Metallation of pyridin-2-yldiazines. Use of pyridine ring as ortho-directing group. Diazines. Part 45

Article abstract of DOI:10.1016/j.tet.2005.07.031

Starting from commercial chlorodiazines, we report the synthesis of pyridin-2-yldiazines. The first lithiation and functionalization of these compounds are reported and the regioselectivity of the metallation is discussed. The functionalization via the metallation reaction, provides a new access to substituted pyridin-2-yldiazines, which could be used as building blocks in supramolecules.

Full text of DOI:10.1016/j.tet.2005.07.031

Tetrahedron 61 (2005) 9637–9644
Metallation of pyridin-2-yldiazines. Use of pyridine ring as
ortho-directing group. Diazines. Part 45
b
b,
Camelia Berghian,a,b Mircea Darabantu,a,b Alain Turck and Nelly Ple
*
´
a
`
Department of Organic Chemistry, ‘Babes-Bolyai’ University, 11 Aranyi Janos Str., RO-400028 Cluj-Napoca, Romania
´
Institut de Recherche en Chimie Organique Fine (I.R.C.O.F.), Universite de Rouen, BP 08, F-76131 Mont Saint-Aignan, France
b
Received 18 March 2005; revised 20 June 2005; accepted 6 July 2005
Available online 19 August 2005
Abstract—Starting from commercial chlorodiazines, we report the synthesis of pyridin-2-yldiazines. The first lithiation and
functionalization of these compounds are reported and the regioselectivity of the metallation is discussed. The functionalization via the
metallation reaction, provides a new access to substituted pyridin-2-yldiazines, which could be used as building blocks in supramolecules.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
withdrawing effect and could play the role of DMG with the
intramolecular ring nitrogen atom complexation. Few
studies dealing with the efficient lithiation of aromatic and
heteroaromatic groups assisted by the pyridyl group have
been previously reported.6
Various polydentate nitrogen ligands based on pyridine,
pyrazine, pyrimidine and pyridazine units have been
described in the literature and have become the scaffold of
choice for designing and assembling novel ligand archi-
tectures.1 Several types of oligoheterocyclic pyridine–
pyrimidine and pyridine–pyridazine are able to induce
helical self-organisation leading to extended supramolecu-
lar fibers.2 Functionalization of pyridin-2-yldiazines via the
metallation reaction could provide an original access to new
building blocks for elaboration of supramolecules.
Starting from commercial materials and using the Stille
cross-coupling reaction, we report here the synthesis of
three pyridin-2-yldiazines 1–3 (Scheme 1).
Following our studies on the metalation of diazines, we
studied the lithiation and the functionalization of the
pyridin-2-yldiazines 1–3.
The regiospecific introduction of lithium onto aromatic
rings requires generally the presence of substituents with
heteroatoms. This transformation (known as ‘ortho-directed
lithiation’) has great synthetic potential and has been
extensively studied in pyridine and diazine series.3 During
the metallation reaction, the assistance of the directing
metallation group (DMG) can be described as follows:
(1) The inductive electron-withdrawing effect of the DMG
activates ortho hydrogens toward strong bases.4 (2) Coordi-
nation of heteroatom-containing DMG to lithium atom leads
to various effects, more especially the complex-induced
proximity effect of the base (CIPE), which favors the
deprotonation and the stabilization of the lithio derivative.5
According to their p-deficient character, heteroaromatic
system such as a pyridine or a diazine ring have electron-
For these compounds, the assistance of the cyclic nitrogen
atom to induce the complexation giving a CIPE effect could
come either from the pyridine nitrogen, a diazine nitrogen or
both. For compound 2, only the pyridine nitrogen could give
this effect, whereas for 1 and 3, both effects must be taken
into account besides the cisoid or transoid conformers. An
evaluation of the relative energy difference between these
conformers has been calculated for 2,20-bipyridine,
2-pyridin-2-yl-pyrazine 3-pyridin-2-yl-pyridazine and
4-pyridin-2-yl-pyrimidine by B3LYP.2 In all cases, the
transoid conformer was 6–7 kcal molK1 lower in energy
than the lowest energy cisoid conformer. Taken into account
these results and considering the compounds 1–3 under
planar transoid conformer, we could anticipate the site of
pyridine ring influenced by the diazine nitrogen and vice
versa (Scheme 2). Comparison with the experimental
regioselectivity for the metallation allows to appreciate
the relative influence of the pyridine or the diazine
nitrogens.
Keywords: Pyridin-2-yldiazines; Metallation; Functionalization; ortho-
directing group.
*
Corresponding author. Tel.: C33 2 35 52 29 02; fax: C33 2 35 52 29 62;
e-mail: nelly.ple@insa-rouen.fr
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.07.031

9638
C. Berghian et al. / Tetrahedron 61 (2005) 9637–9644
Scheme 1.
Scheme 4.
Scheme 2.
linkage (81–100%), whereas a low percentage of deuteria-
2. Results
tion was obtained at C-30 position of the pyridine ring
(14–21%). It must be noted that for compounds 1 and 2, a
low percentage of deuteriation (11–16%) was also observed
at the other positions of the diazine moiety.
In a prelimary study, we examined the lithiation of 1–3 with
an excess of LTMP in THF at K78 8C. The lithiated
intermediates were quenched at K78 8C by DCl or EtOD
leading to the deuteriated pyridin-2-yldiazines (Scheme 3).
Several experimental conditions have been tested, the best
results are obtained with 3 or 4 equiv of LTMP, a reaction
time t1 of 15 min followed by an immediate quenching with
the deuteriated reagent (t2Z0).
Metallation at the ortho positions of the pyridine–diazine
linkage could be explained by assistance of the ring nitrogen
atom as DMG, which stabilizes by complexation the lithio
derivative. In such a hypothesis, the results highlight a
greater deprotonation of the diazine ring, which indicates
that the 2-pyridyl group could be considered as a far better
DMG than the diazinyl group. This can be rationalized in
terms of pKa values: the stronger basicity of the pyridine
nitrogen (pKaZ5.2) in comparison with the diazine
nitrogens (pKaZ0.5–2.1). This effect ensures a better
stabilisation of the lithiated intermediates on the pyridine
ring. To bear out this proposition, heats of formation of
various monolithio pyridine-2-yldiazines have been
determined by semi-empirical Li/PM3 method (Table 2,
Scheme 5).
Scheme 3.
1
Examination of the H NMR spectra of the crude reaction
mixtures allowed us to appreciate the percentage of the
incorporated deuterium and to determine the regioselec-
tivity of the metallation. So, we compared the intensity of
the signal of an unaffected proton (for example, H4 or H5 of
pyridine ring) with a decreased signal of a deuteriated
position. The results are given in Table 1, (Scheme 4).
