Unusual tandem alkynylation and trans-hydrosilylation to form oxasilacyclopentenes

Article abstract of DOI:10.1021/ol051996r

(Chemical Equation Presented) An unusual tandem reaction sequence to form oxasilacyclopentenes from carbonyls and alkynylsilanes in the presence of a catalytic amount of nucleophilic initiator has been discovered. The reaction proceeds readily at room tem

Full text of DOI:10.1021/ol051996r

ORGANIC
LETTERS
2005
Vol. 7, No. 22
4995-4998
Unusual Tandem Alkynylation and
trans-Hydrosilylation To Form
Oxasilacyclopentenes
Sarah V. Maifeld and Daesung Lee*
Department of Chemistry, UniVersity of Wisconsin, Madison, Wisconsin 53706
dlee@chem.wisc.edu
Received August 17, 2005
ABSTRACT
An unusual tandem reaction sequence to form oxasilacyclopentenes from carbonyls and alkynylsilanes in the presence of a catalytic amount
of nucleophilic initiator has been discovered. The reaction proceeds readily at room temperature and is applicable to a wide variety of carbonyl
substrates. While the reaction scope tolerates variable substitutions on the alkynylsilane, phenylacetylene-derived silane variants consistently
achieved the best yield.
Organosilanes, such as silyl ethers and vinylsilanes, play an
important and diverse role in organic chemistry.1 The silyl
ether functionality is widely employed as a protecting group2
and also serves as a temporary tether to adapt intermolecular
reactions to more favorable intramolecular processes.3 Ad-
ditionally, vinylsilanes can be employed for a variety of
purposes4 including palladium-catalyzed cross-coupling reac-
tions.5 For these reasons, we have been interested in
developing a new and efficient methodology to synthesize
these versatile building blocks based on catalytic activation
of silane starting materials.6
An extensive variety of metal complexes have been
reported to activate hydridosilanes during the dehydrogena-
tive condensation with alcohols6b,c,7 and the hydrosilylation
of carbonyls6c,8 and alkynes.6a,9 Additionally, the Lewis base
activation of silanes to form pentacoordinate hydrosilicates
is a well-established method to activate the silicon-hydrogen
bond toward the reduction of carbonyls with concomitant
silylation of the resultant alkoxide yielding the corresponding
(5) For reviews on the cross-coupling reactions of organosilicon com-
pounds, see: (a) Denmark, S. E.; Sweis, R. F. In Metal-Catalyzed Cross-
Coupling Reactions, 2nd ed.; de Meijere, A., Diederich, F., Eds.; Wiley-
VCH: Weinheim, Germany, 2004; Vol. 1, pp 163-216. (b) Denmark, S.
E.; Sweis, R. F. Acc. Chem. Res. 2002, 35, 835-846. (c) Horn, K. A. Chem.
ReV. 1995, 95, 1317-1350. (d) Hatanaka, Y.; Hiyama, T. Synlett 1991,
845-853.
(6) (a) Maifeld, S. V.; Tran, M. N.; Lee, D. Tetrahedron Lett. 2005, 46,
105-108. (b) Miller, R. L.; Maifeld, S. V.; Lee, D. Org. Lett. 2004, 6,
2773-2776. (c) Maifeld, S. V.; Miller, R. L.; Lee, D. Tetrahedron Lett.
2002, 43, 6363-6366.
(7) (a) Zhang, C.; Laine, R. M. J. Am. Chem. Soc. 2000, 122, 6979-
6988. (b) Blackwell, J. M.; Foster, K. L.; Beck, V. H.; Piers, W. E. J. Org.
Chem. 1999, 64, 4887-4892 and references therein. (c) Ojima, I.; Kogure,
T.; Nihonyangi, M.; Kono, H.; Inaba, S. Chem. Lett. 1973, 501-504.
(8) (a) Chrisman, W.; Noson, K.; Lipschutz, B. H. J. Organomet. Chem.
2001, 624, 367-371. (b) Bushell, S. M.; Lawrence, N. J. Tetrahedron Lett.
