An efficient approach to alkenyl nitriles from allyl esters

Article abstract of DOI:10.1055/s-0030-1259719

A novel and efficient approach to alkenyl nitriles from allyl esters has been developed. A tandem Pd-catalyzed substitution and the subsequent oxidative rearrangement are involved in this transformation. The method provides an important supplement for the synthesis of alkenyl nitriles from allyl esters. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0030-1259719

LETTER
887
An Efficient Approach to Alkenyl Nitriles from Allyl Esters
triles ng Zhou,a,b Jiaojiao Xu, Liangren Zhang, Ning Jiao*
b
b
b,c
A
W
pproach to Alkenyl Ni
a
a
College of Chemical Engineering, Xiangtan University, Hunan 411105, P. R. of China
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, School of Pharmaceutical Sciences, Peking University,
Xue Yuan Rd. 38, Beijing 100191, P. R. of China
b
Fax +86(10)82805297; E-mail: jiaoning@bjmu.edu.cn
State Key Laboratory of Organometallic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. of China
c
Received 2 December 2010
Dedicated to Professors Xiyan Lu and Li-Xin Dai
proach.11a However, to the best of our knowledge, the con-
version from readily available allyl esters has not been
disclosed. Herein, we demonstrate an efficient transfor-
Abstract: A novel and efficient approach to alkenyl nitriles from
allyl esters has been developed. A tandem Pd-catalyzed substitution
and the subsequent oxidative rearrangement are involved in this
transformation. The method provides an important supplement for mation from allyl esters to alkenyl nitriles through a cas-
the synthesis of alkenyl nitriles from allyl esters.
cade Pd-catalyzed substitution and subsequent oxidative
rearrangement (path b2, Scheme 1).
Key words: alkenyl nitriles, allyl esters, allyl azides, oxidative re-
arrangement
Recently, we reported a direct transformation from allyl
halides to alkenyl nitriles1 via a tandem substitution and
oxidative rearrangement of the corresponding azides.11
1b
Alkenyl nitriles are important structures in organic syn-
thesis because of their ability to serve as building blocks
for natural products, pharmaceuticals, agrochemicals, and
However, when the simple and readily available allyl es-
ters, such as allyl acetate 1a in which the ester group is a
relative weak leaving group, were employed as the sub-
strate, none of the expected (E)-3-phenyl-2-propenenitrile
1
dyes. In the past, versatile methods for their preparations
2
have been widely investigated. The general retrosynthe-
(
2a) was obtained under those conditions. We envisioned
sis of alkenyl nitriles is outlined in Scheme 1. For path a
that allyl esters could serve this transformation through a
3
(
carbon–carbon bond formation), a transition-metal-cat-
12,13
cascade Pd(0)-catalyzed Tsuji–Trost reaction
subsequent oxidative rearrangement in suitable conditions
Scheme 2).
and the
alyzed coupling reaction of alkenyl halides with a cyanide
source which generally is toxic, has been developed (path
(
4
a, Scheme 1). Many efficient methodologies have been
developed through path b (carbon–nitrogen bond forma-
tion, Scheme 1), including the oxidative conversion of
[
Pd]
[O]
CN
corresponding aldehydes, carboxylic acids, esters,7
5
6
R
LG
N3–
R
N3
R
8
9
10
1
A
2
amides, aldoximes, and hydrazones
(path b1,
Scheme 1). It is concluded that all the above reported
methods are under the strategy starting from a Csp2 precur-
sor. Alternatively, the conversion of simple and readily
LG = OAc, OPO(OEt)2,
OBz, OCO2Me, etc.
Scheme 2 Strategies for preparation of alkenyl nitriles via Tsuji–
available Csp3 precursors should present a new ap- Trost reaction and subsequent oxidation
Csp2 precursors
X
R1
+
MCN
ref. 3
a
O
Csp3 precursors
ref. 5–10
R1
X
b
or
R1
LG
[
N]/[O]
b1
a
[N]/[O]
b2
X
R1
C
N
N
R
LG = OAc, OBz
OPO(OEt)2,
2
3
4
X = H, Cl, OR , NR R
OCO2Me, etc.
new strategy
Scheme 1 Strategies for preparation of alkenyl nitriles
SYNLETT 2011, No. 7, pp 0887–0890
x
x.
x
x.
2
0
1
1
Advanced online publication: 10.03.2011
DOI: 10.1055/s-0030-1259719; Art ID: W32610ST
©
Georg Thieme Verlag Stuttgart · New York

