2
A. T. Zdvizhkov et al. / Tetrahedron Letters xxx (2016) xxx–xxx
Table 1
The I2/H2O2 system applied in the present study has been used
Synthesis of tetrahydro-3H-furo[2,3-c][1,2]dioxoles 2a–f and 2d0–f0 from diketones
1a–f23
for iodoalkoxylation of alkenes,10 iodination of arenes,11 ketones,12
and alkynes,13 Baeyer–Villiger oxidation of ketones to lactones,14
ring contraction of 1,2-quinones to form cyclopentenones,15 oxida-
tive C–N16 and C–O17 coupling, and oxidative cyclization to hetero-
cyclic compounds.18 Additionally, the I2/H2O2 system was used in
peroxide synthesis for double bond iodoperoxidation19,20 and for
the synthesis of geminal bishydroperoxides and tetraoxanes.21,22
Entrya Product 2a–f
Product 2d0–f0 (yield of 2a–f + 2a0–f0 %; dr)
H3C
H
HO
O
—
1
(50c)
O
O
I
CH3
2ab
Results and discussion
(H3C)3C
H
HO
In this study, using the reaction of 2-allyl-1,3-diketones 1, we
obtained bicyclic compounds 2 containing annulated tetrahydrofu-
ran and 1,2-dioxolane rings instead of the expected bridged
tetraoxanes, products of the addition of I2 and H2O2 to the double
bond or products of the diperoxidation of carbonyl groups19–22
(Scheme 1).
O
—
2
3
O
O
I
(81d)
C(CH3)3
2b
H3C
CH3
HO
Peroxides 2a–f and 2d0–f0 were synthesized in DCM at 20–25 °C
using a fivefold molar excess of H2O2 and a twofold molar excess of
I2 (Table 1).
O
—
(50d)
O
O
I
CH3
2c
In entries 1–5, independent of the presence of substituents in
Ph
Ph
O
H3C
HO
H3C
HO
the
a position, fused cyclic compounds were obtained. Generally,
peroxides 2a, b with a CH moiety in the 3a position of the carbon
skeleton are less stable in comparison with peroxides 2c–f(f0) bear-
ing non-hydrogen substituents in this position.
O
O
4
O
O
I
O
I
CH3
CH3
2d
O
2d’ (68 d; 2d / 2d’ (dr 1.8:1))
CH3
The introduction of substituents at the
bonyl compounds has little effect on the yield of the reaction but
influences the ratio of stereoisomers. The reaction of diketones
a position of the dicar-
CH3
O
H3C
H3C
HO
1a–c containing a methyl group or a hydrogen atom in the
a posi-
HO
tion gives one stereoisomer. The presence of two bulky sub-
stituents at the keto groups of diketone 1b facilitates the
formation of tetrahydrofurodioxole 2b containing the C(3) atom
with a configuration that is different from that in products 2a,c.
An increase in the bulkiness of the substituents at the C(3a) atom
leads to the formation of two stereoisomers, which differ in the
position of the CH2I group. In the case of sterically hindered 3-
allyl-3-benzylpentane-2,4-dione 1d, the reaction affords an isomer
with a cis arrangement of CH2I and PhCH2 groups as the major
product. The reaction of 3,3-diallylpentane-2,4-dione 1f with the
5
6
O
O
O
O
O
O
I
I
CH3
CH3
2e’ (56 d; 2e / 2e’ (dr 1:1))
2e
O O
O O
H3C
CH3
H3C
CH3
O
H
O
O
O
H
H
H
I
I
I
I
2f
2f’ (72 d; 2f / 2f’ (dr 1:1))
a
Reagents and conditions: H2O2 (5.3 mL, 1.88 M Et2O, 10 mmol), I2 (1.015 g,
4 mmol) in DCM (10 mL), diketone 1a–f (2 mmol), 20–25 °C, 1 h.
In the case of H2O2 (2 mmol; 1 equiv) dihydrofuran 3 was obtained in 69% yield.
Product 2a was detected in trace amounts.
NMR data.
Isolated yield.
b
O
H3C
c
H
O
O
HO
d
I2, H2O2
O
H3C
O
CH3
O
O
I
O
CH3
I
I2/H2O2 system produces a mixture of stereoisomers of tricyclic
peroxide 2f and 2f0 in a 1:1 ratio in a total yield of 72%.
The reaction of ketones 4a,b containing an aromatic ring adja-
cent to the carbonyl group with the I2/H2O2 system gives, instead
of cyclization products 2, only oxidation and iodination products
5a,b in 11% and 24% yields, respectively (Scheme 2).
1a
2a, unstable compound
3
O
R
H3C
R'
R'
3a
4
4
HO
HO
2
I2, H2O2
O 3
2 O 3
5
5
3a
R
R
1O 6aO6
I
I
1O 6aO6
R'
CH3
R
Taking into account the published data24 on the reactions of
2-allyl-1,3-diketones with molecular iodine, we propose the fol-
lowing mechanism for the formation of products 2, 3, and 5
(Scheme 3).
1b-e
2b-e
2d', 2e'
1b: R = t-Bu; R' = H; 1c: R = Me; R' = Me;
1d: R = Me; R' = CH2Ph; 1e: R = Me; R' = CH2CH2COCH3
The first step involves the reaction of iodine with a double bond
to form iodonium cation I, which undergoes cyclization to tetrahy-
drofuran intermediate II and is stabilized by a lone pair of the
oxygen atom. Then, addition of H2O2 to II followed by the cycliza-
tion of III gives bicyclic compound 2. The reaction of monosubsti-
tuted diketone 2a in the presence of only one equivalent of
hydrogen peroxide proceeds via an alternative pathway involving
the deprotonation of cation II to form product 3. In the case of com-
pounds 4 the large substituent R = Ph prevents cyclization. After
8
7
8
7
O
O
O O
O O
H3C
CH3 H3C
CH3
8a 6a
8a 6a
I2, H2O2
H3C
CH3
1
6
1
6
O
3a
O
O
3a
O
2
5
2
5
3
4
3
4
I
I
I
I
1f
2f
2f'
Scheme 1. Reaction of 1a–f with the I2/H2O2 system. Descriptors b–e indicate cis-,
R, CH2I, stereochemistry, while d0, f0 indicate trans-, CH3, CH2I, stereochemistry.