Rhodium-catalyzed carbometalation of ynamides with organoboron reagents

Article abstract of DOI:10.1016/j.tet.2010.06.021

In the presence of catalytic [Rh(cod)(MeCN)₂]BF₄, ynamides undergo carbometalation with boronic acids, arylboronic esters, and triarylboroxines. These reactions enable the regio- and stereocontrolled synthesis of multisubstituted ena

Full text of DOI:10.1016/j.tet.2010.06.021

Tetrahedron 66 (2010) 6026e6031
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Rhodium-catalyzed carbometalation of ynamides with organoboron reagents
*
Benoit Gourdet, Donna L. Smith, Hon Wai Lam
School of Chemistry, University of Edinburgh, Joseph Black Building, The King’s Buildings, West Mains Road, Edinburgh EH9 3JJ, United Kingdom
a r t i c l e i n f o
a b s t r a c t
Article history:
In the presence of catalytic [Rh(cod)(MeCN)2]BF4, ynamides undergo carbometalation with boronic acids,
arylboronic esters, and triarylboroxines. These reactions enable the regio- and stereocontrolled synthesis
of multisubstituted enamides.
Received 12 April 2010
Accepted 7 June 2010
Available online 12 June 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
a process for preparing multisubstituted enamides.13 In this arti-
cle, the successful implementation of this strategy is described.
As a result of the increasing interest in the chemistry of enam-
ides,1 we recently initiated a program to address limitations asso-
ciated with the synthesis of more highly substituted congeners.2
These studies resulted in the development of rhodium-catalyzed
carbozincations of ynamides3 using organozinc reagents.2 Virtues
2. Results and discussion
Reactions between oxazolidin-2-one-substituted ynamides and
arylboronic acids were used to evaluate various metal precatalysts
and reaction conditions. These experiments led to the finding that
heating a mixture of ynamide, arylboronic acid (2.0 equiv), and [Rh
(cod)(MeCN)2]BF4 (8 mol %) in 20:1 THF/H2O for 10 min at 90 ꢀC
under microwave irradiation was effective in promoting carbome-
talation.14 Representative results using these conditions are pre-
sented in Table 1.
of these processes include the preparation of
b,b
0-disubstituted and
a,b,b
0-trisubstituted enamides with high levels of regio- and ster-
eocontrol, and the ability to employ organozinc halides containing
moderately base- and nucleophile-sensitive functional groups.4
To increase the range of enamides accessible through ynamide
carbometalation reactions further, we became interested in the
development of new catalytic protocols employing organometal-
lics that exhibit even greater functional group compatibility.
Boronic acids, boronic esters, and boroxines are attractive candi-
dates, given their ready availability and high stability to air and
moisture.5 In this regard, metal-catalyzed hydroarylations of
alkynes using arylboron compounds have been studied in some
depth.6e11 With unsymmetrical alkynes, control of regioselectivity
is one of the principal challenges, and high regioselectivities are
typically observed when there are substantial differences in the
steric and/or electronic properties between the two substituents
attached to the alkyne. The use of a directing group in the sub-
strate7b,c,8c,12 is another tactic to control regioselectivity, and it was
our hope that the directing effect of the carbonyl group of yna-
mides as proposed in previous ynamide carbometalation pro-
cedures2,4 could also be beneficial in carbometalation reactions
involving organoboron reagents. To our knowledge, the simple
carbometalation of ynamides using organoboron compounds has
not been described previously, despite the potential utility of such
In addition to phenylboronic acid, which resulted in enamides
2a, 2e, and 2h, the process tolerated arylboronic acids containing
electron-donating (products 2b and 2c) or electron-withdrawing
substituents (products 2f, 2g, 2i, and 2l). Sterically hindering ortho-
substitution on the arylboronic acid was also tolerated, though
yields were slightly diminished (products 2d and 2j). The sense of
regioselection observed in these reactions was as expected, with
the aryl group introduced distal to the ynamide nitrogen atom in
regioisomeric ratios ranging from modest (6:1 rr) to high (>19:1).
Regarding the scope of the ynamide, oxazolidin-2-one-containing
substrates with aliphatic or aromatic substituents underwent the
reaction with comparable efficiency, though with 1a, small quan-
tities of the imide 3a (Fig. 1) resulting from hydration of the yna-
mide were sometimes observed (with products 2a, 2b, and 2d).
Pyrrolidin-2-one-containing ynamides, such as 1d proved to be
inferior to oxazolidin-2-one-substituted ynamides 1aec, which
was surprising in light of related Rh-catalyzed ynamide carbo-
zincations.2 For example, carbometalation of 1d with 4-acetyl-
phenylboronic acid produced a complex mixture of products from
which 2l was isolated in only 25% yield. Acyclic ynamides, such as
1e were not effective substrates; although carbometalation was
successful, regioselectivity was negligible. Similar behavior has
* Corresponding author. Tel.: þ44 131 650 4831; fax: þ44 131 650 6453; e-mail
address: h.lam@ed.ac.uk (H.W. Lam).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.06.021

B. Gourdet et al. / Tetrahedron 66 (2010) 6026e6031
6027
Table 1
Rhodium-catalyzed carbometalation of ynamides with arylboronic acidsa
O
O
OTBS
O
O
R
N
O
ArB(OH)2 (2 equiv)
Ar
[Rh(cod)(MeCN)2]BF4 (8 mol %)
X
N
X
N
3a
20:1 THF/H2O,10 min
90 °C (microwave)
R
1a-1d
2a-2l
Figure 1. Side-product resulting from hydration of ynamide 1a.
Ynamides
Ph
been documented previously in related rhodium-catalyzed carbo-
zincations of ynamides.2
O
O
R
Ph
Boc
1a R = CH2CH2OTBS
1b R = CH2CH2Ph
1c R = Ph
N
O
N
N
Boronic acids containing non-benzene groups are also viable
reagents in this process. For example, carbometalation of ynamide
1a with 2-furanboronic acid proceeded smoothly to give enamide
2m as the only observable regioisomer in 66% yield (Scheme 1),
while the use of (E)-2-phenylvinylboronic acid gave dienamide 2n
in 52% yield.
Ph
1d
1e
OMe
O
O
Ph
N
O
N
O
OTBS
OTBS
2a
(2 equiv)
2b
O
O
(HO)2B
[Rh(cod)(MeCN)2]BF4 (8 mol %)
>19:1 rr, 63%b
>19:1 rr, 75%c
O
O
O
N
20:1 THF/H2O,10 min
90 °C (microwave)
OTBS
2m
Me
>19:1 rr, 66%
O
1a
O
as above with
(HO)2B
O
Ph
O
N
O
Ph
N
OTBS
2c
N
O
OTBS
2n
OTBS
6:1 rr, 52%
2d
14:1 rr, 61%
8:1 rr, 46%d
Scheme 1. Rhodium-catalyzed ynamide carbometalation with heteroaryl and alke-
nylboronic acids. rr¼Regioisomeric ratio as determined by 1H NMR analysis of the
unpurified reaction mixtures. Cited yields are of isolated major regioisomers.
