Redox-active triazolium-derived ligands in nucleophilic fe-catalysis - Reactivity profile and development of a regioselective o-allylation

Article abstract of DOI:10.1002/ejoc.201300902

Triazolium-derived N-heterocyclic carbene (aNHC) ligands, which are readily accessible by deprotonation of the corresponding triazolium salts, proved to be versatile ligands in diverse allylic substitution reactions. The corresponding triazolium salts are formed from azides and alkynes through the application of 1,3-dipolar cycloaddition and N-alkylation reactions. The unique property of these ligands is to be zwitterionic in their liberated form and to act as strong redox-active σ-donor ligands. By virtue of these qualities, these ligands enable the development of an unprecedented Fe-catalyzed regioselective aryloxylation of allylic carbonates. Copyright

Full text of DOI:10.1002/ejoc.201300902

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FULL PAPER
DOI: 10.1002/ejoc.201300902
Redox-Active Triazolium-Derived Ligands in Nucleophilic Fe-Catalysis –
Reactivity Profile and Development of a Regioselective O-Allylation
Johannes E. M. N. Klein,[a] Michael S. Holzwarth,[a] Stephan Hohloch,[b] Biprajit Sarkar,*[b]
and Bernd Plietker*[a]
Keywords: Iron / Carbene ligands / Allylation / Regioselectivity
Triazolium-derived N-heterocyclic carbene (aNHC) ligands,
which are readily accessible by deprotonation of the corre-
sponding triazolium salts, proved to be versatile ligands in
diverse allylic substitution reactions. The corresponding tri-
azolium salts are formed from azides and alkynes through
the application of 1,3-dipolar cycloaddition and N-alkylation
reactions. The unique property of these ligands is to be zwit-
terionic in their liberated form and to act as strong redox-
active σ-donor ligands. By virtue of these qualities, these li-
gands enable the development of an unprecedented Fe-cata-
lyzed regioselective aryloxylation of allylic carbonates.
ligand motif might be regarded as a redox-active abnormal
Introduction
N-heterocyclic carbene (aNHC) [Equation (3), Figure 1].[3]
Heteroatom-stabilized singlet carbenes have evolved into
privileged ligands for organometallic chemistry and cataly-
sis.[1] The most prominent example for this class of ligands
are certainly the N,N-heterocyclic carbenes in which the
lone pair of electrons of the carbene carbon atom occupies
the exocyclic position whereas, the remaining (empty) π-
orbital is stabilized by the adjacent lone electron pairs of
the (electronegative) N-atoms. Depending on the electronic
properties of the N-substituent N,N-heterocyclic carbenes
are often categorized as strong σ-donor and poor π-ac-
ceptor ligands [Equation (1), Figure 1]. Upon changing one
of the nitrogen atoms to a carbon atom, the situation
changes drastically. Instead of deprotonating an imid-
azolium salt, the generation of the carbene is performed
using strong alkyllithium bases. The resulting (carbanionic)
carbene might be regarded as being one of the strongest σ-
donor ligands. The negative charge is transferred to the
Figure 1. N,N-heterocyclic carbenes, N-heterocyclic carbenes and
triazolium-based carbenes – generation and binding properties.
Whereas, N-heterocyclic carbene ligands are frequently
metal center [Equation (2), Figure 1]. Recently this concept used in homogeneous catalysis, the latter two carbene li-
was extended to triazolium-based ligands,[2] in which one gand classes have only very recently been employed in
of the backbone atoms is a quaternary ammonium cation. homogeneous catalysis.[4]
The implementation of an electron sink leads to carbenes
Within the past five years the Plietker group[5] has been
with ylide-like structures that bind to the metal center in a involved in the development of catalytic transformations
dual fashion. Either the electron density is shifted to the using electron-rich ferrates like Bu4N[Fe(CO)3(NO)]
metal or back donation of one-electron from the metal to (TBAFe).[6] The redox-active nitrosyl ligand in this complex
the ligand leads to a metal–ligand double bond. Hence, this was identified as being essential to retaining catalytic ac-
tivity throughout the reaction. Furthermore, N-heterocyclic
carbene ligands were found to significantly increase the re-
activity of the catalytic systems.[7] The Sarkar group, on the
other hand, was able to showcase triazolium-based carbene
ligands as suitable ligands for Pd- or Cu-catalyzed transfor-
mations.[8] With regard to the unique properties of triazol-
ium-based aNHCs we wondered in which way these ligands
might influence the catalytic outcome of TBAFe-catalyzed
[a] Institut für Organische Chemie, Universität Stuttgart,
Pfaffenwaldring 55, 70569 Stuttgart, Germany
E-mail: bernd.plietker@oc.uni-stuttgart.de
[b] Institut für Chemie und Biochemie, Anorganische Chemie,
Freie Universität Berlin,
Fabeckstraße 34–36, 14195 Berlin, Germany
E-mail: biprajit.sarkar@fu-berlin.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300902.
