Synthesis of bishomoinositols and an entry for construction of a substituted 3-oxabicyclo[3.3.1]nonane skeleton

Article abstract of DOI:10.1021/jo202494v

1,3,3a,7a-Tetrahydro-2-benzofuran was used as key compound for the synthesis of various bishomoinositol derivatives. The diene was subjected to an epoxidation reaction for further functionalization of the diene unit. The bisepoxide obtained was submitted

Full text of DOI:10.1021/jo202494v

Featured Article
pubs.acs.org/joc
Synthesis of Bishomoinositols and an Entry for Construction
of a Substituted 3-Oxabicyclo[3.3.1]nonane Skeleton
Arif Baran,*,† Merve Bekarlar,‡ Gokay Aydin,† Mehmet Nebioglu,† Ertan S
̧
̈
†Department of Chemistry, Sakarya University, 54100 Sakarya, Turkey
‡Department of Chemistry, Middle East Technical University, 06800 Ankara, Turkey
§Department of Chemistry, Ataturk University, 25240 Erzurum, Turkey
̈
S
* Supporting Information
ABSTRACT: 1,3,3a,7a-Tetrahydro-2-benzofuran was used as key com-
pound for the synthesis of various bishomoinositol derivatives. The diene
was subjected to an epoxidation reaction for further functionalization of the
diene unit. The bisepoxide obtained was submitted to a ring-opening
reaction with acid in the presence of water. Various bishomoinositols were
synthesized. However, when the reaction was carried out in the presence of
acetic anhydride, a substituted 3-oxabicyclo[3.3.1]nonane skeleton was
formed. The mechanism of the formation of the products is discussed.
we reported the synthesis of various isomeric inositol deriva-
tives with skeleton of 3, starting from the diene 7 (Figure 1).11
Motivated by the important biological activities of inositol
derivatives, we formulated a new strategy of synthesis for new
bishomoinositols based on the photooxygenation of diene 7
followed by transformation of the bicyclic endoperoxide
formed.
INTRODUCTION
■
Cyclitols are sugar-like molecules. They have for the past few
decades attracted interest because of their significant biological
properties and diverse synthetic intermediates.1 Among the
cyclitols, chemists have extensively studied inositols because of
their remarkable, comprehensive, and important biological
functions.2 The most prominent naturally occurring form is
myo-inositol, cis-1,2,3,5-trans-4,6-cyclohexanehexol (1) (Figure 1),
RESULTS AND DISCUSSION
■
The previously known diene 711 was prepared in five steps
starting with the addition of maleic anhydride to in situ
generated butadiene. The reduction of the anhydride
functionality in 4 followed by tosylation of diol 5 afforded
the desired tetrahydrofuran derivative 6. Bromination of the
resulting tetrahydrofuran, and 1,8-biazabicyclo[5.4.0]undec-7-
ene (DBU) induced elimination furnished diene 7. Addition of
singlet oxygen12 to the diene moiety in 7 afforded bicyclic
endoperoxide 8 as the sole product (Scheme 1).
Figure 1. Representative cyclitols.
which is actively involved in cellular events and processes. In
recent years, inositol phosphates in particular have been studied
and new derivatives have been discovered that possess vital
biological and physiological functions in cellular signaling
events. Numerous synthetic approaches for inositol derivatives
have been developed including the use of naturally occurring
inositols,3 sugars,4 aromatic compounds,5 chiral acids,6
tetrahydrobenzoquinone,7 and cyclohexene and its derivatives.8
Moreover, an increasing number of reports also describe the
synthesis of analogues of various inositol derivatives with novel
architectures.9
Unsaturated bicyclic endoperoxides can be conveniently
converted into the corresponding diepoxides with syn-
configuration by treatment with cobalt(II) tetraphenylporphyr-
in (CoTPP).12,13 The reaction of the endoperoxide 8 with
CoTPP at 0 °C resulted in the formation of bisepoxide 9 in
84% yield. The symmetrical structure was confirmed by the 13C
NMR spectrum consisting of four carbon resonances.
Bisepoxide 9 was subjected to an acid-catalyzed ring-opening
reaction in the presence of water (to avoid any neighboring
Recently, we have prepared bicyclic bishomoinositol
derivative 2 and other isomeric derivatives, which are locked
in rigid conformations with six hydroxyl groups.10 Furthermore,
Received: December 8, 2011
Published: January 9, 2012
© 2012 American Chemical Society
1244
dx.doi.org/10.1021/jo202494v | J. Org. Chem. 2012, 77, 1244−1250

The Journal of Organic Chemistry
Featured Article
the protons H-5−H-4 as well as the protons H-5−H-6. The
acetoxy proton H-6 also resonates as a doublet of doublets with
coupling constants of J = 9.1 and 10.0 Hz, clearly indicating the
trans relation of the protons H-6−H-7. On the basis of these
findings we assigned a trans−trans−trans relationship to the
acetate groups in 10.
Scheme 1. Preparation of Bisepoxide 9 from Anhydride 4
After complete structural characterization of three tetraace-
tates 10−12, we turned our attention to the opening of the
tetrahydrofuran ring and removal of the acetate groups. Sulfamic
acid14 was used as an efficient catalyst in acetic anhydride to pro-
mote the acetolysis reaction of the tetrahydrofuran ring. Reaction
of sulfamic acid with tetraacetate 10 at reflux temperature of a
mixture of acetic acid and acetic anhydride (1:1) afforded the
desired hexaacetate 13, which was characterized by spectral data
(Scheme 3). The structure and stereochemistry of this tetraacetate
were rigorously established by inspection of NMR spectra.
Furthermore, the spectral data of 13 were identical with those
synthesized by ring-opening reaction of the dihydroxy epoxide 15.10
The configuration at the carbon atom C-4 in 13 compared
with the configuration in 10 was inversed. The exclusive forma-
tion of 13 can be explained by neighboring group participa-
tion,15 which controls the mode of the reaction. Probably, initially
protonated dihydrofuran ring 16 undergoes an attack by the adjacent
acetoxy group to form cyclic oxolonium ion 17, which can undergo
ring-opening through attack by the acetate ion, causing ring-opening
and configuration isomerization (Scheme 4). Deacetylation of tetra-
acetate 13 with ammonia was carried out in methanol to give the free
hexol, bishomo-chiro-inositol 14 (Scheme 3).
