Thiophenol-mediated 1,5-hydrogen atom abstraction: Easy access to mono- and bicyclic compounds

Article abstract of DOI:10.1002/adsc.200505211

A thiophenol-mediated method for cyclization of alkynes is described. The reaction cascade involves the intermolecular addition of a phenylthiyl radical to a terminal triple bond generating an alkenyl radical, followed by a 1,5-hydrogen atom transfer and a 5-exo-trig radical cyclization. This very efficient tin-free procedure allows one to prepare highly functionalized cyclopentane derivatives as well as fused bicyclic and spirocyclic compounds from easily available precursors. During this cyclization process, a phenylthio moiety is incorporated into the final cyclized products. This functionalization is particularly attractive for further transformation of the products.

Full text of DOI:10.1002/adsc.200505211

FULL PAPERS
DOI: 10.1002/adsc.200505211
Thiophenol-Mediated 1,5-Hydrogen AtomAbstraction: Easy
Access to Mono- and Bicyclic Compounds
a
a
a
a,
´ `
Florent Beaufils, Fabrice Denes, Barbara Becattini, Philippe Renaud, *
Kurt Schenkb
a
Universität Bern, Departement für Chemie und Biochemie, Freiestrasse 3, CH-3000 Bern 9, Switzerland
Fax: (þ41)-31-631-3426, e-mail: philippe.renaud@ioc.unibe.ch
b
Laboratoire de Cristallographie 1, EPFL SB IPMC LCR1, BSP 521, CH-1015 Lausanne, Switzerland
Received: May 22, 2005; Accepted: August 1, 2005-09-01
Supporting Information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: A thiophenol-mediated method for cycliza- clic and spirocyclic compounds from easily available
tion of alkynes is described. The reaction cascade in- precursors. During this cyclization process, a phenyl-
volves the intermolecular addition of a phenylthiyl thio moiety is incorporated into the final cyclized
radical to a terminal triple bond generating an alkenyl products. This functionalization is particularly attrac-
radical, followed by a 1,5-hydrogen atomtransfer and
tive for further transformation of the products.
a 5-exo-trig radical cyclization. This very efficient tin-
free procedure allows one to prepare highly function- Keywords: alkynes; cyclization; hydrogen transfer;
alized cyclopentane derivatives as well as fused bicy- radicals; spiro compounds; sulfur
Introduction
tion, the new radical species can cyclize to give a cyclo-
pentane derivative (Scheme 1).[3–5]
Radical reactions represent a valuable tool for organic
The alkenyl radicals are usually prepared by reaction
synthesis.[1] For instance, carbon-carbon bonds can be of the corresponding vinyl halide with a stannyl radi-
formed under mild conditions with a unique functional cal.[3–5] The pioneering work of Curran demonstrated
group tolerance. Moreover, radical reactions can be the potential of this reaction [see Scheme 1, Eq. (1)]
highly regio- and stereoselective and their ability to be and following this work many applications have been
involved in cascade reactions makes them particularly developed.[2,6] However, the practicability of this proc-
attractive. The use of hydrogen atomabstraction is of
ess is hampered by the use of tin derivatives and by the
particular interest since it allows functionalization of re- formation of uncyclized product via direct reduction of
mote unreactive positions without using of transition the intermediate alkenyl radical. Radical addition to ter-
metal catalysts.[2] The highly reactive alkenyl radicals minal or disubstituted alkynes offers an attractive alter-
are suitable precursors for efficient intramolecular 1,5- native for the generation of alkenyl radicals that under-
À
hydrogen abstraction at C H bonds. After transloca- go 1,5-translocation to alkyl radicals and 5-exo-trig cy-
clization (related reactions involving the formation of
heterocycles via transient silyl,[7,8] alkoxyl[9,10] and imid-
yl[11] radicals are also reported). Inter- and intramolecu-
lar additions of carbon-centered radicals are utilized to
initiate such cascade processes.[4,12–14] Bachi and later
Alcaide employed the intermolecular radical addition
of tin hydride[15,16] and more recently, in parallel to the
present work, we developed a dialkyl phosphite-mediat-
ed reaction.[17]
Thiyl radicals are easily generated fromthiols and di-
sulfides and add efficiently in a reversible manner to car-
bon-carbon multiple bonds leading to carbon-centered
Scheme 1. 1,5-Hydrogen transfer-cyclization process.