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Scheme 1. Regioselective Fe-catalyzed allylic aryloxyallylation.
transformations such as allylic substitutions with special
emphasis on problematic cases such as O-allylations.
Herein, we summarize the results of this study which led to
Results and Discussion
Compared to the NHC-ligands, the synthesis of aNHC-
the development of a regioselective Fe-catalyzed O-allyl- ligands is straightforward and modular. Huisgen [3+2]-cy-
ation of phenols.[9] Whereas N,N-heterocyclic carbene li- cloaddition using Sharpless conditions between an alkyne
gands like SIMES [1,3-bis(2,4,6-trimethylphenyl)-4,5-dihy- and an azide yields the corresponding triazole, which upon
droimidazol-2-ylidene] did not show any preference with re- methylation at N-3 gives the corresponding triazolium salt.
gard to regioselectivity, the corresponding triazolium-based At the outset of our studies we prepared different triazol-
ligand TRIMPH (triazolium methyl phenyl) enabled selec- ium-based ligands following a recently published pro-
tive ipso-substitution (Scheme 1).
cedure[8] (Scheme 2).
Scheme 2. Triazolium-based carbene ligand library.
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Redox-Active Ligands in Nucleophilic Fe-Catalysis
Scheme 3. Carbene ligand screening in Fe-catalyzed allylic substitutions.
This set of triazolium-salts was subsequently deproton- gand. Ligands L3–L8 gave only low regioselectivity and
ated using KOt-amylate as a base and the liberated ligands poor to moderate yields. The allylation of phenols pro-
were employed in various allylic alkylation reactions ceeded in only moderate yields. However, excellent regiose-
(Scheme 3).
lectivity was observed for the first time when ligands L1
C-,[7h] O-,[10] S- (sulfenylation[11] and sulfonation[12]) and and L2 were used. In the allylic sulfenylation very good
the intercepted allylation[13] were selected. All reactions selectivity was observed in almost all cases. Ligand L8
have literature precedence and allow for direct comparison. proved to be inferior resulting in poor selectivity and al-
In the allylation of C-nucleophiles, ligands L1 and L2 gave most no catalytic turnover. Furthermore, ligands L1 and L2
results we had seen previously with the sterically hindered displayed what appears to be poor reactivity. These trends
SIBU [1,3-bis(tert-butyl)-4,5-dihydroimidazol-2-ylidene] li- are contrary to the ones observed for O-allylation. It is pos-
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sible that the more sterically encoumbered ligands L3–L6 Table 1. Variation of the ligand.
are not directly involved. Allylic sulfonation followed the
same trends observed for C-allylation. We have previously
employed phosphane-based ligands in this reaction; triazole
ligands could be an alternative in this case.
The intercepted allylation was rather insensitive to the
choice of ligand. Only the use of iodide salts L6 and L8
resulted in inhibition of the reaction. This is probably a
result of the iodide counterion, rather than the ligands
themselves. Overall, it must be noted that triazole-based
carbenes can serve as potent ligands in a number of allylic
alkylation reactions. Ligands L1 and L2 appear to be gen-
erally applicable and should be included when screening li-
gand effects in transition metal-catalyzed reactions. In gene-
ral, a preference for the formation of the ipso-substitution
product was observed in these iron-catalyzed allylation re-
actions. This was previously obtained only when employing
sterically demanding tert-butyl-substituted NHC-li-
gands.[7h] Furthermore, the substitution pattern at the N-
substituent was found to have a strong impact on conver-
sion rate and chemoselectivity. As can be seen from this
screening, the nature of the counter anion plays an impor-
tant role in the catalytic conversion;[14] the use of tetra-
fluorborate salts significantly enhanced reactivity. Only in
one instance was an increase in reactivity observed. The O-
allylation proceeded in slightly better yield when using li-
gand L6 possessing an iodide counterion when compared to
ligand L5 which possesses the BF4– counterion. However, a
slightly decreased selectivity was observed.
