Oxyfunctionalization of non-natural targets by dioxiranes. 5. Selective oxidation of hydrocarbons bearing cyclopropyl moieties

Article abstract of DOI:10.1021/jo034768o

The powerful methyl(trifluoromethyl)dioxirane (lb) was employed to achieve the direct oxyfunctionalization of 2,4-didehydroadamantane (5), spiro[cyclopropane-1,2′-adamantane] (9), spiro[2.5]-octane (17), and bicyclo[6.1.0]nonane (19). The results are compared with those attained in the analogous oxidation of two alkylcyclopropanes, i.e., n-butylcyclopropane (11) and (3-methyl-butyl)-cyclopropane (14). The product distributions observed for 11 and 14 show that cyclopropyl activation of α-C-H bonds largely prevails when no tertiary C-H are present in the open chain in the tether; however, in the oxyfunctionalixation of 14 cyclopropyl activation competes only mildly with hydroxylation at the tertiary C-H. The application of dioxirane 1b to polycyclic alkanes possessing a sufficiently rigid framework (such as 5 and 9) demonstrates the relevance of relative orientation of the cyclopropane moiety with respect to the proximal C-H undergoing oxidation. At one extreme, as observed in the oxidation of rigid spiro compound 9, even bridgehead tertiary C-H's become deactivated by the proximal cyclopropyl moiety laying in the unfavorable eclipsed (perpendicular) orientation; at the other end, a cyclopropane moiety constrained in a favorable bisected orientation (as for didehydroadamantane 5) can activate an α methylene CH₂ to compete effectively with dioxirane O-insertion into tertiary C-H bonds. Comparison with literature reports describing similar oxidations by dimethyldioxirane (1a) demonstrate that methyl(trifluoromethyl)dioxirane (1b) presents similar selectivity and remarkably superior reactivity.

Full text of DOI:10.1021/jo034768o

Oxyfu n ction a liza tion of Non -Na tu r a l Ta r gets by Dioxir a n es. 5.
Selective Oxid a tion of Hyd r oca r bon s Bea r in g Cyclop r op yl
Moieties1
Lucia D’Accolti,† Anna Dinoi,† Caterina Fusco,‡ Antonella Russo,† and Ruggero Curci†,*
Dipartimento Chimica, Universita` di Bari, v. Amendola 173, I-70126 Bari, Italy, and C.N.R.-Istituto di
Chimica dei Composti Organometallici (ICCOM), Bari Section
csmirc17@area.ba.cnr.it
Received J une 5, 2003
The powerful methyl(trifluoromethyl)dioxirane (1b) was employed to achieve the direct oxyfunc-
tionalization of 2,4-didehydroadamantane (5), spiro[cyclopropane-1,2′-adamantane] (9), spiro[2.5]-
octane (17), and bicyclo[6.1.0]nonane (19). The results are compared with those attained in the
analogous oxidation of two alkylcyclopropanes, i.e., n-butylcyclopropane (11) and (3-methyl-butyl)-
cyclopropane (14). The product distributions observed for 11 and 14 show that cyclopropyl activation
of R-C-H bonds largely prevails when no tertiary C-H are present in the open chain in the tether;
however, in the oxyfunctionalixation of 14 cyclopropyl activation competes only mildly with
hydroxylation at the tertiary C-H. The application of dioxirane 1b to polycyclic alkanes possessing
a sufficiently rigid framework (such as 5 and 9) demonstrates the relevance of relative orientation
of the cyclopropane moiety with respect to the proximal C-H undergoing oxidation. At one extreme,
as observed in the oxidation of rigid spiro compound 9, even bridgehead tertiary C-H’s become
deactivated by the proximal cyclopropyl moiety laying in the unfavorable “eclipsed” (perpendicular)
orientation; at the other end, a cyclopropane moiety constrained in a favorable “bisected” orientation
(as for didehydroadamantane 5) can activate an “R” methylene CH2 to compete effectively with
dioxirane O-insertion into tertiary C-H bonds. Comparison with literature reports describing similar
oxidations by dimethyldioxirane (1a ) demonstrate that methyl(trifluoromethyl)dioxirane (1b)
presents similar selectivity and remarkably superior reactivity.
