Influence of the substitution pattern on the Pb(OAc)4 mediated oxidative cleavage of steroidal 1,2-diols

Article abstract of DOI:10.1016/S0957-4166(99)00407-3

A rapid increase in molecular complexity, modulated by the substitution pattern, upon treatment of steroidal unsaturated diols with lead tetraacetate is presented. The steric and electronic factors involved in these cascade type transformations are investigated, the products serving as useful mechanistic probes.

Full text of DOI:10.1016/S0957-4166(99)00407-3

Pergamon
Tetrahedron: Asymmetry 10 (1999) 3977–3989
Influence of the substitution pattern on the Pb(OAc)4 mediated
oxidative cleavage of steroidal 1,2-diols
José Ignacio Martín Hernando,a Maria del Rosario Rico Ferreira,a José Ignacio Candela Lena,a
Loïc Toupet,b Nicolas Birlirakis a and Siméon Arseniyadis a,∗
aInstitut de Chimie des Substances Naturelles, CNRS, F-91198 Gif-sur-Yvette, France
bURA 804 au CNRS, Université de Rennes I, F-35042 Rennes, France
Received 20 August 1999; accepted 10 September 1999
Abstract
A rapid increase in molecular complexity, modulated by the substitution pattern, upon treatment of steroidal
unsaturated diols with lead tetraacetate is presented. The steric and electronic factors involved in these cascade
type transformations are investigated, the products serving as useful mechanistic probes. © 1999 Elsevier Science
Ltd. All rights reserved.
1. Introduction
Previously, we have demonstrated that bicyclic unsaturated 1,2-diols react with lead tetraacetate in a
cascade fashion with high yields.1 Extension of the chemistry to involve steroidal unsaturated 1,2-diols of
type 1a was successful and products 2 were obtained in high yields, which were improved by conducting
the reaction in acetic acid.2 As illustrated in Scheme 1, subjection of testosterone based 2,3-diol 1a
to Pb(OAc)4 mediated oxidative cleavage led to a B-ring-enlarged-A-nor-steroid of type 2, deriving
from C10–C5 bond migration. The resultant ring-expanded compounds were readily transformed to a
bicyclo[3.2.2]ring system of type 3 via a mild fused to bridged ring system interchange. To explore
further the scope of these one-pot multistage transformations, nor-testosterone derived unsaturated 1,2-
diol 1b leading to 4 was examined. Finally, in order to better assess the role of substitution during these
cascade transformations, 1c leading to type 5c compounds was targeted for study. This paper describes a
series of experiments addressed to probe the influence of the substitution pattern; options 1b and 1c were
selected, in attempts to understand the factors involved in the three related processes (they all proceed via
the same half-cascade intermediate of type 5). In Scheme 1, ‘P’ at C-17 stands for tBu or TBS protection
∗
Corresponding author. Fax: 33-1-69.07.72.47; e-mail: simeon.arseniyadis@icsn.cnrs-gif.fr
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00407-3

3978
J. I. Martín Hernando et al. / Tetrahedron: Asymmetry 10 (1999) 3977–3989
but with a carbonyl group at C-17, protected as a ketal, the same cascade transformations were also
carried out.
Scheme 1. (a) Pb(OAc)4, in CH3CN or CH3CO2H. (b) K2CO3–MeOH–H2O
2. Results and discussion
The required 1,2-unsaturated steroidal-diol derivatives were prepared according to a general synthetic
protocol involving conversion of an enone to the corresponding α-acetoxy derivative, followed by lithium
aluminum hydride reduction. The preparation of 1b, lacking the angular methyl group at C-10 (Me-19,
steroid numbering), which was considered to be a challenging substrate for the cascade transformations,3
was achieved straightforwardly starting from the commercially available 19-nor-testosterone 6. As
before,4 the synthesis began with α-acetoxylation and subsequent reduction of the known5 steroidal
enone 7 (Scheme 2). Thus, 17β-(tert-butyldimethylsilyloxy)ester-4-ene-3-one 7 was reacted with lead
tetraacetate in refluxing benzene under argon to give a mixture of two isomeric diacetates in about 80%
yield, which were reduced without separation using lithium aluminum hydride. Exposure of the resulting
unsaturated diol 1b (diastereomeric mixture) to Pb(OAc)4 (1.1 equiv.) at 0°C in acetonitrile effected
a smooth conversion into the cyclic ene-acetal 5b in 40% yield, along with the corresponding C2–C3
dialdehyde (30%). Use of excess (2.2 equiv.) of Pb(OAc)4 was found to initiate further rearrangement
affording the acetoxy bis-acetal ring system 4 (35%) together with 17% of 5b and dialdehyde resulting
from the oxidative cleavage (28%), which did not undergo further rearrangement but rather showed
some tendency to isomerize (Z/E enal geometry). Treatment of 1b or cyclic acetal 5b, the result of
initial ‘half-cascade’ transformations, with Pb(OAc)4 in acetic acid gave 4 (47%) after 15 h of stirring at
room temperature, along with dialdehyde. Extensive NMR studies (COSY, HMQC, HMBC) established
the A-nor-steroidal structure 4 and permitted the assignment of all the proton and carbon resonances.
The relative configuration of the bis-acetal portion was secured by 1D NOEDIFF experiments. Lithium
aluminum hydride reduction of 4 in dry THF (0°C to rt, 5 h) and subsequent acetylation of the crude triol
thus obtained with Ac2O in pyridine, in the presence of 4-DMAP, gave the corresponding triacetylated A-
seco derivative 10 (95%, two steps). Lastly, deprotection of the TBS ether 4 was accomplished utilizing
standard conditions (40% aqueous HF in acetonitrile, 1 h at 0°C) which provided the alcohol 8 in 85%
yield.

J. I. Martín Hernando et al. / Tetrahedron: Asymmetry 10 (1999) 3977–3989
3979
Scheme 2. (a) TBSCl–Im, rt. (b) Pb(OAc)4, PhH, ∆. (c) LiAlH4. (d) 3 equiv. Pb(OAc)4, MeCN, 50 h, rt or in AcOH, 15 h, rt.
(e) 1.1 equiv. Pb(OAc)4, MeCN, −20°C to rt. (f) Ac2O, Py, DMAP, 0°C. (g) HF–MeCN, 0°C. (h) p-BrBzCl, Py–DMAP, 0°C to
rt
Single-crystal X-ray diffraction analysis of the crystalline 17-p-bromobenzoate derivative 9
(Scheme 2) enabled unequivocal stereochemical assignment and further confirmed the accuracy
of previous assignments by NMR techniques. The latter was obtained upon treatment of 8 with
p-bromobenzoyl chloride in dry pyridine in the presence of DMAP (0°C to room temperature, 12 h). The
desired p-bromobenzoate 9 thus obtained crystallized, allowing for an X-ray crystallographic study, the
computer generated drawing of which is shown in Fig. 1 (left), along with an MM3 minimized structure
of the hypothetical precursor organolead intermediate (right).
Figure 1. Perspective drawing of the X-ray structure of 9 (left), and a hypothetical precursor structure (right)
In an effort to elucidate a reaction mechanism, we examined the effect of changing several reaction
parameters. To this end, the effect of solvent was briefly investigated in the reaction of 1b with lead
tetraacetate. Replacing acetonitrile with other solvents, such as acetic acid or (S)-O-acetyllactic acid, led
to an increase of rate but no significant improvement in yield was observed. Use of deuterium labeled
acetic acid led to the formation of 11a (39%), accompanied by the corresponding dialdehyde. Removal of
the TBS protective group as above afforded cleanly the deuterium labeled C-17 free hydroxy derivative
11b. On the other hand, using (S)-O-acetyllactic acid as solvent led to 12 (40%) together with 3% of 4 and
dialdehyde as above (Scheme 3). It is noteworthy that there was no sign of the alternative ring-enlarged
type 2 product, arising from C10–C5 bond migration, in any of these reactions.
The conclusion of the current phase of our investigation involved the allylically substituted 1c as a

