[Bis(2-pyridyldimethylsilyl)methyl]lithium. New reagent for the stereoselective synthesis of vinylsilanes

Article abstract of DOI:10.1021/ol005735n

(formula presented) The generation of (2-PyMe₂Si)₂CHLi was easily accomplished by the deprotonation of (2-PyMe₂Si)₂CH₂ using n-BuLi in Et₂O. Thus generated (2-PyMe₂Si)₂

Full text of DOI:10.1021/ol005735n

ORGANIC
LETTERS
2000
Vol. 2, No. 9
1299-1302
[Bis(2-pyridyldimethylsilyl)methyl]lithium.
New Reagent for the Stereoselective
Synthesis of Vinylsilanes
Kenichiro Itami, Toshiki Nokami, and Jun-ichi Yoshida*
Department of Synthetic Chemistry & Biological Chemistry, Kyoto UniVersity,
Yoshida, Kyoto 606-8501, Japan
yoshida@sbchem.kyoto-u.ac.jp
Received February 29, 2000
ABSTRACT
The generation of (2-PyMe2Si)2CHLi was easily accomplished by the deprotonation of (2-PyMe2Si)2CH using n-BuLi in Et2O. Thus generated
2
(2-PyMe2Si)2CHLi was found to react with a variety of aldehydes and ketones to give the corresponding vinylsilanes in extremely high yields
with complete stereoselectivities.
The generation and reactions of R-silyl carbanions are
subjects of great interest in organic synthesis.1 Despite many
useful reactions such as the Peterson olefination,2 nucleo-
philic hydroxymethylation,3 and their variants, R-silyl carb-
anion chemistry still suffers from its substrate dependence.
In most cases, the deprotonation methodology is only feasible
when the additional stabilizing effects by neighboring
heteroatom or electron-withdrawing groups can be expected.1
Recently, we have embarked on a program directed toward
the development of removable intramolecular ligands (direct-
ing groups), which control the metal-mediated and -catalyzed
processes by a complex induced proximity effect (CIPE).4
For example, the facile deprotonation of the otherwise
difficult trimethylsilyl group5 was achieved by utilizing a
2-pyridyldimethylsilyl (2-PyMe2Si) group as the intramo-
lecular ligand (Scheme 1).6 We envisioned that appending
multiple 2-PyMe2Si groups should lead to interesting reactiv-
ity. Herein, we report on our investigations of R-silyl
carbanion chemistry using (2-PyMe2Si)2CH2 (2).
Scheme 1
The starting material 2 can be easily prepared in 63% yield
by the reaction of 2-PyMe2SiCH2Li, generated from 1, and
(5) (a) Peterson, D. J. J. Organomet. Chem. 1967, 9, 373. (b) Gornowicz,
G. A.; West, R. J. Am. Chem. Soc. 1968, 90, 4478. (c) Frye, C. L.; Salinger,
R. M.; Fearon, F. W. G.; Klosowski, J. M.; DeYoung, T. J. Org. Chem.
1970, 35, 1308. (d) Pinkerton, F. H.; Thames, S. F. J. Organomet. Chem.
1971, 29, C4. (e) Hosomi, A.; Kohra, S.; Tominaga, Y.; Shoji, M.; Sakurai,
H. Chem. Pharm. Bull. 1987, 35, 1663. (f) Friesen, R. W.; Sturino, C. F.;
Daljeet, A. K.; Kolaczewska, A. J. Org. Chem. 1991, 56, 1944. (g) Imanieh,
H.; Quayle, P.; Voaden, M.; Conway, J.; Street, S. D. A. Tetrahedron Lett.
1992, 33, 543. (h) Luitjes, H.; de Kanter, F. J. J.; Schakel, M.; Schmitz, R.
F.; Klumpp, G. W. J. Am. Chem. Soc. 1995, 117, 4179. (i) Brough, P. A.;
Fisher, S.; Zhao, B.; Thomas, R. C.; Snieckus, V. Tetrahedron Lett. 1996,
37, 2915. (j) Abele, B. C.; Strohmann, C. In Organosilicon Chemistry III;
Auner, N., Weis, J., Eds.; Wiley-VCH: Weinheim, 1998; p 206.
(1) (a) Brook, M. A. Silicon in Organic, Organometallic, and Polymer
Chemistry; John Wiley & Sons: New York, 2000. (b) Colvin, E. W. Silicon
Reagents in Organic Synthesis; Academic Press: London, 1988. (c) Weber,
W. P. Silicon Reagents for Organic Synthesis; Springer-Verlag: Berlin,
1983. (d) Magnus, P. Aldrichimica Acta 1980, 13, 238.
(2) Peterson, D. J. J. Org. Chem. 1968, 33, 780. For an excellent review,
see: Ager, D. J. Org. React. 1990, 38, 1.
(3) Tamao, K.; Ishida, N.; Ito, Y.; Kumada, M. Org. Synth. 1990, 69,
96.
(4) For a review on CIPE, see: Beak, P.; Meyers, A. I. Acc. Chem. Res.
1986, 19, 356. See also: Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem.
ReV. 1993, 93, 1307.
10.1021/ol005735n CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/04/2000

