Cr/Ni-catalyzed vinylation of aldehydes: A mechanistic study on the catalytic roles of nickel and chromium

Article abstract of DOI:10.1002/chem.201003366

The roles of nickel and chromium catalysts in the coupling reaction of vinyl halides and aldehydes, the so-called Nozaki-Hiyama-Kishi (NHK) reaction, have been studied by UV/Vis spectroscopy, electrochemical, and spectroelectrochemical methods. Electrochemical studies revealed that nickel plays the central role in activating the vinyl halide by reductive cleavage, to form a rapidly decomposing vinyl-Ni species. The latter can, however, be stabilized in the presence of the Cr complex. The redox behavior of the Ni complexes in the presence of vinyl halide demonstrated that the vinyl halide activation results from interaction with a one-electron reduced nickel species [formally Ni^I], not necessarily with a Ni⁰ species. It was furthermore shown by UV/Vis spectroscopy and spectroelectrochemical methods that low-valent nickel [Ni⁰] results from the interaction of the Ni^II catalyst with CrCl₂. It takes two to tango! The initial stages of the Cr/Ni-catalyzed vinylation of aldehydes (the Nozaki-Hiyama-Kishi reaction) were analyzed by electrochemical methods. The role of low-valent nickel in the C-halogen(Hal) cleavage of the vinyl halide was established, as well as the generation of the former from Ni^II and Cr^II. Copyright

Full text of DOI:10.1002/chem.201003366

FULL PAPER
DOI: 10.1002/chem.201003366
Cr/Ni-Catalyzed Vinylation of Aldehydes: A Mechanistic Study on the
Catalytic Roles of Nickel and Chromium
Wacharee Harnying,[a] Andrꢀ Kaiser,[b] Axel Klein,*[b] and Albrecht Berkessel*[a]
Abstract: The roles of nickel and chro-
mium catalysts in the coupling reaction
of vinyl halides and aldehydes, the so-
called Nozaki–Hiyama–Kishi (NHK)
reaction, have been studied by UV/Vis
spectroscopy, electrochemical, and
spectroelectrochemical methods. Elec-
trochemical studies revealed that
nickel plays the central role in activat-
ing the vinyl halide by reductive cleav-
age, to form a rapidly decomposing
vinyl–Ni species. The latter can, howev-
er, be stabilized in the presence of the
Cr complex. The redox behavior of the
Ni complexes in the presence of vinyl
halide demonstrated that the vinyl
halide activation results from interac-
tion with a one-electron reduced nickel
species [formally NiI], not necessarily
with a Ni0 species. It was furthermore
shown by UV/Vis spectroscopy and
spectroelectrochemical methods that
low-valent nickel [Ni0] results from the
interaction of the NiII catalyst with
CrCl2.
Keywords: chromium
Nozaki–Hiyama–Kishi reaction
·
nickel
·
·
reaction mechanisms · vinylation
Introduction
propargyl, alkynyl, alkyl, alkenyl, and aryl halides or sulfo-
nates are suitable precursors for the formation of the reac-
tive organochromium nucleophiles. This unrivalled profile of
NHK reactions has led to a large number of applications,
particularly in the synthesis of structurally diverse natural
products.
The nucleophilic addition of organochromium reagents to
aldehydes, the so-called Nozaki–Hiyama–Kishi (NHK) reac-
tion, is a versatile carbon–carbon bond-forming reaction
(Scheme 1). It features excellent chemoselectivity and com-
The organochromium reagents can easily be prepared by
oxidative addition of chromium(II) species to organic hal-
ides under anhydrous conditions. The rate of the reduction
depends on the nature of the organic group, the halide, and
the reaction conditions (solvents, ligands, temperature).
Active halides, such as allyl and benzyl halides are smoothly
reduced with CrII salts in aprotic solvents to provide allyl-
and benzylchromium reagents, respectively. In contrast, no
reduction of alkenyl and aryl iodides takes place with CrII
salts in aprotic solvents.[2] In fact, the reduction of halogens
connected to sp2 carbons can proceed under nickel catalysis,
discovered independently by Kishi et al.[3] and Nozaki
et al.[4] in 1986. It has been assumed that CrII serves to
reduce NiII to Ni0. An oxidative addition of the vinyl halide
to Ni0 results in a vinyl nickel(II) species, which undergoes
transmetallation with CrIII to the proposed nucleophilic
Scheme 1. Stoichiometric and catalytic NHK reactions.
patibility with a wide range of functionalities in both compo-
nents including ester, amide, nitrile, ketone, alcohol, and
various alcohol protecting groups, as well as centers suscep-
tible to epimerization or elimination, because of the weak
basicity of organochromium compounds.[1] With regard to
the nucleophile, a wide range of substrates including allyl,
vinyl chromiumACTHNUTRGNEUNG(III), which in turn adds to the aldehyde.
The above discovery has significantly improved the reliabili-
ty of these “one-pot” Barbier type addition reactions, and
doping of CrCl2 with catalytic amounts of NiII became a
standard “trick” for reactions involving less reactive sub-
strates such as alkenyl and aryl halides or triflates.
[a] Dr. W. Harnying, Prof. Dr. A. Berkessel
Department of Chemistry (Organic Chemistry)
University of Cologne
Greinstrasse 4, 50939 Cologne (Germany)
Fax : (+49)221-4705102
E-mail: berkessel@uni-koeln.de
The major drawback of the original NHK procedure was
the requirement for larger than stoichiometric amounts of
toxic CrII salts (usually in the range of 400–1600 mol%) for
[b] A. Kaiser, Prof. Dr. A. Klein
Department of Chemistry (Inorganic Chemistry)
University of Cologne
the formation of the organochromium nucleophile.[5]
A
breakthrough in the development of catalytic NHK reac-
tions was achieved by Fꢀrstner and Shi in 1996,[6] who used
Mn0 as the stoichiometric reducing agent of catalytic
Greinstrasse 6, 50939 Cologne (Germany)
Fax : (+49)221-4705196
E-mail: axel.klein@uni-koeln.de
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Results and Discussion
Preparation of Cr and Ni com-
plexes: All complexes used in
our studies, that is, 4-CrCl3,[7b]
4-NiCl2,[7b]
7-NiCl2,[7b]
8-
NiCl2,[11b–c,13] were prepared ac-
cording to literature proce-
[10]
dures, whereas 5-CrCl2 and 6-
[7a]
CrCl2 were generated in situ
from the corresponding ligand
and CrCl2 in the presence of
NEt3 and used immediately.
