Modified julia-kocienski reaction promoted by means of m-NPT (nitro-phenyltetrazole) sulfone

Article abstract of DOI:10.1055/s-0029-1219386

m-Nitrophenyltetrazole sulfone (2) was employed in the Julia-Kocienski reaction. The olefination reaction between 2 and carbonyl compounds proceeded smoothly under Masamune-Roush conditions (DBU and LiCl). These conditions were also applicable to our catechin derivative synthesis. Furthermore, phenolic mesylate was also tolerated in this mild reaction.

Full text of DOI:10.1055/s-0029-1219386

LETTER
827
Modified Julia–Kocienski Reaction Promoted by Means of m-NPT
(Nitrophenyltetrazole) Sulfone
M
odifiedJulia–K
o
u
cienski Reac
k
tion i Sakai, Kazutada Ikeuchi, Yuji Yamada, Toshiyuki Wakimoto, Toshiyuki Kan*
School of Pharmaceutical Sciences, University of Shizuoka and Global COE Program, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
Fax +81(54)2645745; E-mail: kant@u-shizuoka-ken.ac.jp
Received 1 December 2009
sponding thioisocyanate; subsequent cycloaddition reac-
Abstract: m-Nitrophenyltetrazole sulfone (2) was employed in the
tion with sodium azide provided the tetrazole derivative as
a mixture of tautomers. Finally, treatment with Et3N, and
conversion from the thione into the corresponding thiol
Julia–Kocienski reaction. The olefination reaction between 2 and
carbonyl compounds proceeded smoothly under Masamune–Roush
conditions (DBU and LiCl). These conditions were also applicable
to our catechin derivative synthesis. Furthermore, phenolic mesy- proceeded smoothly to give desired products 5 and 6
late was also tolerated in this mild reaction.
(from 3 and 4, respectively).
N
N
Key words: olefination, Julia–Kocienski reaction, sulfone
NH2
N
SH
N
1) CSCl2, benzene
r.t.
R2
2) NaN3, MeOH; Et3N
80 °C
Olefination reactions (Wittig, Peterson, and Julia reac-
tions) are significant because of their applicability to the
synthesis of natural products as well as pharmaceutical
drugs.1 In particular, the Horner–Wadsworth–Emmons
reaction is attractive because the required carbanion can
be generated under mild conditions such as treatment with
LiCl and DBU.2 Although many functional groups are
compatible with the olefination reaction conditions,
preparing the precursor phosphate derivatives by the
Arbuzov reaction requires harsh conditions. Recently, the
Julia–Kocienski reaction (J–K reaction)3 has attracted
much attention because the phenytetrazole sulfone (PT-
