Oxidative heck coupling of allylic amines with 2,2,6,6- Tetramethylpiperidine-N-oxyl (TEMPO) as oxidant for the preparation of tetrasubstituted alkenes

Article abstract of DOI:10.1002/adsc.201300846

The paper describes the oxidative Heck arylation of various allylic amines using arylboronic acids for the preparation of tetrasubstituted alkenes. As oxidant the commercially available 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) is used and coupling rea

Full text of DOI:10.1002/adsc.201300846

FULL PAPERS
DOI: 10.1002/adsc.201300846
Oxidative Heck Coupling of Allylic Amines with
2,2,6,6-Tetramethylpiperidine-N-oxyl (TEMPO) as Oxidant for
the Preparation of Tetrasubstituted Alkenes
Zhiheng He,a Birgit Wibbeling,a and Armido Studera,*
a
Westfꢀlische Wilhems-University, Institute of Organic Chemistry, Corrensstrasse 40, 48149 Mꢁnster, Germany
Fax : (+49)-251-833-6523; e-mail: studer@uni-muenster.de
Received: September 18, 2013; Revised: October 24, 2013; Published online: December 11, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300846.
Abstract: The paper describes the oxidative Heck ar- control of the diastereoselectivity. Substrate scope
ylation of various allylic amines using arylboronic with respect to the allylic amine and the arylboronic
acids for the preparation of tetrasubstituted alkenes. acid is investigated.
As oxidant the commercially available 2,2,6,6-tetra-
methylpiperidine-N-oxyl (TEMPO) is used and cou-
pling reactions occur under very mild conditions at Keywords: allylic amines; catalysis; cross coupling;
room temperature. The densely substituted alkenes nitroxides; palladium; 2,2,6,6-tetramethylpiperidine-
are formed in good to excellent yields with complete N-oxyl (TEMPO)
Introduction
The Heck reaction as one of the most valuable meth-
À
ods for C C bond formation has been intensively
used in organic synthesis.[1] In this Pd-catalyzed cou-
pling reaction halides or pseudohalides are cross-cou-
pled with olefins. In the oxidative version (oxidative
Heck reaction) arylboronic acids are generally used
as aryl-Pd sources and a stoichiometric external oxi-
Scheme 1. Triaryl-substituted alkenes via oxidative Heck
dant is necessary to run the catalytic process. Com- coupling of allylic alcohols.
pared to the heavily investigated parent Heck reac-
tion this oxidative variant is less well explored.[2,3] In
general the oxidative process works under milder con- were recently shown to be valuable substrates for re-
ditions and allows for the preparation of densely sub- gioselective oxidative Heck chemistry.[3j] In that paper
stituted olefins with high regio- and stereocontrol. the synthesis of trisubstituted alkenes was reported
Despite the great achievements in the field of transi- but examples on the successful preparation of tetra-
tion metal-catalyzed cross-coupling chemistry, the substituted olefins were not included. Moreover, re-
synthesis of highly substituted alkenes is still a de- sults on the synthesis of tetrasubstituted alkenes were
manding task.[4]
recently disclosed using the Fujiwara–Moritani var-
We have recently[5] shown that the oxidative Heck iant of the oxidative Heck reaction.[8] However, in
coupling using either the 2,2,6,6-tetramethylpiperi- these transformations high reaction temperatures are
dine-N-oxyl radical (TEMPO),[6,7] a related bulky ni- necessary which makes the control of the stereoselec-
troxide 1 or O2 as external stoichiometric oxidants tivity difficult to achieve. Moreover, the aryl-Pd
can be used for the synthesis of triaryl-substituted al- source, which is an arene in those cases, has to be
lylic alcohols under very mild conditions (Scheme 1). used in a large excess as a cosolvent.
As a continuation of these investigations we report
À
herein stereoselective Pd-catalyzed C H arylations of
protected allylic amines for the synthesis of tetrasub-
stituted alkenes. Notably, Boc-protected allylic amines
Adv. Synth. Catal. 2013, 355, 3639 – 3647
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3639

Zhiheng He et al.
FULL PAPERS
Results and Discussion
(Table 1, entry 1). Importantly, 5a was formed with
complete stereocontrol as checked by NMR spectros-
The allylic amines used in this study were readily pre- copy. The relative configuration was unambiguously
pared according to a literature procedure.[9] In the assigned by X-ray analysis (Figure 1).[11]
first step, four different aldehydes were reacted in
Efficient coupling was also achieved using O2 as ox-
a Morita–Baylis–Hillman reaction[10] with methyl ac- idant. However, the reaction was significantly slower
rylate to give the corresponding allylic alcohols 2a–d and yield decreased (entry 2). Reducing the amount
in good yields (Scheme 2). Stereoselective bromina- of KF and TEMPO led to slightly decreased yields
tion with LiBr/H2SO4 and subsequent amination with
aniline afforded the allylic amines 3a–d which were
eventually N-acylated to provide substrates 4a–d in
good overall yields. To investigate the effect of the N-
substituents, we also prepared the analogues 4e–j and
the effect of the ester moiety on the coupling reaction
was addressed by including the nitrile congener 4k,
the aryl derivatives 4l–n and the methyl compound 4o
into these studies (for their preparation see the Sup-
porting Information).
Table 1. Oxidative Heck coupling of 4a with 4-
MeC6H4B(OH)2 (4 equiv.) under different conditions.
Oxidative Heck arylation was optimized using sub-
strate 4a (R=Ph) in combination with para-tolylbor-
onic acid as arene source. Oxidants and solvents were
systematically varied. We were pleased to find that
with TEMPO (4 equiv.) in the presence of KF
(4 equiv.) in propionic acid at room temperature for
2 h, 5a was obtained in near quantitative yield
Entry
Oxidant
Solvent
Yield [%]
1
2
3
4
5
6
7
8
TEMPO
O2
TEMPO
TEMPO
1
propionic acid
propionic acid
propionic acid
propionic acid
propionic acid
propionic acid
propionic acid
propionic acid
propionic acid
CH2Cl2
97
78[a]
84[b]
89[c]
51
1,4-benzoquinone
no reaction
30
traces
no reaction
no reaction
no reaction
no reaction
14
Cu
ACHTUNGTRENNUNG
PhI
A
9
AgOAc
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
10
11
12
13
14
DMF
MeOH
acetic acid
butyric acid
73
[a]
Reaction run for 24 h.
With 3 equiv. TEMPO.
With 3 equiv. KF.
[b]
[c]
Scheme 2. Preparation of allylic amine derivatives.
Figure 1. X-ray structure of 5a.
3640
asc.wiley-vch.de
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 3639 – 3647

Oxidative Heck Coupling of Allylic Amines with 2,2,6,6-Tetramethylpiperidine-N-oxyl
mized conditions afforded alkene 10 in 89% isolated
yield. Interestingly, derivative 4h lacking the phenyl
protecting group showed high reactivity. However, be-
sides the targeted Heck coupling product 9a (53%),
the isomer 9b was isolated as diastereoisomerically
pure compound in 41% yield (relative configuration
assigned by NOE experiments). The N-benzyl deriva-
tive 4j showed slightly decreased reactivity compared
to the N-phenyl compound 4a and alkene 11 was ob-
tained in 87% yield in 16 h.
