Catalytic 1,2-dicyanation of alkynes by palladium(II) under aerobic conditions

Article abstract of DOI:10.1002/adsc.200900334

A stereoselective 1,2-dicyanation of various alkynes in the presence of trimethylsilyl cyanide (TMSCN) by palladium(II) catalysis under aerobic conditions is investigated. This reaction includes two cyanation pathways, syn- and anti-cyanopalladation to alkynes that are activated by Pd(II). High syn-selectivity was observed in the reaction using terminal alkynes that have bulky substituents at a propargyl position and aliphatic internal alkynes. Furthermore, a dramatic acceleration was observed with substrates having an N-arenesulfonyl functionality at a propargyl position, this indicates that both sulfoxide and carbon-carbon triple bond act as Lewis bases to Pd(II).

Full text of DOI:10.1002/adsc.200900334

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DOI: 10.1002/adsc.200900334
Catalytic 1,2-Dicyanation of Alkynes by Palladium(II) under
Aerobic Conditions
Shigeru Arai,a,* Takashi Sato,a and Atsushi Nishidaa
a
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Fax : (+81)-43-290-2909; e-mail: arai@p.chiba-u.ac.jp
Received: May 14, 2009; Revised: June 18, 2009; Published online: July 31, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900334.
Abstract: A stereoselective 1,2-dicyanation of vari- position and aliphatic internal alkynes. Furthermore,
ous alkynes in the presence of trimethylsilyl cyanide a dramatic acceleration was observed with substrates
(TMSCN) by palladium(II) catalysis under aerobic having an N-arenesulfonyl functionality at a proparg-
conditions is investigated. This reaction includes two yl position, this indicates that both sulfoxide and
cyanation pathways, syn- and anti-cyanopalladation carbon-carbon triple bond act as Lewis bases to
to alkynes that are activated by Pd(II). High syn-se- Pd(II).
lectivity was observed in the reaction using terminal
alkynes that have bulky substituents at a propargyl Keywords: alkynes; cyanation; oxygen; palladium
Introduction
shown in Scheme 1, treatment of phenylacetylene and
TMSCN with PdCl2 under an oxygen atmosphere pro-
A cyano group is one of the most important function- ceeded via 1,2-dicyanation effectively. Although Cha-
alities in organic synthesis because it has been consid- tani and co-workers have reported the palladium-cat-
ered to be an equivalent to carbonyl, carboxyl, amino alyzed silylcyanation of terminal alkynes under
and hydroxymethyl groups and its introduction, par- argon,[6] our protocol enables the realization of the
ticularly to carbon-carbon multiple bonds, has been 1,2-dicyanation under an oxygen atmosphere
one of the major topics in synthetic organic chemis- (Scheme 1). This novel catalytic cyanation did not
try.[1] Palladium[2] and nickel[3] chemistry have been give any trace of silylated products and these interest-
mainly focused to achieve such transformations. Very ing results were sufficient to prompt us to examine
recently, we reported a catalytic 1,2-dicyanation of the mechanistic perspective and origin of stereoselec-
various alkynes using TMSCN with Pd(II) under an tivity. In this article, we report on the catalytic 1,2-di-
oxygen atmosphere (1 atm),[4] and this protocol can cyanation in detail (scope, limitation and perspective)
be recognized as a unique cyanation of alkynes.[5] As with syn- and anti-cyanopalladation as key catalytic
processes.
Results and Discussion
In the beginning, we investigated the scope of sub-
strates in the 1,2-dicyanation using aromatic alkynes.
After a survey of the reaction conditions, we realized
that the best result was obtained under following con-
ditions: PdCl2 (2 mol%) with TMSCN (2.5 equiv.) in
toluene (0.5M) under oxygen (1 atm) at 1008C. The
results of several aromatic alkynes are shown in
Table 1. The reactions effectively proceeded to give
the corresponding 1,2-dicyano adducts (2a–e) with a
range of 50–82% yields. In particular, the aryl Br
Scheme 1. Pd-catalyzed cyanation of phenylacetylene with
TMSCN.
À
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Shigeru Arai et al.
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Table 1. 1,2-Dicyanation of aromatic alkynes.
Table 2. 1,2-Dicyanation of aliphatic alkynes.
bond was inert during the reaction (entry 5), this indi-
cates Pd(0) species would not be concerned in a cata-
lytic cycle.[7] As given in Table 1, the stereoselectivity
In the case of aliphatic terminal alkynes, the reac-
observed with up to 3:1 of syn/anti-adducts was not tion also proceeded with wide tolerance of functional-
influenced by the electronic or steric effects of the ar- ities, including acetate, ethers and amides, to give 2f–
omatic rings. On the other hand, the chemical yields k in moderate to good yields (Table 2, entries 1–6).
were found to be dependent on substituents. The re- Based on the results that 1n gave slightly better syn-
action of 1b which has an electron-withdrawing group selectivity than 1m (entry 7 vs. 8), the stereoselectivity
(CF3) gave 2b in 50% yield which is lower than with could be influenced by substituents at the propargyl
H and an MeO group (entries 1–3). These results sug- position.
