The search for tolerant Lewis acid catalysts. Part 1: Chiral silicon Lewis acids derived from (-)-myrtenal

Article abstract of DOI:10.1016/S0040-4039(00)01694-4

We have shown that association of a bulky silicon group with the bis(trifluoromethanesulfonyl)imide leaving group unexpectedly enhances the electrophilic character of the R₃SiNTf₂ silylating agent. The presence of a chiral substituent derived from (-)-myrtenal on the silicon atom led to a Lewis acid, which efficiently catalyzes the Diels-Alder reaction of α,β-unsaturated esters. Although not yet preparatively useful, the enantiomeric excesses (up to 54%) were the highest ever reported for a chiral silicon Lewis acid. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01694-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9561–9564
The search for tolerant Lewis acid catalysts.
Part 1: Chiral silicon Lewis acids derived from (−)-myrtenal†
Benoit Mathieu,a Laurence de Faysb and Le´on Ghoseza,b,
*
aLaboratoire de Chimie Organique de Synthe`se, Universite´ catholique de Louvain, Place Louis Pasteur 1,
B-1348 Louvain-la-Neuve, Belgium
bInstitut Europe´en de Chimie et Biologie, c/o ENSCPB, Avenue Pey Berland, BP-108,
F-33402 Talence cedex, France
Received 10 August 2000; accepted 26 September 2000
Abstract
We have shown that association of a bulky silicon group with the bis(trifluoromethanesulfonyl)imide
leaving group unexpectedly enhances the electrophilic character of the R3SiNTf2 silylating agent. The
presence of a chiral substituent derived from (−)-myrtenal on the silicon atom led to a Lewis acid, which
efficiently catalyzes the Diels–Alder reaction of a,b-unsaturated esters. Although not yet preparatively
useful, the enantiomeric excesses (up to 54%) were the highest ever reported for a chiral silicon Lewis acid.
© 2000 Elsevier Science Ltd. All rights reserved.
Keywords: Lewis acid; silylation; asymmetric Diels–Alder reaction.
We recently reported that many Lewis acids, which were shown to efficiently promote
cycloadditions of simple dienes, could not be used for the catalysis of Diels–Alder reactions of
1- and 2-azadienes.1 This probably resulted from competitive bindings of the Lewis acid by the
diene and the dienophile. We recently showed that trimethylsilyl bis(trifluoromethanesul-
fonyl)imide, TMSNTf2, was an efficient and tolerant catalyst for the Diels–Alder reaction of
methyl acrylate with 2-azadienes and highly functionalized dienes as well as for representative
ene reactions.2 This initial study showed that TMSNTf2 was much more electrophilic than
TMSOTf which did not catalyze these reactions. This was confirmed and further illustrated by
Simchen and Jonas who also prepared the corresponding triisopropylsilyl bis(trifluoromethane-
sulfonyl)imide, TIPSNTf2.3
* Corresponding author. Fax: 32-10-474168 or 33-557-96 22 26; e-mail: ghosez@chor.ucl.ac.be, leon.ghosez@iecb-
polytechnique.u-bordeaux.fr
†
Dedicated to Professor Henry Wasserman, a wonderful colleague editor.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01694-4

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1
A comparative H NMR study of the complexation of methyl crotonate4 with various
R3SiNTf2 reagents unexpectedly showed that TIPSNTf2 induced a higher downfield shift of the
H3 proton signal of methyl trans-crotonate than TMSNTf2 (Scheme 1). This suggested to us that
bulkier groups on silicon favored the silylation of the carbonyl group. Confirmation of this
surprising behavior came from the comparison of the catalytic efficiencies of 1a and 1b (10
mol%) on the cycloaddition of cyclohexadiene with methyl acrylate: TIPSNTf2 was found to be
superior to TMSNTf2 (kTIPS/kTMS=4.19).
Scheme 1.
We found no convincing evidence5 for the occurrence of a SN1 type mechanism involving a
solvated ion-pair in the case of the bulky TIPSNTf2 catalyst. A more probable interpretation of
this surprising observation is that the higher I-strain in TIPSNTf2 would thermodynamically
favor the formation of the complex with the smaller carbonyl ligand. We concluded from these
studies that R3SiNTf2 reagents bearing bulky chiral groups could be effective catalysts for
asymmetric Diels–Alder reactions.6
The first example of Diels–Alder reactions catalyzed by a chiral electrophilic silylating agent
has been recently described.7 However facial selectivities were still very modest (ee510%).
We first decided to examine silylated sulfonimides 3 derived from (−)-myrtenal.8 The silyl-
cupration of (−)-myrtenal was readily effected by a known procedure to give the trans adduct 4.9
Its absolute stereochemistry was assigned by an X-ray diffraction analysis.10 Aldehyde 4 was
transformed into 5a–d by conventional chemistry involving a Wittig reaction/hydrogenation or
Scheme 2. Conditions: (A) CH3CHPPh3 then H2, Pd/C (5a, 50%); (B) LiAlH4 then NaH and MeI (5b, 83%),
PhCH2Br (5c, 90%), or DMAP/PhCOCl (5d, 85%); (C) HCl in CHCl3, then AgNTf2 in situ