The synthesis of the ligand 6,
however, had not been report-
ed. By using our synthetic strat-
egy, the ligand 6 was prepared
starting from commercially
available methyl 2-nitro-3,4,5-
Scheme 2. Proposed mechanistic scheme for the Cr/Ni-catalyzed vinylation of aldehydes: The chromium
ACHTUNGTNER(NUNG III)
alkoxide formed was trapped by means of TMSCl[6] or [Cp2ZrCl2],[10b] liberating the chromium
AHCTUNGTRENNUNG
which is converted to the active chromium(II) species by manganese powder as the stoichiometric reductant,
thus propagating the catalytic cycle.
trimethoxybenz-oate
Scheme 4).
(9;
chromium
ACHTUNGTRENNUNG
termediate chromiumAHCTUNGTRENNUNG
Scheme 2). Later, Kishi et al. developed the use of
[Cp2ZrCl2] as the dissociating agent (instead of TMSCl),
which was shown to be more effective than TMSCl.[7] Nota-
bly, the regeneration of CrII by the reduction of CrIII with Al
(instead of Mn powder),[8] or by electroreduction,[9] was also
reported by others.
The important finding by Fꢀrstner and Shi triggered nu-
merous efforts to develop a catalytic and enantioselective
version of this reaction. In strong contrast to many success-
ful publications about chromium-catalyzed enantioselective
additions of allylic halides to aldehydes,[1d] however, very
few publications are devoted to asymmetric Ni/Cr-mediated
alkenylations of aldehydes, generating enantiomerically en-
riched allylic alcohols. So far, only two catalytic and asym-
metric variants of NHK alkenylation reactions using chiral
CrII complexes, derived from DIANANE–salen by Berkes-
sel et al.[10] and from oxazoline–sulfonamides by Kishi
et al.,[7a,11] have been reported.
In practice, the method still suffers from limited substrate
scope, low predictability of rates and enantioselectivity, high
catalyst loadings,[12] and relatively complex, difficult to
access ligand structures. To achieve major progress in this
area, it is necessary to elucidate the mechanism of these re-
actions. Currently, there is no spectroscopic evidence for any
of the mechanistic steps put forward for the Cr/Ni-catalyzed
vinylation of aldehydes, and very little is known about the
postulated intermediates and their reactivity.
Herein, we report our studies on the mechanism of the
Cr/Ni-catalyzed vinylation of aldehydes, especially on the
role of the nickel and chromium catalysts, by electrochemis-
try and spectroelectrochemistry using Cr and Ni complexes
with proven catalytic activity, resulting from the studies of
the Kishi and the Berkessel groups (Scheme 3).
Scheme 3. Ni and Cr complexes used in this study for the coupling reac-
tion of 1 and 2.
As the first step, the ester 9 was converted to the tert-leu-
cinol amide 10 in 81% overall yield. It should be mentioned
that some additional esterification of the hydroxyl group of
the tert-leucinol with the acid chloride occurred as well, af-
fording the ester 12. However, the resulting ester 12 could
be hydrolyzed back to 10, by treatment of the crude reaction
mixture with KOH. The amide 10 was next subjected to the
cyclization reaction with thionyl chloride to give the oxazo-
line 11, together with a small amount of 13 arising from the
substitution of the hydroxyl group by chloride ion. The
latter, however, could be transformed to 11 by treatment of
the crude reaction mixture with KOH. Finally, a reduction
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Cr/Ni-Catalyzed Vinylation of Aldehydes
FULL PAPER
Scheme 4. Synthesis of the sulfonamide ligand 6.
of the nitro compound 11 with stannous chloride and subse-
quent coupling of the resulting aniline with 2-naphthalene-
sulfonyl chloride successfully furnished the desired sulfona-
mide ligand 6 in very good yield.
Electrochemistry of Cr and Ni complexes: Having in hand a
number of Cr and Ni complexes, we started an investigation
on the electrochemistry of the complexes, and on the reac-
tivities of their redox states. As shown in Scheme 2, the cur-
rent mechanistic view of the catalytic Cr/Ni-catalyzed vinyl-
ation of aldehydes involves the interlocking of a total of
three redox cycles, and concomitant transfer of the vinyl
unit. It is obvious that an efficient overall reaction hinges on
well-matched redox potentials, rapid transmetallation, and
efficient asymmetric induction in the vinyl transfer to the al-
dehyde. To establish the redox potentials of the Cr/Ni cata-
lysts in the reaction, we first defined the electrochemical
properties of Cr and Ni complexes by cyclic voltammetry
(CV), conducted in MeCN solution, which had proven to be
an excellent solvent for the coupling reaction,[7,11] containing
0.1m Bu4NPF6 as the supporting electrolyte (Figure 1).
Figure 1. Cyclic voltammograms of 4-CrCl3 (deep green solid), 5-CrCl2
(deep brown solution, generated in situ), 6-CrCl2 (green solution, gener-
ated in situ), 4-NiCl2 (green solid), 7-NiCl2 (deep green solid), 8-NiCl2
(yellow solid, pink solution) in Bu4NPF6–MeCN solution (scan rate=
0.1 VsÀ1); ferrocene (FeCp2/FeCp2+) was used as an internal reference; *
marks the redox waves of the ferrocene/ferrocenium standard.