In tr od u ction
found that tertiary C-H bonds are considerably more
reactive toward dioxirane O-insertion than their second-
ary C-H or primary complements.1-3 Thus, high tertiary
vs secondary selectivities (Rts from 15 to over 250) can be
routinely achieved;2b as an example, the selective bridge-
head hydroxylation of adamantane (eq 1) by methyl-
(trifluoromethyl)dioxirane (TFD) (1b) yields adamantan-
1,3,5,7-tetraol along with the 1,3,5-triol, in 73% and 24%
yield, respectively.2c In these oxidations, kinetic data have
shown that 1b is more reactive than dimethyldioxirane
(DMD) (1a ) by a factor of over 700, with no loss of
selectivity.2c,3a
During the past decade, the direct oxyfunctionalization
of “unactivated” C-H bonds of simple and structurally
complex alkanes1,2 using dioxiranes (1) became a high-
light of the chemistry of these powerful oxidants.3 These
reactions are characterized by high selectivity, and it is
* To whom correspondence should be addressed. Fax: +39-080-
5442924. Phone: +39-080-5442070.
† University of Bari
‡ CNR-ICOMM, Bari.
(1) Part 4: D’Accolti, L.; Fusco, C.; Lucchini, V.; Carpenter, G. B.;
Curci, R. J . Org. Chem. 2001, 66, 9063 and references therein.
(2) (a) Murray, R. W.; J eyaraman, R. J . Org. Chem. 1985, 50, 2847.
(b) Mello, R.; Fiorentino, M.; Fusco, C.; Curci, R. J . Am. Chem. Soc.
1989, 111, 6749. (c) Mello, R.; Cassidei, L.; Fiorentino, M.; Fusco, C.;
Curci, R. Tetrahedron Lett. 1990, 31, 3067. (d) Adam, W.; Curci, R.;
Gonza´lez Nun˜ez, M. E.; Mello, R. J . Am. Chem. Soc. 1991, 113, 7654.
(e) Fusco, C.; Fiorentino, M.; Dinoi, A.; Curci, R.; Krause, R. A.; Kuck,
D. J . Org. Chem. 1996, 61, 8681. (f) Adam, W.; Curci, R.; D’Accolti, L.;
Dinoi, A.; Fusco, C.; Gasparrini, F.; Kluge, R.; Paredes, R.; Schulz, M.;
Smerz, A. K.; Veloza, L. A.; Weinko¨tz, S.; Winde, R. Chem. Eur. J .
1997, 3, 105. (g) D’Accolti, L.; Kang, P.; Khan, S.; Curci, R.; Foote, C.
S. Tetrahedron Lett. 2002, 43, 4649.
(3) For reviews, see: (a) Curci, R.; Dinoi, A.; Rubino, M. F. Pure
Appl. Chem. 1995, 67, 811. (b) Adam, W.; Hadjiarapoglou, L. P.; Curci,
R.; Mello, R. In Organic Peroxides; Ando, W., Ed.; Wiley: New York,
1992; Chapter 4, pp 195-219. (c) Curci, R. In Advances in Oxygenated
Processes; Baumstark, A. L., Ed.; J AI: Greenwich, CT, 1990; Vol. 2,
Chapter I, pp 1-59. (d) Murray, R. W. Chem. Rev. 1989, 89, 1187. (e)
Adam, W.; Curci, R.; Edwards, J . O. Acc. Chem. Res. 1989, 22, 205. (f)
Denmark, S. E.; Wu, Z. Synlett 1999, S1, 847.
More recent data suggest that alkane C-H bonds
positioned “R” to a cyclopropane ring might become
“activated” toward dioxirane O-insertion.4 In fact, in the
dioxirane oxyfunctionalization of Binor S (a polycyclic
10.1021/jo034768o CCC: $25.00 © 2003 American Chemical Society
Published on Web 08/30/2003
7806
J . Org. Chem. 2003, 68, 7806-7810

Oxyfunctionalization of Non-Natural Targets
hydrocarbon of complex architecture),1,5 we reported that
applying the powerful TFD yields the valuable ketone
resulting from C-9 methylene oxidation,1 along with
products expected from preferential hydroxylation at
bridgehead C-H bonds.1,3
(7)8 could be cleanly transformed into 8 (>95% GC yield,
93% conv, 2 h) using TFD (2 equiv). The novel ketol (8)
presents a strong IR CdO absorption at 1689 cm-1, as
well as inter- and intramolecular bonded OH stretching
bands; it was fully characterized by HRMS and by NMR.