Next, the ring-opening reaction of 11 was studied. The
tetraacetate 11 was treated with sulfamic acid in a mixture of
acetic acid and acetic anhydride to give the hexaacetate 18 as
the sole product in 74% yield. Hydrolysis of 18 with ammonia
in MeOH resulted in the formation of bishomo-muco-inositol
19 in 92% yield (Scheme 5). Studies of the NMR spectra did
not reveal any configuration change in the product. In
particular, C-13 NMR of 19 showing only 4 carbon resonances
clearly indicates that the original configuration of the
tetraacetate 11 was preserved in the product. The geometry
optimized structure of the tetraacetate 11 shows that the
acetate groups attached to C-4 and C-7 carbon atoms are
remote from the methylene groups and can not approach from
the back of the methylene carbon atom.
group participation) followed by acetylation with acetic an-
hydride in pyridine resulting in the formation of three separable
tetraacetates 10−12 (two of them with symmetrical structures)
in 15, 50, and 19% yields, respectively (Scheme 2). The spectral
Scheme 2. Reaction of Bisepoxide 9 with H2SO4 in Water
data of the symmetrical tetraacetates were in complete agree-
ment with the proposed structures 11 and 12, which are for-
med by symmetrical trans-opening of the epoxide rings in 9.
The 13C NMR spectra of 11 and 12 having eight carbon
resonances also support the proposed structures. However, we
were not able to make a clear-cut differentiation between those
isomers on the basis of NMR data alone. Finally, the structure
12 was further confirmed by single crystal X-ray analysis
(Figure 2).
Finally, the tetraacetate 12 was submitted to a sulfamic acid
catalyzed ring-opening reaction in the presence of acetic
anhydride. Two diastereoisomers 20 and 21 were isolated after
1
column chromatography on silica gel (Scheme 6). The H
NMR spectral data of 21 showed that the configuration of
acetate groups in 12 was not changed during the ring-opening
reaction. The 1H NMR and 13C NMR spectra of 21 supported
the symmetrical structure in the molecule. However, the con-
figuration at C-4 carbon atom in 20 was changed. The 20-line
13C NMR spectrum clearly indicated the presence of an un-
symmetrical structure. This outcome was expected. As
discussed in the case of 10, the acetate group attached to C-4
carbon atom is responsible for this configuration isomerization.
Hydrolysis of 20 and 21 with ammonia in methanol afforded
the corresponding hexols 22 and 23 with neo-inositol and allo-
inositol configuration in high yield.
We then turned our attention to the acid-catalyzed ring-
opening reaction of 9 in acetic anhydride instead of water. The
attempted analogous epoxide opening with H2SO4 in acetic
anhydride, however, resulted in the formation of a rearranged
product 24 (Scheme 7). First we determined the constitution
Figure 2. Crystal structures of 12.
The structure of 10 was found to be in a trans−trans−trans
configuration based on the analysis of NMR spectroscopic data
(COSY, HSQC, HMBC). The resonance signal of H-5 appears
as a doublet of doublets at 5.27 ppm with coupling constants of
J = 9.5 and 9.1 Hz, which clearly supports the trans relation of
1245
dx.doi.org/10.1021/jo202494v | J. Org. Chem. 2012, 77, 1244−1250

The Journal of Organic Chemistry
Featured Article
Scheme 3. Synthesis of Bishomo-chiro-inositol 14
Scheme 4. Mechanism of Formation of 13
that both products were converted to tetrahydropyran derivative
24 in high yields.
At this stage, we suggest the following mechanism for the
formation of the products 26 and 27. We assume that the
acetate anion prefers first to attack the protonated epoxide ring
in 28 from the back (solid arrows in Scheme 8) to form 26. On
the other hand, the acetate anion can also attack the methylene
carbon atom followed by cleavage of the carbon−oxygen bond
and subsequent formation of the double bond in 29 (broken
arrows in Scheme 8).
For the formation of 24 from 27, the following mechanism is
suggested. Removal of the acetate group attached to the methylene
carbon atom will form a primary carbocation 30 which will be
stabilized by the neighboring oxygen atom. The formed oxonium
ion can be attacked by double bond electrons to complete the
cyclization reaction (Scheme 9). The formed carbocation will be
then captured by the acetate anion from the less crowded side to
furnish pyrane derivative 24.16 The fact that the reaction of 9 with
acid in the presence of acetic anhydride forms the rearranged
product 24 can be attributed to the weak nucleophilicity of acetic
anhydride compared to water.
of 24 by using NMR spectroscopic data (COSY, HSQC,
HMBC). The COSY spectrum of 24 showed correlation
between the high field acetoxy proton H-9 resonance appearing
at 4.96 ppm as a broad triplet (J = 2.7 Hz) with two bridgehead
protons H-1 and H-5, indicating clearly that this acetoxy proton
is located between two bridgehead protons. To confirm this
finding and to determine the exact configuration of the acetate
groups, an X-ray diffraction study of 24 was undertaken (Figure 3).
The results of this study showed that 24 is rearranged and the
relations of the acetate groups attached to C-6, C-7, and C-8
carbons are cis and trans. To gain insight into the mechanism
of formation of this product, we ran the reaction in the
presence of lower acid concentration eventually to isolate any
intermediate formed during the reaction. During the conversion
of 9 to 24, there are two successive reactions: the opening of
one of the epoxide rings and the opening of the second
epoxide-ring followed by migration of the alkyl group. For this
purpose, the bisepoxide 9 was submitted to ring-opening
reaction with a catalytic amount of H2SO4 in the presence of
acetic anhydride. After consumption of the starting material, a
mixture of two compounds 26 and 27 was formed in yields of
48% and 39%, respectively. The structures of these compounds
were determined unambiguously. To demonstrate the feasibility
of converting these products to 24, they were separately sub-
mitted to an acid-catalyzed reaction as applied in case of convers-
ion of 9 to 24. Analysis of the reaction mixture clearly indicated
Attempts were made to cleave the pyran ring in 24 with
sulfamic acid under drastic conditions. However, in all cases the
starting material was isolated. Finally, deacetylation of 24 with
ammonia gave tetrol 25 with a pyran skeleton in the molecule.
