Practical β-masked formylation and acetylation of electron-deficient olefins utilizing tetra(n-butyl)ammonium peroxydisulfate

Article abstract of DOI:10.1016/j.tetlet.2011.06.116

Various electron-deficient olefins reacted readily with 1,3-dioxolane or 2-methyl-1,3-dioxlane in the presence of TBAP to afford the corresponding 1,3-dioxolanylated or 2-methyl-1,3-dioxolanylated products in a complete regioselective manner in good to ex

Full text of DOI:10.1016/j.tetlet.2011.06.116

Tetrahedron Letters 52 (2011) 4662–4664
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Tetrahedron Letters
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Practical b-masked formylation and acetylation of electron-deficient
olefins utilizing tetra(n-butyl)ammonium peroxydisulfate
Jae Chul Jung a, Yong Hae Kim a, , Kieseung Lee b,
⇑
⇑
a Department of Chemistry, Korea Advanced Institute of Science & Technology, Daejon 305-701, Republic of Korea
b Department of Applied Chemistry, Woosuk University, Chonbuk 565-701, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Various electron-deficient olefins reacted readily with 1,3-dioxolane or 2-methyl-1,3-dioxlane in the
presence of TBAP to afford the corresponding 1,3-dioxolanylated or 2-methyl-1,3-dioxolanylated prod-
ucts in a complete regioselective manner in good to excellent yields.
Received 27 June 2011
Accepted 30 June 2011
Available online 8 July 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Electron-deficient olefins
Formylation
Acetylation
1,4-Diketone
Peroxydisulfate
Carbon–carbon bond formation via radical addition to alkenes is
one of the most important synthetic methodologies in the con-
struction of organic molecules. In such radical addition reactions,
it is the key point that the adduct radicals should be trapped by
a donor subsequent to the C–C bond formation in order to prevent
radical polymerization. Organotin and organomercury hydride
have been utilized for such a task.1
reactions, for example, iodination of electron-deficient olefins,5a
epoxidation of
a
,b-unsaturated ketones,5b tetrahydropyranylation
of alcohols,5c and tetrahydrofuranylation.5d
In continuation of our research on utilizing TBAP for useful or-
ganic reactions, we have recently found that electron-deficient ole-
fins (1) react readily with 1,3-dioxolane in the presence of TBAP (2)
at 25 °C to afford 1,3-dioxolanylated products (3) in a complete
regioselective manner in good to excellent yields (Table 1).6
Regioselective b-masked formylation of electron-deficient
olefins is a very important and useful reaction. In the addition of
Practical and efficient 1,3-dioxolanylation of
a,b-unsaturated
2-lithio-1,3-dithiane to
a
,b-unsaturated carbonyl compounds, the
carboxylates (runs 1–4), cycloalkenones (runs 5–7), and sulfone
(run 8) can be successfully carried out in 1,3-dioxolane used as a
solvent and the reagent in the presence of TBAP (2 equiv) at
25 °C under Ar. After the complete 1,3-dioxolanylation reaction,
tetra(n-butyl)ammonium sulfonic acid, a byproduct derived from
TBAP, was isolated and identified.
In connection with this novel reaction, we have also examined
the addition of 2-methyl-1,3-dioxolan-2-yl radical to electron-defi-
cient olefins since the 2-methyl-1,3-dioxolanylation reaction4a,7 is
equivalent to acetylation at the b-position of electron-deficient
olefins (Table 2).8
ratio of 1,2- and 1,4-addition was remarkably dependent upon the
reaction system with the predominant formation of 1,2-addition
products.2 1,3-Dioxolanylation at electron-deficient olefins is syn-
thetically equivalent to formylation since 1,3-dioxolane unit can
be readily converted to the aldehyde group selectively under various
reaction conditions.3 A few groups reported that 1,3-dioxolanyl rad-
ical generated by photo-irradiation added to electron-deficient ole-
fins to give the insufficient results of 1,3-dioxolanylated products.4
Therefore, highly regioselective 1,3-dioxolanylation at the b-posi-
tion of electron-deficient olefins has been desired.
Previously we have described the synthesis of tetra
(n-butyl)ammonium peroxydisulfate (TBAP), a new type of peroxy-
disulfate soluble in organic solvents, by introducing tetra(n-
butyl)ammonium moiety as a cation.5d By utilizing TBAP as the
key reagent in organic solvent, we have developed useful organic
For the 2-methyl-1,3-dioxolanylation reaction, 1,2-dichloroeth-
ane was used as a solvent together with a excess amount of
2-methyl-1,3-dioxolane in the presence of TBAP (2.0 equiv). Higher
reaction temperature (70 °C) compared with 25 °C of the 1,3-
dioxolanylation reaction was required to complete the reaction
most probably due to the steric hindrance of 2-methyl group of
2-methyl-1,3-dioxolane. This reaction is particularly noteworthy
since the 1,4-dioxo compounds9 are known to be valuable
⇑
Corresponding authors. Tel.: +82 42 350 2818; fax: +82 42 350 2810 (Y.H.K.).
E-mail addresses: kyh@kaist.ac.kr (Y.H. Kim), kslee@woosuk.ac.kr (K. Lee).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.06.116