turally characterized in the form of a dimeric molecule con-
taining two antiferromagnetically coupled five-coordinated
nickel(II) atoms.[13c] Unfortunately, our attempts to obtain
conclusive information on the metal or ligand contribution
for the species resulting from the electrochemical reduction
of the 8-NiCl2 complex by an EPR spectroelectrochemical
method were frustrated, even at low temperature. Based on
analogy, we assume that the first reversible curve corre-
sponds to ligand-centered reduction.[14,15]
The cyclic voltammograms of the Ni and Cr complexes in-
vestigated are characterized by mostly irreversible reduction
waves, which can be attributed to the loss of halide upon ad-
dition of one electron to the complex (ECE mechanism).[14]
The only exception is the 8-NiCl2 complex, that is, [Ni-
ACHTUNGTRENNUNG(dmp)Cl2] (dmp=2,9-dimethyl-1,10-phenanthroline), which
exhibits full reversibility of the first three reduction process-
es (see also Figure 3a). Each one of the waves accounts for
a one-electron transfer, as shown by quantitative measure-
ments using weighted samples of the complex and of ferro-
cene. This complex 8-NiCl2 undergoes three fully reversible
one-electron reductions, which are probably both metal- and
ligand-centered. Indeed, the molecular structure of the com-
As can be seen in Figure 1, the reduction of the CrII com-
plexes, that is, 5-CrCl2 and 6-CrCl2, occurred at more nega-
tive potentials compared to the NiII complexes 4-NiCl2, 7-
NiCl2, and 8-NiCl2. In other words, NiII can be reduced to
NiI and possibly to Ni0 by the CrII complexes.
Ligand exchange between Cr and Ni complexes: For the
plex [Ni
G
mechanistic understanding, it is of importance to know
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4767

A. Berkessel, A. Klein et al.
ence of the vinyl iodide 2 (Figure 3b). The appearance of
the cyclic voltammogram of 4-NiCl2 changes completely
upon addition of the vinyl iodide 2, and a clear catalytic
wave is observed. No such catalytic wave is observed with
any of the Cr complexes in the presence of the vinyl iodide
2 (see Figure 3d), and not in the presence of the aldehyde
substrate either (not shown in Figure 3). Interestingly, the
catalytic waves start at a similar potential around À1 V
versus Ag/AgCl in all cases, even in the (additional) pres-
ence of the Cr complex. This result supports the conclusion
À
that the reductive cleavage of the vinyl I bond is effected
by the Ni complex, not Cr. Importantly, repeated scanning
of the catalytic wave led to a dramatic decrease in current
response, indicating rapid decomposition of the Ni electro-
catalyst (see Figure 3b, top). Upon addition of the Cr com-
plex 4-CrCl3 (Figure 3b, c, and d), the catalytic wave persists
significantly longer with a gradual decrease in peak intensi-
ty, indicating a retardation of the decay of the Ni complex.
The latter observation adds a very important piece of infor-
mation to our mechanistic understanding of the NHK vinyl-
Figure 2. Cyclic voltammograms of a) a mixture of 6-CrCl2 and 8-NiCl2;
b) a mixture of 4-CrCl3 and 4-NiCl2, in Bu4NPF6–MeCN solution (scan
rate=0.1 VsÀ1); ferrocene (FeCp2/FeCp2+) was used as an internal refer-
ence.
À
ation: the reductive cleavage of the vinyl I bond is effected
by the Ni complex (not Cr), but the resulting Ni–vinyl com-
plex is stabilized by interaction with the Cr component. This
conclusion is also supported by the previous experimental
observations reported by Kishi et al. that in the absence of
Ni catalyst, both the aldehyde 1 and the vinyl iodide 2 were
recovered unchanged, whereas, in the absence of Cr catalyst,
whether or not ligand exchange between the Ni- and the Cr-
complexes can take place (Figure 2).
Due to the easily distinguishable electrochemical “finger-
print” of 8-NiCl2, this complex was employed in the investi-
gation of ligand-exchange processes between the Ni and Cr
complexes. As illustrated in Figure 2a, upon addition of 6-
CrCl2 to the solution of 8-NiCl2, the typical CV pattern of
the Ni complex was no longer present, indicative of ligand
exchange.[16] Clearly, the second reversible wave of 8-NiCl2
completely disappeared. However, the first fully reversible
wave does not suffer any perceptible change. A possible ex-
planation of this data would be that this first reversible
wave occurs by one-electron reduction of the dmp ligand,
which is independent of the metal ion. When Ni and Cr
complexes possessing the same ligand were employed, in the
experiment shown in Figure 2b for a mixture of 4-CrCl3 and
4-NiCl2, ligand exchange is degenerate. Nevertheless, the
CV of the mixture of the complexes 4-CrCl3 and 4-NiCl2 is
not a simple superposition of the individual CVs of the Cr
and the Ni complexes. This result points to an interaction
between the two metal complexes.
the homodimer of 2, that is, [CH3ACHTUNGTRNNEUG(CH2)3CHCAUTNTGREN(NUNG =CH2)]2, was ob-
tained nearly quantitatively, along with the intact aldehyde
1.[7b] However, at this point, the exact mode of the nickel–
vinyl stabilization by interaction with the Cr species, for ex-
ample, vinyl transfer to Cr, or the formation of a bimetallic
complex, is not clear. A more definitive conclusion on this
point must await further clarification.
Investigation of the formation of Ni0 from CrII and NiII: To
have a clear answer to the question whether or not CrII can
reduce NiII to Ni0, we next investigated the formation of Ni0,
with the [(bpy)NiACTHNUTRGNEUNG(cod)] complex (bpy=2,2’-bipyridine,
cod=cis,cis-1,5-cyclooctadiene) serving as an “indicator”.
The latter complex is a deep purple compound which can be
easily detected by UV/Vis spectroscopic analysis. The UV/
Vis spectrum of this complex exhibits a low-energy charge
transfer band at 565 nm and a broad long-wavelength ab-
sorption around 838 nm (Figure 4, red line).