CONCLUSION
■
In conclusion, the methodology detailed herein resulted in the
convenient conversion of the diene 7 into various bishomoi-
nositol derivatives. The oxygen functionalities were introduced
by an epoxide-ring-opening reaction in the presence of water or
acetic anhydride. This methodology opens up also an entry to the
synthesis of bishomoaminoinositol derivatives. Furthermore, it has
been shown in this paper that the bisepoxide 9 can be used for the
construction of a bicyclic pyran skeleton. Further work to generate
Scheme 5. Synthesis of Bishomo-muco-inositol 19
1246
dx.doi.org/10.1021/jo202494v | J. Org. Chem. 2012, 77, 1244−1250

The Journal of Organic Chemistry
Featured Article
Scheme 6. Synthesis of Bishomo-neo-inositol 22 and
Bishomo-allo-inositol 23
Scheme 8. Mechanism of Formation of 26 and 27
Scheme 9. Mechanism of Formation of 24 from 27
Scheme 7. Reaction of Bisepoxide 9 with H2SO4 in Acetic
Anhydride
hexane/EtOAc (2:3) gave diepoxide 9 (1.68 g, 84%), which was
1
crystallized from chloroform: colorless crystals; mp 73−75 °C; H
NMR (400 MHz, CDCl3) δ 3.91 (br t, A-part of AB-system, J = 7.6 Hz,
2H), 3.62 (dd, B-part of AB-system, J = 8.4 and 4.5 Hz, 2H), 3.41 (d, J =
1.3 Hz, 2H), 2.87 (br d, J = 1.3 Hz, 2H) 2.64−2.58 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 71.0, 50.4, 47.6, 36.8; IR (KBr, cm−1) 3003, 2956,
2879, 1423, 1365, 1267, 1195, 1070.49, 1049, 1033, 952, 929, 894. Anal.
Calcd for C8H10O3: C, 62.33; H, 6.54. Found: C, 62.36; H, 6.65.
Reaction of Bisepoxide with H2SO4 in Water. To a slurry of
bisepoxide 9 (4.0 g, 26.0 mmol) in 20 mL of water was added H2SO4
(4 mL), and the resulting mixture was stirred at room temperature for
24 h. For neutralization of acid NaHCO3 (8.0 g) was added. After
evaporation of water, the residue was treated with MeOH and the solid
was filtered. MeOH was evaporated, and the residue, without any
purification, was treated with pyridine (7 mL) and Ac2O (10 mL). The
resulting mixture was stirred at room temperature for 24 h. EtOAc
(300 mL) was added to the mixture and stirred for 5 min, then
aqueous ice-cooled HCl (30 mL 5−7%) was added, and the mixture
was stirred for a while at room temperature. The organic layer was
washed with saturated aqueous NaHCO3 (3 × 100 mL) and water
(3 × 200 mL), dried (Na2SO4), and concentrated to give 9.0 g of a
mixture of isomeric tetraacetates 10−12. The mixture of isomers was
chromatographed on a silica gel column (150 g) eluting with EtOAc/
hexane (1:3). Three compounds were isolated in the following order:
rel-(3aR,4R,5S,6S,7R,7aS)-Octahydroisobenzofuran-4,5,6,7-
tetrayl tetraacetate (10): 1.39 g, 15% as colorless crystals from
hexane/EtOAc (1:4); mp 133−135 °C; 1H NMR (400 MHz, CDCl3)
δ 5.27 (dd, A-part of AB-system, J45 = 9.5 Hz, J56 = 9.1 Hz, 1H, H-5),
5.22 (dd, B-part of AB-system, J45 = 9.5 Hz, J43a = 6.3 Hz, 1H, H-4),
5.12 (t, J77a = J76 = 10.0 Hz, 1H, H-7), 5.4 (dd, J67 = 10.0 Hz, J56 = 9.1
Hz, 1H, H-6) 3.83 (d, J33′ = 9.7 Hz, 2H, H-3, H-3′) 3.75 (d, A part of
AB system, J11′ = 8.9 Hz, 1H, H-1), 3.69 (dd, B part of AB system,
J1′7a = 4.4 Hz, J11′ = 8.9 Hz, 1H, H-1′), 2.98 (tt, J = 9.5 and 6.3 Hz, 1H,
H-3a), 2.35 (ddd, J = 10.0, 6.3, and 4.5 Hz, 1H, H-7a), 1.97 (s, 6H,
CH3), 1.94 (s, 3H, CH3), 1.93 (s, 3H, CH3); 13C NMR (100 MHz,
CDCl3) δ 169.9, 169.8, 169.7, 169.6, 72.8, 71.1, 70.93, 70.3, 70.0, 67.4,
42.2, 40.5, 20.70, 20.68, 20.57, 20.53; IR (ATR) 2944, 2918, 2882,
Figure 3. Crystal structures of 24.
a pyran skeleton with various substituents is currently under
investigation by our group.
EXPERIMENTAL SECTION
■
rel-(1aR,1bS,2aS,2bS,5aR,5bR)-Octahydrobis(oxireno)[2,3-
e:2′,3′-g]isobenzofuran (9). To a magnetically stirred solution of
bicyclic endoperoxide 8 (2.0 g, 13 mmol) in 40 mL of CH2Cl2 was
added a solution of cobalt meso-tetraphenylporphyrin (60 mg) in
10 mL of CH2Cl2 at 0 °C. After complete addition (10 min), the mixture
was stirred for 2 h at room temperature. Removal of solvent and
chromatography of the residue on 50 g of silica gel eluting with
1247
dx.doi.org/10.1021/jo202494v | J. Org. Chem. 2012, 77, 1244−1250

The Journal of Organic Chemistry
Featured Article
1
1745, 1734, 1456, 1367, 1265, 1215, 1114, 1053, 1033, 975, 940, 923,
894. Anal. Calcd for C16H22O9: C, 53.63; H, 6.19. Found: C, 53.50; H,
5.94.
(0.47 g, 74%) from EtOAc/n-hexane (1:4); mp 117−119 °C; H-NMR
(300 MHz, CDCl3) δ 5.30 (br s, 4H, H-1, H-2, H-3, H-4); 4,35 (dd, A
part of AB System, J = 11.2 and 6.7 Hz, 2H, CH2), 4.17 (dd, B part of AB
System, J = 11.2 and 6.0 Hz, 2H, CH2), 2.57−2.53 (m, 2H, H-5, H-6),
2.09 (s, 2 × CH3), 2.07 (s, 2 × CH3), 2,06 (s, 2 × CH3); 13C NMR
(75 MHz, CDCl3) δ; 170.8, 169.8, 169.7, 70.3, 68.0, 61.7, 38.8, 21.1,
21.0, 20.9 ppm; IR (KBr, cm−1) 1735, 1435, 1367, 1219, 1205, 1180,
1105, 1082, 1031, 989, 945. Anal. Calcd for C20H28O12: C, 52.17; H,
6.13. Found; C, 52.19; H, 6.25.
1H NMR (400 MHz, benzene-d6) δ 5.49 (t, J = 9.3 Hz, 1H, H-5),
5.33 (t, J = 10.1 Hz, 1H, H-7), 5.25 (dd, J = 9.3 and 6.6 Hz, H-4), 5.22
(t, J = 9.3 Hz, H-6), 3.72 (dd, J = 8.7 and 1.1 Hz, 1H, CH2), 3.61−3.53
(m, 2H, CH2), 3.31 (dd, J = 8.7 and 4.5 Hz, 1H, CH2), 2.42 (tt, J =
9.76 and 6.6 Hz, H-3a), 1.89−1.63 (m, 1H, H-7a), 1.67 (s, CH3), 1.66
(s, CH3), 1.62 (s, CH3), 1.51 (s, CH3).
