Catalytic activation of diazo compounds using electron-rich, defined iron complexes for carbene-transfer reactions

Article abstract of DOI:10.1002/anie.201201409

Carbene transfer: The electron-rich iron complex Bu₄N[Fe(CO) ₃(NO)] efficiently catalyzes different carbene-transfer reactions. Various diazo compounds can be used. The high stability of the employed iron complexes is demonstrated by the generation of the diazo reagent in situ and a sequential iron-catalyzed allylic sulfenylation/Doyle-Kirmse reaction. Copyright

Full text of DOI:10.1002/anie.201201409

Angewandte
Chemie
DOI: 10.1002/anie.201201409
Iron Carbene Catalysis
Catalytic Activation of Diazo Compounds Using Electron-Rich,
Defined Iron Complexes for Carbene-Transfer Reactions
Michael S. Holzwarth, Isabel Alt, and Bernd Plietker*
The activation of diazo compounds by nitrogen extrusion in
the presence of transition-metal complexes is a convenient
method for the transfer of a carbene to an organic substrate
in, for example, [2+1] cycloadditions with olefins[1] or
carbonyl compound[2] to give three-membered-ring com-
pounds, or in reactions with electron-rich heteroatoms like
sulfur,[3] phosphorus,[4] and nitrogen[5] to generate ylides.[6] In
general, these types of reactions are catalyzed by oxidized
transition-metal complexes based upon copper,[1,7] rhodiu-
m,[5a–d] ruthenium,[8] palladium,[9] cobalt,[10] iron,[4,11] and
silver.[12] In the initial step the metal center is reduced by
nucleophilic addition of the diazo compound. The subsequent
back-donation of an electron from the metal to the carbon
atom with concomittant release of nitrogen results in the
formation of the metal–carbon double bond [Eq. (1) in
Figure 1].
ever, the latter mechanism might favor the undesired carbene
dimerization to the corresponding olefins.
We were wondering whether the electron-rich ferrate
complex Bu4N[Fe(CO)3(NO)] (TBAFe), in which the metal
center has a formal oxidation state of ÀII and which has been
investigated in detail by us and others over the past years,[14]
might be able to activate diazo compounds for carbene-
transfer reactions. Herein we report the successful realization
of this concept in various catalytic transformations including
Wittig-type olefinations,[15] the insertion into heteroatom–
hydrogen bonds,[16] and the Doyle–Kirmse reaction.[17]
Since to the best of our knowledge the activation of diazo
compounds by reduced metal catalysts has not been reported,
we initiated our studies by investigating the carbene transfer
using ethyl diazoacetate (6, EDA) as the electrophilic carbene
precursor in different model reactions. Apart from its
electronic properties, which could result in an increased
reactivity toward electron-rich metal complexes, this diazo
compound is stable and commercially available in pure form.
Gratifyingly, a system consisting of catalytic amounts of
TBAFe and stoichiometric amounts of 6 showed good
reactivity in 1,2-dichloroethane (Scheme 1).
À
À
Both the insertion into S H and N H bonds as well as the
transfer of the carbenoide to electron-rich heteroatoms with
intermediate formation of an ylide (olefination[18,19] and
Doyle–Kirmse reaction) were accomplished under almost
Figure 1. Mechanistic model for the decomposition of diazo com-
pounds by electrophilic or nucleophilic metal catalysts.
In contrast, the corresponding activation of stabilized,
electron-poor diazo compounds by nucleophilic and hence
electron-rich transition-metal complexes is unprecented.
From a mechanistic point of view the metal center would
=
add into the C N bond of the diazo compounds followed by
an electron back-donation with release of nitrogen and
formation of the metal–carbon double bond [Eq. (2),
Figure 1].[13] With respect to the oxidation state of the metal
center both mechanistic manifolds are redox-neutral; how-
[*] Dipl.-Chem. M. S. Holzwarth, I. Alt, Prof. Dr. B. Plietker
Institut fꢀr Organische Chemie, Universitꢁt Stuttgart
Pfaffenwaldring 55, 70569 Stuttgart (Germany)
E-mail: bernd.plietker@oc.uni-stuttgart.de
Scheme 1. TBAFe-catalyzed carbene-transfer reactions. Reaction condi-
tions: a) 10 mol% TBAFe, 1.2 equiv 6, 1,2-dichloroethane, 608C, 18 h;
b) 10 mol% TBAFe, 1.2 equiv 6, 1.5 equiv AsPh3, 1,2-dichloroethane,
608C, 18 h; c) 10 mol% TBAFe, 1.2 equiv 6, 1,2-dichloroethane, 608C,
2 h. *: yield of isolated product.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201201409.
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identical reaction conditions. Since the Doyle–Kirmse reac-
tion proved to be the highest yielding model reaction, further
optimizations concentrated on variation of solvent, temper-
ature, ligand effects, and catalyst loadings.
The subsequent optimization studies indicated that
a decrease in the temperature down to 408C and catalyst
concentration down to only 2.5 mol% is possible even in the
absence of ligands. Furthermore 1,2-dichloroethane (DCE)
proved to be the solvent of choice.[20] A variety of alkyl/
arylthioethers were subjected to the optimized reaction
conditions using 6 as the carbene precursor (Table 1).
Table 1: The iron-catalyzed Doyle–Kirmse reaction.
Scheme 2. Iron-catalyzed Doyle–Kirmse reaction of propargyl sulfides.
Entry[a]
R1
R2
R3
R4
Prod.
Yield [%][b]
1
2
Ph
Ph
Ph
Ph
H
H
H
Me
H
H
H
H
H
H
H
H
H
Me
H
H
Me
Me
Me
Me
Me
10
11
8
12
13
14
15
16
17
18
88
76
77
63
70
81
90
68
69
92
Further investigations showed that the reaction conditions
