Regioselective synthesis of 1,4,6-trisubstituted-2-pyridinones and 2,3-disubstituted (2H)-isoquinolin-1-ones via tandem stille reaction/ heterocyclisation

Article abstract of DOI:10.1055/s-2005-870009

A general route to 1,4,6-trisubstituted 2-pyridinones and 2,3-disubstituted (2H)-isoquinolin-1-ones from (Z)-3-iodovinylic amides 1a-h and 2-iodo N-substituted benzamides 2a-f is described, including compounds bearing a substituent on the aromatic ring. Treatment of (Z)-β-iodovinylic amides 1a-h and 2-iodobenzamides 2a-f with various allenyltributyltin reagents in the presence of palladium acetate, triphenylphosphine and tetrabutylammonium bromide in acetonitrile provided good yields of the corresponding 1,4,6-trisubstituted 2-pyridinones 3a-k and 2,3-disubstituted (2H)-isoquinolin-1-ones 4a-i via tandem Stille reaction and 6-endo-dig azacyclisation. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-870009

PAPER
2349
Regioselective Synthesis of 1,4,6-Trisubstituted-2-Pyridinones and 2,3-Disub-
stituted (2H)-Isoquinolin-1-ones via Tandem Stille Reaction/Heterocyclisation
S
ynthesis of 2-Pyr
h
idinones
a
nd
a
(2
H
)
-Isoqu
l
inolin-
i
1-onesl Cherry,a Alain Duchêne,a Jérôme Thibonnet,a,b Jean-Luc Parrain,b Mohamed Abarbri*a
a
Laboratoire de Synthèse et Physicochimie Organique et Thérapeutique, Faculté des Sciences de Tours, Parc de Grandmont, EA 3857,
37200 Tours, France
Fax +33(2)47367073; E-mail: mohamed.abarbri@univ-tours.fr
b
Laboratoire Symbio, Equipe Synthèse par Voie Organométallique, associé au CNRS (UMR 6178, Université Paul Cézanne,
Aix Marseille III, Campus scientifique de Saint Jérôme, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
Received 21 February 2005; revised 23 March 2005
and alkyne reagents.18 These methodologies were then
applied to the synthesis of g-tributyltin methyl-
idenebutenolides19 and g-alkylidene pyrrol-2(5H)-ones.18
In continuation of our studies on the synthesis of unsatur-
Abstract: A general route to 1,4,6-trisubstituted 2-pyridinones and
2,3-disubstituted (2H)-isoquinolin-1-ones from (Z)-3-iodovinylic
amides 1a–h and 2-iodo N-substituted benzamides 2a–f is de-
scribed, including compounds bearing a substituent on the aromatic
ring. Treatment of (Z)-b-iodovinylic amides 1a–h and 2-iodobenza- ated heterocycles,20 we have recently described our first
mides 2a–f with various allenyltributyltin reagents in the presence
results on the synthesis of the 2-pyridinones by approach-
of palladium acetate, triphenylphosphine and tetrabutylammonium
es involving intramolecular addition of amides to allenyl-
bromide in acetonitrile provided good yields of the corresponding
stannanes (Scheme 1).21 We now present our full results
1,4,6-trisubstituted 2-pyridinones 3a–k and 2,3-disubstituted (2H)-
in this field and their extension to regioselective synthesis
isoquinolin-1-ones 4a–i via tandem Stille reaction and 6-endo-dig
azacyclisation.
of isoquinolinones.
Key words: pyridinones, isoquinolinones, tributylstannylallenes,
palladium catalyst, azacyclisation
Synthesis of (1H)-Pyridin-2-ones
Our investigation began with the coupling of
tributylstannylallenes22 with (Z)-N-benzyl-3-iodopropen-
amide17,21 (1a) under various conditions (solvent, catalyst,
presence of additives, etc.). THF was found to be ineffec-
tive whereas DMF afforded a poor yield of cyclised prod-
uct (< 40%). We also observed that phosphine-ligated
palladium appeared to be more efficient than other palla-
dium salts such as palladium acetate (without additional
triphenylphosphine) or bis(acetonitrile)palladium chlo-
ride. Tetrakis(triphenylphosphine)palladium gave ap-
proximately identical yields to the Pd(OAc)2/Ph3P couple.
The use of excess (1.5 equiv) of allenyltributyltin is essen-
tial to obtain good yields of these pyridinones 3a–k, and a
stoichiometric quantity of allenyltributyltin provides the
desired pyridinones, but in poor yields (<40%). As previ-
ously reported, the use of sodium carbonate as base is not
necessary in these heterocyclisation reactions.21 In the ab-
sence of a palladium complex, no reaction occurred be-
tween the (Z)-iodovinylic amides 1a–h and the
allenyltributyltins, and the starting materials were recov-
ered. After experimenting with a variety of conditions and
methods, it was found that the best result for the final cy-
clisation step providing 83% yield of 2-pyridinone 3a was
obtained by using 5% palladium acetate, 10% triphe-
nylphosphine and tetrabutylammonium bromide in aceto-
nitrile at 80 °C (Scheme 1). The results are summarised in
Table 1.
Pyridones and isoquinolinones constitute an important
class of heterocyclic compounds. There are several meth-
ods available1,2 for the preparation of these unsaturated
heterocycles. The 2-pyridinone substructure is found in
many biologically active natural products and in the pyri-
dine nucleotide cycle in plants and also has several phys-
iological activities,3 such as potent antitumor,4
antifungal,5 antiviral,6 psychotherapeutic,7 and antibiotic.8
Moreover, 2-pyridones are key intermediates in the syn-
thesis of the corresponding pyridines.9 N-Substituted 2-
pyridinones have been employed as active ingredients in
drugs for the treatment of fibrotic diseases.10 As a conse-
quence, much attention has been paid to the synthesis of
2-pyridinone derivatives. 2-Pyridinones have been pre-
pared by numerous methods,11 for example by the oxida-
tion of an N-substituted pyridinium salt,12 by
Knœvenagel-type reaction,13 such as cross-condensation
of cyanoacetoamide and b-dicarbonyl compounds by ba-
sic catalyst or by the reaction of 2-pyrones with primary
amines.14 These heterocycles have also been synthesised
through a variety of cycloaddition procedures.15
We have previously described the synthesis of dienoic ac-
ids and enynes bearing a carboxylic acid function from b-
iodovinylic acids and vinyltin or alkynylzinc reagents.16
We have also reported the synthesis of dienamides and
enynamides from dienoic acids17 or by iodovinylic amides
The reaction of tributylstannylallene with a range of (Z)-
3-substituted 3-iodopropenamides 1a–h under regio- and
stereocontrol gave good yields of 1,4,6-trisubstituted py-
SYNTHESIS 2005, No. 14, pp 2349–2356
Advanced online publication: 13.07.2005
DOI: 10.1055/s-2005-870009; Art ID: Z04005SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
5