rel-(3aR,4R,5S,6R,7S,7aS)-Octahydroisobenzofuran-4,5,6,7-
rel-(1R,2S,3R,4S,5S,6R)-5,6-Bis(hydroxymethyl)cyclohexane-
1,2,3,4-tetraol (19). The hexaacetate 18 (1.0 g, 2.17.mmol) was
hydrolyzed with NH3(g) as described above to give hexol 19 (0.41 g,
tetrayl tetraacetate (11): (4.65 g, 50%) colorless crystals from
1
hexane/EtOAc; mp 120−122 °C; H NMR (400 MHz, CDCl3) δ
1
5.33−5.22 (m, 4H, H-4, H-5, H-6, H-7), 3.92−3.88 (m, 4H, H-1, H-
3), 2.62−2.57 (m, 2H, H-3a, H-7a), 2.10 (s, 6H, 2 × CH3), 2.06
(s, 6H, 2 × CH3); 13C (100 MHz, CDCl3) δ 170.0, 169.9, 70.2, 69.6,
68.1, 42.9, 21.2, 21.0; IR (KBr, cm−1) 3002, 2890, 1739, 1367, 1251,
1213, 1060, 1041, 1028, 933, 906. Anal. Calcd for C16H22O9: C, 53.63;
H, 6.19. Found: C, 53.58; H, 6.31.
92%) as a colorless viscous oil: H NMR (300 MHz, CD3OD) δ 4.88
(bs, 6H, OH), 3.89−3.83 (m, 4H, CH), 3.79−3.73 (m, 4H, CH2),
2.18−2.13 (m, 2H, CH); 13C NMR (75 MHz, CD3OD) δ 73.3, 71.6,
61.2, 43.2; IR (KBr, cm−1) 3294, 2922, 1402, 1039, 999, 769, 632.
Anal. Calcd for C8H16O6: C, 46.15; H, 7.75. Found: C; 46.01, H, 7.78.
Reaction of Tetraacetate 12 with Sulfamic Acid. Tetraacetate
12 (1.0 g, 2.8 mmol) was hydrolyzed with sulfamic acid as desribed
above. The mixture was separated by silica gel chromatography eluting
with EtOAc/hexane (1:3). The first fraction was the hexaacetate 20.
The second fraction was identified as the symmetrical hexaacetate 21.
rel-(1S,2R,3S,4S,5S,6R)-5,6-Bis(acetoxymethyl)cyclohexane-
1,2,3,4-tetrayl tetraacetate (20): 0.58 g (45%); colorless crystals
rel-(3aR,4S,5R,6S,7R,7aS)-Octahydroisobenzofuran-4,5,6,7-
tetrayl tetraacetate (12): colorless crystals (1.77 g, 19%) from
hexane/EtOAc; mp 115−116 °C; 1H NMR (400 MHz, CDCl3) δ 5.40
(br s, 4H, H-4, H-5, H-6, H-7), 3.89 (d, J = 6.4 Hz, 4H, CH2), 2.94 (br
s, 2H, H-3a, H-7a), 2.11 (s, 6H, 2 × CH3), 2.08 (s, 6H, 2 × CH3); 13
C
NMR (CDCl3, 75 MHz) δ 170.3, 170.0, 69.5, 69,2, 68.7, 40.1, 21,2,
21.0; IR (KBr, cm−1) 3000, 2955, 1745, 1732, 1369, 1255, 1222, 1213,
1093, 1074, 1031, 885. Anal. Calcd for C16H22O9: C, 53.63; H, 6.19.
Found: C, 53.59; H, 6.37.
1
from EtOAc/n-hexane (1:2); mp 153−155 °C; H NMR (300 MHz,
CDCl3) δ 5.58 (br s, 1H, CH), 5.37 (dd, A part of AB system, J = 10.8,
3.2 Hz, 1H, CH), 5.36−5.30 (m, 1H, CH), 5.31 (dd, B part of AB
system, J = 10.6, 5.3 Hz, 1H, CH), 4.31 (dd, 1H, A part of AB system,
J = 12.0, 2.4 Hz, 1H, CH2), 4.21 (dd, B part of AB system, J = 12.0, 3.2
Hz, 1H, CH2), 4.15 (d, J = 5.5 Hz, 2H, CH2), 2.72−2.64 (m, 2H, CH),
2.16 (s, CH3), 2.15 (s, CH3), 2.10 (s, CH3), 2.04 (s, CH3), 2.03 (s,
CH3), 2.01 (s, CH3); 13C NMR (75 MHz, CDCl3) δ 170.7, 170.5,
170.4, 170.2, 169.9, 169.8, 69.9, 69.5, 68.3, 67.5, 61.9, 59.6, 36.6, 36.0,
21.3, 21.1, 21.0, 20.9, 20.86 (2C); IR (KBr, cm−1): 2938, 2870, 1740,
1443, 1368, 1243, 1108, 1066, 965. Anal. Calcd for C20H28O12: C,
52.17; H, 6.13. Found: C; 52.08, H, 6.23.
General Procedure for Ring-Opening of Tetrahydrofuran
Derivatives (10−12). To a stirred solution of 1.0 g (2.80 mmol) of
tetraacetate in Ac2O/AcOH (10 mL 1:1) was added sulfamic acid
(40 mg) at room temperature, followed by heating at reflux temperature
for 24 h. After the mixture was cooled to room temperature, HCl was
added (50 mL, 5%) and extracted with ethyl acetate (300 mL). The
organic phase was washed with water (2 × 100 mL) and saturated
NaHCO3 (2 × 50 mL) and dried (MgSO4). After removal of the
solvent under reduced pressure the residue was crystallized from
EtOAc/n-hexane (1:4) to give the corresponding hexaacetate.
rel-(1R,2S,3S,4S,5S,6R)-5,6-Bis(acetoxymethyl)cyclohexane-
1,2,3,4-tetrayl Tetraacetate (13). Tetraacetate 10 (1.0 g, 2.79 mmol)
was reacted with sulfamic acid as described above to give hexaacetate
rel-(1R,2S,3R,4S,5R,6S)-5,6-Bis(acetoxymethyl)cyclohexane-
1,2,3,4-tetrayl tetraacetate (21): 0.39 g (30%); colorless crystals
from EtOAc/n-hexane (1:2); mp 106−109 °C; NMR (300 MHz,
CDCl3) δ 5.30 (br d, 2H, J = 6.8 Hz, 2H, CH), 5.15 (bs, 2H, CH),
4.24 (bs, 4H, CH2), 2.66 (bs, 2H, CH), 2.11 (s, 2 × CH3), 2.05 (s, 2 ×
CH3), 2.03 (s, 2 × CH3); 13C NMR (75 MHz, CDCl3) δ 170.7, 169.8,
169.7, 69.5, 67.6, 61.4, 37.3, 21.1, 21.1, 21.0; IR (KBr, cm−1) 1732,
1367, 1230, 1209, 1188, 1064, 1043, 1024, 904. Anal. Calcd for
C20H28O12: C, 52.17; H, 6.13. Found: C; 52.36, H, 6.27.