Table 2. Heats offormation of 2-pyridyl diazines monolithiated (kcal molK1
)
Compounds
isomers
a
b
c
1
2
3
83.13
81.43
125.03
87.44
98.52
129.18
87.84
83.80
140.71
A high regioselectivity of deuteriation was observed on the
diazine ring at the ortho position of the pyridine–diazine
Table 1. Metallation and deuteriation of compounds 1–3
Lithiation conditions
Incorporated deuterium (%) d (ppm) and (multiplicity)
Diazine ring
Pyridine ring
H-30
n (equiv LTMP)
t1 (min) DC
H-2
—
H-3
H-4
—
H-5
H-6
1-d
3
20
DCl or
81, 9.61 (s)
16, 8.58–8.56 (m)
21, 8.33 (d)
DCl/ETOD
DCl/EtOD
EtOD
2-d
3-d
4
3
15
20
11 9.22 (s)
—
—
—
100, 9.30 (s)
89, 8.61 (d)
—
0
11 9.30 (s)
—
14, 7.73 (d)
19, 8.75 (d)

C. Berghian et al. / Tetrahedron 61 (2005) 9637–9644
9639
explained by metallation without metalling-directed-group
as reported previously in the diazines series.9 The heat of
formation of lithio derivative 2b is much lower than the
other uncomplexed of isomers 1c–3c and could explain the
deuteriation observed at C30 position of the compound 2.
This preliminary study of metallation of compounds 1–3
with deuteriated reagents as the electrophile highlights
ability to functionalize the diazine ring, more particulary at
the ortho position of the pyridine–diazine linkage. Thus, we
have then extended our study to other electrophiles.
Metallations were carried out with an excess of LTMP
(3 or 4 equiv) at K100 8C or K78 8C in THF, with short
reaction time (15 min). The results are consigned in
Scheme 6.
With p-methoxybenzaldehyde as the electrophile, com-
pounds monofunctionalized on the diazine ring were
obtained in moderate yields. Nevertheless, in case of the
pyridin-2-ylpyrazine 1, a small amount (8%) of a position
isomer 5c was observed besides the major product 4c. For
the 3-(pyridin-2-yl)pyrimidine 2, use of diphenyl sulfide or
tributyltin chloride as electrophile led to the compounds 8a
and 8b disubstituted at the ortho position of the pyridine–
pyrimidine linkage. It must be noted that for compound 3,
reaction of 1 equiv of SnBu3Cl afforded the monosubsti-
tuted compound 10b as the major product besides the
disubstituted compound 11b.
Scheme 5.
The lowest heat of formation of pyridin-2-yldiazines was
observed for the lithio derivatives complexed by the
nitrogen atom of the pyridine moiety (isomers a). In
comparison, the complexation with a nitrogen atom of the
diazine ring (1b, 3b) causes an increase of the heat of
formation of more than 4 kcal molK1. This is well
correlated with the deuteriation percentages given in
Table 1. In the case of compounds 1 and 2, some
deuteriation occurred at C2 and C5 positions. This can be
A Stille cross-coupling reaction has been tested with
Scheme 6.

9640
C. Berghian et al. / Tetrahedron 61 (2005) 9637–9644
Scheme 7.
compound 8b and iodobenzene. Reaction with 2 equiv of
iodobenzene in toluene under reflux for 48 h with Pd(PPh3)4
as catalyst gave a mixture of the expected 4,6-diphenyl-5-
(2-pyridyl)-pyrimidine 12 as minor product and a dimer the
bis-(4-phenyl-5-(2-pyridyl)-pyrimidine) 13 (Scheme 7).
K78 8C with an appropriate deuteriate electrophile
(6 equiv). Temperature was increased to room temperature,
then dichloromethane (20 mL) and water (20 mL) were
added to the mixture. The aqueous phase was extracted with
dichloromethane (2!20 mL). The combined organic
extracts were washed with water (2!20 mL) then dried
over magnesium sulfate and evaporated. The crude product,
1
3. Conclusion
as a brownish solid was analyzed by H NMR.
Starting from commercial chlorodiazines, we synthesized
three pyridine-2-yldiazines. The first lithiation and
functionalization of these compounds are reported allowing
to access to pyridine-2-yldiazines substituted on the
diazines moiety. Synthesis of supramolecules using these
compounds as building blocks are in progress.
4.3. General procedure C for metallation of pyridine-2-
yldiazines by lithium 2,2,6,6-tetramethylpiperidide
A solution of n-butyllithium (1.6 M in hexane) was added to
cold (K78 8C), stirred and anhydrous mixture of THF
(15 mL) and 2,2,6,6-tetramethylpiperidine (TMPH) under
an atmosphere of dry nitrogen. The mixture was warmed to
0 8C. After 30 min, the mixture temperature was carried to T
8C and added to cold (T 8C) solution of the 2-pyridyldiazine
dissolved in THF (10 mL). Then, the mixture was stirred for
t1 at T 8C, then the electrophile introduced and stirring was
continued for t2 hour(s) at this temperature. Hydrolysis was
then carried out at q 8C using a solution of THF/EtOH/water
(5:4:1). Temperature was increased to room temperature,
then dichloromethane (10 mL) and water were added to the
mixture. After decantation, the organic layer was washed
with water to neutrality and the aqueous phase was twice
extracted with dichloromethane. The combined organic
extracts were then dried over magnesium sulfate and
evaporated. The crude product was purified by column
chromatography on silica gel.
4. Experimental
Melting points were determined on a Electrothermal 1100
1
instrument. The H and 13C spectra were recorded on a
1
Bruker AC 300 (300 MHz H, 75 MHz 13C) instrument.
Microanalyses were performed on a Carlo Erba CHNOS
1160 apparatus. The IR spectra were obtained as potassium
bromide pellets with a Perkin-Elmer 16 PC FT-IR
spectrometer. Mass spectra were recorded on an ATI-
Unicam Automassw apparatus.
4.1. General procedure A for synthesis of pyridine-2-
yldiazines by cross-coupling reaction
A solution of 2-tributylstannylpyridine (2.531 g, 80%,
5.5 mmol) halogenodiazine (5.5 mmol) and Pd(PPh3)4
(0.433 g, 0.375 mmol) in degassed toluene (50 mL) was
heated under reflux under nitrogen atmosphere for 24 h.