Catalyst–substrate interaction: To gain further insight into
the interaction of the Ni/Cr catalysts with the substrate, we
next investigated the electrochemical behavior of the Ni and
We first investigated the reaction between CrIICl2 and
[NiII
ACHTUNGTRENNUNG
Cr complexes in the presence of the vinyl iodide
2
ACHTUNGTRENNUNG
(Figure 3). The effect of the addition of the vinyl iodide 2
on the redox behavior of the complex 8-NiCl2 is shown in
Figure 3a. Significantly, all original three reversible waves
disappeared. They are replaced by a single irreversible
wave, a so-called “catalytic current”, thereby indicating elec-
trocatalytic reduction of the vinyl halide. This suggests that
vinyl halide activation results from interaction with NiI, not
necessarily Ni0 (see Scheme 1). This same effect is also ob-
served with the voltammetric curve of 4-NiCl2 in the pres-
(2 equiv) in the presence of bpy (1.5 equiv), and cod
(excess) in THF under an Ar atmosphere at 08C. After the
mixture had been stirred for 10 min, a dark purple solution
was obtained, followed by a color change from deep purple
to green within the next 15 min at 08C (Figure 4, top). By
performing the reaction directly in the UV cell, we were
able to monitor the reaction by UV/Vis spectroscopy.
Figure 4 shows the UV/Vis spectra taken from the reac-
tion mixture as a function of time (black lines), in which the
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Cr/Ni-Catalyzed Vinylation of Aldehydes
FULL PAPER
demonstrates the decomposi-
tion of the resulting Ni0 species.
Control experiments with either
[NiACHTNURGTEN(UNG acac)2] or CrCl2 in the pres-
ence of bpy and cod ligands
proved that no absorption band
appeared corresponding to
[(bpy)Ni
ACHTUNGTRENNUNG
mixture of [NiACHTUNGTRENNUNG
cod gives a clear green solution,
whereas the mixture of CrCl2,
bpy, and cod gives a yellow sus-
pension. In none of these cases,
the deep purple solution, indi-
cative of [(bpy)NiACTHUNRGTNE(NUG cod)], was
obtained. From these results,
we can conclude that in the
presence of CrII, NiII can be re-
duced to Ni0.
Spectroelectrochemical studies
on the formation of Ni0 from
CrIII and NiII: As reported nu-
merous times, in the presence
of Mn0 as the stoichiometric re-
ducing agent,
a
catalytic
amount of either CrII or CrIII
can be used together with a cat-
alytic amount of NiII in the
NHK alkenylation of aldehydes.
The electrochemical reduction
of NiII in the presence of CrIII
was therefore studied next by
using UV/Vis spectroelectro-
chemical methods (Figure 5).
In this experiment, a mixture
of [NiACHTUNGRTNEG(UN acac)2], 4-CrCl3, bpy, and
cod in THF–0.1m Bu4NPF6 so-
lution was submitted to spec-
troelectrochemical experiments
(using an OTTLE cell)[17] for
monitoring changes of the ab-
sorption spectrum upon reduc-
tion. Figure 5A shows the UV/
Vis absorption spectra of a mix-
Figure 3. Cyclic voltammograms in Bu4NPF6–MeCN solution at a 0.2 VsÀ1 scan rate of a) 8-NiCl2, followed by
the addition of the vinyl iodide 2; b) a mixture of 4-NiCl2 and the vinyl iodide 2, followed by the addition of
4-CrCl3; c) a mixture of 4-NiCl2 and 4-CrCl3, followed by the addition of the vinyl iodide 2; d) a mixture of 4-
CrCl3 and the vinyl iodide 2, followed by the addition of 4-NiCl2. Potentials versus Ag/AgCl, no addition of
ferrocene in these studies.
ture of [NiACHTNUTRGNE(UNG acac)2], 4-CrCl3,
bpy, and cod taken during re-
ductive spectroelectrochemistry.
The appearance of the absorp-
tion band at around 565 nm,
color changes rapidly from deep purple to green within
5 min at room temperature, which can also be observed vis-
ually. Clearly, by comparing the absorption spectra shown in
Figure 4 to the reference spectrum of [(bpy)NiACHTNUTRGNE(UNG cod)] (red
line), the corresponding first four spectra of the deep purple
reaction mixture (from the top) can be attributed to the ex-
which indicates the formation of [(bpy)NiACTHGNUTERNNU(G cod)], was ob-
served starting from a reduction potential of À0.9 V (versus
Ag/AgCl). Gradual increase in absorption intensity at
565 nm is observed upon lowering the potential applied
(from À1.0 to À1.2 V). As a control, by performing the ex-
periment with a mixture of [NiACHTNUGRTENUNG(acac)2], bpy, and cod in the
pected [(bpy)Ni
G
absence of 4-CrCl3 (Figure 5b), the potential required for
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4769

A. Berkessel, A. Klein et al.
Figure 4. UV/Vis absorption spectra obtained from the reaction of [Ni-
ACHTUNGTRENNUNG(acac)2], CrCl2, bpy and cod in THF, in which the color changes from
deep purple to green within 5 min (black lines, the first four lines corre-
spond to the deep purple solution). Red, green, and blue lines show the
absorption spectra of [(bpy)Ni
a mixture of [Ni(acac)2], bpy, and cod, and [Ni
ly. Top: the dark purple solution obtained from the reaction mixture of
[Ni(acac)2], CrCl2, bpy, and cod in THF (left); the color changes from
A
ACHTUNGRTEN(NUNG cod)2] and bpy],
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
deep purple to green (right) within 15 min at 08C.
the direct reduction to Ni0 is about À1.8 V, which is much
more negative than the potential required in the presence of
4-CrCl3. This result points to electron transfer from Cr to
Ni, which renders the reduction of NiII to Ni0 feasible at a
higher potential.
A control experiment with a mixture of 4-CrCl3, bpy, and
cod in the absence of [Ni
ure 5C). Clearly, no absorption band reminiscent to that of
[(bpy)Ni
(cod)] was observed. Nevertheless, CrIII reduction
ACHTUNGERTN(NUNG acac)2] was also carried out (Fig-
ACHTUNGTRENNUNG
was observed by a change in absorption bands and intensity
starting from a given potential of À0.8 V, which is similar to
the first cationic peak observed from the cyclic voltammo-
gram of 4-CrCl3 at a potential of À0.80 V versus Ag/AgCl
+
(Figure 1, À1.33 V versus FeCp2/FeCp2 in MeCN). This po-
tential is in the same range as that required for the genera-
tion of [(bpy)Ni
ure 5A).
