An unusual and diastereoselective rearrangement during an intramolecular ene reaction involving a disilane

Article abstract of DOI:10.1002/ejoc.201300849

A chiral 1-isopropenyl-1-(3-oxopropyl)disilane derivative undergoes a type II ene reaction under Lewis acid catalyzed conditions to afford the silacyclic compound and an unexpected rearranged product with high diastereoselectivities. This rearrangement oc

Full text of DOI:10.1002/ejoc.201300849

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201300849
An Unusual and Diastereoselective Rearrangement during an Intramolecular
Ene Reaction Involving a Disilane
Audrey Giros,[a] Régis Guillot,[b] Luis Blanco,[a] and Sandrine Deloisy*[a]
Keywords: Silicon / Ene reaction / Cyclization / Rearrangement / Diastereoselectivity
A chiral 1-isopropenyl-1-(3-oxopropyl)disilane derivative un-
dergoes a type II ene reaction under Lewis acid catalyzed
conditions to afford the silacyclic compound and an unexpec-
ted rearranged product with high diastereoselectivities. This
rearrangement occurs through 1,2-migration of a trimethyl-
silyl group. A common intermediate was proposed to explain
the formation of both products.
junction, starting from 2-methylidene-1-silacyclohexanes
bearing a 3-oxopropyl chain on the silicon atom.[3] The high
stereoselectivity observed in this Lewis acid (LA) catalyzed
ene cyclization should result from the required cis geometry
between the transferred allylic proton and the oxopropyl
chain, which thus gives rise to a hydroxy group in a trans
relationship with the substituent on the silicon atom
(Scheme 2).
Introduction
In the course of our work on the synthesis of organo-
silicon cyclic compounds, we focused our attention on the
preparation of a 1-trimethylsilyl-2-methylidene-1-silacy-
clohexanol derivative by intramolecular ene reaction from
a 1-isopropenyl-1-(3-oxopropyl)disilane (Scheme 1; R1
=
SiMe3, R2 = Me, R3 = R4 = H). The expected cyclic com-
pound was envisioned as a starting material to build more
elaborate scaffolds after cleavage of the silicon–silicon
bond.[1] Such a carbonyl ene reaction was reported by
Robertson et al. for isopropenyl(3-oxopropyl)silanes. Gen-
erally, the methylaluminum dichloride-catalyzed cyclization
occurs with high diastereoselectivity if at least one
stereogenic center is present on the 3-oxopropyl chain
(Scheme 1; R1 = R2 = Me, iPr; R3 = H, Me, Ph; R4 = H,
Me, iPr, Bn).[2]
Scheme 2. Synthesis of silabicyclo[4.4.0]decenes by ene reaction.
We herein report a highly diastereoselective rearrange-
ment concomitant with the expected ene reaction. A mecha-
nism was proposed to rationalize these transformations,
which involve a disilane with a stereogenic silicon atom.
Results and Discussion
We first investigated the preparation of isopropenyl(3-
oxopropyl)disilane 9, precursor of the ene reaction, from
dichlorodisilane 3. Treatment of chloro(methyl)diphenyl-
silane (1) with lithium in THF at room temperature (under
ultrasonic agitation until precipitation of LiCl, then under
magnetic stirring) followed by addition of chlorotrimethyl-
silane delivered 1,1,1,2-tetramethyl-2,2-diphenyldisilane (2)
in high yield after distillation (Scheme 3).
Scheme 1. Retrosynthesis for the preparation of 2-methylidene-1-
silacyclohexanols.
In this field, we have reported the stereoselective synthe-
sis of bicyclic compounds with a silicon atom at the ring
[a] Laboratoire de Synthèse Organique et Méthodologie,
I.C.M.M.O. (UMR 8182-CNRS),
Bât. 420, Université Paris-Sud 11,
91405 Orsay cedex, France
E-mail: sandrine.deloisy@u-psud.fr
Homepage: http://www.icmmo.u-psud.fr/Labos/LSOM/cv/
sd.php
[b] Service de Cristallographie, I.C.M.M.O. (UMR 8182-CNRS),
Bât. 420, Université Paris-Sud 11,
91405 Orsay cedex, France
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300849.
Scheme 3. Preparation of dichlorodisilane 3.
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A. Giros, R. Guillot, L. Blanco, S. Deloisy
SHORT COMMUNICATION
Scheme 4. Preparation of aldehyde 9 from dichlorodisilane 3.
In our hands, all attempts of chlorodephenylation of 2
by using the standard methods (AlCl3 and HCl gas from
a gas cylinder or preformed from NaCl/H2SO4) failed.[4–6]
Preparation of 3 was successfully achieved in an almost
quantitative yield by treatment of 2 under Friedel–Crafts
conditions by employing acetyl chloride and aluminum
chloride in refluxing hexane (Scheme 3).[7] One-pot substi-
tution of the chlorine atoms of 3 by successive additions of
ethereal solutions of isopropenylmagnesium bromide
(1 equiv.) and allylmagnesium bromide (1 equiv.) gave
mainly a 75:25 mixture of allyl(isopropenyl)disilane 4 and
di(isopropenyl)disilane 5. A small amount of diallyldisilane
6 was also detected. Treatment at room temperature of this
unpurified mixture with 9-borabicyclo[3.3.1]nonane (9-
BBN) followed by oxidation at 50 °C with hydrogen perox-
ide under basic conditions led to (3-hydroxypropyl)disilane
