Nickel-catalyzed decyanation of inert carbon-cyano bonds

Article abstract of DOI:10.1039/c2cc36883h

Nickel catalyzed decyanation of aryl and aliphatic cyanides with hydrosilane as the hydride source has been developed. This method is easy to handle, scalable and can be carried out without a glove box. The method has been applied in the cyanide directed functionalization reaction and α-substitution of benzyl cyanide.

Full text of DOI:10.1039/c2cc36883h

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Nickel-catalyzed decyanation of inert carbon–cyano
bonds†
Cite this: Chem. Commun.,
2013, 49, 69--71
Tuhin Patra, Soumitra Agasti, Akanksha and Debabrata Maiti*
Received 22nd September 2012,
Accepted 6th November 2012
DOI: 10.1039/c2cc36883h
www.rsc.org/chemcomm
Nickel catalyzed decyanation of aryl and aliphatic cyanides with
hydrosilane as the hydride source has been developed. This
method is easy to handle, scalable and can be carried out without
a glove box. The method has been applied in the cyanide directed
functionalization reaction and a-substitution of benzyl cyanide.
Removal of a specific functional group after using its beneficial
aspects plays an important role in synthetic chemistry.1 Although a
wide variety of effective approaches now exists for a number of
defunctionalization reactions,2 some of these have been only
recently discovered and need further improvement. Synthetic
methodology for the removal of the cyano group can be advanta-
geous due to its ortho-directing ability and a-C–H acidity.3,4 The
electron withdrawing character of a cyano group brings about
challenging coupling reactions by making metal-mediated steps
i.e. oxidative addition and reductive elimination faster than the
unsubstituted analogues and thus a decyanation protocol will allow
synthetic chemists to take advantage of the cyano group.1a,b
The high bond dissociation energy of the C–CN bond and
limited successes of (aryl/alkyl) cyanides as the coupling partner
compared to (aryl/alkyl) halides imposes a scientific challenge to
develop mild and efficient methods for its reductive cleavage.5
Previous decyanation reactions relied on oxidative addition to the
silyl hydride and then silicon-assisted carbon–cyano bond cleavage
reactions.3a,c,h Another powerful approach could be via insertion of a
transition metal into the C–CN bond and subsequent formation of
the decyanated product with a hydride source (Scheme 1). In this
context, we note that nickel mediated oxidative addition to the
C–CN bond and related transformations are reported in the litera-
ture.1a,6 Herein, we report a general and mild Ni-catalyzed method
for reductive cleavage of unactivated C–CN bonds with (Me2SiH)2O
[tetramethyldisiloxane, TMDSO] as the hydride source.
Scheme 1 Catalytic decyanation reactions of R–CN.
the presence of various hydride donors such as TMDSO, Et3SiH,
iPr3SiH, and Ph2SiH2. We studied 2-cyanonaphthalene as the sub-
strate in the presence of various nickel sources including Ni(COD)2
(COD, 1,5-cyclooctadiene), Ni(acac)2 (acac, acetylacetonate), NiCl2,
Ni(OAc)2 etc. Use of Lewis acid (AlMe3) can facilitate oxidative addition
into the C–CN bond6 and was, therefore, found to be beneficial in
terms of substrate scope and yields of the decyanation reactions.
These extensive experimentations showed that the Ni(acac)2
complex of PCy3 (or PCy3ÁHBF4 with equimolar K3PO4) in
combination with TMDSO [(Me2SiH)2O] can catalyze the reduc-
tive decyanation of R–CN substrates efficiently.
Encouraged by our initial findings, we set out to explore the
substrate scope for this Ni(acac)2 catalyzed reductive decyana-
tion reaction (Table 1). The aryl alkyl ether bonds (Ar–O–R; R =
Me, nBu) were tolerated (1a, 1b and 1j) under our reaction
conditions, thus exhibiting a preference for reductive cleavage
of the C–CN bond over Ar–O–R.2b,c,7 A monodecyanated product
was observed from substrates bearing dicyano groups (1a and
1g). Ester (1c and 1h) and keto (1i) groups were also tolerated.
Although not essential, presence of an ortho-directing group or
an ortho-substituent was found to be beneficial in achieving
better yield of the desired decyanated product.
In order to realize the C–CN bond cleavage, we began our
investigation by evaluating a variety of ligand systems for nickel in
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai
400076, India. E-mail: dmaiti@chem.iitb.ac.in
Having demonstrated the protocol on aryl derivatives, we next
focused on heterocyclic cyano compounds. As expected, nickel
catalyst can be employed in combination with a hydride source for
† Electronic supplementary information (ESI) available: Detailed description of
experimental procedures, characterization of all compounds. See DOI: 10.1039/
c2cc36883h
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Table 1 Ni–catalyzed reductive decyanation of aryl cyanides
Table 3 Ni–catalyzed reductive decyanation of alkyl cyanides
R–CN (0.5 mmol), Ni(acac)2 (30 mol%), PCy3b(60–90 mol%), (Me2SiH)2O,
a
AlMe3 in toluene, 130 1C, 24 h. GC yield. m-Xylene as solvent.
130 1C, 24 h. a R–CN (0.5 mmol), Ni(acac)2 (15 mol%), PCy3 (30 mol%),
b
(Me2SiH)2O, AlMe3, toluene. R–CN (0.5 mmol), Ni(acac)2 (20 mol%),
Scheme 2 Deuterium labeling.
c
