A nickel(0) catalyzed cycloaddition of alkynes and isocyanates that affords pyrimidine-diones

Article abstract of DOI:10.1016/j.tet.2006.03.119

A Ni/N-heterocyclic carbene catalyzed cycloaddition of one alkyne and two isocyanates that affords pyrimidine-dione is described. The key to the success of this protocol is the use of unsymmetrically substituted alkynes that favors the formation of pyrimi

Full text of DOI:10.1016/j.tet.2006.03.119

Tetrahedron 62 (2006) 7552–7559
A nickel(0) catalyzed cycloaddition of alkynes and
isocyanates that affords pyrimidine-diones
*
Hung A. Duong and Janis Louie
Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, UT 84112-0850, USA
Received 12 January 2006; revised 6 March 2006; accepted 6 March 2006
Available online 15 June 2006
Dedicated to Professor G€unther Wilke for his contribution to the field of organonickel chemistry
Abstract—A Ni/N-heterocyclic carbene catalyzed cycloaddition of one alkyne and two isocyanates that affords pyrimidine-dione is
described. The key to the success of this protocol is the use of unsymmetrically substituted alkynes that favors the formation of pyrimi-
dine-diones over pyridones. A variety of pyrimidine-diones were prepared. A one-pot cycloaddition and Stille coupling were reported for
tributyl(1-propynyl)tin. Competition studies also provide insights into the mechanism of the cycloaddition.
Ó 2006 Elsevier Ltd. All rights reserved.
Table 1. Ni-catalyzed cycloaddition of alkynes and isocyanates
1. Introduction
O
R2
5 mol% Ni(COD)2
10 mol% L
R1
R1
R2
R
O
R1
R2
R1
O
The transition metal catalyzed cycloaddition of unsaturated
coupling partners has developed into a powerful and effi-
cient method for the construction of heterocycles.1 Such
reactions generally involve the coupling of two alkynes
with a heteroatom-containing substrate. For example,
Co,2 Ru,3 and Ni4 based systems catalyze cycloaddition
reactions that yield pyrones, pyridones, pyrans, and pyri-
dines. Any other combination of these coupling partners
is rare.5 We report that pyrimidine-diones can be prepared
from the Ni-catalyzed cycloaddition of one alkyne and two
isocyanates.
N
+
+
NCO
(1)
R
toluene, RT, 1h
N
R
N
R
2
R2
1
Entry L
RNCO
Alkyne
% Alkyne 1
conversion (% Yield) (% Yield)
2
R
concn R1 R2 concn
(M) (M)
1
2
3
4
5
6
IPr Ph 0.2 Et Et 0.1 100
IPr Ph 0.8 Et Et 0.1 100
IPr Ph 0.2 Ph Ph 0.1
IPr Ph 0.2 TMS TMS 0.1
IPr Ph 0.8 TMS Me 0.1 100
None Ph 0.2 TMS Me 0.1
1a (0)
2a (87)a
1a (30)a 2a (53)a
1b (0)b 2b (0)b
5
0
1c (0)b
2c (0)b
1d (75)a 2d (0)a
1d (0)b 2d (0)b
2. Results and discussion
7
a
We recently showed that the combination of Ni and IPr (or
SIPr)6 is an effective catalyst system for the cycloaddition
of alkynes and isocyanates to afford pyridones in excellent
yield.4c Included was the cycloaddition of 3-hexyne and
phenyl isocyanate, which gave an excellent yield of tetra-
ethylpyridone 2a (entry 1, Table 1).4c During our investiga-
tions, we discovered that reactions run in excess of
isocyanate led to the formation of a new heterocyclic prod-
uct, pyrimidine-dione 1a, in appreciable amounts (entry 2,
Table 1).
Isolated yield.
Determined by GC.
b
R1
R2
R2
O
R
R1
R2
R1
N
R
N
Ni0Ln
N
R
O
O
1
2
R1
R2
R1
R2
R1
R2
O
R2
R1
RNCO
R1
LnNi
N
LnNi
R
N
N
R
A mechanism that diverges at a common intermediate and
accounts for both pyridone and pyrimidine-dione products
is shown in Scheme 1.7 Initial oxidative coupling between
R
R2
LnNi
O
O
4b
4a
RNCO
R1
O
R2
N
R
3
* Corresponding author. Tel.: +1 801 581 7309; fax: +1 801 581 8433;
e-mail: louie@chem.utah.edu
Scheme 1. Proposed mechanisms of the Ni-catalyzed cycloaddition.
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.03.119

H. A. Duong, J. Louie / Tetrahedron 62 (2006) 7552–7559
5 mol% Ni(COD)2
7553
an alkyne and the isocyanate leads to nickelacycle 3. When
isocyanate concentrations are high, subsequent reaction with
isocyanate, rather than alkyne, occurs and yields pyrimidine-
dione products. This mechanism suggests that an increase in
steric bulk on alkyne substrates would promote selective
insertion of isocyanate rather than alkyne. Indeed, although
diphenyl acetylene and bis(trimethylsilyl) acetylene failed
to react (entries 3 and 4, Table 1), 1-trimethylsilyl propyne
gave excellent yield of the pyrimidine-dione (1d) without
the need for excess isocyanate concentrations (entry 5).
Interestingly, the same reactants afforded only pyridone 2d
when Ni/PEt3 was used as the catalyst.4e Thus, the steric
hindrance of the IPr ligand may help to encourage isocya-
nate insertion over the insertion of another hindered alkyne.
No cycloaddition occurred when Ni(COD)2 was used in the
absence of IPr ligand (entry 6).
O
N
10 mol% IPr
4 eq EtNCO
Bu3Sn
N
Bu3Sn
Me
°
C
toluene, 80
overnight
O
O
10 mol% Pd(PPh3)4
1 eq CuI, 2 eq PhI
N
O
DMF, 60 °C, 3h
N
5
75 % over 2 steps
Scheme 2. One-pot cycloaddition and Stille coupling.
Avariety of pyrimidine-diones were prepared via this proce-
dure (Table 2). Pyrimidine-diones were obtained with aryl
isocyanates although pyridone products were also observed
in some cases (entries 2–4). Alkyl isocyanates were cleanly
converted to the corresponding pyrimidine-dione (entries
5–7). Electron-withdrawing groups (such as –CO2Et and
–C2H3) were also tolerated (entries 8, 9). Dialkyl-substituted
acetylene such as 4,4-dimethyl-2-pentyne also worked well
under the cyclization conditions to give the corresponding
product in good yield (entry 10). Less sterically-encumbered
alkynes such as 4-methyl-2-pentyne gave lower yields
and selectivities (entry 11). A mixture of the pyrimidine-
dione regioisomers and pyridone products were obtained
(entry 11).
Furtherinsightsintothemechanismofthecycloadditionwere
obtained through the competition reaction of 1-trimethyl-
silyl-1-propyne and two different isocyanates (Scheme 3).
