Nickel-catalyzed hydrogenolysis of unactivated carbon-cyano bonds

Article abstract of DOI:10.1039/c3cc44562c

Selective hydrogenolysis of C-CN bonds can allow chemists to take advantage of ortho-directing ability, α-C-H acidity and electron withdrawing ability of the cyano group for synthetic manipulations. We have discovered hydrogenolysis of aryl and aliphatic cyanides under just 1 bar of hydrogen by using a nickel catalyst. This protocol was applied in the aryl cyanide directed functionalization reaction and α-substitution of benzyl cyanides.

Full text of DOI:10.1039/c3cc44562c

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Nickel-catalyzed hydrogenolysis of unactivated
carbon–cyano bonds†
Cite this: DOI: 10.1039/c3cc44562c
Tuhin Patra, Soumitra Agasti, Atanu Modak and Debabrata Maiti*
Received 18th June 2013,
Accepted 17th July 2013
DOI: 10.1039/c3cc44562c
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Selective hydrogenolysis of C–CN bonds can allow chemists to take
advantage of ortho-directing ability, a-C–H acidity and electron
withdrawing ability of the cyano group for synthetic manipula-
tions. We have discovered hydrogenolysis of aryl and aliphatic
cyanides under just 1 bar of hydrogen by using a nickel catalyst.
This protocol was applied in the aryl cyanide directed function-
alization reaction and a-substitution of benzyl cyanides.
Scheme 1 Different approaches to hydrodecyanation.
Functional group assisted transformations are most widely either relatively active strained molecules14c,d or harsh reaction
used in synthetic chemistry.1 In this regard, a cyano group has conditions involving heterogeneous catalytic systems14e, f or
been found to be beneficial in terms of its a-acidity, electron- employing specially designed pincer ligands.14g To date, only a
withdrawing properties and ortho-directing ability.2,3 Recently, few examples of reductive cleavage of unactivated C–C bonds
using a locked long chain structural motif, meta-directing ability using H2 gas have been reported.14a,h,i
of a cyano group has been explored.4 Notably, during cross
Conversely, hydrogen is less nucleophilic compared to the
coupling reactions, the cyano group can alleviate metal-mediated carbon nucleophiles generated upon oxidative addition to C–CN
steps e.g. oxidative addition, reductive elimination etc.5 By using and may thus lead to catalyst deactivation during decyanation
the inherent stability and the electron withdrawing nature of the of C–CN bonds.7a Herein, we report the first hydrogenolysis of
cyano group, otherwise unreactive arenes were fluorinated via C–CN bonds using H2 gas as the hydride source.
Pd-catalyzed cross-coupling reaction.6 In this context, removal of
a functional group that has fulfilled its obligation plays a key role reaction using (Me2SiH)2O [tetramethyldisiloxane, TMDSO] as
in generation of the desired product.7–9 the hydride source.15 To develop hydrogenolysis of unactivated
Recently we have reported a nickel catalyzed decyanation
High bond dissociation energy of C–CN bonds limits the C–CN bonds, we started with 2-cyanonaphthalene using Ni(acac)2–
easy removal of a cyano group;10 therefore earlier reports PCy3 combination under 1 bar pressure of H2 which gave
consisted of harsh reaction conditions using highly reactive the desired product in 35% yield. Encouraged by our initial
alkali metals for removal of a cyano group.11 On the other findings, different combinations of nickel catalyst–ligand
hand, newly developed transition metal catalyzed decyanation systems were investigated along with different bases and addi-
methods rely on hydrosilanes as hydride sources (Scheme 1).12 tives.16 After extensive experimentations we have realized that
The Enthaler group has introduced Grignard reagents as sources catalytic Ni(COD)2 in combination with PCy3 (45–90 mol%) and
of hydride for hydrodecyanation reaction (Scheme 1).13 In this AlMe3 (3 equiv.) under 1 bar pressure of H2 gas can produce the
context, use of H2 gas for C–CN bond cleavage is a superior desired decyanated product in good yield. The role of AlMe3 as
choice since H2 is extremely abundant and most importantly no an additive is found to be crucial. Firstly, as a Lewis acid it
extra waste is introduced into the reaction system.7,14 Earlier activates the inert C–CN bond for facile oxidative addition of
efforts devoted to utilization of H2 as the reductant are limited to Ni(COD)2.10q–t,15 Secondly, it can help to remove and consume
the HCN gas produced under the reaction conditions.17 Although
Ni-catalyzed aryl ether hydrogenolysis was unsuccessful with PCy3
Department of Chemistry, IIT Bombay, Powai, Mumbai-400076, India.
and required use of an expensive carbene ligand, decyanation
E-mail: dmaiti@chem.iitb.ac.in
