Oxidative cleavage of unsaturated 1,2-diols using chiral lead-tetracarboxylates obtained by in situ metathesis

Article abstract of DOI:10.1016/S0040-4039(00)01887-6

A combination of an acetate metathesis/cascade transformations process, providing ring enlarged systems decorated with a chiral auxiliary, is presented. The use of a chiral carboxylic acid, such as (S)-2-acetoxypropionic acid, gives diastereomeric mixtures when performed in the racemic series, offering the possibility of chemical resolution.

Full text of DOI:10.1016/S0040-4039(00)01887-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 21–24
Oxidative cleavage of unsaturated 1,2-diols using chiral
lead-tetracarboxylates obtained by in situ metathesis
8
Jose´ Ignacio Candela Lena, Ozge Sesenoglu, Nicolas Birlirakis and Sime´on Arseniyadis*
Institut de Chimie des Substances Naturelles, CNRS, F-91198 Gif-sur-Yvette, France
Received 16 October 2000; accepted 25 October 2000
Abstract—A combination of an acetate metathesis/cascade transformations process, providing ring enlarged systems decorated
with a chiral auxiliary, is presented. The use of a chiral carboxylic acid, such as (S)-2-acetoxypropionic acid, gives diastereomeric
mixtures when performed in the racemic series, offering the possibility of a chemical resolution. © 2000 Published by Elsevier
Science Ltd.
reagent used, namely benzene, trifluorotoluene, ace-
tone, methylene chloride, chloroform, DME, DMF,
THF and acetic acid. The product ratios and reaction
rates were clearly dependent on solvent polarity and the
observed solvent effect on the rate of cascade transfor-
mations can be rationalized by examining the proposed
mechanism of this reaction sequence.4 In this communi-
cation, we report examples of this methodology carried
out in a chiral carboxylic solvent, ensuring high com-
plexity but also enantiomeric purity in a single synthetic
operation. During a preliminary study5 we noticed that
the use of deuterium labeled acetic acid led to the
While designing strategies for the taxoid diterpene
skeleton construction, a serendipitous discovery led to
the development of a new ‘cascade-type’ ring-expan-
sion/rearrangement methodology.1 The utility of this
methodology with regard to the synthesis of biologi-
cally active natural products was demonstrated by the
large scale preparation of a conveniently functionalized
taxoid C-ring precursor2 which in turn was elaborated
into the highly oxygenated taxoid ABC tricyclic sys-
tem.3 Exploring the solvent effect on the above men-
tioned transformations, mediated by Pb(OAc)4, we
examined a number of solvents compatible with the
Scheme 1. (a) Pb(OAc)4, CD3COOD, rt. (b) Pb(OAc)4, (S)-2-acetoxypropionic acid, rt.
Keywords: ring expansion; cascade transformations; acetate metathesis; chiral carboxylic solvents.
* Corresponding author. Fax: 33-1-69.07.72.47; e-mail: simeon.arseniyadis@icsn.cnrs-gif.fr
0040-4039/01/$ - see front matter © 2000 Published by Elsevier Science Ltd.
PII: S0040-4039(00)01887-6

22
J. I. Candela Lena et al. / Tetrahedron Letters 42 (2001) 21–24
exclusive formation of CD3-labeled compounds, indi-
cating that metathesis6 of the acetic acid by its labeled
counterpart has occurred during the process. As por-
trayed in Scheme 1, room temperature treatment of the
Hajos–Parrish ketone derived hydrindene diol 1 with 2
equiv. of lead tetraacetate in deuterated acetic acid (ca.
5 mL per mmol) afforded exclusively 3 ([h]D −30, c 3.1,
mp: 134–135°C, heptane–ether), while similar treat-
ment of the Wieland–Miescher ketone derived unsatu-
rated diol 2 afforded 4 (68%, [h]D −64, c 1.8), along
with the half cascade intermediate 57 (5%) and a small
amount of the tricyclic lactone 8 (11%, [h]D +13, c 1.4),
which presumably derives from 5.
In the Wieland–Miescher series, proceeding as above,
bis-lactyloxy acetal 7 ([h]D −80, c 1.7) and lactone 8
were obtained in 70 and 11% yields, respectively. It was
interesting to observe that the use of (S)-2-acetoxypro-
pionic acid as solvent gave rise to a dramatic accelera-
tion, furnishing a high isolated yield of 7 after only 1 h
of stirring at room temperature.10 The process passed
the test successfully affording, in a single step, a ring
expansion along with a functional reorganization and,
above all, resolution (Scheme 2). Upon treatment with
2 equiv. of Pb(OAc)4 in (S)-2-acetoxypropionic acid
and proceeding as above, diol [ ]-2 gave, following
chromatographic separation, 7 (36%) and 9 (34%, [h]D
−4, c 1.2) in 70% combined isolated yield, together with
lactone 8 (8%).