are applicable for propargyl sulfides (Scheme 2). Various
propargylic thioethers were transformed into the correspond-
ing allenes in good to excellent yields using slightly modified
reaction conditions.
Finally we investigated the scope with respect to the diazo
compounds. The catalytic systems proved to be robust.
Electron-rich as well as 1,1-disubstituted diazo compounds
were successfully employed in the Doyle–Kirmse reaction
[Eq. (3), Scheme 3]. However, the catalyst concentration,
stoichiometry, and/or reaction temperature have to be
Me
Me
H
3[c]
4[d]
5[c]
6[c]
7
Ph
Ph
p-ClC6H4
p-MeOC6H4
p-MeC6H4
Bn
Me
Me
Me
Me
Me
8
9[d]
10[c]
nHex
11[c]
12[c]
13[c]
H
H
H
H
H
H
H
H
H
19
20
21
65
51
49
14[c]
15
H
H
H
H
H
H
H
H
H
22
23
24
74
75
76
16
[a] All reactions were performed on a 1 mmol scale in 1,2-dichloroethane
(1 mL) under a N2 atmosphere at 408C. [b] Yields of isolated products.
[c] T=608C. [d] T=808C.
The reaction shows a remarkable scope. The desired
rearrangement products were obtained in good to excellent
yields in the presence of only a slight excess of 6. Base-labile
functional groups like boronates (entry 11, Table 1) or func-
tional groups that are reactive toward carbene-transfer
reactions (e.g. alcohols, amines, olefins, entries 11–16,
Table 1) proved to be compatible with the reaction conditions.
Byproducts indicative of an undesired side reaction were not
observed. This observation might be explained by the lower
reactivity of these groups as observed in our initial model
studies (Scheme 1).
Scheme 3. Iron-catalyzed Doyle–Kirmse reaction of various diazo com-
pounds. [a] T=808C. [b] T=1208C; catalyst concentration: 10 mol%.
2
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adjusted for the respective reagents. The preparation and
handling of diazo compounds certainly represents a serious
limitation from a preparative point of view. Based upon the
recent work carried out in the Carreira group,[21] a one-pot
procedure consisting of in situ generation of the active diazo
compound and subsequent Doyle–Kirmse reaction, was
realized [Eq. (4), Scheme 3]. The catalytic transformation
can be performed in a two-phase mixture of water and 1,2-
dichloroethane without any intermediate purification steps.
The desired product 37 was obtained in moderate (non-
optimized) yield. This result underlines the extraordinary
stability of the catalyst.
Recently we reported that TBAFe is able to catalyze the
regioselective allylation of thiols in the absence of any
ligand.[13f] With regard to the results reported above, we
speculated that we could employ this complex in a sequential
sulfenylation/Doyle–Kirmse reaction. Treatment of allylic
carbonate 38 with thiophenol and subsequent addition of 6 to
the reaction mixture allowed for the successful realization of
this concept. The corresponding ethyl a-mercapto-a-allyl-
acetate (10) was obtained in good yield (Scheme 4).
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Kirmse reaction.
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We have shown that electron-rich iron complexes like
Bu4N[Fe(CO)3(NO)] (TBAFe), in which the metal center has
a formal oxidation state of ÀII, activate diazo compounds for
carbene-transfer reactions. In the presence of catalytic
amounts of the iron complex, an insertion into heteroatom–
hydrogen bonds, an olefination of carbonyl compounds, and
a Doyle–Kirmse reaction were realized even in the absence of
any ligand. The latter transformation displays a broad func-
tional-group tolerance. The mild reaction conditions and the
stoichiometric use of the reagent are interesting with regard
to possible synthetic applications. The remarkable stability of
the catalyst was demonstrated by the in situ generation of the
diazo compound and a sequential allylic substitution/Doyle–
Kirmse reaction. These results represent the starting point for
the preparation of iron–carbene complexes which we will
examined in our future research.
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Received: February 20, 2012
Published online: && &&, &&&&
Keywords: carbenes · homogeneous catalysis · iron ·
rearrangements · thioethers
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[19] We agree with one of the reviewers that olefinations using
stoichiometric amounts of AsPh3 are not contemporary . The
olefination shown in this article was meant to be a “proof-of-
concept” example and not necessarily a new synthetic method.
The exploration of more environmentally benign olefination is
currently a research focus. The olefination using catalytic
amounts of AsPh3 (Ref. [18]), however, exemplifies the potential
of these neutral olefinations.
[20] For details see the Supporting Information.
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Communications
Iron Carbene Catalysis
Carbene transfer: The electron-rich iron
complex Bu4N[Fe(CO)3(NO)] efficiently
catalyzes different carbene-transfer reac-
tions. Various diazo compounds can be
used. The high stability of the employed
iron complexes is demonstrated by the
generation of the diazo reagent in situ
and a sequential iron-catalyzed allylic
sulfenylation/Doyle–Kirmse reaction.
M. S. Holzwarth, I. Alt,
B. Plietker*
&&&& — &&&&
Catalytic Activation of Diazo Compounds
Using Electron-Rich, Defined Iron
Complexes for Carbene-Transfer
Reactions
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5
These are not the final page numbers!