Studies in silanol synthesis: Internal nucleophiles and steric hindrance

Article abstract of DOI:10.1016/S0040-4039(01)00576-7

As a model system for the synthesis of complex silanediols, N,N-dimethyl 3-(tert-butyldiphenylsilyl)propionamide was prepared and treated with triflic acid, resulting in the removal of one phenyl group and yielding a silanol. Even with a large excess of triflic acid, only a single phenyl group could be removed. This contrasts with a diphenylsilyl group flanked by a pair of amides, for which both phenyl groups are rapidly cleaved. A combination of steric hindrance by the tert-butyl group and lack of a second internal nucleophile appears to limit triflic acid-mediated phenyl hydrolysis from the silicon.

Full text of DOI:10.1016/S0040-4039(01)00576-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 3799–3801
Studies in silanol synthesis: internal nucleophiles and
steric hindrance
Athanasios Glekas and Scott McN. Sieburth*
Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA
Received 26 March 2001; revised 29 March 2001; accepted 6 April 2001
Abstract—As a model system for the synthesis of complex silanediols, N,N-dimethyl 3-(tert-butyldiphenylsilyl)propionamide was
prepared and treated with triflic acid, resulting in the removal of one phenyl group and yielding a silanol. Even with a large excess
of triflic acid, only a single phenyl group could be removed. This contrasts with a diphenylsilyl group flanked by a pair of amides,
for which both phenyl groups are rapidly cleaved. A combination of steric hindrance by the tert-butyl group and lack of a second
internal nucleophile appears to limit triflic acid-mediated phenyl hydrolysis from the silicon. © 2001 Published by Elsevier Science
Ltd.
Nearly 100 dialkyl and aryl silanediols have been pre-
pared and characterized.1 Some of these, such as
dimethylsilanediol 1, are notoriously unstable toward
dehydration and polymerization. Others have been
found to be quite stable and unusual properties have
been noted: diisobutylsilanediol 2 is a liquid crystal,
self-assembling through strong intermolecular hydrogen
bonding;2 diphenylsilanediol 3 has been studied for its
anti-epileptic properties.3 Recently, we have reported
the first silanediol-based protease inhibitor 4, designed
as a transition state analog of the tetrahedral intermedi-
ate of amide hydrolysis4 (Fig. 1).
diphenylsilane bearing a single amide group. The results
are consistent with cleavage of the siliconꢀcarbon bond
involving assistance of the internal amide nucleophile.
As the model substrate for this investigation, N,N-
dimethyl amide 9 was prepared from the commercially
available tert-butyldiphenylchlorosilane 5, via the
known allyl silane 6.6,7 Hydroboration of 68 and oxida-
tion with TPAP9 followed by buffered potassium
permanganate10 gave acid 8, which was coupled with
dimethylamine to yield 911 (Fig. 2).
As a reagent for cleavage of arylꢀsilicon bonds, triflic
acid has been broadly applied,12,13 in part because it
can be rendered anhydrous, and the cleavage is an
efficient method for generating silyl triflates.14 In a
number of cases, diphenylsilanes have been converted
to silyl ditriflates.15 Once formed, the highly elec-
trophilic silyl triflates will react with a wide variety of
electrophiles, including amide carbonyls.14,16,17 In the
case of 9, conversion of an arylꢀsilicon bond to a
siliconꢀtriflate bond would be expected to rapidly O-
Most silanediols have been prepared by hydrolysis of
dichlorosilanes.5 In contrast, synthesis of silanediol 4
had, as its pivotal and ultimate step, acid-catalyzed
hydrolysis of the corresponding diphenylsilane, employ-
ing the well known acidic cleavage of the arylꢀsilicon
bond. As part of this investigation, we postulated that
the amides surrounding the diphenylsilane would par-
ticipate in this hydrolysis. We describe here an investi-
gation of the triflic acid-mediated hydrolysis of a
HO
OH
HO
OH
HO
OH
HO
OH
H
N
Si
Si
Si
Ph
Si
N
CO2H
O
O
1
2
3
4
Figure 1. Representative silanediols.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Published by Elsevier Science Ltd.
PII: S0040-4039(01)00576-7

