An expedient, flexible and convergent access to selectively protected 1,5-dicarbonyl compounds. Applications to the synthesis of 2,6-disubstituted pyridines and thiopyridines

Article abstract of DOI:10.1055/s-2006-926464

Intermolecular addition of 2-oxoalkyl radicals generated from the corresponding S-alkyl-O-ethyl dithiocarbonates on vinyl ketals afforded selectively protected 1,5-dicarbonyl compounds in good yields. These key-intermediates can be converted into a plethora of useful substances. Transformations to pyridines and thiopyridines were given as examples. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-926464

1664
PAPER
An Expedient, Flexible and Convergent Access to Selectively Protected
1,5-Dicarbonyl Compounds. Applications to the Synthesis of 2,6-Disubstituted
Pyridines and Thiopyridines
Synthesis
e
of 1,5-Dica
a
rbonyl
C
om
n
pounds
a
nd 2,6-D
B
isubstituted Pyrid
o
ine
s
ivin,* Floriane Carpentier, Rafik Jrad
Institut de Chimie des Substances Naturelles, Gif-sur-Yvette 91198, France
Fax +33(1)69077247; E-mail: jean.boivin@icsn.cnrs-gif.fr
Received 12 July 2005; revised 18 January 2006
S
R
R'
O
Abstract: Intermolecular addition of 2-oxoalkyl radicals generated
from the corresponding S-alkyl-O-ethyl dithiocarbonates on vinyl
ketals afforded selectively protected 1,5-dicarbonyl compounds in
good yields. These key-intermediates can be converted into a pleth-
ora of useful substances. Transformations to pyridines and thiopy-
ridines were given as examples.
O
O
R
a,b
O
S
OEt
+
O
R'
O
A
B
C
c
Key words: ketals, alkenes, ketones, pyridines, radical reactions
d
R
N
R'
E
R
R'
D
O
O
The powerful radical chemistry of the xanthate group was
nicely developed by Barton, Zard and their co-workers
during the last two decades.1,2 Many radical processes that
would be otherwise difficult to realize by classical meth-
ods because of unavoidable and useless side reactions
could be achieved. Besides the reduction to the corre-
sponding alkane,3 a special mention must be made to in-
termolecular addition of 2-oxoalkyl radicals to
unactivated olefins that produces xanthate adducts in gen-
erally good yields and tolerates many functional groups.
This method has become an easy and efficient way to
form carbon–carbon bonds under smooth conditions. In
most cases the xanthate moiety present in the adduct be-
comes useless and is reduced to an alkane.3,4 In this paper,
we wish to describe an approach in which a carbon skele-
ton is assembled by addition of a 2-oxoalkyl radical to a
vinyl ketal that produces a selectively protected 1,5-dicar-
bonyl compound. The strategy we have developed for this
purpose is summarized in Figure 1. It is worthy of note
that, by suitably choosing the starting materials, i.e. A and
B, or B¢ and A¢, two different mono-protected diketones,
C and C¢ respectively, can be obtained. Upon hydrolysis
both C and C¢ furnish diketone D. Moreover, because in-
termolecular radical additions tolerate an ample substitu-
tion pattern in both xanthate and olefin moieties and also
display a high chemoselectivity, the range of molecules C,
C¢ and D is infinitely sizeable.
e
R
N
H
R'
c
F
S
R'
R
O
a,b
R'
+
O
O
S
OEt
O
O
R
O
B'
A'
C'
R"NH2
[H]
f
R'
R
b
c
O
R'
N
R
O
R'
N
R
NH
"R
R"
R"
G
I
H
R
R'
N
O
J
Ph
Figure 1 a) intermolecular radical addition; b) reduction; c) hydro-
lysis; d) ammonia source in the presence of dioxygen; e) ammonia
source in the absence of dioxygen; f) reductive amination.
To illustrate the potential of our strategy, we chose to con-
vert compounds D into 2,6-disubstituted pyridines E. Of
course, an interesting chemistry leading to dihydropyr-
idines F, tetrahydropyridines H, and piperidines I from
synthons C or C¢ might have been also envisioned
(Figure 1). Incidentally, the chirality might be introduced
in a reductive amination step (f) or through oxazolopiper-
idines J, highly valuable intermediates in the CN(R,S)
method.8b
The chemistry of these molecules is exceptionally rich
and important: selectively protected 1,5-diketones have
been used as building blocks mainly in the synthesis of
carbocycles5,6 and 1,5-diketones intervene in many syn-
thetic processes aimed to elaborate carbocycles7 and het-
erocycles.8a
At least in the case of pyridines many synthetic methods
rely on the transformation of the preexisting nucleus un-
der rather harsh conditions poorly adapted to sensitive
functions. A stepwise construction of the pyridine nucleus
requires also rather drastic reaction conditions.9 Organo-
metallic chemistry might be an interesting alternative.
SYNTHESIS 2006, No. 10, pp 1664–1672
x
x.
x
x
.
2
0
0
6
Advanced online publication: 27.04.2006
DOI: 10.1055/s-2006-926464; Art ID: T09905SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 1,5-Dicarbonyl Compounds and 2,6-Disubstituted Pyridines
1665
Thus, cycloaddition of two alkynes and a nitrile to a pyri- Intermolecular additions of xanthates 2 to olefins 6, cata-
dine, catalyzed with organocobalt complexes under mild lyzed by dilauroyl peroxide (DLP), in refluxing cyclohex-
conditions, was published recently.10 However, in many ane proceeded smoothly under inert atmosphere and were
instances, ring closure of a convenient precursor is con- performed as usual,13 affording the corresponding adducts
sidered as a more flexible and smooth process.11,12
7 (Scheme 3, Table 1). In most experiments, we used cat-
alytic amounts of 2,6-lutidine to prevent a putative hy-
drolysis of the ketal group because of the formation of
lauric acid, a by-product from the decomposition of DLP.
In fact, further experiments proved that this precaution
was useless, mainly because only very small amounts of
DLP were introduced [typically 5–10% (mol/mol xan-
thate)]. The results are summarized in Table 1. Entries 1–
6 show that additions of xanthates 2a–c onto olefins 6a
and 6b gave fair to good yields of adducts 7a–f.
Radical chemistry usually operates under neutral condi-
tions and therefore is appropriate to wield sensitive com-
pounds. In a preceding paper, we showed that addition of
a 2-oxoalkyl radical to an allylic amine constitutes an at-
tractive, flexible, and high-yielding way to gain access to
these molecules under very mild conditions.13 This ap-
proach was utilized recently in a synthesis of precursors of
Eburna and Lupin alkaloids.14
Xanthates derivatives 2a–c used in the present paper were
prepared quantitatively by displacement of the corre-
sponding halides 1a–c in the usual way (Scheme 1).
In order to gain access later to 2,6-disubstituted pyridines,
we had to proceed to the cleavage of the ketal group and
to the reductive removal of the xanthate group. Hence a
two-step process, i.e. reduction–hydrolysis or hydrolysis–
reduction was applied to adducts 7 to reach diketones 10
(Tables 2 and 3). Hydrolysis with a mixture of trifluoro-
acetic acid/water/dichloromethane at room temperature
permitted to prepare 2-oxoalkyl xanthates 9a–d
(Scheme 3) from the corresponding ketals 7a–d in good
yields (Table 2, entries 1–4).
S
R
R
X
S
O
O
O
1a R = t-Bu, X = Cl
1b R = p-biphenyl, X = Br
1c R = p-methoxyphenyl, X = Br
2a R = t-Bu
2b R = p-biphenyl
2c R = p-methoxyphenyl
Scheme 1 Reagents and conditions: KSCSOEt in EtOH or acetone
at 20 °C.