2350
K. Cherry et al.
PAPER
R
I
Synthesis of (2H)-Isoquinolin-1-ones
R
R2
R2
i
NHR1
+
•
NR1
Bu3Sn
The isoquinolinone skeleton constitutes the framework of
a wide variety of plant alkaloids and drugs.23 The many
synthetic methods devised for the development of this iso-
quinolinone framework generally involve the transforma-
tion of homophthalic acids,24 condensation of
homophthalic anhydrides with imidates,25 substitution
reaction by primary amines on the corresponding
isocoumarins,26 treatment of dilithiated N,2-dimethyl-
benzamides with N,N-dimethylcarboxamides27 or the reac-
tion of ortho-lithiated deprotonated N-methylbenzamide
O
O
i: Pd(OAc)2 (5%), PPh3 (10%),
n-Bu4NBr (2 equiv), CH3CN, 80 °C
1a–h
3a–k
Scheme 1 Reagents and conditions: i. Pd(OAc)2 (5%), Ph3P (10%),
Bu4NBr (2 equiv), MeCN, 80 °C
ridinones 3a–k as sole products (Table 1, entries 1–5, 8, 9
and 11). The use of 3-alkylallenylstannanes (Table 1, en-
tries 6, 7 and 10) showed that the regioselective heteroan- with 1,2-diketones followed by convenient aromatisation
nulation reaction occurred only on carbons 1 and 2 of the of the resulting diols.28 In our case, the reaction conditions
allenyltin reagent. The regioselectivity of this process chosen were those used for the synthesis of 2-pyridinones.
probably arose from the nucleophilic attack of the amide Thus, the coupling of 2-iodobenzamide derivatives 2a–f
function at the central carbon of the allenyl moiety. The with tributylstannylallene at 80 °C under identical condi-
tions provided a highly regioselective method for the syn-
thesis of isoquinolinones 4a–i (Scheme 2). The results are
summarised in Table 2.
methodology also proved to be very convenient and gen-
eral for the synthesis of various substituted 2-pyridinones
with good yields. In all cases, the pyridinones 3a–k were
obtained without any trace of 3-allenyl or 3-alkynyl pro-
penamides or 2-pyrolones. It should be noted that the tem-
perature was a crucial parameter, because no reaction
occurred at room temperature.
I
R2
R2
i
•
NHR1
N
+
Bu3Sn
R1
R
O
R
O
These amides 1a–h were obtained in good yields by treat-
ment of the corresponding b-iodovinylic acids with oxalyl
chloride followed by addition of primary amine.17 We ob-
tained optically pure 2-pyridinones 3h–i from the avail-
able optically active amides (Table 1, entries 8, 9).
i: Pd (OAc)2 (5%), PPh3 (10%),
2a–f
4a–i
n-Bu4NBr (2 equiv), CH3CN, 80 °C
Scheme 2 Reagents and conditions: i. Pd(OAc)2 (5%), Ph3P (10%),
Bu4NBr (2 equiv), MeCN, 80 °C
In continuation of our studies on the synthesis of 2-pyrid-
inones by approaches which involve intramolecular addi-
tion of amides to allenylstannanes, we next examined the
possibility of regioselectively preparing isoquinolin-1-
ones by the same methodology and report the results here.
As shown in Table 2, the reaction of tributylstannylal-
lenes with 2-iodo N-substituted benzamides 2a–f under
regio- and stereocontrol gave reasonable yields of 2,3-di-
substituted (2H)-isoquinolin-1-ones 4a–i. In all cases, di-
Table 1 Regioselective Preparation of 2-Pyridinones 3a–k
Entry
R
R1
R2
H
2-Pyridinone
Yield (%)a
1
2
H
Bn
1a
1b
1c
1d
1e
1b
1c
1f
3a
3b
3c
3d
3e
3f
83
85
81
87
79
84
85
86
84
84
82
Me
Ph
Bn
H
3
Bn
H
4
Et
Bn
H
5
SiMe3
Me
Ph
Bn
H
6
Bn
Me
Me
H
7
Bn
3g
3h
3i
8
Me
Me
Me
Me
CH(Ph)Me
CH(i-Pr)Me
Bn
9
1g
1b
1h
H
10
11
n-Bu
H
3j
allyl
3k
a Isolated yield of analytically pure products.
Synthesis 2005, No. 14, 2349–2356 © Thieme Stuttgart · New York

PAPER
Synthesis of 2-Pyridinones and (2H)-Isoquinolin-1-ones
2351
Table 2 Regioselective Preparation of (2H)-Isoquinolin-1-ones 4a–i
Entry
R
H
H
H
H
F
R1
R2
H
Isoquinolinone
Yield (%)a
1
2
3
4
5
6
7
8
9
Bn
2a
2b
2c
2d
2e
2f
4a
4b
4c
4d
4e
4f
65
61
60
64
63
62
63
60
61
n-Bu
CH(Ph)Me
allyl
Bn
H
H
H
H
F
allyl
Bn
H
H
F
2a
2e
2a
Me
Me
n-Bu
4g
4h
4i
Bn
H
Bn
a Isolated yield of analytically pure products.
verse (2H)-isoquinolin-1-one products were obtained pathway involving addition of the vinylic palladium to the
without any trace of alkylidene isoindolones,29 giving a central carbon atom of the stannylallene could be exclud-
regioselective character to the cyclisation process.
ed on the basis of the experiments conducted with 1 or 3-
substituted allenylstannanes, since other regioisomers
should have been obtained rather than 3a–k or 4a–i.31
Both 2-iodobenzamide derivatives 2a–f and a variety of
allenyltributyltins have been used to obtain various substi-
tuted (2H)-isoquinolin-1-ones 4a–i with reasonable
yields, easily isolated in most cases as pure compounds by
crystallisation from the crude reaction mixture. Isoquino-
linones bearing a fluorine atom on the aromatic ring
(Table 2, entries 5, 6 and 8) were synthesised with reason-
able yields and proved to be nearly as successful as 2-io-
dobenzamide itself (Table 2, entries 5, 6 and 8). These
results are all the more important, because only few exam-
ples are reported for the synthesis of isoquinolinones pos-
sessing an electron-withdrawing group such as fluorine.
We obtained optically pure (2H)-isoquinolin-1-one 4c
from the available optically active benzamide (Table 2,
entry 3, Table 2).
I
Pd0
NHR
•
O
NHR
O
Pd-I
Pd
O
•
NHR
NHR
NR
O
O
Bu3Sn
•
Bu3SnI
As illustrated in Tables 1 and 2, better yields were ob-
tained in the case of 2-pyridinones compared to isoquino-
linones. On the basis of the above results, we believe that
this isoquinolinone synthesis proceeds by the same mech-
anism as that proposed for the synthesis of 2-pyridinones.