When 1-trimethylsilyl-1-propyne was exposed to equal
concentrations of 4-CF3PhNCO and 4-MeOPhNCO, a mix-
ture of heterocyclic products was obtained (Table 3, entry
1). The product mixture included pyrimidine-dione 1g
(derived from the cycloaddition of only the electron-deficient
isocyanate) as well as pyrimidine-dione 10g (derived from the
cycloaddition of both isocyanates). Other pyrimidine-dione
regioisomers were not observed. Similarly, when the same
alkyne was subjected to equal mixtures of 4-MeOPhNCO
and EtNCO, only two (out of the possible eight) pyrimidine-
dione products were observed (entry 2). Only one pyridone
was obtained in both competition reactions. Thus, the
product distributions provide further evidence that hetero-
oxidative coupling occurs (Scheme 1) and that nickelacycle
3 can react with either an alkyne or an isocyanate. The first
step, oxidative coupling of the alkyne and an isocyanate,
favors the more electron-deficient isocyanate (such as
4-CF3PhNCO and 4-MeOPhNCO in entries 1 and 2, Table 3,
respectively) and all observed heterocyclic products re-
flect this phenomenon. Nickelacycle 3 can insert either an
alkyne or isocyanate to give pyridones or pyrimidine-diones,
respectively.
Tributyl(1-propynyl)tin cyclized to afford a pyrimidine-
dione selectively (Scheme 2). Furthermore, exposure of the
cycloaddition reaction mixture directly to standard Stille
coupling conditions8 resulted in the phenyl-substituted
pyrimidine-dione 5 in 75% yield (Scheme 2). Thus, aryl
pyrimidine-diones can be readily prepared through a two-
step, one-pot reaction.
Table 2. Pyrimidine-diones prepared from Ni-catalyzed cycloadditiona
5 mol% Ni(COD)2
10 mol% IPr
Entry RNCO
R
Alkyne
R2
Pyrimidine-dione Pyridone 2
1 (% yield)b
(% yield)b
TMS
Me + R1NCO + R2NCO
R1
toluene, rt, 1h
0.1 M
O
0.2 M
0.2 M
1
Ph
TMS Me
1d (75)c
1e (68)
1f (49)
1g (17)
1h (83)
1i (72)d
1j (60)
—
2
3
4-MeOPh TMS Me
3-MeOPh TMS Me
2e (24)
2f (24)
2g (68)
—
—
—
O
O
TMS
Me
R1
TMS
R1
O
TMS
Me
R2
N
N
N
4
5
4-CF3Ph
Et
Bn
Cy
Cy
TMS Me
TMS Me
TMS Me
TMS Me
TMS CO2Et
TMS C2H3
+
+
Me
Me
N
R1
N
O
6
7e
8f
9
TMS
R1
1k (43)
1l (38)c
1m (81)d
1n (35)g
—
1
1'
2
Ph
2l (38)
—
2n (18)
10
11
Et
Ph
tBu
iPr
Me
Me
Scheme 3. Cycloaddition with a mixture of isocyanates.
Table 3. Yields of pyrimidine-diones and pyridones
a
Reaction conditions: 0.1 M diyne, 0.2 M isocyanate, 5 mol % Ni(COD)2,
10 mol % IPr, toluene, rt.
Isolated yields (average of two runs).
Isocyanate (0.8 M) was used.
Isocyanate (0.4 M) was used.
Desilylated pyridone product was observed.
Cyclotrimerized alkyne product (3k) was obtained in 45% yield.
The other regioisomer (10n) was also obtained in 14%.
b
c
d
e
f
Entry
R1
R2
1
% Yielda 10
2
1
2
4-CF3Ph
4-MeOPh
4-MeOPh
Et
1g (11)
1e (28)
10g (14)
10e (29)
2g (44)
2e (18)
g
a
Isolated yields.

7554
H. A. Duong, J. Louie / Tetrahedron 62 (2006) 7552–7559
3. Conclusion
by column chromatography on silica gel (5:40:55 acetone/
methylene chloride/hexane). Compound 1a was further
purified by column chromatography on silica gel (20% ethyl
acetate/hexane then methylene chloride) to afford 1a
(33 mg, 30%) as a white solid. Compound 2a was further
purified by column chromatography on silica gel (10%
acetone/methylene chloride) to afford 2a (26 mg, 53%) as
a white solid.4c
The combination of Ni and IPr catalyzes the cycloaddition
of alkynes and isocyanates. When untethered alkynes that
possess a large substituent are employed, coupling of two
isocyanates and an alkyne affords pyrimidine-diones. Com-
petition reactions suggest that initial hetero-oxidative cou-
pling between an isocyanate and an alkyne occurs. Further
application of this chemistry in the synthesis of other hetero-
cycles is currently being investigated.
4.2.1.1. Analytical data for 1a.
O
N
4. Experimental
4.1. General
N
O
1a
Ni(COD)2 was purchased from Strem and used without
further purification. 1,3-Bis(2,6-diisopropylphenyl)-imi-
dazol-2-ylidene (IPr) was prepared according to literature
procedure.9 Phenyl isocyanate, ethyl isocyanate, benzyl
isocyanate, 3-methoxyphenyl isocyanate, 4-methoxyphenyl
isocyanate, a,a,a-trifluoro-p-tolyl isocyanate, cyclohexyl
isocyanate, and butyl isocyanate were purchased from
Aldrich, dried over phosphorous pentoxide, and degassed
prior to use. 4-Methyl 2-pentyne (Aldrich), ethyl 3-(tri-
methylsilyl)propynoate (Aldrich), tributyl(1-propynyl)tin
(Aldrich), and 4,4-dimethyl-2-pentyne (GFS) were pur-
chased, dried over calcium hydride, and degassed prior to
use. 1-Trimethylsilyl-pent-3-en-1-yne was prepared accord-
ing to literature procedure.10 1H and 13C NMR spectra were
recorded on a Varian VXL-300 spectrometer and a Varian
VXR-500 spectrometer and referenced to residual protiated
solvent (resonances downfield to the standard are reported
as positive). All 13C NMR spectra were proton decoupled.
IR bands were measured as a thin film on a NaCl plate
on a Bruker Tensor 27 FTIR spectrometer. The assignments
of atom connectivity and spatial relationships are ex-
1H NMR (500 MHz, CDCl3, ppm): d 7.51–7.26 (m, 10H),
2.52 (q, 7.4 Hz, 2H), 2.37 (q, 7.4 Hz, 2H), 1.19 (t, 7.4 Hz,
3H), 1.03 (t, 7.4 Hz, 3H). 13C {1H} NMR (125 MHz,
CDCl3, ppm): d 163.3, 152.5, 152.1, 137.5, 135.6, 129.7,
129.4, 129.3, 129.2, 128.6, 128.5, 113.6, 23.2, 19.9, 14.2,
13.3. IR (CHCl3, cmꢀ1): 1707. Anal. Calcd for
C20H20N2O2: C, 74.98; H, 6.29; N, 8.74, found: C, 74.88;
H, 6.31; N, 8.69.