3980
J. I. Martín Hernando et al. / Tetrahedron: Asymmetry 10 (1999) 3977–3989
Scheme 3. (a) Pb(OAc)4, CD3COOD, rt. (b) HF–MeCN, 0°C. (c) Pb(OAc)4, CH3CH(OAc)COOH, rt
substrate. To this end, we generated the allylic alcohols 15 from the corresponding acetoxy enone 13 by
way of the intermediate dienol acetate species, using known procedures (Scheme 4). The dienol acetate,
obtained by heating 13 in pyridine in the presence of acetic anhydride and 4-DMAP, was then subjected to
epoxidation using methyltrioxorhenium (MTO)6 as catalyst and aqueous hydrogen peroxide as terminal
oxidant. A clean reaction ensued and the product had 1H and 13C NMR spectra concordant with structure
15Mm (in a roughly 4:1 β-OH/α-OH ratio; M stands for major, m for minor). The resulting mixture was
protected at C-6 by treatment with TMSOTf (trimethylsilyltrifluoromethane sulfonate) in the presence of
collidine in dry toluene (10 mL/mmol), at −40°C under argon, affording cleanly the desired TMS–ether
16Mm, in quantitative yield. Lithium aluminum hydride reduction of the crude thus obtained in ether at
0°C furnished the target diols in quantitative yield. In order to facilitate characterization, a small part of
the initial mixture (1cMm) was chromatographically separated on silica gel. In line with our expectations
were the results obtained from lead tetraacetate mediated cleavage of allylically substituted steroidal diols
of type 1c.
Scheme 4. (a) Ac2O, Py, DMAP, 80–100°C. (b) MTO, 30% H2O2, py, CH2Cl2, rt. (c) TMSOTF, collidine, PhMe, −40°C. (d)
LiAlH4, Et2O, 0°C. (e) Pb(OAc)4 in MeCN or in AcOH
Chromatographically purified 1cM (β-OTMS) and the mixture of α,β-OTMS derivative 1cMm were
tested separately, both of which afforded the corresponding cyclic ene-acetal, derived from oxidative
cleavage and subsequent intramolecular 4+2 cycloaddition (half-cascade cursus).7 Thus, subjection of
either 1cM or 1cMm to lead tetraacetate, as above, afforded 5cM for the former and a separable mixture
of 5cM+5cm for the latter, in high isolated yields. The configurational assignments of 13, 14, 1cM, 5cM,
and 5cm were determined with the aid of NMR techniques, especially by studying spatial proximities
using the 1D NOEDIFF spectra.
We next examined the reactivity of the half-cascade intermediates 5cM or 5cm, formed on cleavage
and IMDA (1c→i→5c, by analogy to 1b→i→5b in Scheme 5), to see if they would undergo ring-
expansion onto the corresponding A-nor-B-homosteroid in analogy with the fragmentation of the related
diol 1a. All efforts to induce 5cM or 5cm to undergo a full-cascade transformation failed to generate

J. I. Martín Hernando et al. / Tetrahedron: Asymmetry 10 (1999) 3977–3989
3981
even a trace of a ring-expanded product. Prolonged room temperature stirring or heating, as well as
changing the solvent and the stoichiometry, did not produce the ring-expanded product of type 2. Instead,
work up provided recovered starting material and extensive decomposition products, which could not be
characterized. It is noteworthy that there was no sign of the alternative full-cascade product, arising from
C10–C5 bond migration. The result is presumably due to steric hindrance.
Scheme 5. A mechanistic rationale for the one-pot multistage transformations in the 19-nor-steroidal unsaturated diol series
3. Prediction and interpretation of skeletal changes
The mechanistic pathway of the cascade for 1b is portrayed in Scheme 5. Thus, upon lead tetraacetate
treatment,8 1b initially undergoes an oxidative cleavage to the dialdehyde i followed by a 4+2 cyclo-
addition leading to the isolable 5b. Upon further treatment with Pb(OAc)4, formation of an inisolable
organolead intermediate of type ii (X=OAc) occurs, which in turn undergoes rearrangement, involving
1,2-oxygen shift of the best aligned C5–O bond. In Scheme 5, it is proposed that the intermediate
bridgehead cation iii is not acylated at C-5 by the acetate ions resulting from the organolead intermediate.
Instead, it suffers a proton abstraction presumably by the acetate ions generated from the reagent acting
as a base, as illustrated, leading to the rearranged compound 4.
In the cases investigated, the outcome of the lead tetraacetate mediated one-pot multistage transfor-
mations depends originally on steric factors, which in turn control the effectiveness of orbital overlap
depending on the initial alignment of relevant bonds.9 In the above observed rearrangements, the
migrating bond was antiperiplanar to the leaving group (‘sp3 alignment factor’). To determine the likely
conformation of type 5 common intermediates (5a, 5b, 5cM and 5cM) a molecular mechanics study was
performed using Allinger’s MM3 force field and Still’s Macromodel program10 (since the effective bulk
of lead triacetate is not easy to assess, consideration of the torsional and steric factors involved is done
on its silicon analog). Examination of the results realized in examples 1a, 1b and 1c provides insight
into the operation of an apparent stereoelectronic control in product distribution and is supportive of
the mechanistic reasoning advanced above. The outcome of the influence of the substitution pattern is
rationalized in terms of the pre-transition state structures (before electrophilic attack of the metal on the
C3–C4 double bond) depicted in Fig. 2.
With regard to the proposed mechanism,11 the key transformation, which is triggered by an electro-
philic attack of the metal on the electron rich double bond C3–C4 (the 1,3-dioxene part of the molecule),
should set up the ring expansion process from 5a. As a result of the configuration-control originating from