It was then of interest to investigate the applicability of
this approach for the synthesis of chiral non-racemic
cyclohexane and cycloheptane derivatives using in situ
generated chiral lead carboxylates. We were thus inter-
ested in checking whether a chiral lead carboxylate
could afford cascade transformations (modification of
the ligands could influence reactivity) and ensure reso-
lution, all in one synthetic operation. This would be of
great synthetic use, especially for the Wieland–Mi-
escher ketone derived diols of type 2, as the enan-
tiomeric excess obtained via the proline catalyzed
Robinson annelation remains moderate.8 To check the
feasibility of this process and to gain familiarity with
the proposed chemistry, the process was first tested on
known optically pure unsaturated diols 1 and 2. (S)-2-
Acetoxypropionic acid ((S)-O-acetyl lactic acid) was
found to be an optimal solvent for this process as it is
liquid, it boils at a much higher temperature than acetic
acid and it is easy to prepare on a large scale from
commercially available inexpensive lactic acid.9 The
experiments undertaken with lead tetraacetate in the
Hajos–Parrish series uniformly gave rise to the ring-en-
larged acetal 6 as the sole detectable product. When
treated with 2 equiv. of lead tetraacetate in (S)-2-ace-
toxypropionic acid (ca. 5 mL per mmol) under reduced
pressure, 1 underwent cascade transformations in less
than 10 h at room temperature to give 6 ([h]D −35, c
1.8) in 85% isolated yield. Taking into account the high
level of molecular complexity attained in a one-pot
transformation, the yield is remarkably high (the only
loss appeared to be due to the work-up conditions).
The construction of the enantiomerically pure seven-
membered ring segments 11 and 12 was then under-
taken. Reduction of 7 (absolute configurations as
depicted in Scheme 2) with LiAlH4 in THF (room
temperature, then reflux for 30 min) afforded the
diastereomeric mixture of the corresponding cyclohep-
tane-triols 10 (1:1 ratio, 99% isolated yield). Selective
protection of the C-4, C-6 hydroxy groups as the
acetonide was accomplished by treating the resulting
triol in methylene chloride with anhydrous acetone and
a catalytic amount of pTsOH under argon at room
temperature (85%). Recrystallization from hexane pre-
cipitated most of the slower eluting cis-fused isomer 11
([h]D +33, c 0.9). The trans-fused acetonide 12 ([h]D
+31, c 1.2) was then separated on silica gel (methylene
chloride–methanol, 98:2 as eluent). Following transfor-
mation of the free primary hydroxyl group at C-2, a
chemoselective functionalization of the secondary hy-
droxyl group of 11 or 12 at C-6 using literature proce-
dures should provide an easy access to optically
homogeneous, polysubstituted cycloheptane derivatives.
The bicyclo[3.2.2]nonane aldol derivatives 13 and 14
were easily obtained in one step from the cis-fused
bicyclic derivative 7, by dissolving the latter in
methanol–water (8:1) and stirring the reaction mixture
in the presence of K2CO3. After an overnight stirring at
room temperature, a fused to bridged ring system inter-
change led to a diastereomeric mixture (nearly 1:1 ratio,
OtBu
OtBu
L*O
OtBu
O
7
L*O
10
9
1
4
10a
6
5
HO
HO
2
OtBu
OtBu
8
H
O
5
H
+
d
1
O
a
O
7
6
8
2
9
3
4
HO
OL*
OL*
O
13
[±]-2
9
+
b
7
OtBu
OtBu
OtBu
O
HO
HO
+
HO
2
H
H
H
H
H
c
4
6
OH
O
O
HO
O
11
O
12
OH
14
10
Scheme 2. (a) Pb(OAc)4, (S)-2-acetoxypropionic acid, rt. (b) LiAlH4, THF, reflux. (c) Acetone, H+. (d) K2CO3, MeOH–H2O, rt.

J. I. Candela Lena et al. / Tetrahedron Letters 42 (2001) 21–24
23
87% yield) of bicyclic aldols 13 ([h]D +92, c 1.1) and 14
([h]D +70, c 1.1), separated by chromatography on
silica gel (elution with ethyl acetate–heptane–
methanol, 1:1:0.01).
6. It is well known that various lead(IV) carboxylates can be
easily prepared by metathesis of the acetate with the
corresponding carboxylic acid, the latter being used as
solvent for the reaction. The acetic acid thus formed is
removed under reduced pressure, thus shifting the equi-
librium to the right. Bachman, G. B.; Wittman, J. W. J.