ACHTUNGTRENNUNG(cod)] in the presence of 4-CrCl3 (see Fig-
In addition, we conducted the reductive spectroelectro-
chemical experiment with the [(bpy)CrCl3] complex, instead
Figure 5. UV/Vis absorption spectra taken during reductive spectroelec-
of 4-CrCl3, in the presence of [Ni
gands, as shown in Figure 5D. The formation of [(bpy)Ni-
(cod)] was observed at a potential of À1.3 V, which is more
negative than the potential needed in the presence of 4-
ACHTUNGTNER(NNUG acac)2], bpy, and cod li-
trochemistry in Bu4NPF6–THF solution: A) a mixture of [Ni
ACHTUNGTRENUNG(acac)2], 4-
CrCl3, bpy, and cod, B) a mixture of [Ni(acac)2], bpy, and cod, C) a mix-
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
ture of 4-CrCl3, bpy, and cod, D) a mixture of [NiACHTNUGRTNEUNG(acac)2], [(bpy)CrCl3],
bpy, and cod. Potentials versus Ag/AgCl.
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Cr/Ni-Catalyzed Vinylation of Aldehydes
FULL PAPER
CrCl2 was purchased from Alfa Aesar-Johnson Matthey Co. (99.9%
CrCl3. However, this potential is still higher than the poten-
tial required in the absence of Cr complexes for the reduc-
tion of NiII to Ni0. These results demonstrate the ligand ef-
fects on the efficiency of the Cr complexes for the reduction
of NiII to Ni0, in which 4-CrCl3 is more effective than
[(bpy)CrCl3]. Indeed, it has been shown experimentally that
bipyridine-based ligands gave effective Ni and Cr catalysts
in the coupling reaction of vinyl halides and aldehydes, and
the catalysts derived from 4,4’-di-tert-butyl-2,2’-bipyridine
are more effective than those of 2,2’-bipyridine.[7b] Interest-
ingly, both 4-CrCl3 and [(bpy)CrCl3] complexes have similar
molecular structures of approximately octahedral coordina-
tion, in which the bipyridine ligands are nonplanar.[18]
purity) and used as received. [CrCl
3ACHUTNGTREN(NGU thf)3] (Aldrich), [NiCl2ACHTUNTGERN(NUGN dme)] (Al-
drich), [Ni(acac)2] (Acros) were purchased from the suppliers indicated
AHCTUNGTRENNUNG
and used as received. NEt3, CH2Cl2, and MeCN were freshly distilled
from CaH2. THF was freshly distilled from Na/benzophenone.
Synthesis of the sulfonamide ligand 6
Synthesis of 10: A suspension of 9 (5.450 g, 20 mmol) in MeOH (20 mL)
was treated with 1m KOH (40 mL), and the mixture was stirred at room
temperature for 3 h. The resulting clear solution was then acidified with
2n HCl at 08C and the precipitate was collected by filtration and dried in
vacuo to give a yellow solid of the corresponding benzoic acid (5.259 g).
To a suspension of the above benzoic acid (5.259 g, 20 mmol) in CH2Cl2
(40 mL) was added anhydrous DMF (0.2 mL) and oxalyl chloride
(2.6 mL, 30 mmol) at 08C. The mixture was stirred at 08C for 3 h to give
a clear solution, then stirring was continued at room temperature over-
night. The solvent was evaporated under reduced pressure to obtain a
yellow solid of the benzoyl chloride.
d-tert-leucinol (2.520 g) [prepared by the reduction of d-tert-leucine
(2.620 g, 20 mmol) with NaBH4-I2 according to the reported procedure,[19]
and used without further purification] was dissolved in CH2Cl2 (40 mL),
followed by the addition of a solution of the above benzoyl chloride in
CH2Cl2 (10 mL) and NEt3 (7 mL, 50 mmol) at 08C. The reaction mixture
was stirred at 08C for 30 min and then at room temperature for 4 h. The
mixture was then diluted with CH2Cl2 and saturated NH4Cl. After sepa-
ration of the organic layer, the aqueous layer was extracted with CH2Cl2.
The combined organic layers were washed with brine, dried over Na2SO4,
and evaporated under reduced pressure to give a viscous yellow liquid of
the crude benzamide, containing the desired amide 10 and a small
amount of the ester 12.
Conclusion
By using UV/Vis spectroscopy, cyclic voltammetry, and spec-
troelectrochemistry, we were able to shed light on the roles
of the Ni and Cr catalysts involved in the reductive coupling
of vinyl halides and aldehydes: 1) Low-valent Ni from one-
electron reduction [formally NiI], not necessarily Ni0 acti-
vates the vinyl halide by reductive cleavage of the carbon–
halogen bond; 2) CrII does not interact with the vinyl
halide; 3) CrCl2 reduces NiII to the low-valent Ni species
necessary for vinyl halide cleavage; 4) in the absence of Cr,
the initially formed vinyl–Ni species is unstable and decom-
poses rapidly with dimerization of the vinyl residue; 5) in
the presence of Cr, the Ni–vinyl species is stabilized; 6) in
the electrochemical reduction of NiII, the generation of low-
The crude benzamide in EtOH (10 mL) was treated with 2m KOH
(10 mL), and the reaction mixture was stirred at room temperature for
2 h. The volatiles were removed in vacuo, and the residue was extracted
with CH2Cl2. The combined organic layers were washed with brine, dried
over Na2SO4, and evaporated under reduced pressure. The crude product
was purified by flash column chromatography on silica gel (EtOAc/
hexane 4:1) to give 10 as a yellow solid (5.783 g, 81% overall yield for
four steps). Rf =0.17 (EtOAc/hexane 4:1); m.p. 478C; 1H NMR
(300 MHz, CDCl3): d=6.89 (s, 1H, Ar-H), 6.34 (br. d, J=9.6 Hz, 1H,
NH), 3.96 (s, 3H, OCH3), 3.91 (s, 3H, OCH3), 3.90 (s, 3H, OCH3), 3.90–
3.81 (m, 2H), 3.60 (dd, J=11.3, 7.7 Hz, 1H), 2.8 (br. s, 1H, OH), 0.97 [s,
valent Ni {specifically [(bpy)NiACTHNUTRGNEUGN(cod)]} occurs at significantly
higher potential when CrIII is present. This points to a cata-
lytic role of CrIII in the generation of low-valent Ni when ex-
ternal chemical reductants are used, as is the case in the
“catalytic” NHK reaction. Finally, we could show that
ligand exchange occurs between the NiII and CrII complexes
involved. Further studies will address the precise nature of
vinylnickel stabilization by chromium.