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reduction/etherification, esterification sequence (Scheme 2). The direct protodesilylation of
phenylsilanes 5 by HNTf2 led to decomposition product. Treatment of 5 with HCl in CHCl3
gave the corresponding silyl chloride which was readily transformed into 3 by in situ treatment
with AgNTf2.11,2
Following our expectation, all silylating agents 3a–d were efficient catalysts for the reaction of
cyclopentadiene with methyl acrylate and methyl trans-crotonate (Scheme 3, Table 1). Absolute
configuration of the cycloadducts were assigned by comparison of their optical rotations with
literature data.12
Scheme 3.
Table 1
Cycloaddition of cyclopentadiene to methyl acrylate and methyl trans-crotonate in the presence of 3a–d
Entry
Catalyst
R
Conditions
endo:exob
Yieldc (%)
ee endob (%)
1
2
3
4
5
6
7
8
3a
3b
3b
3b
3b
3b
3c
3d
H
H
H
H
Me
Me
H
Toluene, −78°C, 1.5 h
Toluene, −45°C, 1.5 ha
Toluene, −78°C, 1.5 h
Toluene, −100°C, 1.5 ha
Toluened, −78°C, 8 ha
Toluene, −45°C, 8 ha
Toluene, −78°C, 1.5 h
Toluene, −78°C, 1.5 h
99:1
99:1
99:1
99:1
–
97:3
99:1
99:1
83
98
83
94
NR
93
79
80
7 (2S)
43 (2S)
54 (2S)
54 (2S)
–
24 (2S)
26 (2S)
13 (2S)
H
a Reactions were run in the presence of 10 mol% of 2,6-bis(t-butyl)-4-methylpyridine.
b ee and endo:exo ratio obtained on a chirasil DEX-CB GC column.
c Yield of isolated compound.
d Ether, propiononitrile and CH2Cl2 were also tested without success.
Catalyst 3a (entry 1) bearing an alkyl chain gave an adduct with low ee. The introduction of
an oxygen atom, which presumably stabilizes the electrophilic center of 3b, significantly
increased the facial selectivity (entries 2 to 6). At −78°C, the ee was 54%, the highest ee ever
reported for an asymmetric silicon Lewis acid catalyzed reaction. Lowering the temperature to
−100°C (entry 4) did not improve the ee. The cycloaddition with methyl crotonate required a
higher temperature (−45°C) and enantioselectivities were lower (entries 5 and 6). Attempts were
made to change the position or the basicity of the oxygen in the R substituent. Unfortunately,
both 3c and 3d gave lower enantioselectivities than 3b.
In summary, we have shown that the association of a bulky leaving group (NTf2) with a
silicon atom bearing large alkyl groups gives rise to efficient Lewis acid catalysts for the
Diels–Alder reaction. Also we have prepared the first chiral silicon Lewis acid which lead to
significant facial selectivities in Diels–Alder reactions. We believe that these results pave the way
for the design and development of tolerant asymmetric Lewis acids catalysts leading to high
enantioselectivities.

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Acknowledgements
Financial support has been provided by the ‘Ministe`re de l’Education et de la Recherche
Scientifique de la Communaute´ franc¸aise de Belgique (Action de recherches concerte´e 96/01-
197)’, FRIA and the University of Louvain (fellowships to B.M.) and Rhodia. We thank Dr R.
Touillaux for NMR analyses and Professor E. de Hoffmann for the mass spectra.
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