4.2.2. 6-Methyl-5-(trimethylsilyl)-1,3-diphenylpyrimi-
dine-2,4(1H,3H)-dione (1d). The general procedure was
used with 1-trimethylsilyl-1-propyne (35 mg, 0.31 mmol,
0.1 M), phenyl isocyanate (297 mg, 2.49 mmol, 0.8 M),
Ni(COD)2 (4.3 mg, 0.016 mmol, 5 mol %), IPr (12 mg,
0.032 mmol, 10 mol %), and 3.1 mL of toluene. The reac-
tion mixture was purified by column chromatography on
silica gel (20% acetone/hexane then 10% ethyl acetate/
hexane) to afford 1d as a white solid (82 mg, 75%).
1
clusively based on 2D NMR correlation (NOESY, H/13C
4.2.2.1. Analytical data for 1d.
1
HMBC, and H/13C HMQC) and 1D NOESY. Elemental
analyses were performed at Midwest Microlab LLC.,
Indianapolis, IN.
10
5
O
1
2
Si
N
6
4.2. General cycloaddition procedure of alkynes and
isocyanates
4
O
3
9
N
8
7
1d
A toluene solution of Ni(COD)2 and IPr was prepared and
allowed to equilibrate for at least 6 h.4a In a glove box,
a solution of alkyne and isocyanate in toluene was added
to an oven-dried vial equipped with a stir bar. To the stirring
solution, a solution of Ni(COD)2 and IPr was added and the
reaction was stirred at room temperature for 1 h, unless
otherwise stated. The mixture was then concentrated and
purified by column chromatography with silica gel that
was pre-treated with triethyl amine.
1H NMR (300 MHz, CD2Cl2, ppm): d 7.52–7.40 (m, 6H),
7.30–7.23 (m, 4H), 1.96 (s, 3H), 0.31 (s, 9H). 13C {1H}
NMR (125 MHz, CD2Cl2, ppm): d 165.6, 157.3, 152.5,
138.5, 136.5, 130.2, 129.6, 129.5, 129.3, 129.1, 128.7,
108.4, 21.9, 1.9. HMBC cross-peaks: H9 and C2, C3; H10
and C2 and other cross-peaks of aromatic protons and aro-
matic carbons. NOE was observed for aromatic protons
and H9. IR (CH2Cl2, cmꢀ1): 1710, 1652, 1581. Anal. Calcd
for C20H22N2O2Si: C, 68.54; H, 6.33; N, 7.99, found: C,
68.49; H, 6.52; N, 7.87.
4.2.1. 5,6-Diethyl-1,3-diphenylpyrimidine-2,4(1H,3H)-
dione (1a) and 3,4,5,6-tetraethyl-1-phenylpyridin-
2(1H)-one (2a). The general procedure was used with
3-hexyne (28 mg, 0.34 mmol, 0.1 M), phenyl isocyanate
(325 mg, 2.27 mmol, 0.8 M), Ni(COD)2 (4.7 mg, 0.017
mmol, 5 mol %), IPr (13 mg, 0.034 mmol, 10 mol %), and
3.4 mL of toluene. The reaction mixture was purified first
4.2.3. 1,3-Bis(4-methoxyphenyl)-6-methyl-5-(trimethyl-
silyl)pyrimidine-2,4(1H,3H)-dione (1e) and 1-(4-meth-
oxyphenyl)-4,6-dimethyl-3,5-bis(trimethylsilyl)pyridin-
2(1H)-one (2e). The general procedure was used with

H. A. Duong, J. Louie / Tetrahedron 62 (2006) 7552–7559
7555
1-trimethylsilyl-1-propyne (35 mg, 0.31 mmol, 0.1 M),
4-methoxyphenyl isocyanate (93 mg, 0.62 mmol, 0.2 M),
Ni(COD)2 (4.3 mg, 0.016 mmol, 5 mol %), IPr (12 mg,
0.032 mmol, 10 mol %), and 3.1 mL of toluene. The reaction
mixture was purified by column chromatography on silica
gel (10% ethyl acetate/hexane then 10% acetone/hexane)
to afford 1e (87 mg, 68%) and 2e (14 mg, 24%) as white
solids.
gel (methylene chloride) to afford 1f as a white solid
(56 mg, 49%). Compound 2f was further purified by column
chromatography on silica gel (1% acetone/methylene chlo-
ride) to afford 2f as a white solid (12 mg, 24%).
4.2.4.1. Analytical data for 1f.
8
5
O
1
N
2
3
Si
10
OMe
4.2.3.1. Analytical data for 1e.
9
7
N
O
4
6
12 OMe
OMe
13
7
12
Si
5
11
O
N
1f
1
N
2
3
6
4
O
11
1H NMR (300 MHz, CDCl3, ppm): d 7.42–7.33 (m, 2H),
7.01–6.81 (m, 6H), 3.83 (s, 3H), 3.80 (s, 3H), 2.05 (s, 3H),
0.36 (s, 9H). 13C {1H} NMR (125 MHz, CDCl3, ppm):
d 165.2, 160.7, 160.4, 156.7, 152.0, 138.7, 136.4, 130.5,
130.0, 121.0, 120.7, 115.1, 114.7, 114.5, 114.1, 108.3, 55.6,
55.4, 21.4, 1.9. HMBC cross-peaks: H7 and C2, C3; H8
and C2; H9 and C10; H11 and C12; and other cross-peaks
of aromatic protons and aromatic carbons. NOE was
observed for aromatic protons and H7. IR (CHCl3, cmꢀ1):
1710, 1651, 1603, 1582. Anal. Calcd for C22H26N2O4Si:
C, 64.36; H, 6.38; N, 6.82, found: C, 64.20; H, 6.29; N,
6.68.
9
8
10
14
1e
OMe
1H NMR (300 MHz, CDCl3, ppm): d 7.21–7.16 (m, 4H),
7.04–7.00 (m, 4H), 3.87 (s, 3H), 3.85 (s, 3H), 2.00 (s, 3H),
0.34 (s, 9H). 13C {1H} NMR (125 MHz, CDCl3, ppm):
d 165.9, 160.4, 159.9, 157.8, 153.0, 131.1, 130.3, 130.0,
129.1, 115.3, 114.8, 108.2, 56.1, 56.0, 21.9, 1.9. HMBC
cross-peaks: H11 and C2, C3; H12 and C2; H13 and C7;
H14 and C10; and other cross-peaks of aromatic protons
and aromatic carbons. NOE was observed for aromatic pro-
tons and H11. IR (CHCl3, cmꢀ1): 1709, 1651. Anal. Calcd
for C22H26N2O4Si: C, 64.36; H, 6.38; N, 6.82, found: C,
64.37; H, 6.41; N, 6.70.