radicals.[18,19] The resulting radicals have been extensive-
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ly used for further cyclization onto alkenes,[20,21] oxime
ethers and hydrazones.[22] To the best of our knowledge,
only one report of a thiophenol-mediated radical addi-
tion onto an alkyne followed by a radical transloca-
tion-cyclization process has been reported.[23] In this re-
port, Burke described the formation of tetrahydrofuran-
2-carboxylic acid derivatives involving the generation of
captodative stabilized radicals. Even in this favorable
system, the formation of non-cyclized products via di-
rect reduction of the alkenyl radical intermediate could
not be totally suppressed. We report here that, despite
its high radical reducing power, the thiophenol-mediat-
ed reaction is far more efficient than initially expected
when run under non-chain reaction conditions and gen-
eration of non-stabilized alkyl radical is even possible.
Expeditious preparation of fused-ring and spirocyclic
compounds illustrates the potential of this approach
and complements our preliminary results reported re-
cently.[24,25]
Scheme 2. Attempt to develop a diphenyl disulfide-mediated
reaction.
Results and Discussion
Development of the Method
An efficient and preparatively useful procedure for the
formation of a 5-membered ring via a radical transloca-
tion-cyclization process should fulfill the following crite-
ria: 1) the starting material and reagents should be easily
available; 2) the direct reduction of the intermediate al-
kenyl radicals leading to non-cyclized product should be
minimized; 3) the final product should be a versatile syn-
thetic intermediate; 4) the toxicity of the reagent should
be as low as possible and product contamination (a ma-
Scheme 3. Optimization of the reaction conditions with thio-
phenol.
jor drawback of the tin hydride procedure) should be best results and the cyclized product 3b is isolated in
eliminated. With these few criteria in mind, we decided 90% yield. The uncyclized product 4b is not detected
to test the use of terminal alkynes as radical precursors by 1H NMR analysis of the crude product. Froma prac-
together with a source of thiyl radicals. Preliminary ex- tical point of view, the procedure is particularly simple
periments were run with diphenyl disulfide and the ter- since no work-up is required. At the end of the reaction,
minal alkyne 1a [Scheme 2, Eq. (2)]. The expected di- the crude reaction mixture is concentrated by evapora-
thioacetal 2a was not observed, indicating that trapping tion of the solvent under reduced pressure and directly
of the final radical with diphenyl disulfide is not work- submitted to purification by flash chromatography.
ing. However, traces of the reduced product 3a were iso-
lated and attributed to the presence of a small amount of amazing when compared with the tin hydride reaction.
thiophenol in the reaction mixture.[26]
Indeed, thiophenol is a much more powerful reducing
The efficiency of this thiophenol-mediated reaction is
Based on this preliminary result, the use of thiophenol agent than tin hydride,[27] however, direct reduction of
was investigated. Under standard reaction conditions the alkenyl radical intermediate is in most cases not ob-
(refluxing benzene, 10 mol % AIBN), only a low con- served. The assumed mechanism of the thiophenol
version was obtained with different substrates. There- mediated reaction is depicted in Scheme 4. The phenyl-
fore, a systematic study for the optimization of the reac- thiyl radical is generated fromthiophenol and AIBN
tion conditions was undertaken with substrate 1b and adds to the terminal alkyne presumably in a reversi-
[Scheme 3, Eq. (3)]. Best results are obtained in reflux- ble manner. The alkenyl radical undergoes 1,5-hydro-
ing t-BuOH by using syringe pump addition of thiophe- gen-transfer followed by 5-exo cyclization and reduction
nol (2 equivalents) over 20 hours under AIBN initiation. of the phenylthio-substituted alkyl radical by thiophe-
The amount of the initiator plays a crucial role in this nol. The phenylthiyl radical can either start a new chain
process. The use of two equivalents of AIBN gives the reaction or dimerize to give the diphenyl disulfide. Un-
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Thiophenol-Mediated 1,5-Hydrogen AtomAbstraction
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Scheme 4. Proposed mechanism.
der our reaction conditions, the disulfide is inert and
does not react with any of the radicals involved in the
chain process. The use of a stoichiometric amount of
AIBN allows regeneration of the thiyl radical by reac-
tion with either thiophenol or diphenyl disulfide.
