Silenes as novel synthetic reagents: synthesis of diols and lactones from simple alkyldienes

Article abstract of DOI:10.1016/j.tetlet.2003.10.056

Aryl substituted silenes can be generated by a modified Peterson olefination reaction and trapped in situ to afford silacycles with high diastereoselectivity. These silacycles can be elaborated by 'Fleming-Tamao' type oxidation to provide access to functionalized diols and lactones.

Full text of DOI:10.1016/j.tetlet.2003.10.056

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 9135–9138
Silenes as novel synthetic reagents: synthesis of diols and
lactones from simple alkyldienes
Malcolm B. Berry,b Russell J. Griffiths,a Mahesh J. Sanganee,b Patrick G. Steela,*
and Daniel K. Whelligana
aDepartment of Chemistry, University of Durham, Science Laboratories, South Road, Durham DH1 3LE, UK
bSynthetic Chemistry, GlaxoSmithKline, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK
Received 27 August 2003; revised 29 September 2003; accepted 7 October 2003
Abstract—Aryl substituted silenes can be generated by a modified Peterson olefination reaction and trapped in situ to afford
silacycles with high diastereoselectivity. These silacycles can be elaborated by ‘Fleming–Tamao’ type oxidation to provide access
to functionalized diols and lactones.
© 2003 Elsevier Ltd. All rights reserved.
Since the first reported demonstration of their existence
by Gusel’nikov and Flowers,1 silenes, compounds con-
taining a CꢀSi bond, have been the subject of a number
of theoretical, structural and mechanistic studies.2 This
has led to their detection as highly reactive intermedi-
ates, an understanding of their basic reactivity and
finally to the isolation and structural characterisation of
‘stable’ silenes.3 However, relatively little effort has
been expended in the application of these species in
organic synthesis. In this communication we report our
initial results describing how silenes can be exploited to
provide a strategy for the elaboration of butadienes
into polyols and lactones.
trisilane unit resisted all attempts to initiate the oxida-
tion and we therefore considered alternative silene gen-
eration strategies and precursors.
Based on the seminal studies by Fleming, we recognised
that the incorporation of an aryl silyl substituent would
provide a trigger to facilitate the oxidation. Further-
more, in a number of cases, the diastereoselectivity of
the thermal cycloaddition was only moderate and we
speculated that this could be enhanced through the use
of a low temperature modified Peterson olefination
strategy to produce silenes.7
In earlier work on the sila-Peterson reaction, Oehme
has demonstrated that a magnesium counter ion (silyl
Our premise was that the generation of a silene, in the
presence of a diene would afford the corresponding
[4+2] silacycloadduct,4 which on Fleming–Tamao oxi-
dative extrusion of the silicon centre would provide
access to a highly functionalised building block.5 In
earlier studies, we had been able to generate silacycles
through the thermal rearrangement of acylpolysilanes
and in situ trapping with a number of dienes (Scheme
1).6 In all cases the [4+2] cycloadduct was formed
selectively in high yields consistent with the known
chemistry of reversed polarity silenes. However, the
Keywords: silene; Diels–Alder cycloaddition; silacycles; Fleming–
Tamao oxidation; diols; lactones.
* Corresponding author. Fax: +44-191-384-4737; e-mail: p.g.steel@
durham.ac.uk
Scheme 1.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.10.056