4.2.4.2. Analytical data for 2f.
10
6
O
1
N
2
Si
12
4.2.3.2. Analytical data for 2e.
OMe
3
5
4
Si
9
7
11
8
13 OMe
12
11
Si
2f
6
O
1
2
3
N
7
1H NMR (500 MHz, CD2Cl2, ppm): d 7.44–7.41 (m, 1H);
7.00–6.98 (m, 1H), 6.76–6.69 (m, 2H), 3.85 (s, 3H), 2.41
(s, 3H), 2.07 (s, 3H), 0.41 (s, 9H), 0.33 (s, 9H). 13C {1H}
NMR (125 MHz, CD2Cl2, ppm): d 166.1, 163.1, 161.2,
151.7, 141.9, 130.6, 125.7, 121.0, 115.2, 114.6, 114.2,
56.0, 26.7, 23.7, 4.0, 2.2. HMBC cross-peaks: H7 and C4,
C5; H8 and C4; H9 and C2, C3, C4; H10 and C2; H11
and C12; and other cross-peaks of aromatic protons and
aromatic carbons. IR (CH2Cl2, cmꢀ1): 1630, 1547. HRMS
(m/z): calcd for C20H31NO2Si (M+) 373.1893, found
373.1891.
5
10
8
4
Si
9
2e
1H NMR (500 MHz, acetone, ppm): d 7.08 (d, 8.8 Hz, 2H),
7.02 (d, 8.8 Hz, 2H), 3.86 (s, 3H), 2.40 (s, 3H), 2.06 (s, 3H),
0.38 (s, 9H), 0.28 (s, 9H). 13C {1H} NMR (125 MHz, ace-
tone, ppm): d 166.4, 162.8, 160.2, 153.2, 133.7, 130.4,
125.5, 115.4, 114.8, 55.9, 26.5, 24.1, 4.0, 2.3. HMBC
cross-peaks: H8 and C4, C5; H9 and C4; H10 and C2, C3,
C4; H11 and C2; H12 and C13; and other cross-peaks of aro-
matic protons and aromatic carbons. IR (CH2Cl2, cmꢀ1):
1629. HRMS (m/z): calcd for C20H31NO2Si (M+)
373.1893, found 373.1880.
4.2.5. 1,3-Bis(4-(trifluoromethyl)phenyl)-6-methyl-5-
(trimethylsilyl)pyrimidine-2,4(1H,3H)-dione (1g) and
1-(4-(trifluoromethyl)phenyl)-4,6-dimethyl-3,5-bis(tri-
methylsilyl)pyridin-2(1H)-one (2g). The general procedure
was used with 1-trimethylsilyl-1-propyne (37 mg, 0.33
mmol, 0.1 M), a,a,a-trifluoro-p-tolyl isocyanate (123 mg,
0.66 mmol, 0.2 M), Ni(COD)2 (4.5 mg, 0.016 mmol,
5 mol %), IPr (13 mg, 0.032 mmol, 10 mol %), and 3.3 mL
of toluene. The reaction mixture was purified first by column
chromatography on silica gel (5% ethyl acetate/hexane) to
afford 2g (46 mg, 68%) as a white solid. Compound 1g
was further purified by column chromatography on silica
gel (10% acetone/hexane then 1:1 methylene chloride/
hexane) to afford 1g as a white solid (27 mg, 17%).
4.2.4. 1,3-Bis(3-methoxyphenyl)-6-methyl-5-(trimethyl-
silyl)pyrimidine-2,4(1H,3H)-dione (1f) and 1-(3-meth-
oxyphenyl)-4,6-dimethyl-3,5-bis(trimethylsilyl)pyridin-
2(1H)-one (2f). The general procedure was used with
1-trimethylsilyl-1-propyne (31 mg, 0.28 mmol, 0.1 M),
3-methoxyphenyl isocyanate (82 mg, 0.56 mmol, 0.2 M),
Ni(COD)2 (3.8 mg, 0.014 mmol, 5 mol %), IPr (11 mg,
0.028 mmol, 10 mol %), and 2.8 mL of toluene. The reac-
tion mixture was purified first by column chromatography
on silica gel (20% ethyl acetate/hexane). Compound 1f
was further purified by column chromatography on silica

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H. A. Duong, J. Louie / Tetrahedron 62 (2006) 7552–7559
4.2.5.1. Analytical data for 1g.
151.9, 107.9, 40.4, 36.5, 19.5, 14.3, 13.0, 2.1. HMBC
cross-peaks: H5 and C1, C4, C6; H6 and C5; H7 and C3,
C4, C8; H8 and C7; H9 and C2, C3; H10 and C2. IR
(CHCl3, cmꢀ1): 1694, 1635, 1584. HRMS (m/z): calcd for
C12H22SiN2O2 (M+) 254.1451, found 254.1448.
CF3
10
Si
5
O
1
N
2
3
6
N
O
9
4
8
7
4.2.7. 1,3-Dibenzyl-6-methyl-5-(trimethylsilyl)pyrimi-
dine-2,4(1H,3H)-dione (1i). The general procedure was
used with 1-trimethylsilyl-1-propyne (35 mg, 0.31 mmol,
0.1 M), benzyl isocyanate (166 mg, 1.24 mmol, 0.4 M),
Ni(COD)2 (8.6 mg, 0.032 mmol, 10 mol %), IPr (24 mg,
0.064 mmol, 20 mol %), and 3.1 mL of toluene. After stir-
ring overnight at 80 ꢁC, the reaction mixture was purified
by column chromatography on silica gel (10% ethyl ace-
tate/hexane) to afford 1i as a white solid (85 mg, 72%).
CF3
1g
1H NMR (500 MHz, acetone, ppm): d 7.91 (d, 8.3 Hz, 2H),
7.81 (d, 8.3 Hz, 2H), 7.75 (d, 8.3 Hz, 2H), 7.54 (d, 8.3 Hz,
2H), 2.08 (s, 3H), 0.33 (s, 9H). 13C {1H} NMR (125 MHz,
acetone, ppm): d 164.8, 156.9, 151.5, 142.0, 140.1, 130.61,
(q, 32 Hz), 130.60, 130.2, 129.7 (q, 32 Hz), 126.8 (q, 3 Hz),
125.9 (q, 3 Hz), 124.5 (q, 271 Hz), 124.3 (q, 271 Hz),
107.5, 21.3, 1.21. HMBC cross-peaks: H9 and C2, C3; H10
and C2 and other cross-peaks of aromatic protons and aro-
matic carbons. NOE was observed for aromatic protons and
H9. IR (CH2Cl2, cmꢀ1): 1712, 1657, 1586. HRMS (m/z):
calcd for C22H20N2O2SiF6 (M+) 486.1198, found 486.1191.