Scheme 3 Proposed mechanism for the formation of 2-pyridinones
and 2H-isoquinolin-1-ones
In conclusion, we have developed a general and a simple
procedure for the regioselective preparation of 1,4,6-
trisubstituted (1H)-2-pyridinones and 2,3-disubstituted
(2H)-isoquinolin-1-ones from (Z)-2-iodopropenamides 1
or 2-iodobenzamide derivatives 2 and allenyltributyltins
in the presence of a palladium catalyst. The heteroannula-
tion reaction proceeded selectively and provided good
isolated yields of a variety of 1,4,6-trisubstituted (1H)-py-
ridin-2-ones and 2,3-disubstituted (2H)-isoquinolin-1-
ones.
Mechanism
Based on our previous studies19,20b,c and the results ob-
tained here, a possible mechanism for the heteroannula-
tion reaction is shown in Scheme 3. First, Pd(OAc)2 is
reduced to a Pd(0) complex, which is the actual catalyst in
the process. After oxidative addition of the vinylic (or ar-
omatic) iodide to palladium (0), a Stille mechanism30
would yield (Z)-3-allenylpropenamide (or N-substituted
benzamide) by transmetallation and reductive elimina-
tion. Cyclisation would then occur via an attack of the
amide function on the allenyl moiety and yield the final
product pyridinone (or isoquinolinone). An alternative
All reactions were carried out under an inert atmosphere (Ar or N2).
THF and Et2O were dried and freshly distilled from sodium/ben-
zophenone. MeCN was distilled from CaCl2. Flash chromatography
1
was carried out with Merck silica gel (230–400 mesh). H NMR
spectra were recorded at 200 MHz using CDCl3 as solvent. The
findings, reported using the residual solvent proton resonance of
Synthesis 2005, No. 14, 2349–2356 © Thieme Stuttgart · New York

2352
K. Cherry et al.
PAPER
CDCl3 (dH = 7.25) as internal reference, were as follows (in that or-
der): chemical shift (d in ppm in relation on to Me4Si), multiplicity
(s, d, t, q, m, br for singlet, doublet, triplet, quartet, multiplet, broad)
and coupling constants (J in Hz). 13C NMR were recorded at 50.32
MHz using the CDCl3 solvent peak at dC = 77.0 as reference. 19F
NMR were recorded in CDCl3 using C6F6 as external reference (19F,
d = –164.9). Mass spectra were obtained in the GC/MS (70 eV)
mode. IR spectra were recorded on a Perkin-Elmer 781 FT-IR spec-
trophotometer and are reported in cm–1. Melting points are uncor-
rected. 2-Iodobenzoic acid and 2-fluoro-6-iodobenzoic acid are
commercially available. 2-Iodo-4-methoxybenzoic acid was pre-
pared by a known procedure32 from 4-methoxybenzoic acid.
IR (KBr): 3428, 3055, 2987, 1659, 1605 cm–1.
1H NMR (CDCl3, 200 MHz): d = 0.23 (s, 9 H), 4.56 (s, 1 H), 4.60
(s, 1 H), 6.14 (NH), 6.92 (s, 1 H), 7.30–7.39 (m, 5 H).
13C NMR (CDCl3, 50.32 MHz): d = –1.3, 44.1, 118.3, 128.1, 128.6
(2 C), 129.2 (2 C), 138.0, 139.7, 166.0.
MS (EI, 70 eV): m/z (%) = 359 (M+, 1), 91 (100), 77 (11), 73 (18),
65 (24).
(Z)-3-Iodo-N-(1-phenylethyl)but-2-enamide (1f)
Yield: 73%; yellow solid; mp 88–90 °C; [a]D20 –97.5 (c = 0.01,
CH2Cl2).
IR (KBr): 3432, 3050, 2985, 1660, 1605 cm–1.
The amides 1a–h and 2a–f were synthesised according to a proce-
dure described previously.17 Petroleum ether with a boiling range of
40–65 °C was used.
1H NMR (CDCl3, 200 MHz): d = 1.59 (d, J = 7.0 Hz, 3 H), 2.68 (d,
J = 1.4 Hz, 3 H), 5.18–5.32 (m, 1 H), 6.03 (NH), 6.26 (q, J = 1.4 Hz,
1 H), 7.32–7.40 (m, 5 H).
(Z)-N-Benzyl-3-iodopropenamide (1a)
Yield: 71%; yellow solid; mp 79–81 °C.
13C NMR (CDCl3, 50.32 MHz): d = 21.2, 36.2, 49.4, 106.4, 126.8
(2 C), 127.8, 129.1 (2 C), 129.7, 143.1, 164.3.
MS (EI, 70 eV): m/z (%) = 315 (M+, 28), 195 (42), 120 (49), 106
(100), 77 (44).
IR (KBr): 3429, 3054, 2986, 1667, 1602 cm–1.
1H NMR (CDCl3, 200 MHz): d = 4.57 (s, 1 H), 4.60 (s, 1 H), 6.91
(d, J = 9.0 Hz, 1 H), 7.10 (d, J = 9.0 Hz, 1 H), 7.36–7.40 (m, 5 H).
13C NMR (CDCl3, 50.32 MHz): d = 44.0, 88.9, 128.1, 128.4 (2 C),
129.2 (2 C), 133.2, 138.1, 165.0.
(Z)-3-Iodo-N-(1,2-dimethylpropyl)but-2-enamide (1g)
Yield: 75%; colourless oil; [a]D20 +9.5 (c = 0.01, CH2Cl2).
MS (EI, 70 eV): m/z (%) = 287 (M+, 2), 181 (16), 160 (100), 91 (87),
77 (45).
IR (neat): 3287, 3063, 2963, 2873, 1651, 1622 cm–1.
1H NMR (CDCl3, 200 MHz): d = 0.87 (d, J = 6.8 Hz, 6 H), 1.05 (d,
J = 6.8 Hz, 3 H), 1.63–1.80 (m, 1 H), 2.58 (d, J = 1.4 Hz, 3 H),
3.80–3.93 (m, 1 H), 6.14 (NH), 6.26 (q, J = 1.4 Hz, 1 H).
13C NMR (CDCl3, 50.32 MHz): d = 17.7, 18.9, 19.2, 33.2, 36.1,
50.2, 105.3, 130.0, 164.6.
MS (EI, 70 eV): m/z (%) = 181 (M+, 5), 238 (35), 195 (64), 44 (100),
39 (28).
(Z)-N-Benzyl-3-iodobut-2-enamide (1b)
Yield: 73%; yellow solid; mp 89–91 °C.
IR (KBr): 3430, 3055, 2987, 1663, 1603 cm–1.