As for reductive cleavage of the xanthate group, proce-
dures based on Bu3SnH/AIBN in refluxing toluene (Meth-
od A) or on propan-2-ol as hydrogen atom donor in the
presence of stoichiometric amounts of dilauroyl peroxide
(Method B) were utilized (Table 3). In some instances,
isopropyl acetate was used instead of propan-2-ol because
of its lower nucleophilicity. Reduction of the xanthate
group was accomplished from ethylene ketals 7a, 7d, 7e
and 7f, to produce compounds 8a–d (Scheme 3, Table 3,
entries 1–5). Compounds 8a, 8c and 8d were hydrolyzed
as above to give diketones 10a, 10d, and 10e (Table 2, en-
tries 5–7). Alternatively, the method described by Huet et
al. (oxalic acid on silica gel, entry 6) gave similar results.17
Vinyl ketals 6 were easily obtained on a large scale ac-
cording to known procedures by elimination of potassium
p-toluenesulfinate from b-toluenesulfonyl ethylene ketals
5 under basic conditions.15 The latter were obtained by
ketalization of the corresponding ketones 4. The sulfonyl
group was introduced by substitution of the corresponding
chloro derivatives 3 either commercially available (3a) or
synthesized by Friedel–Crafts reaction16 between ethyl-
ene and the appropriate acyl chloride in the presence of
aluminum chloride at low temperature (compound 3b,
Scheme 2).
Table 1 Intermolecular Addition of Xanthates onto Vinyl Ketals in
the Presence of Catalytic Amounts of DLPa and 2,6-Lutidineb in Re-
fluxing Cyclohexane
O
O
a
R'
Cl
Entry
Xanthate Olefin
(equiv vs xanthate)
Adduct (yield, %)
R'
SO2Tol
54% R' = Ph
85% R' = Et
3a R' = Ph
3b R' = Et
4a R' = Ph
4b R' = Et
1
2
3
4
5
6
7
2a
2a
2b
2b
2c
2c
9a
6a (0.66)
6b (0.66)
6a (0.66)
6b (0.66)
6a (0.66)
6b (0.66)
6b (0.66)
7a (82)
7b (52)
7c (71)
7d (58)
7e (83)
7f (69)
13a (32)c
54% R' = Ph
85% R' = Et
b
O
c
O
O
O
54% R' = Ph
85% R' = Et
R'
R'
SO2Tol
5a R' = Ph
5b R' = Et
6a R' = Ph
6b R' = Et
Scheme 2 Reagents and conditions: (a) TolSO2Na, EtOH, reflux, 4
h; (b) ethylene glycol, p-TsOH (cat.), toluene, reflux, 8 h; (c) dime-
thylethylene urea (DMEU), t-BuOK, toluene, reflux, for 6a; same
conditions but without toluene for 6b.
a 5–15% mol vs xanthate.
b 0.2 equiv vs olefin.
c 65% conversion.
Synthesis 2006, No. 10, 1664–1672 © Thieme Stuttgart · New York

1666
J. Boivin et al.
PAPER
Table 3 Reduction of Xanthatesa
S
S
S
OEt
R'
Entry
Xanthate
7a
Alkane (yield%)
8a (63)
Method
O
O
a
R
R
+
OEt
S
R'
1
2
B
C
A
D
A
A
B
B
C
A
O
O
O
O
7d
8b (93)
2a R = t-Bu
2b R = p-biphenyl
2c R = p-methoxyphenyl
6a R' = Ph 7a R = t-Bu, R' = Ph
6b R' = Et
7b R = t-Bu, R' = Et
7c R = p-biphenyl, R' = Ph
7d R = p-biphenyl, R' = Et
3
7e
8c (92)
4
7e
8a (31)
7e R = p-methoxyphenyl, R' = Ph
7f R = p-methoxyphenyl, R' = Et
5
7f
8d (78)
6
9c
10b (22)
10b (58)
10c (63)
13b (89)
13b (56)
b
c
7
9c
S
8
9d
S
OEt
R'
R
R'
9
13a
13a
R
O
O
O
10
O
O
9a R = t-Bu, R' = Ph
9b R = t-Bu, R' = Et
9c R = p-biphenyl, R' = Ph
9d R = p-biphenyl, R' = Et
a Method A: Bu3SnH, AIBN in refluxing toluene; Method B: Stoichi-
ometric amount of DLP (1–1.2 equiv vs xanthate) in propan-2-ol;
Method C: H2PO3, Et3N, AIBN, dioxane; Method D: stoichiometric
amounts of DLP (1–1.2 equiv vs xanthate) in isopropyl acetate.
8a R = t-Bu, R' = Ph
8b R = p-biphenyl, R' = Et
8c R = p-methoxyphenyl, R' = Ph
8d R = p-methoxyphenyl, R' = Et
b
c
pophosphorous method had been used, as shown by
comparison between entries 9 and 10 (Table 3).
R
R'
O
O
Diketones 10a,c,d,e were converted to the corresponding
pyridines by heating in AcOH in the presence of ammoni-
um acetate, according to Pchelintseva’s method.11 Spon-
taneous oxidation with air afforded the corresponding 2,6-
disubstituted pyridines 11a–e in non-optimized 24–93%
yields (Scheme 4, Table 4, entries 1–5).
10a R = t-Bu, R' = Ph
10b R = p-biphenyl, R' = Ph
10c R = p-biphenyl, R' = Et
10d R = p-methoxyphenyl, R' = Ph
10e R = p-methoxyphenyl, R' = Et
Scheme 3 Reagents and conditions: (a) DLP (5–15% mol vs
xanthate) and 2,6-lutidine (0.2 equiv vs olefin) in refluxing cyclohe-
xane; (b) see Table 2 (c) see Table 3.
Interestingly, when the reaction with ammonium acetate
was performed on diketones 9a and 9d, respectively,
without prior reduction of the xanthate moiety, thiopy-
ridines 12a and 12b were isolated in 91 and 32% yields,
respectively (Scheme 4, Table 4, entries 6 and 7). To our
knowledge these compounds represent the first example
of pyridines bearing a xanthate function. The latter of
course could be hydrolyzed to the corresponding thiol.
Much of the work reported herein was achieved when we
discovered that reduction based on phosphorous deriva-
tives (Method C) was generally far more efficient.4
Hence, the yields given for reduction with Bu3SnH or pro-
pan-2-ol would have been certainly much higher if the hy-
Table 2 Hydrolysis of Ketalsa
Table 4 Formation of pyridines 11, 12 and 14 from Diketones 10,
9, and 13b in the Presence of Ammonium Acetate in AcOH
Entry
Ketal
7a
Ketone (yield, %)
9a (78)
Entry
Diketone
10a
10b
10c
Pyridine (yield, %)
11a (62)
1
2
3
4
5
6
7
1
2
3
4
5
6
7
8
7b
7c
9b (81)
11c (47)
9c (83)
11b (31)
7d
8a
9d (87)
10d
10e
11d (93)
10a (51)
10d (57)b
10e (99)
11e (24)
8c
9a
12a (91)
8d
9d
12b (32)
a Hydrolysis with a mixture of F3CCO2H–H2O–CH2Cl2 (3.5:0.35:10,
c = 100 mg/mL) at r.t. (4 h).
b Hydrolysis performed by treatment with oxalic acid on silica gel.20
13b
14 (66)
Synthesis 2006, No. 10, 1664–1672 © Thieme Stuttgart · New York

PAPER
Synthesis of 1,5-Dicarbonyl Compounds and 2,6-Disubstituted Pyridines
1667
spectrum of the crude. This explains that only one regio-
isomer was formed.
R
R'
a
O
O
R
N
R'
The preliminary results reported herein suggest that the
scope of this strategy can be widely generalized. Because
of the smoothness of the reaction conditions, intermolec-
ular addition of 2-oxoalkyl radical onto terminal olefin
containing a masked carbonyl group may represent a very
efficient way to produce differentiated dicarbonyl com-
pounds and hence, a plethora of useful transformations
can be envisioned. We are currently working along these
lines.