This latter transformation is remarkable since both our
and Tunge’s group[11] have observed that the use of O-nu-
cleophiles in allylic substitutions using TBAFe is problem-
atic with regards to regioselectivity. However, excellent re-
gioselectivity was observed using ligands L1 and L2. These
observations appeared to be an important starting point for
filling this gap in Fe-catalyzed regioselective allylic substitu-
tions. From the data set shown above it is obvious that ste-
ric hindrance at the N-aromatic substituent disfavors the
ipso-substitution pathway (L3 and L4). The absence of a
substituent at the o,o-position seems to favour a high degree
of regioselectivity. This is complementary to the allylic alk-
ylation of C-nucleophiles where ipso-substitution is greatly
enhanced with increased steric bulk. In order to showcase
the interplay of electronic parameters and the counter
anion effect, different triazolium cations were used in ary-
[a] Reactions were performed using 0.375 mmol PhOH and
0.5 mmol carbonate, TBAFe (7.5 mol-%), and ligand (7.5 mol-%)
in THF (0.5 mL) at 80 °C for 20 h, ligands were deprotonated using
KOtamylate solution in PhMe (7.5 mol-%). [b] Determined by GC.
[c] GC yield using n-dodecane as an internal standard.
loxyallylation reactions using either their iodide or tetra- ated and even ortho-substituents did not inhibit the reac-
fluorborate salts (Table 1). tion. Introduction of an acyl group or a bromide resulted
As can be seen from these results, little or no effect on in diminished yields albeit with retention of excellent re-
the reaction was attributable to para-substitution. The most gioselectivity (Table 2, Entries 5 and 8). In addition, no for-
remarkable changes were achieved using o,o-substituents mation of product was observed when using highly acidic
(vide supra). Furthermore, the counter anion had a signifi- pentafluoro-substituted phenol (Table 2, Entry 10).
cant influence on the yield. In general, triazolium iodide
Tunge was able to show that TBAFe in the presence of
salts were less suitable as ligand precursors. Based on these a phosphane ligand allows for efficient decarboxylative ary-
results, ligand L1 was chosen for subsequent screenings to loxyallylation.[15] However, the regioselective course of this
evaluate reaction scope and limitations (Table 2). A variety transformation points to that of a π-allyl mechanism.
of different phenol derivatives were allylated in moderate to Hence, independent of the structure of the starting material,
excellent yields and with excellent regioselectivity through- a clear preference for the formation of the linear product
out. An array of functional groups were found to be toler- was observed. Furthermore, a fast [3,3]-sigmatropic re-
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Redox-Active Ligands in Nucleophilic Fe-Catalysis
Table 2. Substrate scope for phenols.
[a] Reactions were performed using 0.375 mmol PhOH and 0.5 mmol carbonate, TBAFe (10 mol-%), and ligand (10 mol-%) in THF
(0.5 mL) at 80 °C, the ligand was deprotonated using KOt-amylate solution in PhMe (10 mol-%). [b] Determined by integration of the
crude NMR spectra. [c] Isolated yields. [d] Determined by GC. [e] 13 mol-% catalyst were used.
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B. Sarkar, B. Plietker et al.
FULL PAPER
arrangement of the ortho-allyl phenol derivatives was re- ligand thus rendering the oxidized iron a better leaving
ported for allyl ethers of the general type shown above. We group. Interestingly, it has been observed that the addition
wondered if the decarboxylative reaction pathway would of catalytic amounts of triazole derived aNHC-ligands re-
also lead to a linear or rearranged product. If ipso-selectiv- sulted in improved reactivities and γ-selectivities in alkyl-
ity would be observed, a different mechanistic manifold for Grignard-mediated alkyl–allyl cross-coupling reactions.[17]
this type of transformation should be operative using the This is consistent with selective SN2Ј allylation of the iron
catalyst system reported here. Very much to our delight, the center by the allyl carbonate in the present case.
course of the reaction was mainly determined by the origi-
nal structure of the employed carbonate [Equations (1)
Conclusions
and (2), Scheme 4]. Starting from branched carbonate 17,
branched product 3b was obtained in high yields with excel-
lent regioselectivity. Subjecting the regioisomeric linear car-
bonate to the standard reaction conditions led to a mixture
of regioisomers with the linear product being the major
product. Moreover, identical regioselectivities were ob-
served for the intermolecular case [Equation (3), Scheme 4].