The 1H NMR spectra of 8 (akin to that of ketone 6)
display inter alia one doublet and one complex multiplet,
respectively, at δ 2.64 and 2.19 (ratio 2:1) due to the C-H
resonances of the constrained cyclopropane ring. In the
13C NMR spectrum, well-resolved methine carbon signals
at δ 34.2, and 35.7 are attributed to the cyclopropane
carbons (reflecting the Cs symmetry of 8), while the Cd
O and the C-OH signals are positioned, respectively, at
δ 211.3 and 72.8.
Similar to the Binor S case mentioned above, the
finding that dioxirane O-insertion at C-10 methylene in
5 can compete effectively with the normally favored
insertion at tertiary bridgehead C-H may be ascribed
to the favorable bisected orientation of the methylene
C-H bonds relative to the cyclopropyl ring. This view is
reinforced by the observation that no hydroxylation
occurs at C-1 and C-5 tertiary C-H; indeed, these
bridgehead bonds would become deactivated toward
O-insertion since their p orbital component nearly lays
in the unfavorable “eclipsed” (“perpendicular”) orientation
with respect to the C2′-C3′ bond of the cyclopropyl
moiety.1,6
The results were rationalized on ground of a FMO
model, suggesting that the mentioned methylene C-H
bonds might become activated by the neighboring cyclo-
propyl group.1 In 2, the rich-in-p character cyclopropane
ring orbitals are constrained by the rigid framework to
lay in the favorable “bisected” orientation1 with respect
to the p component of the “R” methylene C-H bonds; the
latter p orbitals interact with the dioxirane empty σ*O-O
orbital during the “oxenoid” O-insertion.1 To test this
hypothesis, we undertook to examine the reactivity of
dioxiranes toward a few hydrocarbons of choice, aiming
to establish the effect of the cyclopropyl moiety on
selectivity. Our findings are reported below.
Resu lts a n d Discu ssion
That the cyclopropyl moiety can exercise a marked
activating effect on dioxirane oxidation at “R” C-H bonds
is illustrated by the case of 2,4-didehydroadamantane (5).
7
For this substrate, Murray et al. have reported that
reaction with 2.2 equiv of DMD (1a ) proceeds at room
temperature with 82% conversion, yielding 2,4-didehy-
droadamantan-10-one (6) and 2,4-didehydroadamantan-
7-ol (7) in 29% and 21% yield, respectively, during 12 h.
We verified that the comparable selectivity is attained
in the oxyfunctionalization of 5 on going from DMD (1a )
to the more powerful TFD (1b). In the presence of 2 equiv
of TFD, hydrocarbon 5 is converted to ketone 6 and
alcohol 7 in 40 and 60% yield, respectively. The oxidation
with TFD is notably faster, achieving 80% conversion in
1.5 h at 0 °C.
Then, treatment of 5 with TFD excess (4 equiv) at the
conditions in eq 3 results in the practically complete
substrate conversion into ketone 6 and the valuable
7-hydroxy-2,4-didehydroadamantan-10-one (8) as the
main products. GC monitoring of the reaction showed
that ketol 8 is generated by the consecutive oxidation of
the alcohol 7. In fact, in control experiments we verified
that authentic samples of 2,4-didehydroadamantan-7-ol
The peculiar arrangement of the spirofused cyclopropyl
moiety in the framework of 9 makes this substrate
another attractive probe. We find that hydroxylation of
spiro adamantanecyclopropane 9 occurs at bridgehead
C-5 exclusively, yielding the bridgehead alcohol 109 (eq
4). In a parallel with the cyclopropylcarbinyl cation case,6
it is likely that the constrained perpendicular conforma-
tion of the transition state for dioxirane O-insertion
results in sizable destabilization. Indeed, the proximal
C-H’s at C-3 and C-1 become deactivated because their
p orbital component is forced to lay in the unfavorable
“eclipsed” arrangement with respect to the cyclopropane
ring. It is instructive to compare the data above with
those collected for representative open-chain alkylcyclo-
propanes such as 11 and 14 (Chart 1). Here, in the
absence of serious steric constrains, the cyclopropane
moiety is relatively free to adopt orientations with almost
continuous angles between the extremes of 0° and 90°
(4) (a) Curci, R.; D’Accolti, L.; Fusco, C. Tetrahedron Lett. 2001, 42,
7087. (b) Newcomb, M.; Choi, S.-Y.; Simakov, P. A. Tetrahedron Lett.