We then investigated the substrate scope with re-
spect to the arylboronic acid component using alkene
4a as substrate (Table 2). For all boronic acids studied
the reaction occurred with complete stereocontrol
and products 5b–i were isolated as single diastereoiso-
mers as evaluated by NMR spectroscopy. We noted
good yields for arylboronic acids bearing electron-do-
nating as well as electron-withdrawing substituents at
the para position (entries 1–7). In general the elec-
tron-poorer boronic acids provided slightly better re-
sults. As expected the meta-tolylboronic acid worked
well (entry 8) but no coupling was achieved with the
Scheme 3. Effect of the N-substituents on the Heck cou- ortho-tolyl derivative for steric reasons (entry 9). Side
pling.
reactions in these couplings are the homocoupling of
the arylboronic acid and the protodeborylation. The
aryl group in the alkene substrate could be varied
(entries 3 and 4). Oxidant 1, which performed very without affecting reactivity and products 12 and 13
well in the oxidative arylation of densely substituted were isolated in very good yields in the reaction with
allylic alcohols (see Scheme 1),[5] provided 5a in phenylboronic acid (entries 10 and 11). Importantly,
a moderate yield (entry 5) and no coupling occurred substrate 4d bearing the methyl group instead of an
with benzoquinone as an oxidant (entry 6). Cu
was also not a good oxidant (entry 7) and little or no 14 in excellent yield and selectivity showing that the
reaction was observed with PhI(OAc)2 or Ag(OAc),
ACHTUNGRTEN(NNUG OAc)2 aryl substituent delivered the corresponding product
A
ACHTUNGTRENNUNG
respectively (entries 8 and 9). The proper choice of
the solvent is crucial since coupling to 5a was not ach-
ieved in CH2Cl2, DMF and MeOH (entries 10–12). In-
terestingly, running the reaction in acetic or butyric
acid as solvents afforded lower yields documenting
the importance the solvent exerts on the coupling re-
action (entries 13 and 14).
Table 2. Substrate scope.
With the optimized conditions in hand we next in-
vestigated the effect of the N-substituents on the reac-
tion outcome. The carbonyl moiety in the N-protect-
ing group is important since with the N-methyl deriv-
ative 4e coupling did not occur (Scheme 3). This as-
sumption was further supported by the successful
transformation of the Boc-protected allylic amine to
tetrasubstituted alkene 7. A quantitative yield was
achieved; however, reaction time had to be increased
to 16 h. The slightly decreased reactivity might be
caused by steric effects. A very good result was also
obtained with the Bz-protected substrate 4g to give 8,
so proving the importance of the carbonyl-containing
substituent on this coupling reaction. The N-phenyl
group in 4a was replaced by the 4-MeOC6H4 substitu-
ent, which can be cleaved under oxidative conditions,
and reaction with para-tolylboronic acid under opti-
Entry Substrate
R
Aryl
Prod- Yield
uct
[%]
1
2
3
4
5
6
7
8
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b
4c
4d
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
4-t-BuC6H4 5b
4-MeOC6H4 5c
72
73
4-PhC6H4
4-AcC6H4
4-ClC6H4
4-FC6H4
4-CF3C6H4
3-MeC6H4
2-MeC6H4
Ph
5d
5e
5f
5g
5h
5i
79[a]
69[a]
85
96
89
82
9
Ph
4-ClC6H4
4-MeC6H4 Ph
Me
5j
n.i.[b]
95
10
11
12
12
13
14
90
96
Ph
[a]
[b]
Reaction for 16 h.
n.i.=not identified.
Adv. Synth. Catal. 2013, 355, 3639 – 3647
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3641

Zhiheng He et al.
FULL PAPERS
Scheme 4. Oxidative Heck coupling on stilbene derivatives.
chemistry is not restricted to cinnamic acid derivatives
(entry 12).
Finally, we studied the effect of the ester moiety on
the coupling reaction and noted that the nitrile deriv-
ative 4k (see Scheme 1) in the reaction with para-tol-
ylboronic acid under optimized conditions did not
provide the corresponding targeted Heck product.
However, with the alkene 4l carrying a phenyl group
in place of the ester moiety, coupling worked with
high yield and alkene 15a was isolated in 99% yield
(Scheme 4). As compared to ester 4a, transformation
was significantly slower and reaction time had to be
extended to 16 h. In analogy, the other two stilbene
derivatives 4m and 4n underwent oxidative Heck cou-
Scheme 5. Suggested mechanism.
pling to give 15b and 15c with perfect stereocontrol in the Pd complex interacts in its dissociated cationic
quantitative yield. The relative configuration of 15c form (+PdAryl) with the acyl protecting group to gen-
was confirmed by X-ray analysis (Figure 2).[12] How- erate complex A. syn-Carbopalladation then provides
ever, reaction with the methyl-substituted congener B which after sigma bond rotation (least motion) un-
4o was not clean and different products which could dergoes b-H-elimination via conformer C to give the
not be separated were identified.[13]
observed Heck product. The Pd(0) formed after a-
Considering the importance of the acyl protecting elimination is eventually oxidized with TEMPO in
group on the reaction outcome we suggest the follow- the presence of propionic acid to regenerate the
ing mechanism (Scheme 5) for the stereoselective oxi- (EtCO2)2Pd complex.
dative Heck arylation. PdX2 in propionic acid likely
present as (EtCO2)2Pd first,[14] then reacts with the ar-
ylboronic acid to give EtCO2PdAryl. We assume that Conclusions
We reported the application of the oxidative Heck
coupling for the arylation of densely substituted allyl-
ic amines which are readily prepared using known
methods. Commercially available TEMPO was shown
to be the ideal oxidant for these transformations
which occur under very mild conditions with complete
stereocontrol. Proper choice of the substituents at the
N atom in the substrate allylic amines was shown to
be important for successful Heck coupling. Best re-
sults were achieved using the N-acyl-N-phenyl deriva-
tives.
Experimental Section
General Procedure (GP) for the Synthesis of Tetra-
substituted Olefins by Oxidative Heck Coupling
An arylboronic acid (1.0 mmol, 4.0 equiv.), potassium fluo-
Figure 2. X-ray structure of 15c.
ride (58 mg, 1.0 mmol, 4.0 equiv.), PdACTHNGUETRNNU(G OAc)2 (2.8 mg,
3642
asc.wiley-vch.de
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 3639 – 3647

Oxidative Heck Coupling of Allylic Amines with 2,2,6,6-Tetramethylpiperidine-N-oxyl
12.5 mmol, 5 mol%), alkene 4 (0.25 mmol, 1.0 equiv.) and
propionic acid (1.0 mL) were stirred at room temperature
for 2 h or 16 h. Na2CO3 (aqueous saturated soluition, 5 mL)
was added and the mixture was extracted with DCM (3ꢃ
10 mL). The combined organic layers were dried over
MgSO4 and the volatiles were removed under reduced pres-
sure. The residue was purified by flash chromatography
(FC).
(E)-Methyl 3-phenyl-2-[(N-phenylacetamido)methyl]-3-
(p-tolyl)acrylate (5a): According to the GP with p-tolylbor-
onic acid (135 mg, 1.0 mmol, 4.0 equiv.) and (E)-methyl 3-
phenyl-2-[(N-phenylacetamido)methyl]acrylate 4a (77 mg,
0.25 mmol, 1.0 equiv.) for 2 h. FC (pentane/acetone=10/1)
gave the desired product 5a as a yellow oil; yierld: 97 mg
(97%). 1H NMR (300 MHz, CDCl3, 300 K): d=7.33–7.31
(m, 3H, CHarom), 7.12–7.10 (m, 5H, CHarom), 6.95–6.92 (m,
2H, CHarom), 6.84 (d, J=7.8 Hz, 2H, CHarom), 6.35 (d, J=
7.8 Hz, 2H, CHarom), 4.60 (s, 2H, CH2), 3.43 (s, 3H, CH3),
2.19 (s, 3H, CH3), 1.73 (s, 3H, CH3); 13C NMR (75 MHz,
CDCl3, 300 K): d=170.3 (C), 169.8 (C), 148.9 (C), 142.0 (C),
141.4 (C), 137.5 (C), 136.3 (C), 129.5 (CH), 129.0 (CH),
128.7 (CH), 128.7 (CH), 128.2 (CH), 128.1 (CH), 127.9
(CH), 127.9 (C), 127.8 (CH), 51.7 (CH3), 48.3 (CH2), 22.6
(CH3), 21.1 (CH3); HR-MS (ESI): m/z=422.1732, calcd. for
C26H25NO3Na [M+Na]+: 422.1727. IR (neat): n=2947w,
1722s, 1662s, 1595m, 1495m, 1387m, 1282m, 1254m, 1119s,
699s cmÀ1.