2000, 41, 4507-4512. (c) Lee, S.; Kim, T. Y.; Park, M. K.; Han, B. H.
Bull. Korean Chem. Soc. 1996, 17, 1082-1085. (d) Wang, D.; Chan, T. H.
Tetrahedron Lett. 1993, 34, 3095-3098. (e) Cornish, A. J.; Lappert, M.
F.; Filatovs, G. L.; Nile, T. A. J. Organomet. Chem. 1979, 172, 153-163.
(9) See ref 1a, Vol. 2, pp 1687-1792.
(1) (a) Ojima, I.; Zhu, J. In The Chemistry of Organosilicon Compounds;
Rappoport, S., Apeloig, Y., Eds.; Wiley: New York, 1998. (b) Langkopf,
E.; Schinzer, D. Chem. ReV. 1995, 95, 1375-1408. (c) Hiyama, T.;
Kusumoto, T. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming,
I., Eds.; Pergamon: Oxford, 1991; Vol. 8, pp 763-792.
(2) (a) Green, W. T.; Wuts, P. G. M. In Protecting Groups in Organic
Synthesis, 3rd ed.; John Wiley & Sons: New York, 1999. (b) Kocienski,
P. J. In ProtectiVe Groups; Enders, D., Noyori, R., Trost, B. M., Eds.;
Thieme: Stuttgart, Germany, 1994. (c) Muzart, J. Synthesis 1993, 11-27.
(3) (a) Gauthier, D. R., Jr.; Zandi, K. S.; Shea, K. J. Tetrahedron 1998,
54, 2289-2338. (b) Fensterbank, L.; Malacria, M.; Sieburth, S. McN.
Synthesis 1997, 813-852. (c) Bols, M.; Skydstrup, T. Chem. ReV. 1995,
95, 1253-1277.
(4) For oxidation of the carbon-silicon bond, see: (a) Jones, G. R.
Tetrahedron 1996, 52, 7599-7662 and references therein. For halogenation,
see: (b) Miller, R. B.; Reichenbach, T. Tetrahedron Lett. 1974, 15, 543-
546.
10.1021/ol051996r CCC: $30.25
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Published on Web 10/06/2005

silyl ether.10,11 Efforts in this area have mainly included
electron deficient silanes such as trimethoxy- and triethoxy-
silane for the synthesis of silyl ethers, and the use of
relatively simple alkyl- and arylsilanes is limited.
As an extension of our efforts to develop efficient routes
to silyl ethers possessing alkynyl substituents in the products,
we examined the reactivity of dialkyl- and diarylalkynylsi-
lanes. We envisioned that the employment of an alkynyl
hydridosilane of type 1 could result in either of the two silyl
ethers, 2 or 3, depending on the migratory aptitude of the
more basic hydride versus the less basic acetylide (Scheme
1).
arising from alkynylation of the ketone followed by an
intramolecular endo mode, trans-hydrosilylation of the triple
bond by the intermediate hydridosilyl ether.13
In contrast to well-established examples of cis-hydrosi-
lylation, trans-hydrosilylation is less documented,14 and only
a single example of a non-transition metal-mediated trans-
hydrosilylation has been reported.15 Herein, we report our
investigation of an unusual tandem reaction sequence to
generate oxasilacyclopentenes from carbonyls and alkynyl-
silanes through a formal intramolecular trans-hydrosilylation.
Scheme 1. Nucleophilic Activation of Hydrido Alkynylsilanes
Employing cyclohexanone and silane 4a as our representa-
tive carbonyl and silane compounds, we screened a variety
of metal alkoxide and fluoride sources for efficacy of
promoting both the alkynylation of the carbonyl as well as
the subsequent hydrosilylation of the alkyne (Table 1).
