Generation of Molecular Complexity from Cyclooctatetraene: Preparation of Aminobicyclo[5.1.0]octitols

Article abstract of DOI:10.1002/chem.201501274

A series of eight stereoisomeric N-(tetrahydroxy bicyclo-[5.1.0]oct-2S-yl)phthalimides were prepared in one to four steps from N-(bicyclo[5.1.0]octa-3,5-dien-2-yl)phthalimide (±)-7, which is readily available from cyclooctatetraene (62% yield). The structural assignments of the stereoisomers were established by ¹H NMR spectral data as well as X-ray crystal structures for certain members. The outcomes of several epoxydiol hydrolyses, particularly ring contraction and enlargement, are of note. The isomeric phthalimides as well as the free amines did not exhibit β-glucosidase inhibitory activity at a concentration of less than 100 μM. Ringing the changes: A spectrum of stereoisomeric protected aminobicyclo[5.1.0]octitols were prepared from the simple hydrocarbon cyclooctatetraene in 6-9 steps (see figure). Whereas certain hydrolyses of epoxydiols proceeded to form tetraols, others resulted in either ring-expanded or ring- contracted structures.

Full text of DOI:10.1002/chem.201501274

DOI: 10.1002/chem.201501274
Full Paper
&
Cyclitols
Generation of Molecular Complexity from Cyclooctatetraene:
Preparation of Aminobicyclo[5.1.0]octitols
Mohamed F. El-Mansy,[a] Matthew Flister,[a] Sergey Lindeman,[a] Kelsey Kalous,[b]
Daniel S. Sem,[b] and William A. Donaldson*[a]
Abstract: A series of eight stereoisomeric N-(tetrahydroxy
bicyclo-[5.1.0]oct-2S*-yl)phthalimides were prepared in one
to four steps from N-(bicyclo[5.1.0]octa-3,5-dien-2-yl)phthal-
imide (Æ)-7, which is readily available from cyclooctatetraene
(62% yield). The structural assignments of the stereoisomers
crystal structures for certain members. The outcomes of
several epoxydiol hydrolyses, particularly ring contraction
and enlargement, are of note. The isomeric phthalimides as
well as the free amines did not exhibit b-glucosidase
inhibitory activity at a concentration of less than 100 mm.
1
were established by H NMR spectral data as well as X-ray
Introduction
Polyhydroxyl aminocyclohexanes (aminocyclitols) are present
as aglycon units in numerous aminoglycoside antibiotics, and
certain of these compounds possess glycosidase inhibitory
activity.[1] A ring-expanded aminocycloheptitol 1 (Figure 1) has
been isolated from the roots of Physalis alkekengi var. franch-
eti;[2] similar structures (À)-2 and (+)-3 are a-d-glucosidase
inhibitors in the low micromolar range.[3,4] There are relatively
few bicyclic aminocyclitiols known. The aminobicyclo[4.1.0]-
heptitols 4a and (+)-4b were designed to mimic the half-chair
conformation of the oxacarbenium ion intermediate in glyco-
lytic bond cleavage. Compound 4a inhibits yeast a-glycosidase
(Ki =0.107Æ0.015 mm), whereas the corresponding acetamido
4b is relatively inactive against this enzyme.[5] Balci and
co-workers have reported the preparation of an amino
bicyclo[4.2.0]octitol (Æ)-5.[6] As part of our continued interest in
the use of the simple hydrocarbon cyclooctatetraene for
the synthesis of complex molecules,[7,8] we herein report on
the preparation of a series of eight protected amino bicyclo-
[5.1.0]octitiols 6.
Figure 1. Representative polyhydroxy aminocycloheptanes and polyhydroxy
aminobicyclo[n.m.0]alkanes.
Scheme 1. Preparation of N-(bicyclo[5.1.0]octa-3,5-dien-2-yl)phthalimide 7
(TMANO=trimethylamine N-oxide).
N-(Bicyclo[5.1.0]hepta-3,5-dien-1-yl)phthalimide (Æ)-7 was
prepared from cyclooctatetraene in five steps and in 62% yield
using
a slight modification to the literature procedure
(Scheme 1).[8b] The use of 2,3-dichloro-5,6-dicyanoquinone
(DDQ) instead of ceric ammonium nitrate (CAN) in the oxida-
tive decomplexation step was found to give superior yields.
Results and Discussion
The treatment of (Æ)-7 with singlet oxygen gave (Æ)-8 as
a single diastereomer (Scheme 2). The relative stereochemistry
of 8 was tentatively assigned on the basis of that previously
observed for the products of 7 with arylnitroso dienophiles.[9]
This tentative assignment was eventually corroborated on the
basis of further reactions. Reduction of 8 with zinc in acetic
acid gave the enediol (Æ)-9. Alternatively, the Kornblum–De-
LaMare rearrangement[10,11] of 8 with triethylamine gave a sepa-
rable mixture of two regioisomeric enones (the bicyclic enone
(Æ)-10 predominantly in 95% yield). Reduction of 10 under
[a] Dr. M. F. El-Mansy, M. Flister, Dr. S. Lindeman, Prof. W. A. Donaldson
Department of Chemistry, Marquette University
P. O. Box 1881 Marquette University, Milwaukee, WI 53201-1881 (USA)
E-mail: William.donaldson@marquette.edu
[b] K. Kalous, Prof. D. S. Sem
School of Pharmacy, Concordia University Wisconsin
Mequon, WI 53097 (USA)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201500274.
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coupling between H-2 and H-3 (Jꢀ11–12 Hz) indicated that
these two protons have a diaxial orientation.
Catalytic dihydroxylation of bicyclic diene (Æ)-7 using one
equivalent of N-methylmorpholine N-oxide (NMO) gave a sepa-
rable mixture of two regioisomeric enediols (Æ)-16 and (Æ)-17
(Scheme 3). The major product arises from dihydroxylation on
the olefin more remote to the electron-withdrawing phthali-
mide substituent at C-2. The structures of 16 and 17 were ten-
1
tatively assigned on the basis of their H NMR spectral data. In
particular, the chemical shift for H-2 of 16 (d=5.68 ppm) com-
pared with that for H-2 of 17 (d=5.25 ppm) is indicative of the
proximity of the double bond to H-2 in 16. Additionally,
a large coupling between H-2 and H-3 of 17 (J=10.6 Hz) is in-
dicative of a diaxial relationship of these protons. Epoxidation
of 16 with trifluoroperacetic acid gave a single epoxydiol (Æ)-
18. The relative stereochemistries of 16 and 18 were tentative-
ly assigned on the basis of the stereochemistries we previously
observed for the dihydroxylation of N-(2,4-cyclohexadien-1-
yl)phthalimide and the epoxidation of this enediol (see inset
Scheme 3), both of which were established by X-ray diffraction
analysis.[13] The tentative stereochemical assignments of 16
and 17 were eventually corroborated by X-ray diffraction
Scheme 2. Oxidation of N-(bicyclo[5.1.0]octa-3,5-dien-2-yl)phthalimide.
Reagents: a) 1O2, hn (sunlamp), TPP; b) Zn/HOAc; c) NEt3; d) NaBH4, CeCl3,
MeOH; e) mCPBA (2 equiv); f) hn (Hg vapor), C6H6; g) CF3CO3H.
Luche conditions gave a unique endiol (Æ)-11. The C2ÀC3 rela-
tive stereochemistry of 9, 10, and 11 were each assigned on
1
the basis of their H NMR spectral data; in particular, a large
coupling between H-2 and H-3 (Jꢀ10 Hz) is indicative of a
diaxial relationship of these protons.
The treatment of 7 with two equivalents of m-chloroperoxy-
benzoic acid gave bisepoxide (Æ)-12. This same compound
was obtained, albeit in lower overall yield, by photolysis of 8
with a medium pressure Hg vapor lamp. Epoxidation of 8 with
trifluoroperacetic acid (generated by reaction of trifluoroacetic
anhydride with hydrogen peroxide) gave the epoxy endo-
peroxide (Æ)-13. The relative stereochemistry of 12 and 13 was
established by using single-crystal X-ray diffraction analysis.[12]
Reduction of 13 with zinc and acetic acid gave the epoxydiol
(Æ)-14. The relative stereochemical assignment for 14 was
based on the assigned structure of 13, and the fact that endo-
peroxide reduction takes place with retention of configuration
at the CÀO bonds. Epoxidation of the enediol 9 with trifluoro-
peracetic acid gave epoxydiol (Æ)-15, whose structure was
tentatively assigned because the stereochemical assignment
indicated that it was unique from that of the diastereomeric
epoxydiol 14. This tentative stereochemical assignment was
eventually corroborated by single-crystal X-ray diffraction
analysis (Figure 2). Notably, for both 14 and 15, a large
Scheme 3. Oxidative functionalization of N-(bicyclo[5.1.0]octa-3,5-dien-2-
yl)phthalimide and precedent for stereochemical assignments.[13] Reagents:
a) OsO4 (cat.)/NMO (1 equiv); b) (CF3CO)2O, H2O2; c) mCPBA (1 equiv).
analysis of the tetraols derived from exhaustive hydroxylation
of 7 (see below).