1H NMR (CDCl3, 200 MHz): d = 2.70 (d, J = 1.5 Hz, 3 H), 4.55 (s,
1 H), 4.58 (s, 1 H), 5.98 (NH), 6.31 (q, J = 1.5 Hz, 1 H), 7.34–7.39
(m, 5 H).
13C NMR (CDCl3, 50.32 MHz): d = 36.2, 44.0, 107.0, 128.0, 128.4
(2 C), 129.1 (2 C), 129.3, 138.2, 165.1.
(Z)-N-Allyl-3-iodobut-2-enamide (1h)
Yield: 76%; colourless oil.
MS (EI, 70 eV): m/z (%) = 301 (M+, 5), 174 (42), 91 (94), 77 (27),
39 (100).
IR (neat): 3290, 3070, 2964, 2913, 1652 cm–1.
1H NMR (CDCl3, 200 MHz): d = 2.60 (d, J = 1.4 Hz, 3 H), 3.85–
3.88 (m, 2 H), 5.02–5.21 (m, 2 H), 5.68–5.97 (m, 1 H), 6.34 (q,
J = 1.4 Hz, 1 H), 6.9 (NH).
13C NMR (CDCl3, 50.32 MHz): d = 36.3, 42.3, 107.0, 117.8, 129.0,
134.3, 165.1.
MS (EI, 70 eV): m/z (%) = 251 (M+, 1), 195 (12), 57 (61), 41 (100),
39 (96).
(Z)-N-Benzyl-3-iodo-3-phenylprop-2-enamide (1c)
Yield: 72%; yellow solid; mp 125–127 °C.
IR (KBr): 3429, 3054, 2987, 1661, 1606 cm–1.
1H NMR (CDCl3, 200 MHz): d = 4.60 (s, 1 H), 4.64 (s, 1 H), 6.14
(NH), 6.64 (s, 1 H), 7.32–7.51 (m, 10 H).
13C NMR (CDCl3, 50.32 MHz): d = 44.3, 110.2, 128.1, 128.6 (2 C),
128.8 (2 C), 129.0 (2 C), 129.2 (2 C), 130.0, 130.8, 138.1, 143.3,
165.4.
N-Benzyl-2-iodobenzamide (2a)
Yield: 77%; white solid; mp 123–125 °C.
MS (EI, 70 eV): m/z (%) = 363 (M+, 1), 236 (59), 102 (68), 91 (100),
77 (40).
IR (KBr): 3426, 3054, 2986, 1664, 1585 cm–1.
1H NMR (CDCl3, 200 MHz): d = 4.68 (s, 1 H), 4.70 (s, 1 H), 6.10
(NH), 7.10–7.18 (m, 2 H), 7.33–7.39 (m, 6 H), 7.90 (d, J = 8.1 Hz,
1 H).
13C NMR (CDCl3, 50.32 MHz): d = 44.7, 93.0, 128.2, 128.4, 128.7
(2C), 128.8, 129.2 (2C), 131.7, 137.9, 140.3, 142.3, 169.6.
MS (EI, 70 eV): m/z (%) = 337 (M+, 62), 231 (93), 127 (12), 91
(100), 77 (94).
(Z)-N-Benzyl-3-iodopent-2-enamide (1d)
Yield: 70%; yellow solid; mp 97–99 °C.
IR (KBr): 3429, 3055, 2987, 1662, 1604 cm–1.
1H NMR (CDCl3, 200 MHz): d = 1.10 (t, J = 7.3 Hz, 3 H), 2.60 (q,
J = 7.3 Hz, 2 H), 4.40 (s, 1 H), 4.43 (s, 1 H), 6.35 (s, 1 H), 7.0 (NH),
7.25–7.31 (m, 5 H).
13C NMR (CDCl3, 50.32 MHz): d = 15.1, 41.5, 43.8, 116.8, 127.3,
127.7, 128.3 (2 C), 129.0 (2 C), 138.5, 165.5.
MS (EI, 70 eV): m/z (%) = 315 (M+, 1), 188 (40), 91 (100), 77 (24),
65 (31).
N-Butyl-2-iodobenzamide (2b)
Yield: 76%; white solid; mp 76–78 °C.
IR (KBr): 3426, 3054, 2986, 1664, 1595 cm–1.
1H NMR (CDCl3, 200 MHz): d = 0.99 (t, J = 7.2 Hz, 3 H), 1.32–1.7
(m, 4 H), 3.43–3.53 (m, 2 H), 5.84 (br s, NH), 7.07–7.16 (m, 1 H),
7.33–7.41 (m, 2 H), 7.88 (d, J = 8.1 Hz, 1 H).
(Z)-N-Benzyl-3-iodo-3-(trimethylsilyl)propenamide (1e)
Yield: 69%; yellow solid; mp 150–152 °C.
Synthesis 2005, No. 14, 2349–2356 © Thieme Stuttgart · New York

PAPER
Synthesis of 2-Pyridinones and (2H)-Isoquinolin-1-ones
2353
13
C NMR (CDCl3, 50.32 MHz): d = 14.2, 20.6, 31.8, 40.2, 93.0,
complete (checked by TLC), the reaction was quenched with aq
NH4Cl solution, extracted with CH2Cl2 and the CH2Cl2 solution was
dried (MgSO4). After evaporation of the solvent under reduced
pressure, the oily mixture was dissolved in a minimum amount of
Et2O to precipitate the Bu4NBr. After filtration, the solution was
treated with EtOAc and an aq 0.5 M solution of KF at 0 °C for 30
min to precipitate the Bu3SnI formed. The resulting mixture was fil-
tered through a Celite pad and after usual treatments, the crude
products were chromatographed on silica gel (petroleum ether–
Et3N, 99:1, then petroleum ether–Et2O–Et3N, 80:19:1) to afford
compounds 3a–k and 4a–i.
128.5, 128.6, 131.3, 140.3, 142.3, 169.8.
MS (EI, 70 eV): m/z (%) = 303 (M+, 19), 261 (33), 260 (25), 231
(100), 77 (15).
N-(1-Phenylethyl)-2-iodobenzamide (2c)
Yield: 70%; white solid; mp 133–135 °C.
IR (KBr): 3420, 3047, 2985, 1665, 1603 cm–1.
1H NMR (CDCl3, 200 MHz): d = 1.66 (d, J = 7.0 Hz, 3 H), 5.31–
5.39 (m, 1 H), 6.20 (NH), 7.10–7.15 (m, 1 H), 7.30–7.48 (m, 7 H),
7.86 (d, J = 8.0 Hz, 1 H).
13C NMR (CDCl3, 50.32 MHz): d = 21.0, 50, 92.8, 127 (2 C), 128.0,
128.6, 128.7, 129.1 (2 C), 131.5, 140.2, 142.6, 143.0, 168.8.
1-Benzyl-6-methylpyridin-2(1H)-one (3a)33
Colourless oil.