(E)-Methyl 3-[4-(tert-butyl)phenyl]-3-phenyl-2-[(N-phen-
ylacetamido)methyl]acrylate (5b): According to the GP with
[4-(tert-butyl)phenyl]boronic acid (178 mg, 1.00 mmol,
4.00 equiv.) and (E)-methyl 3-phenyl-2-[(N-phenylacetami-
do)methyl]acrylate 4a (77 mg, 0.25 mmol, 1.0 equiv.) for 2 h.
FC (pentane/acetone=10/1) gave the desired product 5b as
a yellow solid; yield: 80 mg (72%). 1H NMR (300 MHz,
CDCl3, 300 K): d=7.33–7.31 (m, 3H, CHarom), 7.14–7.09 (m,
5H, CHarom), 7.04 (d, J=8.4 Hz, 2H, CHarom), 6.97–6.94 (m,
2H, CHarom), 6.41 (d, J=8.4 Hz, 2H, CHarom), 4.62 (s, 2H,
CH2), 3.44 (s, 3H, CH3), 1.73 (s, 3H, CH3), 1.19 (s, 9H,
CH3); 13C NMR (75 MHz, CDCl3, 300 K): d=170.1 (C),
169.8 (C), 150.6 (C), 148.9 (C), 142.1 (C), 141.5 (C), 136.2
(C), 129.5 (CH), 129.0 (CH), 128.4 (CH), 128.2 (CH), 128.0
(CH), 128.0 (C), 127.9 (CH), 127.7 (CH), 124.8 (CH), 51.7
(CH3), 48.2 (CH2), 34.5 (C), 31.3 (CH3), 22.7 (CH3); HR-MS
(ESI): m/z=464.2196, calcd. for C29H31NO3Na [M+Na]+:
464.2202;IR (neat): n=2958w, 1723s, 1663s, 1495m, 1389s,
1355s, 1257s, 1123s cmÀ1.
m/z=438.1676, calcd. for C26H25NO4Na [M+Na]+: 438.1681;
IR (neat): n=2948w, 1721s, 1661s, 1606m, 1495m, 1388m,
1283s, 1246s, 1119m, 699s cmÀ1.
(E)-Methyl 3-[(1,1’-biphenyl)-4-yl]-3-phenyl-2-[(N-phenyl-
acetamido)methyl]acrylate (5d): According to the GP with
[1,1’-biphenyl]-4-ylboronic
acid
(198 mg,
1.0 mmol,
4.0 equiv.) and (E)-methyl 3-phenyl-2-[(N-phenylacetami-
do)methyl]acrylate 4a (77 mg, 0.25 mmol, 1.0 equiv.) for 2 h.
FC (pentane/acetone=10/1) gave the desired product 5d as
a yellow oil;: yield: 92 mg (79%). 1H NMR (300 MHz,
CDCl3, 300 K): d=7.46–7.43 (m, 2H, CHarom), 7.35–7.25 (m,
8H, CHarom), 7.16–7.12 (m, 5H, CHarom), 7.01–6.98 (m, 2H,
CHarom), 6.53 (d, J=8.1 Hz, 2H, CHarom), 4.64 (s, 2H, CH2),
3.46 (s, 3H, CH3), 1.74 (s, 3H, CH3); 13C NMR (75 MHz,
CDCl3, 300 K): d=170.3 (C), 169.7 (C), 148.3 (C), 142.1 (C),
141.1 (C), 140.5 (C), 140.4 (C), 138.2 (C), 129.6 (CH), 129.2
(CH), 129.1 (CH), 128.8 (CH), 128.4 (C), 128.3 (CH), 128.2
(CH), 128.1 (CH), 127.9 (CH), 127.5 (CH), 127.0 (CH),
126.7 (CH), 51.9 (CH3), 48.4 (CH2), 22.6 (CH3); HR-MS
(ESI): m/z=484.1883, calcd. for C31H27NO3Na [M+Na]+:
484.1889; IR (neat): n=2949w, 1713s, 1661s, 1595m,
1494m, 1389m, 1283s, 1256s, 1120m, 733 s, 697s cmÀ1.
(E)-Methyl 3-(4-acetylphenyl)-3-phenyl-2-[(N-phenylacet-
amido)methyl]acrylate (5e): According to the GP with 4-
acetylbenzeneboronic acid (164 mg, 1.0 mmol, 4.0 equiv.)
and (E)-methyl 3-phenyl-2-[(N-phenylacetamido)methyl]a-
crylate 4a (77 mg, 0.25 mmol, 1.0 equiv.) for 2 h. FC (pen-
tane/acetone=5/1) gave the desired product 5e as a white
1
solid; yield: 74 mg (69%); mp 1338C. H NMR (300 MHz,
CDCl3, 300 K) d 7.63 (d, J=8.0 Hz, 2H, CHarom), 7.36–7.35
(m, 3H, CHarom), 7.16–7.11 (m, 5H, CHarom), 6.97–6.94 (m,
2H, CHarom), 6.57 (d, J=7.8 Hz, 2H, CHarom), 4.54 (s, 2H,
CH2), 3.48 (s, 3H, CH3), 2.47 (s, 3H, CH3), 1.73 (s, 3H,
CH3). 13C NMR (75 MHz, CDCl3, 300 K) d 197.4 (C), 170.2
(C), 169.2 (C), 146.9 (C), 144.0 (C), 142.0 (C), 140.2 (C),
136.2 (C), 129.7 (CH), 129.2 (C), 129.0 (CH), 129.0 (CH),
128.3 (CH), 128.2 (CH), 128.2 (CH), 128.1 (CH), 128.1
(CH), 51.9 (CH3), 48.4 (CH2), 26.5 (CH3), 22.6 (CH3); HR-
MS (ESI): m/z=450.1676, calcd. for C27H25NO4Na [M+
Na]+: 450.1681; IR (neat): n=2948w, 1725s, 1683s, 1664s,
1596m, 1495m, 1391m, 1265s, 1122m cmÀ1.