COMe
O
O
Ph
Ph
O
N
O
N
Next, the use of organoboron reagents other than boronic acids
was explored. Pleasingly, arylboronic esters and triarylboroxines
were found to be competent arylating reagents under conditions
identical to those employed using arylboronic acids, as demon-
strated by the formation of enamides 2g and 2a. (Scheme 2, Eq. 1
and 2, respectively, compare with results in Table 1). However,
attempted carbometalation of ynamide 1a with potassium phe-
nyltrifluoroborate was unrewarding, providing a complex mixture
of products.15
Ph
2e
2f
10:1 rr, 89%
6:1 rr, 60%
CO2Et
O
O
Ph
Ph
O
N
O
N
Ph
2h
2g
CO2Et
7:1 rr, 56%
67%e
(2.0 equiv)
CO2Et
(1)
O
(pin)B
Me
Cl
O
O
[Rh(cod)(MeCN)2]BF4 (8 mol %)
1b
O
O
N
20:1 THF/H2O,10 min
90 °C (microwave)
O
N
O
N
Ph
2g
Ph
Ph
16:1 rr, 53%
O
2j
2i
65%e
10:1 rr, 53%
(PhBO)3 (1.0 equiv)
[Rh(cod)(MeCN)2]BF4 (8 mol %)
Ph
Cl
1a
(2)
N
COMe
20:1 THF/H2O,10 min
90 °C (microwave)
O
Oi-Pr
O
O
OTBS
2a
11:1 rr, 58%
N
2l
N
Ph
Scheme 2. Rhodium-catalyzed ynamide carbometalation with an arylboronic ester
and triphenylboroxine. rr¼Regioisomeric ratio as determined by 1H NMR analysis of
the unpurified reaction mixtures. Cited yields are of isolated major regioisomers.
Ph
2k
>19:1 rr, 82%
25%e
By analogy with related processes,7 a possible catalytic cycle for
these reactions is illustrated in Scheme 3. Presumably, a rhodium(I)
hydroxide species 4 is generated under the reaction conditions,
which can undergo transmetalation with the organoboron com-
pound to provide organorhodium intermediate 5. A carbonyl-di-
rected12 syn-carborhodation of 5 with the ynamide 1 would then
result in chelated alkenylrhodium species 6. Finally, protonation of
6 with water would release the product 2 and regenerate 4.
rr¼Regioisomeric ratio as determined by1H NMR analysis of the unpurifiedreaction
a
mixtures. Unless otherwise indicated, cited yields are of isolated major regioisomers.
b
Isolated as an 8:1 inseparable mixture of 2a and the imide 3a (Fig. 1). Cited yield
of 2a has been adjusted to reflect this impurity.
c
Isolated as a 16:1 inseparable mixture of 2b and the imide 3a (Fig. 1). Cited yield
of 2b has been adjusted to reflect this impurity.
d
Isolated as a 13:1 inseparable mixture of 2d and the imide 3a (Fig. 1). Cited yield
of 2d has been adjusted to reflect this impurity.
e
The regioisomeric ratio could not be determined with accuracy.

6028
B. Gourdet et al. / Tetrahedron 66 (2010) 6026e6031
254 nm, and subsequently developed using potassium permanga-
[Rh(cod)(MeCN)2]BF4
O
H
nate or ceric ammonium molybdate solution as appropriate. Flash
R1
H2O
X
N
column chromatography was carried out using silica gel (Fisher
R1B(OH)2
or R1B(pin)
or (R1BO)3
ꢀ
R3
Scientific 60 A particle size 35e70
mm). Melting points were recor-
2
LnRh
4
OH
ded on a Gallenkamp melting point apparatus and are uncorrected.
Infra-red spectra were recorded on a Jasco FT/IR-460 Plus in-
strument as a thin film on sodium chloride plates or as a dilute so-
lution in CHCl3. 1H NMR spectra were recorded on a Bruker AV500
(500 MHz), a Bruker DMX500 (500 MHz) spectrometer, a Bruker
DPX360 (360 MHz) spectrometer, or a Bruker ARX250 (250 MHz)
(R2O)2B OH
H2O
X
O
RhLn
R1
LnRh
5
R1
spectrometer. Chemical shifts (d) are quoted in parts per million
N
(ppm) downfield of tetramethylsilane, using residual protonated
solvent as internal standard (CDCl3 at 7.27 ppm). Abbreviations used
in the description of resonances are: s (singlet), d (doublet), t (trip-
let), q, (quartet), app (apparent), br (broad). Coupling constants (J)
are quoted to the nearest 0.1 Hz. Proton-decoupled 13C NMR spectra
were recorded on a Bruker AV500 (125.8 MHz) spectrometer,
a Bruker DPX360 (90.6 MHz) spectrometer, or a Bruker ARX250
R3
R3
6
O
N
X
1
Scheme 3. Possible catalytic cycle.
(62.9 MHz) spectrometer. Chemical shifts (d) are quoted in parts per
In seminal work by Hayashi and co-workers describing related
alkyne hydroarylations,7a alkenylrhodium intermediates analogous
to 6 were found to undergo 1,4-rhodium migration16 from the
alkenyl position to an ortho-position of the phenyl group, as sug-
gested by deuterium labeling studies. To establish whether this
pathway is significant in the reactions described herein, carbome-
talation of ynamide 1a with triphenylboroxine was conducted in
20:1 THF/D2O (Eq. 3). In addition to providing a small quantity of
the imide 3b (mixture of isotopologues) resulting from hydration of
1a, this experiment provided enamide 7 with >97% deuterium
incorporation at the alkenyl position.17 This result suggests that 1,4-
rhodium migration does not occur to any considerable extent.
Presumably, the extra stability conferred onto alkenylrhodium 6
through chelation with the carbonyl group disfavors rhodium
migration.7c
million (ppm) downfield of tetramethylsilane, using deuterated
solvent as internal standard (CDCl3 at 77.0 ppm). Assignments were
made using the DEPT sequence with secondary pulses at 90ꢀ and
135ꢀ. High resolution mass spectrawererecorded on a Finnigan MAT
900 XLT spectrometer or a Finnigan MAT 95XP spectrometer at the
EPSRC National Mass Spectrometry Service Centre, University of
Wales, Swansea, or on a Finnigan MAT 900 XLT spectrometer at the
School of Chemistry, University of Edinburgh. Microwave reactions
were performed using a Biotage microwave synthesizer. Ynamides
1aee were prepared as described previously.2a
4.2. Rhodium-catalyzed carbometalation of ynamides with
organoboron reagents: general procedure
A solution of the appropriate ynamide (0.40 mmol), the orga-
>97:3 D/H
noboron reagent (1.0e2.0 equiv), and [Rh(cod)(MeCN)2]BF4 (12 mg,
0.032 mmol) in THF (2 mL) and H2O (100 m
L) was heated at 90 ꢀC
O
D
for 10 min under microwave irradiation. Saturated aqueous
NaHCO3 solution (5 mL) was added and the mixture was extracted
with CH2Cl2 (3ꢁ10 mL). The combined organic layers were dried
(MgSO4), filtered, and concentrated in vacuo. Purification of the
residue by column chromatography gave the desired enamide.