3982
J. I. Martín Hernando et al. / Tetrahedron: Asymmetry 10 (1999) 3977–3989
Figure 2. Lowest energy conformers of 5a, 5b, 5cm and 5cM, as determined by molecular mechanics calculations, used to
rationalize the steric course of the electrophilic attack of Pb4+ on the C3–C4 olefin
the angular methyl group Me-19, the organolead intermediate has the C10–C5 bond in a trans coplanar
arrangement to the carbon–lead bond, which is most likely to migrate. The formation of 4 in the 19-nor-
steroid series, via 5b, could be rationalized by the generation of an organolead intermediate on the more
accessible β-face of the C3–C4 olefin. The C5–oxygen bond is perfectly aligned for a backside colinear
displacement on such an intermediate while the C5–C10 bond cannot assume geometry favorable to
the migration. The results are consistent with the above mechanistic rationale. That is, depending on
the substitution pattern at C-10, which controls the stereochemistry of the key step, the rearrangement
products arise via backside attack of the migrating bond on the C-4 carbon, bearing the lead triacetate
group. Furthermore, either top or bottom face substitution at C-6 inhibits electrophilic attack by the metal
on the C3–C4 olefin (the key step), thus stopping the transformations on the ‘half-cascade’ level.
4. Conclusion
Lack of an angular methyl substitution at C-10 led to a different cascade transformation, in complete
agreement with the influence of the bond alignment of the migrating and leaving groups (bond C10–C5
migration versus bond C5–O migration). The path is predictably determined by geometry in the reactant
(bond alignment factor), which in turn depends on the substitution pattern of the substrates investigated.
Allylic substitution at C-6, either α- or β-, led to an incomplete cascade transformation due to steric
interactions between both the α- or β-trimethylsyliloxy substituents and the attacking metal. We are
currently in the process of further investigation of this reaction sequence and its extension to other
systems.

J. I. Martín Hernando et al. / Tetrahedron: Asymmetry 10 (1999) 3977–3989
3983
5. Experimental
5.1. General
Experimental details were as previously described.12 NMR spectra were run in CDCl3 and specific
rotations were measured in chloroform, unless otherwise noted. NMR experiments (800 MHz) were
carried out on a Bruker Avance DRX-800 spectrometer, equipped with a triple resonance H/C/N
probehead and a three-axis pulsed field gradient module. Gradients were used for the coherence transfer
pathway selection in HMBC and HMQC experiments. In the latter, broadband decoupling was performed
by using adiabatic WURST-40 pulses. For the proof of stereochemistry of investigated products we
carried out an elaborate series of nuclear Overhauser enhancement (NOE) experiments using difference
spectra, in order to establish the configuration of the key centers in the target products. ‘Usual work
up’ means washing of the organic layer with brine, drying over anhydrous magnesium sulfate, and
evaporating in vacuo with a rotary evaporator at aspirator pressure. Flash chromatographies were run
on silica gel (230–400 mesh).
5.2. Preparation of the 19-nor substrates: the 1b series and the interrupted cascade
The procedure previously described by us2 was used to convert the known 7 to the C-2 acetoxy
derivatives, obtained as an epimeric mixture (80%, ca. 1:1) which was directly reduced with lithium
aluminum hydride in ether to give the desired unsaturated 1,2-diol 1b. Placed in a flame dried flask, the
target diol 1b (630 mg, 1.5 mmol) and Pb(OAc)4 (820 mg, 1.9 mmol) were vacuumed and flashed with
argon, cooled to −20°C and 10 mL of acetonitrile were added. TLC control during 24 h room temperature
stirring indicated total consumption of the starting diol and appearance of a higher spot corresponding to
the product of the half-cascade 5b together with another one of lower Rf corresponding to the dialdehyde.
The A-nor-steroid thus obtained was purified by chromatography (heptane:EtOAc, 10:1 to 3:1) to afford
250 mg (40%) of 5b along with the dialdehyde resulting from the oxidative cleavage, which does not
give cycloaddition but rather tends to isomerize and decompose on standing. Compound 5b: [α]D +56.5
(c 1.45, CHCl3). IR (film): 2954, 2928, 2857, 1637, 1471, 1248, 1214, 1139, 1089, 1073, 1022, 944, 898,
876, 836, 776 cm−1. 1H NMR (250 MHz): 0.01 (6H, s), 0.73 (3H, s), 0.88 (9H, s), 0.62–1.74 (13H, m),
1.85–1.98 (3H, m), 2.14–2.23 (1H, m), 2.45 (1H, dd, J=7.6, 14.0), 3.55 (1H, dd, J=7.8, 8.6), 4.84 (1H,
d, J=6.0), 5.69 (1H, d, J=5.5), 6.17 (1H, d, J=6.0). 13C NMR (62.9 MHz): −4.8, −4.5, 11.3, 18.1, 23.3,
25.2, 25.8 (3C), 26.2, 30.9, 31.5, 37.0, 39.2, 41.2, 43.7, 46.3, 49.2, 53.8, 80.3, 81.7, 100.1, 111.7, 139.9.
CIMS: 405 ([MH]+, 100), 361 (13), 273 (8), 146 (10), 117 (6), 73 (27). HRCIMS: calcd for C24H41O3Si
m/z 405.2825, found 405.2829.
5.3. One-pot preparation of nor-steroidal acetoxy acetals 4, 11 and 12 from 1b: the C-10 modulated full-
cascade transformations
Using acetic acid as solvent: to a flame dried flask containing 1.22 g (3.0 mmol) of diol 1b and 4.00
g (9.0 mmol, 3 molar equiv.) of Pb(OAc)4, evacuated and flashed with argon, were added 15 mL of dry
and degassed acetic acid at room temperature. After 15 h of stirring, the reaction mixture was diluted
with ethyl acetate, washed with aqueous saturated NaHCO3 and worked up as usual. Chromatography
(heptane:ethyl acetate, 6:1) afforded 652 mg (47%) of the rearranged compound 4 together with 25% of
dialdehyde.