ꢀ
gest the electron density of C C triple bond is impor-
tant to be activated by Pd(II) for the efficient dicya- ing a tetrasubstituted carbon at a propargyl position
Next, we examined the reaction of substrates bear-
nation.
in the presence of 5 mol% of catalyst (Figure 1). As
Further modification to use other metal catalysts expected, 2o was obtained from the corresponding
(Ni and Pt), cyanating agents [n-Bu3SnCN, alkyne with high syn-selectivity. Other syn-products
Me2(OH)CN], ligands (phosphines, phosphites, COD, including an alkyl ether (2p) and a fully carbon-sub-
isonitrile and pyridine derivatives) and additives (Ag stituted stereogenic center (2q) were obtained in the
and Cu salts and TMSOTf) all failed to improve the respective yields of 53 and 63% with high selectivity.
chemical yield or stereoselectivity. The reaction of 1a Tetrasubstitution was essential for high syn-selectivity
with a stoichiometric amount of Pd(CN)2 under argon regardless of substitution pattern (alkyl, aryl, alkoxy,
did not furnish the 1,2-dicyanation at all. Finally, care- siloxy and cycloalkyl) (2r–t) and tritylacetylene gave
ful investigations revealed that there is no intercon- syn-2u, exclusively.
version between syn- and anti-adducts under the reac-
Because the molecular oxygen is essential for this
tion conditions. For example, the treatment of syn-2a catalytic cyanation, we examined the PdO2 as a pro-
under the optimized conditions gave no products and moter in the absence of oxygen (Table 3). A Pd com-
was recovered quantitatively.
plex, (PPh3)2PdO2 was prepared according to the re-
Figure 1. Products, yields and syn/anti ratios in the 1,2-dicyanation of terminal alkynes bearing a tetrasubstituted carbon at
the propargyl position.
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Catalytic 1,2-Dicyanation of Alkynes by Palladium(II) under Aerobic Conditions
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À
Table 3. Reaction of 1a with palladium oxide.
Si CN bond can be activated to promote nucleophilic
attack giving syn-cyanopalladation. On the other
hand, direct cyanation into an internal carbon can be
proposed to explain the formation of anti-adducts.[9]
This cyanation is occurred at the more substituted
carbon (path B: anti-cyanopalladation) and could be
prevented by bulky substituents at the propargyl posi-
tion due to steric effects. As mentioned above, these
cyanopalladations could be triggered by nucleophilic
cyanation by the external CN source, because a CN
group on Pd(II) acts as a pseudohalide and is not fea-
sible to be transferred to alkynes directly.[1] The re-
sulting cyanoalkenyl-palladium cyanides give the
ported procedure[8] and employed in the 1,2-dicyana- products by reductive elimination together with
tion reaction under argon atmosphere. Although no Pd(0), which is quickly converted to Pd(CN)2, proba-
re-oxidation process of the Pd(0) species was present bly via PdO2. Based on this proposal, bulkier substitu-
under these conditions, the above complex (50 mol%) ents would prevent the initial cyanation to the inter-
proceeded the reaction to give 36% of 2a (entry 1). nal carbon (path B) and seem to be reasonable to ex-
This complex also catalyzed the reaction under the plain the high syn-selectivity shown in Figure 1.
standard conditions to give a similar result as in
An additional study on concentration effects[9]
Table 1 (entry 2). These results suggest that PdO2, would also support the above plausible cyanation
generated by the oxidation of Pd(0), is proposed to pathways. As shown in Table 4, the stereoselectivity
be one of the important species in a catalytic cycle.
of 2f was strongly influenced by the concentration of
Based on above results, we herein propose new pal- the substrate and the syn-adduct was predominant
ladium-catalyzed cyanation pathways including nucle- under highly diluted conditions (entries 1–6) or lower
ꢀ
ꢀ
ophilic attack of C N to C C triple bond (Scheme 2). catalyst loading (entries 7–9) when 1f was used as a
The reaction is triggered by activation of terminal al- substrate. These results suggest that the formation of
kynes by Pd(II) and the resulting p-complex reacts the syn-adduct is preferred because the activation of
with external TMSCN. According to the facts that 1) both TMSCN and alkyne by Pd(II) (Ts-A) seems to
the selectivity observed in 2 was quite dependent on be more feasible than direct cyanation to p-complex
the structure of the substrates and 2) 1o–u gave (Ts-B) under high dilution conditions.
higher syn-selectictivity, we herein propose different
Having succeeded in the development of Pd-cata-
cyanation pathways. Path A shows a cyanation at the lyzed 1,2-dicyantion using terminal alkynes, we next
terminal carbon via activation of carbon-silicon bond, focused on internal alkynes (Table 5). Because no re-
that is, X on a Pd complex acts as a Lewis base. An action was observed under the above conditions
Scheme 2. Plausible catalytic cycle for the 1,2-dicyanation of terminal alkynes.
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Table 4. Concentration effect on the catalytic 1,2-dicyana-
tion of 1f.
tries 5 and 6). It should be noted that ethyl and
methyl groups can be critically discriminated, and the
former completely prevented the reaction. In the case
of aromatic alkynes, the length of the alkyl chain was
not significant. For example, both 3e and 3f were con-
verted to the corresponding dicyano adducts in re-
spective yields of 36 and 26% (entries 7 and 8). Even
though their yields and selectivity are lower, it should
be noted that anti-adducts were obtained when a
phenyl group is introduced to the alkynes. These re-
sults show that the cyanation is dependent on both
steric and electronic factors and nucleophilic cyana-
tion could occur at an sp-carbon connected to a
phenyl group. Conjugated enyne (3g) was found to be
inert, affording no reaction under similar conditions
(entry 9).
The above results indicate that the cyanation could
occur when the stronger Lewis acidic Pd(II) complex
activates the internal alkynes. Such a hypothesis
prompted us to continue the survey of the Lewis
basic functionalities, and the N-sulfonyl group was
found to be most effective, as shown in Table 6.