10
11a R = t-Bu, R' = Ph
11b R = p-biphenyl, R' = Et
11c R = p-biphenyl, R' = Ph
11d R = p-methoxyphenyl, R' = Ph
11e R = p-methoxyphenyl, R' = Et
S
S
OEt
S
OEt
R'
S
a
R
R
N
R'
O
O
FTIR spectra were recorded on a PerkinElmer BX FT-IR instru-
ment. Absorptions are given in cm–1. 1H and 13C NMR spectra were
measured using either a Bruker AM-300, AM-400 or AC-250 in-
strument with chemical shifts reported as d (ppm) downfield from
TMS (d = 0.00) using the residual solvent signal of CHCl3 (1H
NMR: d = 7.27, singlet; 13C NMR: d = 77.0, triplet) as internal stan-
dard. Mass spectra were recorded on a Thermoquest Navigator
mass spectrometer with electrospray ionization (ESI). Electron im-
pact (EI) mass spectra were obtained with an AEI MS-50 instru-
ment. Chemical ionization (CI) mass spectra were recorded on a
HP5989B spectrometer. Melting points were determined with the
aid of a Büchi B-540 apparatus. Analytical TLC was performed us-
ing F254 pre-coated silica gel plates. After elution, UV active ma-
terials were visualized by UV illumination at 254 nm while non-
active materials were visualized by staining with ethanolic vanillin
solution (5% w/v solution of H2SO4 in EtOH), followed by charring
with a heat gun. Silica gel (Kieselgel 60, Merck) was used for flash
chromatography. All reactions were performed under argon unless
otherwise stated. Commercial reagents were used as received and
anhydrous solvents were either distilled from suitable drying agent
or purchased.
9
12a R = t-Bu, R' = Ph
12b R = p-biphenyl, R' = Et
c
6b
O
O
O
a
X
Ph
N
Ph
O
O
14
13a X = SCSOEt
13b X = H
Scheme 4 Reagents and conditions: (a) AcOH, AcONH4, reflux;
(b) catalytic amounts of DLP, cyclohexane, reflux.
Few methods describe the preparation of 3-thiopyridines.
Most of them start from the corresponding 3-halo deriva-
tive.18,19 Noteworthy, 3-mercaptopicolinic acid displays
an interesting antidiabetic activity and some analogues
have also been synthesized.20
Dithiocarbonic Acid S-(3,3-Dimethyl-2-oxobutyl)Ester O-Ethyl
Ester (2a)
This known compound was obtained from chloropinacolone in 97%
yield according to the procedure described for the preparation of
compound 2b (see below).23
As emphasized above, compounds 9 possess a xanthate
moiety in a position to a carbonyl group. Therefore, an it-
erative addition from a newly formed electrophilic, stabi-
lized carbon radical to an olefin can be foreseen.21 a-Ketal
xanthates 7 can be considered as sources of nucleophilic
carbon radicals. Such radicals have been used to achieve
cyclizations onto aromatic rings. These reactions lead to
the formation of a-tetralones, indanes, indolines, etc. In
these cases, stoichiometric amounts of peroxide are need-
ed as the rearomatization step does not allow a radical
chain mechanism and harsh reaction conditions are re-
quired because of an impeded process that demands much
energy.22
Dithiocarbonic Acid S-[2-(Biphenyl-4-yl)-2-oxoethyl] Ester O-
Ethyl Ester (2b)13
Potassium O-ethylxanthate (10.58 g, 66 mmol) was added to a
stirred solution of 1-bromo-4¢-phenylacetophenone (16.5 g, 60
mmol) in acetone (170 mL) at 0 °C. At the end of the addition, the
mixture was allowed to warm to r.t. and then poured into H2O. The
white precipitate was collected by filtration and dried. Crystalliza-
tion from EtOH gave the title compound 2b; yield: 11.39 g (60%).
IR (Nujol): 1675, 1245, 1114, 1054, 763 cm–1.
1H NMR (CDCl3): d = 8.13–8.01 (m, 2 H), 7.75–7.63 (m, 4 H),
7.52–7.42 (m, 3 H), 4.70 (s, 2 H), 4.66 (q, J = 7.1 Hz, 2 H), 1.42 (t,
J = 7.1 Hz, 3 H).
To illustrate this possibility, we reacted xanthate 9a with
vinyl dioxolane 6b under usual conditions (catalytic
amounts of DLP in refluxing cyclohexane) (Scheme 4).
Adduct 13a was formed in a modest but not optimized
32% yield. After desulfurization (Table 3, entries 9 and
10), compound 13b was converted into pyridine 14 in a
fair 66% yield (Table 4, entry 6). Interestingly, no cycliza-
tion of the transient xanthate 13a on the phenyl group was
observed. The hydrolysis of the ketal group occurred dur-
ing the purification over silica gel as proven by the NMR
13C NMR (CDCl3): d = 213.1, 192.0, 146.6, 139.8, 134.7, 129.2,
128.6, 127.6, 127.4, 70.8, 43.7, 13.9.
HRMS-ESI: m/z calcd for C17H16O2S2 + Na [M + Na]+: 339.0489;
found: 339.0487.
Dithiocarbonic Acid O-Ethyl Ester S-[2-(4-Methoxyphenyl)-2-
oxoethyl] Ester (2c)24
Potassium ethylxanthogenate (4.45 g, 27.7 mmol) was added slowly
to a solution of 1-bromo-(4¢-methoxy)acetophenone (5.72 g, 25
mmol) in anhydrous acetone (50 mL). Upon addition of H2O (200
mL), the title compound 2c precipitated. The solid was collected by
Synthesis 2006, No. 10, 1664–1672 © Thieme Stuttgart · New York

1668
J. Boivin et al.
PAPER
filtration and dried affording 2c as a white powder; yield: 6.07 g
(89%).
1H NMR (CDCl3): d = 7.96 (d, J = 8.4 Hz, 2 H), 7.66–7.32 (m, 12
H), 4.56 (q, J = 7.1 Hz, 2 H and m, 1 H), 4.13 (m, 2 H), 3.85 (m, 2
H), 3.14 (m, 2 H), 2.29 (m, 1 H), 1.9 (m, 1 H), 1.37 (t, J = 7.1 Hz,
3 H).
IR (Nujol): 1664, 1598, 1574, 1255, 1214, 1174, 1109, 1056, 1032
cm–1.
13C NMR (CDCl3): d = 214.6, 199.0, 145.7, 140.2, 140.0, 135.6,
129.0, 128.7, 128.5, 128.2, 127.3, 126.5, 110.5, 70.3, 65.7, 65.3,
59.0, 36.0, 24.7, 13.8.
1H NMR (CDCl3): d = 8.02 (d, J = 8.9 Hz, 2 H), 6.97 (d, J = 8.9 Hz,
2 H), 4.64 (q, J = 7.1 Hz, 2 H), 4.63 (s, 2 H), 3.89 (s, 3 H), 1.40 (t,
J = 7.1 Hz, 3 H).
HRMS-ESI: m/z calcd for C28H28O4S2 + Na [M + Na]+: 515.1327;
found: 515.1323.
13C NMR (CDCl3): d = 213.6, 190.9, 164.2, 130.9, 129.0, 114.1,
70.7, 55.6, 43.5, 13.8.
MS (ID, IC): m/z = 288 (M + NH4 ), 271 (M + H+).
+
Dithiocarbonic Acid S-[4-(Biphenyl-4-yl)-1-(2-ethyl[1,3]dioxo-
lan-2-yl)-4-oxobutyl] Ester O-Ethyl Ester (7d)
Dithiocarbonic Acid S-[5,5-Dimethyl-4-oxo-1-(2-phenyl[1,3]di-
oxolan-2-yl)hexyl] Ester O-Ethyl Ester (7a); Typical Procedure
A solution of xanthate 2a (0.937 g, 4.26 mmol), olefin 6a (0.5 g,
2.84 mmol) and 2,6-lutidine (0.066 mL, 0.2 equiv vs olefin) in cy-
clohexane (4 mL) was refluxed under argon for 30 min. Dilauroyl
peroxide (DLP) was then added portionwise (0.05 equiv vs xan-
thate, then 0.02 equiv every 2 h). The reaction was monitored by
TLC. After completion of the reaction (0.11 equiv of DLP added),
the solvent was evaporated under reduced pressure and the residue
was placed onto a column of silica gel. Elution with a mixture of
heptane–EtOAc (9:1) containing few drops of Et3N afforded the ti-
tle compound 7a (0.927 g, 82%) as a pale-yellow oil.