sulfone) group can be prepared under mild conditions
(Scheme 1). However, the generation of the anion of 1
requires a strong base at low temperature (LHMDS,
–78 °C). During the course of our investigations into the
synthesis of nitrogen-containing natural products, we
found that the nitrobenzenesulfonamide anion plays a key
role in the excellent performance of a number of intermo-
lecular as well as intramolecular reactions.4–7 Inspired by
this finding, we have investigated the synthesis of nitro-
PT-sulfone 2, which should generate the anion under mild
conditions. Herein, we report the synthesis of nitro-PT-
sulfone 2 and on its application in the J–K reaction.
R
R1
R2
R1
3 R1 = NO2, R2 = H
4 R1 = H, R2 = NO2
5 p-NPTSH : R1 = NO2, R2 = H, 20% (2 steps)
6 m-NPTSH : R1 = H, R2 = NO2, 60% (2 steps
Scheme 2 Syntheses of nitrophenyltetrazolethiols 5 and 6
Initially, we focused on p-nitro-PT-sulfone 8, which
should be more active than the corresponding m-nitro-
phenyl derivatives. PT-sulfone 8 was prepared by conden-
sation of alkyl halides 7 with 5 under basic conditions and
subsequent oxidation with m-CPBA (Scheme 3). As
shown in Table 1, several basic conditions were tested for
the condensation with benzaldehyde (9). Although the re-
action proceeded, satisfactory results were not obtained
even in the presence of a mild base such as Cs2CO3 or
DBU. Furthermore, the decomposition product9 was ob-
served under all the basic conditions; thus, we focused on
m-nitrophenyltetrazolesulfone (m-NPT sulfone) deriva-
tive 12.
O
O
1) 5, K2CO3
I
S
DMF
p-NPT
p-NPT =
N
N
2) mCPBA, CH2Cl2
92% (2 steps)
N
7
8
N
OHC
conditions
+
8
O
X
CHO
R
O
O
9
10
NO2
base
X
S
N
N
+
+
N
N
N
N
Scheme 3 Synthesis of p-NPT sulfone 8 and olefination to 10
Table 1 Coupling of 8 and 9
N
+
SO2
N
1 (PT sulfone: X = H)
2 (m-NPT sulfone: X = NO2)
Entry
Conditions
Yield (%) E/Za
Scheme 1 The Julia–Kocienski reaction and its modification
1
2
3
4
LHMDS, THF, –78 °C
Cs2CO3, MeCN, r.t.
DBU, MeCN, 0 °C
DBU, LiCl, MeCN, 0 °C
46
19:1
10:1
5:1
As shown in Scheme 2, nitrophenyltetrazolethiols 5 and 6
were prepared according to Aïssa’s protocol.8 Treatment
of aniline derivatives 3 and 4 with CSCl2 gave the corre-
37
trace
28
SYNLETT 2010, No. 5, pp 0827–0829
1
6.
3
.2
0
1
0
9:1
Advanced online publication: 10.02.2010
DOI: 10.1055/s-0029-1219386; Art ID: U11409ST
a Determined by 1H NMR.
© Georg Thieme Verlag Stuttgart · New York