Org. Chem. 1963, 28, 65–68.
7. Arseniyadis, S.; Quilez del Moral, J.; Brondi Alves, R.;
Potier, P.; Toupet, L. Tetrahedron: Asymmetry 1998, 9,
2871–2878.
The results described above demonstrate the power of
the lead tetraacetate mediated one-pot multi-stage
transformation methodology for the rapid synthesis of
complex molecules. Inexpensive (S)-2-acetoxypropionic
acid proved compatible with the cascade transforma-
tions; the process offers the possibility of a chemical
resolution, via chromatographic separation or recrystal-
lization, when performed in the racemic series. So far,
these promising results have a shortcoming: the use of a
twofold excess of the toxic lead tetraacetate; we are
currently engaged in further improvement of the scope
and extension of this process to a catalytic system.11 In
all cases, structures and configuration of products were
assigned by comprehensive spectral data; optical rota-
tions were measured in chloroform and NMR spectra
in CDCl3.12
8. Barbas III, C. F. Tetrahedron Lett. 2000, 41, 6951–6954;
Arseniyadis, S.; Rodriguez, R.; Mun˜oz Dorado, M.;
Brondi Alves, R.; Ouazzani, J.; Ourisson, G. Tetrahedron
1994, 50, 8399–8426.
9. For contributions from this laboratory on practical uses
of (S)-2-acetoxypropionic acid in synthesis, see: Ar-
seniyadis, S.; Yashunsky, D. V.; Mun˜oz Dorado, M.;
Brondi Alves, R.; Wang, Q.; Potier, P.; Toupet, L. Tetra-
hedron 1996, 52, 6215–6232; Arseniyadis, S.; Rico Fer-
reira, M.; Quilez del Moral, J.; Martin Hernando, J.;
Potier, P.; Toupet, L. Tetrahedron: Asymmetry 1998, 9,
4055–4071; Arseniyadis, S.; Brondi Alves, R.; Yashun-
sky, D. V.; Potier, P.; Toupet, L. Tetrahedron 1997, 53,
1003–1014.
Acknowledgements
10. Using acetonitrile, trifluorotoluene or benzene as solvent
the corresponding bis-acetoxy acetal required 50 h of
stirring at room temperature for completion.
The authors thank the European Commission for a
Research Training Grant to Dr. J. I. Candela Lena,
and the Scientific and Technical Research Council of
8
a grant to Ms. Ozge
11. For the electrocatalytic oxidative cleavage of 1,2-diols by
electrogenerated Pb(IV), see: Marken, F.; Squires, A. M.;
Alden, J. A.; Compton, R. G.; Buston, J. E. H.;
Moloney, M. G. J. Phys. Chem. B 1998, 102, 1186–1192.
12. Typical procedure: A dry flask was charged with 700 mg
(2.92 mmol) of ( )-2 and 2.7 g (6.1 mmol) of Pb(OAc)4,
vacuumed, flushed with argon and then again vacuumed
for 1 h. (S)-2-acetoxypropionic acid (10 mL) was then
added at room temperature and stirring continued for 30
min under argon and an additional 30 min under reduced
pressure (ca. 4 mmHg). The reaction mixture was then
diluted with ether (200 mL), washed with water (3×20
mL), 6N NaOH (3×10 mL) and water again (2×20 mL).
The organic layer was dried over magnesium sulphate
and the solvent evaporated under reduced pressure. The
residue was purified on silica gel (toluene–ether 4:1) to
yield 536 mg of 7 (36%), 506 mg of 9 (34%) along with 62
mg of lactone 8 (8%). Compound 7: [h]D −80 (c 1.7). IR
(film): 2982, 2943, 1746, 1456, 1371, 1345, 1312, 1246,
1187, 1127, 1101, 1062, 1049, 989, 943, 910, 737 cm−1. 1H
NMR (600 MHz): 1.14 (9H, s, tBu), 1.30 (3H, s, Me-
10a), 1.48 (3H, d, J=7.2), 1.55 (3H, d, J=67.2), 1.62
(1H, m, H-8a), 1.72 (1H, dt, J=4.3, 14.9, H-9a), 1.84
(1H, dd, J=1.4, 14.8, H-1b), 1.88 (1H, dd, J=4.2, 14.8,
H-1a), 1.93 (1H, m, H-8b), 2.00 (1H, dq, J=2.6, 14.9,
H-9b), 2.08 (3H, s, MeCO), 2.11 (3H, s, MeCO), 2.42
(1H, m, H-7), 2.54 (1H, m, H-7%), 2.93 (1H, d, J=3.4,
H-5), 2.95 (1H, d, J=8.9, H-10), 4.92 (1H, q, J=7.2),
5.08 (1H, q, J=7.2), 6.30 (1H, d, J=3.4, H-4), 6.47 (1H,
dd, J=1.4, 3.8, H-2). Diagnostic NOE’s: {Me-10a}: H-4,
H-1beq., H-5, H-9bax; {H-4}: H-5, Me-10a; {H-10}:
H1aax, H-8a; {H-5}: H-4, H7b, H-9b, Me-10a; {H-9b}:
Me-10a, H-5, H-9a (NOE gem). 13C NMR (75 MHz):
16.4 (MeCH), 16.7 (MeCH), 20.1 (Me-10a), 20.5
Turkey (TUBITAK) for
Sesenoglu.