A solution of xanthate 2b (4.121 g, 13.03 mmol), olefin 6b (1.129
g, 8.81 mmol) and 2,6-lutidine (0.20 mL, 0.2 equiv vs olefin) in cy-
clohexane (12 mL) was treated as above to furnish the title com-
pound 7d (2.266 g, 58%) as white crystals; mp 53–57.8 °C (EtOH).
IR (Nujol): 2977, 2937, 2890, 1682, 1604, 1582, 1560, 1514, 1486,
1449, 1403, 1364, 1217, 1111, 1048 cm–1.
1H NMR (CDCl3): d = 8.05 (d, 2 H, J = 8.1 Hz), 7.65 (2 d, J = 8.0
Hz, 4 H), 7.45 (m, 4 H), 4.59 (m, 2 H), 4.30 (dd, J = 3.6, 11.0 Hz, 1
H), 4.06 (m, 4 H), 2.66 (m, 1 H), 1.94 (m, 1 H), 1.84 (dq, J = 2.1,
7.3 Hz, 2 H), 1.38 (t, J = 7.2 Hz, 3 H), 0.98 (t, J = 7.3 Hz, 3 H).
13C NMR (CDCl3): d = 214.9, 199.0, 145.6, 135.6, 129.0, 128.6,
128.2, 127.3, 127.2, 112.3, 70.4, 66.0, 66.3, 57.2, 35.9, 28.3, 24.7,
13.8, 7.4.
IR (film): 3089, 3061, 3028, 2968, 2891, 1959, 1891, 1815, 1705,
1609, 1477, 1448, 1403, 1365, 1291, 1218, 1176, 1155, 1111, 1050,
985, 946, 776, 759, 701 cm–1.
MS (CI): m/z = 446, 463.
1H NMR (CDCl3): d = 7.53–7.48 (m, 2 H), 7.38–7.26 (m, 3 H), 4.58
(dq, J = 7.1 Hz, 2 H), 4.42 (dd, J = 3.3, 10.9 Hz, 1 H), 4.12–4.04
(m, 2 H), 3.89–3.72 (m, 2 H), 2.70–2.49 (m, 2 H), 2.11–2.00 (m, 1
H), 1.73–1.60 (m, 1 H), 1.39 (t, J = 7.1 Hz, 3 H), 1.06 (s, 9 H).
Anal. Calcd for C24H28O4S2 (444.14): C, 64.83, H, 6.35. Found: C,
64.82; H, 6.35.
Dithiocarbonic Acid O-Ethyl Ester S-[4-(4-Methoxyphenyl)-4-
oxo-1-(2-phenyl[1,3]dioxolan-2-yl)butyl] Ester (7e)
A solution of xanthate 2c (0.679 g, 2.51 mmol), olefin 6a (0.664 g,
3.767 mmol) and 2,6-lutidine (0.088 mL, 0.2 equiv vs olefin) in cy-
clohexane (3 mL) was treated as above to furnish the title compound
7e (0.93 g, 83%) as a viscous oil.
13C NMR (CDCl3): d = 215.2, 214.7, 140.2, 128.4, 128.1, 126.5,
110.5, 70.2, 65.6, 65.3, 58.8, 44.0, 33.8, 26.5, 24.0, 13.7.
HRMS-ESI: m/z calcd for C20H28O4S2 + Na [M + Na]+: 419.1326;
found: 419.1318.
Dithiocarbonic Acid O-Ethyl Ester S-[1-(2-Ethyl[1,3]dioxolan-
2-yl)-5,5-dimethyl-4-oxohexyl] Ester (7b)
IR (film): 2893, 2838, 1676, 1600, 1575, 1509, 1447, 1418, 1364,
1311, 1259, 1217, 1170, 1111, 1049, 991 cm–1.
A solution of xanthate 2a (2.057 g, 9.34 mmol), olefin 6b (0.798 g,
6.23 mmol) and 2,6-lutidine (0.145 mL, 0.2 equiv vs olefin) in cy-
clohexane (9 mL) was treated as above and furnished the title com-
pound 7b (1.126 g, 52%) as white crystals; mp 37–40 °C.
1H NMR (CDCl3): d = 7.85 (dd, J = 2.0, 6.9 Hz, 2 H), 7.52 (dd,
J = 2.0, 7.6 Hz, 2 H), 7.32 (m, 3 H), 6.88 (dd, J = 2.0, 6.9 Hz, 2 H),
4.56 (m, 3 H), 4.09 (m, 2 H), 3.83 (s, 3 H), 3.88–3.76 (m, 2 H), 3.04
(m, 2 H), 2.23 (m, 1 H), 1.87 (m, 1 H), 1.35 (t, J = 7.13 Hz, 3 H).
IR (Nujol): 2969, 2885, 1705, 1477, 1464, 1365, 1290, 1216, 1147,
1111, 1050 cm–1.
13C NMR (CDCl3): d = 214.3, 197.6, 163.2, 140.1, 130.1 C, 128.2,
127.9, 126.3, 113.5, 110.4, 70.0, 65.4, 65.1, 58.8, 55.3, 35.4, 24.6,
13.5.
1H NMR (CDCl3): d = 4.63 (dq, J = 7.2 Hz, 2 H), 4.16 (dd,
J = 3.3, 11.2 Hz, 1 H), 4.03 (m, 4 H), 2.69 (m, 2 H), 2.24 (m, 1 H),
1.78 (dd, J = 7.3, 7.3 Hz, 1 H), 1.68 (m, 1 H), 1.42 (t, J = 7.3 Hz, 1
H), 1.12 (s, 9 H), 0.94 (t, J = 7.3 Hz, 3 H).
HRMS-ESI: m/z calcd for C23H26O5S2 + Na [M + Na]+: 469.1119;
found: 469.1136.
13C NMR (CDCl3): d = 215.2, 215.2, 112.3, 70.3, 66, 66.3, 57.1,
44.1, 33.8, 28.1, 26.6, 24.4, 13.8, 7.3.
Dithiocarbonic Acid O-Ethyl Ester S-[4-(4-Methoxyphenyl)-1-
(2-Ethyl[1,3]dioxolan-2-yl)-4-oxobutyl] Ester (7f)
A solution of xanthate 2c (0.628 g, 2.323 mmol), olefin 6b (0.447
g, 3.40 mmol) and 2,6-lutidine (0.081 mL, 0.2 equiv vs olefin) in cy-
clohexane (3 mL) was treated as above to give the title compound
7f (0.64 g, 69%) as a pale-yellow solid.
MS (CI): m/z = 365, 349.
Anal. Calcd for C16H28O4S2 (348.14): C, 55.14; H, 8.09. Found: C,
55.56; H, 8.08.
IR (Nujol): 2974, 2935, 2891, 2839, 1678, 1600, 1575, 1510, 1463,
1418, 1258, 1216, 1170, 1111, 1049 cm–1.
Dithiocarbonic Acid S-[4-(Biphenyl-4-yl)-4-oxo-1-(2-phen-
yl[1,3]dioxolan-2-yl)butyl] Ester O-Ethyl Ester (7c)
A solution of xanthate 2b (1.346 g, 4.26 mmol), olefin 6a (0.5 g,
2.84 mmol) and 2,6-lutidine (0.066 mL, 0.2 equiv vs olefin) in cy-
clohexane (5 mL) was treated as above and furnished the title com-
pound 7c (0.994 g, 71%) as pale-yellow oil.
1H NMR (CDCl3): d = 7.93 (d, J = 8.8 Hz, 2 H), 6.92 (d, J = 8.8
Hz, 2 H), 4.57 (m, 2 H), 4.26 (dd, J = 3.0, 11.0 Hz, 1 H), 4.05 (m, 4
H), 3.83 (s, 3 H), 3.13 (m, 2 H), 2.45 (m, 1 H), 1.88 (dd, J = 2.3, 7.5
Hz, 1 H and m, 2 H), 1.37 (t, J = 7.1 Hz, 3 H), 0.98 (t, J = 7.4 Hz, 3
H).