Preparation of Cyclopentane Derivatives
The scope and limitations of the process were investigat-
ed next. For this purpose, a series of substrates, easily
prepared by alkylation of dimethyl propargylmalonate,
were treated under our optimized reaction conditions
[Scheme 5, Eq. (4)]. When the translocated radical is
stabilized by a heteroatom(substrate 1b, 1c and 1d), ex-
cellent yields of cyclic products 3b, 3c and 3d are ob-
tained and no traces of non-cyclized products are detect-
ed. Similar results are obtained with translocated radi-
cals stabilized by delocalization (products 3e, 3f and
3a). The relative configurations of the major isomers
of 3a and 3b–3f have not been assigned, however, relat-
ed systems possessing gem-diester substituents are
known to give the cis-cyclopentanes as major isomers
when R1 ¼CO2R or alkyl and R2 ¼H, and the trans-iso-
mer when R1 ¼OTBDMS or phenyl and R2 ¼H.[5,28,29]
Interestingly, the formation of non-substituted alkyl
radicals is also possible. For instance, the tertiary alkyl
radical derived from 1g affords the cyclic compound 3g
in 83% yield. A primary alkyl radical generated from
1h affords the cyclic product 3h as a single product albeit
in moderate yield.
Scheme 5. Reaction with propargylmalonate derivatives.
Scheme 6. Limitation of the method: formation of reduced
The results described in Scheme 5 (compounds 3b, 3c,
3e, 3f and 3g) compare well with the results obtained by
Curran starting fromalkenyl bromides using tin hydride
products and benzothiophene derivatives.
as reducing agent.[5] The thiophenol method was further 5i defines clearly the limit of the thiophenol method.
investigated with substrate 1i [Scheme 6, Eq. (5)]. The When the hydrogen abstraction step is too slow (a rate
reaction affords a mixture of three products: the desired constant of ¼5ꢀ105 MÀ1 sÀ1 can be estimated for this
cyclic product 3i (57%), the non-cyclized alkenyl thio- 1,5 H-transfer)[5] the intramolecular addition of the vinyl
ether 4i (17%) and the benzothiophene derivative 5i re- radical onto the aromatic ring becomes a competitive
sulting fromthe intramolecular addition of the transient
process and the use of higher dilution will not allow us
alkenyl radical onto the phenyl ring.[30] The side product to enhance the ratio of hydrogen transfer. Attempts to
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Scheme 7. Effect of the substitution at the propargylic center.
Scheme 8. Determination of the relative configuration of 7 by
X-ray crystal structure analysis.
generate a primary radical from 1j [Scheme 6, Eq. (5)]
affords the thioether 4j in 54% yield together with
some benzothiophene 5j (X5%). In a similar example,
the tin hydride method failed also to give the product
of radical translocation-cyclization and a rate constant
for the 1,5-hydrogen-transfer was estimated to be
<105 MÀ1 sÀ1 [5]
.
Substrates bearing an alkyl substituent at the propar-
gylic position were investigated next (Scheme 7). Inter-
estingly, most of these substrates give very high yields of
hydrogen transfer. For instance, the generation of terti-
ary alkyl radicals from 1k affords the cyclic compound
3k in 79% yield as single diastereomer. The ester deriv-
ative 1l affords the cyclopentane 3l in 97% yield. Gener- Scheme 9. Effect of vicinal substituents.
ation of secondary (from 3m) and primary (from 3n) al-
kyl radicals is also possible and leads to the expected cy-
clic compounds in 62% and 20% yield, respectively. beneficial effect on the rate of hydrogen transfer. The
Similar results are obtained with precursors bearing an presence of vicinal substituents (the propargylic sub-
n-pentyl substituent at the propargylic position. Cyclo- stituent and the gem-diesters) is at the origin of a rate ac-
pentanes 3o and 3p are isolated both in 90% yield with celeration similar to the one observed by Jung in related
a complete regioselectivity. Indeed, a competitive 1,5- vic-disubstituted systems.[32] To test further this hypoth-
hydrogen-transfer involving the propargyl n-pentyl esis, substrate 8 possessing only vicinal substituents was
side chain is not observed, presumably because of the prepared (Scheme 9). Upon treatment with thiophenol/
absence of a Thorpe–Ingold effect. In order to assess AIBN, the cyclized product 9 (85% yield, one diaster-
the relative configuration of the products, a closely relat- eomer) is obtained. This result supports the presence
ed crystalline sulfone was prepared. The reaction of 1k of vic-disubtituent effect enhancing the rate of hydrogen
was repeated with thiocresol and the p-tolyl thioether transfer.