828
Y. Sakai et al.
LETTER
OMs
As shown in Scheme 4, m-NPT sulfone 12 was prepared
from 11 and 6 in a manner similar to that for 8. Table 2
summarizes the results of the coupling reaction with 9.
With this reagent, the reaction proceeded in the presence
of either Cs2CO3 or DBU at room temperature (entries 2
and 3). Because decomposition products were not ob-
served in the reaction with DBU, further modifications
were tested (Table 2). We found that the addition of LiCl
to DBU (entry 4) increased the yield significantly. To our
knowledge, this is the first example of the J–K reaction
performed under such mild conditions.
OMs
H
OTBS
O
OTBS
18
O
PT
LHMDS
THF
–78 °C
46%
S
19
O
17
18
DBU, LiCl
14
19
MeCN
0 °C
79%
Scheme 6 Comparison of reaction conditions
O
O
1) 6, K2CO3
Furthermore, one advantage of the modified J–K reaction
conditions in comparison with the usual conditions is
demonstrated in Scheme 6. Because hydrolysis of phenol-
ic mesylate readily occurs upon exposure to LHMDS,13 a
coupling reaction of 17 and 18 under the usual conditions
resulted in low yield. In contrast, the coupling reaction be-
tween 14 and 18, in the presence of a combination of LiCl
and DBU, proceeded smoothly to provide 19 in high
yield.
Br
S
DMF
m-NPT
m-NPT =
N
N
2) mCPBA, CH2Cl2
77% (2 steps)
N
11
12
N
OHC
conditions
+
12
O2N
9
10
Scheme 4 Synthesis of m-NPT sulfone 12 and olefination with 9
Table 2 Coupling of 12 and 9
In conclusion, we have successfully developed an effi-
cient Julia–Kocienski reaction mediated by m-NPT sul-
fone. Considering the mild reaction conditions, this
reaction should proceed in the presence of a wide range of
functional groups. Further applications of this method are
currently underway in our laboratory.
Entry
Conditions
Yield (%)
E/Za
23:1
9:1
1
2
3
4
5
LHMDS, THF, –78 °C
Cs2CO3, MeCN, 0 °C
DBU, MeCN, 0 °C
DBU, LiCl, MeCN, 0 °C
DBU, NaI, MeCN, 0 °C
76
41
50
86
77
10:1
7:1
Acknowledgment
This work was financially supported by Takeda Science Foundati-
on, Naito Foundation, Nagase Science, and a Grant-in-Aid from the
Ministry of Education, Culture, Sports, Science and Technology of
Japan.
27:1
a Determined by 1H NMR.
Further applications of the modified J–K reaction were
demonstrated in the synthesis of an intermediate for use in
the synthesis of catechin (Scheme 5).10 PT-sulfone 14 was
prepared by a condensation reaction of 13 and 6, with sub-
sequent oxidation by m-CPBA.11 Upon treatment of 14
and 15 with LiCl and DBU, the E-selective olefination
reaction proceeded smoothly to provide 16. 12
References and Notes
(1) Aïssa, C. Eur. J. Org. Chem. 2009, 12, 1831.
(2) Blanchette, M. A.; Choy, W.; Davis, J. T.; Essenfeld, A. P.;
Masamune, S.; Roush, W. R.; Sakai, T. Tetrahedron Lett.
1984, 25, 2183.
(3) Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.; Morley, A.
Synlett 1998, 26.
(4) Kan, T.; Fukuyama, T. Chem. Commun. 2004, 353.
(5) For the use of nitro-substituted aromatic rings for selenation,
see: Grieco, P. A.; Gilman, S.; Nishizawa, M. J. Org. Chem.
1976, 41, 1485.
(6) For azidation, see: Mizuno, M.; Shioiri, T. Chem. Commun.
1997, 2165.
(7) For macrolactonization, see: (a) Shiina, I.; Ibuka, R.;
Kubota, M. Chem. Lett. 2002, 286. (b) Shiina, I. Chem. Rev.
2007, 107, 239.
(8) Aïssa, C. J. Org. Chem. 2006, 71, 360.
(9) Upon treatment of similar p-NPT sulfone derivative 20,
under basic conditions, the self-condensation reaction
proceeded through Meisenheimer complex 21 to provide 22,
as shown in Scheme 7.
OTBS
1) 6, K2CO3
DMF
OTBS
m-NPT
2) mCPBA, CH2Cl2
62%
S
I
O
14
O
13
OBn
OBn
DBU, LiCl
OBn
OBn
OBn
MeCN, 0 °C
14
+
81%
OTBS
OHC
OBn
E/Z = 27:1
15
16
Scheme 5 Synthesis of catechin derivative intermediate 16
Synlett 2010, No. 5, 827–829 © Thieme Stuttgart · New York