(E)-Methyl
3-(4-chlorophenyl)-3-phenyl-2-[(N-phenyl-
acetamido)methyl]acrylate (5f): According to the GP with
(4-chlorophenyl)boronic acid (156 mg, 1.0 mmol, 4.0 equiv.)
and (E)-methyl 3-phenyl-2-[(N-phenylacetamido)methyl]a-
crylate 4a (77 mg, 0.25 mmol, 1.0 equiv.) for 2 h. FC (pen-
tane/acetone=10/1) gave the desired product 5f as a white
(E)-Methyl 3-(4-methoxyphenyl)-3-phenyl-2-[(N-phenyl-
acetamido)methyl]acrylate (5c): According to the GP with
1
solid; yield: 89 mg (85%); mp 1428C. H NMR (300 MHz,
(4-methoxyphenyl)boronic
acid
(152 mg,
1.0 mmol,
CDCl3, 300 K): d=7.46–7.42 (m, 3H, CHarom), 7.29–7.22 (m,
5H, CHarom), 7.12 (d, J=8.3 Hz, 2H, CHarom), 7.06–7.03 (m,
2H, CHarom), 6.49 (d, J=8.3 Hz, 2H, CHarom), 4.66 (s, 2H,
CH2), 3.56 (s, 3H, CH3), 1.84 (s, 3H, CH3); 13C NMR
(75 MHz, CDCl3, 300 K): d=170.3 (C), 169.4 (C), 147.0 (C),
142.0 (C), 140.6 (C), 137.6 (C), 133.7 (C), 130.1 (CH), 129.7
(CH), 129.0 (CH), 128.9 (C), 128.3 (CH), 128.2 (CH), 128.2
(CH), 128.1 (CH), 128.1 (CH), 51.9 (CH3), 48.4 (CH2), 22.6
(CH3); HR-MS (ESI): m/z=442.1180, calcd. for
C25H22ClNO3Na [M+Na]+: 442.1186; IR (neat): n=2949w,
1722s, 1661s, 1494s, 1390s, 1278s, 1253s, 1122m cmÀ1.
4.0 equiv.) and (E)-methyl 3-phenyl-2-((N-phenylacetami-
do)methyl)acrylate 4a (77 mg, 0.25 mmol, 1.0 equiv.) for 2 h.
FC (pentane/acetone=10/1) gave the desired product 5c as
a colorless oil; yield: 76 mg (73%). 1H NMR (300 MHz,
CDCl3, 300 K): d=7.33–7.31 (m, 3H, CHarom), 7.13–7.12 (m,
5H, CHarom), 6.94–6.91 (m, 2H, CHarom), 6.58 (d, J=8.5 Hz,
2H, CHarom), 6.41 (d, J=8.5 Hz, 2H, CHarom), 4.64 (s, 2H,
CH2), 3.67 (s, 3H, CH3), 3.42 (s, 3H, CH3), 1.73 (s, 3H,
CH3); 13C NMR (75 MHz, CDCl3, 300 K): d=170.2 (C),
169.8 (C), 159.1 (C), 148.8 (C), 142.1 (C), 141.6 (C), 131.6
(C), 130.2 (CH), 129.5 (CH), 129.0 (CH), 128.3 (CH), 128.1
(CH), 127.9 (CH), 127.8 (CH), 127.7 (C), 113.4 (CH), 55.2
(CH3), 51.7 (CH3), 48.3 (CH2), 22.7 (CH3). HR-MS (ESI)
(E)-Methyl 3-(4-fluorophenyl)-3-phenyl-2-[(N-phenylacet-
amido)methyl]acrylate (5g): According to the GP with (4-
fluorophenyl)boronic acid (140 mg, 1.0 mmol, 4.0 equiv.)
Adv. Synth. Catal. 2013, 355, 3639 – 3647
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3643

Zhiheng He et al.
FULL PAPERS
and (E)-methyl 3-phenyl-2-[(N-phenylacetamido)methyl]-ac-
rylate 4a (77 mg, 0.25 mmol, 1.0 equiv.) for 2 h. FC (pen-
tane/acetone=10/1) gave the desired product 5g as a yellow
gave the desired product 7 as a yellow oil; yield: 113 mg
(99%); mp 1148C. H NMR (300 MHz, CDCl3, 300 K): d=
1
7.23 (t, J=7.3 Hz, 2H, CHarom), 7.15 (t, J=7.3 Hz, 1H,
CHarom), 7.12–7.05 (m, 5H, CHarom), 6.94–6.91 (m, 2H,
CHarom), 6.87 (d, J=7.8 Hz, 2H, CHarom), 6.45 (d, J=7.8 Hz,
2H, CHarom), 4.52 (s, 2H, CH2), 3.41 (s, 3H, CH3), 2.20 (s,
3H, CH3), 1.31 (s, 9H, CH3); 13C NMR (75 MHz, CDCl3,
300 K): d=169.8 (C), 154.6 (C), 147.9 (C), 141.5 (C), 141.5
(C), 137.5 (C), 136.5 (C), 128.9 (CH), 128.9 (C), 128.8 (CH),
128.7 (CH), 128.4 (CH), 128.3 (CH), 127.9 (CH), 127.7
(CH), 125.6 (CH), 80.3 (C), 51.6 (CH3), 49.8 (CH2), 28.3
(CH3), 21.2 (CH3); HR-MS (ESI): m/z=480.2145, calcd. for
C29H31NO4Na [M+Na]+: 480.2151; IR (neat): n=2948w,
1698s, 1384s, 1303m, 1255s, 1165s, 1119s cmÀ1.
1
solid; yield: 97 mg (96%); mp 1458C. H NMR (300 MHz,
CDCl3, 300 K): d=7.34–7.32 (m, 3H, CHarom), 7.15–7.11 (m,
5H, CHarom), 6.96–6.93 (m, 2H, CHarom), 6.73 (t, J=8.5 Hz,
2H, CHarom), 6.46–6.41 (m, 2H, CHarom), 4.57 (s, 2H, CH2),
3.45 (s, 3H, CH3), 1.73 (s, 3H, CH3); 13C NMR (75 MHz,
CDCl3, 300 K): d=170.3 (C), 169.5 (C), 162.2 (d, J=
247.5 Hz, C), 147.4 (C), 142.1 (C), 140.9 (C), 135.1 (d, J=
3.4 Hz, C), 130.5 (d, J=8.5 Hz, CH), 129.6 (CH), 129.0
(CH), 128.6 (C), 128.2 (CH), 128.2 (CH), 128.1 (CH), 128.1
(CH), 115.1 (d, J=21.5 Hz, CH), 51.9 (CH3), 48.3 (CH2),
22.6 (CH3). HR-MS (ESI) m/z=404.1662, calcd. for
C25H22FNO3H [M+H]+, found: 404.1565. IR (neat): n=
2948w, 1717s, 1660s, 1596m, 1494m, 1390s, 1252s, 1216s,
1119s, 700 s cmÀ1.
(E)-Methyl 3-phenyl-2-[(N-phenylbenzamido)methyl]-3-
(para-tolyl)acrylate (8): According to the GP with para-tol-
ylboronic acid (135 mg, 1.0 mmol, 4.0 equiv.) and (E)-methyl
(E)-Methyl 3-phenyl-2-[(N-phenylacetamido)methyl]-3-
[4-(trifluoromethyl)phenyl]-acrylate (5h): According to the
GP with [4-(trifluoromethyl)phenyl]boronic acid (190 mg,
1.0 mmol, 4.0 equiv.) and (E)-methyl 3-phenyl-2-((N-phenyl-
acetamido)methyl)acrylate 4a (77 mg, 0.25 mmol, 1.0 equiv.)
for 2 h. FC (pentane/acetone=10/1) gave the desired prod-
uct 5h as a yellow solid; yield: 101 mg (89%); mp 1498C.
