exclusive oxidation of endo π-bonds.3 In sharp contrast,
tricyclohexabenzene gave products exclusively from benzylic
oxidation.
fine needles of this compound produced by crystallization
from benzene-ethyl acetate. The structure of 2 (Figure 2A)
followed directly from 3, largely based on the facile
transformation noted earlier. Diazomethane esterification and
subsequent chromatography afforded dimethyl glutarate. The
course of ozonolysis of trindane (1) is rationalized in Figure
1, where the yields of the various products secured are also
given. A noteworthy feature here is the simple manner in
which the bicyclic species 2 folds to generate the complex
tetracyclic system 3, initiated by enolate addition from the
top side, as shown in Figure 1.
The action of either ruthenium tetroxide or ozone gave,
largely or exclusively, products arising from attack on the
π-bond endo to the cyclopentane present in 1. While the
“milder” ruthenium reagent led to oxidation products of all
three π-bonds, ozonolysis resulted in the oxidative cleavage
of two of the three endocyclic olefins. What seems to be
general is that trindane and its derivatives can give oxidation
products retaining the pericycle in complex condensed
compounds. Surprisingly, although the pathways are grossly
dissimilar, with both oxidizing agents the substances formed
were closely related to the complex naturally occurring
products.
The present work tends to further support the concept of
a preference for endo π oxidation in 1 that retains the
pericycle and should provide a general route to medium ring
oxygenated compounds that can undergo further intramo-
lecular changes to complex condensed systems having
features similar to those of naturally occurring compounds.
A methylene chloride solution of trindane was ozonized
for 3 h. Reductive workup using dimethyl sulfide, followed
by chromatography of the neutral fraction on silica gel,
yielded compounds 2, 3, and 4 (Figure 1).4 The 1H and 13
C
The remarkable similarity of the product from ruthenium
tetroxide oxidation of 1 to ginkgolides has been mentioned
(4) Spectral data and experimental procedures for compounds 2-4:
Ozone was bubbled through a solution of trindane (0.495 g, 2.5 mmol) in
dry CH2Cl2 (30 mL) at ∼ -70 to -80 °C for 3.0 h, admixed with dimethyl
sulfide (0.8 mL), and left stirring for 2 h, during which time it was allowed
to reach room temperature, treated with saturated NaHCO3 (10 mL), and
stirred for an additional 1 h. The organic layer was separated, the aqueous
layer was washed with additional CH2Cl2 (3 × 10 mL), the layers were
combined, washed with distilled water (1 × 10 mL), dried (MgSO4), and
evaporated in vacuo, and the residue was chromatographed on a silica gel
column, prepared initially in hexane. Elution with benzene:ethyl acetate
(6:4) afforded, in sequence, 4 (0.100 g, 19%), 2 (0.105 g, 16%), and 3
(0.138 g, 21%), which crystallized from benzene:ethyl acetate as fine
needles, mp 138-140 °C. 2: 1H NMR (500 MHz, CDCl3) δ 1.80-2.32
(m, 6H, CH2), 2.40-2.60 (m, 8H, COCH2), 2.72-3.14 (m, 4H, allyl CH2);
13C NMR (400 MHz, CDCl3) δ 18.14, 19.62, 21.58. 29.63, 33.92, 34.30,
34.95, 35.34 (CH2), 140.88 (CdC), 154.50 (CdC), 198.41 (CdO), 212.51
(R,â-unsaturated CdO); IR (neat) 3064, 1737, 1698, 1596, 1450, 1301,
1201, 1178, 1016, 690 cm-1; GC-MS (m/z) (%) 262 (M) (11), 244 (M -
18) (13), 234 (M -1 × 28) (9), 206 (M -2 × 28) (14), 178 (M - 3 × 28)
(16), 150 (M - 4 × 28) (78). 3: 1H NMR (300 MHz, CDCl3) δ 1.41-
2.21 (m, 10H, CH2), 2.31-2.71 (m, 3H, COCH2, t-CH), 2.75-3.29 (m,
4H, allyl CH2); 13C NMR (300 MHz, CDCl3) δ 18.32, 20.01, 21.38, 30.15,
33.77, 34.32, 35.47, 35.81 (CH2), 141.12 (CdC), 154.55 (CdC), 198.89
(CdO), 213.43 (R,â-unsaturated CdO); IR (neat) 3400, 2944, 1752, 1680,
1440, 1344, 1040 cm-1; EI-MS (m/z) (%) 262 (M) (17), 246 (M - 16) (9),
234 (M - 1 × 28) (39), 206 (M - 2 × 28) (17). Anal. Calcd for C15 H18
O4: C, 68.70; H, 6.87. Found: C, 68.57; H, 6.61. 4: 1H NMR (300 MHz,
CDCl3) δ 2.10-2.25 (m, 4H, CH2), 2.65-3.05 (m, 10H, benzylic), 3.12-
3.23 (m, 2H, COCH2); 13C NMR (300 MHz, CDCl3) δ 24.46, 24.98, 25.66.