9H,
155.1, 146.2, 144.1, 137.9, 125.8 (5ꢂArC), 106.4 (ArCH), 62.5 (CH), 62.2
(CH2), 61.2, 60.2, 56.5 (3ꢂOCH3), 33.9 [C(CH3)3], 26.9 [C(CH3)3] ppm;
IR (ATR): n˜ =3381, 3291, 2951, 1641, 1576, 1530 (s), 1489, 1356 (s), 1242,
1196, 1115 (s), 1024, 731 cmÀ1
CACTHNGUTERNNUG
(CH3)3] ppm; 13C NMR (75 MHz, CDCl3): d=165.6 (OC=N),
A
ACHTUNGTRENNUNG
.
Compound 12: a yellow viscous liquid; Rf =0.65 (EtOAc/hexane 4:1);
1H NMR (300 MHz, CDCl3): d=7.34 (s, 1H, Ar-H), 6.95 (s, 1H, Ar-H),
6.15 (br. d, J=10.1 Hz, NH), 4.64 (dd, J=11.5, 6.7 Hz, 1H), 4.44–4.28 (m,
2H), 3.99, 3.98, 3.96, 3.95, 3.943, 3.939 (each s, 6ꢂ OCH3), 1.05 [s, 9H, C-
Experimental Section
AHCTUNGTRENNG(NU CH3)3] ppm; IR (ATR): n˜ =3318, 2947, 1724, 1650, 1577, 1537 (s), 1491,
1454, 1342 (s), 1227, 1195, 1114 (s), 1023, 981, 812, 789, 732 cmÀ1. Com-
pound 12 can be converted quantitatively to 10 by treatment with 1m
KOH in H2O–EtOH at room temperature.
General experimental: Cyclic voltammetry and square-wave voltammetry
were carried out in acetonitrile (MeCN) containing 0.1m Bu4NPF6 using
a
three-electrode configuration (glassy-carbon working electrode, Pt
Synthesis of 11: To a solution of 10 (1.770 g, 5 mmol) in CH2Cl2 (10 mL)
was added SOCl2 (1.3 mL, 17.9 mmol) at 08C. The reaction mixture was
stirred at room temperature overnight and then evaporated under re-
duced pressure. The residue, containing a mixture of 11 and 13 (ca. 8:1),
was treated with 1m KOH in MeOH (5 mL). The reaction mixture was
stirred vigorously at room temperature for 3 h. The volatiles were then
removed in vacuo and the residue was extracted with CH2Cl2. The com-
bined organic layers were washed with brine, dried over Na2SO4, and
evaporated under reduced pressure. The crude product was purified by
flash column chromatography on silica gel (Et2O/hexane 1:1) to give 11
as a pale yellow liquid (1.510 g, 90%). Rf =0.46 (EtOAc/hexane 1:1);
1H NMR (300 MHz, CDCl3): d=7.21 (s, 1H, Ar-H), 4.32 (dd, J=10.2,
8.7 Hz, 1H, NCHCHHO), 4.22 (dd, J=8.7, 7.7 Hz, 1H, NCHCH2O),
4.05 (dd, J=10.2, 7.7 Hz, 1H, NCHCHHO), 3.98, 3.97, 3.96 (each s, 9H,
counter electrode, Ag/AgCl reference) and Metrohm Autolab
a
PGSTAT30 Potentiostat and function generator. The solution was deoxy-
genated for at least 10 min by bubbling argon, and the cell was main-
tained under an argon atmosphere during the experiment. The ferrocene/
ferrocenium couple served as internal reference. UV/Vis absorption spec-
tra were recorded on a Cary 50 Scan or a DU 800 spectrophotometer.
UV/Vis spectroelectrochemical measurements (in 0.1m Bu4NPF6 solu-
tions) were performed by using an optically transparent thin-layer elec-
trode (OTTLE) cell.[17] NMR spectra were recorded on a Bruker AC300
(300 MHz) or a Bruker Advance II 600 spectrometer and were refer-
enced to residual solvent. IR spectra were measured on a Shimadzu
IRAffinity-1 instrument. Optical rotations were measured on a Perkin–
Elmer 343 Plus polarimeter. Melting points were determined on a Bꢀchi
apparatus and are uncorrected.
3ꢂOCH3), 0.94 [s, 9H, CACTHNUTRGNEUNG
(CH3)3] ppm; 13C NMR (75 MHz, CDCl3): d=
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A. Berkessel, A. Klein et al.
156.8, 154.1, 145.9, 144.8, 115.6 (ArC), 107.6 (ArCH), 76.4 (CH), 69.3
(CH2), 62.6, 62.1, 56.5 (3ꢂOCH3), 31.2 [C(CH3)3], 25.8 [C(CH3)3] ppm;
IR (ATR): n˜ =2949, 1658, 1575, 1539 (s), 1494, 1454, 1403, 1362 (s), 1250,
1225, 1113 (s), 1018 (s), 977, 819, 732 cmÀ1
[1] For reviews, see: a) A. Fꢀrstner, Chem. Rev. 1999, 99, 991–1045;
b) L. A. Wessjohann, G. Scheid, Synthesis 1999, 1–36; c) K. Takai,
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gaden, P. J. Guiry, Adv. Synth. Catal. 2007, 349, 2407–2424.
[2] Reduction of alkenyl and aryl iodides to alkenyl and aryl chromium
reagents with CrCl2 and subsequent addition to aldehydes was first
performed without additional Ni catalyst (K. Takai, K. Kimura, T.
Kuroda, T. Hiyama, H. Nozaki, Tetrahedron Lett. 1983, 24, 5281–
5284). Later, it was found that the success of the reaction depended
on the source and batch of CrCl2. X-ray fluorescence analysis of the
effective lots revealed that nickel was the major contaminant.