3800
A. Glekas, S. M. Sieburth / Tetrahedron Letters 42 (2001) 3799–3801
BH3
ClMg
NaOH, H2O2
Si
Si
Si
OH
Cl
(references 6,7)
(90%)
5
6
7
1. TPAP (70%)
i. PvCl, Et3N
Si
OH
Si
N
2. KMnO4 (90%)
ii. Me2NH (58%)
O
O
8
9
Figure 2. Synthesis of model substrate 9.
silylate the nearby amide. Alternatively, formation of
the siliconꢀamide bond could pre-empt a triflate inter-
mediate (Fig. 3).
100 equiv. failed to alter the outcome. Higher tempera-
tures led to decomposition. In addition to loss of one
aromatic ring, the presence of a stereogenic center in
product 12 was indicated by the diastereotopicity of the
four methylene protons. Also notable is the coalescence
of the amide methyl groups of 12, possibly indicating
an interaction of the amide carbonyl with the silanol.21
Treatment of 9 with triflic acid would be expected to
initially protonate the amide carbonyl. Cleavage of the
arylꢀsilicon bond would be initiated by ipso protona-
tion of the aromatic ring (10, Fig. 3).14 Cleavage of the
CꢀSi bond would then occur, during or following
attack of a nucleophile. With the silicon beta to an
amide, the reversibly protonated oxygen can act as an
intramolecular nucleophile, forming a five-membered
intermediate, 11. Hydrolysis of the five-membered silyl
ether ring of 11 would be facilitated by ring strain.18
The reticence of 9 to lose both aryl groups is somewhat
surprising. Ditriflates have been prepared by triflic acid
substitution of two phenyl groups to make dimethylsil-
yl,15b diphenylsilyl15e and divinylsilyl15g ditriflates. The
very hindered di-tert-butylsilyl ditriflate has been pre-
pared using triflic acid, albeit by replacement of chlo-
rine and hydrogen and not phenyl groups.22,23 Both
sterics and electronics can play a role in triflic acid-
mediated substitution of phenyl and other groups, with
electron withdrawing groups on silicon attenuating the
cleavage rate.14,24
Cleavage of the remaining phenyl group of 11 would
also require ipso protonation to give 14. Without a
second internal nucleophile, loss of the phenyl group
would require displacement of the phenyl by triflate.
This may not be possible with the tert-butyl group
shielding the silicon from this weak nucleophile.19
The tert-butyl group in 9, incorporated to ensure that
the desired silanediol product would be stable, sub-
verted the second hydrolytic step. This result indicates
that alternative synthesis strategies may be required for
the construction of complex silanediols.25
In the event, treatment of 9 with 5 equiv. of triflic acid
in methylene chloride at −78°C for 30 min led to the
isolation of a single product, silanol 12.20 Raising the
temperature to 25°C and increasing the triflic acid to
TfO
H
TfO
OH
- C6H6
TfOH
NH4OH
Si
N
Si
Si
N
9
O
N
O
O
10
11
12
?
TfOH
H
TfO
2 TfO
TfO
- C6H6
Si
Si
O
O
N
N
13
14
Figure 3. Treatment of 9 with excess triflic acid yields only silanol 12.

A. Glekas, S. M. Sieburth / Tetrahedron Letters 42 (2001) 3799–3801
3801
Acknowledgements
13. For an excellent overview of the electrophiles that are
useful for cleavage of a phenylꢀsilicon bond, see: Flem-
ing, I.; Henning, R.; Parker, D. C.; Plaut, H. E.; Sander-
son, P. E. J. J. Chem. Soc., Perkin Trans. 1 1995,
317–337.
This work was supported by grants from the National
Institutes of Health (HL62390) and the National Sci-
ence Foundation (CHE-9712772).
14. Uhlig, W. Chem. Ber. 1996, 129, 733–739.
15. A variety of diorganosilyl ditriflates have been prepared.
Dimethyl: (a) Matyjaszewski, K.; Chen, Y. L. J.
Organomet. Chem. 1988, 340, 7–12; (b) Uhlig, W. Helv.
Chim. Acta 1994, 77, 972–980; (c) Uhlig, W.; Tzschach,
A. Z. Chem. 1988, 28, 104–106; Di-tert-butyl and di-iso-
propyl: (d) Corey, E. J.; Hopkins, P. B. Tetrahedron Lett.
1982, 23, 4871–4874; Diphenyl: (e) Uhlig, W. J.
Organomet. Chem. 1991, 409, 377–383; Methylvinyl: (f)
Uhlig, W. J. Organomet. Chem. 1993, 452, 29–32;
Divinyl: (g) Goetze, B.; Herrschaft, B.; Auner, N. Chem.
Eur. J. 1997, 3, 948–957; Silacyclobutane: (h) Denmark,
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16. Noyori, R.; Murata, S.; Suzuki, M. Tetrahedron 1981, 37,
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