3984
J. I. Martín Hernando et al. / Tetrahedron: Asymmetry 10 (1999) 3977–3989
Using acetonitrile as solvent: to a flame dried flask containing 350 mg (0.86 mmol) of diol 1b and
840 mg (1.89 mmol, 2.2 molar equiv.) of Pb(OAc)4, vacuumed and flashed with argon, were added 5
mL of dry acetonitrile at 0°C. The mixture was stirred at room temperature for 30 h, diluted with ether
and filtered through Celite. The residue was purified on silica gel (heptane:EtOAc, 6:1) to yield 59 mg
(17%) of 5b along with 139 mg (35%) of 4 and 98 mg (28%) of dialdehyde resulting from the oxidative
cleavage. Compound 4: mp 119–121°C (CH2Cl2–EtOH). [α]D −41.7 (c 1.99, CHCl3). IR (film): 2953,
2928, 2857, 1747, 1675, 1366, 1238, 1139, 1126, 1091, 1039, 1025, 985, 877, 835, 775 cm−1. 1H NMR
(300 MHz): 0.01 (6H, s), 0.73 (3H, s), 0.87 (9H, s), 0.80–1.80 (13H, m), 1.82–1.94 (1H, m), 2.04–2.18
(1H, m), 2.10 (3H, s), 2.38–2.52 (1H, m), 3.57 (1H, t, J=7.8), 4.60 (1H, d, J=3.7), 5.57 (2H, bs), 6.03
(1H, d, J=3.7). 13C NMR (75 MHz): −4.8, −4.5, 11.2, 18.1, 21.1, 23.2, 25.5, 25.8 (3C), 30.4, 30.7, 35.6,
36.7 (2C), 37.0, 43.3, 45.0, 50.0, 79.5, 81.7, 96.0, 103.0, 126.0, 132.4, 169.9. CIMS: 403 ([MH]+–AcOH,
100), 359 (13), 289 (6), 271 (12), 133 (5), 73 (10).
Using acetic acidD4 as solvent (deuterium labeling experiment): to a flask charged with 1b (167
mg, 0.41 mmol) and Pb(OAc)4 (546 mg, 1.20 mmol, 3 molar equiv.), vacuumed and flashed with
argon, was added 4 mL of CD3CO2D and the mixture was stirred under argon for 14 h at room
temperature. Purification by chromatography (heptane:EtOAc, from 10:1 to 3:1) afforded 74 mg (39%)
of the deuterium labeled A-nor-steroid 11a. Similarly, the half-cascade intermediate 5b (292 mg, 0.70
mmol) when treated with Pb(OAc)4 (960 mg, 2.2 mmol, 3 molar equiv.) in 5 mL of CD3CO2D afforded
168 mg (50% isolated yield) of 11a: [α]D −39.3 (c 1.95, CHCl3). IR (film): 3058, 2954, 1754, 1472,
1434, 1387, 1360, 1332, 1251, 1138, 1089, 1034, 1007, 987, 968, 878, 836, 774, 739, 704, 668 cm−1. 1H
NMR (300 MHz): 0.00 (3H, s), 0.01 (3H, s), 0.73 (3H, s), 0.88 (9H, s), 0.62–1.78 (12H, m), 1.83–1.93
(1H, m), 2.03–2.17 (2H, m), 2.39–2.45 (1H, m), 3.58 (1H, dd, J=8.0, 8.4), 4.60 (1H, d, J=4.0), 5.59 (2H,
bs), 6.03 (1H, d, J=4.0). 13C NMR (75 MHz): −4.9, −4.5, 11.2, 18.1, 23.2, 25.6, 25.8 (3C), 30.4, 30.7,
35.6, 36.7, 36.8, 37.0, 43.4, 45.1, 50.0, 79.5, 81.7, 96.0, 103.0, 126.0, 132.4, 169.9. CIMS: 466 ([MH]+,
11), 403 (100), 391 (8), 374 (10), 146 (13), 117 (11), 73 (30). TBS removal at C-17 was then carried
out as follows. To a magnetically stirred solution of 11a (35 mg, 0.075 mmol) in 3 mL of acetonitrile at
0°C was added 0.1 mL of aqueous 40% HF. Stirring was continued at 0°C for 1 h, then quenching with a
saturated solution of sodium bicarbonate, extraction with ethyl acetate and usual work up furnished 25 mg
(95%) of 11b: mp 128–130°C (ether–heptane). [α]D −49.0 (c 0.93, CHCl3). IR (film): 3255, 2924, 2854,
1
1759, 1678, 1461, 1364, 1230, 1132, 1070, 1031, 1004, 992, 964, 951, 882, 851, 816 cm−1. H NMR
(800 MHz): 0.69 (3H, s, Me-13), 0.87 (1H, dc, J=4.6, 10.6, H-9), 0.93 (1H, dt, J=7.2, 11.8, H-14), 1.03
(1H, dt, J=3.9, 12.9, H-12ax), 1.10 (1H, dc, J=3.9, 13.0, H-11ax), 1.21 (1H, dc, J=6.0, 12.3, H-15ax),
1.26–1.31 (2H, m, H-8, H-1ax), 1.35–1.40 (1H, m, H-16ax), 1.50–1.54 (1H, m, H-15eq), 1.57–1.61 (1H,
m, H-7ax), 1.65 (1H, ddd, J=3.9, 7.3, 13.3, H-11eq), 1.73 (1H, td, J=3.4, 12.5, H-12eq), 1.95–2.03 (2H,
m, H-7eq, H-16eq), 2.01 (3H, s, OCOMe), 2.05 (1H, dd, J=1.8, 7.1, H-1eq), 2.34–2.40 (1H, m, H-10),
3.58 (1H, t, J=8.7, H-17), 4.52 (1H, d, J=4.2, H-4), 5.50–5.52 (2H, bs, H-2, H-6), 5.96 (1H, d, J=4.2,
H-3). 13C NMR (75 MHz): 10.9, 23.1, 25.5, 30.3 (2C), 35.6, 36.2, 36.7, 36.9, 43.0, 44.9, 50.3, 79.5, 81.7,
95.9, 103.0, 125.9, 132.4, 187.7. CIMS: 369 ([MNH4]+, 100), 184 (6), 152 (14), 118 (13), 105 (9), 88
(17), 52 (99), 35 (99).
Using (S)-O-acetyllactic acid as solvent: proceeding as above, 745 mg (1.83 mmol) of 1b were treated
with 2.44 g (5.5 mmol, 3 molar equiv.) of Pb(OAc)4, in 10 mL of (S)-O-acetyllactic acid. After stirring at
room temperature for 13 h the reaction mixture was worked up as above and purified by chromatography
using heptane:ethyl acetate, 6:1 to 1:1, as eluent. The crude residue afforded 28 mg (3%) of 4 and 393
mg (40%) of 12: [α]D −61.4 (c 1.14, CHCl3). IR (film): 2954, 1749, 1472, 1372, 1249, 1103, 1046,
1027, 1008, 985, 905, 879, 836, 758 cm−1. 1H NMR (300 MHz): 0.00 (3H, s), 0.01 (3H, s), 0.71 (3H, s),
0.78–1.63 (8H, m), 0.87 (9H, s), 1.45 (3H, d, J=7.1), 1.64–1.78 (3H, m), 1.82–1.95 (1H, m), 1.97–2.20