Epoxidation of 7 with one equivalent of mCPBA gave a sepa-
rable mixture of monoepoxide (Æ)-19 and enone (Æ)-20
(Scheme 4). The structural assignment for 19 was established
by single-crystal X-ray diffraction analysis,[12] whereas the struc-
tural assignment for 20 is based on its NMR spectral data. In
particular, the presence of signals at d=198.9, 141.9, and ap-
proximately 123.8 ppm in the 13C NMR spectrum of 20 are con-
sistent with a a,b-unsaturated ketone. Additionally, signals at
1
d=2.95 and 3.11 ppm (Jgem =15.2 Hz) in the H NMR spectrum
and a CH2 signal at d=41.5 ppm in the distortionless enhance-
ment by polarization transfer (DEPT) NMR spectrum of 20 are
indicative of a diastereotopic set of geminal protons adjacent
to a carbonyl group and the carbon to which they are at-
tached. Because the relative ratio of 19 to 20 depended on
the quality of the meta-chloroperbenzoic acid (mCPBA) used as
well as on reaction time and time of exposure of the reaction
mixture to silica gel, we propose that enone 20 arises from 19
Figure 2. Structure of (Æ)-15 (arbitrary atomic numbering).
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by acid-promoted rearrangement. Thus, protonation of the ep-
oxide in 19 followed by regioselective cleavage of the CÀO
bond adjacent to the cyclopropane ring leads to carbocation
21. Hydride migration affords the protonated enone 22, which
upon deprotonation affords 20. This type of epoxide-to-ketone
rearrangement is reminiscent of the “NIH-shift” for enzymatic
hydroxylation of arenes.[14] Dihydroxylation of 19 gave a single
Figure 4. Structure of (Æ)-25·2H2O (arbitrary atomic numbering).
17 was subjected to dihydroxylation gave a mixture of 25/24
in the same ratio. Dihydroxylation of enediol 9 gave a single
tetraol (Æ)-26, whereas a similar reaction of 11 gave a separable
mixture of (Æ)-27 and (Æ)-28. The structures of polyols 24, 25,
26, 27, and 28 were tentatively assigned on the basis of their
1H NMR spectral data (see below) and the fact that dihydroxy-
Scheme 4. Oxidative functionalization of N-(bicyclo[5.1.0]octa-3,5-dien-2-
yl)phthalimide. Reagents: a) mCPBA (1 equiv); b) OsO4 (cat.)/NMO (1 equiv).
epoxydiol (Æ)-23, whose structure was established by single-
crystal X-ray diffraction analysis.[12]
As we have previously reported,[8b] osmium-catalyzed
hydroxylation of 7 with excess NMO as a reoxidant gave a sepa-
rable mixture of two tetraols (Æ)-24 and (Æ)-25 (Scheme 5).
The structures of 24 and 25 were tentatively assigned on the
1
basis of their H NMR spectral data (see below); these tentative
Scheme 5. Preparation of aminopolyols by dihydroxylation. Reagents:
a) OsO4 (cat.)/NMO (2 equiv); b) OsO4 (cat.)/NMO (1 equiv).
lation occurs in a syn-fashion; the spectral analysis of the
bicyclic tetraols will be discussed separately.
Hydrolysis of epoxydiols 18 or 23 using CBr4/THF/H2O[16]
gave a single tetraol (Æ)-29 or (Æ)-27, respectively (Scheme 6).
In contrast, hydrolysis of bisepoxide 12 gave a separable
mixture of bicyclic tetraol (Æ)-30 and the cyclooctene tetraol
(Æ)-31. Hydrolysis of the epoxydiol 14 gave the tetraol (Æ)-32.
In contrast, reaction of the diastereomeric epoxydiol 15 gave
a unique aldehyde (Æ)-33. The structures of the epoxide
hydrolysis products were tentatively assigned on the basis of
their NMR spectral data; the spectral analysis of the bicyclic
tetraols 29, 30, and 32 will be discussed in a separate
paragraph. The tentative structural assignment for 32 was
eventually corroborated by using single-crystal X-ray diffraction
analysis (Figure 5).[12]
Figure 3. Structure of (Æ)-24 (arbitrary atomic numbering).
assignments were eventually corroborated by single-crystal
X-ray diffraction analysis (Figure 3 and Figure 4).[12]
Furthermore, the unambiguous identification of the struc-
tures of 24 and 25 bolstered the stereochemical assignments
for 17 and 16. Presumably, the introduction of two pairs of
hydroxyl groups to 7 occurs in a stepwise fashion, and thus
tetraol 24 arises through dihydroxylation of 17 on face of the
olefin opposite to the C-4 hydroxyl group, according to the
Kishi model for stereoselectivity.[15] Alternatively, tetraol 25
arises from dihydroxylation of 16; however, in this case the hy-
droxyl groups are introduced anti to the phthalimide group at
C-2. Notably, a separate experiment in which a mixture of 16/
1
For cyclooctene 31, vicinally coupled signals in its H NMR
spectrum at d=5.74 and 5.81 ppm (Jcis =10.8 Hz) and geminal-
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1H NMR spectrum, and signals at d=194.0, 148.0, and
144.6 ppm in its 13C NMR spectrum are indicative of the 2,3-dis-
ubstituted enal functionality present. In addition, the relatively
large coupling between H-4 and H-5 (J=9.8 Hz) is consistent
with these two protons having a trans-diaxial relationship. The
Figure 7. Structure of (Æ)-33 (arbitrary atomic numbering).
tentative structure for 33 was eventually corroborated by
using single-crystal X-ray diffraction analysis (Figure 7).[12]
The structural assignments for many of the diastereomeric
1
Scheme 6. Preparation of aminopolyols by epoxide hydrolysis. Reagents:
a) THF/H2O/CBr4.
polyhydroxyl bicyclo[5.1.0]octanes are based on their H NMR
spectral data. The carbon skeleton present in these com-
pounds adopts an expanded chair-like conformer, with the cy-
clopropane ring acting similar to a methylene group in a cyclo-
hexane ring and the phthalimide substituent at C-2 occupying
an equatorial orientation; this can be observed in the crystal
structures of 24, 25, and 32. For this reason, it is possible to
utilize the Karplus relationship between the coupling constant
and dihedral angle of coupled protons.[17] In particular, for the
six diastereomers in which the C-2 phthalimide and the C-3 hy-
droxyl are trans (i.e., diequatorial; 24, 25, 26, 27, 28, and 32),
the coupling between H-2 and H-3 is relatively large (J
ꢀ11 Hz). Conversely, for the two diastereomers in which the C-
2 phthalimide and C-3 hydroxyl are cis (29 and 30), the cou-
pling between H-2 and H-3 is considerably smaller (2.2 Hz). In
addition, for the diastereomers in which the C-3 and C-4 hy-
droxyl groups are diequatorial (26, 28, and 32), the coupling
between H-3 and H-4 is relatively large (ꢀ10 Hz), whereas for
those diastereomers in which the C-3 hydroxyl is equatorial
and the C-4 hydroxyl is axial (24, 25, and 27) the coupling be-
tween H-3 and H-4 is considerably smaller (ꢀ0–2 Hz). For
those diastereomers in which the C-5 and C-6 hydroxyl groups
are diequatorial (27 and 30), or the C-4 and C-5 hydroxyls are
diequatorial (32), the coupling between the protons on these
carbons is relatively large (ꢀ9 Hz). In addition, the relative ste-
reochemistry of certain adjacent hydroxyl groups was assigned
on the basis of the known syn relationship engendered by
osmium-catalyzed dihydroxylation and the known anti
relationship engendered by epoxide hydrolysis under these
conditions.
Figure 5. Structure of (Æ)-32·CH3OH (arbitrary atomic numbering).
ly coupled signals at d=2.31 and 2.89 ppm (Jgem =12.4 Hz) are
consistent with the cis olefinic functionality and adjacent
methylene group, respectively. The stereochemistry of the four
hydroxyl substituents relative to the phthalimide group in (Æ)-
31 was eventually assigned on the basis of the single-crystal
X-ray diffraction analysis (Figure 6).[12]
For 2-formylbicyclo[4.1.0]hept-2-ene (33),
a singlet and
narrow doublet at d=9.54 and 6.52 ppm, respectively, in its
The outcome of the epoxide hydrolyses deserves comment.
The hydrolysis of epoxydiol 18 to give 29 proceeds through
selective cleavage of the C3ÀO bond. The resulting trans-
diaxial orientation of the C3 and C4 hydroxyl groups can be ra-
tionalized on the basis of the Furst–Plattner rule for ring
opening through a chair-like transition state.[18] In contrast,
hydrolysis of epoxydiol 23 proceeds through cleavage of the
Figure 6. Structure of (Æ)-31 (arbitrary atomic numbering).
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C6ÀO bond to generate a trans-diequatorial relationship. This
selective cleavage is the result of a greater stabilization of the
partial positive charge on the protonated form of the epoxy-
diol at C-6 because of the stabilizing influence of the adjacent
cyclopropane ring.[19]
The hydrolysis of bisepoxide 12 yields two products. It is
proposed that the bicyclo[5.1.0]octanetetraol 30 arises through
initial opening of the C3-C4 oxirane ring in a diaxial fashion to
generate the C3 diastereomer of 23; subsequent epoxide
opening of the C5-C6 oxirane occurs at the C6ÀO bond similar
to 23. We propose that the cyclooctene product 31 is the
product of initial protonation at the C5ÀC6 oxirane (34,
Scheme 7). A number of possible routes may be envisioned
(Scheme 7): 1) a cyclopropyl to butenyl carbocation rearrange-
ment to generate 35, followed by a facially selective reaction
with water to afford 36; or 2) an SN2’-type opening in which
attack of a molecule of water at C1 of the protonated epoxide
cleaves both the cyclopropane ring and the epoxide ring to di-
rectly generate 36; or 3) an intramolecular attack of one of the
phthalimide oxygens at C1 of the cyclopropane with concomi-
tant opening of both three-membered rings to generate 38,
followed by addition of water to give the hydroxyisoindolinone
39, which can collapse to 37.[20] We favor the latter mechanism
(3) for a number of reasons. It seems unlikely that a “free” car-
bocation such as 35 would lead to a stereoselective outcome.