4.2.7.1. Analytical data for 1i.
8
O
1
2
Si
5
N
7
3
4
O
N
4.2.5.2. Analytical data for 2g.
6
1i
CF3
9
O
1
2
3
Si
N
1H NMR (300 MHz, CDCl3, ppm): d 7.51–7.15 (m, 10H),
5.19–5.18 (m, 4H), 2.25 (s, 3H), 0.33 (s, 9H). 13C {1H}
NMR (125 MHz, CDCl3, ppm): d 165.0, 156.3, 153.0, 137.5,
136.7, 129.2, 129.1, 128.5, 127.8, 127.6, 126.3, 108.5,
48.4, 44.7, 20.0, 2.0. HMBC cross-peaks: H5 and C1, C4;
H6 and C3, C4; H7 and C2, C3; H8 and C2 and other cross-
peaks of aromatic protons and aromatic carbons. NOE was
observed for H7 and H6 and aromatic protons. IR (CHCl3,
cmꢀ1): 1695, 1638, 1584. Anal. Calcd for C22H26N2O2Si:
C, 69.80; H, 6.92; N, 7.40, found: C, 69.84; H, 6.91; N, 7.47.
5
4
Si
8
6
7
2g
1H NMR (500 MHz, acetone, ppm): d 7.87 (d, 8.3 Hz, 2H),
7.48 (d, 8.3 Hz, 2H), 2.43 (s, 3H), 2.08 (s, 3H), 0.40 (s, 9H),
0.29 (s, 9H). 13C {1H} NMR (125 MHz, acetone, ppm):
d 165.3, 162.8, 151.2, 144.3, 130.0–129.4 (m, 2C), 126.6
(m), 125.0, 124.5 (q, 271 Hz), 114.7, 25.9, 23.4, 3.2, 1.5.
HMBC cross-peaks: H6 and C4, C5; H7 and C4; H8 and
C2, C3; H9 and C2; and other cross-peaks of aromatic pro-
tons and aromatic carbons. IR (CH2Cl2, cmꢀ1): 1630, 1488.
Anal. Calcd for C20H28NOSi2F3: C, 58.36; H, 6.86; N, 3.40,
found: C, 58.74; H, 6.52; N, 3.51.
4.2.8. 1,3-Dicyclohexyl-6-methyl-5-(trimethylsilyl)pyri-
midine-2,4(1H,3H)-dione (1j). To a solution of Ni(COD)2
(4.7 mg, 0.016 mmol, 5 mol %) and IPr (13 mg, 0.032 mmol,
10 mol %) in 1.4 mL of toluenewas added dropwise a solution
of 1-trimethylsilyl-1-propyne (38 mg, 0.34 mmol, 0.1 M),
and cyclohexyl isocyanate (85 mg, 0.90 mmol, 0.2 M) in
2.0 mL of toluene. After stirring at room temperature for
1 h, the reaction mixture was purified by column chromato-
graphy on silica gel (2:3 methylene chloride/hexane) to af-
ford 1j as a white solid (74 mg, 60%). Some decomposition
product of a pyridone product was also observed by 1H NMR.
4.2.6. 1,3-Diethyl-6-methyl-5-(trimethylsilyl)pyrimidine-
2,4(1H,3H)-dione (1h). The general procedure was used
with 1-trimethylsilyl-1-propyne (51 mg, 0.45 mmol, 0.1 M),
ethyl isocyanate (65 mg, 0.90 mmol, 0.2 M), Ni(COD)2
(6.2 mg, 0.023 mmol, 5 mol %), IPr (17 mg, 0.046 mmol,
10 mol %), and 4.5 mL of toluene. The reaction mixture
was purified by column chromatography on silica gel (5%
acetone/methylene chloride) to afford 1h as a colorless oil
(96 mg, 83%).
4.2.8.1. Analytical data for 1j.
8
O
1
4.2.6.1. Analytical data for 1h.
2
Si
N
10
7
3 N 4 O
O
5
1
N
2
Si
6
6
5
N
O
4
9
3
1j
7
8
1h
1H NMR (500 MHz, CD2Cl2, ppm): d 4.67–4.62 (m, 1H),
3.83 (m, 1H), 2.54–2.47 (m, 2H), 2.38–2.29 (m, 2H), 2.25
(s, 3H), 2.85–1.77 (m, 4H), 1.65–1.37 (m, 6H), 1.36–1.53
(m, 6H), 0.26 (s, 9H). 13C {1H} NMR (125 MHz, CD2Cl2,
1H NMR (300 MHz, CDCl3, ppm): d 3.94 (m, 4H), 2.31 (s,
3H), 1.27 (t, 7.0 Hz, 3H), 1.19 (t, 7.0 Hz, 3H), 0.30 (s, 9H).
13C {1H} NMR (125 MHz, CDCl3, ppm): d 165.0, 155.5,

H. A. Duong, J. Louie / Tetrahedron 62 (2006) 7552–7559
7557
ppm): d 166.2, 156.4, 152.0, 108.4, 60.2, 29.8, 29.1, 27.1,
27.0, 26.1, 25.8, 20.9, 2.3. HMBC cross-peaks: H7 and
C2, C3; H8 and C2, and other cross-peaks of cyclohexyl pro-
tons and cyclohexyl carbons. NOE was observed for cyclo-
hexyl protons and H7. IR (CH2Cl2, cmꢀ1): 1697, 1637,
1582; Anal. Calcd for C20H34N2O2Si: C, 66.25; H, 9.45;
N, 7.73, found: C, 66.36; H, 9.18; N, 7.60.
phenyl isocyanate (234 mg, 1.96 mmol, 0.2 M), Ni(COD)2
(3.4 mg, 0.012 mmol, 5 mol %), IPr (9 mg, 0.024 mmol,
10 mol %), and 2.4 mL of toluene. The reaction mixture
was purified first by column chromatography on silica gel
(methylene chloride) to afford 2l (18 mg, 38%) as a white
solid. 1l was further purified by column chromatography
on silica gel (5% ethyl acetate/hexane) to afford 1l (35 mg,
38%) as a white solid.
4.2.9. Triethyl 1,3-dicyclohexyl-1,2,3,6-tetrahydro-5-(tri-
methylsilyl)-2,6-dioxopyrimidine-4-carboxylate (1k)
and triethyl 3,5,6-tris(trimethylsilyl)benzene-1,2,4-
tricarboxylate (3k). The general procedure was used with
ethyl 3-(trimethylsilyl)propynoate (46 mg, 0.27 mmol,
0.1 M), cyclohexyl isocyanate (68 mg, 0.54 mmol, 0.2 M),
Ni(COD)2 (3.7 mg, 0.013 mmol, 5 mol %), IPr (10 mg,
0.026 mmol, 10 mol %), and 2.7 mL of toluene. The reac-
tion mixture was purified by column chromatography on
silica gel (5% ethyl acetate/hexane) to afford 1k (49 mg,
43%) and 3k as white solids (21 mg, 45%).