After cooling at room temperature, dichloromethane
(50 mL) was added. The organic phase was washed with
aqueous ammonia (15%, 100 mL), then with water to
neutrality, dried over magnesium sulfate, filtered and
evaporated in vacuo. The crude product was purified by
column chromatography on silica gel.
4.4. Procedure D for cross-coupling of iodobenzene with
4,6-bistributylstannyl-5-(2-pyridyl)-pyrimidine under
Stille conditions
A solution of 4,6-bistributylstanny-5-(2-pyridyl)-pyrimi-
dine 8b (120 mg, 0.16 mmol), iodobenzene (0.04 mL,
65.3 mg, 0.32 mmol) and Pd(PPh3)4 (20 mg, 0.016 mmol)
in degassed toluene (15 mL) was heated under reflux and
under nitrogen atmosphere for 48 h. After cooling, the
reaction mixture was evaporated under vacuum to dryness,
then aqueous ammonia (5%, 10 mL) and ethyl acetate
(50 mL) were added with stirring. The organic phase was
washed with water to neutrality, dried over magnesium
sulfate, filtered and evaporated in vacuo. The crude product
was purified by column chromatography on silica gel
(eluent ethyl acetate) and giving a mixture of equimolecular
compounds 12 and 13.
4.2. General procedure B for deuteriation via metalla-
tion of pyridine-2-yldiazines
A solution of n-butyllithium (0.790 mL, 1.6 M, 1.26 mmol
in hexane) was added to cold (K10 8C), stirred and
anhydrous mixture of THF (30 mL) and 2,2,6,6-tetra-
methylpiperidine (0.216 mL, 0.178 g, 1.26 mmol) under
an atmosphere of dry nitrogen. After 30 min at this
temperature, the mixture temperature was carried to q 8C
and added to cold (q 8C) solution of the pyridine-2-yldiazine
(n equiv) in THF (10 mL). Then, the mixture was stirred for
t1 at q 8C, then the reaction mixture was quenched at
4.4.1. 2-(20-Pyridyl)-pyrazine (1).7 Reaction of chloro-
pyrazine (572 mg, 0.456 mL, 5 mmol) according the
general procedure A gave after purification by column
chromatography (silica, eluent petroleum ether/ethyl acetate

C. Berghian et al. / Tetrahedron 61 (2005) 9637–9644
9641
(2:1)) and sublimation 550 mg of 1 (70%) as a colorless
solid, mp 57–58 8C; H NMR (CDCl3): d 9.61 (1H, d, JZ
H-4), 8.19–8.15 (1.94H, m, HPh), 7.98 (1.00H, s, H-5), 7.87
(1.05H, ddd, JZ7.9, 7.5, 1.6 Hz, H-40), 7.57–7.49 (3.19H,
m, HPh), 7.37 (1.18H, ddd, JZ7.5, 4.5, 1.1 Hz, H-50).
1
1.5 Hz, H-3), 8.69 (1H, d, JZ4.5 Hz, H-60), 8.60–8.57 (2H,
m, H-5, H-6), 8.33 (1H, d,0JZ7.9 Hz, H-30), 7.82 (1H, ddd,
JZ7.9, 7.5, 1.8 Hz, H-4 ), 7.34 (1H, ddd, JZ7.5, 4.5,
1.1 Hz, H-50); 13C NMR (CDCl3): d 154.6 (1C, C-20), 151.5
(1C, C-2), 149.9 (1C, C-60), 144.8 (1C, C-5), 143.9 (1C,
C-6), 143.7 (1C, C-3), 137.5 (1C, C-40), 124.8 (1C, C-50),
121.8 (1C, C-30); MS (CI); m/z (rel int. %) 157 [MC] (100),
129 (5), 105 (38), 79 (32), 52 (18). Anal. Calcd for C9H7N3
(MwZ157.18) C, 68.78; H, 4.49; N, 26.73. Found: C, 68.67;
H, 4.56; N, 26.66.
4.4.7. 2-(20-Pyridyl)-3-phenylthiopyrazine 4a. Metalla-
tion of 1 (100 mg, 0.64 mmol) according to the general
procedure C with n-BuLi (4 equiv, 1.58 mL), TMPH
(4 equiv, 0.44 mL, TZK100 8C), followed by reaction
with diphenylsulfide (4 equiv, 574 mg) in solution with
anhydrous THF (10 mL), t1Z15 min, t2Z30 min, gave
after purification by column chromatography (silicagel,
eluent petroleum ether/ethyl acetate (4:1)) 99 mg (59%) of
1
4a as a yellow solid, mp 99–100 8C; H NMR (CDCl3): d
4.4.2. 5-(20-Pyridyl)-pyrimidine (2).8 Reaction of 5-bromo-
pyrimidine (832 mg, 5 mmol) according to the general
procedure A gave after purification by column chromato-
graphy (silica, eluent petroleum ether/ethyl acetate (4:1))
and sublimation 644 mg of 2 (82%) as a colorless solid, mp
8.81 (1H, d, JZ4.9 Hz, H-60), 8.28 (1H, d, JZ2.5 Hz, H-5),
8.23 (1H, d, JZ2.5 Hz, H-6), 8.20 (1H, d, JZ7.9 Hz, H-30),
7.86 (1H, ddd, JZ7.9, 7.5, 1.5 Hz, H-40), 7.55–7.52 (2H, m,
H-phenyl), 7.40–7.36 (4H, H-phenyl, H-500); 13C NMR
(CDCl3): d 157.0 (1C, C-2), 155.8 (1C, C-2 ), 148.9 (1C,
C-3), 148.4 (1C,0 C-60), 143.4 (1C, C-6), 139.1 (1C, C-5),
137.2 (1C, C-4 ), 136.0 (2C, CH-phenyl), 131.8 (1C,
Cq-phenyl), 129.5 (2C, CH-phenyl), 129.3 (1C, CH-
phenyl), 124.3 (1C, C-50), 123.9 (1C, C-30); MS (CI, rel
int. %) 266 [MCC1] (100). Anal. Calcd for C15H11N3S
(MwZ265.34) C, 67.90; H, 4.10; N, 15.84. Found: C, 68.01;
H, 4.05; N, 15.97.
1
130–132 8C; H NMR (CDCl3): d 9.31 (2H, s, H-4, H-6),
9.24 (1H, s, H-2), 8.74 (1H, d, JZ4.7 Hz, H-60), 7.82 (1H,
ddd, JZ7.9, 7.5, 1.6 Hz, H-40), 7.74 (1H, dd, JZ7.9,
1.1 Hz, H-30), 7.34 (1H, ddd, JZ7.5, 4.7, 1.1 Hz, H-50); 13C
NMR (CDCl3): d 159.0 (1C, C-2), 155.5 (2C, C-4, C-6),
152.4 (1C, C-20), 150.8 (1C, C-60), 137.6 (1C, C-40), 132.8
(1C, C-5), 124.0 (1C, C-50), 120.9 (1C, C-30); MS (CI); m/z
(rel int. %) 157 [MC] (100), 130 (68), 79 (93), 51 (47). Anal.