In fact, attempts to computationally model the protonated bi-
sepoxide 34 using B3LYP/6-311+G(d,p) instead resulted in 38
as a minimized structure. Addition of explicit water to the opti-
mization of protonated 34 did result in a minimized structure,
in which the distance between the C1 cyclopropane carbon
and the phthalimide oxygen was 3.2 Š. This structure also
revealed that approach of an external water molecule (i.e.,
pathway 2) would be significantly hindered by the phthalimide
substituent.
Scheme 7. Intramolecular participation of the phthalimide oxygen in ring
opening of 12 to afford cyclooctene 31.
Scheme 8. Proposed mechanism for ring contraction of 15.
Finally, the ring-contracted aldehyde 33, formed from expo-
sure of 15 to the standard hydrolysis conditions, arises because
of a concerted 1,2-shift of C7 to C5 with concomitant opening
of the protonated epoxide ring (Scheme 8).[21] Deprotonation
of the resultant oxocarbenium ion 40, followed by dehydration
gives 33. We rationalize the divergent reaction pathways for
diastereomeric epoxydiols 14 and 15 on the basis of stereo-
electronic control. As can be seen in the crystal structure for
15 (Figure 2), the bond that shifts is aligned nearly antiperipla-
nar with the C5ÀO bond. This alignment would not be present
in diastereomer 14, which undergoes a more classical epoxide
ring opening.
ever, separation of these compounds from the byproduct 2,3-
dihydro-1,4-phthalazinedione 41 eluded attempts in our hands
with normal and reversed-phase chromatography. Nonetheless,
the inhibitory activity of 24–29, 30, 32, and the mixtures of
amine diastereomers 6 and 41 against b-glucosidase was
Deprotection of the phthalimide group proved to be chal-
lenging. The attempted acid hydrolysis of the phthalimide
group leads to products in which the cyclopropane ring is no
1
longer intact, as evidenced by H NMR spectroscopy. The exact
nature of these ring-opened products was not established. Use
of anion exchange resins,[22] partial reduction with NaBH4 in
acidic medium followed by heating at reflux,[23] or treatment
with n-butylamine[24] or methylamine[25] similarly led to com-
plex mixtures of unidentified products. Ultimately, cleavage of
the phthalimide groups of 24–29, 30, and 32 with hydrazine
[Eq. (1)] proceeded to give the corresponding amines 6; how-
evaluated.[26] In all cases we observed no inhibition at
concentrations of less than 100 mm.
Conclusion
Eight racemic stereoisomeric N-(tetrahydroxybicyclo-[5.1.0]oct-
2S*-yl)phthalimides 24–29, 30, and 32, have been prepared
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4.2 Hz, 1H), 3.31 (dd, J=2.4, 4.4 Hz, 1H), 1.46 (tt, J=6.0, 9.6 Hz,
1H; H-9), 1.29 (td, J=4.0, 6.0 Hz, 1H; H-10’), 1.05–1.12 ppm (m,
2H; H-1, H-10); 13C NMR (100 MHz, CDCl3): d=168.1 (C=O), 134.4,
132.1, 123.6, 58.5, 53.7, 52.2, 51.2, 47.6, 19.9, 11.3, 11.1 ppm; ele-
mental analysis calcd (%) for C16H13NO4: C 67.84; H 4.62; found: C
67.44; H 4.68. The same bisepoxide could be generated by irradia-
tion of a solution of (Æ)-8 in benzene with a medium-pressure Hg
lamp (67%).
from
N-(bicyclo[5.1.0]octa-3,5-dien-2-yl)phthalimide
(Æ)-7,
which is itself prepared from cyclooctatetraene. The structural
assignments for these stereoisomers was established by using
3JHÀH coupling values and corroborated for 24, 25, and 32 by
using X-ray diffraction analysis. Certain epoxydiol hydrolyses
resulted in ring-expanded or ring-contracted products. Hydrazi-
nolysis of the phthalimide group led to the corresponding
amines, which were inseparable from the 2,3-dihydro-1,4-
phthalazinedione byproduct. Neither the phthalimides nor the
free amines exhibited b-glucosidase inhibitory activity at
concentrations of less than 100 mm.
N-(3R*,6R*-Dihydroxybicyclo[5.1.0]oct-4-en-2R*-yl)phthalimide
(Æ)-9: Activated zinc dust (250 mg) was added to a solution of en-
doperoxide (Æ)-8 (250 mg, 0.880 mmol) in CH2Cl2 (20 mL), followed
by dropwise addition of
a solution of acetic acid (537 mg,
8.803 mmol) in CH2Cl2 (2 mL) over a 10 min period. The reaction
mixture was stirred for 2 h at 08C, and then filtered through
a Celite column. The column was then washed with methanol. The
fractions collected were allowed to slowly evaporate under atmos-
pheric pressure, and the residue was purified by column chroma-
tography (SiO2, hexanes/ethyl acetate=1:4) to give (Æ)-9 (249 mg,
98%) as colorless crystals. M.p.=217–2198C; 1H NMR (600 MHz,
CD3OD): d=7.90–7.79 (m, 4H; Phth), 5.82 (ddd, J=2.1, 6.3, 12.0 Hz,
1H; H-5), 5.62 (ddd, J=1.2, 3.6, 12.0 Hz, 1H; H-4), 4.78 (td, J=3.0,
10.8 Hz, 1H; H-3), 4.66 (dd, J=4.2, 10.8 Hz, 1H; H-2), 4.47 (dt, J=
1.5, 5.8 Hz, 1H; H-6), 1.35 (tt, J=5.7, 9.0 Hz, 1H; H-7), 1.21 (ddt, J=
4.5, 6.3, 9.0 Hz, 1H; H-1), 0.95 (q, J=5.8 Hz, 1H; H-8endo),
0.81 ppm (dt, J=5.4, 9.0 Hz, 1H; H-8exo); 13C NMR (100 MHz,
CD3OD): d=170.3 (C=O), 135.4, 134.0, 133.5, 133.3, 124.1, 70.6,
67.2, 53.5, 23.2, 17.1, 9.2 ppm. HRMS (FAB): m/z calcd for
C16H15NO4 +Na+: 308.0893 [M+Na+]; found: 308.0895.
Experimental Section
General methods
All reactions involving moisture or air-sensitive reagents were car-
ried out under a nitrogen atmosphere in oven-dried glassware
with anhydrous solvents. THF and diethyl ether were distilled from
sodium/benzophenone. Purifications by flash chromatography
were carried out using silica gel (32–63 m). NMR spectra were re-
corded on either a Varian Mercury+ 300 MHz or a Varian UnityIno-
va 400 MHz instrument. CDCl3, CD3OD, [D6]DMSO, and [D6]acetone
were purchased from Cambridge Isotope Laboratories. 1H NMR
spectra were calibrated to d=7.27 ppm for residual CHCl3,
3.31 ppm for CD2HOD, 2.50 ppm for [D5]DMSO, or 2.05 ppm for
[D5]acetone. 13C NMR spectra were calibrated from the central peak
at d=77.23 ppm for CDCl3, 49.15 ppm for CD3OD, 39.52 ppm for
[D5]DMSO, or 29.92 ppm for [D6]acetone. Coupling constants are
reported in Hz.
N-(3R*-Hydroxy-6-oxo-bicyclo[5.1.0]oct-4-en-2R*-yl)phthalimide
(Æ)-10 and N-(6S*-Hydroxy-3-oxo-bicyclo[5.1.0]oct-4-en-2R*-
yl)phthalimide: A solution of Et3N (0.25 mL, 1.761 mmol) in CH2Cl2
(5 mL) was added to a solution of endoperoxide (Æ)-8 (250 mg,
0.880 mmol) in freshly distilled CH2Cl2 (15 mL) at 08C. The reaction
mixture was stirred at 08C for 2 h, the solvent evaporated, and the
residue was purified by column chromatography (SiO2, CH2Cl2) to
give (Æ)-10 (238 mg, 95%) followed by (Æ)-N-(6S*-Hydroxy-3-oxo-
bicyclo[5.1.0]oct-4-en-2R*-yl)phthalimide (5 mg, 2%), both as color-
Syntheses
5-Phthalimido-7,8-dioxatricyclo[4.2.2.02,4]dec-9-ene (Æ)-8: Tetra-
phenylporphorine (TPP) (9 mg, 0.139 mmol) was added to a solu-
tion of diene (Æ)-7 (350 mg, 1.394 mmol) in CHCl3 (20 mL). The
deep-purple solution was irradiated with a 100 W halogen lamp,
while ultra-pure O2 was bubbled through the solution and stirred
in an ice bath for 6 h. The reaction mixture was concentrated, and
the residue was purified by column chromatography (SiO2, hex-
anes/ethyl acetate=2:3) to give (Æ)-8 (286 mg, 72%) as a colorless
solid. M.p.=159–1628C; 1H NMR (400 MHz, CDCl3): d=7.70–7.90
(m, 4H; Phth), 6.55 (dd, J=8.2, 8.6 Hz, 1H; C=CH), 6.26 (dd, J=8.2,
9.0 Hz, 1H; C=CH), 5.33–5.26 (m, 2H; H-2, H-6), 4.48–4.45 (brs, 1H;
H-5), 1.71–1.62 (m, 2H; H-2, H-4), 1.44 (pent, J=8.4, 1H; H-3’),
0.74–0.64 ppm (m, 1H; H-3); 13C NMR (100 MHz, CDCl3): d=168.4
(C=O), 134.4, 132.0, 128.7, 127.4, 123.6, 77.9, 77.4, 52.2 (C-5), 17.5,
15.4, 11.1 ppm; elemental analysis calcd (%) for C16H13NO4: C 67.84;
H 4.62; found: C 67.81; H 4.64.