reactions were effective with easily available and economical PCy3.7
† Electronic supplementary information (ESI) available: Detailed experimental
Furthermore no ring hydrogenation product from arene p-bonds
procedures and characterization data for all products. See DOI: 10.1039/
c3cc44562c
was observed during the present study.18
c
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Table 1 Hydrogenolysis of aryl cyanidesa 16,20
Table 2 Hydrogenolysis of heteroaryl cyanidesa 16
a
Ar–CN (0.25 mmol), Ni(COD)2 (30 mol%), PCy3 (90 mol%), AlMe3
b
(0.75 mmol), H2 gas (1 bar), toluene (1 mL), 130 1C, 24 h. Minor
products and Ar–Me are depicted in parenthesis. ArMe product iso-
lated. Ni(COD)2 (15 mol%), PCy3 (45 mol%). 10–25% recovered
starting materials (rsm). 18% biphenyl.
c
d
e
f
a
Ar–CN (0.25 mmol), Ni(COD)2 (30 mol%), PCy3 (90 mol%), AlMe3
b
(0.75 mmol), H2 gas (1 bar), toluene (1 mL), 130 1C, 24 h. Ni(COD)2
(15 mol%). 12% methylated product. 9% methylated product.
c
d
Selective hydrogenolysis of C–CN bonds over C–OMe bonds7,9,19
was observed under the present conditions (entries 1g, 1h and 2c).
Tolerance towards ester (1i and 1m) groups is also advantageous
because the use of a Grignard reagent as a hydride source might be
difficult for such compounds.13 For substrates bearing dicyano
groups, monodecyanation resulted in the formation of the major
product (1k). It should be noted that, sequential removal of cyano
groups is possible from a dicyano substrate by employing our
present protocol (entries 1k and 1l).
Aryl cyanides with hydroxyl (ArOH, 1c), amide (1d), keto (1e),
trifluoromethyl (1f), ester (1i and 1m) and fluoro (1j) groups
underwent hydrogenolysis of cyano groups in good yield (Table 1).
In order to further explore the substrate scope, heterocyclic
cyanide compounds (HetAr-CN) were reacted under the optimized
reaction conditions. In general, irrespective of the position
of the cyano group, good to excellent yields of the desired
decyanated products were obtained for different HetAr-CN
compounds (Table 2). Of note is that indole derivatives with
cyano groups at 3- and 4-positions were decyanated (entries 2e
and 2d, respectively). Furthermore, 2- and 3-cyanobenzothio-
phene can be employed successfully (entries 2f and 2g, respec-
tively) under the present reaction conditions. Five membered
heterocyclic cyanide with two heteroatoms (e.g. entry 2k) was
elimination is
a major problem for aliphatic substrates
when involved in metal mediated oxidative addition reactions.21
Interestingly, benzyl cyanides (3d) and aliphatic nitrile (3b) with
b-hydrogen underwent smooth hydrogenolysis with only 1 bar
H2 gas (Table 3).
In complex molecular set up only desired hydrogenolysis of
cyano groups was observed without reduction of internal alkene in
the cholesterol core (Scheme 2, 4b). Using a-acidity of cyano groups
alkylation is possible for benzyl cyanide (Scheme 2, 4i). In a similar
manner, cyano directed ortho-arylation22 (Scheme 2, 4c) and ortho-
alkoxylation23 (Scheme 2, 4e and 4g) can be implemented in a
molecule of interest. After its beneficial use, the cyano group can be
removed effectively by using the current hydrogenolysis protocol
(Scheme 2, entries 4d, 4f, 4h and 4j).
In summary, an alternate and general protocol for nickel-
catalyzed hydrogenolysis of aryl and alkyl cyanides by using
cheaper, greener and milder hydrogen gas as the hydride source
has been developed. Different electronic and steric substituents as
well as substrates with b-hydrogen were successfully reacted using
also decyanated effectively. A 73% yield was obtained with the Table 3 Hydrogenolysis of alkyl cyanidesa 16,20
dibenzo[b,d]thiophene containing substrate. We found that 2a
can be obtained in 93% yield with 30 mol% of catalyst, whereas
15 mol% of catalyst gave 78% product. Also, hydrogenolysis was
successful with cyanoarenes with sterically demanding ortho-
substituents (entries 2a, 2b and 2c) or with ortho-directing
groups (entries 2j and 2m). Therefore, a desired transformation
can be carried out at the 6-position of the arene by using a
cyano group as a temporary protecting group at the 2-position.
Benzyl cyanides without b-hydrogen gave the desired product
in preparatively useful yield (entries 3a and 3c). Different alkyl
a
Reaction conditions: Ar–CN (0.25 mmol), Ni(COD)2 (30 mol%), PCy3
(90 mol%), AlMe3 (0.75 mmol), H2 gas (1 bar), toluene (1 mL), 130 1C,
24 h. Minor products and Ar–Me are depicted in parenthesis. GC
b
c
d
e
cyanides with b-hydrogens were examined as the b-hydride yield. Ni(COD)2 (15 mol%), PCy3 (45 mol%). ArMe product isolated.
c
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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 CSIR-India (fellowship to S.A. and A.M.) is grate-
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Chem. Commun.