IR (film): 3058, 3031, 2979, 2957, 2935, 2893, 2250, 1682, 1604,
1582, 1560, 1513, 1487, 1448, 1403, 1365, 1265, 1218, 1111, 1050,
1005, 910, 762, 733, 698 cm–1.
13C NMR (CDCl3): d = 214.7, 197.8, 163.3, 130.2, 129.9, 113.6,
112.2, 70.3, 66.1, 65.9, 57.0, 55.4, 35.4, 28.2, 24.7, 13.6, 7.3.
Synthesis 2006, No. 10, 1664–1672 © Thieme Stuttgart · New York

PAPER
Synthesis of 1,5-Dicarbonyl Compounds and 2,6-Disubstituted Pyridines
1669
HRMS-ESI: m/z calcd for C19H26O5S2 + Na [M + Na]+: 421.1119;
found: 421.1093.
1H NMR (CDCl3): d = 8.01 (d, J = 8.5 Hz, 2 H), 7.68 (d, J = 8.5 Hz,
2 H), 7.62 (d, J = 7.7 Hz, 2 H), 7.43 (m, 3 H), 4.63 (m, 3 H), 3.15
(m, 2 H), 2.72 (m, 2 H), 2.48 (m, 1 H), 2.17 (m, 1 H), 1.4 (t, J = 7.0
Hz, 3 H), 1.11 (t, J = 7.3 Hz, 3 H).
Dithiocarbonic Acid S-(1-Benzoyl-5,5-dimethyl-4-oxohexyl)
Ester O-Ethyl Ester (9a); Typical Procedure
13C NMR (CDCl3): d = 211.9, 206.5, 197.8, 145.4, 139.3, 134.9,
128.6, 128.3, 128.0, 126.9, 70.5, 57.3, 35.0, 33.9, 24.0, 13.3, 7.7.
To a solution of ketal 7a (1.564g, 3.94 mmol) in CH2Cl2 (10 mL)
was added a solution of aq trifluoroacetic acid [3.94 mL, prepared
by mixing H2O (1.8 mL, 100 mmol) and TFA (18 mL, 230 mmol)].
After 4 h at r.t., the mixture was poured into aq sat. NaHCO3. The
organic layer was decanted, washed with H2O and brine, and dried
(MgSO4). Evaporation of the solvent afforded the title compound
9a (1.077 g, 78%) as pale-yellow oil.
MS (ESI): m/z = 401 [M + H]+, 423 [M + Na]+.
Anal. Calcd for C22 H24O3S2 (400.12): C, 65.97; H, 6.04. Found: C,
64.77; H, 5.91.
2,2-Dimethyl-6-(2-phenyl[1,3]dioxolan-2-yl)hexan-3-one (8a)
A solution of xanthate 7a (0.287g, 0.72 mmol) in propan-2-ol (3.5
mL) was refluxed for 15 min under argon. DLP (0.1 equiv) was add-
ed every hour. The reaction needed a total of 1 equiv of DLP to
reach completion as indicated by TLC monitoring. After removal of
the solvent under reduced pressure, the crude mixture was subjected
to column chromatography over silica gel. Elution with a mixture of
heptane–EtOAc (9:1) gave the title compound 8a (0.126g, 63%) as
an oil.
IR (film): 2968, 2935, 2870, 1702, 1685, 1596, 1580, 1477, 1448,
1365, 1226, 1111, 1050 cm–1.
1H NMR (CDCl3): d = 8.07 (d, J = 7.3 Hz, 2 H), 7.56 (m, 2 H), 7.48
(t, J = 7.4 Hz, 1 H), 5.56 (dd, J = 5.9, 3.0 Hz, 1 H), 4.58 (dq,
J = 7.1, 3.1 Hz, 2 H), 2.68 (m, 2 H), 2.38 (m, 1 H), 2.04 (m, 1 H),
1.32 (t, J = 7.1 Hz, 3 H), 1.1 (s, 9 H).
13C NMR (CDCl3): d = 214.8, 212.5, 196.6, 135.4, 133.8, 128.8,
70.8, 54.0, 44.2, 33.3, 26.6, 25.6, 13.7.
IR (film): 3060, 3029, 2966, 2887, 1704, 1477, 1448, 1408, 1394,
1366, 1306, 1269, 1237, 1189, 1100, 1046, 995, 948, 918 cm–1.
MS (CI): m/z = 353, 370.
Anal. Calcd for C18H24O3S2 (352.12): C, 61.33, H, 6.86. Found: C,
61.24; H, 6.75.
1H NMR (CDCl3): d = 7.44 (d, J = 7.9 Hz, 2 H), 7.31 (m, 3 H), 4.01
(m, 2 H), 3.75 (m, 2 H), 2.48 (t, J = 7.2 Hz, 2 H), 1.88 (m, 2 H), 1.61
(m, 2 H), 1.09 (s, 9 H).
Dithiocarbonic Acid S-(5,5-Dimethyl-4-oxo-1-propionylhexyl)
Ester O-Ethyl Ester (9b)
Same procedure as for the preparation of 9a; pale-yellow oil; yield:
81%.
13C NMR (CDCl3): d = 215.5, 142.5, 128.1, 127.8, 125.7, 110.3,
64.5, 43.9, 39.7, 36.2, 26.4, 18.1.
HRMS-ESI: m/z calcd for C17H24O3 + Na [M + Na]+: 299.1623;
found: 299.1602.
IR (film): 2971, 2938, 2907, 2873, 1706, 1477, 1460, 1407, 1394,
1365, 1291, 1223, 1148, 1112, 1049, 1001 cm–1.
1-(Biphenyl-4-yl)-4-(2-ethyl[1,3]dioxolan-2-yl)butan-2-one (8b)
Xanthate 7d (0.25g, 0.56 mmol) was dissolved in a mixture of hy-
pophosphorous acid (50% aq commercial solution, d = 1.27, 0.29
mL, 2.81 mmol), Et3N (0.43 mL, 3.09 mmol) and dioxane (5 mL).
The mixture was refluxed for 15 min under argon, then cooled to r.t.
A solution of AIBN (0.4 M in dioxane, 0.20 mL) was added and the
mixture was refluxed for 30 min. After cooling, the mixture was
poured into H2O (50 mL) and extracted with Et2O (4 × 15 mL). The
combined organic layers were washed with H2O, brine, filtered
through a short column of neutral alumina and evaporated to dry-
ness; white crystals; yield: 0.17 g (93%); mp 63.9–67.3 °C.
1H NMR (CDCl3): d = 4.58 (dq, J = 7.0, 1.3 Hz, 2 H), 4.45 (dd,
J = 8.5, 5.7 Hz, 1 H), 2.62 (m, 5 H), 2.19 (m, 1 H), 1.91 (m, 1 H),
1.37 (t, J = 7.0 Hz, 3 H), 1.08 (s, 9 H), 1.03 (t, J = 7.2 Hz, 3 H).
13C NMR (CDCl3): d = 214.5, 212.5, 206.9, 70.7, 57.6, 44.0, 34.0,
33.2, 26.2, 23.9, 13.7, 7.9.
HRMS-ESI: m/z calcd for C14H24O3S2 + Na [M + Na]+: 327.1065;
found: 327.1052.
Dithiocarbonic Acid S-[1-Benzoyl-4-(biphenyl-4-yl)-4-oxobu-
tyl] Ester O-Ethyl Ester (9c)
Same procedure as for the preparation of 9a; pale-yellow oil; yield:
83%.
IR (Nujol): 2924, 2854, 2333, 1685, 1631, 1603, 1461, 1376, 1189,
1163, 1083, 816 cm–1.