1
less solids. (Æ)-10: M.p. 227–2288C; H NMR (400 MHz, CDCl3): d=
7.85–7.83 (4H, m, Phth), 6.40 (dd, J=2.4, 13.2 Hz, 1H; H-4), 5.91
(ddd, J=1.6, 2.8, 13.6 Hz, 1H; H-5), 4.97 (tdd, J=2.4, 9.6, 10.0 Hz,
1H; H-2), 4.80 (d, J=10.0 Hz, 1H; H-3), 2.23 (d, J=9.2 Hz, 1H; OH),
2.14 (ddt, J=1.6, 5.4, 9.1 Hz, 1H; H-7), 1.73 (q, J=8.7 Hz, 1H; H-
8endo), 1.62 (td, J=5.8, 7.2 Hz, 1H; H-1), 1.45 ppm (dt, J=6.0,
8.7 Hz, 1H; H-8exo); 13C NMR (100 MHz, [D6]acetone): d=199.0 (C-
6), 168.7 (C=O Phth), 145.0, 135.1, 133.2, 127.0, 123.9, 68.0, 53.4,
28.2, 21.2, 13.5 ppm; elemental analysis calcd (%) for C16H13NO4: C
67.84; H 4.62; found: C 67.92; H 4.65.
(Æ)-N-(6S*-Hydroxy-3-oxo-bicyclo[5.1.0]oct-4-en-2R*-yl)phthali-
mide: M.p. 182–1838C; 1H NMR (400 MHz, CD3OD): d=7.92–7.82
(m, 4H; Phth), 7.01 (dd, J=3.0, 12.0 Hz, 1H; H-5), 6.07 (dd, J=2.8,
12.0 Hz, 1H; H-4), 4.52 (d, J=10.8 Hz, 1H), 4.48 (td, J=2.6, 9.2 Hz,
1H), 2.08 (ddt, J=4.8, 7.0, 10.6, 1H; H-1), 1.69–1.61 (m, 1H; H-7),
1.25 (dt, J=5.6, 7.6 Hz, 1H; H-8exo), 1.01 ppm (q, J=4.9 Hz, 1H; H-
8endo); 13C NMR (100 MHz, CD3OD): d=194.7 (C-3), 169.5 (C=O
Phth), 158.2, 135.8, 133.2, 129.5, 124.5, 74.1, 64.3, 27.5, 18.2,
13.6 ppm.
10-Phthalimido-2,5-dioxatetracyclo[7.1.01,3.04,6]decane
(Æ)-12:
m-Chloroperoxybenzoic acid (319 mg, ꢀ70% wt., ꢀ1.29 mmol)
was added to a solution of diene (Æ)-7 (130 mg, 0.516 mmol) in
freshly distilled CH2Cl2 (5 mL). The reaction mixture was stirred
under N2 for 12 h, after which monitoring by TLC indicated the dis-
appearance of starting material. The mixture was concentrated and
the solid residue was treated with saturated aqueous bicarbonate
(5 mL) with stirring for 30 min. The mixture was extracted several
times with ethyl acetate, dried (Na2SO4), and concentrated. Recrys-
tallization of the residue from benzene gave colorless crystals of
N-(3R*,6S*-Dihydroxybicyclo[5.1.0]oct-4-en-2R*-yl)phthalimide
(Æ)-11: [CeCl3]·7H2O (604 mg, 1.620 mmol) was added to a solution
of (Æ)-10 (230 mg, 0.810 mmol) in THF (4 mL) and methanol
(7 mL). The mixture was stirred at room temperature until all the
material dissolved (ꢀ30 min). The solution was cooled to À788C
and NaBH4 (62 mg, 1.620 mmol) was added portionwise. The reac-
tion mixture was stirred at À788C for 5 h, the solvent concentrat-
1
(Æ)-12 (137 mg, 93%). M.p.>2508C; H NMR (400 MHz, CDCl3): d=
7.92–7.72 (m, 4H; Phth), 5.16 (d, J=5.6 Hz, 1H; H-8), 3.70 (dd, J=
4.2, 5.4 Hz, 1H), 3.51 (dd, J=4.4, 6.0 Hz, 1H), 3.47 (dd, J=2.6,
Chem. Eur. J. 2015, 21, 10886 – 10895
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Full Paper
ed, and the resultant residue was partitioned between water and
ethyl acetate. Evaporation of the solvent gave (Æ)-11 (220 mg,
94%) as a colorless solid. M.p. 225–2278C; 1H NMR (400 MHz,
CD3OD): d=7.90–7.78 (m, 4H; Phth), 5.55 (td, J=2.4, 13.2 Hz, 1H;
H-4), 5.47 (qd, J=1.7, 13.2 Hz, 1H; H-5), 4.84–4.81 (m, 1H; H-6),
4.60 (qd, J=2.4, 10.1 Hz, 1H; H-3), 4.49 (d, J=10.4 Hz, 1H; H-2),
1.42–1.34 (m, 1H; H-7), 1.21 (dt, J=6.1, 9.3 Hz, 1H; H-1), 0.96 (q,
J=5.9 Hz, 1H; H-8endo), 0.70 ppm (dt, J=5.9, 8.8 Hz, 1H; H-8exo);
13C NMR (100 MHz, CD3OD): d=170.0, 135.4, 133.6, 132.0, 130.4,
124.2, 69.1, 68.4, 53.6, 19.9, 16.2, 2.5 ppm; HRMS (FAB): m/z calcd
for C16H15NO4 +Na+: 308.0893 [M+Na+]; found: 308.0895.
N-(5S*,6R*-Dihydroxybicyclo[5.1.0]oct-3-en-2R*-yl)phthalimide
(Æ)-16 and N-(3R*,4S*-dihydroxybicyclo[5.1.0]oct-5-en-2S*-yl)ph-
thalimide (Æ)-17:
A solution of N-methylmorpholine-N-oxide
(0.32 mL, 1.2 mmol, 50 wt% in water) was added to a solution of
diene (Æ)-7 (300 mg, 1.20 mmol) in acetone (10 mL), followed by
a solution of OsO4 (0.2 mL, 0.2m in toluene). The mixture was
stirred for 1 h at room temperature. The reaction was quenched
with NaHSO3 (100 mg) and stirred for 30 min then adsorbed onto
silica gel for purification by column chromatography (SiO2, hex-
anes/ethyl acetate=2:3) to give recovered 7 (81 mg), followed by
(Æ)-16 (138 mg, 56% b.r.s.m.) followed by (Æ)-17 (72 mg, 29%
1
b.r.s.m.), both as colorless solids. (Æ)-16: M.p. 218–2218C; H NMR
Epoxidation of (Æ)-8: H2O2 (0.25 mL, 3.5 mmol, 50 wt% solution)
was added to an ice-cold solution of trifluoroacetic anhydride
(0.50 mL, 3.5 mmol) in CH2Cl2 (5 mL), and the mixture was stirred
for 5 min at 08C and then at room temperature for 1 h. The previ-
ously prepared trifluoroperacetic acid solution was then added
dropwise to an ice-cold solution of endoperoxide (Æ)-8 (130 mg,
0.458 mmol) in CH2Cl2 (2.5 mL) and THF (2.5 mL). After addition
was complete, the mixture was warmed to room temperature and
stirred for 4 h. The solvent was evaporated by blowing nitrogen
gas over the solution to give (Æ)-13 (136 mg, 99%) as a colorless
(400 MHz, CDCl3): d=7.90–7.70 (m, 4H; Phth), 5.68 (pent, J=
2.8 Hz, 1H; H-2), 5.55 (ddd, J=2.0, 5.2, 12.8 Hz, 1H; C=CH), 5.43
(ddd, J=2.0, 3.6, 12.8 Hz, 1H; C=CH), 4.60–4.68 (m, 1H; H-5), 4.10–
4.20 (m, 1H; H-6), 2.41 (d, J=8.4 Hz, 1H; OH), 2.25 (d, J=3.6 Hz,
1H; OH), 1.48 (tt, J=6.7, 9.1 Hz, 1H; H-7), 1.22–1.14 (m, 1H; H-1),
1.08 (q, J=5.9 Hz, 1H; H-8endo), 0.83 ppm (dt, J=5.9, 8.7 Hz, 1H;
H-8exo); 13C NMR (100 MHz, CDCl3): d=168.0, 134.3, 132.2, 128.6,
127.2, 123.5, 73.0, 71.9, 48.7, 17.9, 16.5, 7.2 ppm; HRMS (FAB): m/z
calcd for C16H15NO4 +Na+: 308.0893 [M+Na+]; found: 308.0894.