7, which was isolated by chromatography in 38% yield over
this four-step sequence (Scheme 4). Moreover, purification
allowed 5 and a small amount of bis(hydroxypropyl)disilane
8 to be obtained. Finally, subsequent oxidation of alcohol
7 under Swern conditions delivered expected aldehyde 9 in
90% yield.
Silicon-tethered ene cyclization of 9 was achieved with
methylaluminum dichloride. Treatment with this Lewis acid
(1.2 equiv.) followed by aqueous work-up (NaHCO3 solu-
tion) resulted in the formation of a 50:50 mixture of desired
silacyclohexanol 10 and unexpected rearranged product 11.
Compounds 10 and 11 were isolated after silica gel column
chromatography in 13 and 30% yield, respectively. Notably,
only one diastereomer for each product was formed exclu-
sively or with high selectivity. The difference between the
yields of 10 and 11 is probably due to the instability of 10
on silica gel. Under similar reaction conditions but allowing
the crude reaction mixture to stand at –18 °C for 16 h, crys-
tals of 11 were isolated in 45% yield (Scheme 5).
Scheme 5. Treatment of aldehyde 9 with MeAlCl2.
with methylaluminum dichloride (1.2 equiv.) under the
same conditions as those described above. However, the 1H
NMR spectrum of the crude reaction product did not re-
veal any signals that could be attributed to 11 if Et3N was
added to the reaction mixture at –78 °C before the addition
of water at room temperature. Under these conditions, the
main reaction product was 10. Nevertheless, various signals
resulting from unidentified products were also present.
Bulb-to-bulb distillation under low pressure (Kugelrohr dis-
tillation) allowed the isolation of 10 in 22% yield. Forma-
tion of 10 and/or 11 was not noticed in a Ti(OiPr)4-cata-
lyzed reaction.
Treatment of the crude reaction product, resulting from
reaction of 9 with MeAlCl2 followed by addition of Et3N
before the aqueous work-up, with methoxymethyl chloride
(MOMCl) in the presence of diisopropylethylamine
(DIPEA) furnished methoxymethyl ether 12. After silica gel
column chromatography, 12 was thus isolated in 36% yield
over this two-step sequence (Scheme 6).
Regardless of the reaction conditions (increasing the re-
action time from 20 min to 6 h, increasing the concentration
of 9 from 0.013 to 0.13 m, or increasing the amount of
Lewis acid from 1.2 to 2.2 equiv.), total conversion of 9 was
observed and the 10/11 ratio remained roughly unchanged
Scheme 6. Preparation of methoxymethyl ether 12.
1
(the ratio was determined by H NMR spectroscopy and
was always between 41:59 and 54:46).
No significant change in the 10/11 ratio was observed if
Structure elucidation of 11 was achieved by single-crystal
the work-up was realized with 1 m HCl after reaction of 9 X-ray diffraction analysis (Figure 1).[8] This analysis sup-
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Rearrangement in an Ene Reaction Involving a Disilane
ports unambiguously that the trimethylsilyl group and the
By using the Merck Molecular Force Field (MMFF),[9]
OH group linked to the silicon atom are in a trans position calculations determined the minimized molecular-modeling
relative to the OH group carried by the carbon atom.
geometries and the relative energies of cis- and trans-10 in
the two possible chair conformations (all attempts by start-
ing with a boat geometry converged to the chair geometry).
Greater stability was found for the trans isomer with the
trimethylsilyl and hydroxy groups in axial positions (Fig-
ure 3).
Figure 1. ORTEP structure of silacyclohexanediol 11.[8] Ellipsoids
are drawn at the 30% probability level.
1
The H NMR spectrum (CDCl3) of 11 shows a doublet
of doublets of doublets of doublets at δ = 3.82 ppm, which
can be attributed to the proton linked to the C-4 carbon
atom bearing the hydroxy group. The coupling constants
(two of ca. 11 Hz and two of ca. 4 Hz) are in agreement
with an axial position of this proton. Thus, the trimethyl-
Figure 3. Calculated[9] geometries and energies of cis- and trans-
silacyclohexanol 10 in the chair conformation.
The orientation of the OH bond in the direction of the
silyl group should be also in the axial position in solution. C=C bond is suggestive of an intramolecular H-bonding in
1
In comparison with the spectrum of 11, the H NMR the most stable conformer of the trans isomer of 10. The
spectrum of 10 shows a signal at δ = 3.90 ppm with a sim- 3607 cm–1 absorption band in the IR spectrum of a dilute
ilar coupling pattern but with two coupling constants of ca. solution of 10 is not in disagreement with a weak H-bond-
6 Hz and two others of ca. 3 Hz, which suggest an equato- ing. The axial positions of the trimethylsilyl and methoxy-
rial position of the proton carried by the C-4 carbon atom. methyloxy groups seem to be maintained in 12. To avoid
A signal at δ = 3.71 ppm with the same shape (two coupling the probably less accurate parameters of the silicon atom,