J. I. Martín Hernando et al. / Tetrahedron: Asymmetry 10 (1999) 3977–3989
3985
(1H, m), 2.06–2.19 (2H, m), 2.11 (3H, s), 2.35–2.47 (1H, m), 3.56 (1H, t, J=8.1), 4.65 (1H, d, J=3.9),
5.14 (1H, q, J=7.1), 5.55–5.63 (2H, m), 6.03 (1H, d, J=3.9). 13C NMR (75 MHz): −4.9, −4.6, 11.1, 16.6,
18.0, 20.5, 23.2, 25.6, 25.8 (3C), 30.3, 30.7, 35.5, 36.6 (2C), 36.7, 43.3, 44.9, 49.9, 67.9, 79.6, 81.6, 97.1,
103.2, 126.4, 132.0, 169.5, 169.9. CIMS: 535 ([MH]+, 6), 403 (100), 385 (9), 375 (10), 361 (11), 349
(8), 133 (99).
5.4. Preparation of the X-ray sample 9
This compound was obtained by desilylation–esterification of the corresponding A-nor-steroid frame-
work 4. The deprotection was effected as follows. To a stirred solution of 4 (303 mg, 0.65 mmol) in
acetonitrile (16 mL) was added 0.3 mL of aqueous 40% HF. The resulting solution was stirred at 0°C
for 1 h (TLC monitoring). It was then poured into a saturated aqueous sodium bicarbonate solution
and extracted with ethyl acetate. Usual work up afforded a crude residue which was purified on silica
eluting with heptane:EtOAc, 2:1. This afforded 194 mg (85%) of 8 as a white solid: mp 129–131°C
(ether–heptane–EtOAc). [α]D −53.1 (c 0.89, CHCl3). IR (nujol): 3259, 2925, 1765, 1434, 1365, 1217,
1
1129, 991, 880, 853, 812, 758 cm−1. H NMR (800 MHz): 0.69 (3H, s, Me-13), 0.87 (1H, dq, J=4.6,
10.6, H-9), 0.93 (1H, dt, J=7.2, 11.8, H-14), 1.03 (1H, dt, J=3.9, 12.9, H-12ax), 1.10 (1H, dq, J=3.9,
13.0, H-11ax), 1.21 (1H, dq, J=6.0, 12.3, H-15ax), 1.26–1.31 (2H, m, H-8, H-1ax), 1.35–1.40 (1H, m,
H-16ax), 1.50–1.54 (1H, m, H-15eq), 1.57–1.61 (1H, m, H-7ax), 1.65 (1H, ddd, J=3.9, 7.3, 13.3, H-
11eq), 1.73 (1H, td, J=3.4, 12.5, H-12eq), 1.95–2.03 (2H, m, H-7eq, H-16eq), 2.01 (3H, s, OCOMe),
2.05 (1H, dd, J=1.8, 7.1, H-1eq), 2.34–2.40 (1H, m, H-10), 3.58 (1H, t, J=8.7, H-17), 4.52 (1H, d, J=4.2,
H-4), 5.50–5.52 (2H, bs, H-2, H-6), 5.96 (1H, d, J=4.2, H-3). 13C NMR (200 MHz): 10.9 (Me-13), 21.0
(OCOMe), 23.0 (C-15), 25.4 (C-11), 30.2 (C-7), 30.3 (C-16), 35.5 (C-10), 36.1 (C-12), 36.6 (C-8), 36.9
(C-1), 43.0 (C-13), 44.8 (C-9), 50.3 (C-14), 79.4 (C-4), 81.6 (C-17), 95.9 (C-3), 103.0 (C-2), 125.9 (C-6),
132.3 (C-5), 169.9 (OCOMe). CIMS: 289 ([MH]+–AcOH, 100), 271 (17), 245 (13), 146 (8), 100 (16),
73 (26). Anal. calcd for C20H28O5·0.55H2O: C, 67.04; H, 8.19; found: C, 67.06; H, 7.97.
To a stirred solution of 8 (53 mg, 0.15 mmol) in dry pyridine (2 mL) at 0°C was added a catalytic
amount of DMAP. After 10 min of stirring, addition of an excess of p-BrBzCl (66 mg, 0.30 mmol)
followed and stirring continued overnight at room temperature. The reaction mixture was then poured
into an equal volume of ice cooled water and extracted with DCM. The combined organic extracts
were washed with 1N HCl, saturated aqueous solution of sodium hydrogen carbonate and brine, dried
(magnesium sulfate) and concentrated in vacuo. The residue was then purified on silica eluting with 3:1
to 1:1 heptane:EtOAc. This afforded 9, as a white solid (92% yield based on recovered starting material).
Compound 9: mp 136–138°C (ether–heptane). [α]D −10.8 (c 1.57, CHCl3). IR (film): 2922, 1740, 1717,
1
1591, 1484, 1397, 1274, 1173, 1126, 1070, 1042, 1012, 986, 881, 851, 812, 759, 737, 704 cm−1. H
NMR (800 MHz): 0.97 (3H, s), 1.02 (1H, dq, J=4.5, 10.6), 1.17–1.23 (2H, m), 1.30 (1H, dt, J=4.1,
13.4), 1.38–1.47 (3H, m), 1.65–1.69 (1H, m), 1.71–1.77 (3H, m), 1.84 (1H, td, J=3.3, 12.9), 2.12 (3H,
s), 2.11–2.16 (2H, m), 2.30–2.35 (1H, m), 2.46–2.51 (1H, m), 4.63 (1H, d, J=4.0), 4.86 (1H, dd, J=7.9,
9.2), 5.60 (1H, t, J=1.7), 5.62 (1H, dd, J=2.3, 5.1), 6.06 (1H, d, J=4.0), 7.58 (2H, d, J=8.6), 7.90 (2H, d,
J=8.6). 13C NMR (75 MHz): 12.2, 21.1, 23.3, 25.3, 27.5, 30.3, 35.5, 36.4, 36.5, 36.9, 43.1, 44.7, 50.1,
79.4, 83.4, 95.9, 103.0, 125.7, 127.8, 129.6, 131.0 (2C), 131.6 (2C), 132.4, 165.7, 169.8. CIMS: 533
([MH]+, 5), 531 ([MH]+, 5), 474 (9), 473 (33), 472 (9), 471 (32), 453 (12), 393 (84), 271 (100), 243 (29),
181 (17), 146 (13), 139 (17), 123 (91).
X-Ray structure determination of 9: BrC27H31O6, Mr=531.43, monoclinic, P21, a=8.596(2),
b=7.809(2), c=37.848(9) Å, β=90.80(2)°, V=2541(1) Å−3, Z=4, Dx=1.657 Mg m−3, λ(MoKα)=0.71073
Å, µ=16.57 cm−1, F(000)=1104, T=293 K. The sample (0.28×0.20×0.15 mm) was studied on an