Although previous reports have shown that the Lewis base
activation of an alkynylsilane promotes the alkynylation of
carbonyls and imines as well as alkyl halides,12 the relative
migratory aptitude between a hydride and an acetylide anion
has not been examined. A simple basicity measure of these
two migrating species indicates that the acetylide should
migrate preferentially to give 3; however, the second pathway
involving hydride migration cannot be excluded because
additional parameters, such as sterics and stereoelectronics,
may affect the outcome. For example, transition metal
catalysts normally activate the stronger (76 kcal/mol), yet
less hindered Si-H bond over the weaker (72 kcal/mol),
more hindered Si-C bond to provide 2 exclusively.6b
With these considerations in mind, we initiated our studies
with commerically available dimethyl(phenylethynyl)silane
4a and acetophenone in the presence of a catalytic amount
of potassium tert-butoxide (eq 1). Although no products
resulting from hydride migration to the carbonyl were
observed, we isolated two products resulting from alkynyl
transfer from the silane to the substrate. While the minor
product corresponded to hydridosilyl ether 5, the major
product was identified as oxasilacyclopentene 6, seemingly
Table 1. Screen of Nucleophilic Initiatorsa
a 1 equiv of cyclohexanone, 1.2 equiv of silane, THF, room temperature.
b Isolated yield.
Among the nucleophiles tried, only potassium tert-butoxide
gave complete conversion of the ketone resulting in the
highest yield of oxasilacyclopentene 7a (86%) and the
smallest amount of tertiary propargylic alcohol 8 (10%),
presumably derived from hydrolysis of the labile hydridosilyl
ether during silica gel chromatography. Less coordinating
cations promoted greater alkynylation of the carbonyl, and
bulkier alkoxides increased oxasilacyclopentene formation.
(10) For additional reviews, see: (a) Brook, M. A. In Silicon in Organic,
Organometallic, and Polymer Chemistry; Wiley-Interscience: New York,
1999. For reviews of pentacoordinate silicates, see: (b) Holmes, R. R. Chem.
ReV. 1996, 96, 927-950. (c) Chuit, C.; Corriu, R. J. P.; Reye, C.; Young,
J. C. Chem. ReV. 1993, 93, 1371-1448.
(11) (a) Nishikori, H.; Yoshihara, R.; Hosomi, A. Synlett 2003, 561-
563. (b) LaRonde, F. J.; Brook, M. A. Tetrahedron Lett. 1999, 40, 3507-
3510. (c) Iwasaki, F.; Onomura, O.; Mishima, K.; Maki, T.; Matsumura,
Y. Tetrahedron Lett. 1999, 40, 2065-2068. (d) Schiffers, R.; Kagan, B.
H. Synthesis 1997, 1175-1178 and references therein. (e) Corriu, R. J. P.;
Guerin, C.; Henner, B.; Wang, Q. Organometallics 1991, 10, 2297-2303
and references therein.
(12) (a) Lettan, R. B., II; Scheidt, K. A. Org. Lett. 2005, 7, 3227-3230.
(b) Kraus, G. A.; Bae, J. Tetrahedron Lett. 2003, 44, 5505-5506. (c)
Baldewin, J. E.; Pritchard, G. J.; Rathmell, R. E. J. Chem. Soc., Perkin
Trans. 1 2001, 2906-2908. (d) Busch-Petersen, J.; Bo, Y.; Corey, E. J.
Tetrahedron Lett. 1999, 40, 2065-2068. (e) Pilcher, A. S.; DeShong, P. J.
Org. Chem. 1996, 61, 6901-6905. (f) Kuwajima, I.; Nakamura, E.;
Hashimoto, K. Tetrahedron 1983, 39, 975-982.
(13) Trost, B. M.; Ball, Z. T.; Laemmerhold, K. M. J. Am. Chem. Soc.
2005, 127, 10028-10038 and references therein.
(14) For intramolecular trans-hydrosilylation, see: (a) Denmark, S. E.;
Pan, W. Org. Lett. 2002, 4, 4163-4166. For intermolecular trans-
hydrosilylation, see: (b) Trost, B. M.; Ball, Z. T. J. Am. Chem. Soc. 2001,
123, 12726-12727. (c) Na, Y.; Chang, S. Org. Lett. 2000, 2, 1887-1889.
(d) Mori, A.; Takahisa, E.; Kajiro, H.; Hirabayashi, K.; Nishihara, Y.;
Hiyama, T. Chem. Lett. 1998, 443-444.