O
O
N
OTBS
(PhBO)3 (1.0 equiv)
7, 59%
[Rh(cod)(MeCN)2]BF4 (8 mol %)
(3)
1a
+
20:1 THF/D2O,10 min
90 °C (microwave)
O
O
4.2.1. With boronic acids.
OTBS
N
4.2.1.1. 3-[(E)-4-(tert-Butyldimethylsilyloxy)-2-phenylbut-1-enyl]
oxazolidin-2-one (2a). The general procedure was followed using
ynamide 1a (108 mg, 0.40 mmol) and phenylboronic acid (98 mg,
0.80 mmol). Purification by column chromatography (10% EtOAc/
hexane/20% EtOAc/hexane) gave an 8:1 inseparable mixture of
the enamide 2a and the imide 3a as a pale orange oil (96 mg, 63%,
adjusted yield of 2a).
(H)D D(H)
3b, 12%
3. Conclusion
In summary, rhodium catalysis enables the carbometalation of
ynamides using a range of organoboron reagents, including aryl,
heteroaryl, and alkenylboronic acids, arylboronic esters, and triar-
ylboroxines. This work further contributes to the growing number
of methods for the synthesis of multisubstituted enamides in regio-
and stereocontrolled fashion.2,4
Data for 2a: Rf¼0.78 (60% EtOAc/hexane); IR (film) 2928, 2857,
1755 (C]O), 1653, 1471, 1297, 1257, 1042, 733 cmꢂ1 1H NMR
;
(360 MHz, CDCl3)
d 7.35e7.25 (5H, m, ArH), 6.61 (1H, s, ]CH), 4.43
(2H, app dd, J¼9.0, 6.9 Hz, CH2O), 4.13 (2H, app dd, J¼9.0, 6.9 Hz,
CH2N), 3.61 (2H, t, J¼6.5 Hz, CH2OSi), 2.83 (2H, t, J¼6.5 Hz, ]CCH2),
0.84 (9H, s, SiC(CH3)3), ꢂ0.05 (6H, s, Si(CH3)2); 13C NMR (62.9 MHz,
CDCl3)
d
157.3 (C), 140.5 (C), 128.3 (2ꢁCH), 127.2 (CH), 126.8 (2ꢁCH),
4. Experimental
4.1. General
126.3 (C), 123.8 (CH), 62.4 (CH2), 61.1 (CH2), 46.2 (CH2), 32.7 (CH2),
25.8 (3ꢁCH3), 18.2 (C), ꢂ5.5 (2ꢁCH3); HRMS (ES) exact mass calcd
for C19H30NO3Si [MþH]þ: 348.1989, found: 348.1992.
THF was dried and purified bypassage through activated alumina
columns using a solvent purification system. All commercially
available reagents were used as received. Thin layer chromatogra-
phy (TLC) was performed on Merck DF-Alufoilien 60F254 0.2 mm
precoated plates. Product spots were visualized by UV light at
4.2.1.2. 3-[(E)-4-(tert-Butyldimethylsilyloxy)-2-(4-methoxy-
phenyl)but-1-enyl]oxazolidin-2-one (2b). The general procedure
was followed using ynamide 1a (108 mg, 0.40 mmol) and 4-
methoxyphenylboronic acid (122 mg, 0.80 mmol). Purification by
column chromatography (15% EtOAc/hexane) gave
a 16:1

B. Gourdet et al. / Tetrahedron 66 (2010) 6026e6031
6029
inseparable mixture of the enamide 2b and the imide 3a as a pale
orange oil (119 mg, 75%, adjusted yield of 2b).
(2ꢁCH), 126.0 (CH), 122.5 (CH), 62.2 (CH2), 46.9 (CH2), 34.2 (CH2),
31.5 (CH2); HRMS (ES) exact mass calcd for C19H23N2O2 [MþNH4]þ:
311.1754, found: 311.1748.
Data for 2b: Rf¼0.72 (60% EtOAc/hexane); IR (film) 2929, 2857,
1747 (C]O), 1654, 1470, 1300, 1248, 1037, 733 cmꢂ1 1H NMR
;
(360 MHz, CDCl3)
d
7.26 (2H, d, J¼8.8 Hz, ArH), 6.85 (2H, d, J¼8.8 Hz,
4.2.1.6. 3-[(E)-2-(4-Acetylphenyl)-4-phenylbut-1-enyl]ox-
azolidin-2-one (2f). The title compound was prepared according to
general procedure using ynamide 1b (86 mg, 0.40 mmol) and 4-
acetylphenylboronic acid (131 mg, 0.80 mmol) and purified by
column chromatography (12% EtOAc/hexane/25% EtOAc/hexane)
to give an orange solid (81 mg, 60%). Rf ¼ 0.47 (60% EtOAc/hexane);
mp 116e118 ꢀC; IR (CHCl3) 2985, 2920, 1759 (C]O), 1679 (C]O),
ArH), 6.50 (1H, s, ]CH), 4.42 (2H, app dd, J¼8.9, 7.0 Hz, CH2O), 4.08
(2H, app dd, J¼8.9, 7.0 Hz, CH2N), 3.81 (3H, s, OCH3), 3.60 (2H, t,
J¼6.5 Hz, CH2OSi), 2.79 (2H, t, J¼6.5 Hz, ]CCH2), 0.84 (9H, s, SiC
(CH3)3), ꢂ0.05 (6H, s, Si(CH3)2); 13C NMR (62.9 MHz, CDCl3)
d 158.9
(C), 157.4 (C), 132.7 (C), 127.9 (2ꢁCH), 126.9 (C), 122.6 (CH), 113.7
(2ꢁCH), 62.4 (CH2), 61.1 (CH2), 55.2 (CH3), 46.4 (CH2), 32.8 (CH2),
25.8 (3ꢁCH3), 18.2 (C), ꢂ5.5 (2ꢁCH3); HRMS (ES) exact mass calcd
for C20H32NO4Si [MþH]þ: 378.2095, found: 378.2103.