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M. B. Berry et al. / Tetrahedron Letters 44 (2003) 9135–9138
Scheme 3.
BF3·2AcOH complex to afford the corresponding
fluorosilane (detectable by 19F NMR but not iso-
lated), silicon oxidation with H2O2, KF, KHCO3
yielded the desired diol 9a (85% over two steps). Fur-
ther oxidation using TPAP, NMO produced the lac-
tone 10a as a 92:8 mixture of diastereoisomers. 2D
NOESY experiments (Fig. 1) established the anti
stereochemistry of the methyl and isopropyl groups.
This was confirmed by independent synthesis of the
alternative cis lactone diastereoisomer 11 following
established literature precedents.13
Scheme 2. Reagents: (i) KOtBu, THF; (ii) MgBr2, Et2O;
(iii) PrCHO, Et2O, −78°C; (iv) BuLi, 1,3-pentadiene, Et2O,
rt then LiBr −45 to −30°C, 16 h.
i
n
Grignard reagent) is required to avoid premature gen-
eration of the silene.7 Consequently, adapting this
precedent, treatment of phenyltris(trimethylsilyl)silane8
5 with KOtBu in THF at room temperature for 2 h9
followed by transmetallation with MgBr2 produced
the required silyl Grignard reagent. This reagent was
then directly combined with isobutyraldehyde to
afford the desired silene precursor 6 as a stable
colourless oil in 50–67% yield, Scheme 2, accompa-
nied by varying amounts of the ester 8, presumably
derived via a Tishchenko type transformation.10 Sub-
sequently, treatment of a solution of alcohol 6 and
1,3-pentadiene in Et2O with BuLi at room tempera-
ture, cooling to −45°C and addition of 10 mol% of
LiBr followed by warming to −30°C and stirring at
this temperature for 16 h afforded the desired silacy-
clohexene 7a in 52% yield accompanied by small
amounts of minor diastereoisomers (dr 83:9:8).11,12
Trace amounts of products from alternative silene
reaction pathways (ene, [2+2] and dimerisation) could
be detected (GCMS) but were not isolated.
The silene geometry was established through the reac-
tion with 2,3-dimethylbutadiene. The [4+2] cycload-
duct 7b could be isolated as a single stereoisomer
although in this case there was considerably greater
competition from ene and [2+2] pathways (82:8:10 by
GC). NOESY experiments (Fig. 1) clearly established
i
a trans relationship between the Ph and Pr groups
for the major silene cycloadduct. In a similar fashion
to that described above, this adduct could be con-
verted to the corresponding lactone. However, with
this more hindered alkene, reduction required the use
of PtO2 and resulted in a significant amount of trans
addition of hydrogen, entry b Table 1.
This methodology can be extended to other alkyl sub-
stituted butadienes (Table 1), to provide a novel route
to substituted lactones. High diastereoselectivity in the
silene cycloaddition was observed in all cases
although, not surprisingly, isoprene and 3-methyl-1,3-
pentadiene demonstrated lower regioselectivity (entries
c and d). As with cycloadduct 7b, reduction of silacy-
cles containing olefinic methyl substituents required
more forcing conditions and was accompanied by sig-
nificant scrambling of stereochemistry at these posi-
tions. A further limitation of the strategy with these
more hindered silacycles is that the Fleming–Tamao
oxidation is somewhat less efficient and we are cur-
rently exploring alternative procedures to enhance this
process. Attempts to extend this result to more hin-
The high diastereoselectivity observed in silacycle for-
mation suggested that both silene generation and sub-
sequent
Diels–Alder
reaction
are
highly
stereoselective. Given that we were unable to ascer-
tain the stereochemistry of silacycle 7a by simple 2D
NMR experiments, we explored the oxidative extru-
sion of the silicon centre (Table 1). Following reduc-
tion of the alkene (H2, Pd–C), treatment with
Figure 1. Selected NOESY responses.

M. B. Berry et al. / Tetrahedron Letters 44 (2003) 9135–9138
9137
Table 1.
dered dienes (e.g. cyclohexadiene) have not been suc-
cessful with silene dimerisation becoming competitive
with the desired [4+2] cycloaddition.
lane nature of the silacycle and, following oxidation,
produces the bis homoallylic alcohol 12.
In conclusion, silenes can be employed as novel
reagents for alkene functionalisation providing stereose-
lective access to diols and lactones. Further extensions
of these studies to explore variables in both silene and
silenophile and alternative functionalisation strategies
are in progress and will be reported in due course. For
example, in a preliminary experiment (Scheme 3) simple
omission of the reduction step exploits the latent allylsi-
Acknowledgements
We thank the EPSRC (GR/N24384) and Glaxo-
SmithKline for financial support of this work (CASE
award to D.K.W.); the EPSRC Mass Spectrometry
Service for accurate mass determinations, Dr. A. M.
Kenwright for assistance with NMR experiments and
Dr. M. Jones for mass spectra.

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M. B. Berry et al. / Tetrahedron Letters 44 (2003) 9135–9138
mote efficient generation of the silene. A number of other
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