Calcd for C9H7N3 (MwZ157.18) C, 68.78; H, 4.49; N,
26.73. Found: C, 68.85; H, 4.28; N, 26.90.
4.4.8. 5,6-Bis(phenylthio)-2-(20-pyridyl)-pyrazine 6a.
Metallation of 1 (100 mg, 0.64 mmol) according to the
general procedure C with n-BuLi (4 equiv, 1.58 mL),
TMPH (4 equiv, 0.44 mL, TZK100 8C), followed by
reaction with diphenylsulfide (4 equiv, 574 mg) in solution
with anhydrous THF (10 mL), t1Z15 min, t2Z30 min, gave
after purification by column chromatography (silicagel,
eluent petroleum ether/ethyl acetate (4:1)) 26 mg (11%) of
6a as a yellow solid, mp 106–108 8C; 1H NMR (CDCl3): d
9.06 (1H, H-3), 8.54 (1H, 0d, JZ4.9 Hz, H-60), 7.65–7.55
(6H, m, H-phenyl, H-3 , H-40), 7.49–7.40 (6H, m,
H-phenyl), 7.18 (1H, ddd, JZ7.2, 4.9, 1.5 Hz, H-50); 13C
NMR (CDCl3): d 154.4 (1C, C-20), 153.3 (1C, C-2), 149.6
(1C, C-60), 147.0 (2C, C-5, C-6), 138.4 (1C, C-3), 137.2
(1C, C-40), 136.0 (2C, CH-phenyl), 134.9 (2C, CH-phenyl),
129.7 (2C, CH-phenyl), 129.6 (1C, CH-phenyl), 129.5
(1C, CH-phenyl), 129.48 (1C, CH-phenyl), 129.43 (2C,
Cq-phenyl), 124.2 (1C, C-50), 121.1 (1C, C-30) ppm; MS
(FABC, rel int. %) 374 [MCC1] (55), 154 (100), 136 (70).
Anal. Calcd for C21H15N3S2 (MwZ373.50) C, 67.53; H,
4.05; N, 11.25. Found: C, 67.68; H, 4.21; N, 11.16.
4.4.3. 6-Phenyl-3-(20-pyridyl)-pyridazine (3). Reaction of
6-chloro-3-phenylpyridazine (970 mg, 5 mmol) according
the general procedure A gave after purification by column
chromatography (silica, eluent petroleum ether/ethyl acetate
(2:1)) 875 mg of 3 (75%) as a yellow solid, mp 155–157 8C;
1H NMR (CDCl3): d 8.73 (1H, d, JZ7.9 Hz, H-30), 8.69
(1H, dd, JZ4.7, 1.8 Hz, H-60), 8.58 (1H, d, JZ8.9 Hz, H-4),
8.17–8.13 (2H, m, HPh), 7.96 (1H, d, JZ8.9 Hz, H-5), 7.86
(1H, ddd, JZ7.9, 7.5, 1.8 Hz, H-40), 7.55–7.45 (3H, m,
HPh), 7.35 (1H, ddd, JZ7.5, 4.9, 1.1 Hz, H-50); 13C NMR
(CDCl3): d 159.1 (1C, C-3), 157.4 (1C, C-6), 153.8 (1C,
C-20), 149.8 (1C, C-60), 137.5 (1C, C-40), 136.5 (1C, CPh),
130.6 (1C, CPh), 129.4 (2C, CPh), 127.5 (2C, CPh), 125.3,
125.0 (2C, C-4, -5), 124.8 (1C, C-50), 121.8 (1C, C-30); MS
(CI); m/z (rel int. %) 233 [MC] (74), 204 (100), 176 (5), 128
(3), 102 (44), 76 (16). Anal. Calcd for C15H11N3 (MwZ
233.28) C, 77.23; H, 4.75; N, 18.01. Found: C, 77.13; H,
4.88; N, 17.90.
4.4.4. [2H]-2-(20-Pyridyl)-pyrazine (1-d). 1H NMR
(CDCl3): d 9.62 (0.18H, s, H-3), 8.70 (1.17H, d, JZ
4.4 Hz, H-60), 8.60–8.57 (1.53H, m, H-5, H-6), 8.34 (0.79H,
d, JZ7.9 Hz, H-30), 7.83 (1.00H, ddd, JZ7.9, 7.5, 1.8 Hz,
H-40), 7.34 (1.00H, dd, JZ7.5, 4.4 Hz, H-50).
4.4.9. 2-(20-Pyridyl)-3-tributylstannylpyrazine 4b. Metal-
lation of 1 (100 mg, 0.64 mmol) according to the general
procedure C with n-BuLi (4 equiv, 1.58 mL), TMPH
(4 equiv, 0.44 mL, TZK100 8C), followed by reaction
with tributyltin chloride (4 equiv, 0.54 mL) in solution with
anhydrous THF (10 mL), t1Z15 min, t2Z30 min, gave
after purification by column chromatography (silicagel,
eluent petroleum ether/ethyl acetate (20:1)) 205 mg (72%)
of 4b as a yellow oil; 1H NMR (CDCl3): d 8.74 (1H, dd, JZ
2.6, 2.3 Hz, H-5)0, 8.57 (1H, d, JZ4.5 Hz, H-60), 8.42 (1H, d,
JZ8.3 Hz, H-3 ), 8.39 (1H, d, JZ2.6 Hz, H-6), 7.79
(1H, ddd, JZ7.9, 7.5, 1.5 Hz, H-40), 7.32 (1H, ddd, JZ
7.5, 4.5, 1.1 Hz, H-50), 1.58–1.37 (6H, m, CH2), 1.30–1.18
(6H, m, CH2), 1.08–0.94 (6H, m, CH2), 0.89–0.77 (9H, m,
CH3); 13C NMR (CDCl3): d 170.9 (1C, C-3), 156.2 (1C,
4.4.5. [2H]-5-(20-Pyridyl)-pyrimidine (2-d). 1H NMR
(CDCl3): d 0.98 (H, s, H-4(6), 9.22 (0.98H, s, H-2), 8.72
(1.18H, d, JZ4.9 Hz, H-60), 7.81 (1.24H, ddd, JZ7.9, 7.5,
1.6 Hz, H-40), 7.73 (1.07H, d, JZ7.9 Hz, H-30), 7.33
(1.24H, dd, JZ7.5, 4.9 Hz, H-50).