Internal alkyne 5a is less reactive in the absence of
additive (entry 1). The addition of TMSOTf accelerat-
(entry 1), we surveyed the additives that could gener- ed the reaction to completion within 3 h and the ste-
ate highly reactive palladium species. In the reaction reoselectivity was assigned by NMR to be syn/anti=
of 3a, the combination of Pd(CN)2 with TMSOTf,[10] 4:5 (entry 2). Substrate 5b gave the syn-adduct exclu-
which would afford a cationic Pd complex or Pd- sively with a longer reaction time (entry 3) and the N-
ACHTUNGTRENNUNG(OTf)2, was found to be the most effective after care- acetyl derivative 5c resulted in no reaction (entry 4).
ful screening of a combination of Pd sources and ad- N-Benzyl derivative 5d required a longer reaction
ditives, giving the desired adduct syn-4a, exclusively time to afford 60% of 6d with lower selectivity
(entry 2). The Lewis acidity of the additive was also (entry 5). Aromatic alkyne 5e was transformed to 6e
important. For example, TMSOMs did not promote within 3 h and the anti-adduct was predominantly ob-
the reaction at all (entry 3). Although 3b also gave tained (entry 6). This is analogous to the above results
syn-4b in 45% (entry 4), the substrates having longer of 3e and 3f in that aromatic alkynes promote both
alkyl chain such as 3c and 3d were ineffective (en- syn- and anti-dicyanation. As described in entry 7, an
Table 5. Catalytic 1,2-dicyanation of internal alkynes 3.
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Catalytic 1,2-Dicyanation of Alkynes by Palladium(II) under Aerobic Conditions
FULL PAPERS
Table 6. Catalytic 1,2-dicyanation of 5.
ethyl group exhibited a similar tendency to prevent Conclusions
the reaction.
Next we investigated the electronic effect of R2 on We have demonstrated a palladium-catalyzed 1,2-di-
the stereoselectivity. When a methoxy group was in- cyanation of various alkynes including syn- and anti-
troduced, the Lewis acidity of Pd(II) could be de- cyanopalladation. The stereoselectivity was found to
creased and the reaction was prevented (entry 8). On be dependent on the structure of the substrates. For
the other hand, an electron-withdrawing group such example, high syn-selectivity was achieved when ter-
as CF3 promoted the reaction with better anti-selec- minal alkynes having a tetrasubstituted carbon at a
tivity (entry 9). The stereochemistry of all the syn-ad- propargyl position (2o–u) and aliphatic internal al-
ducts was confirmed by NOE observations between kynes (3a, b) were used. Aromatic internal alkynes
allylic methylene and methyl or aromatic protons.
were converted to both syn- and anti-adducts via nu-
These results suggest that a propargyl N-sulfonyl cleophilic cyanation. Furthermore, the internal al-
ꢀ
group and a C C triple bond act as a bidentate tem- kynes having an N-tosylamino group at a propargyl
plate, as shown in Scheme 3. The steric bulk of R3 is position were transformed to the corresponding dicya-
important to achieve higher anti-selectivity (entry 2 no adducts. These observations give us a new perspec-
vs. 6). Because of the steric effect of a phenyl group tive on a palladium-catalyzed dicyanation of alkynes,
and X, anti- rather than syn-attack of TMSCN would and further applications are currently underway.
proceed predominantly (Scheme 3).
Scheme 3. Plausible reaction pathways from 5e.
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7.00–7.10 (m, 2H), 7.47–7.55 (m, 2H); 13C NMR (100 MHz,
CDCl3): d=55.6, 111.7, 114.1, 116.0, 119.2, 121.0, 130.0.
131.1, 133.6, 156.9; IR (ATR): n=3036, 2212, 1602, 1510,
1259 cmÀ1; LR-MS (EI): m/z=184 (M+), 169 (M+ÀMe),
154, 84; HR-MS (FAB): m/z=185.0717, calcd. for C11H8N2O
(M+ +H): 185.0715.
Experimental Section
All the analytical and spectral data of 2a, 2f, 2k–o, 2q–u,
4a,b and 4e that have been previously reported[4,11] are ex-
cluded in following section.
2-(2-Methoxyphenyl)maleonitrile (syn-2d): mp 130–
1
1318C; H NMR (400 MHz, CDCl3): d=3.96 (s, 3H), 6.99
General Remarks
(s, 1H), 7.03 (d, J=8.4 Hz, 1H), 7.07–7.12 (m, 1H), 7.46–
7.52 (m, 1H), 7.69 (dd, J=8.0, 1.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d=55.8, 111.0, 111.9, 114.7, 115.6, 118.5,
121.2, 130.4, 131.2, 133.6, 158.6; IR (ATR): n=3115, 2212,
1551, 1259 cmÀ1; LR-MS (FAB): m/z=185 (M+ +H), 154,
136; HR-MS (FAB): m/z=185.0716, calcd. for C11H8N2O
(M+ +H): 185.0715.
All reactions were performed with dry solvents and reagents
were purified by the usual methods. Reactions were moni-
tored by thin-layer chromatography carried out on 0.25 mm
Merck silica gel plates (60F–254). Column chromatography
was performed with silica gel (Fuji Silysia, PSQ-60B). IR
spectra were recorded on a JASCO FT/IR-230 Fourier
transform spectrophotometer. NMR spectra were recorded
on JEOL-JMN-Alpha-400 and/or JEOL-JMN-ECP-600
2-(2-Methoxyphenyl)fumaronitrile (anti-2d): mp 95–
1
1008C; H NMR (400 MHz, CDCl3): d=3.94 (s, 3H), 6.17
(s, 1H), 7.01 (d, J=8.4 Hz, 1H), 7.04–7.10 (m, 1H), 7.47–
7.55 (m, 2H); 13C NMR (100 MHz, CDCl3): d=55.6,
111.7,111.8, 114.1, 116.0, 119.2, 121.0, 130.0, 131.1, 133.6,
156.9; IR (ATR): n=3052, 2221, 1598, 1488, 1255 cmÀ1; LR-
MS (EI): m/z=184 (M+), 156, 135; HR-MS (EI): m/z=
184.0644, calcd. for C11H8N2O (M+): 184.0636.