1479, 1404, 1212, 1087, 910, 731 cmꢂ1
;
1H NMR (500 MHz, CDCl3)
d
7.97e7.95 (2H, m, ArH), 7.50e7.48 (2H, m, ArH), 7.30e7.27 (2H, m,
ArH), 7.22e7.18 (1H, m, ArH), 7.13e7.11 (2H, m, ArH), 6.56 (1H, s, ]
CH), 4.34e4.31 (2H, m, CH2O), 3.66e3.63 (2H, m, CH2N), 2.91 (2H, t,
J¼7.6 Hz, CH2CH2Ph), 2.68 (2H, t, J¼7.6 Hz, CH2CH2Ph), 2.62 (3H, s,
4.2.1.3. 3-[(E)-4-(tert-Butyldimethylsilyloxy)-2-p-tolylbut-1-enyl]
oxazolidin-2-one (2c). The title compound was prepared according
to the general procedure using ynamide 1a (108 mg, 0.40 mmol)
and 4-tolylboronic acid (109 mg, 0.80 mmol) and purified by col-
umn chromatography (15% EtOAc/hexane/20% EtOAc/hexane) to
give a pale orange oil (89 mg, 61%). Rf¼0.81 (60% EtOAc/hexane); IR
(film) 2928, 2857, 1754 (C]O), 1654, 1481, 1297, 1257, 1042,
CH3); 13C NMR (125.8 MHz, CDCl3)
d 197.5 (C), 156.9 (C), 145.2 (C),
141.0 (C), 135.9 (C), 128.7 (2ꢁCH), 128.4 (4ꢁCH), 128.3 (C), 126.8
(2ꢁCH), 126.2 (CH), 124.3 (CH), 62.3 (CH2), 45.7 (CH2), 34.4 (CH2),
31.1 (CH2), 26.6 (CH3); HRMS (ES) exact mass calcd for C21H22NO3
[MþH]þ: 336.1594, found: 336.1592.
778 cmꢂ1
;
1H NMR (360 MHz, CDCl3)
d
7.23 (2H, d, J¼8.1 Hz, ArH),
7.13 (2H, d, J¼8.1 Hz, ArH), 6.57 (1H, s, ]CH), 4.43 (2H, app dd,
J¼8.9, 7.0 Hz, CH2O), 4.11 (2H, app dd, J¼8.9, 7.0 Hz, CH2N), 3.61 (2H,
t, J¼6.5 Hz, CH2OSi), 2.82 (2H, t, J¼6.5 Hz, ]CCH2), 2.35 (3H, s,
ArCH3), 0.85 (9H, s, SiC(CH3)3), ꢂ0.04 (6H, s, Si(CH3)2); 13C NMR
4.2.1.7. 4-{1-[1-(2-Oxooxazolidin-3-yl)meth-(E)-ylidene]-3-phe-
nylpropyl}benzoic acid ethyl ester (2g). The title compound was
prepared according to the general procedure using ynamide 1b
(86 mg, 0.40 mmol) and 4-ethoxycarbonylphenylboronic acid
(155 mg, 0.80 mmol) and purified by column chromatography (10%
EtOAc/hexane/20% EtOAc/hexane) to give a pale yellow oil
(82 mg, 56%). Rf¼0.44 (50% EtOAc/hexane); IR (film) 2982, 2926,
1759 (C]O), 1712 (C]O), 1479, 1403, 1212, 1107, 910, 756 cmꢂ1; 1H
(62.9 MHz, CDCl3)
d
157.4 (C), 137.4 (C), 136.9 (C), 129.0 (2ꢁCH),
126.7 (2ꢁCH), 126.5 (C), 123.1 (CH), 62.4 (CH2), 61.2 (CH2), 46.3
(CH2), 32.7 (CH2), 25.8 (3ꢁCH3), 21.0 (CH3), 18.2 (C), ꢂ5.5 (2ꢁCH3);
HRMS (ES) exact mass calcd for C20H32NO3Si [MþH]þ: 362.2146,
found: 362.2143.
NMR (500 MHz, CDCl3)
d
8.05 (2H, d, J¼8.5 Hz, ArH), 7.47 (2H, d,
J¼8.5 Hz, ArH), 7.30e7.27 (2H, m, ArH), 7.22e7.19 (1H, m, ArH),
7.13e7.11 (2H, m, ArH), 6.54 (1H, s, ]CH), 4.41 (2H, q, J¼7.1 Hz,
OCH2CH3), 4.35e4.32 (2H, m, OCH2CH2N), 3.66e3.63 (2H, m,
CH2N), 2.92 (2H, t, J¼7.6 Hz, CH2CH2Ph), 2.69 (2H, t, J¼7.6 Hz,
CH2CH2Ph), 1.43 (3H, t, J¼7.1 Hz, OCH2CH3); 13C NMR (125.8 MHz,
4.2.1.4. 3-[(E)-4-(tert-Butyldimethylsilyloxy)-2-(4-dibenzofur-
anyl)but-1-enyl]oxazolidin-2-one (2d). The general procedure was
followed using ynamide 1a (108 mg, 0.40 mmol) and 4-dibenzo-
furanboronic acid (169 mg, 0.80 mmol). Purification by column
chromatography (10% EtOAc/hexane/20% EtOAc/hexane) gave
a 13:1 inseparable mixture of the enamide 2d and the imide 3a as
a cream solid (84 mg, 46%, adjusted yield of 2d).
CDCl3)
d
166.3 (C), 156.9 (C), 144.9 (C), 141.1 (C), 129.8 (2ꢁCH), 129.2
(C), 128.8 (C), 128.4 (4ꢁCH), 126.6 (2ꢁCH), 126.2 (CH), 124.0 (CH),
62.3 (CH2), 60.9 (CH2), 45.7 (CH2), 34.3 (CH2), 31.2 (CH2), 14.3 (CH3);
HRMS (ES) exact mass calcd for C22H24NO4 [MþH]þ: 366.1700,
found: 366.1697.
Data for 2d: Rf¼0.49 (50% EtOAc/hexane); mp 88e91 ꢀC; IR
(CHCl3) 2954, 2928, 2857, 1759 (C]O), 1655, 1404, 1264, 1226, 1187,
1090, 837, 750, 704 cmꢂ1; 1H NMR (500 MHz, CDCl3)
d 7.96 (1H, d,
J¼7.7, ArH), 7.88 (1H, dd, J¼7.5, 1.4 Hz, ArH), 7.57 (1H, d, J¼8.2 Hz,
ArH), 7.48e7.45 (1H, m, ArH), 7.38e7.34 (2H, m, ArH), 7.31 (1H, t,
J¼7.6 Hz, ArH), 6.91 (1H, s, ]CH), 4.51e4.47 (2H, m, OCH2CH2N),
4.30e4.26 (2H, m, CH2N), 3.62 (2H, t, J¼6.4 Hz, CH2OSi), 3.11 (2H, t,
J¼6.4 Hz, ]CCH2), 0.84 (9H, s, SiC(CH3)3), ꢂ0.08 (6H, s, Si(CH3)2);
4.2.1.8. 3-[2,2-Diphenylvinyl]oxazolidin-2-one (2h). The title
compound was prepared according to the general procedure using
ynamide 1c (75 mg, 0.40 mmol) and phenylboronic acid (98 mg,
0.80 mmol) and purified by column chromatography (15% EtOAc/
hexane/20% EtOAc/hexane) to give a colorless solid (71 mg, 67%).