1
4.4.6. [2H]-6-Phenyl-3-(20-pyridyl)-pyridazine (3-d). H
NMR (CDCl3) d: 8.75 (0.89H, d, JZ7.9 Hz, H-30), 8.71
(1.00H, d, JZ4.5 Hz, H-60), 8.61 (0.11H, d, JZ9.0 Hz,

9642
C. Berghian et al. / Tetrahedron 61 (2005) 9637–9644
C-20), 154.5 (1C, C-2), 147.8 (1C, C-60), 145.9 (10C, C-5),
141.5 (1C, C-6), 137.1 (1C, C-40), 124.3 (1C, C-5 ), 122.0
(1C, C-30), 29.7 (3C, CH2), 27.9 (3C, CH2), 14.2 (3C, CH3),
13.2 (3C, CH2); MS (FABC, rel int. %) 446 [MCC1] (!1),
390 (100), 276 (32). Anal. Calcd for C21H33N3Sn (MwZ
446.21) C, 56.50; H, 7.40; N, 9.42. Found: C, 56.38; H,
7.34; N, 9.29.
with anhydrous THF (10 mL), t1Z15 min, t2Z30 min, gave
after purification by column chromatography (silicagel,
eluent petroleum ether/ethyl acetate (2:1)) 110 mg (46%) of
8a as a yellow solid, mp 176–178 8C; 1H NMR (CDCl3): d
8.88 (1H, d, JZ4.5 Hz, H-60), 8.48 (1H, s, H-2), 7.90 (1H,
ddd, JZ7.9, 7.5, 1.6 Hz, H-40), 7.63 (1H, d, JZ7.9 Hz,
H-30), 7.51–7.37 (11H, H-phenyl, H-50); 13C NMR (CDCl3):
d 167.4 (2C, C-4, C-6), 157.2 (10C, C-2), 153.2 (1C, C-20),
151.1 (1C, C-60), 137.6 (1C, C-4 ), 135.9 (4C, CH-phenyl),
129.8 (2C, CH-phenyl), 129.6 (4C, CH-phenyl), 128.8
(2C, Cq-phenyl), 128.1 (1C, C-5), 126.2 (1C, C-30),
124.4 (1C, C-50) ppm; MS (CI, rel int. %) 172 [MCK
PhSPh–NH](100). Anal. Calcd for C21H15N3S2 (MwZ
373.50) C, 67.53; H, 4.05; N, 11.25. Found: C, 67.50; H,
4.19; N, 11.20.
4.4.10. 3-(Hydroxy-(p-methoxyphenyl)methyl)-2-(20-pyr-
idyl)-pyrazine 4c. Metallation of 1 (100 mg, 0.64 mmol)
according to the general procedure C with n-BuLi (4 equiv,
1.58 mL), TMPH (4 equiv, 0.44 mL, TZK100 8C), fol-
lowed by reaction with p-methoxybenzaldehyde (4 equiv,
0.348 mg) in solution with anhydrous THF (10 mL), t1Z
15 min, t2Z30 min, gave after purification by column
¨
chromatography (silicagel, eluent dichloromethaneacetone
(10:1), 96 mg (51%) of 4c as a reddish oil; 1H NMR
(CDCl3): d 8.61 (1H, d, JZ4.9 Hz, H-60), 8.58 (2H, s, H-5,
-6), 7.97 (1H, d, JZ7.9, H-30), 7.78 (1H, ddd, JZ7.9, 7.5,
1.8 Hz, H-40), 7.32 (1H, ddd, JZ7.5, 4.9, 1.1 Hz, H-50), 7.09
(2H, d, JZ8.7 Hz, H-phenyl), 7.05 (1H, d, JZ7.0 Hz,
CHOH), 6.69 (2H, d, JZ8.7 Hz, H-phenyl), 6.29 (1H, d,
JZ7.0 Hz, CHOH), 3.69 (3H, s, OCH3); 13C NMR
(CDCl3): d 158.8 (1C, Cq-phenyl), 157.5 (1C, C-3), 156.4
(1C, C-20), 151.3 (1C, C-2), 148.0 (1C, C0-60), 143.0 and
142.7 (2C, C-5, C-6), 138.0 (1C, C-4 ), 134.3 (1C,
Cq-phenyl), 128.1 (2C, CH-phenyl), 125.1 (1C, C-30),
124.4 (1C, C-50), 113.6 (2C, CH-phenyl), 74.9 (1C, CHOH),
55.5 (1C, CH3) ppm; MS (ESI, rel int. %) 316 [MCCNaC]
(5), 276 (13), 262 (6), 184 (9), 171 (79), 126 (100). Anal.
Calcd for C17H15N3O2 (MwZ293.33) C, 69.61; H, 5.15; N,
14.13. Found: C, 69.37; H, 5.21; N, 14.14.
4.4.13. 4,6-Bistributylstannyl-5-(20-pyridyl)-pyrimidine
8b. Metallation of 2 (100 mg, 0.64 mmol) according to the
general procedure C with n-BuLi (4 equiv, 1.58 mL),
TMPH (4 equiv, 0.44 mL, TZK78 8C), followed by
reaction with diphenylsulfide (4 equiv, 574 mg) in solution
with anhydrous THF (10 mL), t1Z15 min, t2Z30 min, gave
after purification by column chromatography (silicagel,
eluent petroleum ether/ethyl acetate (5:1)) 306 mg (65%) of
1
8b as a yellow oil; H NMR (CDCl3): d 9.23 (1H, s, H-2),
8.67 (1H, d, JZ4.5 Hz, H-60), 7.75 (1H, ddd, JZ7.9, 7.5,
1.6 Hz, H-40), 7.320(1H, dd, JZ7.9, 7.5 Hz, H-50), 7.31 (1H,
d, JZ7.9 Hz, H-3 ), 1.37–1.27 (12H, m, CH2), 1.23–1.11
(12H, CH2), 0.90–0.67 (30H, m, CH2CH3); 13C NMR
(CDCl3): d 180.7 (2C, C-4, C-6), 159.9 (1C, C-20), 155.6
(1C, C-2), 151.2 (1C, C-5), 150.0 (1C, C-60), 136.7 (1C,
C-40), 124.3 and 123.0 (2C, C-30, -50), 29.3 (6C, CH2), 27.6
(6C, CH2), 14.0 (6C, CH3), 11.6 (6C, CH2); MS (CI, rel int.