(15) (a) Sudo, T.; Asao, N.; Yamamoto, Y. J. Org. Chem. 2000, 65,
8919-8923. For an additional example of a trans-hydrometalation with
aluminum, see: (b) Eckrich, T. M.; Corey, E. J. Tetrahedron Lett. 1984,
25, 2415-2418.
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Org. Lett., Vol. 7, No. 22, 2005

The steric and stereoelectronic influences exerted by the
groups at the silicon atom were also investigated (Table 2).
Table 3. Synthesis of Oxasilacyclopentenesa
Table 2. Effect of Substituents at Silicona
a 1 equiv of cyclohexanone, 1.2 equiv of silane, THF, room temperature.
b Isolated yield. c At 0 °C, the yields of 7 and 8 were 29% and 42%,
respectively.
Replacing methyl groups (4a) with phenyl groups (4b)
resulted in a good yield of the oxasilacyclopentene 7b (67%)
with a small amount of the alkynyl silyl ether 10b (10%)
resulting from hydride transfer to the carbonyl carbon.
Although alkynylation proceeded readily in the presence of
isopropyl substituents (4c), only a trace amount of oxasila-
cyclopentene 7c was observed, and tertiary propargyl alcohol
8c and hydridosilyl ether 9c were isolated in 22% and 61%
yield, respectively.
Using our optimized conditions employing 4a and 10 mol
% potasssium tert-butoxide, we examined the scope of the
reaction toward a wide variety of ketones and aldehydes
(Table 3). All reactions were extremely facile giving
complete conversion within 20 min at room temperature.
Aromatic as well as R,â-unsaturated aldehydes yielded
oxasilacyclopentenes 11a-c in moderate to high yields
(entries 1-3). A variety of cyclic, acyclic, aromatic, and
aliphatic ketones proved to be good substrates as well,
providing the expected oxasilacyclopentenes 11d-f in good
yields (entries 4-8).
a 1 equiv of carbonyl, 1.2 equiv of silane, THF, room temperature.
b Isolated yield.
tion of the corresponding oxasilacyclopentene 13b was noted,
likely due to steric hindrance around the triple bond presented
by the o-methyl group on the arylsilane. In contrast, arylsi-
lanes bearing p-methyl (12c), p-fluoro (12d), and p-trifluoro-
methyl substituents (12e) resulted in the formation of oxasila-
cyclopentenes 13c-e in good to high yields (entries 3-5).
Table 4. Effect of Substituent on Phenylacetylenea
We next investigated the effect of the group occupying
the alkyne terminus. Additional alknylsilanes bearing various
groups including furyl, pyridyl, trimethylsilyl, alkyl, sulfonyl,
and cyclohexenyl were prepared and tested.16 Upon subjec-
tion to the reaction conditions, none of these alkynylsilanes
were as efficient participants in the tandem alkynylation-
hydrosilylation sequence as 4a, which possesses a terminal
phenyl substituent.
We also examined the electronic and steric effects exerted
by the substituents on the aryl ring (Table 4). The presence
of a strongly electron donating substituent in 12a proved
detrimental to the alkynylation of the carbonyl, presumably
by retarding the silicon-carbon bond cleavage (entry 1).
Although alkynylation proceeded well with 12b, no forma-
a 1 equiv of cyclohexanone, 1.2 equiv of silane, THF, room temperature.
b Isolated yield.
(16) See the Supporting Information for reaction details.
Org. Lett., Vol. 7, No. 22, 2005
4997

Although the mechanistic picture of oxasilacyclopentene
formation is unclear, we propose a plausible scenario shown
in Scheme 2. Following the formation of pentacoordinate
Oxasilacyclopentenes are versatile synthetic intermediates
and undergo a variety of transfomations (Scheme 4).19 Tamao
Scheme 4. Synthetic Elaboration of Oxasilacylcopentene 7a
Scheme 2. Mechanistic Proposal for the Tandem
Alkynylation-Hydrosilylation Sequence
silicate intermediate by the addition of tert-butoxide to silane
4a and transfer of the alkyne to the carbonyl to form activated
hydridosilyl ether 15, subsequent hydride transfer from the
silicon to the nearby alkyne would provide oxasilacyclopen-
tene 16.