3986
J. I. Martín Hernando et al. / Tetrahedron: Asymmetry 10 (1999) 3977–3989
automatic diffractometer CAD4 NONIUS with graphite monochromated MoKα radiation.13 The cell
parameters were obtained by fitting a set of 25 high-theta reflections. The data collection (2θmax=54°,
scan ω/2θ=1, tmax=60 s, range HKL: H 0,10 K 0,9 L −45,45, intensity controls without appreciable
decay (1.2%) gave 6268 reflections of which 5886 were independent (2524 with I>2.0σ(I)). After Lorenz
and polarization corrections14 the structure was solved with SIR-9715 which reveals the non-hydrogen
atoms of the structure. After anisotropic refinement, all the hydrogen atoms were found with a Fourier
difference. The whole structure was refined with SHELXL9716 by the full-matrix least-square techniques
(use of F magnitude; x, y, z, βij for Br, C, and O atoms, x, y, z in riding mode for H atoms; 614 variables
and 5886 observations; calcd w=1/[σ2(Fo2)+(0.1499P)2 +0.0040P] where P=(Fo2+2Fc2)/3 with the
resulting R=0.077, Rw=0.194 and Sw=1.001 (residual ∆ρ=0.93 eÅ−3)). Absolute configuration verified
with the Flack parameter17 0(2). Atomic scattering factors from the International Tables for X-ray
Crystallography.18 Ortep views realized with PLATON98.19 All the calculations were performed on a
Silicon Graphics Indy computer.
5.5. Preparation of the A-seco-steroid 10
Compound 4 (162.5 mg, 0.35 mmol) was reduced with excess of LiAlH4 (70 mg) in 7 mL of THF (5
h, from 0°C to room temperature). Proceeding as above, after quenching and filtration on SiO2 (eluent:
EtOAc) the crude was directly acetylated under usual conditions as follows. To a stirred solution of the
crude triol in 2 mL of pyridine and 0.05 molar equiv. of DMAP was added 5 molar equiv. of acetic
anhydride. The reaction mixture was stirred at 0°C for 2 h. After completion (TLC monitoring) saturated
aqueous sodium bicarbonate was added and the reaction mixture was extracted with dichloromethane.
Washings with 1N HCl, then NaHCO3, usual work up and chromatography, using heptane:EtOAc, 4:1,
as eluent, furnished 156 mg (95%) of 10: [α]D +45.0 (c 1.81, CHCl3). IR (film): 2956, 2857, 1743, 1658,
1471, 1368, 1243, 1142, 1098, 1044, 943, 904, 873, 837, 776 cm−1. 1H NMR (800 MHz): −0.01 (3H, s),
0.00 (3H, s), 0.72 (3H, s, Me-18), 0.88 (9H, s, t-Bu), 0.92–0.96 (1H, m, H-14), 1.02–1.07 (2H, m, H-9,
H-12), 1.17–1.29 (3H, m, H-8, H-11, H-15), 1.42–1.47 (1H, m, H-16), 1.49–1.56 (2H, m, H-7, H-15),
1.76 (1H, td, J=3.2, 12.6, H-12), 1.85–1.91 (2H, m, H-11, H-16), 1.98–2.03 (3H, m, 2 H-1, H-7), 2.03
(3H, s, MeCO), 2.05 (3H, s, MeCO), 2.06 (3H, s, MeCO), 2.16–2.18 (1H, m, H-10), 3.56 (1H, t, J=8.4,
H-17), 3.92–3.96 (1H, m, H-2), 4.03–4.07 (1H, m, H-2), 4.19 (1H, dd, J=8.6, 11.8, H-3), 4.31 (1H, dd,
J=3.7, 11.8, H-3), 5.51 (1H, dd, J=3.7, 8.6, H-4), 5.97 (1H, dd, J=1.8, 6.8, H-6). 13C NMR (200 MHz):
−4.9 (Me), −4.6 (Me), 11.2 (Me-18), 18.0 (Cq, TBS), 20.7 (MeCO), 20.9 (MeCO), 21.1 (MeCO), 23.2
(C-15), 25.8 (3C, t-Bu), 26.9 (C-11), 27.9 (C-1), 30.0 (C-7), 30.8 (C-16), 36.7 (C-8), 36.8 (C-12), 40.5
(C-10), 43.0 (C-9), 43.3 (C-13), 49.9 (C-14), 61.6 (C-2), 64.4 (C-3), 72.5 (C-4), 81.6 (C-17), 130.0 (C-6),
135.2 (C-5), 170.3 (MeCO), 170.6 (MeCO), 171.0 (MeCO). CIMS: 568 ([MNH4]+, 100), 510 (36), 452
(9), 241 (7), 192 (23), 184 (9), 152 (11), 132 (5), 118 (16), 88 (10), 77 (9). Anal. calcd for C30H50O7Si:
C, 65.42; H, 9.15; found: C, 65.72; H, 9.11.
5.6. Preparation and cascade type reactions of the allylically substituted substrates: the 1c series
Starting from the known C-2β acetoxy enone 13, obtained as previously described by us,2 the required
C-6 hydroxylated diol 1c was synthesized in four straightforward steps as follows. To a magnetically
stirred solution of acetoxy enone 13 (3.145 g, 7.82 mmol) and DMAP (521 mg, 4.26 mmol) in pyridine
(12 mL), acetic anhydride (12 mL, 108 mmol) was added at 0°C. The reaction mixture was allowed to
reach room temperature, then heated at 100°C for 27 h, after which solvent was removed under reduced
pressure. Usual work up gave after silica gel chromatography (using heptane:EtOAc, 8:1 to 3:1, as eluent)