LETTER
Modified Julia–Kocienski Reaction
829
(neat): 837, 1101, 1157, 1352, 1539, 2929 cm–1; 1H NMR
(500 MHz, CDCl3): d = 0.28 (s, 6 H), 1.01 (s, 9 H), 3.27 (t,
J = 8.2 Hz, 2 H), 4.07 (t, J = 8.2 Hz, 2 H), 6.83 (d, J = 8.0
Hz, 1 H), 6.91 (t, J = 8.0 Hz, 1 H), 7.18 (t, J = 8.0 Hz, 1 H),
7.20 (d, J = 8.0 Hz, 1 H), 7.84 (t, J = 8.5 Hz, 1 H), 8,09 (dt,
J = 8.5, 1.0 Hz, 1 H), 8.51 (dt, J = 8.5, 1.0 Hz, 1 H), 8.61 (t,
J = 1.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3): d = –4.0,
18.3, 24.4, 25.9, 55.7, 118.7, 120.8, 121.5, 126.2, 126.4,
128.9, 130.8, 130.9, 131.0, 133.9, 148.7, 153.7, 154.0; FAB-
MS: m/z = 490 [M + H]+; HRMS: m/z [M + H]+ calcd for
C21H28O5N5SSi: 490.1580; found: 490.1595.
N
N
N N
O
O
N
N
O
O
S
S
N
N
base
MeO
MeO
NO2
NO2
20
MeO
N
N
O
O
O
N
O
S
N
N
S
N
N
HN
(12) Synthesis of 16: To a stirred solution of sulfone 14 (11 mg,
22 mmol), aldehyde 15 (13 mg, 26 mmol) and LiCl (4.0 mg,
78 mmol) in MeCN (1.0 mL) at 0 °C, DBU (12 mL, 78 mmol)
was added dropwise. After stirring for 20 min, the reaction
mixture was quenched with sat. aq NH4Cl and extracted with
CH2Cl2. The organic layer was washed with sat. aq NH4Cl
and brine, dried over MgSO4, and concentrated in vacuo.
The residue was purified by preparative TLC to yield 16
(11 mg, 18 mmol, 81%). Spectral data for 16: IR (neat): 839,
1116, 1573, 1693, 2927 cm–1; 1H NMR (500 MHz, CDCl3):
d = 0.25 (s, 6 H), 1.02 (s, 9 H), 3.50 (d, J = 7.3 Hz, 2 H), 5,04
(s, 2 H), 5.08 (s, 4 H), 6.25–6.27 (m, 2 H), 6.65 (d, J = 11.6
Hz, 1 H), 6.82 (s, 2 H), 6.91 (d, J = 8.5 Hz, 1 H), 7.10–7.43
(m, 17 H); 13C NMR (68 MHz, CDCl3): d = –4.1, 18.3, 25.8,
33.6, 71.1, 71.2, 75.3, 105.9, 118.4, 121.1, 127.2, 127.3,
127.4, 127.7, 127.8, 128.1, 128.4, 128.5, 128.6, 130.3,
130.5, 130.7, 133.5, 137.2, 137.8, 137.9, 152.9, 153.4; FAB-
MS: m/z = 642 [M]+; HRMS: m/z [M]+ calcd for C42H46O4Si:
642.3165; found: 642.3162.
MeO
NO2
21
NO2
22
Scheme 7 Decomposition of 20 under basic conditions
(10) Hirooka, Y.; Nitta, M.; Furuta, T.; Kan, T. Synlett 2008,
3234.
(11) Synthesis of sulfone 14: To a stirred solution of iodide 13 (26
mg, 70 mmol) and m-NPTSH 6 (25 mg, 110 mmol) in DMF
(1.0 mL), was added K2CO3 (15 mg, 110 mmol) at room
temperature. After stirring for 90 min, the reaction mixture
was quenched with sat. aq NH4Cl and extracted with
CH2Cl2. The organic layer was washed with sat. aq NH4Cl
and brine, dried over MgSO4, and concentrated in vacuo.
The residue (28 mg) dissolved in CH2Cl2 (1.0 mL) was
treated with m-CPBA (42 mg, 244 mmol) and, after stirring
at 40 °C for 10 h, the reaction mixture was quenched with
sat. aq Na2SO3 and extracted with CH2Cl2. The organic layer
was washed with sat. aq Na2SO3 and sat. aq NaHCO3 and
brine, dried over MgSO4, and concentrated in vacuo. The
residue was purified by preparative TLC to yield sulfone 14
(21 mg, 43 mmol, 62%, 2 steps). Spectral data for 14: IR
(13) (a) Kita, Y.; Toma, T.; Kan, T.; Fukuyama, T. Org. Lett.
2008, 10, 3251. (b) For a similar deprotection of the Ms
group by LDA, see: Ritter, T.; Stanek, K.; Larrosa, I.;
Carreira, E. M. Org. Lett. 2004, 6, 1513.
Synlett 2010, No. 5, 827–829 © Thieme Stuttgart · New York

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