1H NMR (300 MHz, CDCl3, 300 K): d=7.47–7.45 (m, 3H,
CHarom), 7.40 (d, J=8.4 Hz, 2H, CHarom), 7.29–7.21 (m, 5H,
CHarom), 7.09–7.05 (m, 2H, CHarom), 6.69 (d, J=8.1 Hz, 2H,
CHarom), 4.64 (s, 2H, CH2), 3.59 (s, 3H, CH3), 1.84 (s, 3H,
CH3); 13C NMR (75 MHz, CDCl3, 300 K): d=170.2 (C),
169.2 (C), 146.4 (C), 142.8 (C), 142.0 (C), 140.1 (C), 129.7
(q, J=13.2 Hz, CH), 129.7 (CH), 129.4 (C), 129.0 (CH),
129.0 (CH), 128.3 (CH), 128.2 (CH), 128.1 (CH), 128.1
(CH), 125.0 (q, J=3.6 Hz, CF3), 122.6 (q, J=216 Hz, C),
52.0 (CH3), 48.3 (CH2), 22.6 (CH3); HR-MS (ESI): m/z=
476.1444, calcd. for C26H22F3NO3Na [M+Na]+: 476.1449; IR
(neat): n=2950 w, 1728s, 1667s, 1496m, 1324s, 1390s, 1252s,
1216s, 1119s, 700s cmÀ1.
3-phenyl-2-((N-phenylbenzamido)methyl)acrylate
4g
(93 mg, 0.25 mmol, 1.0 equiv.) for 2 h. FC (pentane/ace-
tone=10/1) gave the desired product 8 as a yellow oil;
yield: 109 mg (94%); mp 1088C. 1H NMR (300 MHz,
CDCl3, 300 K): d=7.19–7.04 (m, 11H, CHarom), 6.99–6.92
(m, 6H, CHarom), 6.60 (d, J=7.9 Hz, 2H, CHarom), 4.81 (s,
2H, CH2), 3.45 (s, 3H, CH3), 2.23 (s, 3H, CH3); 13C NMR
(75 MHz, CDCl3, 300 K): d=170.7 (C), 169.8 (C), 148.6 (C),
142.6 (C), 141.5 (C), 137.6 (C), 136.5 (C), 136.2 (C), 129.4
(CH), 128.9 (CH), 128.9 (CH), 128.8 (CH), 128.8 (CH),
128.5 (CH), 128.4 (CH), 128.1 (C), 127.9 (CH), 127.8 (CH),
127.6 (CH), 126.9 (CH), 51.8 (CH3), 49.7 (CH2), 21.2 (CH3);
HR-MS (ESI): m/z=484.1883, calcd. for C31H27NO3Na [M+
Na]+: 484.1889; IR (neat): n=2948w, 1712s, 1651s, 1493m,
1381m, 1363m, 1304m, 1255m, 1220s, 1166s cmÀ1.
(E)-Methyl 2-(acetamidomethyl)-3-phenyl-3-(para-tolyl)-
acrylate (9a) and (Z)-Methyl 3-acetamido-2-(phenylACHTUNGTRENNUNG(p-tol-
yl)methyl)-acrylate (9b): According to GP with para-tolyl-
boronic acid (135 mg, 1.0 mmol, 4.0 equiv.) and (E)-methyl
2-(acetamidomethyl)-3-phenylacrylate
4 h
(58 mg,
(E)-Methyl 3-phenyl-2-[(N-phenylacetamido)methyl]-3-
(meta-tolyl)acrylate (5i): According to the GP with meta-tol-
ylboronic acid (135 mg, 1.0 mmol, 4.0 equiv.) and (E)-methyl
3-phenyl-2-[(N-phenylacetamido)methyl]acrylate 4a (77 mg,
0.25 mmol, 1.0 equiv.) for 2 h. FC (pentane/acetone=10/1)
gave the desired product 5i as a colorless oil; yield: 82 mg
(82%). 1H NMR (300 MHz, CDCl3, 300 K): d=7.35–7.32
(m, 3H, CHarom), 7.13–7.12 (m, 5H, CHarom), 6.98–6.91 (m,
4H, CHarom), 6.30 (d, J=6.7 Hz, 1H, CHarom), 6.16 (s, 1H,
CHarom), 4.58 (s, 2H, CH2), 3.46 (s, 3H, CH3), 2.07 (s, 3H,
CH3), 1.72 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3, 300 K):
d=170.2 (C), 169.7 (C), 148.7 (C), 142.0 (C), 141.4 (C),
139.1 (C), 137.6 (C), 129.5 (CH), 129.1 (CH), 129.0 (CH),
128.4 (CH), 128.1 (CH), 128.1 (CH), 128.1 (C), 128.0 (CH),
127.9 (CH), 127.8 (CH), 125.7 (CH), 51.8 (CH3), 48.2 (CH2),
22.6 (CH3), 21.3 (CH3); HR-MS (ESI): m/z=422.1727,
calcd. for C26H25NO3Na [M+Na]+: 422.1732; IR (neat): n=
2948w, 1723s, 1662s, 1595m, 1495m, 1387m, 1286s, 1261s,
1119m cmÀ1.
0.25 mmol, 1.0 equiv.) for 2 h. FC (pentane/acetone=10/1)
gave the desired product 9a as a yellow solid (yield: 43 mg,
53%) along with 9b as a yellow solid (yield: 33 mg, 41%).
9a: mp 908C; 1H NMR (300 MHz, CDCl3, 300 K): d=
7.20–7.18 (m, 3H, CHarom), 7.09–7.00 (m, 6H, CHarom), 5.99
(s, 1H, NH), 4.11 (d, J=5.4 Hz, 2H, CH2), 3.40 (s, 3H,
CH3), 2.26 (s, 3H, CH3), 1.87 (s, 3H, CH3); 13C NMR
(75 MHz, CDCl3, 300 K): d=107.3 (C), 169.8 (C), 150.7 (C),
141.9 (C), 138.4 (C), 136.8 (C), 129.2 (CH), 129.1 (CH),
128.5 (CH), 128.0 (CH), 128.0 (CH), 127.7 (C), 51.7 (CH3),
40.1 (CH2), 23.2 (CH3), 21.2 (CH3); HR-MS (ESI): m/z=
346.1414, calcd. for C20H21NO3Na [M+Na]+: 346.1419; IR
(neat): n=2948w, 1714s, 1651s, 1546s, 1433m, 1275s, 1236s,
1126s cmÀ1.
9b: mp 1348C; 1H NMR (300 MHz, CDCl3, 300 K): d=
10.57 (d, J=10.7 Hz, 1H, NH), 7.22–7.17 (m, 2H, CHarom),
7.14–7.10 (m, 1H, CHarom), 7.03–6.98 (m, 4H, CHarom), 6.91–
6.89 (m, 2H, CHarom), 5.26 (s, 1H, CH), 3.56 (s, 3H, CH3),
2.23 (s, 3H, CH3), 2.03 (s, 3H, CH3); 13C NMR (75 MHz,
CDCl3, 300 K): d=169.6 (C), 167.9 (C), 142.5 (C), 139.1
(CH), 138.2 (C), 136.1 (C), 129.2 (CH), 128.9 (CH), 128.9
(CH), 128.4 (CH), 126.5 (CH), 112.2 (C), 51.7 (CH3), 50.0
(CH), 23.7 (CH3), 21.0 (CH3); HR-MS (ESI): m/z=
346.1414, calcd. for C20H21NO3Na [M+Na]+: 346.1419; IR
(neat): n=2951w, 1709m, 1683s, 1624s, 1434m, 1194s cmÀ1.
(E)-Methyl
2-{[(tert-butoxycarbonyl)ACTHNGUTERNNU(G phenyl)amino]-
methyl}-3-phenyl-3-(para-tolyl)acrylate (7): According to
the GP with para-tolylboronic acid (135 mg, 1.0 mmol,
4.0 equiv.)