J. C. Jung et al. / Tetrahedron Letters 52 (2011) 4662–4664
4663
Table 1
Table 2
b-(1,3-Dioxolanylation) of electron-deficient olefins
b-(2-Methyl-1,3-dioxolanylation) of electron-deficient olefins
O
O
O
O
O
Me
Me
R2
R1
R2
X
O
X
X
R1
R2
X
(n-Bu4N)2S2O8
O
O
+
(n-Bu4N)2S2O8
+
25 oC, Ar
R1
R1
ClCH2CH2Cl,
70 oC, Ar
R2
1
2
3
1
2
5
Yielda
(%)
Run Olefin (1)
Rxn time
(h)
Product (3)
Yielda
(%)
Run Olefin (1)
Time
(min)
Product (5)
O
O
O
MeO2C
CO2Me
CO2Me
MeO2C
CO2Me
CO2Me
Me
CO2Me
CO2Me
O
CO2Me
CO2Me
1
1.5
98
1
20
96
70
MeO2C
MeO2C
O
O
O
Me
O
MeO2C
O
2
3
MeO2C
Me
1.5
15
98
98
2
MeO2C
Me
30
MeO2C
CO2Me
CO2Me
O
O
Me
CO2Me
O
CO2Me
3
4
5
150
30
99
60
66
Me
O
Me
O
CO2Et
Me
O
CO2Et
O
O
4
5
20
18
71
97
O
O
O
O
O
O
Me
O
90
O
O
O
O
O
O
O
O
6
54
73
O
O
Me
Me
6
7
90
30
80
48
O
O
O
SO2Ph
7
8
44
3
90
99
O
SO2Ph
O
O
O
SO2Ph
SO2Ph
a
Isolated yield after flash column chromatography.
O
a
Isolated yield after flash column chromatography.
4. (a) Campari, G.; Fagnoni, M.; Mella, M.; Albini, A. Tetrahedron: Asymmetry 2000,
11, 1891; (b) Manfrotto, C.; Mella, M.; Freccero, M.; Fagnoni, M.; Albini, A. J. Org.
Chem. 1999, 64, 5024; (c) Mase, N.; Watanabe, Y.; Toru, T. Bull. Chem. Soc. Jpn.
1998, 71, 2957; (d) Inomata, K.; Suhara, H.; Kinoshita, H. Chem. Lett. 1988, 813;
(e) Matsukawa, M.; Inanaga, J.; Yamaguchi, M. Tetrahedron Lett. 1987, 28, 5877;
(f) Giordano, C.; Minisci, F.; Vismara, F.; Levi, S. J. Org. Chem. 1986, 51, 536; (g)
Watanabe, Y.; Tsuji, Y.; Takeuchi, R. Bull. Chem. Soc. Jpn. 1983, 56, 1428.
5. (a) Hwang, J. P.; Yang, S. G.; Kim, Y. H. J. Chem. Soc., Chem. Commun. 1997, 1335;
(b) Kim, Y. H.; Hwang, J. P.; Yang, S. G. Tetrahedron Lett. 1997, 38, 3009; (c) Choi,
H. C.; Cho, K. I.; Kim, Y. H. Synlett 1995, 207; (d) Jung, J. C.; Choi, H. C.; Kim, Y. H.
Tetrahedron Lett. 1993, 34, 3581.
precursors for the synthesis of cyclopentanoids and furanoids,10
heteroaromatics,11 and also bioactive natural products such as
cis-jasmone, rethrolones, and prostaglandin B2.12
In summary, we have shown that various types of electron-defi-
cient olefins reacted readily with 1,3-dioxolane or 2-methyl-1,3-
dioxlane in the presence of TBAP to provide the corresponding
1,3-dioxolanylated or 2-methyl-1,3-dioxolanylated products,
formylation or acetylation equivalents, in a complete regioselective
way in good to excellent yields. These novel 1,4-addition reactions
are practically useful for the synthesis of formyl and acetyl func-
tional groups which could play a commanding role in the construc-
tion of complex molecular architecture. Further studies to
determine the scope and the reaction mechanism are actively
going on, and the results will be reported in due course.