[3] H. Jin, J.-I. Uenishi, W. J. Christ, Y. Kishi, J. Am. Chem. Soc. 1986,
108, 5644–5646.
G
ACHTUNGTRENNUNG
.
Compound 13: a colorless solid; Rf =0.45 (EtOAc/hexane 1:1); 1H NMR
(300 MHz, CDCl3): d=6.94 (s, 1H, Ar-H), 6.10 (br. d, J=10.1 Hz, 1H,
NH), 4.21 (m, 1H), 3.98, 3.94, 3.93 (each s, 9H, 3 x OCH3), 3.85 (dd, J=
11.7, 3.8 Hz, 1H, NCHCHHO), 3.55 (dd, J=11.7, 8.7 Hz, 1H,
NCHCHHO), 1.01 [s, 9H, CACHTNUTGRNEUNG
(CH3)3] ppm; 13C NMR (75 MHz, CDCl3):
d=164.7 (OC=N), 155.1, 146.3, 144.3, 138.1, 125.5 (5ꢂArC), 106.5
(ArCH), 62.6 (CH), 61.2, 58.8, 56.5 (3ꢂOCH3), 45.0 (CH2), 35.2 [C-
ACHTUNGTRENNUNG(CH3)3], 26.7 [CACHTUNGTRENNUNG(CH3)3] ppm; IR (ATR): n˜ =3283, 2947, 1645, 1576, 1533
(s), 1491, 1360 (s), 1242, 1198, 1117 (s), 1026, 729 cmÀ1. Compound 13
can be converted quantitatively to 11 by treatment with 1m KOH in
H2O–EtOH at room temperature.
[4] K. Takai, M. Tagashira, T. Kuroda, K. Oshima, K. Utimoto, H.
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Synthesis of the ligand 6: A mixture of 11 (1.014 g, 3 mmol) and anhy-
drous SnCl2 (2.845 g, 15 mmol) in absolute EtOH (20 mL) was stirred at
reflux for 1 h under an argon atmosphere.[20] After the reaction was com-
pleted, the reaction mixture was cooled to room temperature, poured
onto ice and then made slightly basic (pH 7–8) with solid NaHCO3. The
mixture was extracted with EtOAc, and the combined organic layers
were washed with brine and dried over Na2SO4. After removal of the sol-
vent in vacuo, the crude product was purified by filtering through a short
path of silica gel (Et2O/hexane 1:1) to give the corresponding aniline as a
light yellow liquid (0.856 g, 93%). Rf =0.71 (EtOAc/hexane 1:1);
1H NMR (300 MHz, CDCl3): d=7.03 (s, 1H, Ar-H), 6.09 (br. s, 2H,
NH2), 4.25 (dd, J=12.9, 11.0 Hz, 1H), 4.16–4.09 (m, 2H), 3.95, 3.90, 3.83
[5] a) Y. Okude, S. Hirano, T. Hiyama, H. Nozaki, J. Am. Chem. Soc.
1977, 99, 3179–3181; b) Y. Okude, T. Hiyama, H. Nozaki, Tetrahe-
dron Lett. 1977, 18, 3829–3830; c) T. Hiyama, Y. Okude, K. Kimura,
H. Nozaki, Bull. Chem. Soc. Jpn. 1982, 55, 561–568; d) T. Hiyama,
K. Kimura, H. Nozaki, Tetrahedron Lett. 1981, 22, 1037–1040; e) K.
Takai, K. Kimura, T. Hiyama, H. Nozaki, Tetrahedron Lett. 1983, 24,
5281–5284.
[6] a) A. Fꢀrstner, N. Shi, J. Am. Chem. Soc. 1996, 118, 2533–2534;
b) A. Fꢀrstner, N. Shi, J. Am. Chem. Soc. 1996, 118, 12349–12357.
[7] a) K. Namba, Y. Kishi, Org. Lett. 2004, 6, 5031–5033; b) K. Namba,
J. Wang, S. Cui, Y. Kishi, Org. Lett. 2005, 7, 5421–5424.
[8] M. Kuroboshi, M. Tanaka, S. Kishimoto, K. Goto, ; H. Tanaka, S.
Torii, Tetrahedron Lett. 1999, 40, 2785–2788; H. Tanaka, S. Torii,
Tetrahedron Lett. 1999, 40, 2785–2788.
(each s, 9H, 3ꢂOCH3), 0.96 [s, 9H, CACHTUNGTRNEUNG
(CH3)3] ppm; 13C NMR (75 MHz,
CDCl3): d=163.1 (OC=N), 145.6, 143.5, 140.3, 138.6 (4ꢂArC), 107.5
(ArCH), 103.4 (ArC), 76.4 (CH), 66.9 (CH2), 60.9, 60.3, 56.5 (3ꢂOCH3),
[9] a) R. Grigg, B. Putnikovic, C. Urch, Tetrahedron Lett. 1997, 38,
6037–6308; b) M. Kuroboshi, M. Tanaka, S. Kishimoto, H. Tanaka,
S. Torii, Synlett 1999, 69–70; c) M. Durandetti, J.-Y. Nꢃdꢃlec, J. Pꢃri-
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[10] a) A. Berkessel, D. Menche, C. A. Sklorz, M. Schrçder, I. Paterson,
Angew. Chem. 2003, 115, 1062–1065; Angew. Chem. Int. Ed. 2003,
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nella, N. Vogl, J. Lex, J. M. Neudoerfl, J. Org. Chem. 2004, 69, 3050–
3056; c) I. Paterson, H. Bergmann, D. Menche, A. Berkessel, Org.
Lett. 2004, 6, 1293–1295.
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K. Wan, Y. Kishi, Org. Lett. 2002, 4, 4435–4438; b) K. Namba, S.
Cui, J. Wang, Y. Kishi, Org. Lett. 2005, 7, 5417–5419; c) H. Guo, C.-
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Henderson, T. Sasaki, Y. Kishi, J. Am. Chem. Soc. 2009, 131, 16678–
16680.