IR (neat): 3062, 3029, 2955, 2922, 1675, 1624, 1573 cm–1.
1H NMR (CDCl3, 200 MHz): d = 2.13 (s, 3 H), 4.53 (s, 2 H), 5.56–
5.60 (m, 1 H), 6.20 (d, 1 H, J = 9.7 Hz), 6.59 (dd, 1 H, J = 9.7, 9.6
Hz), 7.25–7.45 (m, 5 H).
MS (EI, 70 eV): m/z (%) = 351 (M+, 33), 231 (100), 203 (26), 104
(63), 77 (72).
N-Allyl-2-iodobenzamide (2d)
13C NMR (CDCl3, 50.32 MHz): d = 19.8, 50.5, 101.4, 118.1, 126.8,
128.4 (2 C), 128.7 (2 C), 133.2, 141.5, 153.7, 158.6.
Yield: 73%; white solid; mp 109–111 °C.
IR (KBr): 3425, 3050, 2990, 1663, 1641, 1600 cm–1.
MS (EI, 70 eV): m/z (%) = 199 (M+, 6), 91 (100), 65 (29), 39 (13).
1H NMR (CDCl3, 200 MHz): d = 4.06–4.13 (m, 2 H), 5.20–5.39 (m,
2 H), 5.91–6.05 (m, 2 H), 7.07–7.17 (m, 1 H), 7.38–7.44 (m, 2 H),
7.88 (d, J = 7.8 Hz, 1 H).
13C NMR (CDCl3, 50.32 MHz): d = 42.9, 92.9, 117.5, 128.6 (2 C),
128.7 (2 C), 131.6, 134.0, 140.3, 142.5, 169.6.
MS (EI, 70 eV): m/z (%) = 287 (M+, 11), 231 (100), 203 (32), 160
(46), 76 (69).
Anal. Calcd for C13H13NO: C, 78.36; H, 6.58. Found: C, 78.29; H,
6.54.
1-Benzyl-4,6-dimethylpyridin-2(1H)-one (3b)34
Colourless oil.
IR (neat): 3062, 3029, 2953, 2918, 1682, 1628, 1583 cm–1.
1H NMR (CDCl3, 200 MHz): d = 1.95 (d, 3 H, J = 1.1 Hz), 2.1 (s, 3
H), 4.52 (s, 2 H), 5.46 (q, 1 H, J = 1.1 Hz), 6.0 (s, 1 H), 7.23–7.43
(m, 5 H).
13C NMR (CDCl3, 50.32 MHz): d = 19.6, 21.3, 50.4, 104.8, 114.6,
126.7, 128.4 (2 C), 128.7 (2 C), 141.7, 144.0, 154.4, 157.4.
N-Benzyl-2-fluoro-6-iodobenzamide (2e)
Yield: 70%; white solid; mp 129–131 °C.
IR (KBr): 3420, 3055, 2985, 1661, 1601 cm–1.
1H NMR (CDCl3, 200 MHz): d = 4.69 (s, 1 H), 4.72 (s, 1 H), 6.10
MS (EI, 70 eV): m/z (%) = 213 (M+, 7), 91 (100), 65 (16), 43 (10),
(NH), 7.07–7.14 (m, 2 H), 7.30–7.43 (m, 5 H), 7.63–7.68 (m, 1 H).
13C NMR (CDCl3, 50.32 MHz): d = 44.6, 94.0, 116.2 (d, JC,F = 21.6
Hz), 128.2, 128.5 (2 C), 129.2 (2 C), 131.5 (d, JC,F = 20.6 Hz), 132.4
(d, JC,F = 8.6 Hz), 135.6 (d, JC,F = 3.0 Hz), 137.7, 159.0 (d,
39 (8).
Anal. Calcd for C14H15NO: C, 78.84; H, 7.09. Found: C, 74.77; H,
7.02.
JC,F = 252.0 Hz), 165.2.
19F NMR (CDCl3, 188 MHz): d = –111.6.
MS (EI, 70 eV): m/z (%) = 355 (M+, 64), 249 (86), 228 (76), 94 (91),
1-Benzyl-6-methyl-4-phenylpyridin-2(1H)-one (3c)
White solid; mp 97–99 °C.
IR (KBr): 3061, 3029, 2955, 2919, 1673, 1623, 1582 cm–1.
91 (100).
1H NMR (CDCl3, 200 MHz): d = 2.16 (s, 3 H), 4.53 (s, 2 H), 5.92
(s, 1 H), 6.44 (s, 1 H), 7.20–7.63 (m, 10 H).
13C NMR (CDCl3, 50.32 MHz): d = 20.0, 51.0, 101.7, 113.8, 126.4
(2 C), 127.0, 128.5 (2 C), 128.8 (2 C), 129.3 (2 C), 129.7, 137.15,
141.6, 144.6, 154.3, 158.4.
N-Allyl-2-fluoro-6-iodobenzamide (2f)
Yield: 70%; white solid; mp 80–82 °C.
IR (KBr): 3427, 3055, 2987, 1660, 1640, 1599 cm–1.
1H NMR (CDCl3, 200 MHz): d = 4.11–4.82 (m, 2 H), 5.22–5.44 (m,
MS (EI, 70 eV): m/z (%) = 275 (M+, 20), 158 (14), 91 (100), 65 (23),
2 H), 5.80–6.10 (m, 2 H), 7.09–7.16 (m, 2 H), 7.49–7.70 (m, 1 H).
13C NMR (CDCl3, 50 MHz): d = 42.8, 94.0, 116.0 (d, JC,F = 21.7
Hz), 117.5, 131.5 (d, JC,F = 21.1 Hz), 132.3 (d, JC,F = 8.0 Hz), 133.8,
135.6 (d, JC,F = 3.0 Hz), 158.9 (d, JC,F = 253.0 Hz), 165.2.
19F NMR (CDCl3, 188 MHz): d = –111.6.
MS (EI, 70 eV): m/z (%) = 305 (M+, 16), 249 (97), 178 (26), 94
43 (13).
Anal. Calcd for C19H17NO: C, 82.88; H, 6.22. Found: C, 82.80; H,
6.17
1-Benzyl-4-ethyl-6-methylpyridin-2(1H)-one (3d)
Colourless oil.
IR (neat): 3065, 3025, 2969, 2924, 1682, 1622, 1582 cm–1.
(100), 41 (46).
1H NMR (CDCl3, 200 MHz): d = 1.13 (t, 3 H, J = 7.5 Hz), 2.11 (s,
3 H), 2.25 (q, 2 H, J = 7.5 Hz), 4.53 (s, 2 H), 5.48 (s, 1 H), 6.02 (s,
1 H), 7.24–7.45 (m, 5 H).
13C NMR (CDCl3, 50.32 MHz): d = 12.5, 19.6, 28.1, 50.5, 103.8,
113.1, 126.7, 128.4 (2 C), 128.7 (2 C), 141.8, 149.5, 154.6, 157.4.