4.2.10.1. Analytical data for 1l.
8
O
1
N
2
3
Si
5
4
N
O
6
7
1l
1H NMR (500 MHz, CD2Cl2, ppm): d 7.52–7.43 (m, 6H),
7.30–7.23 (m, 4H), 5.88–5.80 (m, 1H), 5.61 (dd, 1.5 and
15.7 Hz, 1H), 1.64 (dd, 1.5 and 7.0 Hz, 3H), 0.25 (s, 9H).
13C {1H} NMR (125 MHz, CD2Cl2, ppm): d 166.3, 158.1,
152.3, 138.4, 137.0, 136.5, 130.0, 129.8, 129.6, 129.3,
129.2, 128.8, 126.3, 108.8, 18.4, 2.1. HMBC cross-peaks:
H5 and C2, C3, C6, C7; H6 and C3, C5, C7; H7 and C5,
C6; H8 and C2; and other cross-peaks of aromatic protons
and aromatic carbons. NOE was observed for aromatic pro-
tons and H5. IR (CH2Cl2, cmꢀ1): 1711, 1653, 1569. Anal.
Calcd for C22H24N2O2Si: C, 70.18; H, 6.42; N, 7.44, found:
C, 70.15; H, 6.51; N, 7.41.
4.2.9.1. Analytical data for 1k.
11
O
1
N
2
Si
O
4
N
O
3
10
O
5
9
6
7
8
1k
1H NMR (500 MHz, CDCl3, ppm): d 4.71–4.67 (m, 1H),
4.38–4.36 (m, 2H), 3.24–3.20 (m, 1H), 2.52–2.45 (m, 2H),
2.40–2.32 (m, 2H), 1.87–1.77 (m, 6H), 1.60–1.59 (m, 4H),
1.40–1.11 (m, 9H), 0.19 (s, 9H). 13C {1H} NMR (125 MHz,
CDCl3, ppm): d 166.0, 163.5, 150.8, 150.3, 107.0, 64.5,
62.7, 54.3, 29.4, 28.7, 26.7, 26.5, 25.4, 25.1, 14.0, ꢀ0.3.
HMBC cross-peaks: H5 and C3, C4, C6, C7; H8 and C9,
C10; H9 and C8; H11 and C2; other cross-peaks of cyclo-
hexyl protons and cyclohexyl carbons. IR (CHCl3, cmꢀ1):
1742, 1704, 1647, 1590. Anal. Calcd for C22H36N2O4Si: C,
62.82; H, 8.63; N, 6.66, found: C, 62.99; H, 8.46; N, 6.68.
4.2.10.2. Analytical data for 2l.
13
O
1
2
Si
N
5
10
11
3
7
4
6
8
Si
9
12
2l
1H NMR (300 MHz, CD2Cl2, ppm): d 7.47–7.34 (m, 3H),
7.09–7.06 (m, 2H), 6.59 (dq, 1.8 and 15.8 Hz, 1H), 5.77–
5.55 (m, 3H), 1.84 (d, 6.6 Hz, 3H), 1.58 (d, 6.6 Hz, 3H),
0.22 (s, 9H), 0.15 (s, 9H). 13C {1H} NMR (125 MHz,
CD2Cl2, ppm): d 165.8, 164.9, 154.8, 140.2, 135.7, 135.3,
130.7, 129.7, 129.5, 128.4, 125.8, 114.8, 18.5, 18.3, 4.3,
2.0. HMBC cross-peaks: H8 and C6, C7; H9 and C4; H10
and C2, C3, C4, C11, C12; H12 and C10, C11; H13 and
C2; and other cross-peaks of olefinic/aromatic protons and
olefinic/aromatic carbons. IR (CH2Cl2, cmꢀ1): 1632. Anal.
Calcd for C23H33NOSi2: C, 69.81; H, 8.41; N, 3.54, found:
C, 69.41; H, 8.25; N, 3.36.
4.2.9.2. Analytical data for 3k.
TMS O
TMS
O
O
TMS
O
O
O
3k
1H NMR (500 MHz, CD2Cl2, ppm): d 4.33–4.21 (m, 6H),
1.39–1.29 (m, 9H), 0.36 (s, 9H), 0.33 (s, 9H), 0.26 (s, 9H).
13C {1H} NMR (125 MHz, CD2Cl2, ppm): d 170.7, 170.0,
153.5, 151.4, 147.7, 139.4, 139.2, 139.0, 62.3 (m, 3C), 14.3
(m, 3C), 4.4, 3.9, 1.8. IR (CH2Cl2, cmꢀ1): 1726. HRMS
(m/z):calcdforC24H42O6Si3 (M+)510.2289, found510.2291.
4.2.11. 5-Tert-butyl-1,3-diethyl-6-methylpyrimidine-
2,4(1H,3H)-dione (1m). The general procedure was used
with 4,4-dimethyl-2-pentyne (34 mg, 0.35 mmol, 0.1 M),
ethyl isocyanate (100 mg, 1.42 mmol, 0.4 M), Ni(COD)2
(9.7 mg, 0.035 mmol, 10 mol %), IPr (27 mg, 0.070 mmol,
20 mol %), and 3.5 mL of toluene. After stirring at 80 ꢁC
overnight, the reaction mixture was purified by column chro-
matography on silica gel (20% ethyl acetate/hexane) to
afford 1m as a yellow solid (68 mg, 81%).
4.2.10. 5-(Trimethylsilyl)-1,3-diphenyl-6-((Z)-prop-1-
enyl)pyrimidine-2,4(1H,3H)-dione (1l) and 3,5-bis(tri-
methylsilyl)-1-phenyl-4,6-di((Z)-prop-1-enyl)pyridin-
2(1H)-one (2l). The general procedure was used with
1-trimethylsilyl-pent-3-en-1-yne (34 mg, 0.24 mmol, 0.1 M),

7558
H. A. Duong, J. Louie / Tetrahedron 62 (2006) 7552–7559
4.2.11.1. Analytical data for 1m.
ppm): d 164.2, 155.7, 152.1, 138.3, 135.6, 130.0, 129.3,
129.2, 128.9, 128.6, 128.4, 108.2, 30.9, 19.7, 12.0. HMBC
cross-peaks: H5 and C2, C3; H6 and C3, C5; H7 and C1,
C2, C3; and other cross-peaks of aromatic protons and aro-
matic carbons. IR (CHCl3, cmꢀ1): 1709, 1654. Anal. Calcd
for C20H20N2O2: C, 74.98; H, 6.29; N, 8.74, found: C, 74.70;
H, 6.46; N, 8.43.
10
11
O
5
1
N
2
6
9
3
8
4
N
7
O
1m
1
1H NMR (300 MHz, CDCl3, ppm): d 4.01–3.92 (m, 4H),
2.39 (s, 3H), 1.44 (s, 9H), 1.28 (t, 7.0 Hz, 3H), 1.21 (t,
7.0 Hz, 3H). 13C {1H} NMR (125 MHz, CDCl3, ppm):
d 162.2, 151.1, 146.5, 120.2, 40.4, 36.9, 35.7, 32.0, 18.9,
14.5, 13.1. HMBC cross-peaks: H5 and C1, C4, C6; H6
and C5; H7 and C3, C4, C8; H8 and C7; H9 and C2, C3;
H10 and C2, C11. IR (CHCl3, cmꢀ1): 1693, 1644, 1587.