1
spectrometers, operating at 400 and 600 MHz for H NMR
and 100 and 150 MHz for 13C NMR with calibration using
residual undeuterated solvent as an internal reference. Mass
spectra were measured by a JEOL JMS-AX 500 (for LR-
and HR-MS) and a JEOL JMS-HX 110 (for HR-MS), re-
spectively.
2-(4-Bromophenyl)maleonitrile (syn-2e): mp 185–1868C;
1H NMR (400 MHz, CDCl3): d=6.38 (s, 1H), 7.53 (d, J=
8.0 Hz, 2H), 7.66 (d, J=8.0 Hz, 2H); 13C NMR (100 MHz,
CDCl3): d=107.8,113.8, 114.5, 127.96, 128.00, 128.8, 132.4,
133.0; IR (ATR): n=3677, 2220, 1581, 1489, 1323 cmÀ1; LR-
Typical Procedure for Pd-Catalyzed 1,2-Dicyanation
of Terminal Alkynes
MS (EI): m/z=232, 234 (M+), 153
ACHTUNGTRENNUNG
To a solution of alkyne (1.0 mmol) in toluene (2.0 mL) were
added palladium chloride (3.5 mg, 0.02 mmol, 2 mol%) and
TMSCN (0.34 mL, 2.5 mmol) at room temperature. The
mixture was stirred for 14–17 h at 1008C under oxygen.
After monitoring the reaction by TLC, the following direct
column chromatography (hexane-AcOEt) gave the desired
1,2-dicyano adducts.
2-[4-(Trifluoromethyl)phenyl]maleonitrile (syn-2b): mp
127–1298C; 1H NMR (400 MHz, CDCl3): d=6.45 (s, 1H),
7.80 (br s, 4H); 13C NMR (100 MHz, CDCl3): d=100.1,
113.7, 114.2, 121.8 (J=203.3 Hz), 126.7 (J=3.1 Hz), 127.2,
132.1, 133.0, 134.3 (J=25.3 Hz); IR (ATR): n=3050, 2224,
1415, 1320, 1067 cmÀ1; LR-MS (EI): m/z=222 (M+), 203
(M+ÀF), 195 (M+ÀHCN), 153; HR-MS (EI): m/z=
222.0414, calcd. for C11H5F3N2: 222.0405 (M+).
(EI): m/z=231.9634, calcd. for C10H579BrN2 (M+): 231.9636.
2-(4-Bromophenyl)fumaronitrile (anti-2e): mp 95–1008C
1H NMR (400 MHz, CDCl3): d=6.17 (s, 1H), 7.69 (d, J=
8.4 Hz, 2H), 7.80 (d, J=8.4 Hz, 2H); 13C NMR (100 MHz,
CDCl3): d=107.9,114.4, 115.8, 127.7, 128.6, 129.5, 131.9,
132.7; IR (ATR): n=3031, 2217, 1488, 1255 cmÀ1; LR-MS
(EI): m/z=232, 234 (M+), 183, 185, 153
ACHTUNGTRENNUNG
MS (EI): m/z=231.9644, calcd. for C10H579BrN2 (M+):
231.9636.
2-[3-(Benzyloxy)propyl]maleonitrile (syn-2g): 1H NMR
(400 MHz, CDCl3): d=1.88–1.95 (m, 2H), 2.55 (dt, J=7.2,
1.6 Hz, 2H), 3.45 (t, J=5.6 Hz, 2H), 4.49 (s, 2H), 5.77 (t,
J=1.6 Hz, 1H), 7.29–7.39 (m, 5H); 13C NMR (100 MHz,
CDCl3): d=27.2, 32.0. 67.4, 73.0, 112.0, 113.7, 114.7, 127.7,
127.8, 128.4, 135.8, 137.8; IR (ATR): n=3060, 2861, 2229,
1717, 1454, 1101 cmÀ1; LR-MS (EI): m/z=226 (M+), 116,
107, 91; HR-MS (FAB): m/z=227.1171, calcd. for
C14H15N2O (M+ +H): 227.1184.
2-[4-(Trifluoromethyl)phenyl]fumaronitrile (anti-2b): mp
1
46–478C; H NMR (400 MHz, CDCl3): d=6.28 (s, 1H), 7.82
(d, J=8.0 Hz, 2H), 8.03 (d, J=8.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d=110.1, 114.0, 115.7, 123.1 (J=
203.6 Hz), 126.5 (J=3.2 Hz), 128.7, 131.8, 132.9, 134.2 (J=
2-[3-(Benzyloxy)propyl]fumaronitrile (anti-2g): 1H NMR
(400 MHz, CDCl3): d=1.94–2.01 (m, 2H), 2.74 (dt, J=7.6,
1.2 Hz, 2H), 3.54 (t, J=5.6 Hz, 2H), 4.52 (s, 2H), 5.94 (t,
J=1.2 Hz, 1H), 7.27–7.39 (m, 5H); 13C NMR (100 MHz,
CDCl3): d=27.5, 30.8. 68.1, 73.1, 112.2, 113.3, 116.0, 127.6,
127.7, 128.4, 136.6, 137.8; IR (ATR): n=3060, 2862, 2231,
1454, 1100 cmÀ1; LR-MS (EI): m/z=226 (M+), 107, 91; HR-
MS (FAB): m/z=276.0739, calcd. for C14H15N2OK (M+ +K):
265.0743.