8
88
W. Zhou et al.
LETTER
Table 1 The Cascade Approach to Alkenyl Nitrile 2a from Allyl
Acetate 1a via Tsuji–Trost Reaction and Subsequent Oxidationa
group with the double-bond migration (59–88% yields,
Scheme 3). This observation would provide a new kind of
substrate scope for the synthesis of alkenyl nitriles.
catalyst, ligand, additives
Me3SiN3 (1.5 equiv), reflux (t)
then DDQ (1.5 equiv)
CN
Ph
OAc
Ph
Pd(PPh3)4 (5 mol%)
Me3SiN3 (1.5 equiv); reflux (1 h)
then S (10 mol%), DDQ (1.5 equiv)
DCE
reflux (1 h)
R1
1a
2a
AcO R1
Ph
CN
Ph
DCE
reflux (t)
Entry Catalyst (equiv)
Ligand
equiv)
Additives
(equiv)
Time Yield
R2
R2
b
(
(h)
24
24
24
1
(%)
40
0
1c
2
Pd(PPh ) (0.05) none
TBAB (0.1)
none
3
4
CN
Ph
Ph
CN
CN
Ph
CuBr (0.1)
L1 (0.2)
Ph
R1 = R2 = H
1
R = H; R2 = Me
R1 = Ph; R2 = H
3
Pd(OAc) (0.1)
L1 (0.12) AgSbF6
<10
66
68
73
79
70
2
1
h, 2a (82%)
3 h, 2k (88%)
3 h, 2l (59%)
(
E/Z = 10:1)
4
Pd (dba) (0.05)
L2 (0.2)
none
none
2
3
Scheme 3 Synthesis of alkenyl nitriles from a-substituted allyl ace-
tates
5
Pd(PPh ) (0.05) none
1
3
4
6d
Pd(PPh ) (0.05) none
CS (0.1)
1
3
4
2
7d
The plausible mechanism of this transformation is shown
in Scheme 4. The initial substitution through Pd(0)-cata-
lyzed Tsuji–Trost reaction of allyl esters produces allyl
azides A. Catalytic amount of sulfur was employed to ef-
ficiently make the Pd-catalyst poisoning at the end of the
Pd(PPh ) (0.05) none
S (0.1)
1
3
4
8d
Pd(PPh ) (0.05) none
Na SO (0.1)
1
3
4
2
4
a
Reaction conditions: 1a (0.5 mmol), TMSN (0.75 mmol), catalyst,
3
additives, DCE (2 mL), refluxed under N for a certain time; then
2
DDQ (0.75 mmol) was added, and the mixture was refluxed for addi- step. Then the generated allyl azides A are oxidized by
1
5
tional 1 h; L1 = 1,10-phenanthroline, L2 = Ph P.
3
DDQ to form allyl cations B, which undergo Schmidt-
b
Isolated yield.
16,17
type rearrangement
to afford the products 2. During
c
NaN (1.5 equiv) was used instead of TMSN .
3
3
this procedure, the intermediate B could be attacked by
water leading to aldehydes,18 which were observed in
some cases.
d
Additive was added together with the oxidant.
We then investigated the feasibility of this proposal
Table 1). Pd(PPh ) (5 mol%) was initially chosen as the
catalyst, interestingly, the reaction of 1a in the presence of
(
H
3
4
N
S
+
N
R
N
R
N
TBAB (10 mol%) and NaN (1.5 equiv) with the subse-
3
••
B
C
N2
quent addition of DDQ (1.5 equiv) in DCE produced the
expected (E)-3-phenyl-2-propenenitrile (2a) in 40% yield
Pd(II)
LG
R
N2, H+
DDQ
Pd(0)
N3–
(
6
entry 1, Table 1). Notably, the yield of 2a increased to
R
–
CN
8% when TMSN (1.5 equiv) was employed as N3
R
N3
3
R
source (entry 5, Table 1). Other catalytic systems such as
A
2
CuBr/1,10-phenanthroline, Pd(OAc) /1,10-phenanthro-
2
1
Pd firewall
line, or Pd (dba) /Ph P, gave low efficiency, respectively
2
3
3
(
entries 2–4, Table 1). Further studies showed that the Scheme 4 Plausible mechanism of the transformation
presence of the Pd catalyst affect the efficiency of the fol-
lowed oxidative rearrangement (Table S1, Supporting In-
formation). Some additives were therefore screened to
weaken the catalyst effect in the second step. Finally,
highest yield (79%) was achieved when sulfur (10 mol%)
was added together with the oxidant (entry 7, Table 1).14
In summary, we have developed a novel cascade approach
to alkenyl nitriles from allyl esters. A tandem Pd-cata-
lyzed substitution and the subsequent oxidative rearrange-
ment are involved in this method. To the best of our
knowledge, this is the first transformation from allyl es-
With the optimized conditions in hand, the reaction scope ters to alkenyl nitriles. Notably, the a-substituted allyl ac-
of allyl esters was investigated (Table 2). The results in etates can be successfully converted into alkenyl nitriles
2
Table 2 demonstrate that this transformation has a high with the transformation of the terminal sp CH to the ni-
2
degree of functional group tolerance. Various allyl esters, trile group. The method provides an important supplement
such as OAc, OPO(OEt) , OBz, and OCOOMe, were for the synthesis of alkenyl nitriles from the readily avail-
2
smoothly converted into alkenyl nitriles under these con- able allyl esters under the mild conditions. Further studies
ditions (entries 1–4, Table 2). Aryl (electron-rich and on the synthetic applications are ongoing in our group.
electron-deficient), alkenyl, and alkyl substrates are well-
tolerated giving moderate to good yields.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
2
Significantly, the terminal sp CH of a-substituted allyl
2
acetates can be successfully converted into the nitrile
Synlett 2011, No. 7, 887–890 © Thieme Stuttgart · New York