1
13 as colorless crystals (0.90 g, 70%): mp 105−107 °C; H NMR
(300 MHz, CDCl3) δ 5.47 (t, J34 = J34 = 3.2 Hz, 1H, H-4), 5.38 (dd, A
part of AB system, J12 = 9.4, J23 = 10.1 Hz, 1H, H-2), 5.29
(dd, B part of AB system, J16 = 11.4 Hz, J12 = 9.4 Hz, 1H, H-1) 5.18
(dd, J23 = 10.1 Hz, J34 = 3.2 Hz, 1H, H-3), 4.29−4.22 (m, 3H), 3.98
(dd, 1H, J = 11.8 and 4.1 Hz, 1H), 2.66−2.56 (m, 1H, H-6), 2.47−
2.36 (m, 1H, H-7), 2.14 (s, 3H), 2.03 (s, 3H), 2.03 (s, 3H), 2.02
(s, 3H), 2.00 (s, 3H), 1.99 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
170.7, 170.6, 170.4, 170.2, 170.1, 170.0, 71.8, 70.3, 70.0, 69.8, 61.7,
61.4, 39.6, 37.0, 21.2, 21.1, 21.0, 20.9, 20.9; IR (KBr, cm−1) 2964,
1747, 1433, 1369, 1230, 1040, 952. Anal. Calcd for C20H28O12: C,
52.17; H, 6.13. Found: C, 51.84; H, 6.09.
rel-(1S,2R,3S,4S,5S,6R)-5,6-Bis(hydroxymethyl)cyclohexane-
1,2,3,4-tetraol (22). Hexaacetate 20 (0.8 g, 1.74 mmol) was
hydrolyzed with NH3(g) as described above to give hexol 22 (0.35 g,
1
97%) as a colorless viscous oil: H NMR (300 MHz, D2O) δ 4.7 (bs,
6H, OH), 3.99 (bd, J = 2.2 Hz, 1H, CH), 3.94−3.91 (m, 1H, CH),
3.88−3.65 (m, 8H, CH and CH2), 2.32−2.24 (m, 1H, CH), 2.18−2.10
(m, 1H, CH); 13C NMR (75 MHz, D2O at 60 °C) δ 70.6, 68.7 (2C),
60.9, 57.0 (2C), 40.8 (2C); IR (KBr, cm−1) 3342, 1661, 1397, 1032, 845.
Anal. Calcd for C8H16O6: C, 46.15; H, 7.75. Found: C, 45.87; H, 7.53.
rel-(1R,2S,3R,4S,5R,6S)-5,6-Bis(hydroxymethyl)cyclohexane-
1,2,3,4-tetraol (23). Hexaacetate 21 (0.6 g, 1.30 mmol) was
hydrolyzed with NH3(g) as described above to give hexol 23 (0.24 g,
General Procedure for Hydrolysis of Hexaacetates 10−12.
Synthesis of Bishomoinositols. Hexaacetate (1.0 mmol) was
dissolved in 60 mL of absolute methanol. While dry NH3(g) was passed
through solution, the mixture was stirred for 5 h at room temperature.
Evaporation of the solvent and formed acetamide gave hexol.
rel-(1R,2S,3S,4S,5S,6R)-5,6-Bis(hydroxymethyl)cyclohexane-
1,2,3,4-tetraol (14). Hexaacetate 13 (1.0 g, 2.17 mmol) was
hydrolyzed as described above to give hexol 14: 0.43 g, 96%, colorless
1
90%) as a colorless viscous oil: H NMR (300 MHz, CD3OD) δ 4.89
(bs, 6H, OH), 3.95−3.62 (m, 8H, CH and CH2) 2.27 (bs, 2H, CH);
13C NMR (75 MHz, CD3OD at 80 °C) δ 70.9, 69.9, 58.2, 40.2. IR
1
viscous oil; H NMR (400 MHz, DMSO) δ 4.55 (bs, 1H), 4.43 (bs,
(KBr, cm−1) 3332, 2926, 1450, 1402, 1039, 999, 769, 632. Anal. Calcd
for C8H16O6: C, 46.15; H, 7.75. Found: C, 45.82; H, 7.37.