%) 446 [MCKSn(n-Bu)3] (80), 332 (15), 219 (29), 184
(60), 170 (100). Anal. Calcd for C33H59N3Sn2 (MwZ
735.24) C, 53.91; H, 8.09; N, 5.72. Found: C, 53.79; H,
8.23; N, 5.78.
4.4.11. 6-(Hydroxy-(p-methoxyphenyl)methyl)-2-(20-
pyridyl)-pyrazine 5c. Metallation of
1 (100 mg,
0.64 mmol) according to the general procedure C with
n-BuLi (4 equiv, 1.58 mL), TMPH (4 equiv, 0.44 mL,
TZK100 8C), followed by reaction with p-methoxy-
benzaldehyde (4 equiv, 0.348 mg) in solution with anhy-
drous THF (10 mL), t1Z15 min, t2Z30 min, gave after
purification by column chromatography (silicagel, eluent
dichloromethane/acetone (10:1), 15 mg (8%) of 5c as a
reddish oil; 1H NMR (CDCl3): d 9.47 (1H, s, H-3), 8.67 (1H,
d, JZ3.8 Hz, H-60), 8.53 (1H, s, H-5), 8.34 (1H, d, JZ
7.9 Hz, H-30), 7.81 (1H, ddd, JZ7.9, 7.5, 1.8 Hz, H-40),
7.35–7.29 (1H, m, H-50), 7.32 (2H, d, JZ8.7 Hz, H-phenyl),
6.85 (2H, d, JZ8.7 Hz, H-phenyl), 5.86 (1H, s, CHOH),
4.80 (1H, br s, CHOH), 3.75 (3H, OCH3); 13C NMR
(CDCl3): d 159.9 (1C, Cq-phenyl), 156.1 (1C, C-6), 154.1
(1C, C-20), 149.9 (1C, C-60), 149.3 (1C, C-2), 143.3 (1C,
C-5), 141.8 (1C, C-3), 137.5 (1C, C-40), 134.5 (1C,
Cq-phenyl), 128.7 (2C, CH-phenyl), 125.0 (1C, C-50),
121.9 (1C, C-30), 114.6 (2C, CH-phenyl), 74.1 (1C, CHOH),
55.7 (1C, CH3); MS (ESI, rel int. %) 316 [MCCNaC] 276
(3), 171 (100), 126 (72). Anal. Calcd for C17H15N3O2
(MwZ293.33) C, 69.61; H, 5.15; N, 14.13. Found: C, 69.81;
H, 5.07; N, 14.39.
4.4.14. 4-(Hydroxy-(p-methoxyphenyl)methyl)-5-(20-
pyridyl)-pyrimidine 7c. Metallation of 2 (100 mg,
0.64 mmol) according to the general procedure C with
n-BuLi (4 equiv, 1.58 mL), TMPH (4 equiv, 0.44 mL,
TZK78 8C), followed by reaction with p-methoxybenz-
aldehyde (4 equiv, 0.348 mg) in solution with anhydrous
THF (10 mL), t1Z15 min, t2Z30 min, gave after purifi-
cation by column chromatography (silicagel, eluent petro-
leum ether/ethyl acetate (1:10)), 81 mg (43%) of 7c as a
reddish oil; 1H NMR (CDCl3): d 9.24 (1H, s, H-2), 8.71 (1H,
s, H-6), 8.66(1H, dd, JZ4.1, 0.8 Hz, H-60), 7.70 (1H, ddd,
JZ7.9, 7.5, 1.8 Hz, H-40), 7.30 (1H, ddd, JZ7.5, 4.6,
1.1 Hz, H-50), 7.19 (1H, d, JZ7.9 Hz, H-30), 6.89 (2H, d,
JZ8.7 Hz, H-phenyl), 6.62 (2H, d, JZ8.7 Hz, H-phenyl),
6.57 (1H, s, CHOH), 6.12 (1H, s, CHOH), 3.67 (3H, s, CH3);
13C NMR (CDCl3): d 168.6 (1C, C-4), 159.2 (1C, Cq-
phenyl), 157.8 (1C, C-2), 157.7 (1C, C-6), 154.1 (1C, C-20),
149.6 (1C, C-60), 137.9 (1C, C-40), 133.6 (1C, Cq-phenyl),
132.5 (1C, C-5), 128.3 (2C, CH-phenyl), 124.3 (1C, C-30),
123.8 (1C, C-50), 113.8 (2C, CH-phenyl), 73.5 (1C, CHOH),
55.5 (1C, CH3); MS (ESI, rel int. %) 293 [MC] (25), 276
(40), 260 (30), 158 (100), 130 (45), 79 (55). Anal. Calcd for
C17H15N3O2 (MwZ293.33) C, 69.61; H, 5.15; N, 14.13.
Found: C, 69.65; H, 5.20; N, 14.40.
4.4.12. 4,6-Bis(phenylthio)-5-(20-pyridyl)-pyrimidine 8a.
Metallation of 2 (100 mg, 0.64 mmol) according to the
general procedure C with n-BuLi (4 equiv, 1.58 mL),
TMPH (4 equiv, 0.44 mL, TZK78 8C), followed by
reaction with diphenylsulfide (4 equiv, 574 mg) in solution

C. Berghian et al. / Tetrahedron 61 (2005) 9637–9644
9643
4.4.15. 6-Phenyl-4-phenylthio-3-(20-pyridyl)pyridazine
10a. Metallation of 3 (200 mg, 0.85 mmol) according to
the general procedure C with n-BuLi (3 equiv, 1.58 mL),
TMPH (3 equiv, 0.44 mL, TZK78 8C), followed by
reaction with diphenylsulfide (3 equiv, 556 mg) in solution
with anhydrous THF (10 mL), t1Z20 min, t2Z4 h, gave
after purification by column chromatography (silicagel,
eluent petroleum ether/etoneac (3:1)) 156 mg (54%) of 10a
as a yellow solid, mp 141–142 8C; 1H NMR (CDCl3): d 8.82
(1H, d, JZ4.9 Hz, H-60), 8.56 (1H, d,0JZ7.9 Hz, H-30), 7.93
(1H, ddd, JZ7.9, 7.5, 1.5 Hz, H-4 ), 7.84–7.80 (2H, m,
H-phenyl), 7.65–7.62 (2H, m, H-phenyl), 7.53–7.51 (3H, m,
H-phenyl), 7.44–7.41 (4H, m, H-phenyl, H-50), 7.20 (1H, s,
H-5); 13C NMR (CDCl3): d 157.3 (1C, C-3), 155.4 (1C,
C-6), 153.6 (1C,0C-20), 148.0 (1C, C-60), 145.5 (1C, C-4),
137.4 (1C, C-4 ), 136.3 (2C, CH-phenyl), 131.0 (2C,
Cq-phenyl), 130.8 (2C, CH-phenyl), 130.7 (1C,
CH-phenyl), 130.4 (1C, CH-phenyl), 129.3 (2C,
CH-phenyl), 127.4 (2C, CH-phenyl), 124.4 (1C, C-50),
123.9 (1C, C-5), 121.3 (1C, C-30) ppm; MS (ESI, rel int. %)
364 [MCCNa] (100). Anal. Calcd for C21H15N3S (MwZ
341.44) C, 73.90; H, 4.40; N, 12.32. Found: C, 73.80; H,
4.36; N, 12.28.