Rf¼0.72 (60% EtOAc/hexane); mp 90e92 ꢀC; IR (film) 2925, 2855,
13C NMR (125.8 MHz, CDCl3)
d 157.2 (C), 155.8 (C), 153.6 (C), 127.3
(CH),127.1 (CH),126.1 (CH),125.7 (C),124.4 (C),124.1 (C),122.9 (CH),
122.7 (CH), 120.9 (C), 120.6 (CH), 119.5 (CH), 111.7 (CH), 62.5 (CH2),
61.2 (CH2), 46.1 (CH2), 32.6 (CH2), 25.8 (3ꢁCH3), 18.2 (C), ꢂ5.6
(2ꢁCH3); HRMS (ES) exact mass calcd for C25H32NO4Si [MþH]þ:
438.2095, found: 438.2091.
1755 (C]O), 1685, 1444, 1265, 1213, 1042, 736 cmꢂ1 1H NMR
;
(360 MHz, CDCl3)
7.20e7.17 (2H, m, ArH), 7.15 (1H, s, ]CH), 4.22e4.18 (2H, m, CH2O),
3.16e3.12 (2H, m, CH2N); 13C NMR (62.9 MHz, CDCl3)
157.2 (C),
d 7.39e7.35 (3H, m, ArH), 7.29e7.22 (5H, m, ArH),
d
140.8 (C), 138.0 (C), 130.8 (2ꢁCH), 128.2 (4ꢁCH), 127.8 (CH), 127.0
(3ꢁCH), 126.1 (C), 122.4 (CH), 62.6 (CH2), 44.9 (CH2); HRMS (ES)
exact mass calcd for C17H16NO2 [MþH]þ: 266.1176, found: 266.1183.
4.2.1.5. 3-[(E)-2,4-Diphenylbut-1-enyl]oxazolidin-2-one (2e). The
title compound was prepared according to the general procedure
using ynamide 1b (86 mg, 0.40 mmol) and phenylboronic acid
(98 mg, 0.80 mmol) and purified by column chromatography (15%
4.2.1.9. 3-[(E)-2-(4-Chlorophenyl)-2-phenylvinyl]oxazolidin-2-
one (2i). The title compound was prepared according to the general
procedure using ynamide 1c (75 mg, 0.40 mmol) and 4-chloro-
phenylboronic acid (125 mg, 0.80 mmol) and purified by column
chromatography (15% EtOAc/hexane/20% EtOAc/hexane) to give
a pale yellow solid (79 mg, 65%). Rf¼0.57 (50% EtOAc/hexane); mp
136e138 ꢀC; IR (film) 2918, 2865, 1759 (C]O), 1637, 1405, 1262,
EtOAc/hexane/20% EtOAc/hexane) to give
(105 mg, 89%). Rf¼0.71 (60% EtOAc/hexane); IR (film) 2985, 2923,
1751 (C]O), 1480, 1405, 1221, 1087, 908, 734 cmꢂ1 1H NMR
(360 MHz, CDCl3) 7.32e7.25 (4H, m, ArH), 7.23e7.15 (3H, m, ArH),
a pale brown oil
;
d
7.11e7.03 (3H, m, ArH), 6.28 (1H, s, ]CH), 4.21e4.17 (2H, m, CH2O),
3.49e3.45 (2H, m, CH2N), 2.78 (2H, t, J¼7.6 Hz, CH2CH2Ph), 2.58 (2H,
1211, 1039, 744 cmꢂ1 1H NMR (360 MHz, CDCl3)
; d 7.39e7.37 (3H,
t, J¼7.6 Hz, CH2CH2Ph); 13C NMR (62.9 MHz, CDCl3)
d
157.0 (C), 141.4
m, ArH), 7.24e7.22 (4H, m, ArH), 7.14e7.10 (3H, m, ArH and ]CH),
(C), 140.0 (C),131.3 (C), 128.5 (4ꢁCH), 128.3 (2ꢁCH), 127.4 (CH), 126.8
4.21 (2H, app t, J¼7.9 Hz, CH2O), 3.14 (2H, app t, J¼7.9 Hz, CH2N); 13
C

6030
B. Gourdet et al. / Tetrahedron 66 (2010) 6026e6031
NMR (62.9 MHz, CDCl3)
d
157.2 (C), 139.4 (C), 137.5 (C), 132.8 (C),
Si(CH3)2); 13C NMR (125.8 MHz, CDCl3)
d 156.9 (C), 154.2 (C), 141.3
130.8 (2ꢁCH), 128.4 (2ꢁCH), 128.3 (2ꢁCH), 128.2 (2ꢁCH), 128.0
(CH), 124.8(C), 122.7 (CH), 62.6 (CH2), 44.8 (CH2); HRMS (ES) exact
mass calcd for C17H1535ClNO2 [MþH]þ: 300.0786, found: 300.0784.
(CH), 121.9 (CH), 112.6 (C), 111.1 (CH), 104.7 (CH), 62.4 (CH2), 61.9
(CH2), 45.6 (CH2), 30.5 (CH2), 25.8 (3ꢁCH3), 18.3 (C), ꢂ5.5 (2ꢁCH3);
HRMS (ES) exact mass calcd for C17H28NO4Si [MþH]þ: 338.1782,
found: 338.1778.
4.2.1.10. 3-[(E)-2-Phenyl-2-o-tolylvinyl]oxazolidin-2-one (2j). The
title compound was prepared according to the general procedure
using ynamide 1c (75 mg, 0.40 mmol) and o-tolylboronic acid
(109 mg, 0.80 mmol) and purified by column chromatography (10%
EtOAc/hexane/12% EtOAc/hexane) to give a pale yellow solid
(59 mg, 53%). Rf¼0.76 (60% EtOAc/hexane); mp 99e101 ꢀC; IR (film)
3059, 2983, 2921, 1759 (C]O), 1636, 1443, 1308, 1219, 1038,
4.2.1.14. 3-{(1E,3E)-2-[2-(tert-Butyldimethylsilyloxy)ethyl]-4-
phenylbuta-1,3-dienyl}-oxazolidin-2-one (2n). The title compound
was prepared according to the general procedure using ynamide 1a
(108 mg, 0.40 mmol) and trans-2-phenylvinylboronic acid (118 mg,
0.8 mmol) and purified by column chromatography (10% EtOAc/
hexane) to give a pale brown solid (78 mg, 52%). Rf¼0.80 (60%
EtOAc/hexane); mp 130e132 ꢀC; IR (film) 2925, 1731 (C]O), 1635,
732 cmꢂ1 1H NMR (500 MHz, CDCl3)
; d 7.34e7.31 (2H, m, ArH),
7.29e7.13 (7H, m, ArH), 6.74 (1H, s, ]CH), 4.30e4.27 (2H, m, CH2O),
1461, 1406, 1337, 1250, 1224, 1044, 756 cmꢂ1
;
1H NMR (500 MHz,
3.37e3.33 (2H, m, CH2N), 2.08 (3H, s, CH3); 13C NMR (125.8 MHz,
CDCl3) 7.39e7.37 (2H, m, ArH), 7.33e7.30 (2H, m, ArH), 7.22e7.19
d
CDCl3)
d
157.5 (C), 140.7 (C), 138.4 (C), 136.8 (C), 130.9 (CH), 130.5
(1H, m, ArH), 6.77 (1H, s, ]CH), 6.75 (1H, d, J¼16.1 Hz, CH]CH),
6.45 (1H, d, J¼16.1 Hz, CH]CH), 4.41 (2H, app dd, J¼9.2, 6.9 Hz,
CH2O), 4.21 (2H, app dd, J¼9.2, 6.9 Hz, CH2N), 3.77 (2H, t, J¼6.4 Hz,
CH2OSi), 2.70 (2H, t, J¼6.4 Hz, ]CCH2), 0.87 (9H, s, SiC(CH3)3), 0.02
(CH), 129.9 (2ꢁCH), 128.0 (2ꢁCH), 127.7 (C), 127.6 (CH), 127.4 (CH),
125.5 (CH), 124.1 (CH), 62.7 (CH2), 45.1 (CH2), 20.6 (CH3); HRMS (ES)
exact mass calcd for C18H18NO2 [MþH]þ: 280.1332, found: 280.1330.