1
(Æ)-17: M.p.=219–2208C; H NMR (400 MHz, CDCl3): d=7.88–7.81
1
solid. M.p. 205–2068C; H NMR (400 MHz, CDCl3): d=7.93–7.85 (m,
(m, 2H; Phth), 7.76–7.67 (m, 2H; Phth), 6.16 (dd, J=5.8, 11.8 Hz,
1H; H-5), 5.65 (dd, J=7.6, 12.0 Hz, 1H; H-6), 5.25 (dd, J=4.0,
10.4 Hz, 1H; H-2), 4.40–4.30 (m, 2H; H-5 and H-6), 2.43 (d, J=
8.0 Hz, 1H; OH), 1.98 (d, J=5.5 Hz, 1H; OH), 1.54–1.45 (m, 1H; H-
1), 1.41 (dq, J=4.0, 8.8 Hz, 1H; H-7), 1.05 (dt, J=4.6, 9.2 Hz, 1H; H-
8exo), 0.90 ppm (q, J=5.9 Hz, 1H; H-8endo); 13C NMR (100 MHz,
CDCl3): d=169.2, 134.7, 134.1, 132.3, 123.4, 123.3, 71.1, 68.7, 50.1,
19.6, 15.9, 13.4 ppm; HRMS (FAB): m/z calcd for C16H15NO4 +Na+:
308.0893 [M+Na+]; found: 308.0894.
2H; Phth), 7.82–7.73 (m, 2H; Phth), 5.59 (dd, J=3.5, 7.0 Hz, 1H),
5.08 (dt, J=3.6, 6.8 Hz, 1H), 4.49 (q, J=3.5 Hz, 1H; H-2), 3.85 (t, J=
4.1 Hz, 1H), 3.40 (t, J=4.5 Hz, 1H), 1.91 (q, J=6.1 Hz, 1H; H-8endo),
1.77 (ddt, J=2.0, 6.8, 8.7 Hz, 1H; H-1), 1.49 (pent, J=7.9 Hz, 1H; H-
7), 0.96 ppm (td, J=6.3, 8.8 Hz, 1H; H-8exo); 13C NMR (100 MHz,
CDCl3): d=168.4, 134.7, 131.8, 123.8, 79.0, 74.7, 52.3, 47.9, 47.0,
16.5, 15.8, 9.7 ppm; HRMS (FAB): m/z calcd for C16H13NO5 +Na+:
322.0686 [M+Na+]; found: 322.0688.
N-(4R*,5S*-Epoxy-3R*,6S*-dihydroxybicyclo[5.1.0]oct-2S*-yl)ph-
thalimide (Æ)-14: The reduction of epoxy endoperoxide (Æ)-13
(110 mg, 0.367 mmol) in CH2Cl2 (5 mL) with activated zinc dust
(110 mg) was carried out in a fashion similar to the preparation of
(Æ)-9. The residue was purified by column chromatography (SiO2,
CH2Cl2/MeOH=19:1) to give (Æ)-14 (63 mg, 63%) as a colorless
solid. M.p. 194–1958C; 1H NMR (400 MHz, CD3OD): d=7.91–7.73
(m, 4H; Phth), 4.80 (dd, J=3.5, 11.0 Hz, 1H; H-2), 4.54 (dd, J=0.8,
11.0 Hz, 1H; H-3), 4.43 (t, J=3.5 Hz, 1H; H-6), 3.29 (d, J=1.2 Hz,
1H), 3.28–3.20 (m, 1H), 1.15 (ddt, J=3.5, 6.7, 9.3 Hz, 1H; H-7), 1.07
(dddt, J=0.8, 4.0, 6.7, 9.3 Hz, 1H; H-1), 0.78 (dt, J=5.5, 9.2 Hz, 1H;
H-8exo), 0.68 ppm (q, J=6.3 Hz, 1H; H-8endo); 13C NMR (100 MHz,
CD3OD): d=170.2, 135.4, 133.5, 124.2, 70.1, 65.6, 61.0, 58.0, 51.6,
19.8, 18.5, 7.2 ppm; HRMS (FAB): m/z calcd for C16H15NO5 +Na+:
324.0842 [M+Na+]; found: 324.0843.
N-(3R*,4R*-Epoxy-5S*,6S*-dihydroxybicyclo[5.1.0]oct-2S*-yl)ph-
thalimide (Æ)-18: The epoxidation of enediol (Æ)-16 (138 mg,
0.484 mmol) in CH2Cl2 (5 mL) with trifluoroacetic acid was carried
out in a fashion similar to the preparation of 15. The residue was
purified by column chromatography (SiO2, hexanes/ethyl acetate=
30:70) to give (Æ)-18 (121 mg, 83%) as a colorless solid. M.p.>
1
2508C; H NMR (400 MHz, [D6]DMSO): d=7.93–7.81 (m, 4H; Phth),
4.94 (d, J=5.9 Hz, 1H; H-2), 4.82 (t, J=6.5 Hz, 1H), 4.59 (d, J=
5.1 Hz, 1H), 4.49 (d, J=8.2 Hz, 1H), 4.36 (t, J=5.9 Hz, 1H), 3.98 (t,
J=5.5 Hz, 1H), 3.73 (d, J=5.9 Hz, 1H), 1.61 (dq, J=5.1, 8.6 Hz, 1H;
H-7), 1.20 (q, J=5.7 Hz, 1H; H-8endo), 1.04 (tt, J=5.9, 8.6 Hz, 1H;
H-1), 0.84 ppm (dt, J=6.7, 8.6 Hz, 1H; H-8exo); 13C NMR (100 MHz,
[D6]DMSO): d=168.5, 134.7, 131.3, 123.1, 82.0, 80.6, 72.9, 70.3, 50.7,
15.5, 14.2, 7.7 ppm; HRMS (FAB): m/z calcd for C16H15NO5 +Na+:
324.0842 [M+Na+]; found: 324.0846.
N-(4S*,5R*-Epoxy-3R*,6S*-dihydroxybicyclo[5.1.0]oct-2S*-yl)ph-
thalimide (Æ)-15: The epoxidation of enediol (Æ)-9 (70 mg,
0.245 mmol) in CH2Cl2/THF (1:1, 5 mL) with trifluoroacetic acid was
carried out in a fashion similar to the preparation of (Æ)-13. Purifi-
cation of the crude residue column chromatography (SiO2, hex-
anes/ethyl acetate gradient=2:3!3:7) to give recovered 9 (9 mg)
followed by (Æ)-15 (53 mg, 83% based on recovered starting mate-
N-(5R*,6S*-Epoxybicyclo[5.1.0]oct-3-en-2S*-yl)phthalimide (Æ)-19
and N-(5-oxobicyclo[5.1.0]oct-3-en-2S*-yl)phthalimide (Æ)-20: A
solution of meta-chloroperoxybenzoic acid (196 mg, ꢀ0.794 mmol,
ꢀ70 wt%) in freshly distilled CH2Cl2 (2 mL) was added dropwise to
a solution of diene (Æ)-7 (200 mg, 0.794 mmol) in freshly distilled
CH2Cl2 (4 mL). The solution was stirred under N2 for 5 h, at which
time monitoring by TLC showed complete disappearance of start-
ing material. The solvent was evaporated and the residue was
treated with saturated bicarbonate solution (5 mL) with stirring for
30 min. The mixture was extracted several times with CH2Cl2, con-
centrated, and purified by column chromatography (SiO2, hexanes/
ethyl acetate=7:3) to give (Æ)-19 (153 mg, 70%) followed by (Æ)-
20 (28 mg, 12%), both as colorless solids. (Æ)-19: M.p. 196–1988C;
1H NMR (400 MHz, CDCl3): d=0.90–0.97 (1H, m, H-8exo), 1.07 (1H,
brq, J=7.6 Hz, H-8endo), 1.58 (2H, m, H-1 and H-7), 3.19 (1H, t, J=
4.8 Hz, H-5 or H-6), 3.57 (1H, t, J=4.8 Hz, H-5 or H-6), 5.63 (1H,
brd, J=12.0 Hz, H-3), 5.78 (1H, J=2.9, 5.5, 12.0 Hz, H-4), 5.91 (1H,
rial (b.r.s.m.)) as
a
colorless solid. M.p. 205–2068C; 1H NMR
(400 MHz, CD3OD): d=7.85 (brs, 4H; Phth), 4.78 (dd, J=7.6,
12.0 Hz, 1H; H-2), 4.01 (dd, J=6.8, 12.0 Hz, 1H; H-3), 3.32–3.19 (m,
2H; H-5 and H-6), 3.03 (dd, J=4.7, 6.8 Hz, 1H; H-4), 1.34 (tt, J=7.2,
9.2 Hz, 1H), 1.29–1.20 (m, 1H), 0.99 (td, J=5.2, 6.4 Hz, 1H; H-
8endo), 0.86 ppm (ddd, J=4.4, 8.8, 9.6 Hz, 1H; H-8exo); 13C NMR
(100 MHz, CD3OD): d=170.5, 170.2, 135.6, 135.4, 133.6, 133.0,
124.3, 124.1, 76.7, 68.6, 60.1, 58.5, 53.4, 23.5, 17.6, 13.1 ppm; HRMS
(FAB): m/z calcd for C16H15NO5 +Na+: 324.0842 [M+Na+]; found:
324.0844.