1998, 39, 8187. (c) Vanni, R.; Garden, S. J .; Banks, J . T.; Ingold, K. U.
Tetrahedron Lett. 1995, 36, 7999.
(5) Pramod. K.; Eaton, P. E.; Gilardi, R.; Flippen-Anderson. J . L. J .
Org. Chem. 1990, 55, 6105.
(6) For instance, see: (a) Hehre, W. J . Acc. Chem. Res. 1975, 8, 369.
(b) Rhodes, Y. E.; DiFate, V. G. J . Am. Chem. Soc. 1972, 94, 7582 and
references therein.
(7) Murray, R. K.; Teager, D. S. J . Org. Chem. 1993, 58, 5548.
(8) Bobek, M. M.; Brinker, U. H. J . Am. Chem. Soc. 2000, 122, 7430.
J . Org. Chem, Vol. 68, No. 20, 2003 7807

D’Accolti et al.
CHART 1
using the powerful TFD (1b) in these oxidation is further
demonstrated by the results reported in Chart 2.
Concerning products of oxyfunctionalization at the CH2
that are activated by the contiguous cyclopropane ring
in 19, it is worth of note that just some of the anti alcohol
21a (and none of the syn 21b) is left behind as intermedi-
ate during the transformation into carbonyl. This might
be ascribed to stereochemical effects that govern the
O-insertion at the syn vs the anti alcohol leading to the
gem-diol precursor of carbonyl. Specifically, in a preferred
quasi chair-boat conformation, the anti alcohol 21a would
experience a greater steric hindrance (Chart 2) to the
optimal stereoalignment required for dioxirane O-inser-
tion,12 hence its slowest conversion into carbonyl with
respect to the its syn counterpart 21b.13
In conclusion, data reported herein confirm that the
cyclopropane moiety can have a marked influence in
activating proximal R-C-H bonds toward dioxirane oxy-
functionalization; normally, this directing effect is dis-
tinctly minor compared to that exercised by a tertiary
C-H. However, the application of dioxiranes to polycyclic
alkanes possessing a sufficiently rigid framework dem-
onstrates the relevance of relative orientation of the
cyclopropane moiety with respect to the C-H bonds
undergoing oxyfunctionalization. For acyclic substrates,
the directing effect is significantly weaker than the
activating influence of a tertiary C-H. At one extreme,
even bridgehead tertiary C-H’s are deactivated by a
perpendicular orientation relative to the plane of a
proximal cyclopropane. At the other extreme, secondary
C-H bonds constrained to a “bisected” orientation rela-
tive to the neighboring cyclopropane are sufficiently
activated to a point that their oxyfunctionalization ef-
fectively competes with the otherwise preferred O-inser-
tion into tertiary C-H bonds at bridgeheads. Thus,
stringent stereoalignment factors seem to dictate transi-
tions in regioselectivity. In fact, even bridgehead tertiary
C-H’s might become deactivated by a proximal cyclo-
propyl moiety laying perpendicularly, as observed in the
oxidation of rigid spiro compound 9 (hence the selective
hydroxylation at the distal (γ) bridgehead C5-H).
CHART 2
with respect to the p orbital component of the proximal
C-H bonds.
The product distributions observed for 11 indicate that
cyclopropyl activation of R-C-H bonds largely prevails
when no tertiary C-H is present. However, the products
formed in the oxidation of 14 (Chart 1) clearly demon-
strate that normally cyclopropyl activation can compete
only mildly with oxidation at tertiary C-H. Cyclopropyl
activation might again be invoked in order to rationalize
the preferential oxyfunctionalization at R-CH2 observed
for spirooctane 17 (eq 5) and for bicyclononane 19 (Chart
2). Indeed, in the oxidation of 17, the spiro[2.5]octan-4-
one (18)10 produced was accompanied by just small
amounts of the isomeric 5-one and 6-one (3% and 4%,
respectively).