1H NMR (CDCl3): d = 7.81 (d, J = 8.4 Hz, 2 H), 7.45 (d, J = 8.4 Hz,
2 H), 7.40 (d, J = 7.3 Hz, 2 H), 7.20 (m, 3 H), 3.72 (s, 4 H), 2.80 (t,
J = 7.1 Hz, 2 H), 1.64 (m, 2 H), 1.52 (m, 2 H), 1.44 (q, J = 7.4 Hz,
2 H), 0.72 (t, J = 7.4 Hz, 3 H).
IR (film): 3348, 3060, 3032, 2983, 2934, 1680, 1603, 1581, 1560,
1514, 1486, 1447, 1404, 1364, 1227, 1149, 1112, 1049, 1001, 978,
910, 844, 810, 763, 732, 697, 649 cm–1.
1H NMR (CDCl3): d = 8.13 (d, J = 7.4 Hz, 2 H), 8.02 (d, J = 8.5 Hz,
2 H), 7.71–7.38 (m, 10 H), 5.70 (dd, J = 5.7, 8.3 Hz, 1 H), 4.57 (m,
2 H), 3.23 (m, 2 H), 2.64 (m, 1 H), 2.28 (m, 1 H), 1.32 (t, J = 7.1
Hz, 3 H).
13C NMR (CDCl3): d = 199.8, 145.6, 140.0, 135.8, 129.0, 128.7,
128.2, 127.3, 111.9, 65., 38.7, 36.1, 30.0, 18.7, 8.2.
Anal. Calcd for C21H24O3 (324.17): C, 77.75; H, 7.46. Found: C,
77.21; H, 7.59.
13C NMR (CDCl3): d = 214.5, 212.5, 206.9’, 70.7, 57.6, 44.0, 34.0,
33.2, 26.2, 23.9, 13.7, 7.9.
1-(4-Methoxyphenyl)-4-(2-phenyl[1,3]dioxolan-2-yl)butan-1-
one (8c)
MS (ESI): m/z = 487 [M + K+], 471 [M + Na]+.
A solution of xanthate 7e (0.673g, 1.5 mmol) and Bu3SnH (0.479
mL) in toluene (2 mL) was refluxed under argon for 30 min. After
cooling to r.t., AIBN (0.030 g, 0.1 equiv vs Bu3SnH) was added and
the mixture was refluxed for 1.5 h. Additional amounts of Bu3SnH
(1 mL) and AIBN (0.010 g) were added and the reflux was contin-
ued for 1 h. CHCl3 (2 mL) was then added cautiously to destroy ex-
cess Bu3SnH. The crude mixture was concentrated under reduced
pressure and the residue was dissolved in Et2O. The organic layer
was washed successively with H2O (15 mL), 10% aq KF (3 × 15
mL), and brine. Usual work-up gave a residue that was submitted to
Anal. Calcd for C26H24O3S2 (448.12): C, 69.61; H, 5.39. Found: C,
69.62; H, 5.31.
Dithiocarbonic Acid S-{1-[3-(Biphenyl-4-yl)-3-oxopropyl]-2-
oxobutyl} Ester O-Ethyl Ester (9d)
Same procedure as for the preparation of 9a; white crystals; mp
98.5–99.3 °C; yield: 87%.
IR (Nujol): 2955, 2932, 2855, 1715, 1681, 1607, 1580, 1560, 1486,
1458, 1446, 1404, 1366, 1237, 1114, 1045, 1002, 858, 756 cm–1.
Synthesis 2006, No. 10, 1664–1672 © Thieme Stuttgart · New York

1670
J. Boivin et al.
PAPER
silica gel column chromatography. Elution with a gradient of hep-
tane–EtOAc (from 9:1 to 8:2) afforded the title compound 8c (0.45
g, 92%) as white crystals; mp 63.2–65.0 °C.
1H NMR (CDCl3): d = 8.06 (d, J = 8.5 Hz, 2 H), 7.99 (d, J = 7.0 Hz,
2 H), 7.71–7.39 (m, 10 H), 3.15 (t, J = 6.9 Hz, 2 H), 3.14 (t, J = 6.9
Hz, 2 H), 2.23 (m, 2 H).
IR (Nujol): 3390, 2956, 2925, 2342, 1672, 1596, 1508, 1459, 1254,
1186, 1170, 1031, 986, 816 cm–1.
13C NMR (CDCl3): d = 199.9, 199.5, 145.8, 139.9, 136.9, 135.6,
133.8, 133.1, 129.0,128.6, 128.3, 128.1, 127.3, 37.7, 18.9.
1H NMR (CDCl3): d = 7.90 (d, J = 8.8 Hz, 2 H), 7.46 (d, J = 7.4 Hz,
2 H), 7.31 (m, 3 H), 6.91 (d, J = 8.8 Hz, 2 H), 4.03 (t, J = 6.8 Hz, 2
H), 3.89 (s, 3 H), 3.77 (t, J = 6.8 Hz, 2 H), 2.90 (t, J = 7.4 Hz, 2 H),
1.99 (m, 2 H), 1.80 (m, 2 H).
HRMS-ESI: m/z calcd for C23H20O2 + Na [M + Na]+: 351.1361;
found: 351.1348.
(1-Biphenyl-4-yl)heptane-1,5-dione (10c)
Reduction with Propan-2-ol: Same procedure was used as for the
preparation of 8a; yield: 63%; mp 129.1–129.7 °C.
13C NMR (CDCl3): d = 198.6, 163.2, 142.4, 130.2, 128.0, 127.7,
125.6, 113.6, 64.4, 55.3, 39.8, 38.0, 18.7.
IR (Nujol): 3424, 2924, 2854, 1710, 1681, 1604, 1459,1417, 1376,
1266, 1198, 1117, 987 cm–1.
HRMS-ESI: m/z calcd for C20H22O4 + Na [M + Na]+: 349.1416;
found: 349.1413.
1H NMR (CDCl3): d = 8.04 (d, J = 8.2 Hz, 2 H), 7.68 (d, J = 8.2
Hz, 2 H), 7.62 (d, J = 7.7 Hz, 2 H), 7.44 (m, 3 H), 3.04 (t, J = 6.9
H, 2 Hz), 2.56 (t, J = 7.0 Hz, 2 H), 2.44 (q, J = 7.3 Hz, 2 H), 2.05
(m, 2 H), 1.07 (t, J = 7.3 Hz, 3 H, H-7).
4-(2-Ethyl[1,3]dioxolan-2-yl)-1-(4-methoxyphenyl)butan-1-one
(8d)
The same procedure as above was applied to xanthate 7f and afford-
ed the title compound 8d (78%) as white crystals; mp 43.4–45.3 °C.
13C NMR (CDCl3): d = 211.2, 199.4, 145.7, 139.8, 135.5, 128.9,
128.6, 128.2, 127.2, 126.8, 41.2, 37.7, 35.9, 29.7, 18.4, 7.8.
IR (Nujol): 2928, 1733, 1700, 1683, 1653, 1635, 1601, 1576, 1559,
1507, 1457, 1419, 1258, 1170, 1072, 825 cm–1.
HRMS-ESI: m/z calcd for C19H20O2 +Na [M + Na]+: 303.1361;
found: 303.1345.
1H NMR (CDCl3): d = 7.91 (d, J = 8.8 Hz, 2 H), 6.89 (d, J = 8.8 Hz,
2 H), 3.91 (s, 4 H), 3.83 (s, 3 H), 2.91 (t, J = 7.1 Hz, 2 H), 1.78 (m,
2 H), 1.68 (m, 2 H), 1.62 (q, J = 7.4 Hz, 2 H), 0.88 (t, J = 7.4 Hz, 3
H).
1-(4-Methoxyphenyl)-5-phenylpentane-1,5-dione (10d)
The title compound 10d was obtained from 8c according to the pro-
cedure described by Huet et al.;17 yield: 57%; mp 85.4–85.6 °C.
13C NMR (CDCl3): d = 198.7, 163.2, 130.3, 130.2, 113.6, 111.9,
65.0, 55.4, 38.2, 36.0, 29.9, 18.8, 8.1.
IR (Nujol): 3433, 2923, 2854, 1682, 1670, 1600, 1577, 1506, 1450,
1415, 1375, 1281, 1256, 1192, 1175, 1027, 987 cm–1.