Anal. Calcd for C13H22N2O2: C, 65.51; H, 9.30; N, 11.75,
found: C, 65.69; H, 9.49; N, 11.64.
4.2.12.3. Analytical data for 2n (impure). H NMR
(300 MHz, CDCl3, ppm): d 7.51–7.36 (3H); 7.18–7.14
(2H), 3.36–3.23 (m, 2H), 2.29 (s, 3H), 1.95 (s, 3H); 1.35–
1.31 (m, 12H).
4.2.13. One-pot cycloaddition followed by Stille coupling:
1,3-diethyl-6-methyl-5-phenylpyrimidine-2,4(1H,3H)-
dione. The general procedure for cycloaddition was used
with tributyl(1-propynyl)tin (134 mg, 0.41 mmol, 0.1 M),
ethyl isocyanate (116 mg, 1.64 mmol, 0.4 M), Ni(COD)2
(5.6 mg, 0.020 mmol, 5 mol %), IPr (16 mg, 0.040 mmol,
10 mol %), and 4.1 mL of toluene. After stirring at 80 ꢁC
overnight, the solvent was removed.
4.2.12. 5-Isopropyl-6-methyl-1,3-diphenylpyrimidine-
2,4(1H,3H)-dione (1n), 6-isopropyl-5-methyl-1,3-diphe-
nylpyrimidine-2,4(1H,3H)-dione (10n), and 3,5-diiso-
propyl-4,6-dimethyl-1-phenylpyridin-2(1H)-one (2n). The
general procedure was used with 4-methyl 2-pentyne
(53 mg, 0.65 mmol, 0.1 M), phenyl isocyanate (154 mg, 1.30
mmol, 0.2 M), Ni(COD)2 (8.9 mg, 0.032 mmol, 5 mol %), IPr
(25 mg, 0.064 mmol, 10 mol %), and 6.5 mL of toluene. The
reaction mixture was purified by column chromatography on
silica gel (15–25% ethyl acetate/hexane) to afford 1n (72 mg,
35%) and 10n (29 mg, 14%) as white solids. A fraction was
also determined to be the impure pyridone 2n (16 mg, 18%).
In a glove box, to a Schlenk flask equipped with a stir bar,
Pd(PPh3)4 (47 mg, 0.041 mmol, 10 mol %), phenyl iodide
(166 mg, 0.082 mmol, 200 mol %), N,N-dimethyl form-
amide (4.1 mL), and copper iodide (78 mg, 0.41 mmol,
100 mol %) were successively added. After stirring for
1 min, the residue from the cycloaddition mixturewas added.
The flask was then taken out of the glove box and stirred
under N2 at 60 ꢁC for 3 h. The reaction mixture was cooled
down, diluted with Et2O, and washed with water. The aque-
ous layer was further extracted with Et2O. The combined
organic layers were dried over MgSO4 and concentrated. The
residue was purified by column chromatography on silica gel
(10% ethyl acetate/hexane then 3% methanol/methylene
chloride) to afford 5 as a white solid (79 mg, 75%).
4.2.12.1. Analytical data for dione 1n.
11
5
O
1
2
10
9
N
6
3 N 4 O
7
4.2.13.1. Analytical data for 5.
8
1n
O
5
1
N
2
3
1H NMR (500 MHz, CDCl3, ppm): d 7.50–7.26 (m, 10H),
3.08–3.05 (sept, 7.0 Hz, 1H), 1.96 (s, 3H), 1.35 (d, 7.0 Hz,
6H). 13C {1H} NMR (125 MHz, CDCl3, ppm): d 162.3,
151.8, 146.9, 138.0, 135.5, 129.9, 129.3, 129.2, 129.0,
128.6, 128.5, 117.2, 28.5, 20.7, 18.1. HMBC cross-peaks: H9
and C2, C3; H10 and C1, C2, C3, C11; H11 and C10; and
other cross-peaks of aromatic protons and aromatic carbons.
IR (CHCl3, cmꢀ1): 1708, 1656. Anal. Calcd for C20H20N2O2:
C, 74.98; H, 6.29; N, 8.74, found: C, 75.0; H, 6.36; N, 8.73.
6
9
4
N
O
7
5
8
1H NMR (500 MHz, CDCl3, ppm): d 7.42–7.33 (m, 3H),
7.22–7.20 (m, 2H), 4.08–3.99 (m, 4H), 2.17 (s, 3H), 1.35
(t, 7.1 Hz, 3H), 1.26 (t, 7.1 Hz, 3H). 13C {1H} NMR
(125 MHz, CDCl3, ppm): d 162.0, 151.4, 147.9, 134.5,
131.0, 128.5, 127.8, 114.6, 40.8, 37.0, 17.5, 14.3, 13.0.
HMBC cross-peaks: H5 and C1, C4; H6 and C5; H7 and
C3, C4, C8; H9 and C2, C3; and other cross-peaks of aro-
matic protons and aromatic carbons. IR (CHCl3, cmꢀ1):
1696, 1644. Anal. Calcd for C15H18N2O2: C, 69.74; H,
7.02; N, 10.84, found: C, 69.44; H, 6.83; N, 10.76.
4.2.12.2. Analytical data for dione 10n.
O
7
1
2
3
N
5
N
O
4
4.2.14. 3-(4-(Trifluoromethyl)phenyl)-1-(4-methoxy-
phenyl)-6-methyl-5-(trimethylsilyl)pyrimidine-2,4(1H,3H)-
dione (1g), 1,3-bis(4-(trifluoromethyl)phenyl)-6-methyl-
5-(trimethylsilyl)pyrimidine-2,4(1H,3H)-dione (10g),
and 1-(4-(trifluoromethyl)phenyl)-4,6-dimethyl-3,5-
bis(trimethylsilyl)pyridin-2(1H)-one (2g). The general pro-
cedure was used with 1-trimethylsilyl-1-propyne (32 mg,
6
1'n
1H NMR (300 MHz, CDCl3, ppm): d 7.54–7.35 (m, 6H),
7.29–7.26 (m, 4H), 2.74 (sept, 7.1 Hz, 1H), 2.17 (s, 3H),
1.26 (d, 7.1 Hz, 6H). 13C {1H} NMR (125 MHz, CDCl3,

H. A. Duong, J. Louie / Tetrahedron 62 (2006) 7552–7559
7559
0.29 mmol, 0.1 M), a,a,a-trifluoro-p-tolyl isocyanate (107 mg,
0.58 mmol, 0.2 M), 4-methoxyphenyl isocyanate (85 mg,
0.58 mmol, 0.2 M), Ni(COD)2 (3.9 mg, 0.014 mmol,
5 mol %), IPr (11 mg, 0.028 mmol, 10 mol %), and 2.9 mL
of toluene. The reaction mixture was purified by column
chromatography on silica gel (4:6 hexane/methylene chloride
then 10% ethyl acetate/hexane) to give 1g (15 mg, 11%),
10g (18 mg, 14%), and 2g (26 mg, 44%) as white solids.