Chem. Eur. J. 2015, 21, 10886 – 10895
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d, J=2.4 Hz, H-2), 7.70–7.93 ppm (4H, m, Phth); 13C NMR (100 MHz,
CDCl3): d=8.3, 13.8, 18.8, 47.6, 52.8, 54.9, 123.4, 123.5, 132.2, 132.8,
134.2, 167.9 ppm; HRMS (FAB): m/z calcd for C16H13NO3 +Na+:
290.0788 [M+Na+]; found: 290.0789. (Æ)-20: M.p. 122–1238C;
1H NMR (400 MHz, CDCl3): d=0.74 (1H, dt, J=6.4 and 9.0 Hz, H-
8exo), 1.03 (1H, q, J=5.7 Hz, H-8endo), 1.20–1.28 (2H, m, H-1 and
H-7), 2.95 (1H, d, J=15.2 Hz, H-6), 3.11 (1H, brd, J=15.2 Hz, H-6’),
5.61–5.64 (1H, brs, H-2), 6.12 (1H, ddd, J=1.8, 3.1, 12.9 Hz, H-4),
6.24 (1H, dd, J=2.6, 13.0 Hz, H-3), 7.75–7.93 ppm (4H, m, Phth);
13C NMR (100 MHz, CDCl3): d=4.7, 8.4, 17.9, 41.6, 49.4, 123.78,
123.84, 132.0, 132.6, 134.6, 141.9, 167.7, 198.9 ppm; HRMS (FAB):
m/z calcd for C16H13NO3 +Na+: 290.0788 [M+Na+]; found:
290.0789.
3), 4.30 (t, J=5.4 Hz, 1H; H-6), 4.05 (dd, J=2.8, 6.0 Hz, 1H; H-5),
3.64 (dd, J=2.6, 9.4 Hz, 1H; H-4), 1.50 (q, J=6.1 Hz, 1H; H-8endo),
1.26–1.18 (m, 1H; H-7), 1.11 (ddt, J=3.6, 6.4, 9.4 Hz, 1H; H-1),
0.71 ppm (1H, dt, J=5.6, 9.2 Hz, H-8exo); 13C NMR (100 MHz,
CD3OD): d=170.2, 135.5, 135.3, 133.9, 133.4, 124.2, 124.0, 76.3,
73.6, 71.9, 66.4, 55.3, 20.5, 17.8, 7.6 ppm; elemental analysis calcd
(%) for C16H17NO6: C 60.18, H 5.36; found: C 60.01, H 5.36.
N-(3R*,4S*,5R*,6R*-Tetrahydroxybicyclo[5.1.0]oct-2S*-yl)phthali-
mide
(Æ)-28
and
N-(3R*,4R*,5S*,6R*-tetrahydroxybicy-
clo[5.1.0]oct-4-en-2S*-yl)phthalimide (Æ)-27: The dihydroxylation
of (Æ)-11 (300 mg, 1.049 mmol) in acetone with catalytic OsO4 and
NMO (184 mg, 1.573 mmol) was carried out in a fashion similar to
the preparation of (Æ)-26. Purification of the residue by column
chromatography (SiO2, CH2Cl2/MeOH=2:3) to give (Æ)-28 (93 mg,
28%) followed by (Æ)-27 (117 mg, 34%), both as colorless solids.
N-(5S*,6S*-Epoxy-3R*,4R*-dihydroxybicyclo[5.1.0]oct-2S*-yl)ph-
thalimide (Æ)-23: The dihydroxylation of (Æ)-19 (100 mg,
0.373 mmol) in acetone (5 mL) with catalytic OsO4 (0.14 mL, 0.2m
in toluene) and N-methylmorpholine-N-oxide (100 mg, 0.857 mmol)
in water (1 mL) was carried out in a fashion similar to the dihydrox-
ylation of (Æ)-7. Purification of the residue by column chromatog-
raphy (SiO2, hexanes/ethyl acetate gradient 1:1!1:4) gave (Æ)-23
1
(Æ)-28: M.p. 201–2038C; H NMR (400 MHz, CD3OD): d=7.91–7.72
(m, 4H; Phth), 4.56 (dd, J=2.7, 11.0 Hz, 1H; H-2), 4.45 (t, J=
10.2 Hz, 1H; H-3), 4.17–4.10 (m, 2H; H-5 and H-6), 3.27 (dd, J=1.6,
9.4 Hz, 1H; H-4), 1.70 (q, J=6.3 Hz, 1H; H-8endo), 1.24–1.14 (m,
1H; H-7), 1.09 (ddt, J=2.7, 6.3, 9.4 Hz, 1H; H-1), 0.69 ppm (dt, J=
5.5, 9.0 Hz, 1H; H-8exo); 13C NMR (100 MHz, CD3OD): d=170.1,
170.0, 135.5, 135.2, 133.8, 133.3, 124.2, 124.0, 77.0, 76.0, 70.1, 66.4,
55.5, 20.2, 17.8, 8.4 ppm; elemental analysis calcd (%) for
C16H17NO6: C 60.18, H 5.36; found: C 59.93, H 5.29. (Æ)-27: M.p.>
2308C; 1H NMR (400 MHz, CD3OD): d=7.90–7.76 (m, 4H; Phth),
5.50 (dd, J=3.0, 11.0 Hz, 1H; H-2), 4.30 (d, J=10.4 Hz, 1H; H-3),
4.26 (dd, J=3.6, 9.6 Hz, 1H; H-6), 4.06 (s, 1H; H-4), 3.34 (d, J=
8.4 Hz, 1H; H-5), 1.31 (ddt, J=3.6, 6.8, 9.6 Hz, 1H; H-7), 1.16 (ddt,
J=3.0, 6.6, 9.6 Hz, 1H; H-1), 0.90 (q, J=6.4 Hz, 1H; H-8endo),
0.67 ppm (dt, J=6.0, 9.0 Hz, 1H; H-8exo); 13C NMR (100 MHz,
CD3OD): d=170.5, 170.2, 135.4, 135.3, 133.8, 133.4, 124.2, 123.9,
78.1, 74.1, 69.3, 68.6, 50.9, 20.0, 18.1, 4.9 ppm; elemental analysis
calcd (%) for C16H17NO6: C 60.18, H 5.36; found: C 59.65, H 5.38.
1
(109 mg, 97%) as a colorless solid. M.p.>2208C; H NMR (400 MHz,
[D6]acetone): d=7.84 (s, 4H; Phth), 5.19 (dd, J=5.8, 11.4 Hz, 1H; H-
2), 4.36–4.41 (m, 2H; H-3 and H-4), 4.16 (d, J=6.8 Hz, 1H; OH),
3.58 (brd, J=4.8 Hz, 1H), 3.35 (ddd, J=0.6, 4.2, 6.8 Hz, 1H), 3.19 (d,
J=5.2 Hz, 1H; OH), 1.56 (brq, J=8.3 Hz, 1H; H-7), 1.23 (tt, J=6.8,
8.8 Hz, 1H; H-1), 0.96 (dt, J=4.9, 6.7 Hz, 1H; H-8endo), 0.84 ppm
(dt, J=4.8, 9.2 Hz, 1H; H-8exo); 13C NMR (100 MHz, [D6]acetone):
d=169.8, 135.4, 133.6, 124.1, 70.7, 67.9, 58.4, 56.5, 53.0, 20.8, 16.8,
7.2 ppm; HRMS (FAB): m/z calcd for C16H15NO5 +Na+: 324.0842
[M+Na+]; found: 324.0843.
N-(3R*,4R*,5S*,6S*-Tetrahydroxybicyclo[5.1.0]oct-2S*-yl)phthali-
mide
(Æ)-25
and
*N-(3R*,4R*,5R*,6R*-tetrahydroxybicy-
clo[5.1.0]oct-2S*-yl)phthalimide (Æ)-24: The exhaustive hydroxyl-
ation of (Æ)-7 (300 mg, 1.20 mmol) in acetone with catalytic OsO4
was carried out in a similar fashion to the dihydroxylation of 7
except that an excess of NMO (419 mg, 3.59 mmol) was used. Pu-
rification of the residue by column chromatography (SiO2, CH2Cl2/
MeOH=10:1) gave (Æ)-25 (187 mg, 49%) followed by (Æ)-24
(79 mg, 21%) both as a colorless solids. (Æ)-25: M.p. 229–2308C;
1H NMR (400 MHz, CD3OD): d=7.89–7.76 (m, 4H; Phth), 5.16 (dd,
J=2.6, 10.6 Hz, 1H; H-2), 4.50–4.44 (m, 1H; H-6), 4.27 (dd, J=1.8,
11.0 Hz, 1H; H-3), 4.14–4.10 (m, 1H; H-4), 3.54 (t, J=2.2 Hz, 1H; H-
5), 1.39 (ddt, J=4.8, 7.0, 9.2 Hz, 1H; H-7), 1.19 (ddt, J=2.6, 6.6,
9.2 Hz, 1H; H-1), 0.89–0.74 ppm (m, 2H; H-8exo and H-8endo);
13C NMR (100 MHz, CD3OD): d=169.9, 135.3, 135.2, 133.7, 133.3,
124.2, 123.8, 81.0, 76.1, 69.7, 68.8, 50.8, 20.8, 18.7, 6.8 ppm; ele-
mental analysis calcd (%) for C16H17NO6·0.2H2O: C 59.51, H 5.43, N
4.34; found: C 59.56, H 5.49, N 4.35. (Æ)-24: M.p. 241–2448C;
1H NMR (400 MHz, CD3OD): d=7.87–7.75 (m, 4H; Phth), 5.05 (dd,
J=2.9, 11.2 Hz, 1H; H-2), 4.59 (d, J=10.6 Hz, 1H; H-3), 4.34 (d, J=
3.5 Hz, 1H; H-6), 4.00 (s, 2H; H-4 and H-5), 1.63–1.53 (m, 1H), 1.23–
1.02 (m, 2H), 0.63 ppm (dt, J=5.3, 9.0 Hz, 1H; H-8exo); 13C NMR
(100 MHz, CD3OD): d=170.2, 135.3, 135.1, 124.1, 123.8, 76.4, 75.9,
68.7, 66.3, 51.7, 19.8, 18.1, 7.3 ppm; elemental analysis calcd (%) for
C16H17NO6: C 60.18, H 5.37; found: C 60.18, H 5.32.