(phenyl)amino]methyl}-3-phenylacrylate
0.25 mmol, 1.0 equiv.) for 16 h. FC (pentane/Et2O=10/1)
and
(E)-methyl
2-{[(tert-butoxycarbonyl)-
ACHTUNGTRENNUNG
4f (92 mg,
3644
asc.wiley-vch.de
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 3639 – 3647

Oxidative Heck Coupling of Allylic Amines with 2,2,6,6-Tetramethylpiperidine-N-oxyl
(E)-Methyl 2-{[N-(4-methoxyphenyl)acetamido]methyl}-
3-phenyl-3-(para-tolyl)acrylate (10): According to the GP
with para-tolylboronic acid (122 mg, 1.0 mmol, 4.0 equiv.)
and (E)-methyl 2-{[N-(4-methoxyphenyl)acetamido]methyl}-
3-phenylacrylate 4i (85 mg, 0.25 mmol, 1.0 equiv.) for 2 h.
FC (pentane/acetone=10/1) gave the desired product 10 as
a colorless oil; yield: 96 mg (89%). 1H NMR (300 MHz,
CDCl3, 300 K): d=7.22–7.20 (m, 3H, CHarom), 7.12 (d, J=
8.0 Hz, 2H, CHarom), 7.12–7.01 (m, 2H, CHarom), 6.94–6.91
(m, 4H, CHarom), 6.47 (d, J=8.0 Hz, 2H, CHarom), 4.65 (s,
2H, CH2), 3.85 (s, 3H, CH3), 3.52 (s, 3H, CH3), 2.28 (s, 3H,
CH3), 1.80 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3, 300 K):
d=170.7 (C), 169.8 (C), 159.2 (C), 148.8 (C), 141.4 (C),
137.4 (C), 136.4 (C), 134.7 (C), 130.0 (CH), 128.7 (CH),
128.7 (CH), 128.2 (CH), 128.0 (CH), 128.0 (C), 127.8 (CH),
114.5 (CH), 51.9 (CH3), 48.3 (CH2), 22.6 (CH3), 21.2 (CH3);
HR-MS (ESI): m/z=452.1832, calcd. for C27H27NO4Na [M+
Na]+: 452.1838; IR (neat): n=2947w, 1723s, 1661s, 1510s,
1247s, 1121s cmÀ1.
(Z)-Methyl 3-phenyl-2-[(N-phenylacetamido)methyl]-3-
(para-tolyl)acrylate (13): According to the GP with phenyl-
boronic acid (122 mg, 1.0 mmol, 4.0 equiv.) and (E)-methyl
2-[(N-phenylacetamido)methyl]-3-(p-tolyl)-acrylate
4c
(81 mg, 0.25 mmol, 1.0 equiv.) for 2 h. FC (pentane/ace-
tone=10/1) gave the desired product 13 as a colorless oil;
1
yield: 95 mg (90%). H NMR (300 MHz, CDCl3, 300 K): d=
7.34–7.32 (m, 3H, CHarom), 7.12–7.01 (m, 5H, CHarom), 6.95
(d, J=8.0 Hz, 2H, CHarom), 6.85 (d, J=8.0 Hz, 2H, CHarom),
6.45–6.42 (m, 2H, CHarom), 4.57 (s, 2H, CH2), 3.50 (s, 3H,
CH3), 2.21 (s, 3H, CH3), 1.74 (s, 3H, CH3); 13C NMR
(75 MHz, CDCl3, 300 K): d=170.3 (C), 169.8 (C), 148.7 (C),
142.0 (C), 139.4 (C), 138.2 (C), 137.8 (C), 129.5 (CH), 129.0
(CH), 128.7 (CH), 128.7 (CH), 128.2 (CH), 128.1 (CH),
128.0 (CH), 127.6 (C), 127.5 (CH), 51.9 (CH3), 48.3 (CH2),
22.6 (CH3), 21.2 (CH3); HR-MS (ESI): m/z=422.1727,
calcd. for C26H25NO3Na [M+Na]+: 422.1732; IR (neat): n=
2948w, 1721s, 1661s, 1387s, 1283s, 1255s, 1119s, 699s cmÀ1.
(E)-Methyl 3-phenyl-2-[(N-phenylacetamido)methyl]-but-
2-enoate (14): According to the GP with phenylboronic acid
(122 mg, 1.00 mmol, 4.00 equiv.) and (E)-methyl 2-((N-phe-
nylacetamido)methyl)but-2-enoate 4d (62 mg, 0.25 mmol,
1.0 equiv.) for 2 h. FC (pentane/acetone=10/1) gave the de-
sired product 14 as a colorless oil; yield: 72 mg (96%).
1H NMR (300 MHz, CDCl3, 300 K): d=7.30–7.28 (m, 3H,
CHarom), 7.09–7.01 (m, 3H, CHarom), 6.95–6.92 (m, 2H,
CHarom), 6.41–6.38 (m, 2H, CHarom), 4.39 (s, 2H, CH2), 3.73
(s, 3H, CH3), 1.97 (s, 3H, CH3), 1.67 (s, 3H, CH3); 13C NMR
(75 MHz, CDCl3, 300 K): d=170.0 (C), 169.3 (C), 146.8 (C),
141.9 (C), 141.0 (C), 129.4 (CH), 128.8 (CH), 128.1 (CH),
127.9 (CH), 127.1 (CH), 126.8 (CH), 126.0 (C), 51.9 (CH3),
47.5 (CH2), 23.4 (CH3), 22.6 (CH3); HR-MS (ESI): m/z=
346.1414, calcd. for C20H21NO3Na [M+Na]+: 346.1419; IR
(neat): n=2948w, 1712s, 1656s, 1495s, 1391s, 1304s, 1283s,
1255s, 1062s cmÀ1.
(E)-Methyl
2-[(N-benzylacetamido)methyl]-3-phenyl-3-
(para-tolyl)acrylate (11): According to the GP with para-tol-
ylboronic acid (135 mg, 1.0 mmol, 4.0 equiv.) and (E)-methyl
2-((N-benzylacetamido)methyl)-3-phenylacrylate 4j (80 mg,
0.25 mmol, 1.0 equiv.) for 2 h. FC (pentane/acetone=10/1)
gave the desired product 11 as a yellow oil; yield: 90 mg
(87%). Two rotamers were obtained, the ratio of rotamer
a:rotamer b=1:1. 1H NMR (300 MHz, CDCl3, 300 K): d=
7.29–7.27 (m, 6H, CHarom), 7.18–7.15 (m, 3H, CHarom), 7.08–
7.02 (m, 4H, CHarom), 6.94 (d, J=7.8 Hz, 1H, CHarom), 4.68
(s, 1H, CH2), 4.57 (s, 1H, CH2), 4.46 (s, 1H, CH2), 4.30 (s,
1H, CH2), 3.51 (s, 3H, CH3), 2.32 (s, 3H, CH3), 2.22 (s,
1.5H, CH3), 2.12 (s, 1.5H, CH3); 13C NMR (75 MHz, CDCl3,
300 K): d=171.3 (C), 169.9 (C), 169.4 (C), 149.1 (C), 148.0
(C), 141.6 (C), 141.1 (C), 138.1 (C), 137.7 (C), 137.2 (C),
136.7 (C), 136.4 (C), 136.1 (C), 129.2 (CH), 129.0 (CH),
128.9 (CH), 128.8 (CH), 128.7 (C), 128.6 (CH), 128.5 (CH),
128.5 (CH), 128.3 (CH), 128.1 (CH), 128.0 (CH), 127.9
(CH), 127.7 (CH), 127.4 (CH), 127.1 (CH), 124.6 (CH), 51.8
(CH3), 51.8 (CH3), 51.4 (CH2), 48.2 (CH2), 47.3 (CH2), 45.7
(CH2), 21.6 (CH3), 21.2 (CH3); HR-MS (ESI): m/z=
436.1883, calcd. for C27H27NO3Na [M+Na]+: 436.1889; IR
(neat): n=2947w, 1717s, 1649s, 1416s, 1256s, 1114m, 728s
cmÀ1.
