Nickel-Catalyzed α-Benzylation of Arylacetonitriles via C-O Activation

Article abstract of DOI:10.1002/adsc.201500822

Efficient Ni-catalyzed direct cross-couplings of benzylic alcohol derivatives with arylacetonitriles via C-O activation are described. Various α-benzylated arylacetonitriles including those with functional groups can be prepared under mild reaction conditions.

Full text of DOI:10.1002/adsc.201500822

UPDATES
DOI: 10.1002/adsc.201500822
À
Nickel-Catalyzed a-Benzylation of Arylacetonitriles via C O
Activation
Jing Xiao,a Jia Yang,a Tieqiao Chen,a,* and Li-Biao Hana,b,*
a
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan
University, Changsha 410082, Peopleꢀs Republic of China
E-mail: chentieqiao@hnu.edu.cn
National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8565, Japan
b
E-mail: libiao-han@aist.go.jp
Received: September 3, 2015; Revised: December 10, 2015; Published online: February 11, 2016
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500822.
Abstract: Efficient Ni-catalyzed direct cross-cou-
do not work in these borrowing hydrogen catalytic
systems (Scheme 1b).[2]
plings of benzylic alcohol derivatives with arylace-
À
À
tonitriles via C O activation are described. Various
Recently, the Ni-catalyzed cross-couplings of C O
À
a-benzylated arylacetonitriles including those with
functional groups can be prepared under mild reac-
tion conditions.
compounds with hydrocarbons via C O activation
have attracted great attention as a new method for
[4,5]
À
constructing C C bonds.
Our group has also con-
tributed to this field. Recently, we reported a Ni-cata-
lyzed sp C sp C bond-forming reaction for the syn-
thesis of heteroatom-containing diarylmethanes via
C O/C H cross coupling (Scheme 2).
the substrate scope was narrowed to primary naph-
thylmethanol derivatives, the secondary alcohol and
simpler benzylic alcohol derivatives did not work well
3
2
À
Keywords: arylacetonitriles; a-benzylation; benzylic
À
alcohol derivatives; C O activation; nickel
[5d]
À
À
However,
Nitriles are widely applied in materials chemistry and under the reaction conditions. During further exten-
organic synthesis. They also occurr frequently in bio- sive studies, we found that nitriles also served as the
active molecules.[1] The a-alkylation of simple nitriles coupling partners of naphthylmethanol derivatives
is one of the most popular methods for the synthesis catalyzed by a nickel catalyst (Scheme 1c). It is worth
of substituted nitriles.[2,3] These procedures are based noting that the secondary alcohol and simple benzylic
on the cross-couplings of nitriles with alkyl halides in alcohol derivatives also proved to be good substrates.
the presence of a stoichiometric amount of strong The transformation concerning the construction of
3
3
base (Scheme 1a).[3] The borrowing hydrogen strategy sp C sp C bonds not only provided a practical access
has also been employed to prepare a-substituted ni- to valuable a-substituted nitriles including those with
triles efficiently. However, noble metal catalysts such functional groups, but also was a supplementary
À
À
À
as Ir, Ru and Os are required and secondary nitriles method for the C C bond-formation via C O activa-
tion.[5] Herein, we report the details.
We initially investigated the a-benzylation of phe-
nylacetonitrile 2a with 2-naphthylmethyl pivalate 1a
and the obtained results are compiled in Table 1.
Scheme 2. Synthesis of heteroatom-containing diarylme-
thanes via C O/C H cross-coupling.
À
À
Scheme 1. a-Alkylation of nitriles.
816
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UPDATES
Nickel-Catalyzed a-Benzylation of Arylacetonitriles
Table 1. Ni-catalyzed cross-coupling of 2-naphthylmethyl
This a-benzylation reaction is applicable to other
substrates. A variety of arylacetonitriles could couple
with benzylic esters to produce the corresponding a-
benzylated nitriles. As shown in Table 2, carbonate
was found to be as reactive as pivalate to couple with
phenylacetonitrile, giving the corresponding nitrile 3a
in 91% yield. Carbamate also acted as a good sub-
strate under similar reaction conditions. Various phe-
nylacetonitriles bearing either electron-donating or
electron-withdrawing groups on the benzene ring such
as Me, Ph, MeO, ester, amine, fluoro and CF3 all were
pivalate with phenylacetonitrile.[a]
Run Ligand Base (equiv.) 2a (equiv.) Solvent Yield[b]
1
2
3
4
5
6
7
8
Et3P
PCy3
Ph3P
dppe
dppb
t-BuOLi (1.0) 1.0
t-BuOLi (2.0) 1.0
t-BuOLi (2.0) 1.0
t-BuOLi (2.0) 1.0
t-BuOLi (2.0) 1.0
toluene 10%
toluene 27%
toluene 16%
toluene 63%
toluene 38%
toluene 36%
toluene 75%
toluene 85%
toluene 98%
toluene 93%
toluene 63%
toluene N.D.