28.89, 30.02, 31.34, 32.26, 36.66 (CH2), 131.20-149.87 (aromatic), 207.80
(CdO); IR (neat) 2944, 1712, 1600, 1400, 1272, 1120 cm-1; FAB-MS (m/
z) (%) 213 (M + H) (74). The bicarbonate layer was adjusted to pH 2 with
citric acid, extracted with ethyl acetate (3 × 15 mL), washed with water (1
× 10 mL), dried (MgSO4), evaporated, and esterified with ethereal
diazomethane to afford 0.06 g (15%) of dimethyl glutarate, identical to an
authentic sample.
Figure 1. Products from ozonolysis of trindane (1).
NMR spectra showed the presence or absence of the benzene
core. Thus, it was easily seen that while compound 4 retained
the trindane core, in 2 and 3 the aromatic framework was
absent. Whereas the structure for 4 could be derived from
spectral data, those for 2 and 3 depended on the crystal
structure of 3 and the ready transformation of compound 2
to its isomer 3.
Analytical and mass spectral data suggested the formulas
of 2 and 3 to be C15H18O4,4 arising from the introduction of
four oxygen atoms to the unsaturated hydrocarbon. Com-
pound 2 was quite sensitive, and traces of acid transformed
it mostly to 3, which could be easily followed by IR and
TLC. While the 1H and 13C NMR spectra of 2 and 3 exhibited
a similar profile, their IR and TLC profiles were quite
divergent. In the IR, the former showed no hydroxyl, which
was present in 3. In terms of polarity, the Rf values of 2 and
3 were respectively 0.75 and 0.25 (TLC, eluent ) 40:60
benzene:ethyl acetate).
(5) Crystal structure data for 3: C15H18O4 (four independent molecules),
space group P(-1), Z ) 8, a ) 11.471(1) Å, b ) 14.158(1) Å, c ) 17.121-
(1) Å, R ) 73.02(0)°, â ) 89.26(0)°, γ ) 89.44(0)°, V ) 2659.1 Å3, dcalc
) 1.310 g/cm3, R1 ) 6.07% for 4855 data observed with Fo > 4σ, Cu KR
radiation. X-ray data collected on Bruker P4 diffractometer, θ-2θ scan
mode, scan speed 13°/min, scan width 1.9°. Structure was determined by
direct phase determination. Coordinates, bond lengths, bond angles,
anisotropic thermal parameters, and hydrogen coordinates are deposited with
the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, U.K.
Compound 3 was found to possess the highly condensed
structure shown in Figure 2B, by X-ray crystallography5 of
(3) Ranganathan, S.; Muraleedharan, K. M.; Bharadwaj, P.; Madhusudan-
an, V. P. Chem. Commun. 1998, 2239-40.
2448
Org. Lett., Vol. 3, No. 16, 2001
Ranganathan