In order to exemplify the TRIMPH-ligand effect, we finally
performed the aryloxylation using SIMES as the NHC-li-
gand [Equation (4), Scheme 4], under otherwise identical
conditions. Under these conditions, the branched product
was formed as the major product in excellent yields. How-
ever, the regioselectivity by no means matched that ob-
tained when using ligand L1. Interestingly, use of the tert-
butyl-substituted NHC-ligand SIBU resulted in very low
conversion under these reaction conditions.
In the present manuscript we report a regioselective Fe-
catalyzed aryloxy allylation of allylic carbonates using tria-
zolium-derived aNHC-ligands. Contrary to the use of phos-
phane or NHC-ligands, the TRIMPH-ligand allows for re-
gioselective preparation of allyl aryl ethers in good to excel-
lent yields in favor of the ipso-substitution product. Conse-
quently, this approach complements existing methodology
developed by Tunge and co-workers. Although, the reason
for this unexpected regioselectivity remains elusive, the un-
usual electronic properties of aNHC-ligands that enable
electron shifts from the metal to the ligand seem to be of
key importance in the transformation. It is our hope that
this ligand motif will allow further broadening of the scope
of TBAFe-catalyzed transformations.
Experimental Section
General Procedure for Fe-Catalyzed Allylation of Phenols: Ligand
L1 (12.1 mg, 0.0375 mmol, 10 mol-%) was weighed into a dried
Schlenk tube (20 mL size) equipped with a PTFE-lined screw-cap
under an atmosphere of dry N2. Freshly distilled anhydrous THF
(500 μL) was added followed by the addition of KOt-amylate
(24 μL, 1.7 m sol. in PhMe). The mixture was stirred for 20 min at
r.t. To the solution was then added Bu4N[Fe(CO)3(NO)] (15.5 mg,
0.0375 mmol, 10 mol-%) while maintaining an N2 atmosphere. The
reaction mixture was then heated to 80 °C for 1 h (reduced times
led to decreased conversion). The mixture was cooled to room tem-
perature prior to the addition of the appropriate allyl-carbonate
(0.5 mmol, 1.33 equiv.) and phenol (0.375 mmol, 1.0 equiv.). n-Do-
decane was added as a standard prior to GC analysis for screening
reactions. Decarboxylative allylation was carried out on
0.375 mmol scale following the above protocol.
a
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures for the preparation of the triazolium
salts, spectroscopic data for novel triazolium salts and for all
allylated phenols.
Scheme 4. Scope and limitations of Fe-catalyzed aryloxy allyl-
ation – the carbonate scope.
Acknowledgments
The analysis of CO frequencies of carbonyl containing
iridium complexes featuring SIMES and structurally analo-
gous triazole-ligand has recently been reported by Terash-
ima et al. and suggests that the triazole ligands are the
stronger σ-donor ligands.[16] When ligated to iron, in the
present case, this would aid nucleophilic attack onto the
allyl carbonate. However, it would also result in a reduction
in leaving group ability. Consistent with previous reports of
redox-participation,[3a] electron transfer from the iron cen-
ter to the ligand could result in formal reduction of the
Financial support by the Deutsche Forschungsgemeinschaft
(DFG) is gratefully acknowledged.
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6
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Redox-Active Ligands in Nucleophilic Fe-Catalysis
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Received: June 20, 2013
Published Online: ᭿
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Iron Catalysis
Triazolium-derived N-heterocyclic carbene
ligands, generated by deprotonation of cor-
responding triazolium salts, are versatile
ligands in diverse allylic substitution reac-
tions. The corresponding triazolium salts
are zwitterionic in their liberated form and
act as strong redox-active σ-donor ligands
thus enabling an unprecedented Fe-cata-
lyzed regioselective aryloxylation of allylic
carbonates.
J. E. M. N. Klein, M. S. Holzwarth,
S. Hohloch, B. Sarkar,*
B. Plietker* ....................................... 1–8
Redox-Active Triazolium-Derived Ligands
in Nucleophilic Fe-Catalysis – Reactivity
Profile and Development of a Regioselec-
tive O-Allylation
Keywords: Iron / Carbene ligands / Al-
lylation / Regioselectivity
8
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