Oxidative cyclization of unsaturated ketene dithioacetals with ceric ammonium nitrate to form bicyclic lactones

Article abstract of DOI:10.1016/S0040-4020(00)00857-7

Ceric ammonium nitrate oxidizes unsaturated ketene dithioacetals in wet MeCN to give cation radicals that cyclize to tri-substituted double bonds and styrenes by cation-like cyclizations leading to cyclic cation radicals that are transformed by further ox

Full text of DOI:10.1016/S0040-4020(00)00857-7

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 10127±10132
Oxidative Cyclization of Unsaturated Ketene Dithioacetals with
Ceric Ammonium Nitrate to Form Bicyclic Lactones
*
Barry B. Snider, Bo Shi and Cheri A. Quickley
Department of Chemistry, Brandeis University, Waltham, MA 02454-9110, USA
Received 21 December 1999; accepted 25 January 2000
AbstractÐCeric ammonium nitrate oxidizes unsaturated ketene dithioacetals in wet MeCN to give cation radicals that cyclize to tri-
substituted double bonds and styrenes by cation-like cyclizations leading to cyclic cation radicals that are transformed by further oxidation,
hydrolysis and cyclization to bicyclic lactones in moderate to good yield. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
Moeller has developed electrochemical oxidative cycliza-
tions of unsaturated enol ethers.1c,4,5 For instance, oxidation
of styrene enol ether 5 afforded 70% of cyclopentane 6 as a
mixture of isomers,4 while oxidation of allylsilane enol
ether 7 provided 74% of 8 as a mixture of isomers
(Scheme 2).5
Oxidation of both alkyl and silyl enol ethers provides an
attractive route to cation radicals that can be trapped intra-
molecularly with alkenes, enol ethers, vinylsilanes, allyl-
silanes, and electron rich aromatic rings.1 These
oxidations can be carried out with one-electron oxidants,
electrochemically,1c or by photochemical electron transfer
by irradiation in the presence of dicyanoanthracene. For
instance, we found that oxidation of silyl enol ether 1 with
either ceric ammonium nitrate (CAN) and NaHCO3 or
Cu(OTf)2 and Cu2O in MeCN generated cation radical 2
that cyclized to give cation radical 3. Desilylation, cycliza-
tion and oxidation afforded 4 stereoselectively in 87%
yield (Scheme 1).2 Livinghouse has recently shown that
(CF3CH2O)VOCl2 is a very effective oxidant for related
cyclizations and oxidative coupling of enol silyl ethers.3
Mattay has developed photochemical electron transfer
(PET) as a method for generation of cation radicals from
enol ethers.6 Irradiation of silyl enol ether 9 and dicyano-
anthracene (DCA) formed cation radical 10 by electron
transfer to the excited state of DCA. Cyclization gave 11,
which lost TMS to give ketone radical 12. Unfortunately,
radical 12 was reduced to afford 25% of decalone 13 by the
DCA radical anion generated by the oxidation of 10, so that
the radical functionality is lost by reduction in PET oxida-
tive cyclization of unsaturated silyl enol ethers (Scheme 3).
Scheme 1.
Scheme 2.
Keywords: cation-like cyclization; ceric ammonium nitrate; bicyclic lactones.
* Corresponding author. Tel.: 1781-736-2550; fax: 1781-736-2516; e-mail: snider@brandeis.edu
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00857-7

10128
B. B. Snider et al. / Tetrahedron 56 (2000) 10127±10132
Scheme 3.
Strong oxidants are required for the oxidation of enol ethers.
Ketene acetals are more electron rich than enol ethers and
should therefore be more readily oxidized. Unfortunately,
they are very hydrolytically unstable and initial attempts at
oxidative cyclizations of unsaturated ketene acetals resulted
only in hydrolysis to the ester.2 Readily available ketene
dithioacetals are relatively stable but should be more easily
oxidized than enol ethers because the double bond is substi-
tuted by two sulfur atoms that are electron donating by
resonance. We therefore prepared a variety of unsaturated
ketene dithioacetals and examined their oxidative cycliza-
tions with a variety of one-electron oxidants.