It should be mentioned that in none of the cases
examined does oxidative scission of the cyclopropyl
moiety take place. This behavior is in contrast with the
application of ozone (a bona fide ground-state singlet
biradical)14 to analogous systems, for instance, 2,4-
didehydroadamantane (5).7 Thus, it seems that dioxi-
ranes are capable of giving oxyfunctionalization exclu-
sively at C-H’s neighboring the cyclopropane moiety,
(12) (a) Bach, R. D.; Glukhovtsev, M. N.; Canepa, C. J . Am. Chem.
Soc. 1998, 120, 10528. (b) Du, X.; Houk, K. N. J . Org. Chem. 1998, 63,
6480. (c) Bach, R. D.; Owensby, A. L.; Andre´s, J . L.; Su, M.-D.;
McDouall, J . J . W. J . Am. Chem. Soc. 1993, 115, 5768 and references
therein.
(13) This was confirmed through competition experiments wherein
authentic samples of the stereomeric alcohols were made to react with
TFD in CH2Cl2 at 0 °C. With 3.8 × 10-2 M 21a and 3.1 × 10-2 M 21b,
both in excess over dioxirane (the limiting reagent, 1.4 × 10-2 M), GC
monitoring and peak integration (Freon A112 internal standard)
allowed us to estimate that the calibrated (Asyn/Aanti) area ratio changes
from 0.95 to 0.46 upon dioxirane complete consumption (10 s, iodom-
etry). Thus, the transformation of syn alcohol 21b into ketone 20 is
over twice faster than that of its anti counterpart 21a .
The reaction of cis-bicyclononane (19) with DMD (1a )
has been previously explored; ketones 20, 22, and 23 were
all produced (with 20 in highest proportion, ca. 65%), but
with a combined yield of a mere 9%.11 The advantage of
(9) Buss, V.; Gleiter, R.; Schleyer, P. R. J . Am. Chem. Soc. 1971,
93, 3927.
(10) Crandall, J . K.; Seidewand, R. J . J . Org. Chem. 1970, 35, 697.
(11) Dehmlow. E. V.; Heiligenstadt, N. Tetrahedron Lett. 1996, 30,
5363.
(14) For instance, see: Harding, L. B.; Goddard, W. A. J . Am. Chem.
Soc. 1978, 100, 7180.
7808 J . Org. Chem., Vol. 68, No. 20, 2003

Oxyfunctionalization of Non-Natural Targets
Didehydroadamantane (5) [mp 201-203 °C; lit.20a mp 201-
204 °C] was prepared upon pyrolysis of the lithium salt of
adamant-2-one-p-tosylhydrazone,20b and purified by column
chromatography (silicagel, pentane). 2-Methyleneadamantane
was obtained upon dehydration (H3PO4) of commercial 2-methyl-
2-adamantanol and purified (99%+, GC) by sublimation (mp
136-137 °C).21 Starting with the corresponding alkenes, spiro-
[cyclopropane-1,2′-adamantane] (9),9 n-butylcyclopropane
(11),22a,23 (3-methyl-butyl)-cyclopropane (14) (HRMS calcd for
C8H16 112.1252, found 112.1251; 1H and 13C NMR cf. Support-
ing Information), spiro[2.5]octane (17),24 and bicyclo[6.1.0]-
nonane (19),24d,25 were obtained upon Simmons-Smith cyclo-
propanation with CH2I2/Zn/CuCl.22 Authentic samples of
oxidation products 1-cyclopropyl butan-1-one (12),26,27 1-cyclo-
propylbutan-2-one (13),27b 4-cyclopropyl-2-methyl-butan-2-ol
(15), 1-cyclopropyl-3-methyl-butan-1-one (16a ),28 1-cyclopropyl-
3-methyl-butan-1-ol (16b),28 cis-bicyclo[6.1.0]nonan-2-one
(20),29,30 and anti- and syn-bicyclo[6.1.0]nonan-2-ol (21a and
21b, respectively)29 were obtained following the literature
procedures.22,31
Oxid a tion of Sp ir o[cyclop r op a n e-1,2′-a d a m a n ta n e] (9)
w ith Meth yl(tr iflu or om eth yl)d ioxir a n e (1b). The follow-
ing procedure is representative of hydrocarbon oxidations