25.3 Hz); IR (ATR): n=3050, 2224, 1415, 1320, 1067 cmÀ1
;
LR-MS (EI): m/z=222 (M+), 203 (M+ÀF), 195 (M+ÀHCN),
153; HR-MS (EI): m/z=222.0404, calcd. for C11H5F3N2:
222.0405 (M+).
2-(4-Methoxyphenyl)maleonitrile (syn-2c): mp 147–
1
1488C; H NMR (400 MHz, CDCl3): d=3.89 (s, 3H), 6.20
(s, 1H), 6.98 (d, J=8.8 Hz, 2H), 7.63 (d, J=8.8 Hz, 2H);
13C NMR (100 MHz, CDCl3): d=55.7, 103.9, 114.3, 115. 2,
122.4, 128.6, 132.6, 133.1, 163.4; IR (ATR): n=3074, 2212,
1599, 1507, 1176 cmÀ1; LR-MS (FAB): m/z=185 (M+ +H),
184 (M+), 154, 136; HR-MS (FAB): m/z=185.0718, calcd.
for C11H8N2O (M+ +H): 185.0715.
2-[3-(tert-Butyldiphenylsilyloxy)propyl]maleonitrile (syn-
1
2h): H NMR (400 MHz, CDCl3): d=1.06 (s, 9H), 1.79–1.89
(m, 2H), 2.55 (t, J=6.8 Hz, 2H), 3.69 (t, J=5.6 Hz, 2H),
5.71 (s, 1H), 7.37–7.48 (m, 6H), 7.60–7.65 (m, 4H);
13C NMR (100 MHz, CDCl3): d=19.0, 26.7, 29.7, 31.7, 61.6,
111.8, 113.7, 114.7, 127.7, 129.8, 133.1, 135.4, 136.0; IR
2-(4-Methoxyphenyl)fumaronitrile (anti-2c): mp 48–508C;
1H NMR (400 MHz, CDCl3): d=3.90 (s, 3H), 5.96 (s, 1H),
1902
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Catalytic 1,2-Dicyanation of Alkynes by Palladium(II) under Aerobic Conditions
FULL PAPERS
(ATR): n=3071, 2931, 2230, 1428, 1108 cmÀ1; LR-MS (EI):
m/z=374 (M+), 359 (M+ÀMe), 317 (M+Àt-Bu), 208, 197,
183, 77; HR-MS (FAB): m/z=375.1880, calcd. for
C23H27N2OSi (M+ +H): 375.1893.
2-[3-(tert-Butyldiphenylsilyloxy)propyl]fumaronitrile
(anti-2h): mp 59–628C; 1H NMR (400 MHz, CDCl3): d=
1.07 (s, 9H), 1.84–1.92 (m, 2H), 2.76 (t, J=7.6 Hz, 2H), 3.72
(t, J=5.6 Hz, 2H), 5.94 (s, 1H), 7.36–7.47 (m, 6H), 7.65–
7.67 (m, 4H); 13C NMR (100 MHz, CDCl3): d=19.1, 26.7,
30.2, 30.6, 62.2, 112.1, 113.3, 116.0, 127.1, 129.8, 133.2, 135.5,
136.8; IR (ATR): n=3071, 2931, 2231, 1428, 1106 cmÀ1; LR-
MS (EI): m/z=374 (M+), 317 (M+Àt-Bu), 208, 199, 183, 77;
HR-MS (EI): m/z=374.1826, calcd. for C23H26N2OSi (M+):
374.1814.
2.32 (dq, J=14.8, 7.2 Hz, 1H), 2.44 (dq, J=14.8, 7.2 Hz,
1H), 3.13 (s, 3H), 6.07 (s, 1H), 7.35–7.45 (m, 5H); 13C NMR
(100 MHz, CDCl3): d=6.8, 24.9, 50.3, 83.3, 111.2, 113.5,
115.6, 126.9, 129.1, 129.2, 138.1, 140.4; IR (ATR): n=2942,
2234, 1447, 1065 cmÀ1; LR-MS (EI): m/z=226 (M+), 197
(M+ÀEt), 165 (M+ÀOMeÀMe), 149 (M+ÀPh), 105; HR-MS
(EI): m/z=226.1117, calcd. for C14H14N2O (M+): 226.1106 .
2-Butyl-3-phenylmaleonitrile
(syn-4f):
1H NMR
(400 MHz, CDCl3): d=0.89 (t, J=7.6 Hz, 3H), 1.30–1.39
(m, 2H), 1.61–1.70 (m, 2H), 2.49 (t, J=7.6 Hz, 2H), 7.27–
7.39 (m, 2H), 7.47–7.51 (m, 3H); 13C NMR (100 MHz,
CDCl3): d=13.5, 22.0, 29.9, 30.9, 116.2, 116.4, 127.3, 128.6,
129.2, 129.8, 130.4, 130.8; IR (ATR): n=2960, 2221, 1445,
1021 cmÀ1; LR-MS (EI): m/z=210 (M+), 168, 154, 141; HR-
MS (EI): m/z=210.1150, calcd. for C14H14N2 (M+): 210.1157.