MS (ESI): m/z = 279 [M + H+].
1H NMR (CDCl3): d = 7.95 (2 d, J = 7.1 Hz, 4 H), 7.48 (m, 3 H),
6.91 (d, J = 8.7 Hz, 2 H), 3.09 (t, J = 6.9 Hz, 2 H), 3.04 (t, J = 6.9
Hz, 2 H), 2.17 (m, 2 H).
Anal. Calcd for C16 H22O4 (278.15): C, 69.04; H, 7.97. Found: C,
69.09; H, 7.94.
6,6-Dimethyl-1-phenylheptane-1,5-dione (10a)
Same procedure was used as for the preparation of 9a; yellow oil;
yield: 51%.
13C NMR (CDCl3): d = 199.9, 198.9, 163.4, 133.0, 130.3, 130.0,
128.5, 128.0, 113.7, 55.4, 37.7, 37.2, 18.9.
MS (EI): m/z = 282, 163, 150, 136, 135, 107, 105, 92, 78, 77, 76,
64, 63, 55, 51.
IR (film): 2961, 2933, 2871, 1703, 1698, 1687, 1682, 1598, 1580,
1478, 1449, 1366, 1225, 1170, 1111, 1091 cm–1.
Anal. Calcd for C18 H18O3 (282.13): C, 76.57; H, 6.43. Found: C,
76.36; H, 6.38.
1H NMR (CDCl3): d = 7.97 (d, J = 8.8 Hz, 2 H), 7.54 (m, 2 H), 7.45
(t, J = 7.4 Hz, 1 H), 3.01 (t, J = 7 Hz, 2 H), 2.64 (t, J = 6.8 Hz, 2
H), 2.01 (q, J = 6.9 Hz, 2 H), 1.15 (s, 9 H).
1-(4-Methoxyphenyl)heptane-1,5-dione (10e)
The title compound 10e was obtained from 8d according to the
same procedure as for preparation of 9a; yield: 99%; mp 76.8–
77.3 °C (EtOH).
13C NMR (CDCl3): d = 215.5, 199.8, 136.7, 132.8, 128.4, 127.9,
43.9, 37.4, 35.3, 26.2, 18.4.
HRMS-ESI: m/z calcd for C15H20O2 + Na [M + Na]+: 255.1361;
found: 255.1372.
IR (Nujol): 3433, 2923, 2853, 1706, 1664, 1602, 1510, 1452, 1420,
1375, 1257, 1208, 1180, 1111, 1030 cm–1.
1-(Biphenyl-4-yl)-5-phenylpentane-1,5-dione (10b)
1H NMR (CDCl3): d = 7.95 (d, J = 8.9 Hz, 2 H), 6.93 (d, J = 8.9 Hz,
2 H), 3.87 (s, 3 H), 2.96 (t, J = 7.0 Hz, 2 H), 2.54 (t, J = 7.0 H, 2
Hz), 2.43 (q, J = 7.3 Hz, 2 H), 2.01 (m, 2 H), 1.06 (t, J = 7.3 Hz, 3
H).
Reduction with Bu3SnH: A solution of xanthate 9c (0.269g, 0.6
mmol) and Bu3SnH (1 mL) in toluene (2 mL) was refluxed under
argon for 30 min. After cooling to r.t., AIBN (0.011 g) was added
and the mixture was refluxed for 1.5 h. CHCl3 (2 mL) was then add-
ed cautiously to destroy excess Bu3SnH. The crude mixture was
concentrated under reduced pressure and the residue was dissolved
in Et2O. The organic layer was washed successively with H2O (15
mL), 10% aq KF (3 × 15 mL), and brine. Usual work-up gave a res-
idue that was submitted to silica gel column chromatography. Elu-
tion with heptane–EtOAc (from 9:1) afforded the title compound
10b (0.04 g, 22%) as white crystals.
13C NMR (CDCl3): d = 211.0, 198.2, 163.3, 130.1, 129.8, 113.6,
55.3, 41.1, 37.0, 35.7, 18.4, 7.7.
HRMS-ESI: m/z calcd for C14H18O3 + Na [M + Na]+: 257.1153;
found: 257.1138.
6-tert-Butyl-2-phenylpyridine (11a); Typical Procedure
A solution of compound 10a (0.09 g, 0.38 mmol) in AcOH (2 mL),
containing NH4OAc (0.24 g, 3.10 mmol) was refluxed for 5 h. The
solvent was evaporated under reduced pressure and the residue was
taken up in Et2O. The organic layer was washed successively with
2 N aq NaOH and brine, then dried (MgSO4). The residue was chro-
matographed over silica gel (eluent; gradient heptane–EtOAc) to
yield the title compound 11a (0.05 g, 62%). This compound was
identical to the compound described in literature.11
Reduction with Propan-2-ol: Same procedure was used as for the
preparation of 8a; yield: 58%; mp 107.9–108.7 °C.
IR (Nujol): 3424, 2924, 2853, 1708, 1679, 1651, 1605, 1557, 1447,
1407, 1366, 1283, 1224, 1112, 1048, 987 cm–1.
Synthesis 2006, No. 10, 1664–1672 © Thieme Stuttgart · New York

PAPER
Synthesis of 1,5-Dicarbonyl Compounds and 2,6-Disubstituted Pyridines
1671
2-(Biphenyl-4-yl)-6-ethylpyridine (11b)
1H NMR (CDCl3): d = 7.95 (m, 2 H), 7.56 (m, 1 H), 7.46 (m, 2 H),
5.06 (t, J = 7.0 Hz), 4.97 (dd, J = 11.0, 3.6 Hz), 4.63 (m), 4.46 (m),
4.31 (m), 4.08–3.8 (m), 2.43 (m), 2.08–0.75 (m); mixture of diaste-
reomers, integrations are not reliable.
A solution of compound 10c (0.391 g, 1.395 mmol) in AcOH (6
mL), containing NH4OAc (0.86 g, 11.16 mmol) was refluxed for 90
min. The solvent was evaporated under reduced pressure and the
residue was taken up in Et2O. The organic layer was washed succes-
sively with 2 N aq NaOH and brine, then dried (MgSO4). The resi-
due was chromatographed over silica gel (eluent; gradient heptane–
EtOAc) to yield the title compound 11b; oil; yield: 0.114 g (31%).
13C NMR (CDCl3): d = 214.6, 212.1, 203.0, 202.4, 136.7, 136.6,
133.2, 128.7, 128.5, 128.4, 112.2, 111.6, 70.5, 66.3, 66.0, 64.9,
56.0, 51.7, 51.0, 44.9, 44.2, 43.3, 42.8, 33.5, 32.9, 32.3, 29.8, 27.9,
27.1, 26.4, 26.2, 25.7, 13.8, 13.4, 8.0, 7.2.
IR (film): 2968, 2933, 1600, 1567, 1547, 1487, 1461, 1449, 1431,
1408, 1378, 1363, 1264, 1235, 1188, 1109, 1039, 1023, 1006 cm–1.
HRMS-ESI: m/z calcd for C25H36O5S2 + Na [M + Na]+: 503.1902;
found: 503.1892.
1H NMR (CDCl3): d = 8.10 (d, J = 8.4 Hz, 2 H), 7.68 (m, 5 H), 7.58
(d, J = 7.8 Hz, 2 H), 7.47 (t, J = 7.3 Hz, 1 H), 7.38 (d, J = 7.3 Hz, 1
H), 7.12 (d, J = 7.4 Hz, 1 H), 2.92 (q, J = 7.6 Hz, 2 H), 1.39 (t,
J = 7.6 Hz, 3 H).
2-[2-(2-Ethyl[1,3]dioxolan-2-yl)-6,6-dimethyl-1-phenylhep-
tane-1,5-dione (13b)
The title compound 13b was obtained from 13a according to the
procedure described for the preparation of 8b; yield: 89%; white
solid.
13C NMR (CDCl3): d = 163.5, 156.3, 141.5, 140.8, 138.8, 137.0,
128.8, 127.4, 127.1, 120.4, 117.6, 31.6, 13.9.