6 was isolated in 95% yield as a single diastereomer. Ox-
idation with magnesium monoperoxyphthalate
(MMPP) afforded the sulfone 7 that gave upon recrys- Fused Bicyclic Compounds
tallization crystals suitable for X-ray analysis
(Scheme 8).[31]
The preparation of fused bicyclic compounds was envis-
Comparison of the results of Schemes 7 and 6 demon- aged next. For this purpose, the cycloalkanones 10a–10c
strates clearly that the propargylic substituent has a very were prepared in 70–77% yield by conjugate addition of
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Scheme 12. Spirocyclic ketones.
uted according to well documented literature prece-
dents.[33–36]
Encouraged by these results, we decided to investigate
the more challenging case of 1,5-hydrogen shift in non-
functionalized cycloalkanes. The substituted cycloal-
kanes 12a–12c were treated with thiophenol/AIBN un-
der the standard conditions [Scheme 11, Eq. (9)]. The
[3.3.0]- and [5.3.0]fused bicyclic products 13a and 13c
were obtained in 79% and 88% yield. Preparation of
the [4.3.0]bicyclic species 13b was less efficient (47%
yield).
Scheme 10. Fused bicyclic ketones.
Spirocyclic Compounds
Standard procedures for spirocyclization of alkynes are
intramolecular carbomercuration,[37–40] and iodocarbo-
cyclization of a-iodocycloalkanones using Lewis acids
such as AlCl3.[41] Free radical cyclizations have emerged
as a powerful method of carbocyclization. For instance,
Clive has reported the use of a-(phenylseleno) ketones
as radical precursors in 5-exo cyclizations.[42] Sha and
co-workers have demonstrated that a-carbonyl radicals
generated from a-iodo ketones cyclize efficiently in a 5-
Scheme 11. Fused bicyclic alkanes.
the commercially available dimethyl propargylmalo- exo-dig mode in the presence of tributyltin hydride and
nate onto the corresponding cycloalkenones in the pres- AIBN.[43,44] Only few reports deal with the use of 1,5-hy-
ence of DBU [Scheme 10, Eq. (7)].
drogen transfer for the preparation of spiroalkanes.[44–47]
Treatment with thiophenol and AIBN under standard The thiophenol-mediated hydrogen transfer-cyclization
conditions affords the expected fused bicyclic deriva- process represents a very attractive procedure for the
tives in good yields as a single regioisomer [Scheme 10, preparation of spirocyclic systems since the precursors
Eq. (8)]. As planned, hydrogen abstraction is only tak- are easily available and the generation of tertiary alkyl
ing place at the a-position of the ketone leading to a sta- radical via 1,5-hydrogen transfer is particularly efficient
bilized enolate radical. In case of the cyclopentanone (vide supra). A first series of experiments was run with
10a, the process is very efficient and the fused bicyclic the easily available cyclic ketones 14a–14c according
compound 11a is obtained as an endo/exo 91:9 mixture to Scheme 12 [Eq. (10)]. The spirocyclic ketones 15a–
of diastereomers in 79% yield after flash chromatogra- 15c are obtained in good yield (73%–92%) and moder-
phy (entry 1). Cyclohexanone 10b and cycloheptanone ate stereoselectivity.[48]
10c derivatives give similar results (11b 75%, 11c 78%)
Substituted 5-cycloalkylpent-1-yne derivatives 16a–
with a lower stereoselectivity control in the cyclization 16d were investigated next according to Scheme 13
step. The relative endo configuration of the major iso- [Eq. (11)]. The non-substituted precursor 16a affords
mers of 11a and 11b is not proven but tentatively attrib- none of the desired spirocyclic derivative 17a. Substrate
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General Procedure for the Thiophenol-Mediated
Reaction
To a solution of the alkyne (1.0 mmol) and AIBN (1.0 mmol,
164 mg) in refluxing t-BuOH (100 mL) was added over 20 h a
solution of AIBN (1 mmol, 164 mg) in benzene (2 mL) and a
solution of thiophenol (2.0 mmol, 220 mg) in benzene (2 mL)
through a syringe pump (the needles were placed in the con-
denser). After completion of the reaction (TLC monitoring),
the solution was cooled down and t-BuOH evaporated under
reduced pressure. The residue was filtered through a short
pad of silica gel (AcOEt/hexane). The filtrate was evaporated
under reduce pressureand flash chromatography (AcOEt/hex-
ane) of the residue afforded the desired cyclized products. The
ratio of isomers was determined by GC-MS analysis of the
crude reaction mixture.