(6H, s, Si(CH3)2); 13C NMR (125.8 MHz, CDCl3)
d 156.7 (C), 137.6 (C),
4.2.1.11. 3-[(E)-2-(3-Chloro-4-isopropoxyphenyl)-2-phenylvinyl]
oxazolidin-2-one (2k). The title compound was prepared according
to the general procedure using ynamide 1c (75 mg, 0.40 mmol) and
3-chloro-4-isopropoxyphenyl boronic acid (172 mg, 0.80 mmol)
and purified by column chromatography (15% EtOAc/hexane/20%
EtOAc/hexane) to give a colorless solid (117 mg, 82%). Rf¼0.68 (60%
EtOAc/hexane); mp 122e124 ꢀC; IR (film) 2978, 2920, 1761 (C]O),
130.9 (CH), 128.6 (2ꢁCH), 127.4 (CH), 127.0 (CH), 126.0 (2ꢁCH),
125.1 (CH), 120.1 (C), 62.3 (CH2), 61.6 (CH2), 45.5 (CH2), 29.0 (CH2),
25.8 (3ꢁCH3), 18.3 (C), ꢂ5.4 (2ꢁCH3); HRMS (ES) exact mass calcd
for C21H32NO3Si [MþH]þ: 374.2146, found: 374.2136.
4.2.2. With arylboronic esters.
4.2.2.1. 4-{1-[1-(2-Oxooxazolidin-3-yl)meth-(E)-ylidene]-3-phe-
nylpropyl}benzoic acid ethyl ester (2g). The title compound was
prepared according to the general procedure using ynamide 1b
(86 mg, 0.40 mmol) and ethyl-(4-(4,4,5,5)-tetramethyl-1,3,2,diox-
aborolan-2-yl)benzoate (220 mg, 0.80 mmol) and purified by col-
umn chromatography (10% EtOAc/hexane/20% EtOAc/hexane) to
give a pale yellow oil (77 mg, 53%).
1639, 1496, 1276, 1214, 1108, 732 cmꢂ1
;
1H NMR (360 MHz, CDCl3)
d
7.39e7.37 (3H, m, ArH), 7.24e7.23 (2H, m, ArH), 7.18 (1H, app d,
J¼1.4 Hz, ArH), 7.06 (1H, s, ]CH), 7.01 (1H, dd, J¼8.5, 1.4 Hz, ArH),
6.84 (1H, d, J¼8.5 Hz, ArH), 4.52 (1H, quint, J¼6.0 Hz, CH(CH3)2), 4.19
(2H, app t, J¼8.0 Hz, CH2O), 3.11 (2H, app t, J¼8.0 Hz, CH2N),1.36 (6H,
d, J¼6.0 Hz, CH(CH3)2); 13C NMR (62.9 MHz, CDCl3)
d 157.2 (C),152.7
(C),137.5 (C),134.5 (C),130.7 (2ꢁCH),128.8 (CH),128.3 (2ꢁCH),127.9
(CH),126.0 (CH),124.7 (C),124.0 (C),121.8 (CH),115.5 (CH), 72.1 (CH),
62.6 (CH2), 44.8 (CH2), 22.0 (2ꢁCH3); HRMS (ES) exact mass calcd for
C20H2135ClNO3 [MþH]þ: 358.1203, found: 358.1203.
4.2.3. With triphenylboroxine.
4.2.3.1. 3-[((E)-4-(tert-Butyldimethylsilyloxy)-2-phenyl)but-1-
enyl]oxazolidin-2-one (2a). The title compound was prepared
according to the general procedure using ynamide 1a (108 mg,
0.40 mmol) and triphenylboroxine (124 mg, 0.40 mmol) and puri-
fied by column chromatography (10% EtOAc/hexane/15% EtOAc/
hexane) to give a pale orange oil (81 mg, 58%).
4.2.1.12. 1-[(E)-2-(4-Acetylphenyl)-2-phenylvinyl]pyrrolidin-2-
one (2l). The title compound was prepared according to general
procedure using ynamide 1d (74 mg, 0.40 mmol) and 4-acetylphe-
nylboronic acid (131 mg, 0.80 mmol) and purified by column chro-
matography (20% EtOAc/hexane) to give an orange oil (31 mg, 25%).
Rf¼0.38 (60% EtOAc/hexane); IR (film) 2958, 2926, 1681 (C]O),
4.3. Deuterium incorporation experiment
1460, 1392, 1269, 1222, 907, 733, 650 cmꢂ1
;
1H NMR (500 MHz,
4.3.1. 3-[((E)-4-(tert-Butyldimethylsilyloxy)-1-deuterio-2-phenyl)
but-1-enyl]oxazolidin-2-one (7). A solution of ynamide 1a (108 mg,
0.40 mmol), triphenylboroxine (124 mg, 0.40 mmol), and [Rh(cod)
CDCl3) d 7.86e7.83 (2H, m, ArH), 7.46 (1H, s, ]CH), 7.42e7.37 (3H, m,
ArH), 7.28e7.26 (2H, m, ArH), 7.23e7.21 (2H, m, ArH), 3.00e2.88 (2H,
m, CH2N), 2.58 (3H, s, CH3), 2.45e2.42 (2H, t, J¼7.7 Hz, CH2C]O),1.89
(MeCN)2]BF4 (12 mg, 0.032 mmol) in THF (2 mL) and D2O (100
mL)
(2H, quint, J¼7.7 Hz, CH2CH2N); 13C NMR (125.8 MHz, CDCl3)
d
197.6
was heated at 90 ꢀC for 10 min under microwave irradiation. Sat-
urated aqueous NaHCO3 solution (5 mL) was added and the mixture
was extracted with CH2Cl2 (3ꢁ10 mL). The combined organic layers
were dried (MgSO4), filtered, and concentrated in vacuo. Purifica-
tion of the residue by column chromatography (10% EtOAc/
hexane/15% EtOAc/hexane) gave a ca. 5:1 inseparable mixture of
the enamide 7 and the imide 3b (mixture of isotopologues) as a pale
orange oil (96 mg, 59%, adjusted yield of 7).