13C NMR (CDCl3): d 160.3 (1C, C-3), 158.3 (1C, C-6),
157.2 (1C, C-20), 146.9 (1C, C-60), 146.7 (1C, C-40), 144.3
(1C, C-4), 138.8 (1C, C-30), 137.5 (1C, Cq-phenyl), 134.7
(1C, C-5), 130.1 (1C, CH-phenyl), 129.4 (2C, CH-phenyl),
127.6 (2C, CH-phenyl), 124.4 (1C, C-50), 29.6 and 29.5 (2C,
CH2), 27.9 and 27.8 (2C, CH2), 14.2 and 14.1 (2C, CH3),
13.3 and 13.0 (2C, CH2); MS (FABC, rel int. %) 811 [MC]
(100). Anal. Calcd for C39H63N3Sn2 (MwZ811.34) C,
57.71; H, 7.77; N, 5.18. Found: C, 57.80; H, 7.90; N, 5.08.
4.4.18. 4-(Hydroxy-(p-methoxyphenyl)methyl)-6-phenyl-
3-(20-pyridyl)-pyridazine 10c. Metallation of 3 (200 mg,
0.85 mmol) according to the general procedure C with
n-BuLi (3 equiv, 1.58 mL), TMPH (3 equiv, 0.44 mL,
TZK78 8C), followed by reaction with p-methoxybenz-
aldehyde (3 equiv, 347 mg) in solution with anhydrous THF
(10 mL), t1Z20 min, t2Z3 h, gave after purification by
column chromatography (silicagel, eluent petroleum ether/
ethyl acetate (1.5:1)) 207 mg (66%) of 10c as a yellow solid,
mp 152–153 8C; 1H NMR (CDCl3): d 8.84 (1H, JZ4.9 Hz,
H-60), 8.61 (1H, d, JZ7.9 Hz, H-30), 8.23–8.20 (2H, m,
H-phenyl), 8.13 (1H, ddd, JZ7.9, 7.5, 1.8 Hz, H-40), 7.89
(1H, br s, CHOH), 7.77 (1H, s, H-5), 7.70–7.66 (3H, m,
H-phenyl), 7.62 (1H, ddd, JZ7.5, 4.9, 1.0 Hz, H-50), 7.45
(2H, d, JZ8.7 Hz, H-phenyl), 7.05 (2H, d, JZ8.7 Hz,
H-phenyl), 6.19 (1H, CHOH), 3.97 (3H, s, CH3); 13C NMR
(CDCl3): d 159.3 (1C, C-3), 159.2 (1C, Cq-phenyl), 157.3
(1C, C-6), 155.8 (1C, C-20), 147.9 (1C, C-60), 144.1 (1C,
C-4), 138.4 (1C, C-40), 136.2 (1C, Cq-phenyl), 132.3
(1C, Cq-phenyl), 130.7 (1C, CH-phenyl), 129.4 (2C,
CH-phenyl), 128.3 (2C, CH-phenyl), 127.6 (2C, CH-
phenyl), 125.7, 124.7 and 124.2 (3C, C-5, -50, -30), 114.1
(2C, CH-phenyl), 72.1 (1C, CHOH), 55.6 (1C, CH3); MS
(ESI, rel int. %) 392 [MCCNa] (100), 177 (38), 126 (47).
Anal. Calcd for C23H19N3O2 (MwZ369.43) C, 74.80; H,
5.15; N, 11.38. Found: C, 74.70; H, 5.20; N, 14.42.
4.4.16. 6-Phenyl-4-tributylstannyl-3-(20-pyridyl)-pyrida-
zine 10b. Metallation of 3 (200 mg, 0.85 mmol) according
to the general procedure C with n-BuLi (3 equiv, 1.58 mL),
TMPH (3 equiv, 0.44 mL, TZK78 8C), followed by
reaction with tributultin chloride (1.1 equiv, 0.79 mL) in
solution with anhydrous THF (10 mL), t1Z20 min, t2Z1 h,
gave after purification by column chromatography (silica-
gel, eluent petroleum ether/ethyl acetate (4:1)) 195 mg
(44%) of 10b as a yellow oil; 1H NMR (CDCl3): d 8.90 (1H,
d, JZ7.9 Hz, H-30), 8.59 (1H, d, JZ4.9 Hz, H-60), 8.21 (1H,
s, H-5), 8.20 (2H, d, JZ9.8 Hz, CH-phenyl), 7.92 (1H, ddd,
JZ7.9, 7.5, 1.1 Hz, H-40), 7.60–7.49 0(3H, m, H-phenyl),
7.41 (1H, ddd, JZ7.5, 4.9, 1.1 Hz, H-5 ), 1.60–1.39 (6H, m,
CH2), 1.35–1.23 (6H, m, CH2), 1.21–0.99 (6H, m, CH2),
0.84 (9H, m, CH3); 13C NMR (CDCl3): d 160.5 (1C, C-3),
157.3 (1C, C-6), 155.0 (1C, C-20), 147.5 (1C, C-60), 143.9
(1C, C-4), 138.0 (1C, C-40), 137.2 (1C, Cq-phenyl), 134.3
(1C, C-5), 130.2 (1C, CH-phenyl), 129.4 (2C, CH-phenyl),
127.6 (2C, CH-phenyl), 124.8 (1C, C-50), 122.1 (1C, C-30),
29.6 (3C, CH2), 27.8 (3C, CH2), 14.1 (3C, CH3), 13.2 (3C,
CH2) ppm; MS (ESI, rel int. %) 546 [MCCNa] (100), 466
(30), 227 (47), 195 (82), 183 (100), 165 (68), 109 (46). Anal.