dioxane 71%
Table 2. Ni-catalyzed a-benzylation of arylacetonitriles with
dcype t-BuOLi (2.0) 1.0
binap t-BuOLi (2.0) 1.0
binap t-BuOLi (2.0) 1.2
binap t-BuOLi (2.0) 1.5
binap t-BuOLi (1.5) 1.5
binap t-BuONa (2.0) 1.5
naphthylmethyl alcohol derivatives.[a]
9
10
11
12
13
14
15
16
binap Cs2CO3 (1.0)
1.5
binap t-BuOLi (2.0) 1.5
binap t-BuOLi (2.0) 1.5
binap t-BuOLi (2.0) 1.5
binap t-BuOLi (2.0) 1.5
THF
DMF
62%
35%
DMSO 17%
toluene 93%
toluene 94%
toluene N.D.
toluene N.D.
17[c] binap t-BuOLi (2.0) 1.5
18[d] binap t-BuOLi (2.0) 1.5
19[e] binap t-BuOLi (2.0) 1.5
20
–
t-BuOLi (2.0) 1.5
[a]
Reaction conditions: a mixture of 1a (0.1 mmol), 2a,
Ni(COD)2 ( 0.01 mmol), a phosphine ligand (P/Ni=2:1)
and a base in the solvent (1.5 mL) was stirred at 1008C
for 12 h.
GC yield using tridecane as an internal standard.
At 808C.
[b]
[c]
[d]
[e]
At 1208C.
In the absence of nickel catalyst.
After extensive studies, we found that Ni/phosphine
could mediate this transformation efficiently and Ni/
binap served as the best one (runs 1–7). Thus, cata-
lyzed by 10 mol% Ni(COD)2/binap, in the presence of
2 equiv. t-BuOLi, the reaction of 1a and 2a took place
smoothly in toluene at 1008C to produce the corre-
sponding product 3a in 75% yield (run 7). The reac-
tion efficiency can be further improved. When
1.2 equiv. of 2a were loaded, an 85% yield of 3a was
generated (run 8). On further increasing the amount
of 2a to 1.5 equiv., an almost quantitative amount of
3a was produced (run 9). t-BuONa could also be used
as a base to give 3a in 63% yield (run 11). However,
when Cs2CO3 was employed, no 3a was formed under
similar reaction conditions (run 12). As to the solvent,
this cross-coupling reaction also proceeded readily in
dioxane and THF, but poorly in DMF and DMSO
(runs 13–16). It should be noted that the Ni/phos-
phine catalyst is essential. In the absence of a Ni com-
plex or a phosphine ligand, no trace of product could
be detected (runs 19 and 20).
[a]
Reaction conditions:
1
(0.1 mmol),
2
(0.15 mmol),
Ni(COD)2 (10 mol%), binap (10 mol%), t-BuOLi
(0.2 mmol), toluene (1.5 mL), 1008C, 12 h. Unless other-
wise noted, R2 =C(O)Bu-t. Isolated yield.
Using Ni(COD)2 (20 mol%), binap (20 mol%).
Using dcype (10 mol%), dr>99/1.
[b]
[c]
[d]
Using Ni(COD)2 (20 mol%), dcype (20 mol%), t-BuOK
(0.2 mmol), dioxane (1.5 mL). 24 h. dr=1.27.
Adv. Synth. Catal. 2016, 358, 816 – 819
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UPDATES
Jing Xiao et al.
Table 3. Ni-catalyzed a-benzylation of arylacetonitriles with
a-benzylated efficiently, producing the corresponding
benzylic alcohol derivatives.[a]
nitriles in moderate to high yields (3b–3k). Notewor-
2
À
thy is the fact that the sp C CN bond which could be
cleaved by nickel catalyst survived as exemplified by
the reaction of 2-(cyanomethyl)benzonitrile.[6] The re-
actions of heteroaromatic nitriles with 2-naphthyl-
methyl pivalate also proceeded readily in the current
catalytic system (3m and 3n). 1-Naphthylacetonitrile
also coupled with 1a, and the expected product 3o
was generated in 73% yield under similar reaction
conditions. Secondary benzyl cyanides also served
well and were converted to the expected products in
which a quaternary carbon was generated (3p and
3q).[7] As to the C O electrophiles, the selected naph-
À
thylmethyl pivalates including those bearing function-
al groups served well and reacted with phenylacetoni-
trile to produce the corresponding products in moder-
ate to high yields (3r–3v). Importantly, two prochiral
carbon centers were generated from the a-benzyla-
tion reaction of arylacetonitriles with secondary ben-
zylic alcohol pivalates (3v and 3w), indicating that
two chiral carbon centers would be constructed in
one-pot from the Ni-catalyzed a-alkylation of arylace-
tonitriles with secondary benzylic alcohol derivatives
[a]
Reaction conditions:
1
(0.1 mmol),
2
(0.3 mmol),
À
by the aid of a suitable chiral ligand via C O activa-
Ni(COD)2 (20 mol%), dcype (20 mol%), t-BuOLi
(2.0 equiv.), toluene (0.3 mL), 808C, 8 h. Isolated yield.