constants of ca. 7 Hz and two coupling constants of ca. further calculations in the MMFF field made with the
3 Hz) is present in the spectrum of 12, which thus indicates chair-conformed methylidenecyclohexane derivatives show
that its conformation should be similar to that of 10. NOE the same orientation of the OH bond with respect to the
experiments performed on 12 showed that the protons of C=C bond. An equatorial position of the trimethylsilyl
the trimethylsilyl group were in proximity to the two pro- group introduces strong allylic1,3-strain. The axial position
tons linked to the C-3 and C-5 carbon atoms of the silacy- of this bulky group, which decreases the interaction with
clohexane ring. These effects suggest the axial position of the exocyclic C=C bond, should be the main reason why
the trimethylsilyl group (Figure 2). Moreover, an NOE ef- trans-10 and 12 remain in this conformation.
fect between an ethylenic proton and the protons of the
The mechanism of the ene reaction is frequently reported
methyl group linked to the cyclic silicon atom is in agree- as the asynchronous formation of a C–C bond followed by
ment with an equatorial position of this methyl substituent. migration of the hydrogen atom.[10] In the case of 9, with
the hypothesis of a chair-like transition state, the formation
of the C–C bond should give a carbenium ion or a partially
positively charged carbon atom in the α position of the ring
silicon atom (and in the β position relative to the SiMe3
group).[11] With the hypothesis of a concerted mechanism,
C–C bond formation is only possible if the carbonyl group
and the methyl substituent of the isopropenyl group are in
Figure 2. NOE effects observed in the spectrum of ether 12.
axial positions. A strong stabilizing interaction of the posi-
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A. Giros, R. Guillot, L. Blanco, S. Deloisy
SHORT COMMUNICATION
Scheme 7. Possible mechanisms for the reaction of aldehyde 9.
tive charge with the Si–Si bond should occur if the trimethyl- center allowed a 1-silacyclohexan-4-ol to be obtained as a
silyl group is in an axial position.[12] Therefore, the reac- single diastereomer. Unexpected 1,2-migration of the tri-
tion with a conformer in which the SiMe3 group is in an methylsilyl group yielded a 1-silacyclohexane-1,4-diol with
equatorial position seems less likely (Scheme 7). From inter- three stereogenic centers. These noteworthy highly dia-
mediate A with such an axial trimethylsilyl group, transfer stereoselective reactions highlight the few examples re-
of the hydrogen atom according to the classical ene reaction ported in the literature in which the configuration of a
mechanism should deliver 10 with the OH group in a trans silicon atom induces efficient control of the creation of
relationship to the trimethylsilyl group (Scheme 7, route a). stereogenic centers.[19] We postulate the formation of both
Also from A, 1,2-migration of the trimethylsilyl group could products via a unique intermediate, which could evolve by
give a silylium ion, which could react with a chloride ion the usual ene reaction mechanism or by migration of the
to yield a chlorosilane (Scheme 7, route b). Whatever the silyl group.
mechanism of this shift, with[13] or without[14] formation of
Supporting Information (see footnote on the first page of this arti-
an intermediate silyl-bridged cation, it should be suprafa-
cial. A similar 1,2-migration of a trimethylsilyl group oc-
curred when 3-[tris(trimethylsilyl)silyl]prop-2-en-1-ol deriv-
atives were treated with BF3, HCl, or H2SO4.[15] In these
examples, formation of a silylium ion by migration of the
silyl group on the carbenium center after the first ionization
step was postulated. Ab initio calculations showed a greater
stabilization (ca. 40 kJmol–1) of the silylium ion compared
to the carbenium ion.[16] We cannot exclude a stereoselec-
tive addition of the chloride anion to the intermediate sil-
ylium ion, but formation of two diastereomeric chlorosi-
lanes seems more likely, and the presence of two dia-
stereomeric silacyclohexanediols could be expected after hy-
drolysis (Scheme 7, route b). Simultaneous addition of the
chloride anion on the ring silicon atom and migration of
the trimethylsilyl group to the positively charged carbon
cle): Full experimental details including procedures and characteri-
zation data for all compounds, crystallographic data, and copies of
the NMR spectra.
Acknowledgments
This work was financially supported by the Centre National de la
Recherche Scientifique (CNRS), by the University of Paris-Sud 11,
and by a grant from the French Ministry of Education and Re-
search awarded to A. G.
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Eur. J. Org. Chem. 2013, 5809–5813

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Received: June 10, 2013
Published Online: August 12, 2013
Eur. J. Org. Chem. 2013, 5809–5813
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