790
Chemistry Letters Vol.35, No.7 (2006)
Arylcyanation of Norbornene and Norbornadiene Catalyzed by Nickel
Yoshiaki Nakao,ꢀ Akira Yada, Jun Satoh, Shiro Ebata, Shinichi Oda, and Tamejiro Hiyamaꢀ
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510
(Received May 10, 2006; CL-060553; E-mail: nakao@npc05.kuic.kyoto-u.ac.jp, thiyama@npc05.kuic.kyoto-u.ac.jp)
Aryl cyanides add to norbornene and norbornadiene under
Table 1. Arylcyanation of norbornene (2a) catalyzed by Ni/
a
nickel catalysis to give (2Rꢀ,3Sꢀ)-3-aryl-2-cyanobicyclo[2.2.1]-
heptanes and (2Rꢀ,3Sꢀ)-3-aryl-2-cyanobicyclo[2.2.1]hept-5-
enes in good yields with a general substrate scope. On the other
hand, the reaction of an aryl cyanide with triethoxy(vinyl)silane
gives a Heck-type arylation product, suggesting the arylnickela-
tion pathway in the catalytic cycle.
PBu3
Ni/PBu3 cat.
Ar
+
Ar CN
NC
1
2a
3
Entry
Ar
Time/h
Yield/%b
1
2
3
4
5c
4-F3C–C6H4 (1a)
4-F–C6H4 (1b)
4-Me(O)C–C6H4 (1c)
4-MeO2C–C6H4 (1d)
4-H(O)C–C6H4 (1e)
4-Ph–C6H4 (1f)
4-Me–C6H4 (1g)
4-MeO–C6H4 (1h)
3,4,5-(MeO)3–C6H2 (1i)
2-F3C–C6H4 (1j)
5-F-2-Me–C6H3 (1k)
2-Pyridyl (1l)
3-Pyridyl (1m)
4-Pyridyl (1n)
2-Furyl (1o)
2-Thienyl (1p)
1-Boc-3-indolyl (1q)
20
20
20
20
38
54
77
77
54
77
77
—
48
48
48
48
48
95 (3aa)
91 (3ba)
86 (3ca)
89 (3da)
56 (3ea)
67 (3fa)
84 (3ga)
76 (3ha)
66 (3ia)
55 (3ja)
73 (3ka)
<5 (3la)
88 (3ma)
92 (3na)
94 (3oa)
90 (3pa)
71 (3qa)
Reactions that allow simultaneous formation of two C–C
bonds in regio-, stereo-, and chemoselective manners should
have innovative utility in organic synthesis. In this context, we
have recently reported that direct addition reactions of aryl and
allyl cyanides across alkynes and those of alkoxylcarbonyl and
acyl cyanides across 1,2-dienes give variously functionalized ni-
triles in a single operation with perfect atom economy.1 Howev-
er, the corresponding reactions of alkenes have remained elu-
sive, which would afford molecules endowed with two newly
formed sp3-carbon stereocenters having functional groups. Here-
in, we report that an aryl group and a cyano group add across
norbornene and norbornadiene highly stereo- and chemoselec-
tively under nickel catalysis, giving various (2Rꢀ,3Sꢀ)-3-aryl-
2-cyanobicyclo[2.2.1]heptanes and (2Rꢀ,3Sꢀ)-3-aryl-2-cyanobi-
cyclo[2.2.1]hept-5-enes.2
Initially, we examined the reaction of 4-trifluoromethylben-
zonitrile (1a: 1.0 mmol) with norbornene (2a: 1.2 mmol) in tol-
uene at 100 ꢁC for 20 h in the presence of Ni(cod)2 (5 mol %)
and PBu3 (10 mol %) and found that (2Rꢀ,3Sꢀ)-2-cyano-3-
[4-(trifluoromethyl)phenyl]bicyclo[2.2.1]heptane (3aa) was pro-
duced in 95% yield (Table 1, Entry 1). The present conditions
were found effective for the addition of a diverse range of aryl
cyanides across 2a. Electron-withdrawing functional groups in-
cluding fluoro, keto, and ester were tolerated to give the corre-
sponding adducts in good yields (Entries 2–4). In the case of
4-cyanobenzaldehyde (1e), use of PMe3 as a ligand was impor-
tant due presumably to competitive C–H activation of the formyl
group under Ni/PBu3 catalysis (Entry 5).3 Electronically neutral
4-phenylbenzonitrile (1f) took longer reaction time for the com-
pletion of the reaction (Entry 6); electron-rich and ortho-substi-
tuted aryl cyanides required 10 mol % loadings of the catalyst to
give the corresponding arylcyanation products in modest to good
yields (Entries 7–11). Heteroaryl cyanides such as 3- and 4-pyr-
idyl- and 2-furyl cyanide also participated in the reaction to give
various (2Rꢀ,3Sꢀ)-2-cyano-3-heteroarylbicyclo[2.2.1]heptanes
in good yields (Entries 13–15), whereas 2-cyanopyridine (1l)
failed to react with 2a and was recovered (Entry 12). 2-Cyano-
thiophene (1p) and 1-Boc-3-cyanoindole (1q) gave the adducts
in good yields with PMe2Ph as a ligand (Entries 16 and 17).
Carbocyanation of norbornadiene (2b) would be also syn-
thetically valuable since the resulting (2Rꢀ,3Sꢀ)-2-cyano-3-orga-
nobicyclo[2.2.1]hept-5-enes would find further applications as
precursors for functionalized cyclopentanes or monomers for
6
7d
8d
9d
10d
11d
12
13
14
15
16e
17e
aReactions were carried out in toluene (0.60 mL) using an aryl
cyanide (1.00 mmol) and 2a (1.20 mmol) in the presence of
Ni(cod)2 (50 mmol) and PBu3 (0.100 mmol). bIsolated yields
based on an aryl cyanide. cPMe3 (0.100 mmol) was used as a li-
gand. d2a (1.50 mmol), Ni(cod)2 (0.100 mmol), and PBu3 (0.20
mmol) were used. ePMe2Ph (0.100 mmol) was used as a ligand.
ring-opening metathesis polymerization.4 Although the standard
conditions were not applicable to arylcyanation of 2b, the ex-
pected arylcyanation product 3ab was obtained in 77% yield
when the reaction of 1a with 2b was conducted in the presence
of Ni(cod)2 (5 mol %) and PMe3 (15 mol %) (Table 2, Entry 1).5
The same catalyst system was further applied to the reactions of
electron-poor aryl cyanides and heteroaryl cyanides to give the
corresponding adducts in modest to good yields (Entries 2–7),
whereas those of electron-neutral or -rich aryl cyanides were
sluggish (<20%) due presumably to reluctant oxidative addition
of unactivated aryl cyanides to Ni(0)/3PMe3. None of double
addition products were observed in all cases.
The arylcyanation product 3ab underwent retro-Diels–Alder
reaction at 190 ꢁC in xylene to give (Z)-2-[4-(trifluoromethyl)-
phenyl]acrylonitrile [(Z)-5] along with a small amount of (E)-
5 that might be derived from thermal isomerization of (Z)-5.6
In addition, oxidative cleavage of the remaining double bond
in 3ab followed by treatment with Me3SiCHN2 afforded func-
tionalized cyclopentane 6 in a stereospecific manner (Scheme 1).
Although other bicyclic alkenes such as N-Boc-7-azabicy-
clo[2.2.1]heptene and bicyclo[2.2.2]octene as well as simple al-
kenes such as styrene, 1-hexene, and cyclopentene failed to give
Copyright ꢀ 2006 The Chemical Society of Japan