(C), 175.7 (C), 146.3 (C), 138.0 (C), 135.3 (C), 130.9 (2ꢁCH), 128.3
(2ꢁCH),128.2 (2ꢁCH),127.9 (CH),127.1 (2ꢁCH),125.1 (C),124.1 (CH),
48.2 (CH2), 30.4 (CH2), 26.6 (CH3), 18.8 (CH2); HRMS (ES) exact mass
calcd for C20H20NO2 [MþH]þ: 306.1489, found: 306.1494.
4.2.1.13. 3-[(E)-4-(tert-Butyldimethylsilyloxy)-2-(2-furanyl)but-
1-enyl]oxazolidin-2-one (2m). The title compound was prepared
according to the general procedure using ynamide 1a (108 mg,
0.40 mmol) and 2-furanboronic acid (90 mg, 0.80 mmol) and pu-
rified by column chromatography (10% EtOAc/hexane/20% EtOAc/
hexane) to give a cream solid (89 mg, 66%). Rf¼0.67 (50% EtOAc/
hexane); mp 54e56 ꢀC; IR (CHCl3) 3055, 2986, 1759 (C]O), 1654,
Data for 7: Rf¼0.80 (60% EtOAc/hexane); IR (film) 2929, 2857,
1753 (C]O), 1639, 1598, 1471, 1297, 1255, 1051, 733 cmꢂ1; 1H NMR
(500 MHz, CDCl3) d 7.34e7.30 (4H, m, ArH), 7.27e7.24 (1H, m, ArH),
4.43 (2H, app dd, J¼8.8, 7.1 Hz, CH2O), 4.14 (2H, app dd, J¼9.0, 6.9 Hz,
CH2N), 3.60 (2H, t, J¼6.5 Hz, CH2OSi), 2.83 (2H, t, J¼6.5 Hz, ]CCH2),
0.84 (9H, s, SiC(CH3)3), ꢂ0.06 (6H, s, Si(CH3)2); 13C NMR (125.8 MHz,
;
1421, 1403, 1265, 1226, 1082, 739, 705 cmꢂ1 1H NMR (500 MHz,
CDCl3)
d
7.33 (1H, d, J¼1.8 Hz, ArH), 7.17 (1H, s, ]CH), 6.37 (1H, dd,
CDCl3)
d
157.3 (C), 140.6 (C), 128.3 (2ꢁCH), 127.1 (CH), 126.8 (2ꢁCH),
J¼3.3, 1.8 Hz, ArH), 6.21 (1H, d, J¼3.3 Hz, ArH), 4.44e4.41 (2H, m,
OCH2CH2N), 4.19e4.17 (2H, m, CH2N), 3.75 (2H, t, J¼6.5 Hz, CH2OSi),
2.71 (2H, t, J¼6.5 Hz, ]CCH2), 0.86 (9H, s, SiC(CH3)3), ꢂ0.02 (6H, s,
125.6 (C), 123.5 (CD, t, JD¼26 Hz), 62.4 (CH2), 61.1 (CH2), 46.1 (CH2),
32.6 (CH2), 25.8 (3ꢁCH3), 18.2 (C), ꢂ5.5 (2ꢁCH3); HRMS (ES) exact
mass calcd for C19H26DNO3Si [MþH]þ: 349.2052, found: 349.2050.

B. Gourdet et al. / Tetrahedron 66 (2010) 6026e6031
6031
4.4. Regio-/stereochemical determinations
References and notes
1. For reviews on enamides, see: (a) Carbery, D. R. Org. Biomol. Chem. 2008, 6,
3455e3460; (b) Matsubara, R.; Kobayashi, S. Acc. Chem. Res. 2008, 41, 292e301;
(c) Larock, R. C. Comprehensive Organic Transformations: A Guide to Functional
Group Preparations; Wiley-VCH: New York, NY, 1999; (d) Tracey, M. R.; Hsung,
R. P.; Antoline, J.; Kurtz, K. C. M.; Shen, L.; Slafer, B. W.; Zhang, Y. In Science of
Synthesis, HoubeneWeyl Methods of Molecular Transformations; Weinreb, S. M.,
Ed.; Georg Thieme KG: New York, NY, 1999; Chapter 21.4.
2. (a) Gourdet, B.; Lam, H. W. J. Am. Chem. Soc. 2009, 131, 3802e3803; (b) Gourdet,
B.; Rudkin, M. E.; Watts, C. A.; Lam, H. W. J. Org. Chem. 2009, 74, 7849e7858.
3. For general reviews of ynamide chemistry, see: (a) Evano, G.; Coste, A.; Jouvin,
K. Angew. Chem., Int. Ed. 2010, 16, 2840e2859; (b) Zificsak, C. A.; Mulder, J. A.;
Hsung, R. P.; Rameshkumar, C.; Wei, L.-L. Tetrahedron 2001, 57, 7575e7606; (c)
Mulder, J. A.; Kurtz, K. C. M.; Hsung, R. P. Synlett 2003, 1379e1390; (d) Katritzky,
A. R.; Jiang, R.; Singh, S. K. Heterocycles 2004, 63, 1455e1475.
4. For related carbometalation reactions of ynamides, see: (a) Chechik-Lankin, H.;
Livshin, S.; Marek, I. Synlett 2005, 2098e2100; (b) Prakash Das, J.; Chechik, H.;
Marek, I. Nature Chem. 2009, 1, 128e132; (c) Yasui, H.; Yorimitsu, H.; Oshima, K.
Chem. Lett. 2007, 36, 32e33; (d) Yasui, H.; Yorimitsu, H.; Oshima, K. Bull. Chem.
Soc. Jpn. 2008, 81, 373e379.
5. (a) Miyaura, N. Bull. Chem. Soc. Jpn. 2008, 81, 1535e1553; (b) Boronic Acids:
Preparation and Application in Organic Synthesis and Medicine; Hall, D. G., Ed.;
Wiley-VCH: Weinheim, 2005; (c) Miyaura, N.; Yamamoto, Y. In Comprehensive
Organometallic Chemistry III; Crabtree, R. H., Mingos, M. P., Eds.; Elsevier: 2007;
Vol. 9, pp 146e244.