2-[3-(tert-Butyldimethylsilyloxy)propyl]maleonitrile (syn-
2i): 1H NMR (400 MHz, CDCl3): d=0.07 (s, 6H), 0.90 (s,
9H), 1.89 (tt, J=7.2, 6.0 Hz, 2H), 2.72 (dt, J=7.2, 1.2 Hz,
2H), 3.70 (t, J=6.0 Hz, 2H), 5.95 (t, J=1.2 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=À5.5, 18.2, 25.9, 30.4, 30.7.
61.4, 112.0, 113.3, 116.1, 137.2; IR (ATR): n=3061, 2232,
1609, 1104 cmÀ1; LR-MS (FAB): m/z=251 (M+ +H), 235
(M+ÀMe), 193 (M+Àt-Bu), 73; HR-MS (FAB): m/z=
251.1566, calcd. for C12H21N2OSi (M+ +H): 251.1580.
2-[2-(tert-Butyldimethylsilyloxy)propyl]fumaronitrile
2-Butyl-3-phenylfumaronitrile
(anti-4f):
1H NMR
(400 MHz, CDCl3): d=1.01 (t, J=7.6 Hz, 3H), 1.52–1.61
(m, 2H), 1.71–1.80 (m, 2H), 2.79 (t, J=7.6 Hz, 2H), 7.27–
7.39 (m, 2H), 7.47–7.51 (m, 3H); 13C NMR (100 MHz,
CDCl3): d=13.6, 21.9, 30.0, 35.3, 115.5, 116.4, 127.2, 128.2,
128.6, 129.1, 130.9, 131.3; IR (ATR): n=2960, 2872, 2224,
1446 cmÀ1; LR-MS (EI): m/z=210 (M+), 168, 154, 141; HR-
MS (EI): m/z=210.1154, calcd. for C14H14N2 (M+): 210.1157.
(Z)-N-(2,3-Dicyanobut-2-enyl)-4-methyl-N-phenylben-
1
(anti-2i): H NMR (400 MHz, CDCl3): d=0.05 (s, 6H), 0.90
AHCTUNGTRENNUNG
zenesulfonamide (syn-6a): mp 598C; 1H NMR (400 MHz,
(s, 9H), 1.83 (tt, J=6.8, 5.6 Hz, 2H), 2.55 (dt, J=6.8, 1.6 Hz,
2H), 3.65 (t, J=5.6 Hz, 2H), 5.90 (t, J=1.6 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=À5.4, 18.2, 25.9, 30.0, 32.1.
60.9, 111.7, 113.8, 128.6, 136.4; IR (ATR): n=3062, 2858,
2231, 1609, 1110 cmÀ1; LR-MS (FAB): m/z=251 (M+ +H),
235 (M+ÀMe), 193 (M+Àt-Bu), 73; HR-MS (FAB): m/z=
251.1598, calcd. for C12H21N2OSi (M+ +H): 251.1580.
CDCl3): d=2.11 (s, 3H), 2.45 (s, 3H), 4.45 (s, 2H), 7.07–7.10
(m, 2H), 7.25–7.30 (m, 3H), 7.34–7.38 (m, 3H), 7.50 (d, J=
8.0 Hz, 2H); 13C NMR (150 MHz, CDCl3): d=17.5, 21.7,
49.3, 115.3, 116.4, 125.1, 127.4, 127.9, 128.9, 129.2, 129.7,
129.9, 134.2, 138.4, 144.8; IR (ATR): n=2225, 1596, 1491,
1346, 1161, 1088 cmÀ1; LR-MS (EI): m/z=351 (M+), 247,
196, 155, 91; HR-MS (EI): m/z=351.1051, calcd. for
C19H17N3O2S (M+): 351.1041.
2-[3-(4-Morpholino)-3-oxopropyl]maleonitrile
(syn-2j):
1H NMR (400 MHz, CDCl3): d=2.65 (t, J=6.8 Hz, 2H),
2.81 (t, J=6.8 Hz, 2H), 3.46 (t, J=4.8 Hz, 2H), 3.61 (t, J=
4.8 Hz, 2H), 3.66–3.73 (m, 4H), 6.01 (s, 1H); 13C NMR
(100 MHz, CDCl3): d=28.5, 29.9, 42.1, 45.6, 66.3, 66.7,
113.0, 113.3, 115.8, 135.6, 167.9; IR (ATR): n=2918, 2228,
1645, 1444, 1115 cmÀ1; LR-MS (EI): m/z=219 (M+), 133,
127, 86; HRMS (FAB): m/z=220.1076, calcd. for C12H14N3
O2 (M+ +H): 220.1086.
(E)-N-(2,3-Dicyanobut-2-enyl)-4-methyl-N-phenylben-
AHCTUNGTRENNUNG
zenesulfonamide (anti-6a): mp 638C; 1H NMR (400 MHz,
CDCl3): d=2.20 (s, 3H), 2.45 (s, 3H), 4.57 (s, 2H), 7.08–7.12
(m, 2H), 7.20–7.42 (m, 6H), 7.50–7.60 (m, 2H); 13C NMR
(100 MHz, CDCl3): d=20.0, 21.5, 52.1, 113.8, 115.0, 125.9,
126.0, 127.8, 128.6, 128.8, 129.3, 129.6, 133.8, 138.3, 144.4; IR
(ATR): n=2232, 1596, 1488, 1326, 1154, 1088 cmÀ1; LR-MS
(EI): m/z: 351 (M+), 247, 196, 155, 91, 58; HR-MS (EI):
m/z=351.1043, calcd. for C19H17N3O2S (M+): 351.1041.