Heteroannulation; Preparation of 3a–k and 4a–i; General Pro-
cedure
Pd(OAc)2 (112 mg, 0.5 mmol), Ph3P (263 mg, 1 mmol) and Bu4NBr
(6.6 g, 20 mmol) were successively added to a degassed solution of
3-iodopropenamide 1 or N-substituted 2-iodobenzamide 2 (10
mmol) in anhyd MeCN (40 mL). The mixture was stirred at r.t. for
10 min, then allenylstannane (15 mmol) was added. The mixture
was stirred and heated at 80 °C for 3 h. After the conversion was
MS (EI, 70 eV): m/z (%) = 227 (M+, 24), 121 (24), 91 (100), 65 (27).
Synthesis 2005, No. 14, 2349–2356 © Thieme Stuttgart · New York

2354
K. Cherry et al.
PAPER
Anal. Calcd for C15H17NO: C, 79.26; H, 7.54. Found: C, 79.32; H,
7.48.
(d, 3 H, J = 1.3 Hz), 1.97 (s, 3 H), 3.41–3.54 (m, 1 H), 5.30 (q, 1 H,
J = 1.3 Hz), 5.83 (s, 1 H).
13C NMR (CDCl3, 50.32 MHz): d = 18.7, 19.5 (2 C), 20.1, 21.1,
34.9, 55.8, 104.1, 114.7, 143.2, 152.4, 157.
MS (EI, 70 eV): m/z (%) = 193 (M+, 3), 150 (52), 96 (34), 43 (100),
41 (23).
1-Benzyl-4-trimethylsilyl-6-methylpyridin-2(1H)-one (3e)
Colourless oil.
IR (neat): 3060, 3033, 2956, 2923, 1668, 1630 cm–1.
1H NMR (CDCl3, 200 MHz): d = 0.17 (s, 9 H), 2.11 (s, 3 H), 4.49
(s, 2 H), 5.57 (s, 1 H), 6.34 (s, 1 H), 7.18–7.47 (m, 5 H).
13C NMR (CDCl3, 50.32 MHz): d = –2.1, 19.6, 50.6, 103.5, 124.1,
Anal. Calcd for C12H19NO: C, 74.57; H, 9.91. Found: C, 74.52; H,
10.03.
126.7, 128.4, 128.6, 141.5, 147, 153.2, 156.5.
1-Benzyl-4-methyl-6-pentylpyridin-2(1H)-one (3j)
Colourless oil.
MS (EI, 70 eV): m/z (%) = 271 (M+, 3), 154 (12), 91 (100), 73 (13),
65 (17).
IR (neat): 3060, 3027, 2956, 2930, 1679, 1620, 1582 cm–1.
Anal. Calcd for C16H21NOSi: C, 70.80; H, 7.80. Found: C, 70.75; H,
7.73.
1H NMR (CDCl3, 200 MHz): d = 0.91–1.65 (m, 9 H), 1.96 (s, 3 H),
2.36 (t, 2 H, J = 7.6 Hz), 4.54 (s, 2 H), 5.54 (s, 1 H), 6.02 (s, 1 H),
7.23–7.42 (m, 5 H).
1-Benzyl-6-ethyl-4-methylpyridin-2(1H)-one (3f)
Colourless oil.
IR (neat): 3067, 3033, 2966, 2922, 1676, 1640, 1616 cm–1.
13C NMR (CDCl3, 50.32 MHz): d = 14.4, 21.3, 22.8, 26.3, 31.6,
33.6, 51.6, 104.0, 114.7, 126.7, 128.3 (2 C), 128.7 (2 C), 141.7,
144.2, 154.7, 161.0.
1H NMR (CDCl3, 200 MHz): d = 1.24 (t, 3 H, J = 7.6 Hz), 1.98 (s,
3 H), 2.41 (q, 2 H, J = 7.6 Hz), 4.53 (s, 2 H), 5.47 (s, 1 H), 6.02 (s,
1 H), 7.23–7.42 (m, 5 H).
MS (EI, 70 eV): m/z (%) = 269 (M+, 9), 91 (100), 65 (15), 39 (10).
Anal. Calcd for C18H23NO: C, 80.26; H, 8.61. Found: C, 80.18; H,
8.73.
13C NMR (CDCl3, 50.32 MHz): d = 11.3, 21.4, 26.8, 50.0, 103.8,
114.3, 127.0, 128.3 (2 C), 128.7 (2 C), 129.5, 141.1, 155.6, 162.4.
1-Allyl-4,6-dimethylpyridin-2(1H)-one (3k)
Yellow oil.
MS (EI, 70 eV): m/z (%) = 227 (M+, 10), 91 (100), 65 (17).
IR (neat): 3067, 2966, 2911, 1683, 1622, 1583 cm–1.
Anal. Calcd for C15H17NO: C, 79.26; H, 7.54. Found: C, 79.19; H,
7.48.
1H NMR (CDCl3, 200 MHz): d = 1.94 (d, 3 H, J = 1.0 Hz), 2.07 (s,
3 H), 3.93 (d, 2 H, J = 5.8 Hz), 5.04–5.28 (m, 2 H), 5.44 (s, 1 H),
5.94 (q, 1 H, J = 1.0 Hz), 5.96–6.12 (m, 1 H).
1-Benzyl-6-ethyl-4-phenylpyridin-2(1H)-one (3g)
White solid; mp 101–103 °C.
IR (KBr): 3067, 3033, 2950, 2916, 1672, 1617, 1560 cm–1.
13C NMR (CDCl3, 50.32 MHz): d = 19.5, 21.2, 49.1, 104.7, 114.5,
115.1, 137.4, 144.0, 154.4, 157.3.
1H NMR (CDCl3, 200 MHz): d = 1.29 (t, 3 H, J = 7.5 Hz), 2.52 (q,
2 H, J = 7.5 Hz), 4.62 (s, 2 H), 5.97 (s, 1 H), 6.50 (s, 1 H), 7.24–7.58
(m, 10 H).
13C NMR (CDCl3, 50.32 MHz): d = 11.4, 27.2, 50.8, 100.2, 113.9,
126.4 (2 C), 126.8, 128.4 (2 C), 128.8 (2 C), 129.3 (2 C), 129.6,
137.3, 141.6, 144.7, 154.4, 163.2.
MS (EI, 70 eV): m/z (%) = 163 (M+, 8), 136 (14), 53 (15), 41 (100),
39 (42).
Anal. Calcd for C10H13NO: C, 73.59; H, 8.03. Found: C, 73.52; H,
7.98.
2-Benzyl-3-methylisoquinolin-1(2H)-one (4a)
Yellow solid; mp 102–104 °C.