2H), 4.34 (bs, 1H), 4.27 (bs, 2H), 3.88 (bs, 1H), 3.70−3.67 (m, 1H),
3.53−3.50 (m, 1H), 3.46−3.43 (m, 1H), 3.37 (bs, 1H), 3.30 (bd, J =
7.9 Hz, 1H), 3.27−3.17 (m, 2H), 2.01−1.94 (m, 2H); 13C NMR
(100 MHz, DMSO) δ 75.4, 71.9, 72.4, 70.2, 60.9, 58.6, 43.2, 40.1; IR
(KBr, cm−1) 3400, 2931, 2904, 1447, 1382, 1343, 1324, 1256, 1239,
1214, 1196, 1150, 1134, 1110. Anal. Calcd for C8H16O6: C, 46.15; H,
7.75. Found: C, 46.52; H, 7.49.
rel-(1R,2S,3R,4S,5S,6R)-5,6-Bis(acetoxymethyl)cyclohexane-
1,2,3,4-tetrayl Tetraacetate (18). Tetraacetate 11 (0.5 g, 1.40 mmol)
was hydrolyzed with sulfamic acid as described above: colorless crystals
Ring-Opening Reaction of the Bisepoxide 9 with H2SO4 in
Acetic Anhydride 9. To a stirred solution of bisepoxide 9 (4.0 g,
26.0 mmol) in 10 mL of acetic anhydride was added dropwise H2SO4
(1.5 mL) and then the mixture was stirred for 12 h at room tem-
perature. After completion of the reaction, dichloromethane (500 mL)
was added. The resulting solution was extracted first with saturated
NaHCO3 solution then with water and dried over MgSO4. Solvent was
evaporated and the residue was chromatographed on a silica gel
1248
dx.doi.org/10.1021/jo202494v | J. Org. Chem. 2012, 77, 1244−1250

The Journal of Organic Chemistry
Featured Article
column (70 g) eluting with hexane/EtOAc (4:1). The rearranged
product 24 was isolated (7.43 g, 80%). Crystallization from hexane/
EtOAc (1:4) gave rel-(1R,5S,6R,7R,8R,9S)-3-oxabicyclo[3.3.1]nonane-
6,7,8,9-tetrayl tetraacetate 24 as colorless crystals, mp 164−166 °C. 1H
NMR (400 MHz, CDCl3) δ 5.72 (dd, J78 = 10.3 Hz, J76 = 5.4 Hz, 1H,
H-7), 5.56 (dd, J87 = 10.3 Hz, J81 = 4.6 Hz, 1H, H-8), 5.50 (ddd,
J67 = 5.4 Hz, J65 = 2.3 Hz, J69 = 0.9 Hz, 1H, H-6), 4.96 (bt,
J = 2.7 Hz, 1H, H-9), 4.14 (bd, A-part of AB system, J22′ = 11.4 Hz,
1H, H-2), 3.94 (d, A-part of AB system, J44′ = 12.1 Hz, 1H, H-4), 3.62
(dd, B-part of AB system, J44′ = 12.1 Hz, J4′5 = 2.2 Hz, 1H, H-4′), 3.54
(d, B-part of AB system, J22′ = 11.4 Hz, 1H, H-2′), 2.43 (m, 1H, H-5),
2.29 (m, 1H, H-1), 2.08 (s, 6H, 2 × CH3), 2.01 (s, 3H, CH3), 1.92 (s,
3H, COCH3); 13C NMR (100 MHz, CDCl3) δ 170.2, 170.1, 169.9,
169.87, 72.8, 71.6, 70.0, 69.5, 68.4, 66.5, 39.6, 38.7, 21.2, 21.0, 20.9,
20.7; IR (ATR) 2978, 2856, 1735, 1369, 1216, 1171, 1132, 1114, 1035,
975, 948, 909, 862. Anal. Calcd for C16H22O9: C, 53.63; H, 6.19.
Found: C, 53.80; H, 6.43.
rel-(1R,5S,6R,7R,8R,9S)-3-Oxabicyclo[3.3.1]nonane-6,7,8,9-
tetraol (25). Tetraacetate 24 (100 mg, 0.28 mmol) was dissolved in
10 mL of methanol. The solution was stirred at room temperature for
24 h while passing NH3(g) through the solution. After evaporation of
the solvent and the removal of the acetamide which was formed during
the reaction, tetrol 25 was obtained as colorles oil (499 mg, 94%): 1H
NMR (400 MHz, CD3OD) δ 4.95 (bs, 4H, OH), 4.27−4.15 (m, 5H,
H-2, H-6, H-7, H-8, H-9), 3.86 (d, A-part of AB system, J44′ = 11.8 Hz,
1H, H-4) 3.63 (dd, B-part of AB system, J44′ = 11.8 Hz, J45 = 2.2 Hz,
1H, H-4), 3.49 (bd, B-part of AB system, J22′ = 11.6 Hz, 1H, H-2′),
2.29 (bs, 1H, H-5), 2.16 (bs, 1H, H-1); 13C NMR (100 MHz,
CD3OD) δ 76.6, 74.8, 74.0, 70.6, 69.6, 66.9, 46.5, 43.2; IR (ATR) 3264,
3356, 2921, 2856, 1659, 1394, 1259, 1142, 1127, 1101, 1059, 970. Anal.
Calcd for C8H14O5: C, 50.52; H, 7.42. Found: C, 50.14; H, 7.34.
Ring-Opening Reaction of the Bisepoxide 9 in Acetic Anhy-
dride with Catalytic Amount of H2SO4. To a stirred solution of
bisepoxide 9 (2.0 g, 13 mmol) in 10 mL of acetic anhydride was added
4−5 drops of H2SO4, and then the mixture was stirred for 12 h at
room temperature. The reaction mixture was worked up as described
above. The residue was chromatographed on a silica gel column
eluting with hexane/EtOAc (3:1). The first fraction was the rearranged
product 27 (1.39 g, 39%). The second fraction was identified as the
epoxide ring-opening product 26 (1.60 g, 48%).
Reaction of the Monoepoxide 26 with H2SO4 in Acetic
Anhydride. To a stirred solution of monoepoxide 26 (1.0 g, 3.9
mmol) in 10 mL of acetic anhydride was added H2SO4 (1.5 mL), and
then the mixture was stirred for 12 h at room temperature. The
reaction mixture was worked up as described above. Chromatography
of the residue on silica gel (40 g) column eluting with hexane/EtOAc
(4:1) gave 1.2 g (86%) tetraactate 24.
Reaction of 27 with H2SO4 in Acetic Anhydride. To a stirred
solution of 27 (1.0 g, 3.9 mmol) in 10 mL of acetic anhydride was
added H2SO4 (1.5 mL), and then the mixture was stirred for 12 h at
room temperature. The reaction mixture was worked up as described
above. Chromatography of the residue on silica gel (40 g) column
eluting with hexane/EtOAc (4:1) gave 1.1 g (86%) tetraacetate 24.
ASSOCIATED CONTENT
■
S
* Supporting Information
NMR spectra (1H and 13C) for all new compounds and X-ray
structures and CIFs of 12 and 24. This material is available free
of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*abaran@sakarya.edu.tr, mbalci@metu.edu.tr
■
ACKNOWLEDGMENTS
■
We are indebted to the Scientific and Technological Research
Council of Turkey (TUBITAK, Grant Nos. 109T817and 108-
M-168), the Departments of Chemistry at Middle East
Technical University and Sakarya University, and the Turkish
Academy of Sciences (TUBA) for financial support of this
work.
REFERENCES
■
(1) (a) Billington, D. C. Chem. Soc. Rev. 1989, 18, 83−122.
(b) Legler, G. Adv. Carbohydr. Chem. Biochem. 1990, 48, 319−384.
(c) Balci, M.; Sutbeyaz, Y.; Secen, H. Tetrahedron 1990, 46, 3715−
3742. (d) Hudlicky, T.; Entwistle, D. A.; Pitzer, K. K.; Thorpe, A. J.
Chem. Rev. 1996, 96, 1195−1220. (e) Balci, M. Pure Appl. Chem. 1997,
69, 97−104. (f) Rudolf, M. T.; Li, W. H.; Wolfson, N.; Traynor-
Kaplan, A. E.; Schultz, C. J. Med. Chem. 1998, 41, 3635−3644.
(g) Maras, A.; Secen, H.; Sutbeyaz, Y.; Balci, M. J. Org. Chem. 1998,
63, 2039−2041. (h) Gultekin, M. S.; Celik, M.; Balci, M. Curr. Org.