6. Typical experimental procedure: Dimethyl maleate (72.1 mg, 0.50 mmol) and
TBAP (677.0 mg, 1.0 mmol) were added to dry 1,3-dioxolane (5 mL), and the
reaction mixture was stirred at 25 °C for 1.5 h under Ar. The reaction mixture
was concentrated to give a viscous oil which was diluted with H2O (5 mL), then
extracted with CH2Cl2 (10 mL Â 3). The combined organic layers were dried
over anhyd MgSO4, filtered and concentrated to give an oily residue which was
flash chromatographed (SiO2, Et2O/hexane = 1:3) to afford pure dimethyl 2-
(1,3-dioxolan-2-yl)butanedioate (106.9 mg, 98%). IR (NaCl, neat) 1737, 1187,
; d 2.63 (dd, 1H, –CHCHH–,
1023, 946 cmÀ1 1H NMR (CDCl3, 400 MHz)
J1 = 17.1 Hz, J2 = 4.9 Hz), 2.80 (dd, 1H, –CHCHH–, J1 = 17.1 Hz, J2 = 9.3 Hz), 3.25
(br q, 1H, –CHCH2–), 3.68 (s, 3H, –OCH3), 3.75 (s, 3H, –OCH3), 3.85–4.01 (m, 4H,
–CH2CH2–), 5.19 (d, 1H, –CHCH–, J = 4.4 Hz); 13C NMR (CDCl3, 100 MHz) d
29.90, 45.54, 51.74, 52.16, 65.24, 102.60, 102.62, 171.28, 172.25, MS (EI) m/z
(rel. intensity %) 99 (11), 73 (100), 59 (27), 55 (38), 45 (48).
Acknowledgments
This work was supported by Korean Science & Engineering
Foundation. Lee, K. gratefully acknowledges the financial support
from the Program of Regional Innovation Center at Woosuk Uni-
versity which was conducted by the Ministry of Knowledge Econ-
omy of the Korean Government.
7. Mosca, R.; Fagnoni, M.; Mella, M.; Albini, A. Tetrahedron 2001, 57, 10319.
8. Typical experimental procedure:
A mixture of methyl crotonate (50.1 mg,
0.50 mmol), TBAP (677.0 mg, 1.0 mmol) and 2-methyl-1,3-dioxolane
(881.1 mg, 10.0 mmol) in anhyd dichloroethane (2 mL) was heated at 70 °C
for 2.5 h under Ar. The reaction mixture was concentrated to give a viscous oil
which was diluted with saturated aqueous NaHCO3 (1 mL) and distilled H2O
(10 mL). The product was extracted with Et2O (10 mL Â 3), and the combined
organic layers were dried over anhyd MgSO4, filtered and concentrated. The
oily residue was purified by flash chromatography on SiO2 (Et2O/hexane = 1:3)
to afford methyl 3-(2-methyl-1,3-dioxolan-2-yl)butanoate (93.0 mg, 99 %). IR
References and notes
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(NaCl, neat) 1733, 1195, 1160, 1051, 951 cmÀ1 1H NMR (CDCl3, 400 MHz) d
;
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J1 = 15.1 Hz, J2 = 8.3 Hz), 2.27–2.37 (m, 1H, –CHCH2–), 2.57 (dd, 1H, –CHCHH–,
J1 = 15.1 Hz, J2 = 5.4 Hz), 3.67 (s, 3H, –CO2CH3), 3.87–4.01 (m, 4H, –CH2CH2–);

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J. C. Jung et al. / Tetrahedron Letters 52 (2011) 4662–4664
13C NMR (CDCl3, 100 MHz) d 15.49, 20.56, 36.76, 38.48, 51.49, 64.64, 64.72,
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