References
1. Arseniyadis, S.; Brondi Alves, R.; Pereira de Freitas, R.;
Mun˜oz-Dorado, M.; Yashunsky, D. V.; Potier, P.;
Toupet, L. Heterocycles 1997, 46, 727–764.
2. Mart´ın Hernando, J. I.; Qu´ılez del Moral, J.; Rico Fer-
reira, M.; Candela Lena, J. I.; Arseniyadis, S. Tetra-
hedron: Asymmetry 1999, 10, 783–797.
3. Mart´ın Hernando, J. I.; Rico Ferreira, M.; Candela Lena,
J. I.; Birlirakis, N.; Arseniyadis, S. Tetrahedron: Asymme-
try 2000, 11, 951–973.
4. As the reaction mechanism includes a carbocation forma-
tion step, unsurprisingly, we have a faster cascade in
acetic acid than in benzene: Arseniyadis, S.; Brondi
Alves, R.; Quilez del Moral, J.; Yashunsky, D. V.; Potier,
P. Tetrahedron 1998, 54, 5949–5958; Arseniyadis, S.;
Yashunsky, D. V.; Pereira de Freitas, R.; Mun˜oz-
Dorado, M.; Potier, P.; Toupet, L. Tetrahedron 1996, 52,
12443–12458. For leading references concerning the oxi-
dative cleavage of 1,2-glycols, see: Malaprade, M. L. Bull.
Soc. Chim. Fr. 1928, 43, 683–696; Criegee, R. Chem. Ber.
1931, 64, 260–266; Rigby, W. J. Chem. Soc. 1950, 1907–
1913.
5. Rico Ferreira, M.; Mart´ın Hernando, J. I.; Candela Lena,
J. I.; Qu´ılez del Moral, J.; Arseniyadis, S. Tetrahedron:
Asymmetry 1999, 10, 1527–1537. Mart´ın Hernando, J. I.;
Rico Ferreira, M.; Candela Lena, J. I.; Toupet, L.;
Birlirakis, N.; Arseniyadis, S. Tetrahedron: Asymmetry
1999, 10, 3977–3989.
(C6 H3CO), 20.6 (C6 H3CO), 22.9 (C-8), 28.7 (tBu), 30.5

24
J. I. Candela Lena et al. / Tetrahedron Letters 42 (2001) 21–24
(C-9), 35.0 (C-1), 37.6 (Cq-10a), 45.5 (C-7), 53.2 (C-5),
68.3 (C*H), 68.4 (C*H), 73.9 (Cq-tBu), 80.0 (C-10), 88.8
(C-4), 93.1 (C-2), 168.8 (2×C, MeCO), 170.2 (MeCO),
MHz): 1.13 (9H, s), 1.21–2.59 (9H, m), 1.29 (3H, s), 1.49
(3H, d, J=6.9), 1.53 (3H, d, J=6.9), 2.09 (3H, s), 2.13
(3H, s), 2.96 (1H, t, J=3.4), 5.07 (1H, q, J=6.9), 5.18
(1H, q, J=6.9), 6.33 (1H, d, J=3.2), 6.47 (1H, bs). 13C
NMR (75 MHz): 16.7, 16.8, 20.5 (3C), 23.1, 28.8 (3C),
30.5, 35.1, 37.4, 45.6, 53.1, 68.5 (2C), 74.0, 80.2, 89.2,
93.7, 168.6, 168.9, 170.1, 170.5, 208.7. CI-MS: 532 ([M+
NH4]+, 97), 460 (47), 400 (100), 383 (6).
6
6
170.4 (MeC6 O), 208.7 (C-6). ESI-MS (MeOH): 537
([MNa]+, 100), 553 ([MK]+, 12), 1051 ([2MNa]+, 20).
Compound 9: [h]D −4 (c 1.2). IR (film): 2975, 2941, 1747,
1716, 1583, 1455, 1372, 1344, 1303, 1237, 1189, 1174,
1127, 1097, 1049, 994, 941, 736 cm−1
.
1H NMR (600
.