Chem. 2004, 13, 1159−1186. (i) Busscher, G. F.; Rutjes, F. P. J. T.;
van Delft, F. L. Chem. Rev. 2005, 105, 775−791. (j) Arjona, O.;
Gomez, A. M.; Lopez, J. C.; Plumet, J. Chem. Rev. 2007, 107, 1919−
2036. (k) Mehta, G.; Talukdar, P.; Pullepu, V.; Pullepu, V.; Sen, S. Eur.
J. Org. Chem. 2009, 4691−4698. (l) Duchek, J.; Adams, D. R.;
Hudlicky, T. Chem. Rev. 2011, 111, 4223−4258.
rel-(((1S,2S,5R,6S)-5-Acetoxy-7-oxabicyclo[4.1.0]hept-3-en-
2-yl)methoxy)methyl acetate (27): 1H NMR (400 MHz, CDCl3) δ
5.57 (dt, J56 = 4.5 Hz, J54 = J53 = 2.1 Hz, 1H, H-5), 5.53 (ddt, A- part of
AB-system, J34 = 10.4 Hz, J31 = J35 = 2.1 Hz, and J32 = 4.7 Hz, 1H,
H-3), 5.46 (ddt, J43 = 10.4 Hz, J45 = 2.1 Hz, and J42 = J46 = 1.6 Hz, 1H,
H-4), 5.20 (d, A-part of AB-system, J92 = 6.3 Hz, 1H, H-9), 5.16 (d,
B-part of AB-system, J9′2 = 6.3 Hz, 1H, H-9′), 3.71 (dd, B-part of AB-
system, J77′ = 9.8 Hz and J72 = 9.8 Hz, 1H, H-7′), 3.52 (dd, B-part of
AB-system, J77′ = 9.8 Hz and J72 = 6.7 Hz, 1H, H-7), 3.47 (ddd, J65
4.2 Hz, J65 = 4.5 Hz, J62 = 2.2 Hz, 1H, H-6), 3.36 (dt, J16 = 4.2 Hz, J13
=
=
J1.2 = 2.1 Hz, 1H, H-1), 2.88 (m, 1H, H-2), 2.08 (s, 3H, CH3), 2.03
(s, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ 170.6, 170.4, 126.3, 124.1,
89.1, 70.5, 67.7, 53.1, 52.4, 36.4, 21.0, 20.96; IR (ATR) 2922, 1730, 1433,
1369, 1225, 1155, 1123, 1011, 939, 899, 866, 808, 772, 733. Anal. Calcd for
C12H16O6: C, 56.24; H, 6.29. Found: C, 56.27; H, 6.40.
(2) (a) Ferguson, M. A. J.; Williams, A. F. Annu. Rev. Biochem. 1988,
57, 285−320. (b) Thomas, J. R.; Dwek, R. A.; Rademacher, T. W.
Biochemistry 1990, 29, 5413−5422. (c) Varki, A. Glycobiology 1993, 3,
97−130. (d) Dwek, A. Chem. Rev. 1996, 96, 683−720. (e) Hinchliffe,
K.; Irvine, R. Nature 1997, 390, 123−124. (f) Ogawa, S. In
Carbohydrate Mimics: Concept and Methods; Chapleur, Y., Ed.; Wiley-
VCH: Weinheim, Germany, 1998; p 87. (g) Schultz, C.; Rudolf, M. T.;
Gillandt, H. H.; Traynor-Kaplan, A. E. Phosphoinositides: Chemistry,
Biochemistry and Biomedical Applications. Am. Chem. Soc. Symp. Ser.
Bruzik, K. S., Ed. 1999; 718, 232−243. (h) Heightman, T. D.; Vasella,
A. T. Angew. Chem., Int. Ed. 1999, 38, 750−770. (i) Asano, N.
Glycobiology 2003, 13, 93R−104R. (j) Irvine, R. F. Nat. Rev. Mol. Cell
Biol. 2003, 4, 586−590. (k) Guo, Z.; Bishop, L. Eur. J. Org. Chem.
2004, 3585−3596. (l) Michell, R. H. Biochem. Soc. Symp. 2007, 74,
223−246. (m) York, J. D.; Lew, D. J. Nat. Chem. Biol. 2008, 4, 16−17.
(n) Chenette, E. J. Nat. Rev. Mol. Cell Biol. 2009, 10, 238−239.
(3) (a) Estevez, V. A.; Prestwich, G. D. J. Am. Chem. Soc. 1991, 113,
9885−9887. (b) Kozikowski, A. P.; Powis, G.; Gallegos, A.;
rel-(1aS,2R,3S,3aR,6aS,6bS)-Octahydrooxireno[2,3-e]-
isobenzofuran-2,3-diyl diacetate (26): 1H NMR (400 MHz,
CDCl3) δ 5.41 (dd, A-part of AB system, J23 = 9.6 and J21a = 1.3 Hz,
1H, H-2), 5.37 (dd, B-part of AB system J32 = 9.6 and J33a = 5.0 Hz,
1H, H-3), 3.90 (dd, A-part of AB system, J44′ = 9.7 and J43a = 6.7 Hz,
1H, H-4 or H-4′), 3.85 (d, J66a = 4.7 Hz, 2H, H-6), 3.70 (dd, B-part of
AB system J44′ = 9.7 and J4′3a = 8.3 Hz, 1H, H-4 or H-4′), 3.39 (dt,
J1a6b = 4.1 and J1a2 = 1.3 Hz, 1H, H-1a), 3.13 (bd, J1a6b = 4.1 Hz, 1H, H-6b),
2.92 (dt, J6a3a = 8.3 and J6a6 = J6a6′ = 4.7 Hz, 1H, H-6a), 2.75−2.85 (m,
1H, H-3a), 2.07, (s, 3H, COCH3), 1.97 (s, 3H, COCH3); 13C NMR
(100 MHz, CDCl3) δ 170.9, 170.2, 71.8, 69.3, 69.2, 68.5, 56.9, 54.8,
41.0, 38.6, 21.13, 21.1; IR (ATR) 2958, 2883, 2856, 1735, 1479, 1440,
1367, 1226, 1097, 1064, 1039, 1020, 985, 921, 910, 893, 831, 798.
Anal. Calcd for C12H16O6: C, 56.24; H, 6.29. Found: C, 55.92; H, 6.35.
Tuckmantel, W. Bioorg. Med. Chem. Lett. 1993, 3, 1323−1326.
̈
1249
dx.doi.org/10.1021/jo202494v | J. Org. Chem. 2012, 77, 1244−1250

The Journal of Organic Chemistry
Featured Article
(c) Martin-Lomas, M. Tetrahedron Lett. 1994, 35, 2969−2972.