using TFD. To a stirred solution of 9 (220 mg, 1.36 mmol)
dissolved in 10 mL of CH2Cl2 (also containing the Freon A112
internal standard) and kept at 0 °C was added methyl-
(trifluoromethyl)dioxirane (2.5 mL of 0.65 M 1b in TFP, 1.6
mmol) in one portion. The reaction was monitored by GC. After
20 min, removal of the volatile solvents in vacuo and column
chromatography afforded pure (99%+, GC) 5-hydroxy-spiro-
[cyclopropane-1,2′-adamantane] (10)9 (225 mg, 1.26 mmol,
isolated yield 93%): white solid, uncorrected mp 138-140 °C
[lit.9 mp 139-140 °C]; spectral characteristics were in agree-
ment with literature data.9
Oxid a tion of 2,4-Did eh yd r oa d a m a n ta n e (5) w ith Me-
th yl(tr iflu or om eth yl)d ioxir a n e. According to the above
procedure, hydrocarbon 5 (116 mg, 0.86 mmol) dissolved in
CH2Cl2 (15 mL) was made to react at 0 °C with excess methyl-
(trifluoromethyl)dioxirane (1b ) (5 mL, 0.74 M in TFP, 3.70
mmol), and the reaction was monitored by GC. After 1.5 h,
removal of the solvents in vacuo and column chromatography
afforded 8,9-didehydroadamantan-2-one 6 (86 mg, 0.58 mmol,
yield 66%; uncorrected mp 206-207 °C;32 spectral data were
in agreement with literature7,32) and ketol 8 (38 mg, 0.23 mmol,
yield 25%). 3-Hydroxy-8,9-didehydroadamantan-2-one (8): white
solid, uncorrected mp 196-197 °C (98%+, GC); 1H NMR
(CDCl3, 500 MHz) δ 3.98 (s, 1H), 2.64 (d, 2H, J ) 2), 2.45 (tt,
2H, J ) 8, J ) 2), 2.20 (complex m, 1H, J ) 10), 2.10 (td, 1H,
leaving cyclopropane C-C bonds intact.15 This is similar
to hydroxylations of several hydrocarbons containing
annealated or spirofused cyclopropane moieties by cyto-
chrome P450 enzymes.16 There are significant differences,
however. For bicyclo[2.1.0]pentane (BCP), a fast radical
“clock”,17 P450 oxidation gives a 7:1 relative yield of
unrearranged to ring-opening products,16a whereas none
of the latter result from the application of DMD (1a ).4a
Altough the reaction of the bacterial enzyme P450cam with
spiro[2.5]octane (17) yields no products derived from ring-
opening of a cyclopropyl carbinyl radical, the product
distribution from this oxidation varies significantly from
dioxirane oxidation (eq 5) since the 6-hydroxy, 5-hydroxy,
and 4-hydroxy derivatives are all produced, with the
latter (amounting to hydroxylation at CH2 â to the
cyclopropane ring) as the major product (63%).16b It is
likely that the direct, highly regio- and stereospecific
dioxirane oxidation of target non-natural molecules
herein and of strained “cage” compounds18 will find
convenient applications in the facile access to new
compounds and useful building blocks.
Exp er im en ta l Section
Ma ter ia ls a n d Meth od s. Boiling points and melting points
were not corrected. The GC analyses were run using a SPB-5
column (30 m × 0.25 µm id); in most cases, 1,1,1,2-tetrachloro-
2,2-difluoroethane (Freon A112) was employed as inert inter-
nal standard. Column chromatography was performed using
silicagel (230-400 mesh), n-pentane to n-pentane/Et2O 9:1
gradient eluent. The MS analyses were performed in EI mode
(70 eV). The 1H NMR spectra were recorded on a 500 MHz
and/or 200 MHz spectrometer; resonances are referenced to
residual isotopic impurity CHCl3 (7.26 ppm) of solvent CDCl3
and/or to TMS. The 13C NMR spectra (125.759 MHz) are
referenced to the middle peak of CDCl3 solvent (77.0 ppm).