J. I. Martín Hernando et al. / Tetrahedron: Asymmetry 10 (1999) 3977–3989
3987
2.39 g (69%) of the desired dienol acetate 14 along with unreacted starting material (21%). Compound
14: mp: 146–149°C (heptane–ether). [α]D −194 (c 0.83, CHCl3). IR (film): 2973, 2935, 2908, 2838,
1
1756, 1736, 1633, 1457, 1432, 1369, 1238, 1209, 1199, 1131, 1072, 1040, 1009, 987, 923 cm−1. H
NMR (300 MHz): 0.74 (3H, s), 0.71–2.23 (15H, m), 1.13 (9H, s), 1.16 (3H, s), 2.06 (3H, s), 2.12 (3H,
s), 3.38 (1H, t, J=8.2), 5.55–5.56 (2H, m), 5.93 (1H, s). 13C NMR (75 MHz): 11.6, 20.8, 20.9, 21.2 (2C),
23.7, 28.7 (3C), 31.1, 31.4, 31.5, 34.4, 36.9, 39.8, 42.4, 48.4, 51.3, 67.2, 72.2, 80.7, 122.7, 127.5, 138.7,
142.0, 169.4, 170.8. CIMS: 462 ([MNH4]+, 12), 436 (9), 402 (21), 385 (100), 343 (36).
Installation of the C-6 hydroxy group was then carried out using methyltrioxorhenium developed by
the Herrmann group.6 To a stirred solution of dienol acetate 14 (1.815 g, 4.09 mmol) in 4.0 mL of
CH2Cl2, pyridine (0.04 mL, 0.49 mmol), 30% H2O2 (0.63 mL, 6.14 mmol) and MeReO3 (5.0 mg, 0.02
mmol) were added and the reaction mixture stirred under argon at room temperature for 26 h. Upon
dilution with CH2Cl2, and washings with Na2S2O3 and brine, the organic layers were dried, concentrated
and chromatographed (SiO2, heptane:EtOAc, 6:1 to 1:1) to afford 1.214 g (71% yield) of 15Mm as
an epimeric mixture at C-6 (approximately 4:1, major:minor, β/α ratio), along with unreacted starting
material. Compound 15M: IR (film): 3468, 2968, 2938, 2869, 1747, 1695, 1614, 1450, 1363, 1232, 1198,
1078, 895 cm−1. 1H NMR (300 MHz): 0.78 (3H, s), 0.72–2.34 (16H, m), 1.14 (9H, s), 1.40 (3H, s), 2.13
(3H, s), 3.36 (1H, dd, J=7.5, 8.7), 4.47 (1H, t, J=2.8), 5.24 (1H, dd, J=5.0, 11.2), 5.85 (1H, s). 13C NMR
(75 MHz): 11.7, 20.9, 21.8, 23.7, 24.0, 28.7 (3C), 30.4, 31.1, 36.8, 37.7, 38.5, 40.5, 42.6, 50.2, 51.5, 70.4,
72.3, 74.1, 80.5, 122.3, 170.2 (2C), 194.2. CIMS: 419 ([MH]+, 100), 401 (21), 377 (16), 359 (64), 341
(11). It should be pointed out that, if the reaction is quenched after only 1 h, the 5,6-epoxide is isolated
in 45% yield along with an equal amount of recovered starting material.
Protection of the C-6 hydroxy group was performed without separation of the major and minor
isomers as follows. To a stirring solution of the epimeric mixture 15Mm (1.214 g, 2.90 mmol) in dry
toluene (30 mL) were added collidine (7.7 mL, 58.1 mmol) and TMSOTf (trimethylsilyl trifluoromethane
sulfonate, 4 mL, 21.80 mmol) at −40°C. Stirring at this temperature continued for 30 min, after which
time the reaction mixture was diluted by addition of heptane (250 mL). Washing with 1N HCl, then a
saturated aqueous solution of NaHCO3 and usual work up, afforded upon purification on silica gel, using
heptane:EtOAc, 1:6, as eluent, 1.335 g (94%) of 16Mm (only the major isomer is described): IR (film):
2970, 2873, 2852, 1751, 1700, 1618, 1457, 1252, 1086, 1064, 944, 908, 843, 736 cm−1. 1H NMR (300
MHz): 0.10 (9H, s), 0.79 (3H, s), 0.80–2.10 (15H, m), 1.13 (9H, s), 1.33 (3H, s), 2.15 (3H, s), 3.37 (1H,
t, J=8.1), 4.38 (1H, t, J=2.8), 5.26 (1H, dd, J=5.1, 12.4), 5.80 (1H, s). 13C NMR (50 MHz): 0.04 (3C),
11.7, 20.9, 21.9, 23.7, 24.1, 28.7 (3C), 30.5, 31.0, 36.8, 38.1, 41.1, 42.1, 42.7, 50.2, 51.2, 70.4, 72.2,
74.4, 80.5, 121.2, 170.2, 170.5, 194.3. CIMS: 491 ([MH]+, 100), 431 (83), 413 (71), 341 (65), 91 (20).
The key intermediate 1cMm was then obtained straightforwardly by reducing the C-6 epimeric mixture
16Mm, via standard literature procedures. Lithium aluminum hydride (380 mg, 10 mmol) was suspended
in dry ether (120 mL) and the mixture cooled to 0°C. The diastereomeric mixture of 16Mm (1.162 g, 2.37
mmol) in dry ether (100 mL) was added slowly, and stirring continued for 30 min at 0°C. The reaction
mixture was then diluted with technical ether, a few drops of water were added and the mixture stirred
at room temperature for 30 min. The crude reaction mixture was filtered through silica (some washings
of the silica with ethyl acetate may be necessary for maximum recovery) and the filtrate concentrated
under reduced pressure to give the target diol 1cMm, nearly quantitatively (1.16 g), as an epimeric
mixture at C-6, which was taken as such for the next step. For characterization purposes only, a small
quantity of the above mixture was purified on silica gel affording pure 1cM (6-β-OTMS): mp: 169–171°C
(heptane–ether). [α]D −44.7 (c 1.04, CHCl3). IR (film): 3381, 2957, 2933, 2873, 2848, 1458, 1389, 1361,
1250, 1198, 1165, 1122, 1083, 1056, 951, 864, 840, 744 cm−1. 1H NMR (300 MHz): 0.05 (9H, s), 0.74
(3H, s), 0.71–1.86 (17H, m), 1.10 (9H, s), 1.24 (3H, s), 3.32 (1H, dd, J=7.8, 8.5), 3.81 (1H, bs), 4.02

3988
J. I. Martín Hernando et al. / Tetrahedron: Asymmetry 10 (1999) 3977–3989
(1H, bs), 4.17 (1H, t, J=2.7), 5.37 (1H, d, J=3.8). 13C NMR (75 MHz): 0.3 (3C), 11.8, 21.0, 23.7, 23.8,
28.7 (3C), 30.3, 31.1, 37.1, 38.0, 40.1, 41.3, 42.6, 50.6, 54.1, 67.1, 67.3, 72.1, 74.6, 80.8, 121.4, 149.7.
CIMS: 451 ([MH]+, 4), 433 (100), 415 (16), 361 (38), 343 (87), 287 (18), 269 (8), 91 (14).
To a flask charged with 1c (246 mg, 0.55 mmol) and Pb(OAc)4 (484 mg, 1.10 mmol, 2 molar equiv.),
vacuumed and flashed with argon, was added 5.0 mL of dry acetonitrile and the mixture was stirred
under argon for 4 h at −30°C then 24 h at room temperature. Dilution with acetonitrile, filtration through
a pad of Celite and MgSO4 using heptane:ether, 1:1, evaporation to dryness and filtration through silica
(heptane:EtOAc, 12:1) afforded, by order of elution, 186 mg (76%) of 5cM, 6-β-OTMS containing major
isomer, along with 47 mg (19%) of 5cm (6-α-OTMS). Increasing the reaction temperature resulted in a
slight decrease in chemical yield with no evidence of significant alteration in the product composition.
Thus, the same reaction, repeated in refluxing acetonitrile for 24 h, afforded a similar result although
the reaction crude was somewhat sluggish. Changing the solvent showed only marginal effects on the
reaction rate and chemical yield. When the reaction was carried out in acetic acid at room temperature for
24 h and then heating at 40°C for 4.5 h, 64% of 5cM (only major) was obtained, the minor stereoisomer
being destroyed. Compound 5cM: mp 113–114°C (heptane–ether). [α]D +1.8 (c 1.61, THF). IR (film):
3074, 2972, 2872, 1631, 1444, 1389, 1361, 1251, 1201, 1149, 1109, 1067, 953, 940, 860, 842, 734 cm−1.
1H NMR (300 MHz): 0.12 (9H, s), 0.75 (3H, s), 0.87–1.67 (11H, m), 1.11 (3H, s), 1.13 (9H, s), 1.77
(1H, td, J=3.3, 12.3), 1.82–1.95 (1H, m), 1.86 (1H, dd, J=0.9, 13.9), 2.17 (1H, dd, J=5.8, 13.9), 3.36
(1H, dd, J=7.9, 8.5), 3.99 (1H, t, J=2.7), 5.27 (1H, d, J=6.2), 5.55 (1H, d, J=5.6), 6.24 (1H, d, J=6.2).
13C NMR (75 MHz): 0.2 (3C), 11.6, 14.9, 21.3, 23.7, 28.7 (3C), 29.1, 31.2, 34.1, 37.4, 42.8, 47.8, 48.2,
50.1, 53.5, 69.2, 72.1, 80.8, 83.0, 99.4, 108.7, 139.2. CIMS: 449 ([MH]+, 100), 431 (16), 377 (20), 375
(20), 146 (27). Anal. calcd for C26H44O4Si: C, 69.59; H, 9.88; found: C, 69.84; H, 10.03. Compound
5cm: [α]D +11.3 (c 0.67). IR (film): 3077, 2970, 2873, 1735, 1634, 1450, 1390, 1361, 1251, 1202, 1108,
1095, 1069, 1032, 974, 878, 841, 734 cm−1. 1H NMR (300 MHz): 0.13 (9H, s), 0.72 (3H, s), 0.75–1.65
(11H, m), 1.07 (3H, s), 1.13 (9H, s), 1.76 (1H, td, J=3.3, 12.3), 1.84–1.94 (1H, m), 1.90 (1H, dd, J=1.2,
13.9), 2.17 (1H, dd, J=5.8, 13.8), 3.37 (1H, dd, J=7.7, 8.7), 3.59 (1H, dd, J=4.7, 11.3), 4.82 (1H, d,
J=6.2), 5.60 (1H, d, J=5.4), 6.25 (1H, d, J=6.2). 13C NMR (75 MHz): 0.5 (3C), 11.7, 14.1, 21.4, 23.7,
28.7 (3C), 31.2, 34.9, 35.2, 37.1, 42.6, 47.2, 47.6, 50.2, 56.0, 71.1, 72.2, 80.6, 85.4, 99.4, 109.1, 139.9.
CIMS: 449 ([MH]+, 100), 391 (11), 377 (11), 359 (10), 315 (8). HRCIMS: calcd for C26H45O4Si m/z
449.3087, found 449.3091.
Acknowledgements
The authors thank Ministerio de Educacion y Cultura (Spain) for a fellowship to Dr. J. I. Martín
Hernando and the European Commission for a Research Training Grant to Dr. J. I. Candela Lena.
References
1. Arseniyadis, S.; Brondi Alves, R.; Quilez del Moral, J.; Yashunsky, D. V.; Potier, P. Tetrahedron 1998, 54, 5949–5958;
Arseniyadis, S.; Brondi Alves, R.; Pereira de Freitas, R.; Muñoz-Dorado, M.; Yashunsky, D. V.; Potier, P.; Toupet, L.
Heterocycles 1997, 46, 727–764.
2. Rico Ferreira, M.; Martín Hernando, J. I.; Candela Lena, J. I.; Quílez del Moral, J.; Arseniyadis, S. Tetrahedron: Asymmetry
1999, 10, 1527–1537.
3. Tetrahedron Symposia-in-Print Number 62, Cascade Reactions; Grigg, R., Ed. 1996, 52, 11385–11664 and references
cited therein.