Lower yields were obtained using Mn(OAc)3´2H2O in
17:2:1 MeCN/TFA/H2O.9 Oxidative cyclization does not
occur with Cu(NO3)2, K3Fe(CN)6, [FeCl2(DMF)2][FeCl4],
or Ag2CO3 on celite. Cu(OTf)2,2 VOCl3, and (CF3CH2O)-
VOCl2 were not investigated since these oxidants are not
compatible with water. Lower yields of lactone 17 were
obtained from the ketene dithioacetal obtained by Peterson
reaction of 14 with 2-trimethylsilyl-1,3-dithiane.7 These
oxidative cyclizations also gave more complex mixtures
because the byproducts derived from 1,3-propanedithiol
were not volatile or water soluble. The ketene dithioacetal
obtained by a Peterson reaction with bis(phenylthio)tri-
methylsilane was less electron rich and did not react with
CAN to give lactone 17.
Results and Discussion
Ketene dithioacetal 18 was prepared analogously to 16 in
85% yield. Slow addition over 4 h to excess CAN in 19:1
MeCN/H2O afforded 40% of the known lactone 1910 stereo-
selectively as the only isolable product. No cyclic products
were obtained by oxidation of ketene dithioacetal 20, which
was prepared analogously from 6-nonenal, indicating that a
moderately electron rich double bond is needed for oxida-
tive cyclization to occur (Scheme 5).
Ketene dithioacetal 16 was prepared in one step in 90%
yield by Seebach's procedure from citronellal (14) by a
Peterson reaction with the lithium salt of bis(methylthio)tri-
methylsilylmethane (15).7 Slow addition of ketene dithio-
acetal 16 over 4 h to 6 equiv. of CAN in 19:1 MeCN/H2O
and stirring overnight afforded 49% of bicyclic lactone 17
stereoselectively as the only characterizable product. Rapid
addition of 16 gave 30% of 17, suggesting that dimerization
may be a side reaction in concentrated solution. Although
the oxidation requires only 2 equiv. of CAN in principal,
excess CAN was needed since the sulfur byproducts were
oxidized by CAN. MeSSO2Me,8 which can be formed by
oxidation of MeSH with 6 equiv. of CAN, was obtained as a
minor byproduct in some reactions. Since the two oxygens
of 17 are derived from water, lower yields of 17 were
obtained if water was not added as a cosolvent. Comparable
yields of 17 were obtained in MeCN containing 2±10%
water. The reaction was most successfully carried out in
air. For reasons that are not clear, lower yields were
obtained under either N2 or O2 atmospheres (Scheme 4).
The stereochemistry of lactone 17 was unambiguously
established by analysis of the coupling constants. The
13.4 Hz coupling constant between H3a and H7a established
that both of these hydrogens are axial on the cyclohexane
ring. The axial H7 absorbs at d 1.00 (ddd, 1, Jˆ12, 12,
11.6 Hz). The large geminal and two large vicinal coupling
constants indicate that the methyl group is equatorial on
the cyclohexane ring. The stereochemistry of 19 was
established by a 1D NOESY experiment. Irradiation of the
methyl doublet at d 1.15 showed strong NOEs to H6 at d 2.4
and H6a at d 2.76 and a weak NOE to H3a at d 2.58, indicat-
ing that the methyl group, H3a, and H6a are on the same face
of 19 (Scheme 6).
Scheme 4.
Scheme 5.

B. B. Snider et al. / Tetrahedron 56 (2000) 10127±10132
10129
Scheme 6.
There are two fundamentally different mechanisms by
which these cyclizations can occur, which are discussed
for 16 as a representative example. Oxidation of 16 will
give cation radical 21, which can undergo a radical-like
cyclization to give 22 as occurs in the oxidative cyclization
of enol silyl ether 1 and PET cyclization of 9. Reaction of 22
with water and loss of a proton and MeSH will give thioester
radical 23, which can be oxidized to thioester cation 25.
Reaction with water to give alcohol thioester 28 and cycli-
zation will provide lactone 17.
substituted double bonds as in the formation of 4.2 This
suggests that cation-radicals obtained from ketene dithio-
acetals undergo cation-like cyclizations, while cation-
radicals obtained from enol ethers undergo radical-like
cyclizations (Scheme 7).
Styrenes are suf®ciently nucleophilic to react with the cation
radicals obtained from ketene dithioacetals. Ketene dithio-
acetals 29 and 35 were obtained in 85 and 82% yield from
7-phenyl-6-heptenal4 and 6-phenyl-5-hexenal,4 respec-
tively, as mixtures of stereoisomers. Slow addition of 29
to CAN in 19:1 MeCN/H2O afforded 22% of the known
lactone 3111 and traces of the known lactones 32±3411 in
the yields indicated. Nitrate thioester 30 was also isolated in
5% yield. Similar product mixtures were obtained from the
pure cis and trans isomers of 29.
Alternatively, cation radical 21 can undergo a cation-like
cyclization to give 24, which will react with water to give
alcohol radical 26. Oxidation of 26 will afford alcohol
cation 27, which will react with water with loss of a proton
and MeSH to afford alcohol thioester 28. The failure of the
less nucleophilic 1,2-disubstituted alkene of 20 to cyclize
suggests that cation radical 21 cyclizes by the cation-like
pathway to provide 24 since the electronic character of the
double bond should be less important in radical-like cycli-
zations. The reactivity of cation radicals obtained from
ketene dithioacetals are thus very different from the cation
radicals obtained from enol ethers, which add to 1,2-di-
The presence of the thioester of 30 was established by the
methyl singlet at d 2.36, the carbonyl carbon at d 202.2, and
the carbonyl absorption at 1686 cm21. The presence of the
nitrate of 30 was established by the absorptions at 1637 and
1281 cm21. The isolation of the nitrate indicates that the
benzylic cation analogous to either 24 or 25 can be trapped
Scheme 7.
Scheme 8.

10130
B. B. Snider et al. / Tetrahedron 56 (2000) 10127±10132
Scheme 9.
by nitrate instead of water. Formation of nitrate esters in
CAN oxidations is well known (Scheme 8).2,12
4,8-Dimethyl-1,1-bis(methylthio)-1,7-nonadiene
(16).
2.5 M n-BuLi in hexanes (0.44 mL, 1.10 mmol) was
added to a solution of bis(methylthio)trimethylsilyl-
methane7 (180 mg, 1.00 mmol) in 10 mL of dry THF
under N2 at 2408C. The solution was warmed to rt, stirred
for 1 h, and recooled to 2408C. Citronellal (185 mg,
1.20 mmol) was added and the solution was warmed to rt
and stirred for 2 h. Distilled water (10 mL) was added and
the THF was removed under reduced pressure. The remain-
ing aqueous solution was extracted with hexanes. The
combined organic layers were dried over Na2SO4 and
concentrated. Flash chromatography of the residue on silica
gel (hexanes) gave 220 mg (90%) of ketene dithioacetal 16
Slow addition of 35 to CAN in 19:1 MeCN/H2O afforded
3% of the analogous nitrate thioester 36, 10% of the known
lactone 38,13 2% of lactone 37, 6% of the strained trans-
fused lactone 39, and 5% of the nitrate acid 40. Examination
of the 1H NMR spectrum of the crude product indicated the
absence of trans-fused lactone 39 and that .10% of nitrate
acid 40 was present. This suggested that 40 cyclized to
lactone 39 during chromatography. This was con®rmed by
the slow conversion of 40 to 39 in CDCl3 containing silica
gel. Presumably the reactive benzylic nitrate undergoes
solvolysis to give a cation which cyclizes to give the
trans-fused lactone with the more stable pseudoequatorial
phenyl group.
1
as a colorless liquid: H NMR 5.93 (dd, 1, Jˆ7.3, 7.3 Hz),
5.09 (br t, 1, Jˆ7.3 Hz), 2.34 (ddd, 1, Jˆ14.1, 7.3, 6.1 Hz),
2.28 (s, 3), 2.27 (s, 3), 2.22 (ddd, 1, Jˆ14.1, 7.9, 7.9 Hz),
2.07±1.91 (m, 2), 1.68 (s, 3), 1.61 (s, 3), 1.58±1.51 (m, 1),
1.34 (dddd, 1, Jˆ13.4, 9.2, 6.1, 6.1 Hz) 1.18 (dddd, 1,
Jˆ13.4, 9.2, 7.3, 6.1 Hz), 0.89 (d, 3, Jˆ6.1 Hz); 13C NMR
134.4, 132.7, 131.2, 124.7, 37.6, 36.7, 33.0, 25.7, 25.6, 19.5,
17.7, 16.9, 16.7; IR (neat) 1676, 1582.
The stereochemistry of lactone 39 was established by the
14.7 Hz vicinal coupling constant between the ring fusion
hydrogens H3a and H6a, the 10.1 Hz vicinal coupling
constant between H3 and H3a, the NOE between H3 and
H6a, and the absence of an NOE between H3 and H3a. The
stereochemistry of lactone 37 was established by the 8.5 Hz
coupling constant between the ring fusion hydrogens H3a
and H6a, and an NOE and 6.7 Hz vicinal coupling constant
between H3 at d 5.73 and H3a at d 3.14 (Scheme 9).
(3aa,6a,7ab)-Hexahydro-3,3,6-trimethyl-1(3H)-isobenzo-
furanone (17). A solution of freshly prepared 16 (110 mg,
0.45 mmol) in 10 mL of MeCN was added over 4 h by
syringe pump to a solution of CAN (1.483 g, 2.70 mmol)
in 40 mL of 95:5 MeCN/water at rt. Additional CAN
(109 mg, 0.20 mmol) was added when the solution turned
colorless. (For the other three substrates, no additional CAN
was needed.) The yellow solution was stirred overnight and
20 mL of H2O was added. MeCN was removed under
reduced pressure. 10 mL of EtOAc and 1 mL of saturated
Na2SO3 aqueous solution were added to the solution, which
was stirred for 5 min to reduce the excess Ce(IV) to give a
colorless solution. (More Na2SO3 aqueous solution was
needed for the other three substrates. However, too much
will cause the formation of emulsions that are extremely
hard to break.) The solution was extracted with three
portions of EtOAc. The combined organic layers were
dried over Na2SO4 and concentrated to give 105 mg of
crude product. Flash chromatography on silica gel (9:1
hexanes/EtOAc) gave 40 mg (49%) of pure lactone 17 as
a white solid. Elution with EtOAc and then MeOH gave
28 mg (35%) of unidenti®ed polar compounds.
In conclusion, we have demonstrated that CAN oxidizes
ketene dithioacetals in wet MeCN to cation radicals that
will cyclize to trisubstituted double bonds and styrenes lead-
ing to lactones and nitrate thioesters and acids. Cyclizations
forming cyclohexanes give primarily or exclusively the
trans-fused lactones 17 and 31, while cyclizations forming
cyclopentanes give primarily or exclusively the cis-fused
lactones 18 and 38. The requirement for electron rich double
bonds suggests that these cyclizations are cation-like as in
the cyclization of 21 to 24 and are mechanistically quite
different from the cyclizations of cation-radicals derived
from enol ethers, which appear to be radical-like. Further
development and application of this reaction is currently
underway.
Experimental
1
Data for lactone 17: mp 68±708C; H NMR 2.23 (ddd, 1,
Jˆ13.4, 11.6, 3.7 Hz), 2.15 (dddd, 1, Jˆ12.8, 3.7, 3.7,
1.2 Hz), 1.89±1.82 (br d, 1, Jˆ13.4 Hz), 1.79 (dddd, 1,
Jˆ12.2, 3.3, 3.3, 3.3 Hz), 1.67 (ddd, 1, Jˆ13.4, 12.2,
3.1 Hz), 1.50±1.38 (m, 1), 1.43 (s, 3), 1.26 (s, 3), 1.24
(dddd, 1, Jˆ12, 12, 12, 3.7 Hz), 1.00 (ddd, 1, Jˆ12, 12,
General
NMR spectra were recorded at 400 MHz in CDCl3. Chemi-
cal shifts are reported in d ppm and coupling constants in
Hz. IR spectra are reported in cm21
.

B. B. Snider et al. / Tetrahedron 56 (2000) 10127±10132
10131
11.6 Hz), 0.99 (d, 3, Jˆ6.7 Hz), 0.97 (dddd, 1, Jˆ13, 13, 13,
3 Hz); 13C NMR 176.5, 85.5, 52.3, 44.1, 34.2, 33.7, 32.6,
27.3, 25.7, 21.9, 20.7; IR (CH2Cl2) 1762.
(m, 4); 13C NMR 137.8, 135.1, 132.3, 130.8, 129.9, 128.5 (2
C), 126.8, 125.9 (2 C), 32.8, 30.3, 28.82, 28.79, 16.83 (2 C);
IR (neat) 1680.
MeSSO2Me present in some reaction mixtures coeluted with
17. It was removed by stirring a solution of 17 or the crude
reaction mixture with EtSH in a two phase mixture of
EtOAc and water, which formed volatile MeSSEt and
water soluble MeSO2H.14
Oxidative cyclization of 29. Oxidation of a 1:2 mixture of
cis- and trans-29 (305 mg, 1.10 mmol) with CAN as
described above for 16 gave 250 mg of crude product.
Flash chromatography on silica gel (1:1 hexanes/CH2Cl2)
gave 11 mg (5%) of 30. Elution with 9:1 to 4:1 hexanes/
EtOAc gave 16 mg (7%) of a 3:6:2:10 mixture of lactones
31, 32, 33, and 34, followed by 44 mg (21%) of lactone 31.
Elution with EtOAc and then MeOH gave 78 mg (36%) of
polar products. Similar mixtures of products were obtained
from either pure cis- or trans-29.
3,7-Dimethyl-1,1-bis(methylthio)-1,6-octadiene (18). (389
mg, 85%) was prepared from 2,6-dimethyl-5-heptenal
(236 mg, 2.20 mmol) and bis(methylthio)trimethylsilyl-
methane (360 mg, 2.00 mmol) as a colorless liquid as
1
described above for 16: H NMR 5.70 (d, 1, Jˆ9.8 Hz),
5.10 (br t, 1, Jˆ7.3 Hz), 2.94±2.83 (m, 1), 2.29 (s, 3),
2.27 (s, 3), 1.97±1.89 (br dt, 2, Jˆ7.3, 7.5 Hz), 1.68 (d, 3,
Jˆ1.2 Hz), 1.59 (s, 3), 1.41±1.24 (m, 2), 0.97 (d, 3,
Jˆ6.7 Hz); 13C NMR 141.7, 131.4, 131.1, 124.5, 37.3,
34.9, 26.0, 25.7, 20.8, 17.7, 16.94, 16.85; IR (neat) 1674,
1582.
Data for S-methyl 2-(a-nitrooxyphenylmethyl)cyclohexane-
carbothioate (30): H NMR 7.40±7.30 (m, 5), 5.60 (d, 1,
1
Jˆ6.7 Hz), 2.48±2.36 (m, 2), 2.36 (s, 3), 1.99±1.92 (m, 1),
1.78±1.63 (m, 2), 1.54±1.47 (m, 2), 1.24±1.12 (m, 3), 0.95±
0.84 (m, 1); 13C NMR 202.2, 135.8, 128.9, 128.5 (2 C),
127.4 (2 C), 87.6, 55.5, 42.3, 31.0, 27.3, 25.0, 24.5, 11.6;
IR (CH2Cl2) 1686, 1637, 1281.
(3aa,6a,7aa)-Hexahydro-3,3,6-trimethyl-1H-cyclopenta-
[c]furanon-1-one (19). Oxidation of 18 (276 mg,
1.20 mmol) with CAN as described above for 16 gave
220 mg of crude product. Flash chromatography on silica
gel (9:1 hexanes/EtOAc) gave 84 mg (41%) of 19. Elution
with EtOAc and then MeOH gave 80 mg (38%) of unidenti-
®ed polar compounds.
Data for (3a,3ab,7aa)-hexahydro-3-phenyl-1(3H)-iso-
benzofuranone (31): mp 80±838C (lit.11 86±888C); 1H
NMR 7.42±7.32 (m, 5), 4.98 (d, 1, Jˆ9.8 Hz), 2.26±2.19
(m, 1), 2.18 (ddd, 1, Jˆ13.1, 11.3, 3.4 Hz), 1.94±1.76 (m,
4), 1.42±1.22 (m, 3), 1.15 (ddddd, 1, Jˆ13, 13, 13, 4, 4 Hz);
the 13C NMR spectrum is identical to that previously
reported.11
1
Data for 19: mp 45±468C (lit.10 15±198C); H NMR 2.76
(dd, 1, Jˆ8.5, 4.3 Hz), 2.58 (ddd, 1, Jˆ8.5, 8.5, 8.5 Hz),
2.43±2.33 (m, 1), 1.91 (dddd, 1, Jˆ12.2, 6.7, 6.7, 3.7 Hz),
1.84±1.76 (m, 1), 1.55 (dddd, 1, Jˆ12.8, 9.8, 9.8, 6.7 Hz),
1.40 (s, 3), 1.39 (s, 3), 1.22 (dddd, 1, Jˆ12.2, 10.4, 8.5,
6.1 Hz), 1.15 (d, 3, Jˆ6.7 Hz); 13C NMR 179.9, 84.1,
53.8, 50.2, 38.2, 35.4, 29.9, 28.0, 23.6, 21.2; IR (CH2Cl2)
1759. A 1D NOESY experiment with irradiation of the
methyl doublet at d 1.15 showed strong NOEs to H6 at d
2.4 and H6a at d 2.76 and a weak NOE to H3a at d 2.58.
Partial data for (3a,3aa,7ab)-hexahydro-3-phenyl-1(3H)-
isobenzofuranone (32)11 were determined from the mixture:
1H NMR 5.61 (d, 1, Jˆ7.9 Hz).
Partial data for (3a,3ab,7ab)-hexahydro-3-phenyl-1(3H)-
isobenzofuranone (33)11 were determined from the mixture:
1H NMR 5.48 (d, 1, Jˆ4.5 Hz).
Partial data for (3a,3aa,7aa)-hexahydro-3-phenyl-1(3H)-
isobenzofuranone (34)11 were determined from the mixture:
1H NMR 5.22 (d, 1, Jˆ3.1 Hz).
1,1-Bis(methylthio)-8-phenyl-1,7-octadiene (29). A 1:2
mixture of cis- and trans-7-phenyl-6-heptenals4 (450 mg,
2.4 mmol) was treated with bis(methylthio)trimethylsilyl-
methane (360 mg, 2.00 mmol) as described above for the
preparation of 16 to give 680 mg of crude product. Flash
chromatography on silica gel (0.5% Et2O in hexanes) gave
18 mg (6%) of cis-29, followed by 418 mg (75%) of a 1:2
mixture of cis- and trans-29, and 39 mg of 50% pure trans-
29. Flash chromatography of the impure trans-29 (hexanes)
gave 12 mg (4%) of trans-29.
cis and trans-1,1-Bis(methylthio)-7-phenyl-1,6-hepta-
diene (35). A 1:1 mixture of cis- and trans-6-phenyl-5-
hexenal4 (630 mg, 3.6 mmol) was treated with
bis(methylthio)trimethylsilylmethane (540 mg, 3.00 mmol)
as described above for the preparation of 16 to give 892 mg
of crude product. Flash chromatography on silica gel (1%
Et2O in hexanes) gave 2 mg (0.2%) of cis-35, followed by
650 mg (82%) of a 1:1 mixture of cis- and trans-35, and
2 mg (0.2%) of trans-35.
1
Data for cis-29: H NMR 7.35±7.19 (m, 5), 6.41 (d, 1,
1
Data for cis-35: H NMR 7.36±7.20 (m, 5), 6.43 (d, 1,
Jˆ11.6 Hz), 5.88 (t, 1, Jˆ7.3 Hz), 5.65 (dt, 1, Jˆ11.6,
7.3 Hz), 2.38±2.30 (m, 4), 2.27 (s, 3), 2.26 (s, 3), 1.52±
1.38 (m, 4); 13C NMR 137.7, 135.1, 132.8, 132.3, 128.9,
128.7 (2 C), 128.1 (2 C), 126.4, 30.3, 29.4, 28.9, 28.4,
16.83, 16.79; IR (neat) 1682.
Jˆ11.6 Hz), 5.87 (t, 1, Jˆ7.3 Hz), 5.67 (dt, 1, Jˆ11.6,
7.3 Hz), 2.41±2.32 (m, 4), 2.27 (s, 3), 2.23 (s, 3), 1.55 (tt,
2, Jˆ7.6, 7.6 Hz).
1
Data for trans-35: H NMR 7.36±7.26 (m, 4), 7.19 (tt, 1,
1
Data for trans-29: H NMR 7.36±7.26 (m, 4), 7.19 (tt, 1,
Jˆ7.0, 1.5 Hz), 6.40 (br d, 1, Jˆ15.9 Hz), 6.22 (dt, 1,
Jˆ15.9, 6.7 Hz), 5.92 (t, 1, Jˆ7.3 Hz), 2.41 (dt, 2, Jˆ7.3,
7.3 Hz), 2.29 (s, 3), 2.27 (s, 3), 2.23 (ddt, 2, Jˆ6.7, 1.2,
7.3 Hz), 1.58 (tt, 2, Jˆ7.3, 7.3 Hz); IR (neat) 1680.
Jˆ7.0, 1.5 Hz), 6.38 (d, 1, Jˆ15.9 Hz), 6.21 (dt, 1, Jˆ15.9,
6.7 Hz), 5.91 (t, 1, Jˆ7.3 Hz), 2.35 (dt, 2, Jˆ7.3, 7 Hz), 2.29
(s, 3), 2.27 (s, 3), 2.22 (ddt, 2, Jˆ7, 1.2, 6.7 Hz), 1.54±1.40

10132
B. B. Snider et al. / Tetrahedron 56 (2000) 10127±10132
Oxidative cyclization of 35. Oxidation of 35 (430 mg,
1.62 mmol) with CAN as described above for 16 gave
306 mg of crude product. Flash chromatography on silica
gel (1:1 hexanes/CH2Cl2) gave 11 mg (3%) of nitrate thio-
ester 36. Elution with 9:1 to 4:1 hexanes/EtOAc gave 33 mg
(10%) of lactone 38, 12 mg (4%) of a 3:1:1 mixture of 37,
38, and 39, and 25 mg (8%) of 70% pure 39. Elution with
1:1 hexanes/EtOAc gave 16 mg (5%) of nitrate acid 40.
Elution with MeOH gave 136 mg (41%) of unidenti®ed
polar products. Rechromatography of the 3:1:1 mixture of
37, 38 and 39 (40:1 hexanes/EtOAc) gave 6 mg (2%) of 37.
Rechromatography of the impure 39 (40:1 hexanes/EtOAc)
gave 16 mg (6%) of 39.
2.87 (dddd, 1, J<8.4, 8.4, 8.4, 8.4 Hz), 2.72 (ddd, 1, J<8, 8,
8 Hz), 2.14±2.04 (m, 1), 1.95 (dddd, 1, J<14, 7, 7, 7 Hz),
1.74±1.59 (m, 3), 1.35 (dddd, 1, J<12.8, 8.5, 8.5, 8.5 Hz);
13C NMR 180.5, 136.7, 129.1, 128.7 (2 C), 127.1 (2 C),
88.2, 47.3, 46.7, 31.1, 29.4, 24.8; IR (CH2Cl2) 3400±2600
(br), 1705, 1636, 1273.
Acknowledgements
We are grateful to the National Institutes of Health (GM-
42670) for generous ®nancial support.
Data for S-methyl 2-(a-nitrooxyphenylmethyl)cyclo-
pentanecarbothioate (36): H NMR 7.40±7.30 (m, 5), 5.60
1
References
(d, 1, Jˆ9.2 Hz), 2.98±2.88 (m, 2), 2.33 (s, 3), 2.09±1.99
(m, 1), 1.92±1.82 (m, 1), 1.72±1.56 (m, 3), 1.33 (dddd, 1,
Jˆ12, 8, 8, 8 Hz); 13C NMR 202.1, 136.7, 129.1, 128.7 (2
C), 127.1 (2 C), 88.3, 56.7, 47.0, 32.1, 29.6, 24.8, 11.8; IR
(CH2Cl2) 1684, 1634, 1277.
1. For reviews see: (a) Schmittel, M. Top. Curr. Chem. 1994, 169,
183±230. (b) Hintz, S.; Heidbreder, A.; Mattay, J. Top. Curr.
Chem. 1996, 177, 77±124. (c) Moeller, K. D. Top. Curr. Chem.
1997, 185, 49±86.
2. Snider, B. B.; Kwon, T. J. Org. Chem. 1992, 57, 2399±2410;
Snider, B. B.; Kwon, T. J. Org. Chem. 1990, 55, 4786±4788.
3. Ryter, K.; Livinghouse, T. J. Am. Chem. Soc. 1998, 120, 2658±
2659.
Data for (3aa,6b,7aa)-hexahydro-3-phenyl-1H-cyclopenta
[c]furanon-1-one (37): H NMR 7.41±7.26 (m, 5), 5.73 (d,
1
1, Jˆ6.7 Hz), 3.26 (ddd, 1, Jˆ8.5, 8.5, 3.1 Hz), 3.14 (dddd,
1, Jˆ8.5, 8, 8, 6.7 Hz), 2.14 (dddd, 1, Jˆ13.4, 6.7, 6.7,
3.1 Hz), 2.04±1.94 (m, 1), 1.57±1.49 (m, 2), 1.40±1.31
(m, 1), 1.22±1.13 (m, 1); 13C NMR 180.5, 137.4, 128.5 (2
C), 127.7, 124.9 (2 C), 81.5, 46.8, 45.5, 29.7, 27.8, 25.8; IR
(neat) 1771.
4. Hudson, C. M.; Marzabadi, M. R.; Moeller, K. D.; New, D. G.
J. Am. Chem. Soc. 1991, 113, 7372±7385.
5. Frey, D. A.; Reddy, S. H. K.; Moeller, K. D. J. Org. Chem.
1999, 64, 2805±2813 (and references cited therein).
È
6. (a) Hintz, S.; Frohlich, R.; Mattay, J. Tetrahedron Lett. 1996,
37, 7349±7352. (b) Ackermann, L.; Heidbreder, A.; Wurche, F.;
Klarner, F.-G.; Mattay, J. J. Chem. Soc., Perkin Trans. 2 1999,
863±869. (c) Hintz, S.; Mattay, J.; van Eldik. R.; Fu W.-F. Eur.
J. Org. Chem. 1998, 1583±1596.
È
7. (a) Seebach, D.; Grobel, B.-Th.; Beck, A. K.; Braun, M.; Geiss,
K.-H. Angew. Chem., Int. Ed. Engl. 1972, 11, 443±444.
Data for (3aa,6a,7aa)-hexahydro-3-phenyl-1H-cyclopenta
[c]furanon-1-one (38):13 1H NMR 7.41±7.27 (m, 5), 5.11 (d,
1, Jˆ3.7 Hz), 3.17 (ddd, 1, Jˆ9.5, 9.5, 2.5 Hz), 2.87 (dddd,
1, Jˆ9.5, 7.5, 3.7, 3.7 Hz), 2.21±2.13 (m, 1), 2.03±1.90 (m,
2), 1.90±1.83 (m, 1), 1.84±1.75 (m, 1), 1.72±1.62 (m, 1);
13C NMR 180.5, 140.9, 128.8 (2 C), 128.2, 124.9 (2 C),
86.4, 48.4, 44.8, 33.6, 30.7, 25.4; IR (neat) 1770.
È
(b) Seebach, D.; Kolb, M.; Grobel, B. T. Chem. Ber. 1973, 106,
2277±2290.
8. Scholz, D. Synthesis 1983, 944±945.
9. Snider, B. B.; Lin, H. Synth. Commun. 1998, 28, 1913±1922.
10. Wolinsky, J.; Wolf, H.; Gibson, T. J. Org. Chem. 1963, 28,
274±275.
Data for (3aa,6a,7ab)-hexahydro-3-phenyl-1H-cyclopenta
[c]furanon-1-one (39): H NMR 7.42±7.33 (m, 5), 5.26 (d,
1
1, Jˆ10.1 Hz), 2.84 (ddd, 1, Jˆ14.7, 11.6, 6.7 Hz), 2.49
(dddd, 1, Jˆ14.7, 11.5, 10.1, 6.1 Hz), 2.30±2.11 (m, 2),
1.92 (dddd, 1, Jˆ10.4, 8.5, 6.7, 3.1 Hz), 1.81 (dddd, 1,
Jˆ11.6, 7.9, 6.1, 2.4 Hz), 1.73±1.56 (m, 2); 13C NMR
173.2, 137.6, 128.6 (2 C), 128.5, 125.6 (2 C), 84.5, 57.3,
53.6, 28.9, 24.0, 20.4; IR (neat) 1782.
11. Miyano, S.; Abe, N.; Fujisaki, F.; Sumoto, K. Heterocycles
1987, 26, 1813±1826.
12. Paolobelli, A. B.; Ceccherelli, P.; Pizzo, F.; Ruzziconi, R.
J. Org. Chem. 1995, 60, 4954±4958.
È
13. Hoppe, D.; Bronneke, A. Tetrahedron Lett. 1983, 24, 1687±
1690.
Data for 2-(a-nitrooxyphenylmethyl)cyclopentanecarboxylic
acid (40): 1H NMR 7.40±7.31 (m, 5), 5.64 (d, 1, Jˆ9.2 Hz),
14. Capozzi, G.; Capperucci, A.; Degl'Innocenti, A.; Del Duce,
R.; Menichetti, S. Tetrahedron Lett. 1989, 30, 2995±2998.