The regioselectivities of the rhodium-catalyzed carbometalation
reactions of alkyl-substituted ynamides 1a and 1b were obvious
from the 1H NMR spectra of the corresponding enamide products
(by consideration of the signals of the alkene proton, which did not
exhibit vicinal protoneproton coupling).
The regiochemical outcome of the rhodium-catalyzed carbo-
metalation reaction producing enamide 2h was determined by
dihydroxylation of 2h, which provided known
a-hydroxyaldehyde
818 in low conversion.
O
O
Ph
OH
OsO4, NMO
4:1 THF/H2O
0 °C to rt
O
N
H
Ph
Ph Ph
2h
8
6. For nickel-catalyzed hydroarylation of alkynes with arylboron compounds, see:
(a) Shirakawa, E.; Takahashi, G.; Tsuchimoto, T.; Kawakami, Y. Chem. Commun.
2001, 2688e2689.
The stereoselectivities of the rhodium-catalyzed carbometala-
tion reactions producing enamides 2c, 2g, 2l, and 2n were de-
termined on the basis of NOESY experiments, which displayed the
following diagnostic enhancements:
7. For rhodium-catalyzed hydroarylation of alkynes with arylboron reagents, see:
(a) Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara, M. J. Am. Chem. Soc. 2001, 123,
9918e9919; (b) Lautens, M.; Yoshida, M. Org. Lett. 2002, 4, 123e125; (c) Lautens,
M.; Yoshida, M. J. Org. Chem. 2003, 68, 762e769; (d) Genin, E.; Michelet, V.; Genêt,
J.-P. Tetrahedron Lett. 2004, 45, 4157e4161; (e) Genin, E.; Michelet, V.; Genêt, J.-P.
J. Organomet. Chem. 2004, 689, 3820e3830; (f) Alfonsi, M.; Arcadi, A.; Chiarini, M.;
Marinelli, F. J. Org. Chem. 2007, 72, 9510e9517; (g) Zhang, W.; Liu, M.; Wu, H.; Ding,
J.; Cheng, J. Tetrahedron Lett. 2008, 49, 5214e5216. For reviews of domino pro-
cesses involving rhodium-catalyzed additions of arylboron compounds to al-
kynes, see: (h) Miura, T.; Murakami, M. Chem. Commun. 2007, 217e224; (i) Youn,
S. W. Eur. J. Org. Chem. 2009, 2597e2605.
8. For palladium-catalyzed hydroarylation of alkynes with arylboron reagents,
see: (a) Oh, C. H.; Jung, H. H.; Kim, K. S.; Kim, N. Angew. Chem., Int. Ed. 2003, 42,
805e808; (b) Oh, C. H.; Ryu, J. H. Bull. Korean Chem. Soc. 2003, 24, 1563e1564;
(c) Kim, N.; Kim, K. S.; Gupta, A. K.; Oh, C. H. Chem. Commun. 2004, 618e619; (d)
Gupta, A. K.; Kim, K. S.; Oh, C. H. Synlett 2005, 457e460; (e) Zeng, H.; Hua, R.
J. Org. Chem. 2008, 73, 558e562 For related processes, see: (f) Zhou, C.; Larock,
R. C. Org. Lett. 2005, 7, 259e262; (g) Zhou, C.; Larock, R. C. J. Org. Chem. 2006, 71,
3184e3191; (h) Zhou, C.; Emrich, D. E.; Larock, R. C. Org. Lett. 2003, 5,
1579e1582; (i) Zhou, C.; Larock, R. C. J. Org. Chem. 2005, 70, 3765e3777.
9. For copper-catalyzed hydroarylation of alkynes with arylboronic reagents, see:
Yamamoto, Y.; Kirai, N.; Harada, Y. Chem. Commun. 2008, 2010e2012.
10. For cobalt-catalyzed hydroarylation of alkynes with arylboronic acids, see: Lin,
P.-S.; Jeganmohan, M.; Cheng, C.-H. Chem.dEur. J. 2008, 14, 11296e11299.
11. For metal-catalyzed hydroarylation of alkynes with arylsilanes or arylsiloxanes,
see: (a) Fujii, T.; Koike, T.; Mori, A.; Osakada, K. Synlett 2002, 295e297; (b)
Nakao, Y.; Takeda, M.; Chen, J.; Hiyama, T. Synlett 2008, 774e776; (c) Lin, B.; Liu,
M.; Ye, Z.; Zhang, Q.; Cheng, J. Tetrahedron Lett. 2009, 50, 1714e1716.
12. For a review of substrate-directable chemical reactions, see: Hoveyda, A. H.;
Evans, D. A.; Fu, G. C. Chem. Rev. 1993, 93, 1307e1370.
H
Me
H
CO2Et
O
H
O
H
H
H
O
N
H
O
N
H
H
OTBS
H
Ph
H
2c
H
2g
O
H
O
O
H
H
Me
Ph
OTBS
N
O
N
H
H
H
H
2n
H
H
2l
Acknowledgements
13. For domino HeckeSuzukieMiyaura reactions of ynamides, see: (a) Couty, S.;
Liegault, B.; Meyer, C.; Cossy, J. Tetrahedron 2006, 62, 3882e3895; (b) Couty, S.;
Liegault, B.; Meyer, C.; Cossy, J. Org. Lett. 2004, 6, 2511e2514.
14. Under identical conditions, replacement of [Rh(cod)(MeCN)2]BF4 with [Rh(cod)
Cl]2 (5 mol %) or Rh(cod)(acac) (5 mol %) gave complex mixtures of products,
while the use of Pd(OAc)2 (5 mol %) along with Na2CO3 (2 equiv) led only to low
conversions into the desired enamides.
15. For reviews of potassium organotrifluoroborate salts, see: (a) Molander, G. A.;
Sandrock, D. L. Curr. Opin. Drug Discovery Dev. 2009, 12, 811e823; (b) Molander,
G. A.; Figueroa, R. Aldrichimica Acta 2005, 38, 49e56; (c) Darses, S.; Genet, J.-P.
Eur. J. Org. Chem. 2003, 4313e4326.
This work was supported by the European Commission (Project
No. MEST-CT-2005-020744), the EPSRC, AstraZeneca, and the Uni-
versity of Edinburgh. We thank the EPSRC National Mass Spec-
trometry Service Centre at the University of Wales, Swansea, for
providing high-resolution mass spectra.
Supplementary data
16. For a review of 1,4-migration of rhodium and palladium in catalytic reactions,
see: Ma, S.; Gu, Z. Angew. Chem., Int. Ed. 2005, 44, 7512e7517.
Copies of 1H and 13C NMR spectra for new compounds. Sup-
plementary data associated with this article can be found in online
version at doi:10.1016/j.tet.2010.06.021.
17. The regioselectivity of this reaction could not be determined with accuracy.
18. Hayashi, M.; Yoshiga, T.; Nakatani, K.; Ono, K.; Oguni, N. Tetrahedron 1994, 50,
2821e2830.