(Z)-N-[2,3-Diphenyl-3-(para-tolyl)allyl]-N-phenylacetam-
ide (15a): According to the GP with para-tolylboronic acid
(122 mg, 1.0 mmol, 4.0 equiv.) and (Z)-N-(2,3-diphenylACHTUNGTRENNUNGallyl)-
N-phenylacetamide 4l (82 mg, 0.25 mmol, 1.0 equiv.) for 2 h.
FC (pentane/acetone=40/1) gave the desired product 15a as
a colorless oil; yield: 100 mg (99%). 1H NMR (300 MHz,
CDCl3, 300 K): d=7.30–7.28 (m, 3H, CHarom), 7.12–7.04 (m,
5H, CHarom), 6.90–6.85 (m, 5H, CHarom), 6.73–6.80 (m, 4H,
CHarom), 6.42 (d, J=7.9 Hz, 2H, CHarom), 4.83 (s, 2H, CH2),
2.22 (s, 3H, CH3), 1.50 (s, 3H, CH3); 13C NMR (75 MHz,
CDCl3, 300 K): d=170.2 (C), 143.0 (C), 142.6 (C), 142.2 (C),
139.5 (C), 139.0 (C), 136.3 (C), 135.9 (C), 130.6 (CH), 130.4
(CH), 129.3 (CH), 129.0 (CH), 128.9 (CH), 128.9 (CH),
128.0 (CH), 127.5 (CH), 127.5 (CH), 126.7 (CH), 126.1
(CH), 50.3 (CH2), 22.6 (CH3), 21.2 (CH3); HR-MS (ESI): m/
z=440.1985, calcd. for C30H27NONa [M+Na]+: 440.1990;
IR (neat): n=3022w, 1656s, 1494m, 1388s, 729s, 698s cmÀ1.
(Z)-N-Phenyl-N-(3-phenyl-2,3-di-para-tolylallyl)acetam-
ide (15b): According to the GP with para-tolylboronic acid
(122 mg, 1.0 mmol, 4.0 equiv.) and (Z)-N-phenyl-N-[3-
phenyl-2-(p-tolyl)allyl]acetamide 4m (85 mg, 0.25 mmol,
1.0 equiv.) for 2 h. FC (pentane/acetone=40/1) gave the de-
sired product 15b as a white solid; yield: 107 mg (99%); mp
1248C. 1H NMR (400 MHz, CDCl3, 300 K): d=7.31–7.29
(m, 3H, CHarom), 7.01 (d, J=8.1 Hz, 2H, CHarom), 6.89–6.86
(m, 7H, CHarom), 6.73–6.69 (m, 4H, CHarom), 6.36 (d, J=
8.0 Hz, 2H, CHarom), 4.80 (s, 2H, CH2), 2.21 (s, 3H, CH3),
(Z)-Methyl
3-(4-chlorophenyl)-3-phenyl-2-[(N-phenyl-
acetamido)methyl]acrylate (12): According to the GP with
phenylboronic acid (122 mg, 1.0 mmol, 4.0 equiv.) and (E)-
methyl 3-(4-chlorophenyl)-2-[(N-phenylacetamido)methyl]-
ACHTUNGTRENNUNGacrylate 4b (86 mg, 0.25 mmol, 1.0 equiv.) for 2 h. FC (pen-
tane/acetone=10/1) gave the desired product 12 as a color-
less oil; yield: 95 mg (95%). 1H NMR (300 MHz, CDCl3,
300 K): d=7.34–7.31 (m, 3H, CHarom), 7.12–7.04 (m, 7H,
CHarom), 6.91–6.88 (m, 2H, CHarom), 6.45–6.41 (m, 2H,
CHarom), 4.57 (s, 2H, CH2), 3.50 (s, 3H, CH3), 1.72 (s, 3H,
CH3); 13C NMR (75 MHz, CDCl3, 300 K): d=170.2 (C),
169.4 (C), 147.2 (C), 141.9 (C), 139.5 (C), 138.7 (C), 133.9
(C), 129.6 (CH), 129.6 (CH), 128.9 (CH), 128.7 (C), 128.6
(CH), 128.3 (CH), 128.2 (CH), 128.2 (CH), 127.9 (CH), 52.0
(CH3), 48.2 (CH2), 22.7 (CH3); HR-MS (ESI): m/z=
442.1180, calcd. for C25H22ClNO3Na [M+Na]+: 442.1186; IR
(neat): n=2948w, 1722s, 1661s, 1494s, 1387s, 1281s, 1254s,
1120s cmÀ1.
Adv. Synth. Catal. 2013, 355, 3639 – 3647
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3645

Zhiheng He et al.
FULL PAPERS
2.19 (s, 3H, CH3), 1.51 (s, 3H, CH3); 13C NMR (100 MHz,
CDCl3, 300 K): d=170.2 (C), 142.8 (C), 142.6 (C), 142.2 (C),
139.6 (C), 136.3 (C), 136.2 (C), 135.8 (C), 135.8 (C), 130.5
(CH), 130.3 (CH), 129.3 (CH), 129.1 (CH), 128.9 (CH),
128.8 (CH), 128.3 (CH), 128.0 (CH), 127.5 (CH), 126.0
(CH), 50.1 (CH2), 22.7 (CH3), 21.3 (CH3), 21.2 (CH3); HR-
MS (ESI): m/z=454.2141, calcd. for C31H29NONa [M+
Na]+: 454.2147; IR (neat): n=3024w, 1655s, 1494m, 1389s,
729s cmÀ1.
5218; e) K. S. Yoo, C. H. Yoon, K. W. Jung, J. Am.
Chem. Soc. 2006, 128, 16384–16393; f) J. Lindh, P. En-
quist, A. Pilotti, P. Nilsson, M. Larhed, J. Org. Chem.
2007, 72, 7957–7962; g) J. H. Delcamp, A. P. Brucks,
M. C. White, J. Am. Chem. Soc. 2008, 130, 11270–
11271; h) E. W. Werner, M. S. Sigman, J. Am. Chem.
Soc. 2010, 132, 13981–13983; i) Y. Liu, D. Li, C.-M.
Park, Angew. Chem. 2011, 123, 7471–7474; Angew.
Chem. Int. Ed. 2011, 50, 7333–7336; j) L. Zhang, C.
Dong, C. Ding, J. Chen, W. Tang, H. Li, L. Xu, J. Xiao,
Adv. Synth. Catal. 2013, 355, 1570–1578; k) S. Sakagu-
chi, K. S. Yoo, J. OꢄNeill, J. H. Lee, T. Stewart, K. W.
Jung, Angew. Chem. 2008, 120, 9466–9469; Angew.
Chem. Int. Ed. 2008, 47, 9326–9329; l) S. E. Walker, J.
Boehnke, P. E. Glen, S. Levey, L. Patrick, J. A. Jordan-
Hore, A.-L. Lee, Org. Lett. 2013, 15, 1886–1889; m) J.
Ruan, X. Li, O. Saidi, J. Xiao, J. Am. Chem. Soc. 2008,
130, 2424–2425; n) P. Sun, Y. Zhu, H. Yang, H. Yan, L.