N-(3R*,4R*,5S*,6R*-Tetrahydroxybicyclo[5.1.0]oct-4-en-2S*-yl)ph-
thalimide (Æ)-27: Carbon tetrabromide (20 mg, 0.058 mmol) was
added as a catalyst to a solution of epoxydiol (Æ)-23 (87 mg,
0.29 mmol) in water (3 mL). The mixture was heated at reflux with
stirring for 8 h, the solvent was evaporated and the residue was re-
crystallized from methanol to give (Æ)-27 as colorless crystals
(61 mg, 66%). The spectral date for this product was consistent
with that previously obtained.
N-(3S*,4S*,5S*,6R*-Tetrahydroxybicyclo[5.1.0]oct-2S*-yl)phthali-
mide (Æ)-30 and N-(1R*,3R*,4R*,5?*-tetrahydroxy-6-cycloocten-
2R*-yl)phthalimide (Æ)-31: The hydrolysis of bisepoxide (Æ)-12
(90 mg, 0.32 mmol) in THF (5 mL), dionized water (7 mL), and a cat-
alytic amount of CBr4 (42 mg, 0.13 mmol) was carried out in a fash-
ion similar to the hydrolysis of (Æ)-23. Purification of the residue
by column chromatography (SiO2, CH2Cl2/MeOH=19:1) gave (Æ)-
30 (46 mg, 46%) followed by (Æ)-31 (17 mg, 18%), both as color-
1
less solids. (Æ)-30: M.p. 218–2208C; H NMR (400 MHz, CD3OD): d=
7.92–7.80 (m, 4H; Phth), 5.16 (t, J=2.2 Hz, 1H; H-2), 4.28 (dd, J=
3.8, 9.6 Hz, 1H; H-6), 4.03 (td, J=1.7, 6.0 Hz, 1H; H-3), 3.98 (dd, J=
2.0, 6.0 Hz, 1H; H-4), 3.64 (dd, J=1.6, 9.6 Hz, 1H; H-5), 1.56 (q, J=
6.0 Hz, 1H; H-8endo), 1.32 (ddt, J=3.2, 6.4, 9.6 Hz, 1H), 1.03 (brq,
J=8.6 Hz, 1H), 0.70 ppm (dt, J=5.6, 8.8 Hz, 1H; H-8exo); 13C NMR
(100 MHz, CD3OD): d=171.1, 135.7, 133.4, 124.4, 75.9, 74.6, 72.1,
70.1, 50.4, 19.7, 16.7, 7.6 ppm; elemental analysis calcd (%) for
N-(3R*,4S*,5R*,6S*-Tetrahydroxybicyclo[5.1.0]oct-2S*-yl)phthali-
mide (Æ)-26: Dihydroxylation of (Æ)-9 (140 mg, 0.489 mmol) in
acetone with catalytic OsO4 and NMO (85 mg, 0.73 mmol) was car-
ried out in a similar fashion to the dihydroxylation of 7. The residue
was purified by column chromatography (SiO2, hexanes/ethyl ace-
tate=1:4) to give (Æ)-26 (133 mg, 85%) as a colorless solid. M.p.
254–2558C; 1H NMR (400 MHz, CD3OD): d=7.90–7.78 (m, 4H;
Phth), 4.71 (dd, J=3.8, 10.2 Hz, 1H; H-2), 4.37 (t, J=10.0 Hz, 1H; H-
1
C16H17NO6: C 60.18, H 5.36; found: C 59.84, H 5.29. (Æ)-31: H NMR
(400 MHz, CD3OD): d=7.90–7.78 (m, 4H; Phth), 5.81 (dd, J=6.0,
10.8 Hz, 1H; H-2), 5.74 (ddt, J=1.6, 6.8, 10.8 Hz, 1H; H-1), 4.93
(brd, J=6.0 Hz, 1H), 4.88 (d, J=4.0 Hz, 1H), 4.30 (d, J=6.0 Hz, 1H;
H-4), 4.08 (dd, J=1.0, 5.8 Hz, 1H; H-3), 3.93–3.86 (m, 1H; H-7), 2.89
(dt, J=9.2, 12.4 Hz, 1H; H-8), 2.31 ppm (td, J=6.6, 12.4 Hz, 1H; H-
Chem. Eur. J. 2015, 21, 10886 – 10895
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8’); 13C NMR (100 MHz, CD3OD): d=170.6, 138.3, 135.5, 133.4, 126.1,
124.2, 77.6, 77.1, 76.3, 69.0, 52.5, 34.7 ppm; HRMS (FAB): m/z calcd
for C16H17NO6 +Na: 342.0948 [M+Na+]; found: 342.0949.
High-resolution mass spectra were obtained at the COSMIC lab
at Old Dominion University. The corresponding author thanks
Dr. David Lindsay for stimulating discussions concerning the
formation of compound 31.
N-(3S*,4R*,5S*,6S*-Tetrahydroxybicyclo[5.1.0]oct-2S*-yl)phthali-
mide (Æ)-29: Hydrolysis of epoxydiol (Æ)-18 (120 mg, 0.399 mmol)
in THF (5 mL) with a catalytic amount of CBr4 (26 mg, 0.079 mmol)
was carried out in a fashion similar to the hydrolysis of (Æ)-23. Pu-
rification of the residue by column chromatography (SiO2, CH2Cl2/
MeOH gradient=19:1!9:1) gave recovered (Æ)-18 (26 mg) fol-
lowed by (Æ)-29 (81 mg, 81%) as a colorless solid. M.p. 202–
2048C; 1H NMR (400 MHz, CD3OD): d=7.92–7.86 (m, 2H; Phth),
7.86–7.81 (m, 2H; Phth), 5.33 (t, J=2.2 Hz, 1H; H-2), 4.63 (d, J=
4.4 Hz, 1H; H-6), 4.07 (td, J=1.6, 6.0 Hz, 1H; H-4), 4.04 (td, J=1.6,
6.0 Hz, 1H; H-3), 3.83 (brs, 1H; H-5), 1.54–1.46 (m, 1H), 1.41–1.28
(m, 1H), 1.11 (q, J=8.0 Hz, 1H; H-8endo), 0.81 ppm (dt, J=5.5,
9.4 Hz, 1H; H-8exo); 13C NMR (100 MHz, CD3OD): d=171.0, 135.7,
133.4, 124.4, 78.2 (br), 76.6, 68.6 (br), 50.4, 20.2, 18.5, 9.2 ppm;
HRMS (FAB): m/z calcd for C16H17NO6 +Na+: 324.0948 [M+Na+];
found: 324.0950.
Keywords: cyclitols
·
diastereoselectivity
·
epoxides
·
hydrocarbons · hydrolysis
[1] a) V. H. Lillelund, H. H. Jensen, X. Liang, M. Bols, Chem. Rev. 2002, 102,
515–553; b) T. Mahmud, P. M. Flatt, X. Wu, J. Nat. Prod. 2007, 70, 1384–
1390; c) S. Ogawa, M. Kanto, Y. Suzuki, Mini-Rev. Med. Chem. 2007, 7,
679–691; d) A. Osuch-Kwiatkowska, S. Jarosz, Curr. Org. Chem. 2014, 18,
1674–1685.
[2] N. Asano, A. Kato, H. Kizu, K. Matsui, Phytochemistry 1996, 42, 719–721.
[3] C. Gravier-Pelletier, W. Maton, T. Dintinger, C. Tellier, Y. Le Merrer, Tetra-
hedron 2003, 59, 8705–8720.
[4] For other recent syntheses of medium-ring cyclitols, see: a) K. Ecer, E.
Salamci, Tetrahedron 2014, 70, 8389–8396; b) G. Mehta, R. Mohanrao, S.
Katukojvala, Y. Landais, S. Sen, Tetrahedron Lett. 2011, 52, 2893–2897;
c) R. Beniazza, V. Desvergnes, G. Mehta, N. Blanchard, F. Robert, Y. Land-
ais, J. Org. Chem. 2011, 76, 791–799; d) E. Girard, V. Desvergnes, C.
Tarnus, Y. Landais, Org. Biomol. Chem. 2010, 8, 5628–5634; e) T. K. M.