IR (KBr): 3065, 3028, 2961, 2935, 1651, 1625 cm–1.
MS (EI, 70 eV): m/z (%) = 289 (M+, 48), 198 (39), 91 (100), 77 (18),
65 (45).
Anal. Calcd for C20H19NO: C, 83.01; H, 6.26. Found: C, 82.94; H,
6.12.
1H NMR (CDCl3, 200 MHz): d = 2.38 (d, J = 0.8 Hz, 3 H), 5.47 (s,
2 H), 6.42 (q, J = 0.8 Hz, 1 H), 7.18–7.38 (m, 5 H), 7.43–7.51 (m, 2
H), 7.62–7.70 (m, 1 H), 8.47 (d, J = 8.0 Hz, 1 H).
1-(1-Methylbenzyl)-4,6-dimethylpyridin-2(1H)-one (3h)
Colourless oil; [a]D20 –210 (c = 0.015, CH2Cl2).
IR (neat): 3061, 3028, 2969, 2923, 1682, 1621, 1583 cm–1.
13C NMR (CDCl3, 50.32 MHz): d = 21.1, 47.5, 106.6, 124.8, 125.5,
126.4, 126.7 (2 C), 127.6, 128.7, 129.2 (2 C), 132.8, 137.3, 137.6,
140.0, 164.0.
1H NMR (CDCl3, 200 MHz): d = 1.51 (d, 3 H, J = 6.7 Hz), 1.92 (d,
3 H, J = 1.2 Hz), 2.03 (s, 3 H), 4.92 (q, 1 H, J = 6.7 Hz), 5.40 (q, 1
H, J = 1.2 Hz), 5.98 (s, 1 H), 7.18–7.47 (m, 5 H).
13C NMR (CDCl3, 50.32 MHz): d = 19.4, 21.2, 25.0, 54.5, 104.5,
114.8, 126.6, 127.1 (2 C), 128.5 (2 C), 144.0, 147.3, 153.1, 157.3.
MS (EI, 70 eV): m/z (%) = 251 (M+, 24), 143 (15), 91 (100), 65 (32).
Anal. Calcd for C17H15NO: C, 81.90; H, 6.06. Found: C, 81.88; H,
6.02.
2-(Butyl)-3-methylisoquinolin-1(2H)-one (4b)2f
Yellow oil.
MS (EI, 70 eV): m/z (%) = 227 (M+, 5), 105 (100), 77 (13).
IR (neat): 3065, 2961, 2932, 1652, 1625 cm–1.
Anal. Calcd for C15H17NO: C, 79.26; H, 7.54. Found: C, 79.20; H,
7.48.
1H NMR (CDCl3, 200 MHz): d = 0.98 (t, J = 7.2 Hz, 3 H), 1.39–
1.50 (m, 2 H), 1.62–1.77 (m, 2 H), 2.41 (s, 3 H), 4.07 (t, J = 8.0 Hz,
2 H), 6.31 (s, 1 H), 7.35–7.42 (m, 2 H), 7.53–7.57 (m, 1 H), 8.37 (d,
J = 8.0 Hz, 1 H).
1-(1,2-Dimethylpropyl)-4,6-dimethylpyridin-2(1H)-one (3i)
Colourless oil; [a]D20 –26 (c = 0.19, CH2Cl2).
IR (neat): 3070, 2961, 2927, 1683, 1632, 1589 cm–1.
13C NMR (CDCl3, 50.32 MHz): d = 14.2, 20.8, 21, 31.4, 44.6,
106.3, 125.0, 125.4, 126.2, 128.2, 132.4, 137.1, 139.5, 163.4.
MS (EI, 70 eV): m/z (%) = 251 (M+, 58), 200 (35), 198 (48), 159
1H NMR (CDCl3, 200 MHz): d = 0.82 (d, 3 H, J = 4.7 Hz), 0.86 (d,
3 H, J = 4.7 Hz), 1.0 (d, 3 H, J = 6.4 Hz), 1.48–1.65 (m, 1 H), 1.83
(100), 41 (51).
Synthesis 2005, No. 14, 2349–2356 © Thieme Stuttgart · New York

PAPER
Synthesis of 2-Pyridinones and (2H)-Isoquinolin-1-ones
2355
Anal. Calcd for C14H17NO: C, 78.10; H, 7.96. Found: C, 78.12; H,
7.91.
(d, JC,F = 4.5 Hz), 133.1, 133.5 (d, JC,F = 10.0 Hz), 140.0, 141.0,
160.4 (JC,F = 6.0 Hz), 163.6 (JC,F = 262.0 Hz).
19F NMR (CDCl3, 188 MHz): d = –111.6.
MS (EI, 70 eV): m/z (%) = 217 (M+, 39), 202 (100), 133 (30), 107
3-Methyl-2-(1-phenylethyl)isoquinolin-1(2H)-one (4c)
Yellow solid; mp 109–111 °C; [a]D20 +6 (c = 0.015, CH2Cl2).
IR (KBr): 3064, 3030, 2979, 2935, 1652, 1622 cm–1.
1H NMR (CDCl3, 200 MHz): d = 1.57 (d, J = 6.6 Hz, 3 H), 2.15 (s,
3 H), 5.18 (q, J = 6.6 Hz, 1 H), 5.90 (s, 1 H), 7.12 (d, J = 7.7 Hz, 1
H), 7.21–7.48 (m, 5 H), 7.55–7.60 (m, 2 H), 8.32 (d, J = 7.8 Hz, 1
H).
13C NMR (CDCl3, 50.32 MHz): d = 19.7, 25.0, 54.7, 102.1, 124.2,
124.5, 126.7, 127.1(2 C), 127.3, 127.4, 128.6 (2 C), 131.8, 133.8,
147.4, 150, 163.0.
(46), 39 (80).
Anal. Calcd for C13H12FNO: C, 71.87; H, 5.57. Found: C, 71.83; H,
5.51.
2-Benzyl-3-ethylisoquinolin-1(2H)-one (4g)
Yellow solid; mp 113–115 °C.
IR (KBr): 3065, 3028, 2961, 2935, 1651, 1625 cm–1.
1H NMR (CDCl3, 200 MHz): d = 1.28 (t, J = 7.5 Hz, 3 H), 2.50 (q,
J = 7.5 Hz, 2 H), 4.76 (s, 2 H), 5.59 (s, 1 H), 7.17 (d, J = 7.6 Hz, 1
H), 7.27–7.59 (m, 7 H), 8.29 (d, J = 7.8 Hz, 1 H).
13C NMR (CDCl3, 50.32 MHz): d = 11.5, 27.0, 50.3, 100.7, 124.1,
125.0, 126.7, 127.2, 127.6, 128.1 (2 C), 128.7 (2 C), 132.0, 133.7,
141.6, 151.8, 158.0.