Scheme 13. Spirocyclic alkanes.
2-Isopropyl-4,4-dimethyl-3-phenylsulfanylmethylcyclo-
pentane-1,1-dicarboxylic acid dimethyl ester (3k): According
to the general procedure, from 1k (268 mg, 1 mmol). Flash
chromatography (hexane/AcOEt, 9:1) gave 3k as a single
product; yield: 299 mg (79%); 1H NMR (300 MHz): d¼7.35–
7.25 (m, 4H), 7.19–7.15 (m, 1H), 3.72 (s, 3H), 3.69 (s, 3H),
3.09 (dd, J¼12.2, 3.8 Hz, 1H), 2.93 (dd, J¼12.2, 10.0 Hz,
1H), 2.72 (dd, J¼10.4, 2.6 Hz, 1H), 2.41 (d, J¼13.9 Hz, 1H),
2.08–1.98 (m, 2H), 1.95 (d, J¼13.9 Hz, 1H), 1.26 (s, 3H), 0.99
(d, J¼7.2 Hz, 3H), 0.95 (s, 3H), 0.83 (d, J¼7.0 Hz, 3H);
13C NMR (75 MHz): d¼174.0, 172.2, 137.7 (Cq), 129.3
(2CH), 129.0 (2CH), 126.0, 62.4 (Cq), 55.2, 52.8, 52.6, 50.4
(CH2), 48.1, 40.0 (Cq), 35.9 (CH2), 30.7, 27.7, 24.0, 23.4, 17.7;
HR-MS: calcd. for C21H30O4S [Mþ]: 378.1864; found: 378.1863.
4-Oxo-3-phenylsulfanylmethylhexahydropentalene-1,1-
dicarboxylic acid dimethyl ester (11a): According to general
procedure, from 10a (252 mg, 1 mmol). Flash chromatography
(hexane/AcOEt, 6:1) gave 11a as a mixture of 2 diastereomers
in a 91:9 ratio; yield: 286 mg (79%). The ratio of the isomers
was determined by 1H NMR analysis of the crude reaction mix-
ture before flash chromatography. Major isomer (endo-11a):
1H NMR (400 MHz, CDCl3): d¼7.12–7.40 (m, 5H), 3.75 (s,
16b, possessing a substituent at the propargylic position,
gives the desired spiro compound 17b in low yield (28%).
The presence of an alkoxy substituent at position 4 in 16c
has a positive effect and the spiro derivative 17c is ob-
tained in 47% yield (29% starting material recovered).
Finally, 4,4-disubstituted pentyne 16d affords the spiro-
cyclic compound 17d in 88% yield demonstrating fur-
ther the importance of gem-disubstituents.
Conclusion
We have developed an efficient procedure to run cas-
cade reactions involving 1,5-hydrogen atomabstraction
followed by a radical cyclization. Such reactions are clas-
sically run under tin hydride conditions starting from
haloalkenes. In the procedure presented here, alkenyl 3H), 3.72 (s, 3H), 3.42–3.55 (m, 2H), 2.88 (dd, 1H, J¼8.82,
10.67), 2.65 (dd, 1H, J¼9.93, 12.93), 2.53 (dd, 1H, J¼6.25,
radicals are generated fromeasily available terminal al-
12.87), 2.43 (m, 1H), 2.25 (m, 3H), 2.06 (m, 1H), 1.54 (dd, 1H,
J¼9.19, 13.24); 13C NMR (100 MHz, CDCl3): d¼24.6 (CH2),
36.2 (CH2), 38.4 (CH2), 39.9 (CH2), 40.1 (CH), 47.1 (CH),
53.0 (CH3), 53.2 (CH), 53.4 (CH3), 63.7 (C), 126.3 (CH),
128.9 (2*CH), 129.7 (2*CH), 136.1 (C), 169.8 (C), 171.8 (C),
218.9 (C); HR-MS: calcd. for C19H22O5S [Mþ]: 362.1188; found:
362.1188.