(d) Kiddle, J. J. Chem. Rev. 1995, 95, 2189−2202. (e) Gigg, J.; Gigg,
R. Carbohydr. Res. 1997, 299, 77−83. (f) Riley, A. M.; Jenkins, D. J.;
Potter, B. V. L Carbohydr. Res. 1998, 314, 277−281. (g) Husson, C.;
́
Odier, L.; Vottero, P. J. A. Carbohydr. Res. 1998, 307, 163−165.
(h) Liu, C.; Riley, A. M.; Yang, X.; Shears, S. B.; Potter, B. V. L J. Med.
Chem. 2001, 44, 2984−2989. (i) Kubiak, R. J.; Bruzik, K. S. J. Org.
Chem. 2003, 68, 960−968. (j) Bello, D.; Aslam, T.; Bultynck, G.;
Slawin, A. M. Z.; Roderick, H. L.; Bootman, M. D.; Conway, S. J.
J. Org. Chem. 2007, 72, 5647−5659. (k) Murali, C.; Gurale, B. P.;
Shashidhar, M. S. Eur. J. Org. Chem. 2010, 755−764.
(4) (a) Guidot, J. P.; Le Gall, T.; Mioskowski, C. Tetrahedron Lett.
1994, 35, 6671−6672. (b) Jenkin, D. J.; Potter, B. V. L J. Chem. Soc.,
Perkin Trans. 1 1998, 41−50. (c) Chen, J.; Feng, L.; Prestwich, G. D.
J. Org. Chem. 1998, 63, 6511−6522. (d) Clive, D. L. J.; He, X.;
Poslema, M. H. D.; Mashimbye, M. J. J. Org. Chem. 1999, 64, 4397−
4410. (e) Suzuki, T.; Suzuki, S. T.; Yamada, I.; Koashi, Y.; Yamada, K.;
Chida, N. J. Org. Chem. 2002, 67, 2874−2880.
(5) (a) Hudlicky, T. Chem. Rev. 1996, 96, 3−30. (b) Desjardins, M.;
Brammer, L. E. Jr.; Hudlicky, T. Carbohydr. Res. 1997, 304, 39−42.
(c) Jung, P. M. J.; Motherwell, W. B.; Williams, A. S. Chem. Commun.
1997, 1283−1284. (d) Nguyen, B. V.; York, C.; Hudlicky, T.
Tetrahedron 1997, 53, 8807−8814. (e) Paul, B. J.; Willis, J.; Martinot,
T. A.; Ghiviriga, I.; Abboud, K. A.; Hudlicky, T. J. Am. Chem. Soc.
2002, 124, 10416−10426. (f) Freeman, S.; Hudlicky, T. Bioorg. Med.
Chem. Lett. 2004, 14, 1209−1212. (g) Pilgrim, S.; Kociok-Kohn, G.;
̈
Lloyd, M. D.; Lewis, S. E. Chem. Commun. 2011, 47, 4799−4801.
(6) (a) Sawada, T.; Shirai, R.; Iwasaki, S. Tetrahedron Lett. 1996, 37,
885−886. (b) Reddy, K. K.; Ye, J.; Falck, J. R.; Capdevila, J. H. Bioorg.
Med. Chem. Lett. 1997, 7, 2115−2116. (c) Colobert, F.; Tito, A.; Khiar,
N.; Denni, D.; Medina, M. A.; Martín-Lomas, M.; Ruano, J.-L. G.;
Solladie, G. J. Org. Chem. 1998, 63, 8918−8921.
(7) Angyal, S. J.; Odier, L.; Tate, M. E. Carbohydr. Res. 1995, 266,
143−146.
(8) Kim, K. S.; Park, J. I.; Moon, H. K.; Yi, H. Chem. Commun. 1998,
1945−1946.
(9) (a) Salamci, E. Tetrahedron 2010, 66, 4010−4015. (b) Mehta, G.;
Senaiar, R. S.; Bera, M. K. Chem.Eur. J. 2003, 9, 2264−2272.
(c) Mehta, G.; Narinder, M. Tetrahedron Lett. 1999, 40, 5791−5794.
(d) Mehta, G.; Reddy, D. S. Tetrahedron Lett. 1999, 40, 9137−9140.
(e) Sengul, M. E.; Menzek, A.; Saracoglu, N. J. Chem. Res. 2005, 382−
384. (f) Mehta, G.; Mohal, N.; Lakshminath, S. Tetrahedron Lett. 2000,
41, 3505−3508. (g) Forman, M. A.; Dailey, W. P. J. Org. Chem. 1993,
58, 1501−1507. (h) Mehta, G.; Ramesh, S. S. Chem. Commun. 2000,
2429−2430. (i) Kara, Y.; Balci, M. Tetrahedron 2003, 59, 2063−2066.
(10) Baran, A.; Gunel, A.; Balci, M. J. Org. Chem. 2008, 73, 4371−
̈
4375.
(11) Baran, A.; Balci, M. J. Org. Chem. 2009, 74, 88−95.
(12) Balci, M. Chem. Rev. 1981, 81, 91−108.
(13) (a) Balci, M.; Sutbeyaz, Y. Tetrahedron Lett. 1983, 24, 311−315.
̈
(b) Balci, M.; Sutbeyaz, Y. Tetrahedron Lett. 1983, 24, 4135−4138.
̈
(c) Balci, M.; Akbulut, N. Tetrahedron 1985, 41, 1315−1322.
(d) Sutbeyaz, Y.; Secen, H.; Balci, M. J. Org. Chem. 1988, 53,
̈
2312−2317.
(14) (a) Gong, W. Z.; Wang, B.; Gu, Y. L.; Yan, L.; Yang, L. M.; Suo, J. S.
Chin. Chem. Lett. 2005, 16, 747−750. (b) Wang, B.; Gu, Y.; Gong, W.;
Kang, Y.; Yang, L.; Suo, J. Tetrahedron Lett. 2004, 45, 6599−6602.
(15) Kimatrai, M.; Cruz-Lopez, O.; Garcia-Rubino, M. E.; Morales, F.;
Gomez-Perez, V.; Campos, J. M. Curr. Org. Chem. 2010, 14, 1461−
1477.
(16) For similar ring-closure reactions, see: (a) Blomquist, A. T.;
Wolinsky, J. J. Am. Chem. Soc. 1957, 79, 6025−6030. (b) Stapp, P. R.;
Randall, J. C. J. Org. Chem. 1970, 35, 2948−2955. (c) Bucci, P.; Lippi,
G.; Macchia, B. J. Org. Chem. 1970, 35, 913−916.
1250
dx.doi.org/10.1021/jo202494v | J. Org. Chem. 2012, 77, 1244−1250