(Z)-N-(3,4-Dicyanopent-3-enyl)-4-methyl-N-phenylben-
2-[3-(4-Morpholino)-3-oxopropyl]fumaronitrile (anti-2j):
mp 70–758C; 1H NMR (400 MHz, CDCl3): d=2.70 (t, J=
6.8 Hz, 2H), 2.95 (t, J=6.8 Hz, 2H), 3.47 (t, J=4.8 Hz, 2H),
3.63 (t, J=4.8 Hz, 2H), 3.66–3.73 (m, 4H), 6.10 (s, 1H);
13C NMR (100 MHz, CDCl3): d=29.8, 30.0, 42.1, 45.6, 66.3,
66.7, 113.5, 114.7, 115.3, 134.7, 168.0; IR (ATR): n=2918,
2228, 1645, 1444, 1115 cmÀ1; LR-MS (EI): m/z=219 (M+),
127, 86; HR-MS (FAB): m/z=220.1094, calcd. for
C12H14N3O2 (M+ +H): 220.1086.
2-(1-Methoxy-1-phenylpropyl)maleonitrile (syn-2p): mp
97–1008C: 1H NMR (600 MHz, CDCl3): d=0.92 (t, J=
7.2 Hz, 3H), 2.29 (dq, J=14.6, 7.2 Hz, 1H), 2.38 (dq, J=
14.6, 7.2 Hz, 1H), 3.05 (s, 3H), 6.53 (s, 1H), 7.34–7.39 (m,
3H), 7.41–7.44 (m, 2H); 13C NMR (100 MHz, CDCl3): d=
6.7, 24.1, 50.6, 82.0, 111.0, 113.5, 114.1, 126.9, 129.0, 129.05,
129.14, 137.3, 140.7; IR (ATR): n=3074, 2987, 2231, 1447,
1067 cmÀ1; LR-MS (EI): m/z=226 (M+), 196 (M+À2Me),
165 (M+ÀOMeÀMe), 149 (M+ÀPh), 105, 77; HR-MS (EI):
m/z=226.1105, calcd. for C14H14N2O (M+): 226.1106.
AHCTUNGTRENNUNG
zenesulfonamide (syn-6b): mp 1488C; 1H NMR (400 MHz,
CDCl3): d=2.07 (s, 3H), 2.43 (s, 3H), 2.68 (t, J=6.8 Hz,
2H), 3.78 (d, J=6.8 Hz, 2H), 7.01–7.05 (m, 2H), 7.25 (d, J=
8.4 Hz, 2H), 7.32–7.36 (m, 3H), 7.42 (d, J=8.4 Hz, 2H);
13C NMR (100 MHz, CDCl3): d=17.5, 21.7, 31.1, 48.5, 115.7,
116.6, 125.8, 126.1, 127.8, 128.5, 128.7, 129.5, 129.7, 134.2,
139.1, 144.2; IR (ATR): n=2927, 2222, 1594, 1341,
1159 cmÀ1; LR-MS (EI): m/z=365 (M+), 260, 155, 91; HR-
MS (EI): m/z=365.1199, calcd. for C20H19N3O2S (M+):
365.1198.
(Z)-N-Benzyl-N-(2,3-dicyanobut-2-enyl)-4-methylben-
AHCTUNGTRENNUNG
zenesulfonamide (syn-6d): mp 157–1598C; 1H NMR
(400 MHz, CDCl3): d=1.96 (s, 3H), 2.48 (s, 3H), 3.97 (s,
2H), 4.45 (s, 2H), 7.25–7.46 (m, 7H), 7.77 (d, J=8.0 Hz,
2H); 13C NMR (100 MHz, CDCl3): d=17.2, 21.6, 44.7, 52.8,
115.2, 115.9, 124.9, 126.4, 127.4, 128.7, 128.8, 129.0, 130.1,
134.2, 135.4, 144.6; IR (ATR): n=2926, 2225, 1329, 1158,
1102 cmÀ1; LR-MS (EI): m/z=365 (M+), 260, 252, 210, 155,
2-(1-Methoxy-1-phenylpropyl)fumaronitrile
(anti-2p):
1H NMR (400 MHz, CDCl3): d=1.00 (t, J=7.2 Hz, 3H),
Adv. Synth. Catal. 2009, 351, 1897 – 1904
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1903

Shigeru Arai et al.
FULL PAPERS
104, 91; HR-MS (EI): m/z=365.1194, calcd. for
C20H19N3O2S (M+): 365.1198.
Acknowledgements
(E)-N-Benzyl-N-(2,3-dicyanobut-2-enyl)-4-methylben-
One of the authors (S.A.) thanks the Inohana Foundation
(Chiba University) for financial support.
ACHTUNGTRENNUNG
zenesulfonamide (anti-6d): mp 71–728C; 1H NMR
(400 MHz, CDCl3): d=1.95 (s, 3H), 2.48 (s, 3H), 4.11 (s,
2H), 4.49 (s, 2H), 7.29–7.41 (m, 7H), 7.80 (d, J=8.0 Hz,
2H); 13C NMR (100 MHz, CDCl3): d=19.8, 21.5, 49.3, 53.9,
113.8, 115.0, 124.7, 127.0, 127.1, 127.6, 128.6, 128.9, 129.0,
130.1, 134.4, 144.5; IR (ATR): n=3268, 2918, 2236, 1598,
1329, 1154 cmÀ1; LR-MS (EI): m/z=365 (M+), 253, 210, 185,
106, 91; HR-MS (EI): m/z=365.1198, calcd. for
C20H19N3O2S (M+): 365.1198.