(s, 3H), 1.29 (t, 7.1 Hz, 3H), 0.30 (s, 9H). 13C {1H} NMR
(125 MHz, CD2Cl2, ppm): d 165.6, 159.8, 157.1, 152.7,
130.0, 129.4, 114.8, 108.3, 56.0, 40.9, 20.1, 14.4, 2.1.
HMBC cross-peaks: H5 and C3, C4, C6; H7 and C2, C3;
H8 and C2. IR (CH2Cl2, cmꢀ1): 1700, 1642, 1580. Anal.
Calcd for C17H24N2O3Si: C, 61.41; H, 7.28; N, 8.43, found:
C, 61.46; H, 7.23; N, 8.34.
4.2.14.1. Analytical data for 10g.
Acknowledgements
We gratefully acknowledge the University of Utah, Merck,
NSF (Career Award), the Camille-Dreyfus Foundation, and
the NIGMS for support of this research.
11
Si
CF3
O
1
N
2
3
4
N
O
10
8
5
Supplementary data
7
6
9
OMe
1'g
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2006.03.119.
1H NMR (500 MHz, acetone, ppm): d 7.80 (d, 8.8 Hz, 2H),
7.52 (d, 8.8 Hz, 2H), 7.34 (d, 8.8 Hz, 2H), 7.05 (d, 8.8 Hz,
2H), 3.85 (s, 3H), 2.05 (s, 3H), 0.30 (s, 9H). 13C {1H}
NMR (125 MHz, acetone, ppm): d 164.9, 160.1, 158.4,
151.8, 140.4, 130.9, 130.2, 129.6 (q, 33 Hz), 125.9, 124.6
(q, 271 Hz), 114.7, 106.7, 55.2, 21.2, 1.2. HMBC cross-
peaks: H5 and C2, C3; H6 and C2; and other cross-peaks
of aromatic protons and aromatic carbons. NOE was ob-
served for H5/H8 and H6, H7, H10; H6/H7 and H9. IR
(CH2Cl2, cmꢀ1): 1710, 1654. HRMS (m/z): calcd for
C22H23N2O3SiF3 (M+) 448.1430, found 448.1426.
References and notes
1. For a review, see: (a) Varela, J. A.; Saa, C. Chem. Rev. 2003,
103, 3787; (b) Louie, J. Curr. Org. Chem. 2005, 9, 605.
2. (a) Earl, R. A.; Vollhardt, K. P. C. J. Org. Chem. 1984, 49, 4786;
(b) Hong, P.; Yamazaki, H. Tetrahedron Lett. 1977, 1333; (c)
Naiman, A.; Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl.
1977, 16, 708; (d) Vollhardt, K. P. C. Angew. Chem. 1984,
96, 525.
3. (a) Yamamoto, Y.; Takagishi, H.; Itoh, K. Org. Lett. 2001, 3,
2117; (b) Yamamoto, Y.; Ogawa, R.; Itoh, K. J. Am. Chem.
Soc. 2001, 123, 6189; (c) Varela, J. A.; Castedo, L.; Saa, C.
J. Org. Chem. 2003, 68, 8595.
4. (a) Louie, J.; Gibby, J. E.; Farnworth, M. V.; Tekavec, T. N.
J. Am. Chem. Soc. 2002, 124, 15188; (b) Tekavec, T. N.;
Arif, A. M.; Louie, J. Tetrahedron 2004, 60, 7431; (c)
Duong, H. A.; Cross, M. J.; Louie, J. J. Am. Chem. Soc.
2004, 126, 11438; (d) McCormick, M. M.; Duong, H. A.;
Zuo, G.; Louie, J. J. Am. Chem. Soc. 2005, 127, 5030; (e)
Duong, H. A.; Louie, J. J. Organomet. Chem. 2005, 690,
5098; (f) Tekavec, T. N.; Louie, J. Org. Lett. 2005, 7, 4037;
(g) Hoberg, H.; Oster, B. W. Synthesis 1982, 324.
5. Hoberg, H.; Oster, B. W. J. Organomet. Chem. 1983, 252,
359.
4.2.15. 1,3-Bis(4-methoxyphenyl)-6-methyl-5-(trimethyl-
silyl)pyrimidine-2,4(1H,3H)-dione (1e), 1-(4-methoxy-
phenyl)-4,6-dimethyl-3,5-bis(trimethylsilyl)pyridin-
2(1H)-one (2e), and 1-ethyl-3-(4-methoxyphenyl)-6-
methyl-5-(trimethylsilyl)pyrimidine-2,4(1H,3H)-dione
(10e). The general procedure was used with 1-trimethylsilyl-
1-propyne (33 mg, 0.29 mmol, 0.1 M), 4-methoxyphenyl
isocyanate (88 mg, 0.58 mmol, 0.2 M), ethyl isocyanate
(42 mg, 0.58 mmol, 0.2 M), Ni(COD)2 (3.9 mg, 0.014 mmol,
5 mol %), IPr (11 mg, 0.028 mmol, 10 mol %), and 2.9 mL
of toluene. The reaction mixture was purified by column
chromatography on silica gel with 10–25% ethyl acetate/
hexane to obtain 2e (10 mg, 18%), then with 10% acetone/
hexane to obtain 10e (28 mg, 29%), and then with 5%
acetone/methylene chloride to obtain 1e (34 mg, 28%).
6. IPr¼1,3-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene; SIPr¼
1,3-bis-(2,6-diisopropylphenyl)-4,5-dihydroimidazolin-2-yli-
dene.
4.2.15.1. Analytical data for 10e.
7. Hoberg, H.; Oster, B. W. J. Organomet. Chem. 1982, 234, C37.
8. (a) Han, X.; Stoltz, B. M.; Corey, E. J. J. Am. Chem. Soc. 1999,
121, 7600; (b) Liebeskind, L. S.; Riesinger, S. W. J. Org. Chem.
1993, 58, 408.
9. (a) Arduengo, A. J., III; Krafczyk, R.; Schmutzler, R.; Craig,
H. A.; Goerlich, J. R.; Marshall, W. J.; Unverzagt, M.
Tetrahedron 1999, 55, 14523; (b) Bohm, V. P. W.;
Weskammp, T.; Gstottmayr, W. K.; Herrmann, W. A. Angew.
Chem., Int. Ed. 2000, 39, 1602.
OMe
8
O
1
N
2
3
Si
4
N
5
O
7
1'e
6
1H NMR (300 MHz, CD2Cl2, ppm): d 7.09 (d, 9.0 Hz, 2H),
6.98 (d, 9.0 Hz, 2H), 3.97 (q, 7.1 Hz, 2H), 3.84 (s, 3H), 2.39
10. Bialy, L.; Waldmann, H. Chem.—Eur. J. 2004, 10, 2759.