Shing, W. F. Wong, T. Ikeno, T. Yamada, Org. Chem. 2007, 9, 207–209;
f) C. Curti, F. Zanardi, L. Battistini, A. Sartori, G. Rassu, L. Auzzas, A.
Roggio, L. Pinna, G. Casiraghi, J. Org. Chem. 2006, 71, 225–230; g) O.
Andriuzzi, C. Gravier-Pelletier, G. Bertho, T. Prange, Y. Le Merrer, Beilstein
J. Org. Chem. 2005, 1, 12.
N-(3R*,4S*,5S*,6S*-Tetrahydroxybicyclo[5.1.0]oct-2S*-yl)phthali-
mide (Æ)-32: The hydrolysis of epoxydiol (Æ)-14 (40 mg,
0.13 mmol) in THF (1 mL) and deionized water (5 mL) with a catalyt-
ic amount of CBr4 (9 mg, 0.03 mmol) was carried out in a fashion
similar to the hydrolysis of (Æ)-23. Purification of the residue by
column chromatography (SiO2, CH2Cl2/MeOH=9:1) gave (Æ)-32
(39 mg, 92%) as a colorless solid. M.p.=126–1288C; 1H NMR
(400 MHz, CD3OD): d=7.91–7.67 (m, 4H; Phth), 4.79 (dd, J=2.8,
10.8 Hz, 1H; H-2), 4.44–4.30 (brm, 1H; H-6), 4.00 (dd, J=9.0,
10.2 Hz, 1H; H-3), 3.53 (t, J=8.8 Hz, 1H; H-4), 3.45 (brd, J=8.8 Hz,
1H; H-5), 1.33 (tt, J=6.2, 9.3 Hz, 1H; H-7), 1.17 (ddt, J=3.1, 6.3,
9.2 Hz, 1H; H-1), 0.90 (q, J=6.3 Hz, 1H; H-8endo), 0.80 ppm (td, J=
6.1, 9.1 Hz, 1H; H-8exo); 13C NMR (100 MHz, CD3OD): d=168.5,
133.8, 132.0, 122.6, 73.2, 71.5, 68.1, 65.7, 51.9, 17.7, 16.7, 6.3 ppm;
elemental analysis calcd (%) for C16H17NO6: C 60.18, H 5.36; found:
C 59.97, H 5.36.
[5] K. S. E. Tanaka, G. C. Winters, R. J. Batchelor, F. W. B. Einstein, A. J.
Bennet, J. Am. Chem. Soc. 2001, 123, 998–999.
[6] L. Kelebekli, M. Celik, E. Sahin, Y. Kara, M. Balci, Tetrahedron Lett. 2006,
47, 7031–7035.
[7] K. W. Glaeske, W. A. Donaldson, Mini-Rev. Org. Chem. 2012, 9, 31–43.
[8] a) N. J. Wallock, W. A. Donaldson, Tetrahedron Lett. 2002, 43, 4541–
4543; b) N. J. Wallock, W. A. Donaldson, J. Org. Chem. 2004, 69, 2997–
3007; c) S. Chaudhury, S. Lindeman, W. A. Donaldson, Tetrahedron Lett.
2007, 48, 7849–7852; d) M. F. El-Mansy, A. Sar, S. Chaudhury, N. J. Wal-
lock, W. A. Donaldson, Org. Biomol. Chem. 2012, 10, 4844–4846; e) M. F.
El-Mansy, A. Sar, S. Lindeman, W. A. Donaldson, Chem. Eur. J. 2013, 19,
2330–2336.
[9] S. S. Templin, N. J. Wallock, D. W. Bennett, T. Siddiquee, D. T. Haworth,
W. A. Donaldson, J. Heterocycl. Chem. 2007, 44, 719–724.
[10] a) N. Kornblum, H. E. DeLaMare, J. Am. Chem. Soc. 1951, 73, 880–881;
b) D. R. Kelly, H. Bansal, J. J. G. Morgan, Tetrahedron Lett. 2002, 43,
9331–9333; c) E. Mete, R. Altundas¸, H. SeÅen, M. Balci, Turk. J. Chem.
2003, 27, 145–153.
[11] For recent applications of the Kornblum–DeLaMare rearrangement, see:
a) M. J. Palframan, G. Kociok-Kohn, S. E. Lewis, Chem. Eur. J. 2012, 18,
4766–4774; b) V. L. Paddock, R. J. Phipps, A. Conde-Angulo, A. Blanco-
Martin, C. Giro-Manas, L. J. Martin, A. J. P. White, A. C. Spivey, J. Org.
Chem. 2011, 76, 1483–1486.
[12] CCDC 1052609 (12), 1052600 (13), 1052603 (15), 1052607 (19), 1052611
(23), 1052614 (24), 1052615 (25), 1052616 (31), 1052617 (32), 1052618
(33) contain the supplementary crystallographic data for this paper.
These data are provided free of charge by The Cambridge Crystallo-
graphic Data Centre.
Formylcyclohexene (Æ)-33: The hydrolysis of epoxydiol (Æ)-15
(150 mg, 0.497 mmol) in THF (2 mL) and deionized water (10 mL)
with a catalytic amount of CBr4 (33 mg, 0.099 mmol) was carried
out in a fashion similar to the hydrolysis of (Æ)-23. Purification of
the residue by column chromatography (SiO2, hexanes/ethyl ace-
tate gradient=11:9 to 3:7) gave (Æ)-33 as a colorless solid (53 mg,
45%) followed by recovered starting material (Æ)-15 (41 mg). (Æ)-
33: M.p. 215–2168C; 1H NMR (400 MHz, CD3OD): d=9.54 (s, 1H;
CHO), 7.96–7.76 (m, 4H; Phth), 6.52 (1H, d, J=1.2 Hz, C=CH), 5.09
(d, J=9.8 Hz, 1H; H-4), 4.49 (dd, J=3.9, 9.8 Hz, 1H; H-5), 2.09 (dt,
J=4.7, 8.2 Hz, 1H; H-1), 1.52 (ddt, J=3.9, 6.3, 8.4 Hz, 1H; H-6), 1.13
(dt, J=5.1, 8.4 Hz, 1H; H-7exo), 1.03 ppm (q, J=5.1 Hz, 1H; H-
7endo); 13C NMR (100 MHz, CD3OD): d=194.0, 170.3, 148.0, 144.6,
135.5, 133.5, 124.2, 64.9, 54.7, 14.9, 14.4, 10.0 ppm; HRMS (FAB): m/
z calcd for C16H13NO4 +Na+: 306.0737 [M+Na+]; found: 306.0739.
b-Glucosidase inhibitions[22]
[13] A. Sar, S. Lindeman, W. A. Donaldson, Org. Biomol. Chem. 2010, 8,
3908–3917.
[14] G. Guroff, J. W. Daly, D. M. Jerina, J. Renson, B. Witkop, S. Udenfriend,
Science 1967, 157, 1524–1530.
[15] J. K. Cha, W. J. Christ, Y. Kishi, Tetrahedron Lett. 1984, 40, 2247–2255.
[16] J. S. Yadav, B. V. S. Reddy, K. Harikishan, C. Madan, A. V. Narsiah, Synthesis
2005, 2897–2900.
Activities against b-glucosidase were determined at 258C at pH in
100 mm sodium acetate buffer with p-nitrophenyl b-d-glucoside as
substrate against b-d-glucosidase (Aldrich). The release of p-nitro-
phenolate was measured continuously at 405 nm.
[17] M. Karplus, J. Am. Chem. Soc. 1963, 85, 2870–2871.
[18] A. Fürst, P. A. Plattner, Helv. Chim. Acta 1949, 32, 275–283.
[19] M. E. Sengül, A. Menzek, E. Sahin, M. Arik, N. Saracoglu, Tetrahedron
2008, 64, 7289–7294.
[20] C. S. Cho, J. W. Lee, D. Y. Lee, S. C. Shim, T. J. Kim, Chem. Commun. 1996,
2115–2116.
Acknowledgements
This work was supported by the National Science Foundation
(CHE-0848870) and NSF instrumentation grants (CHE-0521323).
Chem. Eur. J. 2015, 21, 10886 – 10895
www.chemeurj.org
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ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
[21] Ring contraction of epoxycyclohexanols catalyzed by LiBr has been re-
ported to generate cyclopentene carboxyaldehydes: a) G. Magnusson,
S. Thoren, J. Org. Chem. 1973, 38, 1380–1384; b) R. Bergman, G. Mag-
nusson, J. Org. Chem. 1986, 51, 212–271; c) F. PontØn, G. Magnusson, J.
Org. Chem. 1997, 62, 7972–7977.
[25] M. S. Motawia, J. Wengel, A. E. S. Abdel-Megid, E. B. Pedersen, Synthesis
1989, 384–387.
[26] M. V. Kelemen, W. J. Whelan, Arch. Biochem. Biophys. 1966, 117, 423–
428.
[22] N. Kuriyama, Y. Inoue, K. Kitagawa, Synthesis 1990, 735–738.
[23] J. O. Osby, M. G. Martin, B. Ganem, Tetrahedron Lett. 1984, 25, 2093–
2096.
Received: March 31, 2015
[24] P. L. Durette, E. P. Meitzner, T. Y. Shen, Tetrahedron Lett. 1979, 20, 4013–
4016.
Published online on June 19, 2015
Chem. Eur. J. 2015, 21, 10886 – 10895
www.chemeurj.org
10895
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim