α′-hydroxy-α,β-unsaturated tosylhydrazones: Preparation and use as intermediates for carbonyl and enone transpositions

Article abstract of DOI:10.1081/SCC-120012982

Regiospecifically generated α,β-unsaturated tosylhydrazones dianions are treated with molecular oxygen, yielding α′-hydroxy-α,β-unsaturated tosylhydrazones, versatile intermediates for organic synthesis. They proved to be useful for 1,2-carbonyl and 1,2-enone transpositions, and also permitted the preparation of α′-hydroxy enones in very high yields.

Full text of DOI:10.1081/SCC-120012982

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α′-HYDROXY-α,β-UNSATURATED TOSYLHYDRAZONES:
PREPARATION AND USE AS INTERMEDIATES FOR
CARBONYL AND ENONE TRANSPOSITIONS
Lúcia H. B. Baptistella a & Adriana M. Aleixo a
a Instituto de Química , Universidade Estadual de Campinas , P.O. Box 6154, Campinas, SP,
13083-970, Brazil
Published online: 16 Aug 2006.
To cite this article: Lúcia H. B. Baptistella & Adriana M. Aleixo (2002) α′-HYDROXY-α,β-UNSATURATED TOSYLHYDRAZONES:
PREPARATION AND USE AS INTERMEDIATES FOR CARBONYL AND ENONE TRANSPOSITIONS, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:19, 2937-2950, DOI: 10.1081/
SCC-120012982
To link to this article: http://dx.doi.org/10.1081/SCC-120012982
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 19, pp. 2937–2950, 2002
a0-HYDROXY-a,b-UNSATURATED
TOSYLHYDRAZONES: PREPARATION
AND USE AS INTERMEDIATES FOR
CARBONYL AND ENONE
TRANSPOSITIONS
*
Lucia H. B. Baptistella and Adriana M. Aleixo
Instituto de Quımica, Universidade Estadual de
Campinas, P.O. Box 6154, 13083-970,
Campinas, SP, Brazil
ABSTRACT
Regiospecifically generated a,b-unsaturated tosylhydrazones
dianions are treated with molecular oxygen, yielding
a0-hydroxy-a,b-unsaturated tosylhydrazones, versatile inter-
mediates for organic synthesis. They proved to be useful for
1,2-carbonyl and 1,2-enone transpositions, and also permitted
the preparation of a0-hydroxy enones in very high yields.
Key Words: Carbonyl transposition; Tosylhydrazones;
Enone transposition
Functional group transpositions may be considered as useful tools in
synthetic chemistry. Enones, for example, are very important groups, and
the ability to transpose them within a molecule offers a wide degree of
*Corresponding author. E-mail: lhbb@iqm.unicamp.br
2937
DOI: 10.1081/SCC-120012982
Copyright & 2002 by Marcel Dekker, Inc.
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2938
BAPTISTELLA AND ALEIXO
latitude in synthesis design, representing a fascinating and challenging
problem.[1] Over the years, a number of methodologies have become
available for effecting enone transpositions with 1,3-[1a,2] or 1,2-carbonyl
displacements, the latter[1,3] being less explored. Additionally, in this special
case, the two possible types of carbonyl migrations, that means, to the
original a-[1,3a–c] or a0-positions (see Sch. 1), have not been equally investi-
gated. In the last years, the latter[1,2a,3d,e] has received little attention.
Now, we wish to present here an efficient synthetic sequence from a,b-
unsaturated ketones that permits, with some variations, 1,2-conjugated
enone transposition or only 1,2-carbonyl transposition, both with migration
of the keto group to the a0-position (Sch. 1).
The key intermediate of these sequences is an a0-hydroxy-a,b-unsatu-
rated tosylhydrazone, prepared through direct a0-hydroxylation of
dilithiated tosylhydrazones with molecular oxygen. The optimized con-
ditions are illustrated on Sch. 2 for the tosylhydrazone of dihydrocarvone
2, chosen as representative example for the enone and carbonyl transposi-
tions. The a0-hydroxy-a,b-unsaturated tosylhydrazone 3 was isolated in
79% yield, as a separable diastereoisomeric mixture (1 : 3 syn : anti).
Table 1 shows the results in applying this procedure to some other
monocyclic and fused-ring systems. They suggest that, under the adopted
reaction conditions, the tosylhydrazone stereochemistry has a pronounced
effect on the ratio of conversion of the hydrazones and/or on the a0-hydro-
xylation yield. We observed that, when only E-tosylhydrazones were present
(with 2 and 4), total conversion of the starting materials and high yield of
the products were obtained, probably due to the easy syn-deprotonation.[5]
On the other hand, when Z-tosylhydrazones were present (with 6, 8 and 11),
the formation of a cross-conjugated azaenolate possibly contributed to a
Scheme 1.

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a0-HYDROXY-a,b-UNSATURATED TOSYLHYDRAZONES
2939
Scheme 2. aC7H7SO2NHNH2, EtOH, refl., 98%; b(i) n-BuLi (2 Eq.), THF : TMEDA
(substrate: TMEDA 1 : 2), ꢀ78ꢁC, 40 min; (ii) molecular O2, ꢀ78ꢁC ! rt, 7 h, 79%;
cNaBH4, t-BuOH, refl., 1 h, 70%; d(COCl)2/DMSO, CH2Cl2 then Et3N (1.5Eq.),
ꢀ60ꢁC ! rt, 70%; ePCC, CH2Cl2, 0ꢁC ! rt, 2 h, 74%; (COCl)2/DMSO, CH2Cl2
f
then Et3N (3.8 Eq.), ꢀ60ꢁC ! rt, 72%; Na, HOCH2CH2OH, 100ꢁC, 30 min, 74%.
g
decrease in the efficiency (rate of conversion and/or yield) of the reaction,
even using a mixture THF/TMEDA as solvent.[6]
Following our studies on enone transposition (Schs. 2 and 3), we used
the versatility of the tosylhydrazone group to promote either its complete
reduction to a saturated carbon without migration of the double bond, or its
reductive elimination, in this case leading directly to the transposed
a,b-unsaturated ketone.
A classical condition to promote complete reduction of tosylhydra-
zone groups to CH2 involves treatment with NaBH4 in refluxing MeOH.[7]
With a,b-unsaturated tosylhydrazones, this reduction may occur without
migration of the double bond,[7] but in our case, working with 5, 16a was
the only product formed (Sch. 3). Substituting refluxing methanol by reflux-
ing t-butanol, a less nucleophilic solvent, the reaction was completed in 1 h
and the homoallylic alcohol 16b (or 13, when 3 was the substrate—Sch. 2)
was isolated in a very good yield, without any allylic alcohol side product.
With other hydride systems, such as LiAlH4 or NaBH3CN, which are cap-

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2940
BAPTISTELLA AND ALEIXO
Table 1. a0-Hydroxylation of a,b-Unsaturated Tosylhydrazones
Products [E : Z Ratio]a,b
(Total Yield)c; [Isomeric Ratio]
Hydrazones [E : Z Ratio]a
aDetermination of the E/Z stereochemistry was based on the
13C NMR data,[4] and the E/Z ratio was determined by
1H NMR data; bE-tosylhydrazones on the products are equivalent
(on their spatial arrangement) to Z-tosylhydrazones on the start-
c
ing material, and vice-versa; yields based on isolated materials;
dbased on the reacted hydrazones. About 30% of the starting
materials were recovered (20% with 6).
able to promote reductions with migration of the double bond,[8] complex
mixtures of products were obtained. For example, treatment of 5 with
NaBH3CN gave 16b in very low yield (32%), however no allylic alcohol
was observed.
Elaboration of the homoallylic alcohol 13 to its oxidized counterpart
14 was accomplished under mild conditions, using (COCl)2/DMSO in
CH2Cl2 and treatment with 1.5Eq. of Et 3N (Sch. 2). The b,g-unsaturated

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a0-HYDROXY-a,b-UNSATURATED TOSYLHYDRAZONES
2941
Scheme 3. aNaBH4, MeOH, refl., 11 h, 78% (OMe syn to the OH); bNaBH4,
t-BuOH, refl., 1 h, 83%; c(COCl)2/DMSO, CH2Cl2 then Et3N (1.5Eq.),
ꢀ60ꢁC ! rt, 73% or PDC, CH2Cl2, 0ꢁC ! rt, 7 h, 70%; (COCl)2/DMSO, CH2Cl2
d
e
then Et3N (3.8 Eq.), ꢀ60ꢁC ! rt, 72%; Na, HOCH2CH2OH, 100ꢁC, 30 min, 77%;
fp-TsOH (cat.), THF/H2O, silica gel, rt, 24 h, 89%.
ketone 14 was obtained in 70% yield without racemization of its stereogenic
center. On the other hand, reaction of 13 with PCC in CH2Cl2 led to the
transposed a,b-unsaturated ketone 15, isolated in 74% yield. In this case,
partial racemization of the stereogenic center a to the ketone was observed
(50% ee, determined by chiral GC). The classical Swern oxidation[9] was
also employed for the direct conversion of 13 to the piperitone (15), using an
excess of Et3N to treat the sulfur intermediate. Finally, the 1,2-enone trans-
position could also be achieved by treating 3 with Na in ethylene glycol,[10]
under the known Bamford–Stevens conditions (Sch. 2). This result may
suggest the formation of an enolate intermediate, which gave the transposed
a,b-enone by equilibration. Unfortunately, in this case it was not possible to
prevent complete racemization of 15. From 16b and 5 (Sch. 3), the two last
mentioned conditions, respectively, promoted a double migration and piper-
itenone 18 was the only isolated product.
In addition to the ketone transpositions, the a0-hydroxy-a,b-unsatu-
rated tosylhydrazones proved to be very useful for the preparation of
a0-hydroxy enones, as exemplified in Sch. 3 for the preparation of 19
from 5. The procedure is a modification of a known method for hydro-
lytic cleavage of dimethylhydrazones,[11] and permits the cleavage of

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2942
BAPTISTELLA AND ALEIXO
the resistant tosylhydrazones under very mild conditions, without any
epimerization.
In conclusion, the approaches described here offer an efficient way to,
selectively, relocate either a carbonyl or an enone group from an a,b-unsa-
turated ketone. Additionally, all the compounds in these sequences may be
considered as highly versatile intermediates in synthetic organic chemistry.
EXPERIMENTAL
Melting points were determined on a Reichert apparatus and are uncor-
rected. Optical rotations were measured on a Carl Zeiss Polamat polarimeter
using a Hg lamp and are corrected. IR spectra were measured for KBr pellets
or films on KBr disks using a BOMEM MB-series FT-IR spectrometer.
NMR spectra were recorded on a Bruker AC.P-300, Varian Gemini-300 or
Varian INOVA-500 spectrometers, using CDCl3 as solvent. GC/MS were
performed on a QP5000 CG-17A Shimadzu equipment, using Supelco
DB-5fused silica capillary column (30 m  0.25mm), or Supelco Beta-
DexTM-120 capillary column (30 m  0.25mm) for the enantiomer separa-
tions. Mass spectra and high resolution MS were recorded on VG
Autospec equipment, with electronic impact at 70 eV or chemical ionization
with isobutane. TLC were performed on silica gel 60 GF254 glass plates and
CC were performed using silica gel 60 70–230 mesh size. All solvents were
distilled before use. Anhydrous THF was distilled from sodium and
benzophenone.
General Procedure for the Preparation of
a0-Hydroxy Tosylhydrazones
Typical procedure for the preparation of 6-hydroxy-5-isopropyl-2-
methylcyclohex-2-en p-toluenesulfonylhydrazone (3): In a two-neck round-
bottomed flask, the tosyl hydrazone 2 [(0.30 g, 0.93 mmol—prepared
by treatment of 1 with p-toluenesulfonylhydrazine (1.1 eq.) in refluxing
anhydrous ethanol[12]—m.p.: 153–156ꢀC; [ꢀ]D À 19ꢀ (c ¼ 1.5, CHCl3)] was
dissolved in a mixture THF : TMEDA (20.0 : 0.3 mL—1.88 mmol of
TMEDA), the solution was cooled to À78ꢀC under argon atmosphere
and n-butyllithium (1.20 mL of 1.6 M solution in hexane, 1.88 mmol) was
added slowly. The resulting red dark solution was stirred at À78ꢀ for 40 min,
then O2 was bubbled through the solution.[13] The cooling bath was
removed, and O2 bubbling maintained for 7 h at room temperature. Ethyl
acetate (10 mL) was added, the reaction mixture washed with saturated

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a0-HYDROXY-a,b-UNSATURATED TOSYLHYDRAZONES
2943
aqueous NH4Cl solution and then with saturated aqueous Na2S2O5
solution.[14] The organic layer was separated, dried and concentrated.
Purification by column chromatography (light petroleum ether : ethyl acet-
ate 7 : 3) gave the a0-hydroxy tosylhydrazone 3 as a diastereomeric mixture
in 79% yield (0.25g, 1 : 3 syn : anti). Preparative thin layer chromatography
(benzene : ethanol 9.9 : 0.1) gave the diastereomers 3-anti (Rf 0.47, 0.18 g)
and 3-syn (Rf 0.43, 0.06 g) in 57% and 19% yield, respectively.
(Z)-(5S,6S)-6-Hydroxy-5-isopropyl-2-methylcyclohex-2-en p-toluene-
sulfonylhydrazone 3-anti: 1H NMR (300 MHz, CDCl3): ꢁ 0.84 and 0.94
(2d, J ¼ 7.0 Hz, 2 Â 3H, CH3-9 and 10); 1.82–2.00 (m, 3H, H-4 and H-8);
1.77 (s, 3H, CH3-7); 2.12 (m, 1H, H-5); 2.32 (s, 3H, CH3–Ts); 4.45(d,
J ¼ 10.0 Hz, 1H, H-6); 6.01 (ld, J ¼ 5.0 Hz 1H, H-3); 7.30 and 7.85 (2 Â d,
J ¼ 8.1 Hz, 2 Â 2H, Ph); 10.17 (ls, 1H, N–H); 13C NMR (75.5 MHz, CDCl3):
ꢁ 16.5and 20.6 (C-9 and C-10); 17.7 (C-7); 21.4 (CH –Ts); 22.4 (C-4); 25.7
3
(C-8); 47.7 (C-5); 70.8 (C-6); 132.3 (C-3); 132.9 (C-2); 152.1 (C-1). HRMS:
Found Mþ 336.4632, C17H24N2O3S requires Mþ 336.4536. Anal. Calcd. for
C17H24N2O3S: C 60.69; H 7.19; N 8.32. Found: C 60.71; H 7.18; N 8.12.
(Z)-(5S,6R)-6-Hydroxy-5-isopropyl-2-methylcyclohex-2-en p-toluene-
1
sulfonylhydrazone 3-syn: H NMR (300 MHz, CDCl3): ꢁ 0.95and 1.02 (2d,
J ¼ 7.0 Hz, 2 Â 3H, CH3-9 and 10); 1.81–2.01 (m, 3H, H-4 and H-8); 1.76 (s,
3H, CH3-7); 2.13 (m, 1H, H-5); 2.42 (s, 3H, CH3-Ts); 4.76 (d, J ¼ 3.3 Hz,
1H, H-6); 6.10 (ld, J ¼ 6.0 Hz, 1H, H-3); 7.30 and 7.88 (2 Â d, J ¼ 8.0 Hz,
2 Â 2H, Ph); 8.41 (ls, 1H, N-H); 13C NMR (75.5 MHz, CDCl3): ꢁ 13.9 and
20.5(C-9 and C-10); 17.2 (C-7); 21.4 (CH –Ts); 20.4 (C-4); 26.7 (C-8); 45.1
3
(C-5); 62.8 (C-6); 132.9 (C-2); 133.9 (C-3); 155.9 (C-1). HRMS: Found Mþ
336.4634, C17H24N2O3S requires Mþ 336.4536.
(Z)-(5S,6S)-(R)-6-Hydroxy-5-isopropenyl-2-methylcyclohex-2-en p-tolu-
enesulfonylhydrazone 5-anti: [ꢀ]D À 133.5ꢀ(c ¼ 1.02, CHCl3); IR (film,
1
cmÀ1): 3487, 3228, 1646, 1598; H NMR (300 MHz, CDCl3): ꢁ 1.72 (s, 3H,
CH3-10); 1.79 (s, 3H, CH3-7); 2.12–2.20 (m, 2H, H-4); 2.42 (s, 3H, CH3–Ts);
2.40–2.50 (m, 1H, H-5); 4.45 (dd, J ¼ 11.1 and 2.4 Hz, 1H, H-6); 4.84 (ls, 1H,
H-9); 4.94 (lt, J ¼ 1.1 Hz, 1H, H-90); 5.98 (t, J ¼ 3.8 Hz, 1H, H-3); 7.30 and
7.85(2 Â d, J ¼ 8.0 Hz, 2 Â 2H, Ph); 10.34 (ls, 1H, N–H); 13C NMR
(75.5 MHz, CDCl3): ꢁ 17.8 (C-7); 18.4 (C-10); 21.3 (CH3–Ts); 27.9 (C-4);
51.0 (C-5); 70.4 (C-6); 115.8 (C-9); 131.0 (C-3); 133.4 (C-2); 143.7 (C-8);
149.3 (C-1); MS: m/z 334 (Mþ); 82 (100%). HRMS: Found Mþ 334.4325,
C17H22N2O3S requires Mþ 334.4378.
(Z)-(5S,6R)-(Q)-6-Hydroxy-5-isopropenyl-2-methylcyclohex-2-en p-tol-
uenesulfonylhydrazone 5-syn: [ꢀ]D þ 39.3ꢀ (c ¼ 0.92, CHCl3); 1H NMR
(300 MHz, CDCl3): ꢁ 1.80 (s, 3H, CH3-7); 1.83 (s, 3H, CH3-10); 1.95–2.10
(m, 2H, H-4); 2.34–2.40 (m, 1H, H-5); 2.42 (s, 3H, CH3–Ts); 4.65(d,
J ¼ 2.6 Hz, 1H, H-6); 4.86 (ls, 1H, H-9); 5.11 (lt, J ¼ 1.1Hz, 1H, H-90);

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BAPTISTELLA AND ALEIXO
6.10 (m, 1H, H-3); 7.30 and 7.86 (2 Â d, J ¼ 8.2 Hz, 2 Â 2H, Ph); 8.45(ls, 1H,
N–H); 13C NMR (75.5 MHz, CDCl3): ꢁ 17.3 (C-7); 21.6 (CH3–Ts); 22.5(C-
10); 23.8 (C-4); 45.7 (C-5); 62.4 (C-6); 114.5 (C-9); 131.3 (C-2); 133.8 (C-3);
144.0 (C-8); 153.5 (C-1); MS: m/z 334 (Mþ); 91 (100%).
(Z)-5-Hydroxy-3-methylcyclopent-2-en p-toluenesulfonylhydrazone 7:
1H NMR (300 MHz, CDCl3): ꢁ 1.89 (d, J ¼ 1.2 Hz, 3H, CH3-6); 2.42 (s, 3H,
CH3–Ts); 2.91 (dd, J ¼ 18.0 and 7.1 Hz, 2H, H-4); 5.00 (dd, J ¼ 7.1 and
1.3 Hz, 1H, H-5); 5.84 (d, J ¼ 1.2 Hz, 1H, H-2); 7.30 and 7.83
(2 Â d, J ¼ 8.2 Hz, 2 Â 2H, Ph); 9.19 (ls, 1H, N–H); 13C NMR (75.5 MHz,
CDCl3): ꢁ 18.1 (C-6); 21.6 (CH3–Ts); 45.2 (C-4); 70.1 (C-5); 124.9 (C-2);
156.7 (C-3); 164.7 (C-1).
(E)-2-Hydroxyoctalone p-toluenesulfonylhydrazone 9 (1 : 1.5 isomers
syn : anti ): 1H NMR (300 MHz, CDCl3): ꢁ 1.10 and 1.20 (2 Â s, 2 Â 3H,
CH3-11); 2.41 and 2.43 (2 Â s, 2 Â 3H, CH3–Ts); 4.30 and 4.38 (2 Â dd,
J ¼ 11.7 and 5.1 Hz, and J ¼ 13.2 and 4.8 Hz, 2 Â 1H, H-2); 5.73 and 5.89
(2 Â s, 2 Â 1H, H-4); 13C NMR (75.5 MHz, CDCl3): ꢁ 65.2 and 65.7 (C-2);
107.7 and 108.6 (C-4); 163.8 and 164.9 (C-1).
1
2-Hydroxyoctalone 10 (1 : 1.5 isomers syn : anti ): H NMR (300 MHz,
CDCl3): ꢁ 1.30 and 1.36 (2 Â s, 2 Â 3H, CH3-11); 3.55 (ls, 2 Â 1H, OH); 4.25
and 4.33 (2 Â dd, J ¼ 13.7 and 6.4 Hz, J ¼ 13.7 and 5.7 Hz, 2 Â 1H, H-2);
5.80 and 5.84 (2 Â ls, 2 Â 1H, H-4); 13C NMR (75.5 MHz, CDCl3): ꢁ 69.0
and 69.4 (C-2); 118.8 and 120.7 (C-4); 172.7 and 173.4 (C-5); 200.1
and 200.2 (C-1).
(Z)-2-Hydroxycolestenone p-toluenesulfonylhydrazone 12: 1H NMR
(300 MHz, CDCl3): ꢁ 2.35and 2.36 (2 Â s, 2 Â 3H, CH3–Ts); 4.17–4.29
and 4.58–4.68 (2 Â m, 2 Â 1H, H-2); 5.65 and 5.90 (2 Â ls, 2 Â 1H, H-4).
(1S,2R,6S)-3-Methyl-2-methoxy-6-isopropenylcyclohex-3-en-1-ol 16a:
Sodium borohydride (64 mg, 1.69 mmol) was added to a stirred solution
of the hydroxy–tosyl hydrazone 5-anti (70 mg, 0.21 mmol) in methanol
(5mL) and the mixture was heated under reflux for 11 h. After cooling,
water (3 mL) was added, the mixture was filtered and the filtrate extracted
with dichloromethane. The combined organic layers were dried (Na2SO4),
filtered and the filtrate concentrated. Purification by column chromatogra-
phy (light petroleum ether : ethyl acetate 8.5: 1.5) gave 16a in 78% yield
1
(27 mg). IR (film, cmÀ1): 3453, 1644, 1097; H NMR (300 MHz, CDCl3):
ꢁ 1.76 (s, 3H, CH3-7); 1.84 (d, J ¼ 1.8 Hz, 3H, CH3-10); 2.00–2.20 (m, 2H,
H-5); 2.52 (td, J ¼ 10.9 and 6.0 Hz, 1H, H-6); 3.58 (d, 1H, J ¼ 4.1 Hz, H-2);
3.64 (s, 3H, CH3O); 3.72 (dd, 1H, J ¼ 10.9 and 4.1 Hz, H-1); 4.89 (d,
J ¼ 6.9 Hz, 2H, H-9); 5.53 (ls, 1H, H-4); 13C NMR (75.5 MHz, CDCl3): ꢁ
18.0 (C-7); 22.3 (C-10); 29.7 (C-5); 45.3 (C-6); 63.4 (CH3–O); 70.5(C-1); 80.5
(C-2); 112.5(C-9); 125.1 (C-4); 130.6 (C-3); 144.7 (C-8).

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a0-HYDROXY-a,b-UNSATURATED TOSYLHYDRAZONES
2945
(6S)-6-Isopropenyl-3-methylcyclohex-3-en-1-ol 16b: The title compound
was prepared from 5-anti (45mg, 0.13 mmol) as described above, replacing
methanol with t-butanol. The mixture was maintained under reflux for 1 h
and, after cooling, drops of water were added, followed by hexane (20 mL).
The solvents were removed under reduced pressure, and the residue was
purified by column chromatography (light petroleum ether : ethyl acetate
9 : 1). A mixture of the diastereomeric alcohols 16b was obtained in 83%
1
yield (17 mg). H NMR (300 MHz, CDCl3): ꢁ 1.62 (s, 2 Â 3H, CH3-7); 1.75
and 1.82 (2 Â s, 2 Â 3H, CH3-10); 1.91–2.39 (m, 2 Â 5H, H-2, H-5 and H-6);
3.80 (td, J ¼ 9.6 and 3.7 Hz, 1H, H-1); 4.13 (ls, 1H, H-10); 4.86, 4.91 and 4.96
(3 Â ls, H-9); 5.46 and 5.48 (2 Â ls, 2 Â 1H, H-4); 13C NMR (75.5 MHz,
CDCl3): ꢁ 19.5and 22.5(C-10); 22.9 and 23.1 (C-7); 23.4 and 29.4 (C-5); 38.0
and 38.5(C-2); 44.2 and 49.8 (C-6); 65.9 and 68.1 (C-1); 111.1 and 113.7 (C-9);
120.0 and 120.3 (C-4); 130.3 and 132.0 (C-3); 146.2 and 146.7 (C-8).
(6S)-6-Isopropyl-3-methylcyclohex-3-en-1-ol 13: The title compound
was obtained from 3 in 70% yield, following the same procedure described
1
for 16b. H NMR (300 MHz, CDCl3): ꢁ 0.80, 0.85, 0.86 and 0.91 (4 Â d,
J ¼ 6.6 Hz, 3H each, CH3-9 and 10); 1.59 and 1.60 (2 Â s, 2 Â 3H, CH3-7);
1.19–2.24 (m, 2 Â 6H, H-2,5,6 and 8); 3.72 (td, J ¼ 9.6 and 6 Hz, 1H, H-1);
4.10 (d, J ¼ 1.8 Hz, 1H, H-10); 5.28 and 5.39 (2 Â ls, 2 Â 1H, H-4); 13C NMR
(75.5 MHz, CDCl3): ꢁ 17.3, 20.5and 20.7 (C-9 and C-10); 23.0 and 23.4
(C-7); 23.8 and 25.0 (C-5); 25.8 and 29.3 (C-8); 39.4 and 39.5 (C2);
44.0 and 45.2 (C-6); 66.1 and 69.1 (C-1); 120.5 and 120.8 (C-4); 130.0 and
131.2 (C-3).
(6S)-3-Methyl-6-isopropylcyclohex-3-en-1-one 14: A solution of oxalyl
chloride (0.02 mL, 0.28 mmol) and dichloromethane (10 mL) was placed in a
three-neck round-bottomed flask equipped with two press-equalizing drop-
ping funnels containing Me2SO (0.04 mL, 0.57 mmol) in dichloromethane
(1 mL) and the alcohol 13 (40 mg, 0.26 mmol) in dichloromethane (1 mL),
respectively. Under argon atmosphere and at À60ꢀC, the Me2SO was added
to the oxalyl chloride solution, stirring was continued for 2 min and then the
alcohol was added. At the same temperature, stirring was maintained for
15min. Triethylamine (0.05mL, 0.39 mmol, 1.5eq.) was then added, the
reaction mixture was stirred for 5min and then allowed to warm to room
temperature. Water was added and the layers separated. The aqueous layer
was reextracted with dichloromethane, the combined organic layers were
washed with NaCl solution, dried (Na2SO4), filtered and the filtrate concen-
trated. Purification of the residue by column chromatography (light petro-
leum ether : ethyl acetate 8.5: 1.5) gave 14 in 70% yield (28 mg). [a]D þ 51.0ꢀ
(c ¼ 0.5, CHCl3); IR (film, cmÀ1): 1713; 1H NMR (300 MHz, CDCl3): ꢁ 0.89
and 0.91 (2 Â d, J ¼ 6 Hz, 2 Â 3H, CH3-9 and 10); 1.71 (s, 3H, CH3-7);
1.17–1.22 and 2.02–2.45 (m, 5H, H-4, 5 and 8); 2.78 (m, 1H, H-6), 5.51

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2946
BAPTISTELLA AND ALEIXO
(ls, 1H, H-4); MS: m/z 137 (Mþ-CH3); 69 (100%). HRMS: Found Mþ-CH3
137.1987, C9H13O requires Mþ 137.2007. Anal. Calcd. for C10H16O: C
78.90; H 10.59. Found: C 79.01; H 10.34.
6-Isopropyl-3-methylcyclohex-2-en-1-one 15 (piperitone): Method (a)
Pyridinium chlorochromate (90 mg, 0.4 mmol) was added to a solution of
13 (30 mg, 0.2 mmol) in dichloromethane (5mL) at 0 ꢀC, and the mixture was
maintained with stirring at room temperature and under argon atmosphere
for 2 h. Dry ether (10 mL) was added, the mixture was passed through a pad
of Florisil and the solvent was removed by distillation. Purification of the
residue by column chromatography (light petroleum ether : ethyl acetate
9 : 1) gave the piperitone (15) in 74% yield (22 mg). IR (film, cmÀ1): 1675,
1462; 1H NMR (300 MHz, CDCl3): ꢁ 0.85and 0.94 (2 Â d, J ¼ 6.7 Hz,
2 Â 3H, CH3-9 and 10); 1.85–1.89 (m, 1H, H-5); 1.93 (ls, 3H, CH3-7);
1.93–2.10 (m, 2H, H-4 and 5); 2.26–2.42 (m, 3H, H-4, 6 and 8); 5.84 (lq,
J ¼ 1.5Hz, 1H, H-2); 13C NMR (75.5 MHz, CDCl3): ꢁ 18.3 and 20.4 (C-9
and 10); 22.7 (C-5); 23.9 (C-7); 25.6 (C-8); 30.2 (C-4); 51.5 (C-6); 127.0 (C-2);
161.4 (C-3); 201.8 (C-1).
Method (b) The title compound was also obtained from 13 in 72%
yield, following the same procedure described for 14, replacing 1.5eq. of
triethylamine by 3.8 eq. of triethylamine.
Method (c) The title compound was also obtained from 3 following
the procedure: Under argon atmosphere and at room temperature, sodium
(8 mg, 0.35mmol) was placed in a round-bottomed flask equipped with
reflux condenser containing ethylene glycol (1 mL). Ultrasound was used
until the complete formation of the soluble alcoholate. The alcohol 3
(30 mg, 0.09 mmol) was then added, and the solution was maintained at
100ꢀC for 30 min. After cooling, water (1 mL) was added and the reaction
medium was extracted with dichloromethane (3x). The combined organic
layers were dried (Na2SO4), filtered and the solvent evaporated. Purification
of the residue by column chromatography (light petroleum ether : ethyl
acetate 9 : 1) gave the piperitone (15) in 74% yield (10 mg).
(6S)-3-Methyl-6-isopropenylcyclohex-3-en-1-one 17: Method (a) The
title compound was obtained from 16b in 73% yield, following the same
procedure described for 14. IR (film, cmÀ1): 1733, 1661; 1H NMR
(300 MHz, CDCl3): ꢁ 1.72 (s, 3H, CH3-10); 1.77 (s, 3H, CH3-7); 2.52 (m,
2H, H-5); 2.83 (m, 2H, H-2); 3.16 (lt, J ¼ 8.4 Hz, 1H, H-6); 4.83 (ls, 1H,
H-9); 4.98 (t, J ¼ 1.5Hz, 1H, H-9 0); 5.60 (m, 2H, H-2); 13C NMR (75.5 MHz,
CDCl3): ꢁ 21.1 (C-10); 22.3 (C-7); 29.5 (C-5); 30.0 (C-2); 55.1 (C-6); 113.2
(C-9); 120.6 (C-4); 126.4 (C-3); 142.7 (C-8); 213.7 (C-1). Anal. Calcd. for
C10H14O: C 79.96; H 9.39. Found: C 79.85; H 9.33.
Method (b) Pyridinium dichromate (76 mg, 0.2 mmol) was added to a
solution of 16b (20 mg, 0.13 mmol) in dichloromethane (5mL) at 0 ꢀC, and

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a0-HYDROXY-a,b-UNSATURATED TOSYLHYDRAZONES
2947
the mixture was maintained with stirring at room temperature and under
argon atmosphere for 7 h. Dry ether (10 mL) was added, the mixture was
passed through a pad of Florisil and the solvent was removed by distillation.
Purification of the residue by column chromatography (light petroleum
ether : ethyl acetate 9.5: 0.5) gave 17 in 70% yield (14 mg).
6-Isopropylidene-3-methylcycloex-2-en-1-one 18 (piperitenone): Method
(a) The title compound was obtained from 16b in 72% yield, following the
1
procedure (b) described for 15. H NMR (300 MHz, CDCl3): ꢁ 1.87 (s, 3H,
CH3-10); 1.94 (s, 3H, CH3-7); 2.10 (s, 3H, CH3-9); 2.31 (lt, J ¼ 6.3 Hz, 2H,
H-4); 2.67 (t, J ¼ 6.3 Hz, 2H, H-5), 5.90 (ls, 1H, H-2); 13C NMR (75.5 MHz,
CDCl3): ꢁ 22.3 (C-10); 22.7 (C-9); 23.6 (C-7); 27.8 (C-5); 31.7 (C-4); 128.6
(C-6) 129.0 (C-2); 142.6 (C-8); 160.0 (C-3); 192.2 (C-1). HRMS: Found Mþ
150.0685, C10H14O requires 150.1201.
Method (b) The title compound was obtained from 5 in 77% yield,
following the procedure (c) described for 15.
(5S,6S)-6-Hydroxy-5-isopropenyl-2-methylcyclohex-2-en-1-one
19:
Silica gel 60 (70–230 mesh; 1.0 g), p-toluenesulfonic acid (0.01 g) and
water (0.3 mL) were added to a solution of 5-anti (0.11 g, 0.33 mmol) in
tetrahydrofuran (3 mL). The suspension was stirred at room temperature
for 24 h, then it was filtered and the residue was washed with dichloro-
methane. The filtrate was dried (MgSO4) and evaporated under reduced
pressure. Purification of the residue by column chromatography (light pet-
roleum ether : ethyl acetate 8.5: 1.5) gave the hydroxy tosyl hydrazone 19 in
1
89% yield (49 mg). IR (film, cmÀ1): 3460, 1678, 1612; H NMR (300 MHz,
CDCl3): ꢁ 1.85(ls, 2 Â 3H, CH3-7 and 10); 2.32–2.56 (m, 2H, H-4); 2.71
(ddd, J ¼ 12.6, 10.2 and 5.4 Hz, 1H, H-5); 3.80 (ls, 1H, OH); 4.16 (d,
J ¼ 12.6 Hz, 1H, H-6); 4.95(m, 2H, H-9); 6.76 (ddd, J ¼ 5.7, 2.7 and
1.4 Hz, 1H, H-3); 13C NMR (75.5 MHz, CDCl3): ꢁ 15.4 (C-7); 18.8 (C-10);
30.7 (C-4); 51.1 (C-5); 74.5 (C-6); 113.6 (C-9); 133.1 (C-2), 144.2 (C-8); 145.6
(C-3); 200.6 (C-1). HRMS: Found Mþ 166.2081, C10H14O2 requires
166.2186.
ACKNOWLEDGMENTS
A.M.A. is grateful to CAPES for a fellowship. We thank Dr. P.M.
Imamura for fruitful discussions and Ilza M.O. Souza for her constant
technical support.
REFERENCES
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positions see: (a) Morris, D.G. Carbonyl Group Transpositions.

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2948
BAPTISTELLA AND ALEIXO
Chem. Soc. Rev. 1982, 11, 397; (b) Kane, V.V.; Singh, V.; Martin, A.;
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of the solvent.

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a0-HYDROXY-a,b-UNSATURATED TOSYLHYDRAZONES
2949
6. (a) TMEDA is considered good for the enhancement of the yields
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13. It is absolutely necessary to assure the formation of the dianion from
the tosylhydrazone maintaining the red dark solution with agitation
for at least 40 min before to start the bubbling of O2, and, especially, to
start this bubbling at À78ꢀC. With these procedures the formation of
the dangerous n-butylhydroperoxide (from n-butyllithium and O2—see
ref. (a) and (b) below) is completely avoided, and also the competitive
Shapiro reaction doesn’t occur. (a) Blilkina, T.G.; Shushunov, V.A.

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2950
BAPTISTELLA AND ALEIXO
Reactions of Organometallic Compounds with Oxygen and Peroxides;
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See (a) Capp, C.W.; Hawkins, E.G.E. Reactions of Organic Peroxides.
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Received in the USA October 4, 2001