Calcd for C27H37N3Sn (MwZ522.31) C, 62.07; H, 7.09; N,
8.05. Found: C, 61.98; H, 7.15; N, 8.12.
4.4.19. 4,6-Diphenyl-5-(20-pyridyl)-pyrimidine 12.
Reaction of 8b according to procedure D gave 16.7 mg
(0.054 mmol, 33%) of 12 as a colorless solid, mp 155–
156 8C; 1H NMR (CDCl3): d 9.32 (1H, s, H-2), 8.43 (1H, dd,
JZ4.9, 1.6 Hz, H-60), 7.42 (1H, ddd, JZ7.9, 7.5, 1.6 Hz,
H-40), 7.26–7.14 (10H, m, H-phenyl), 7.06 (1H, ddd, JZ7.9,
4.9, 1.0 Hz, H-50), 6.94 (1H, d, JZ7.5 Hz, H-30); 13C NMR
(CDCl3): d 165.9 (2C, C-4, C-6), 158.2 (1C, C-2), 156.3
(1C, C-200), 150.0 (1C, C-60), 138.4 (2C, Cq-phenyl), 136.5
(1C, C-4 ), 131.3 (1C, C-5), 129.8 (4C, CH-phenyl),1290.4
(2C, CH-phenyl), 128.4 (4C, CH-phenyl), 126.8 (1C, C-3 ),
122.7 (1C, C-50); MS (FABC, rel int. %) 310 [MCC1]
(100), 154 (40). Anal. Calcd for C21H15N3 (MwZ309.17) C,
81.55; H, 4.85; N, 13.59. Found: C, 81.60; H, 4.79; N, 13.74.
4.4.17. 4-Tributylstannyl-3-(30-tributylstannylpyrid-20-
yl)-6-phenylpyridazine 11b. Metallation of 3 (200 mg,
0.85 mmol) according to the general procedure C with
n-BuLi (3 equiv, 1.58 mL), TMPH (3 equiv, 0.44 mL,
TZK78 8C), followed by reaction with tributultin chloride
(3 equiv, 2.15 mL) in solution with anhydrous THF
(10 mL), t1Z20 min, t2Z2 h, gave after purification by
column chromatography (silicagel, eluent petroleum ether/
ethyl acetate (25:1)) 317 mg (46%) of 11b as a yellow oil;
1H NMR (CDCl3): d 8.52 (1H, dd, JZK4.5, 1.5 Hz, H-60),
8.21 (1H, s, H-5), 8.19–8.16 (2H, m, H-phenyl), 8.13 (1H,
dd, JZ7.2, 1.5 Hz, H-40), 7.61–7.49 (3H, m, H-phenyl),
7.36 (1H, dd, JZ7.2, 4.5 Hz, H-50), 1.55–1.42 (12H, m,
CH2), 1.35–1.08 (24H, m, CH2), 0.91–0.80 (18H, m, CH3);
4.4.20. Bis-4,4-[6-phenyl-5-(20-pyridyl)]pyrimidine 13.
Reaction of 8b according to procedure D gave 25 mg
(0.054 mmol, 66%) of 13 as a yellow solid, mp 202–204 8C;
1H NMR (CDCl3): d 8.90 (2H, s, H-2), 8.20 (2H, d, JZ
4.9 Hz, H-60), 7.21–7.01 (12H, m, H-phenyl, H-40), 6.86
(2H, m, H-50), 6.82 (2H, d, JZ7.5 Hz, H-30); 13C NMR
(CDCl3): d 165.5 (2C, C-6), 164.2 (2C, C-4), 157.2 (2C,
C-2), 154.8 (2C, C-20), 149.8 (2C, C-60), 137.8 (2C,
Cq-phenyl), 136.1 (2C, C-40), 131.5 (2C, C-5), 130.1 (4C,
CH-phenyl), 129.8 (2C, 0 CH-phenyl), 1028.5 (4C,
CH-phenyl), 126.6 (2C, C-3 ), 122.6 (2C, C-5 ) ppm; MS

9644
C. Berghian et al. / Tetrahedron 61 (2005) 9637–9644
(FABC, rel int. %) 465 [MCC1] (89), 138 (100), 77 (58).
Anal. Calcd for C30H20N36 (MwZ464.53) C, 77.59; H, 4.31;
N, 18.10. Found: C, 77.65; H, 4.40; N, 18.19.
7191. (b) Krizan, T. D.; Martin, J. C. J. Org. Chem. 1982, 47,
2681.
5. (a) Snieckus, V. Chem. Rev. 1990, 90, 879. (b) Snieckus, V.
Acc. Chem. Res. 1982, 15, 306. (c) Beak, P.; Basu, A.;
Gallagher, D. J.; Park, Y. S.; Thayumanavan, S. Acc. Chem.
Res. 1996, 29, 552.
6. (a) Itami, K.; Kamei, T.; Mitsudo, K.; Nokami, T.; Yoshida, J.-I.
J. Org. Chem. 2001, 66, 3970. (b) Mugesh, G.; Singh, H. B. Acc.
Chem. Res. 2002, 35, 226. (c) Zoltewicz, J. A.; Dill, C. D.
Tetrahedron 1996, 52, 14469. (d) Fort, Y.; Rodriguez, L. J. Org.
Chem. 2003, 68, 4918. (e) Parmentier, M.; Gros, P.; Fort, Y.,
Tetrahedron, 2005, 61, 3261.
References and notes
¨
1. (a) Bejan, E.; Aıt-Haddou, H.; Daran, J.-C.; Balavoine, G. G. A.
Synthesis 1996, 1012. (b) Beauchamp, D. A.; Loeb, S. J. Chem.
Commun. 2002, 2484.
2. Cuccia, L. A.; Ruiz, E.; Lehn, J.-M.; Homo, J.-C.; Schmutz, M.
Chem. Eur. J. 2002, 3448.
´
3. (a) Mongin, F.; Queguiner, G. Tetrahedron 2001, 57, 4059 and
7. Hasebe, M.; Kogawa, K.; Tsuchiya, T. Tetrahedron Lett. 1984,
25, 3887.
8. Hitchcock, S. A.; Mayhugh, D. R.; Stuart Gregory, G.
Tetrahedron Lett. 1995, 36, 9085.
´ ´
9. Ple, N.; Turck, A.; Couture, K.; Queguiner, G. J. Org. Chem.
´
references therein. (b) Turck, A.; Ple, N.; Mongin, F.;
´
Queguiner, G. Tetrahedron 2001, 57, 4489 and references
therein.
4. (a) Bauer, W.; Schleyer, P. v. R. J. Am. Chem. Soc. 1989, 111,
1995, 60, 3781.