To validate the intermediacy of a hydridosilyl ether of type
3 (and also 5 and 15) leading to oxasilacyclopentene
formation, the corresponding silyl ether was synthesized from
tertiary propargyl alcohol 8 and tetramethyldisilazane.17
Treatment of the preformed hydridosilyl ether with 20 mol
% of potassium tert-butoxide resulted in clean formation of
the expected oxasilacyclopentene 7a in 76% yield (eq 2).
oxidation of 7a yielded the â-hydroxy ketone 19 efficiently
(77%).20 This transformation is notable as 19 formally results
from an aldol reaction, which is known to encounter
difficulties with ketone electrophiles.21 Expoxidation of 7a
with dimethyldioxirane gave epoxide 20 in 70% yield based
on recovered starting material. In particular, the trisubstituted
vinylsilane moiety in 7a is noteworthy since it is not easily
accessed by conventional hydrosilylation of internal triple
bonds due to issues of regioselectivity.13b By using the
chemistry developed by Takeda and co-workers,22 oxasila-
cyclopentene 7a could also be transformed into 1,4-diene
21 in high yield.
In summary, the chemistry described above represents a
novel tandem and mild base-promoted alkynylation of
carbonyl substrates followed by in situ trans-hydrosilylation
of the alkynyl moiety to generate oxasilacyclopentenes. This
protocol avoids the use of highly basic metal alkynyl species
while achieving two consecutive transformations by a
substoichiometric amount of alkoxide initiator.
To ascertain whether the alkynyl transfer occurs via an
organized transition state, a crossover experiment was carried
out between cyclohexanone and two similar alkynylsilanes,
4a and 17 (Scheme 3). The observation of all four possible
Acknowledgment. D.L. greatly acknowledges generous
support of this research from the NIH (RO1 CA106673-01).
We thank Professor Hans Reich for insights and helpful
discussions. Support from the NSF and NIH for NMR and
mass spectrometry instrumentation is also greatly appreciated.
Scheme 3. Crossover Experiment
Supporting Information Available: General procedures
and characterization for the represented compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL051996R
(18) For examples of intramolecular transfer of alkyl and aryl groups
from â-silyl enones to the adjacent enone carbon, see: (a) Trost, B. M.;
Ball, Z. T. J. Am. Chem. Soc. 2004, 126, 13942-13944. (b) Jung, M. E.;
Piizzi, G. J. Org. Chem. 2002, 67, 3911-3914. (c) Aronica, L. A.; Morini,
F.; Caporusso, A. M.; Salvadori, P. Tetrahedron Lett. 2002, 43, 5813-
5815. (d) Fleming, I.; Newton, T. W.; Sabin, V.; Zammattio, F. Tetrahedron
Lett. 1992, 48, 7793-7802.
oxasilacyclopentenes (7a, 7b, 12c, and 18) by 1H NMR and
mass spectroscopy indicates that the reaction proceeds via a
naked alkynyl anion rather than a tightly organized, chelated
delivery of the alkynyl group from the pentacoordinate
silicate.18
(19) (a) Calad, S. A.; Woerpel, K. A. J. Am. Chem. Soc. 2005, 127,
2046-2047. (b) Clark, T. B.; Woerpel, K. A. J. Am. Chem. Soc. 2004,
126, 9522-9523.
(20) Tamao, K.; Kumada, M. Tetrahedron Lett. 1984, 25, 321-324.
(21) Trost, B. M.; Ball, Z. T. J. Am. Chem. Soc. 2004, 126, 13942-
13943 and references therein.
(17) Tamao, K.; Maeda, K.; Tanaka, T.; Ito, Y. Tetrahedron Lett. 1988,
29, 6955-6956.
(22) Taguchi, H.; Ghoroku, K.; Tadaki, M.; Tsubouchi, A.; Takeda, T.
J. Org. Chem. 2002, 67, 8450-8456.
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