PCy3 (40 mol%), (Me2SiH)2O, AlMe3, toluene. R–CN (0.5 mmol), Ni(acac)2
d
(30 mol%), PCy3 (90 mol%), (Me2SiH)2O, AlMe3, toluene. 12% Biphenyl.
Table 2 Ni–catalyzed reductive decyanation of heterocycles
Fig. 1 ORTEP diagram of trans-[Ni(PCy3)2(CN)2]. Hydrogen atoms are omitted for clarity.
Synthetic transformations involving alkyl groups (RalkylX) are
considered challenging due to their propensity to undergo side
reactions from alkyl-metal intermediates to b-hydride elimination.8
Consistent with our expectations, aliphatic nitriles (3f and 3g) were
successfully decyanated under the present conditions.
Isolation of the deuterated product by using Ph2SiD2 indicated
that hydrosilane is the source of hydrogen in the resulting
decyanated product (Scheme 2). Selective incorporation of the
deuterium atom in unbiased arenes can thus easily be done under
neutral conditions.
A stable trans-[Ni(PCy3)2(CN)2] was isolated and characterized
by X-ray crystallography9 (Fig. 1) from various decyanation reac-
tions (e.g. entries 1f, 1g, 1i and 3f). Attempted decyanation
reactions of 1-cyanonaphthalene by using trans-[Ni(PCy3)2(CN)2]
as the catalyst [instead of Ni(acac)2] did not produce any of the
desired decyanated product. Therefore, we suspected that the
130 1C, 24 h. a R–CN (0.5 mmol), Ni(acac)2 (15 mol%), PCy3 (30 mol%),
(Me2SiH)2O, AlMe3, toluene. R–CN (0.5 mmol), Ni(acac)2 (30 mol%),
PCy3 (60–90 mol%), (Me2SiH)2O, AlMe3, toluene.
b
effective decyanation of heterocyclic cyanides (Table 2). Substrates
with two different heteroatoms can be employed successfully (2a, 2b,
2i and 2j) indicating lower Lewis acidity of the nickel catalyst.
Notably, reductive decyanation reactions were efficient even with
ortho-directing groups like pyrazole (2a and 2b), ester (1c) and
oxazoline (2i and 2j).
Table 4 Competition experiment with 2-cyanonaphthalene and 2-X-naphthalene
Next we focused on catalytic decyanation of alkyl cyanides since
such C–CN bond activations are problematic.8 We first tested the
ability of the nickel-catalyzed method to transform benzylic C–CN
bonds (Table 3) into C–H bonds (3a–3e). 2-(4-Hydroxyphenyl)aceto-
nitrile produced the expected product in preparatively useful yields
(3a). Benzylic cyanide with a long chain alkyl substituent also
afforded the corresponding decyanated product (3c).
X
Temp (1C)
a (mmol)
b (mmol)
c (mmol)
SMe
90
130
130
130
0.29
0.495
0.18
0.20
—
0.04
0.06
0.005
—
0.24
0.245
O-p-tol
OMe
0.175
c
70 Chem. Commun., 2013, 49, 69--71
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This activity is supported by BRNS (2011/20/37C/13/BRNS),
India. Financial support received from UGC-India (fellowship
to T.P.) and IIT Bombay (fellowship to S.A. and Akanksha)
is gratefully acknowledged. X-ray structural study was carried
out at the National Single Crystal Diffractometer Facility, IIT
Bombay.
Notes and references
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quick formation of this nickel complex, trans-[Ni(PCy3)2(CN)2], is
possibly contributing to catalyst deactivation.
We next set out to determine the realtive ease of nickel
catalyzed defunctionalization reactions with aryl–CN, –SMe,
–OMe and –OAr functional groups under the present reaction
conditions (Table 4). We have carried out competition experi-
ments with 2-cyanonaphthalene and 2-X-naphthalene (X =
OMe, OAr and SMe) where two substrates were reacted in one
flask. We observed that reduction of the aromatic C–CN bond
occurs faster than ArOAr and ArOMe. Further investigations
showed that removal of –SMe is faster than that of the
–CN group.2a Thus our present study along with the recent
literature2a–c,7 enabled us to find a reactivity pattern which is
summarized below:
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The decyanation reaction proved to be scalable, with
2-(1H-pyrrol-1-yl)benzonitrile producing 96% isolated yield of
the expected product (Scheme 3, 2d). Benzyl cyanide can be
alkylated upon NaH treatment. Subsequent decyanation of the
resulting product will therefore allow use of benzyl cyanide as a
benzyl anion equivalent (Scheme 3, 4a). A cyano group is also
ortho directing10 and therefore direct C–H arylation at the ortho-
position and successive decyanation would allow efficient
synthesis of biaryls (Scheme 3, 1k). These two-step methods
(Scheme 3) demonstrate the power of this decyanation strategy
to synthesize useful molecules.
In summary, we have developed a general protocol for
nickel-mediated decyanation of aryl and alkyl cyanides. A wide
range of nitriles with varying electronic and steric substituents
were successfully decyanated as well as the substrates with
b-hydrogen. Synthetic advantages of the cyano group including
ortho-directing ability, a-C–H acidity and electron-withdrawing
ability can thus temporarily be used. The Ni-catalyzed decyana-
tion reaction is expected to be applicable in synthetic chemistry
due to its wide availability and easy to handle protocol. Studies
are ongoing in our research group to develop related synthetic
transformations and to elucidate mechanistic details for the
reductive decyanation of the C–CN bond.
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c
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Chem. Commun., 2013, 49, 69--71 71