kynes and thiophenol. This tin-free procedure gives high
yields of radical translocation products. By proper de-
sign of gem- and vic-disubstituents effects, it is possible
to generate efficiently non-stabilized radicals via 1,5-hy-
drogen transfer. This efficient and convenient proce-
dure allows the formation of fused rings and spiro deriv-
atives under tin-free conditions. Interestingly, the prod-
ucts bear a phenylthio substituent that offers many op-
portunities for further transformations. Application in
the total synthesis of active compounds containing fused
ring or spiro-bicyclic skeletons are currently under in-
vestigation and will be reported in due course.[49]
3-Phenylsulfanylmethylhexahydropentalene-1,1-dicar-
boxylic acid dimethyl ester (13a): According to the general
procedure, from 12a (238 mg, 1 mmol). Flash chromatography
(hexane/AcOEt, 9:1) gave 13a as a mixture of diastereomers in
a 94:6 ratio; yield: 268 mg (77%). Major isomer (endo-13a):
1H NMR (300 MHz): d¼7.36–7.26 (m, 4H), 7.22–7.16 (m,
1H), 3.71 (s, 3H), 3.70 (s, 3H), 3.27 (q, J¼9.2 Hz, 1H), 3.01–
2.89 (m, 2H), 2.66 (m, 1H), 2.29–2.17 (m, 1H), 2.16–2.05 (m,
2H), 1.86–1.68 (m, 3H), 1.41–1.14 (m, 2H), 1.03–0.86 (m,
1H); 13C NMR (75 MHz): d¼172.6, 170.9, 136.8 (Cq), 129.5
(2CH), 128.9 (2CH), 126.1 (CH), 63.4 (Cq), 52.8, 52.3, 47.8,
45.1, 38.8, 36.6 (CH2), 34.9 (CH2), 30.5 (CH2), 28.0 (CH2),
27.2 (CH2); HR-MS: calcd. for C19H22O4S [Mþ]: 346.1239;
found: 346.1239.
Experimental Section
General information, full experimental procedures and analyt-
ical data are available as Supporting Information.
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2-Isopropyl-1-phenylsulfanylmethylspiro[4.5]decan-6-
one (15c): According to the general procedure, from 14c
(206 mg, 1 mmol). Flash chromatography (cyclohexane/t-
BuOMe, 95:5) gave 15c as a mixture of diastereomers in a
67:33 ratio; yield: 277 mg (88%). Major diastereomer:
1H NMR (400 MHz): d¼7.33–7.25 (m, 4H), 7.16–7.12 (m,
1H), 3.01 (dd, J¼10.7, 4.1 Hz, 1H), 2.91–2.82 (m, 1H), 2.82
(dd, J¼10.7, 9.2 Hz, 1H), 2.49–2.35 (m, 2H), 2.03–1.92 (m,
1H), 1.90–1.59 (m, 10H), 1.41–1.32 (m, 1H), 0.91 (d, J¼
6.8 Hz, 3H), 0.81 (d, J¼Hz, 3H); 13C NMR (100 MHz): d¼
213.7, 138.1, 128.9 (2C), 128.6 (2C), 125.6, 58.7 (Cq), 49.8,
43.2, 39.8, 36.3, 35.0, 31.2, 29.4, 26.0, 24.4, 22.5, 21.6, 17.0;
HR-MS: calcd. for C20H28OS [Mþ]: 316.1861; found: 316.1862.
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tert-Butyl-(dimethylsilyl) 1-Methyl-4-
[(phenylsulfanyl)methyl]spiro[4.4]non-1-yl Ether
(17d)
To a solution of 16d (140 mg, 0.5 mmol) and AIBN (41 mg,
0.25 mmol) in t-BuOH (50 mL) were added during 24 h
PhSH (55 mg, 0.5 mmol) and AIBN (123 mg, 0.75 mmol)
both via syringe pump as two solutions in benzene (2ꢀ
2 m L).t-BuOH was evaporated and the residue purified by
flash chromatography (hexane/EtOAc, 100:1) to afford 17d
as a 60:40 mixture of two diastereomers; yield: 160 mg
(82%); colorless oil; anal. calcd. for C23H38OSSi (390.70): C
70.71, H 9.80; found: C 70.76, H 9.78.
´ `
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We thank the Swiss national science foundation (Grant 20–
103627), the Roche Foundation (post-doctoral fellowship to
FD) and the University of Berne for supporting this work.
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