Lu, X. Zhang, J. Mao, Org. Biomol. Chem. 2012, 10,
4512–4515; o) Y. Su, N. Jiao, Org. Lett. 2009, 11, 2980–
2983.
(Z)-N-[2-(4-Chlorophenyl)-3-phenyl-3-(para-tolyl)allyl]-
N-phenylacetamide (15c): According to the GP with p-tolyl-
boronic acid (122 mg, 1.0 mmol, 4.0 equiv.) and (Z)-N-(2-(4-
chlorophenyl)-3-phenylallyl)-N-phenylacetamide 4n (90 mg,
0.25 mmol, 1.0 equiv.) for 2 h. FC (pentane/acetone=40/1)
gave the desired product 15c as a white solid; yield: 111 mg
1
(99%); mp 1258C. H NMR (400 MHz, CDCl3, 300 K): d=
7.32–7.30 (m, 3H, CHarom), 7.06–7.05 (m, 4H, CHarom), 6.90–
6.87 (m, 5H, CHarom), 6.72–6.67 (m, 4H, CHarom), 6.37 (d, J=
8.0 Hz, 2H, CHarom), 4.81 (s, 2H, CH2), 2.21 (s, 3H, CH3),
1.52 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3, 300 K): d=
170.3 (C), 143.8 (C), 142.2 (C), 142.0 (C), 139.2 (C), 137.5
(C), 136.5 (C), 134.7 (C), 132.5 (C), 132.0 (CH), 130.3 (CH),
129.4 (CH), 128.9 (CH), 128.9 (CH), 128.7 (CH), 128.2
(CH), 127.8 (CH), 127.7 (CH), 126.4 (CH), 50.0 (CH2), 22.6
(CH3), 21.2 (CH3); HR-MS (ESI): m/z=474.1595, calcd. for
C30H26NClONa [M+Na]+: 474.1601; IR (neat): n=3024w,
1655s, 1494m, 1389s, 729s cmÀ1.
[4] a) K. Itami, T. Kamei, J.-i. Yoshida, J. Am. Chem. Soc.
2003, 125, 14670–14671; b) C. Zhou, R. C. Larock, J.
Org. Chem. 2005, 70, 3765–3777; c) M. Shimizu, C. Na-
kamaki, K. Shimono, M. Schelper, T. Kurahashi, T.
Hiyama, J. Am. Chem. Soc. 2005, 127, 12506–12507;
d) Z. Tan, E.-i. Negishi, Angew. Chem. 2006, 118, 776–
779; Angew. Chem. Int. Ed. 2006, 45, 762–765; e) J.
Simard-Mercier, A. B. Flynn, W. W. Ogilvie, Tetrahe-
dron 2008, 64, 5472–5481; f) N. Ishida, Y. Shimamoto,
M. Murakami, Org. Lett. 2009, 11, 5434–5437; g) K.
Endo, M. Hirokami, T. Shibata, J. Org. Chem. 2010, 75,
3469–3472; h) Y. Nishihara, Y. Okada, J. Jiao, M. Suet-
sugu, M.-T. Lan, M. Kinoshita, M. Iwasaki, K. Takagi,
Angew. Chem. 2011, 123, 8819–8823; Angew. Chem.
Int. Ed. 2011, 50, 8660–8664.
Supporting Information
1
Copies of the H NMR and 13C NMR spectra for all com-
pounds and experimental procedures and physical data of
the protected allylic amines 4a–4o are available in the Sup-
porting Information.
Acknowledgements
[5] Z. He, S. Kirchberg, R. Frçhlich, A. Studer, Angew.
Chem. 2012, 124, 3759–3762; Angew. Chem. Int. Ed.
2012, 51, 3699–3702.
We thank the Chinese Scholarship Council for supporting
this work (stipenduium to Z.H.).
[6] Reviews on the use of TEMPO in synthesis: a) T.
Vogler, A. Studer, Synthesis 2008, 1979–1993; b) L.
Tebben, A. Studer, Angew. Chem. 2011, 123, 5138–
5174; Angew. Chem. Int. Ed. 2011, 50, 5034–5068; S.
Wertz, A. Studer, Green Chem. 2013, 15, 3116–3134.
[7] Use of TEMPO Pd-catalyzed oxidative couplings: a) S.
Kirchberg, T. Vogler, A. Studer, Synlett 2008, 2841–
2846; b) S. Kirchberg, R. Frçhlich, A. Studer, Angew.
Chem. 2009, 121, 4299–4302; Angew. Chem. Int. Ed.
2009, 48, 4235–4238; c) S. Kirchberg, R. Frçhlich, A.
Studer, Angew. Chem. 2010, 122, 7029–7032; Angew.
Chem. Int. Ed. 2010, 49, 6877–6880.
References
[1] a) R. F. Heck, Org. React. 1982, 27, 345–390; b) I. P. Be-
letskaya, A. V. Cheprakov, Chem. Rev. 2000, 100, 3009–
3066; c) M. Oestreich, The Mizoroki–Heck reaction,
Wiley, Chichester, 2009; d) V. Coeffard, P. J. Guiry,
Curr. Org. Chem. 2010, 14, 212–229; e) J. Ruan, J. Xiao,
Acc. Chem. Res. 2011, 44, 614–626; f) D. McCartney,
P. J. Guiry, Chem. Soc. Rev. 2011, 40, 5122–5150.
[2] B. Karimi, H. Behzadnia, D. Elhamifar, P. F. Akhavan,
F. K. Esfahani, A. Zamani, Synthesis 2010, 1399–1427.
[3] Oxidative Heck reactions using arylboronic acid deriva-
tives: a) X. Du, M. Suguro, K. Hirabayashi, A. Mori, T.
Nishikata, N. Hagiwara, K. Kawata, T. Okeda, H. F.
Wang, K. Fugami, M. Kosugi, Org. Lett. 2001, 3, 3313–
3316; b) J. P. Parrish, Y. C. Jung, S. I. Shin, K. W. Jung,
J. Org. Chem. 2002, 67, 7127–7130; c) Y. C. Jung, R. K.
Mishra, C. H. Yoon, K. W. Jung, Org. Lett. 2003, 5,
2231–2234; d) M. M. S. Andappan, P. Nilsson, H. von
Schenck, M. Larhed, J. Org. Chem. 2004, 69, 5212–
[8] H. S. Lee, K. H. Kim, S. H. Kim, J. N. Kim, Adv. Synth.
Catal. 2012, 354, 2419–2426.
[9] G. Martelli, M. Orena, S. Rinaldi, Eur. J. Org. Chem.
2011, 7199–7206.
[10] D. Basavaiah, B. S. Reddy, S. S. Badsara, Chem. Rev.
2010, 110, 5447–5674.
[11] CCDC 961205 (5a) contains the supplementary crystal-
lographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif.
3646
asc.wiley-vch.de
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 3639 – 3647

Oxidative Heck Coupling of Allylic Amines with 2,2,6,6-Tetramethylpiperidine-N-oxyl
[12] CCDC 967270 (15c) contains the supplementary crys-
tallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif.
tion b-H- elimination can also occur at the methyl sub-
stituent under formation of the methylene which can
then act as a substrate for a second arylation.
[14] In an NMR experiment we mixed PdACTHNURTGNENG(U OAc)2 in pro-
pionic acid and observed the complete formation of
(EtCO2)2Pd.
[13] According to mass spectrometric analysis double aryla-
tion product was also formed. In the initial Heck reac-
Adv. Synth. Catal. 2013, 355, 3639 – 3647
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3647