J. I. Martín Hernando et al. / Tetrahedron: Asymmetry 10 (1999) 3977–3989
3989
4. Arseniyadis, S.; Rodriguez, R.; Muñoz Dorado, M.; Brondi Alves, R.; Ouazzani, J.; Ourisson, G. Tetrahedron 1994, 50,
8399–8426. Arseniyadis, S.; Rodriguez, R.; Cabrera, E.; Thompson, A.; Ourisson, G. Tetrahedron 1991, 47, 7045–7058.
5. Menberu, D.; Nguyen, P. V.; Onan, K. D.; Le Quesne, P. W. J. Org. Chem. 1992, 57, 2100–2104.
6. Herrmann, W. A.; Fischer, R. W.; Marz, D. W. Angew. Chem., Int. Ed. Engl. 1991, 30, 1638–1641. Herrmann, W. A. J.
Organomet. Chem. 1995, 500, 149–173. Herrmann, W. A.; Fischer, R. W.; Rauch, M. U.; Scherer, W. J. Mol. Catal. 1994,
86, 243–266. Herrmann, W. A.; Kuhn, F. E. Acc. Chem. Res. 1997, 30, 169–180.
7. Arseniyadis, S.; Quílez del Moral, J.; Brondi Alves, R.; Potier, P.; Toupet, L. Tetrahedron: Asymmetry 1998, 9, 2871–2878.
8. Articles dealing with specific aspects of organolead chemistry. For a review on α0-acetoxylation of α,β-unsaturated
ketones see: Demir, A. S.; Jeganathan, A. Synthesis 1992, 235–247. For oxidative transformations, see: Rubottom, G.
M. Oxidation in Organic Chemistry; Trahanowsky, W. H., Ed.; Academic Press: London, 1982; part D. For carbon–carbon
bond forming reactions, see: Pinhey, J. T. Aust. J. Chem. 1991, 44, 1353–1382. For leading references concerning the
oxidative 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.
9. Deslongchamps, P. Stereoelectronic Effects in Organic Chemistry; Pergamon: New York, 1983.
10. Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C. Chang, G.; Hendrickson, T.; Still,
W. C. J. Comput. Chem. 1990, 11, 440–467.
11. Precedents for the electrophilic attack of an olefin by metals which react as typical electrophiles; for Tl3+ see: McKillop,
A. Pure Appl. Chem. 1975, 43, 463–479; for Hg2+: Larock, R. C. Tetrahedron 1982, 38, 1713–1754; Arseniyadis, S.; Goré,
J. Tetrahedron Lett. 1983, 24, 3997–4000; for Pb4+: Levisalles, J.; Molimard, J. Bull. Soc. Chim. Fr. 1971, 2037–2047;
Rubottom, G. M.; Marrero, R.; Gruber, J. M. Tetrahedron 1983, 39, 861–865; for Ag+: Arseniyadis, S.; Sartoretti, J.
Tetrahedron Lett. 1985, 26, 729–732.
12. Arseniyadis, S.; Rico Ferreira, M.; Quilez del Moral, J.; Martin Hernando, J.; Potier, P.; Toupet, L. Tetrahedron: Asymmetry
1998, 9, 4055–4071.
13. Fair, C. K. MolEN, An Interactive Intelligent System for Crystal Structure Analysis, User Manual; Enraf–Nonius: Delft,
The Netherlands, 1990.
14. Spek, A. L. HELENA. Program for the Handling of CAD4-Diffractometer Output SHELX(S/L); Utrecht University:
Utrecht, The Netherlands, 1997.
15. Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A.; Moliterni, A. G. G.; Polidori, G.;
Spagna, R. Sir97: A New Tool for Crystal Structure Determination and Refinement; 1998; Vol. 31, pp. 74–77.
16. Sheldrick, G. M.; Schneider, T. R. SHELXL: High Resolution Refinement. Methods in Enzymology; Sweetand, R. M.;
Carter Jr., C. W., Eds.; Academic Press: Orlando, 1997; 277, pp. 319–343.
17. Flack, H. D. Acta Cryst. A 1983, 39, 876–881.
18. International Tables for X-Ray Crystallography; Kynoch Press: Birmingham, 1974; Vol. IV.
19. Spek, A. L. PLATON. A Multipurpose Crystallographic Tool; Utrecht University: Utrecht, The Netherlands, 1998.