References
[1] For a review of transition-metal-catalyzed carbocyana-
tion of carbon-carbon multiple bonds, see; C. Nꢁjera,
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Angew. Chem. Int. Ed. 2009, 48, 2452-2456.
(Z)-N-(2,3-Dicyano-3-phenylallyl)-4-methyl-N-phenylben-
zenesulfonamide (syn-6e): mp 978C; 1H NMR (600 MHz,
CDCl3): d=2.39 (s, 3H), 4.50 (s, 2H), 6.95 (d, J=8.0 Hz,
2H), 7.14–7.20 (m, 4H), 7.25–7.34 (m, 5H), 7.40–7.85 (m,
2H), 7.51–7.55 (m, 1H); 13C NMR (150 MHz, CDCl3): d=
21.6, 49.8, 115.4, 115.6, 125.6, 128.0, 128.4, 128.9, 129.0,
129.1, 129.4, 129.6, 129.7, 131.5, 134.1, 138.6, 144.6; IR
(ATR): n=3060, 2362, 1593, 1355, 1159 cmÀ1; LR-MS (EI):
m/z=413 (M+), 363, 258, 167, 111, 91; HR-MS (EI): m/z=
413.1187, calcd. for C24H19N3O2S (M+): 413.1198.
[2] a) M. Suginome, H. Kinugasa, Y. Ito, Tetrahedron Lett.
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2711.
(E)-N-(2,3-Dicyano-3-phenylallyl)-4-methyl-N-phenylben-
zenesulfonamide (anti-6e): mp 588C; 1H NMR (600 MHz,
CDCl3): d=2.46 (s, 3H), 4.78 (s, 2H), 7.15–7.55 (m, 14H);
13C NMR (150 MHz, CDCl3): d=21.4, 53.5, 114.6, 115.0,
121.2, 122.6, 127.0, 128.1, 128.7, 128.8, 128.9, 129.3, 129.6,
131.8, 133.8, 138.4, 144.4; IR (ATR): n=3059, 2361, 1594,
1491, 1354, 1159 cmÀ1; LR-MS (EI): m/z=413 (M+), 258,
182, 155, 91; HR-MS (EI): m/z=413.1183, calcd. for
C24H19N3O2S (M+): 413.1198.
[3] a) T. Funabiki, Y. Yamazaki, K. Tarama, J. Chem. Soc.
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Martinelli, S. Sottocornola, Chem. Rev. 2007, 107, 5318.
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riuchi, T. Hanafusa, J. Org. Chem. 1988, 53, 3539.
[7] Chatani reported that ArI reacts with TMSCN in the
presence of Pd(0) gave ArCN, see: N. Chatani, T. Ha-
nafusa, J. Org. Chem. 1986, 51, 4714.
(Z)-N-(2,3-Dicyano-3-phenylallyl)-N-(4-trifluoromethyl-
phenyl)-4-methylbenzenesulfonamide (syn-6h): mp 143–
1
1458C; H NMR (400 MHz, CDCl3): d=2.42 (s, 3H), 4.53
(s, 2H), 7.10 (d, J=8.0 Hz, 2H), 7.21–7.35 (m, 6H), 7.45–
7.59 (m, 6H); 13C NMR (100 MHz, CDCl3): d=21.6, 49.3,
115.2 (J=39.6 Hz), 122.1, 124.7, 126.6 (J=13.2 Hz), 127.8,
128.8, 129.0, 129.4, 129.8, 129.9, 130.6, 130.9, 131.3, 131.6,
133.5, 141.9, 144.9; IR (ATR): n=2922, 2224, 1323, 1160,
1067 cmÀ1; LR-MS (EI): m/z=481 (M+), 326, 315, 155, 91;
HR-MS (EI): m/z=481.1066, calcd. for C25H18F3N3O2S
(M+): 481.1072.
(E)-N-(2,3-Dicyano-3-phenylallyl)-N-(4-trifluoromethyl-
phenyl)-4-methylbenzenesulfonamide (anti-6h): mp 1498C;
1H NMR (400 MHz, CDCl3): d=2.47 (s, 3H), 4.78 (s, 2H),
7.26–7.34 (m, 3H), 7.48–7.55 (m, 6H), 7.65–7.70 (m, 4H);
13C NMR (100 MHz, CDCl3): d=21.4, 53.3, 114.8 (J=
118.8 Hz), 119.4, 122.1, 126.5 (J=13.2 Hz), 127.1, 127.7,
127.8, 128.2, 129.0, 129.2, 129.67, 129.74, 129.8, 129.9, 132.1,
133.4, 142.1, 145.0; IR (ATR): n=3069, 2233, 1614, 1322,
1160, 1046 cmÀ1; LR-MS (EI): m/z=481 (M+), 315, 298, 250,
155, 91; HR-MS (EI): m/z=480.1025, calcd. for
C25H17F3N3O2S (M+ÀH): 480.0993.
[8] G. W. Schott, P. Heimbach, Angew. Chem. Int. Ed.
1967, 6, 92.
[9] syn- and anti-chlorination of alkynes promoted by
Pd(II) have been reported, see: J.-E. Backvꢂll, Y. I. M.
Nilsson, R. G. P. Gatti, Organometallics 1995, 14, 4242.
[10] Pd(II) with TMSOTf would give cationic palladium
species; see, S. Ogoshi, S. Tomiyasu, M. Morita, H. Kur-
osawa, J. Am. Chem. Soc. 2002, 124, 11598.
[11] Y. M. Chung, J. H. Gong, T. H. Kim, J. N. Kim, Tetrahe-
dron Lett. 2001, 42, 9023.
1904
asc.wiley-vch.de
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 1897 – 1904