FTIR spectra are relative to KBr pellets or films (deposited
on KBr plates). High-resolution MS spectra were run in EI+
mode (source temperature 200 °C, trap current 150 µA, EE
30 eV, DIP). Commercial 1,1,1-trifluoro-2-propanone (TFP) (bp
22 °C) was purified by fractional distillation over granular
P2O5, stored over 5 Å molecular sieves, and routinely redistilled
prior to use. Commercial starting materials, methylene chlo-
ride, and other solvents were purified by standard methods.
Curox triple salt 2KHSO5‚KHSO4‚K2SO4 (a gift from Peroxid-
Chemie GmbH, Mu¨nich, Germany) was our source of potas-
sium peroxymonosulfate employed in the synthesis of dioxi-
rane. Solutions of 0.8-1.0 M methyl(trifluoromethyl)dioxirane
(1b) in TFP and solutions of 0.08-0.16 M dimethyldioxirane
(1) in acetone were obtained by adopting procedures, equip-
ment, and precautions already reported in detail.2b,19 2,4-
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Udding, A. C.; Strating, J .; Wynberg, H.; Schlatmann, J . L. M. A. J .
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(15) The only exception reported so far is constituted by the
dioxirane oxidation of the unstable 1,3-didehydroadamantane, which
presents a highly strained cyclopropane C-C bond having marked
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J . Org. Chem, Vol. 68, No. 20, 2003 7809

D’Accolti et al.
J ) 9, J ) 2), 1.90 (m, 4H), 1.62 (dd, 1H, J ) 9, J ) 2); {1H}13C
NMR (CDCl3, 125 MHz) δ 211.3 (CdO), 72.8 (C-OH), 50.5,
45.4, 39.7, 35.7, 34.2; IR (CH2Cl2) 3590, 3473, 3054, 2926, 1689,
1458, 1142, 1044 cm-1; GC/MS (70 eV) m/z (rel intensity) 164
(M+, 9), 136 (12), 79 (52), 58 (100), 43 (15); HRMS calcd for
2,4-dinitrophenylhydrazone provided a light-orange crystalline
derivative: mp 158-159 °C.34
Ack n ow led gm en t. Partial support of this work by
the Ministry of University and Scientific and Research
of Italy (COFIN National Project) is gratefully acknowl-
edged. Thanks are due to Dr. R. Mello (University of
Valencia, Spain) for performing the HRMS analyses.
C
10H12O2 164.0839, found 164.0837.
7-Hyd r oxy-d id eh yd r o-2,4-a d a m a n ta n e (7) was prepared
upon oxidation of 2,4-didehydroadamantane (5) with 1 equiv
of methyl(trifluoro-methyl)dioxirane (1b) in CH2Cl2 (10 mL)
on a 1 mmol scale. Solvent removal in vacuo and column
chromatography afforded alcohol 7: uncorrected mp 200-201
°C (98%+, GC); 1H and 13C NMR data in agreement with
literature.7,8 Oxidation of spiro[2.5]octane (17) (1.8 mmol) in
CH2Cl2 (10 mL) with 2.2 equiv of TFD (1b), after solvent
removal and distillation. provided pure spiro[2.5]octan-4-one
(18): uncorrected bp 85-86 °C/26 mmHg [lit.10 bp 82-84 °C/
Su p p or tin g In for m a tion Ava ila ble: Characterization
data for compounds 14, 15, 16a , and 16b, and copies of 1H
NMR, {1H}13C NMR, and HRMS spectra for ketol 8. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O034768O
1
24 mmHg] (98%+, GC); GC/MS, H and 13C NMR character-
(33) Leriverend, P.; Conia, J .-M. Bull. Soc. Chim. Fr. 1966, 121.
(34) Conia, J . M.; Leriverend, P.; Bouket, J .-L. Tetrahedron Lett.
1964, 43, 3189.
istics consistent with the given structure and with reported
literature data.10,33 Conversion of 18 into the corresponding
7810 J . Org. Chem., Vol. 68, No. 20, 2003