MS (EI, 70 eV): m/z (%) = 263 (M+, 12), 159 (100), 130 (13), 105
(33), 77 (19).
Anal. Calcd for C18H17NO: C, 82.10; H, 6.51. Found: C, 82.12; H,
6.54.
MS (EI, 70 eV): m/z (%) = 263 (M+, 29), 172 (46), 91 (100), 89 (24),
65 (37).
2-Allyl-3-methylisoquinolin-1(2H)-one (4d)
Yellow oil.
IR (neat): 3077, 3027, 2962, 1660, 1628, 1610 cm–1.
Anal. Calcd for C18H17NO: C, 82.10; H, 6.51. Found: C, 82.05; H,
6.54.
1H NMR (CDCl3, 200 MHz): d = 2.40 (d, J = 0.8 Hz, 3 H), 4.76–
4.80 (m, 2 H), 4.97–5.22 (m, 2 H), 5.90–6.06 (m, 1 H), 6.35 (q,
J = 0.8 Hz, 1 H), 7.37–7.64 (m, 3 H), 8.40 (d, J = 8.6 Hz, 1 H).
13C NMR (CDCl3, 50.32 MHz): d = 20.6, 46.4, 106.4, 116.4, 124.8,
125.4, 126.3, 128.4, 132.6, 133.3, 137.2, 139.8, 163.3.
MS (EI, 70 eV): m/z (%) = 199 (M+, 36), 184 (99), 77 (18), 41 (68),
39 (100).
2-Benzyl-3-ethyl-8-fluoroisoquinolin-1(2H)-one (4h)
Yellow solid; mp 116–117 °C.
IR (neat): 3065, 3026, 2960, 2932, 2873, 1650, 1623, 1597 cm–1.
1H NMR (CDCl3, 200 MHz): d = 1.26 (t, J = 7.5 Hz, 3 H), 2.47 (q,
J = 7.5 Hz, 2 H), 4.83 (s, 2 H), 5.93 (s, 1 H), 6.93–7.09 (m, 2 H),
7.25–7.45 (m, 4 H), 7.52–7.56 (m, 2 H).
Anal. Calcd for C13H13NO: C, 78.36; H, 6.58. Found: C, 78.35; H,
6.53.
13C NMR (CDCl3, 50.32 MHz): d = 11.4, 26.7, 50.8, 100.5, 113.2,
115.5 (d, JC,F = 25 Hz), 120.6 (d, JC,F = 4.2 Hz), 126.7, 128.0 (2 C),
128.7 (2 C), 132.8 (d, JC,F = 10.0 Hz), 137.0, 141.3, 158.8, 159 (d,
2-Benzyl-8-fluoro-3-methylisoquinolin-1(2H)-one (4e)
Yellow solid; mp 110–112 °C.
IR (KBr): 3064, 3027, 2962, 1650, 1628, 1612 cm–1.
1H NMR (CDCl3, 200 MHz): d = 2.37 (s, 3 H), 5.41 (s, 2 H), 6.36
(s, 1 H), 7.08 (dd, J = 8.0, 8.0 Hz, 1 H), 7.20–7.38 (m, 6 H), 7.51–
7.61 (m, 1 H).
13C NMR (CDCl3, 50.32 MHz): d = 21.1, 47.2, 106.0, 113.2 (d,
JC,F = 21.5 Hz), 114.1, 121.3 (d, JC,F = 4.5 Hz), 127.0 (2 C), 127.7,
129.2 (2 C), 133.7 (d, JC,F = 10.0 Hz), 137.5, 140.0, 141.4, 161.0 (d,
JC,F = 6.0 Hz), 163.0 (d, JC,F = 263.0 Hz).
JC,F = 5.0 Hz), 161, 163 (d, JC,F = 265 Hz).
MS (EI, 70 eV): m/z (%) = 281 (M+, 10), 91 (100), 57(18).
Anal. Calcd for C18H16FNO: C, 76.85; H, 5.73. Found: C, 76.84; H,
5.74.
2-Benzyl-3-pentylisoquinolin-1(2H)-one (4i)
Yellow solid; mp 74–76 °C.
IR (KBr): 3065, 3026, 2960, 2932, 2873, 1650, 1623, 1597 cm–1.
1H NMR (CDCl3, 200 MHz): d = 1.08 (t, J = 7.2 Hz, 3 H), 1.17–
1.66 (m, 6 H), 2.61 (td, J = 7.1, 1.5 Hz, 2 H), 5.48 (s, 2 H), 6.43 (t,
J = 1.5 Hz, 1 H), 7.15–7.66 (m, 8 H), 8.47 (d, J = 8.0 Hz, 1 H).
13C NMR (CDCl3, 50.32 MHz): d = 14.4, 22.8, 29.0, 31.8, 33.4,
47.0, 105.6, 124.8, 125.7, 126.4, 126.6 (2 C), 127.5, 128.7, 129.2 (2
C), 132.8, 137.3, 138.0, 144.0, 164.0.
19F NMR (CDCl3, 188 MHz): d = –111.2.
MS (EI, 70 eV): m/z (%) = 267 (M+, 19), 161 (16), 107 (24), 91
(100), 65 (35).
Anal. Calcd for C17H14FNO: C, 76.39; H, 5.28. Found: C, 76.37; H,
5.25.
MS (EI, 70 eV): m/z (%) = 305 (M+, 12), 249 (10), 158 (14), 91
(100), 65 (23).
2-Allyl-8-fluoro-3-methylisoquinolin-1(2H)-one (4f)
Anal. Calcd for C21H23NO: C, 82.58; H, 7.59. Found: C, 82.57; H,
7.63.
Yellow solid; mp 97–99 °C.
IR (KBr): 3077, 3027, 2962, 1660, 1628, 1610 cm–1.
1H NMR (CDCl3, 200 MHz): d = 2.43 (d, J = 0.8 Hz, 3 H), 4.74–
4.78 (m, 2 H), 5.04–5.24 (m, 2 H), 5.92–6.10 (m, 1 H), 6.34 (q,
J = 0.8 Hz, 1 H), 6.99–7.10 (m, 1 H), 7.19 (d, J = 8.0 Hz, 1 H),
7.48–7.59 (m, 1 H).
13C NMR (CDCl3, 50.32 MHz): d = 20.7, 46.2, 105.7 (d, JC,F = 2.3
Hz), 113.0 (d, JC,F = 21.5 Hz), 114.0 (d, JC,F = 5.0 Hz), 116.8, 121.3
Acknowledgment
We thank MESR and CNRS for providing financial support and the
‘service d’analyse chimique du vivant de tours’ for recording NMR
and mass spectra.
Synthesis 2005, No. 14, 2349–2356 © Thieme Stuttgart · New York

2356
K. Cherry et al.
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Synthesis 2005, No. 14, 2349–2356 © Thieme Stuttgart · New York