[12] A reduction of catalyst loading from typically 10–20 mol% Cr cata-
lyst and 1–5 mol% Ni catalyst to 1–2 mol% with acceptable rates
was recently achieved by using Ni/Cr heterobimetallic catalysts, see
reference [11d].
33.8 [C
1636 (s), 1591, 1545, 1464 (s), 1377, 1283, 1200, 1148 (s), 1051, 1018 (s),
986 (s), 918 cmÀ1
ACHTUNGTRENNUNG(CH3)3], 25.9 [CACHTUNGTRENNUNG(CH3)3] ppm; IR (ATR): n˜ =3471, 3292, 2951,
.
To a solution of the above aniline (0.668 g, 2.17 mmol) in pyridine (5 mL)
was added a catalytic amount of 4-(dimethylaminopyridine) (DMAP;
10 mg) and 2-naphthalenesulfonyl chloride in portions at 08C. The mix-
ture was stirred at 08C for 4 h and then poured into a mixture of ice
(20 g) and 2n HCl (20 mL). The aqueous phase was extracted with
CH2Cl2, and the combined organic layers were washed with 1n HCl,
brine, dried over Na2SO4, and evaporated under reduced pressure. The
crude product was purified by flash column chromatography on silica gel
(Et2O/hexane 1:1) to give 6 as a colorless solid (0.964 g, 89%). Rf =0.63
(EtOAc/hexane 1:1); m.p. 1458C, [a]D20 =+41.7 (c=1 in CHCl3);
1H NMR (300 MHz, CDCl3): d=11.84 (br. s, 1H, NH), 8.54 (s, 1H, Ar-
H), 8.03–7.89 (m, 4H, Ar-H), 7.61 (m, 2H, Ar-H), 7.10 (s, 1H, Ar-H),
4.26–4.10 (m, 2H), 4.04 (dd, J=10.3, 7.8 Hz, 1H), 3.88, 3.85, 3.18 (each s,
9H, 3ꢂOCH3), 0.99 [s, 9H, CACHTNUGRTNEUNG
(CH3)3] ppm; 13C NMR (75 MHz, CDCl3):
d=162.8 (OC=N), 149.6, 147.0, 145.8, 139.4, 134.5, 132.0 (6ꢂArC), 129.2,
128.3 (2ꢂArCH), 128.2 (ArC), 127.8, 127.6, 127.2, 123.0 (ArCH), 112.4
(ArC), 107.1 (ArCH), 76.1 (CH), 67.8 (CH2), 61.0, 59.7, 56.2 (3ꢂOCH3),
33.9 [CACHTUNGTRENNUNG(CH3)3], 25.8 [CACHTUNGTRENNUNG(CH3)3] ppm; IR (ATR): n˜ =3057, 2947, 1635,
[13] a) H. S. Preston, C. H. L. Kennard, R. A. Plowman, J. Inorg. Nucl.
Chem. 1968, 30, 1463–1467; b) H. S. Preston, C. H. L. Kennard, J.
Chem. Soc. A 1969, 2682–2685; c) R. J. Butcher, E. Sinn, Inorg.
Chem. 1977, 16, 2334–2343; d) R. J. Butcher, C. J. OꢄConnor, E.
Sinn, Inorg. Chem. 1979, 18, 492–497; e) B. W. Dockum, W. M.
Reiff, Inorg. Chem. 1982, 21, 2613–2619.
1589, 1493, 1458, 1373, 1321 (s), 1152, 1126 (s), 1065 (s), 1020 (s), 986,
921, 818, 737, 665 (s) cmÀ1; MS (EI, 70 eV): m/z (%): 498 (3) [M]+, 307
(48), 293 (11), 250 (33), 207 (34), 160 (58), 128 (100), 115 (36), 91 (9), 77
(11), 64 (13), 51 (11); elemental analysis calcd (%) for C26H30N2O6S: C
62.63, H 6.06, N 5.62; found: C 62.51, H 6.09, N 5.58.
[14] A. Klein, A. Kaiser, B. Sarkar, M. Wanner, J. Fiedler, Eur. J. Inorg.
Chem. 2007, 965–976.
[15] Upon addition of one equivalents of LiEt3BH (superhydride), we
observed a narrow isotropic unresolved EPR signal centered at g=
2.0007, indicative of a mainly ligand-centered radical.
Acknowledgements
[16] Studies of ligand exchange between a CrIII–sulfonamide complex
and [{(dmp)NiCl2}2] (8-NiCl2) in the presence of Mn0 by NMR spec-
troscopy indicated no ligand exchange (see reference [11b]). Howev-
er, due to paramagnetism of the metal complexes involved, we con-
sider our spectroelectrochemical studies more reliable.
This work was supported by the Fonds der Chemischen Industrie. W.
Harnying gratefully acknowledges the Alexander von Humboldt Founda-
tion for a research fellowship. A. Kaiser and A. Klein thank the DFG
(K.L. 1194/5-1) for financial support. We thank the Evonik Degussa
GmbH, Hanau, for generous gifts of amino acids.
ˇ
ˇ
[17] M. Krejcꢅk, M. Danek, F. Hartl, J. Electroanal. Chem. 1991, 317,
179–187.
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Chem. Eur. J. 2011, 17, 4765 – 4773

Cr/Ni-Catalyzed Vinylation of Aldehydes
FULL PAPER
[18] For the X-ray structures of the 4-CrCl3-OH2 complex [(4,4’-
[19] M. J. McKennon, A. I. Meyers, J. Org. Chem. 1993, 58, 3568–3571.
[20] F. D. Bellamy, K. Ou, Tetrahedron Lett. 1984, 25, 839–842.
tBu2bpy)CrCl
3ACHTUNGTRENNUNG(OH2)], see reference [10d], and of the [(bpy)CrCl3-
ACHTUNGTRENNUNG(OH2)] complex, see: N. F. Brennan, B. Blom, S. Lotz, P. H. van
Rooyen, M. Landman, D. C. Liles, M. J. Green, Inorg. Chim. Acta
2008, 361, 3042–3052.
Received: November 22, 2010
Published online: March 21, 2011
Chem. Eur. J. 2011, 17, 4765 – 4773
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4773