Using 2 (0.15 mmol), toluene (0.5 mL), 12 h.
tion.[8] When naphthalen-2-yl pivalate was allowed to
react with phenylacetonitrile under the current reac-
tion conditions, only a trace amount of the corre-
sponding product was detected by GC-MS.
[b]
Interestingly, the simple benzylic alcohol deriva-
tives also served well in the Ni-catalyzed a-benzyla-
tion of arylacetonitriles. As shown in Table 3, by
switching the ligand binap to dcype [1,2-bis(dicyclo-
hexylphosphino)ethane], benzyl pivalate coupled
readily with phenylacetonitrile, producing the corre-
sponding product 3x in 69% yield. Other benzylic piv-
alates and arylacetonitriles all went through this
transformation to give the corresponding products in
moderate yields (3y–3ab). Worth noting is that secon-
dary benzyl cyanides including those with high steric
hindrance reacted readily with benzyl pivalate, fur-
nishing the desired products in high yields (3ac–3ae).
On the basis of previous investigations,[5,9,10] a plausi-
ble mechanism for the a-benzylation of arylacetoni-
triles is proposed as shown in Scheme 3. Ni(0) com-
Scheme 3. Proposed mechanism. Ligands are omitted for
clarity.
À
plex A firstly undergoes oxidative addition to C O
electrophiles, producing complex B, followed by kylated arylacetonitriles. Further studies on the
ligand exchange with a nitrile by the aid of a base to nickel-catalyzed stereospecific a-alkylation of arylace-
yield C. Reductive elimination of C produces the cor- tonitriles are underway in our laboratory.
responding a-benzylated nitriles and regenerates
Ni(0) complex A.
In summary, we have disclosed a Ni-catalyzed a-
benzylation of arylacetonitriles with easily available
Experimental Section
benzylic alcohol derivatives (ester, carbonate and car-
bamate) via C O activation. This transformation fea-
tures a broad substrate scope, and provides a simple
Typical Procedure
À
In a nitrogen-filled glove-box, a 10-mL sealed Schlenk tube
and efficient method for the synthesis of various a-al- equipped with a magnetic stir bar was charged with 1a
818
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UPDATES
Nickel-Catalyzed a-Benzylation of Arylacetonitriles
(0.1 mmol), Ni(COD)2 (0.01 mmol), binap (0.01 mmol), t-
BuOLi (0.2 mmol), 2a (0.15 mmol) and toluene (1.5 mL).
The reaction mixture was stirred at 1008C for 12 h. After
cooling the reaction mixture to room temperature, the mix-
ture was passed through a short silica gel column with
EtOAc as eluent. The filtrate was concentrated and the resi-
due was further purified by column chromatography on
silica gel (ethyl acetate/petroleum ether, 1:40) to give the
product 3a in 89% isolated yield (98% GC yield).
h) T. Chen, L.-B. Han, Angew. Chem. 2015, 127, 8722–
8724; Angew. Chem. Int. Ed. 2015, 54, 8600–8602.
[5] Ni-catalyzed cross-coupling for the formation of sp C
3
À
3
À
sp C bonds via C O activation has not been achieved
and this transformation would be useful as a supple-
mentary method for C C bond-formation via activa-
tion of C O bonds. For recent examples of Ni-cata-
lyzed cross-coupling of C O compounds with hydrocar-
À
À
À
À
bons via C O activation, see: a) J. Cornella, E. P. Jack-
son, R. Martin, Angew. Chem. 2015, 127, 4147–4150;
Angew. Chem. Int. Ed. 2015, 54, 4075–4078; b) E.
Koch, R. Takise, A. Studer, J. Yamaguchi, K. Itami,
Chem. Commun. 2015, 51, 855–857; c) T. Mukai, K.
Hirano, T. Satoh, M. Miura, Org. Lett. 2010, 12, 1360–
1363; d) J. Xiao, T. Chen, L.-B. Han, Org. Lett. 2015,
17, 812–815; e) K. Muto, J. Yamaguchi, K. Itami, J.
Am. Chem. Soc. 2012, 134, 169–172; f) L. Meng, Y.
Kamada, K. Muto, J. Yamaguchi, K. Itami, Angew.
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Acknowledgements
Partial financial support from NSFC (21373080, 21403062),
HNNSF (2015JJ3039), and the Fundamental Research Funds
for the Central Universities (Hunan University) is gratefully
acknowledged.
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À
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