IR (Nujol): 2968, 2936, 2880, 1704, 1678, 1596, 1580, 1478, 1464,
1448, 1366, 1189, 1071, 949, 908, 816, 702 cm–1.
HRMS-ESI: m/z calcd for C19H18N [M + H]+: 260.1439; found:
260.1432.
1H NMR (CDCl3): d = 7.96 (d, J = 7.7 Hz, 2 H), 7.56 (m, 1 H),
7.46 (m, 2 H), 3.88 (m, 4 H), 3.54 (m, 1 H), 2.46 (m), 2.01 (m), 1.84
(m), 1.59 (m), 1.05 (s, 9 H), 0.85 (t, J = 7.4 Hz, 3 H).
2-(4-Methoxyphenyl)-6-phenylpyridine (11d)
The title compound 11d was obtained from 10d according to the
procedure described for the preparation of 11b; oil; yield: 93%; mp
133 °C.
13C NMR (CDCl3): d = 215.5, 203.8, 137.2, 133.0, 128.6, 128.1,
111.6, 64.8, 44.5, 44.0, 33.8, 33.3, 30.2, 29.6, 26.3, 25.9, 7.9.
IR (Nujol): 2923, 2853, 1631, 1607, 1587, 1377, 1247, 1188, 1162,
1112, 1083, 1028 cm–1.
HRMS-ESI: m/z calcd for C22H32O4 + Na [M + Na]+: 383.2198;
found: 383.2181.
1H NMR (CDCl3): d = 8.13 (m, 2 H), 7.76 (m, 1 H), 7.62 (d, J = 7.7
Hz, 2 H), 7.45 (m, 3 H), 7.02 (d, J = 8.8 Hz, 2 H), 3.87 (s, 3 H).
1-(6-tert-Butyl-2-phenylpyridin-3-yl)pentan-3-one (14)
The title compound 14 was obtained from 13b according to the pro-
cedure described for the preparation of 11b; oil; yield: 66%.
13C NMR (CDCl3): d = 160.4, 156.6, 156.4, 139.6, 137.3, 132.1,
128.8, 128.6, 128.2, 126.9, 117.8, 114.0, 55.3.
IR (film): 2957, 2872, 1715, 1640, 1589, 1562, 1478, 1457, 1440,
1380, 1362, 1186, 1112, 1086, 1065 cm–1.
HRMS-ESI: m/z calcd for C18H16NO [M + H]+: 262.1232; found:
262.1212.
1H NMR (CDCl3): d = 7.47 (m, 6 H), 7.24 (d, J = 8.0 Hz, 1 H), 2.96
(t, J = 7.7 Hz, 2 H), 2.53 (t, J = 7.7 Hz, 2 H), 2.30 (q, J = 7.3 Hz, 2
H), 1.38 (s, 9 H), 0.98 (t, J = 7.3 Hz, 3 H).
2-Ethyl-6-(4-methoxyphenyl)pyridine (11e)
The title compound 11e was obtained from 10e according to the
procedure described for the preparation of 11b; pale-yellow oil;
yield: 24%.
13C NMR (CDCl3): d = 210.4, 166.6, 156.8, 141.1, 137.4, 130.3,
129.0, 128.1, 127.6, 117.4, 42.8, 37.1, 35.8, 30.1, 26.3, 7.7.
IR (film): 1644, 1608, 1572, 1514, 1452, 1249, 1176, 1159, 1117,
1087, 1043, 807 cm–1.
HRMS-ESI: m/z calcd for C20H26NO + Na [M + Na]+: 296.2014;
found: 296.1984.
1H NMR (CDCl3): d = 7.96 (d, J = 8.7 Hz, 2 H), 7.61 (t, J = 7.6 Hz,
1 H), 7.46 (d, J = 7.8 Hz, 1 H), 7.03 (d, J = 7.5 Hz, 1 H), 6.68 (d,
J = 8.7 Hz, 2 H), 3.85 (s, 3 H), 2.87 (q, J = 7.5 Hz, 2 H), 1.35 (t,
J = 7.5 Hz, 3 H).
Dithiocarbonic Acid S-(6-tert-Butyl-2-phenylpyridin-3-yl) Es-
ter O-Ethyl Ester (12a)
The title compound 12a was obtained from 9a according to the pro-
cedure described for the preparation of 11b; yellow oil; yield: 91%.
13C NMR (CDCl3): d = 163.2, 160.2, 156.3, 136.8, 132.5, 128.2,
119.6, 116.9, 114.0, 55.3, 31.5, 13.87.
IR (film): 2958, 2925, 2854, 1566, 1548, 1422, 1149, 1110, 1047,
1031, 1020 cm–1.
HRMS-ESI: m/z calcd for C14H16NO [M + H]+: 214.1232; found:
214.1245.
1H NMR (CDCl3): d = 7.79 (d, J = 8.3 Hz, 1 H), 7.65 (m, 2 H), 7.41
(m, 3 H), 7.34 (d, J = 8.3 Hz, 1 H), 4.49 (q, J = 7.2 Hz, 2 H),
1.40 (s, 9 H), 1.25 (t, J = 7.2 Hz, 3 H).
Dithiocarbonic Acid S-[3-Benzoyl-1-(2-ethyl[1,3]dioxolan-2-
yl)-7,7-dimethyl-6-oxooctyl] Ester O-Ethyl Ester (13a, Mixture
of Diastereomers)
13C NMR (CDCl3): d = 212.1, 170.9, 160.0, 145.3, 139.9, 129.5,
128.4, 127.7, 125.5, 121.6, 118.0, 70.3, 65.8, 37.8, 30.0, 15.2, 13.5.
A solution of xanthate 9a (0.293 g, 0.83 mmol), olefin 6b (0.159 g,
1.24 mmol) and 2,6-lutidine (0.028 mL, 0.2 equiv vs olefin) in cy-
clohexane (1 mL) was refluxed under argon for 30 min. Dilauroyl
peroxide (DLP) was then added portionwise (0.05 equiv vs xan-
thate, then 0.02 equiv every 2 h). The reaction was monitored by
TLC. After completion of the reaction (0.25 equiv of DLP added),
the solvent was evaporated under reduced pressure and the residue
was placed onto a column of silica gel. Elution with heptane–EtOAc
(95:5 and 9:1) afforded the title compound 13a (0.12 g, 32%) as a
pale-yellow oil, and the starting material 9a (0.103 g).
HRMS-ESI: m/z calcd for C18H22NOS2 [M + H]+: 332.1142; found:
332.1133.
Dithiocarbonic Acid S-[6-(Biphenyl-4-yl)-2-ethylpyridin-3-yl]
Ester O-Ethyl Ester (12b)
The title compound 12b was obtained from 9d according to the pro-
cedure described for the preparation of 11b; yellow oil; yield: 32%.
IR (film): 2930, 1567, 1432, 1365, 1226, 1110, 1040, 824 cm–1.
1H NMR (CDCl3): d = 8.17 (d, J = 8.5 Hz, 2 H), 7.80 (d, J = 8.1 Hz,
1 H), 7.71 (d, J = 8.5 Hz, 2 H), 7.66 (m, 4 H), 7.46 (t, J = 7.2 Hz, 1
IR (film): 3435, 2963, 2928, 1704, 1679, 1632, 1597, 1581, 1477,
1448, 1366, 1189, 1162, 1112, 1083, 1045, 816 cm–1.
Synthesis 2006, No. 10, 1664–1672 © Thieme Stuttgart · New York

1672
J. Boivin et al.
PAPER
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J = 7.5 Hz, 2 H), 1.35 (m, 6 H).
13C NMR (CDCl3): d = 230.1, 144.8, 140.5, 128.8, 127.5, 127.1,
118.0, 70.6, 29.7, 29.5, 13.6, 13.3.
HRMS-ESI: m/z calcd for C22H22NOS2 [M + H]+: 380.1143; found:
380.1134.
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Synthesis 2006, No. 10, 1664–1672 © Thieme Stuttgart · New York