyl and aromatic
amines‡ to give the corresponding N-substituted glycine ethyl
esters (Scheme 1). The reaction proceeds under mild conditions
with reasonable to very good yields (Table 2). Both primary and
secondary amines react with EDA. However reaction condi-
4
β-lactams, intermolecular reactions are still interesting, par-
5
,6
ticularly as a versatile route to α-amino carboxylic derivatives.
Recently, rhodium porphyrin complexes have been found to be
very effective catalysts for the insertion of ethyl diazoacetate
7
,8
(EDA) into hydroxylic bonds.
Having established that
II
tions are different from those described in the Ru porphyrin
ruthenium porphyrin complexes are very active catalysts in the
9
catalyzed S᎐H insertion reactions, since it is necessary to add
simultaneously the diazo ester and the substrate into the solu-
tion to avoid too large an excess of amine in the presence of the
catalyst. Indeed, the nucleophilic amines clearly coordinate to
cyclopropanation of olefins, we now report their catalytic
properties toward EDA insertion into S᎐H and N᎐H bonds.
II
,10
The complex Ru (TMP)CO,† in catalytic amounts, reacts
with ethyl diazoacetate in the presence of thiols‡ to give α-thio
ethyl esters (Scheme 1). Both aromatic and aliphatic thiols
1
3
the ruthenium and to a certain extent poison the catalyst.
Accordingly, secondary amines are better substrates than pri-
mary: a higher yield and a shorter reaction time are observed
when diethylamine is used instead of n-propylamine.
H
CO2Et
CO2Et
1
2
H
H
2
CO Et
R R NH
Ru(TMP)CO
1
2
NR R
The difference in reactivity of the catalyst toward R NH and
N2
2
RNH is imputable to the less bulky primary amine which is a
2
better ligand for the metal than the secondary amine. Indeed,
when Ru(TMP)CO is stirred with an excess of diethylamine, the
H
RSH
H
H
CO2Et
SR
Ru(TMP)CO
N2
Table 1 Yields of α-thio ethyl esters obtained from the reaction of
thiols and EDA in the presence of Ru(TMP)CO
Scheme 1
a
RSH
Product
Yield (%)
can be used as substrates (Table 1). The insertion process is
regiospecific since dithiothreitol reacts to give the S᎐H insertion
product without any trace of the ether compound. The main
PhSH
PhSCH CO Et
<95
2
2
(p-ClC
H
)SH
(p-ClC
Bu SCH CO Et
H
)SCH CO Et
<95
<95
90
6
4
6
4
2 2
t
t
3
Bu SH
advantage of this system over rhodium() acetate is the SH/
2 2
HOCH CH SH
HSCH CH(OH)-
CH(OH)CH SH
HOCH CH SCH CO Et
2 2 2 2
2
2
OH selectivity. This regiospecificity also offers a quick route to
ethyl 2-(2-hydroxyethylthio)acetate, which is useful in the build-
EtO CCH SCH CH(OH)-
87
2
2
2
2
CH(OH)CH SCH CO Et
2
2 2 2
1
1
ing of organic donors for conducting cation radical salts. In
this case, 2-mercaptoethanol and EDA were used as starting
a
Yields determined by NMR analysis.
Table 2 Yields of N-substituted glycine ethyl esters obtained from the
†
‡
TMP = 5,10,15,20-tetramesitylporphyrin dianion.
reaction of amines and EDA in the presence of Ru(TMP)CO
General procedures. α-Thio ethyl esters: EDA (0.439 mmol) was slowly
1
2
a
added (1.5 h) at room temperature and under inert atmosphere to a
vigorously stirred solution of thiol (0.571 mmol) and catalyst (4.4
µmol) in dry toluene. The reaction mixture was then stirred for 30 min.
R R NH
Product
Yield (%)
Et NH
Et NCH CO Et
81
75
72
76
63
64
2
i
2
i
2
2
1
5
The products were identified by comparison with data in the literature.
Pr NH
Pr NCH CO Et
2
2 2 2
N-Substituted glycine ethyl esters: a solution of EDA (0.439 mmol)
and amine (0.658 mmol) was slowly added (2.5 h) at room temperature
and under inert atmosphere to a vigorously stirred solution of catalyst
PhMeNH
PhMeNCH CO Et
2 2
t
t
Bu NH
Bu NHCH CO Et
2 2
n
2
n
Pr NH2
Pr NHCH CO Et
2 2
(4.4 µmol) in dry benzene. The reaction mixture was then stirred for 3 to
(p-MeC H )NH
(p-MeC H )NHCH CO Et
6
4
2
6 4 2 2
1
8 h (stirring for secondary amine: 2 h). The products were identified
15
a
by comparison with data in the literature.