LETTER
Approach to Alkenyl Nitriles
889
Table 2 Synthesis of Alkenyl Nitriles from Allyl Esters via Tsuji–Trost Reaction and Subsequent Oxidationa
Pd(PPh3)4 (5 mol%), Me3SiN3 (1.5 equiv),
reflux (1 h); then S (10 mol%), DDQ (1.5 equiv)
CN
R
LG
R
DCE
reflux (t)
1
2
Entry
1
1
2
Time (h)
1
Yield (%)b
79
CN
CN
CN
CN
Ph
OAc
Ph
1
a
2a
2
Ph
OPO(OEt)2
Ph
1
1
1
1
73
1
b
2b
3
Ph
82
Ph
OBz
1
c
2a
4
Ph
65
Ph
OCOOMe
OAc
1
d
2a
5c
CN
55 (10:1)
Ph
Ph
1
e
2e
CN
OAc
6
7
8
1
1
76
67
1
f
2f
CN
OAc
MeO
MeO
1
g
2g
CN
OAc
1
63
30
MeOC
MeOC
1
h
2h
CN
9
( )9
OAc
( )9
24
1
i
2i
a
Reaction conditions: 1 (0.5 mmol), TMSN (0.75 mmol), Pd(PPh ) (0.025 mmol) in DCE (2 mL), refluxed under N for 1 h; then sulfur (0.05
3
3 4
2
mmol), DDQ (0.75 mmol) was added, and the reaction was refluxed for the indicated time.
b
Isolated yield.
c
1
The number in parentheses is the ratio of the E- to Z-isomers of the product determined by H NMR analysis.
Acknowledgment
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Financial support from National Science Foundation of China (Nos.
2
0702002, 20872003), National Basic Research Program of China
(
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LETTER
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