Yields determined by NMR analysis.
J. Chem. Soc., Perkin Trans. 1, 1997
2455

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complex Ru(TMP)CO(Et NH)§ is isolated, but the Ru᎐N bond
We conclude that ruthenium porphyrins efficiently catalyze
2
is quite weak. Thus, addition of 4 equiv. of n-propylamine is
the carbene insertion into N᎐H and S᎐H bonds by use of ethyl
diazoacetate. Mechanistic and preparative implications of these
results are under investigation in our laboratory.
sufficient to remove completely in 10 min the diethylamino
n
ligand to give Ru(TMP)CO(Pr NH ).§ Substitution of pro-
2
pylamine in the latter complex is much more difficult. The
n
reverse reaction of Ru(TMP)CO(Pr NH ) with 4 equiv. of
2
diethylamine does not proceed to any observable extent after
Acknowledgements
1
h. After long reaction times (>5 h) we have found, however,
We gratefully acknowledge the financial support of the MESR
for a grant to E. G.
that the reaction allows the observation of Ru(TMP)-
CO(Et NH) in low yield (15%). Such a poisoning has already
2
6
been reported with another catalyst. In contrast, no detectable
coordination occurs with thiols as substrates, and the reaction
quickly reaches completion. We presume that the active inter-
mediate in the catalyzed ethyl diazoacetate insertion into the
References
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2
S᎐H or N᎐H bond is a carbene complex. Thus addition of a
n
slight excess of EDA to a solution of Ru(TMP)CO(Pr NH )
2
leads to the formation of a new red complex and to the
expected glycine ester together with diethyl maleate and
4
5
1
fumarate (Scheme 2). The H NMR data of this complex indi-
CO
RuII
RNH2 + Ru (TMP) (CO)
7 H. J. Callot and E. Schaeffer, Nouv. J. Chim., 1980, 4, 311.
8
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9
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1
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slight excess
of EDA
1
1
0 J. S. Lindsey and R. W. Wagner, J. Org. Chem., 1989, 54, 828.
1 J. Hellberg, M. Moge, D. Bauer and J.-U. von Schutz, J. Chem. Soc.,
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+ RNHCH CO Et + diethyl maleate
2
2
+
diethyl fumarate
C
13 S. S. Eaton, G. R. Eaton and R. H. Holm, J. Organomet. Chem.,
H
CO2Et
1
972, 39, 179.
Scheme 2
14 J. P. Collman, E. Rose and G. D. Venburg, J. Chem. Soc., Chem.
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1
4
catethepresenceof a carbenefragment ligated to theruthenium,
as previously detected in the cyclopropanation reaction.¶
1
5 Z. Zhu and J. H. Espenson, J. Am. Chem. Soc., 1996, 118, 9901.
,
9
§
Ru(TMP)CO(Et NH): δ (CDCl , J/Hz) 8.34 (s, 8H, H ), 7.24 (s, 4H,
2 H 3 β
H ), 7.21 (s, 4H, HmЈ), 2.58 (s, 12H, p-Me), 1.97 (s, 12H, o-Me), 1.77
m
(
s, 12H, oЈ-Me); amine: Ϫ1.79 (t, 6H, J 7.15, CH ), Ϫ2.68 (m, 4H,
3
CH ), Ϫ6.31 (m, 1H, NH).
2
n
Ru(TMP)CO(Pr NH): δ (CDCl , J/Hz) 8.34 (s, 8H, H ), 7.22
2
H
3
β
(
s, 4H, H ), 7.20 (s, 4H, HmЈ), 2.57 (s, 12H, p-Me), 1.87 (s, 12H, o-Me),
m
1
.86 (s, 12H, oЈ-Me); amine: Ϫ0.96 (t, 3H, J 7.30, CH ), Ϫ1.33 (m, 2H,
3
Paper 7/04687A
Received 3rd July 1997
Accepted 3rd July 1997
CH ), Ϫ3.03 (m, 2H, CH ), Ϫ5.75 (m, 2H, NH).
¶
gested in our previous paper.
2
2
However there is no evidence for a CO ligand, as erroneously sug-
9
2
456
J. Chem. Soc., Perkin Trans. 1, 1997