Table 1. Reactions of (2-PyMe2Si)2CHLi with Carbonyl Compoundsa
a Unless otherwise noted, the reactions were performed in dry Et2O using (2-PyMe2Si)2CHLi and carbonyl compounds (1.5 equiv) at -78 °C for 30 min
1
and then at room temperature for 1 h under argon. b Isolated yields. c Determined by H and 13C NMR analysis and NOE experiments. d The reaction was
performed using (2-PyMe2Si)2CHLi (2.5 equiv).
2-PyMe2SiH, as reported previously.6c At the outset, we
examined the deprotonation of 2 to generate (2-PyMe2Si)2-
CHLi. It has been reported that the deprotonation of 1 is
highly dependent on the lithiating agent employed: t-BuLi
leads to quantitative deprotonation, whereas n-BuLi leads
to a complex mixture.6b As in the case for 1, the deproton-
ation of 2 was successfully accomplished by 1.1 equiv of
t-BuLi in Et2O at -78 °C, and subsequent reaction with allyl
bromide gave the corresponding adduct (2-PyMe2Si)2CHCH2-
CHdCH2 (3) in 82% yield. Anticipating the increased
reactivity of 2, we next employed n-BuLi under otherwise
identical conditions, and 3 was isolated in 92% yield. Simple
alkyl bromides were not applicable in this reaction because
of their lower reactivities toward nucleophiles.
Having established the facile deprotonation of 2, we further
investigated the reactions of (2-PyMe2Si)2CHLi with various
1300
Org. Lett., Vol. 2, No. 9, 2000

carbonyl compounds. It has been reported6c that the reactions
of 2-PyMe2SiCH2Li with aldehydes and ketones gave the
â-hydroxysilanes without any formation of alkenes by a
Peterson-type elimination.2 However, in the case of 2,
Peterson-type olefination was found to take place, after or
concurrently with the addition, to give the corresponding
vinylsilanes stereoselectively (Scheme 2). The results are
depicted in Table 1.
direct addition/elimination sequences.7,8 For example, the
condensation of (Me3Si)2CHLi with benzaldehyde gave a
mixture of stereoisomers (E/Z ) 1.4/1).8b If the selectivities
are governed by the well-accepted syn-elimination2,7 from
the â-silyl alkoxide (A or B), the selectivity differences
between (2-PyMe2Si)2CHLi and (Me3Si)2CHLi should not
be as dramatic as it is (Figure 1). Moreover, the use of the
Scheme 2
The reactions with primary, secondary, and tertiary
aliphatic and aromatic aldehydes gave the corresponding
vinylsilanes in quantitative yields (entries 1-7). Noteworthy
is that the reaction is also applicable to the sterically hindered
aldehydes (entries 3 and 6) and bisaldehyde (entry 7).
Ketones gave the disubstituted vinylsilanes with somewhat
lower yields (entries 8-10). Presumably, proton transfer
competed with addition for enolizable ketones such as
acetophenone (entry 9), where (2-PyMe2Si)2CHLi serves as
the base. The reaction can be applied to the stereoselective
synthesis of dienylsilanes as well (entries 11-13).
Figure 1. The origin of stereoselectivity.
The extremely high stereoselectivities (>99% E) are worth
mentioning. It has been well documented that acid- or base-
catalyzed elimination from isolated â-hydroxysilanes is
highly stereoselective.7 However, this is not the case for the
more sterically demanding t-BuMe2Si group instead of a
Me3Si group only led to a slight increase in the E selectivity,
indicating that the steric factor is not a sole decisive factor
for the high selectivity.7 There must be some contribution
from the pyridyl group in the observed high stereoselectivity.
We surmise that, before the elimination of the siloxy group,
the chairlike conformer (C or D) might be involved as a
stereodetermining intermediate where the intramolecular
coordination of the pyridyl group locks the conformation.8o
Of the two, D should be preferred over C, since both silyl
and RL groups can occupy the equatorial positions. Thus
preferred D may lead to the observed E-isomer. However,
we must stress that these discussions are purely speculative
with no experimental evidence.
To assess the elimination aptitude of the 2-PyMe2Si group
in the Peterson-type elimination, we next conducted a control
experiment using 2-PyMe2SiCH2SiMe2Ph (5). As reported
previously, 5 can be prepared in 99% yield by the reaction
of 2-PyMe2SiCH2Li and PhMe2SiCl.6c The generation of
2-PyMe2SiCH(Li)SiMe2Ph was successfully accomplished
by the reaction of 5 with t-BuLi in Et2O. The carbanion thus
generated was subsequently allowed to react with benzal-
dehyde to give the PhMe2Si-substituted styrene 6 in 95%
yield (Scheme 3). The formation of a 1:1 mixture of two
(6) (a) Yoshida, J.; Itami, K.; Mitsudo, K.; Suga, S. Tetrahedron Lett.
1999, 40, 3403. (b) Itami, K.; Mitsudo, K.; Yoshida, J. Tetrahedron Lett.
1999, 40, 5533. (c) Itami, K.; Mitsudo, K.; Yoshida, J. Tetrahedron Lett.
1999, 40, 5537.
(7) Hudrlik, P. K.; Agwaramgbo, E. L. O.; Hudrlik, A. M. J. Org. Chem.
1989, 54, 5613.
(8) Although similar E selectivities for [bis(silyl)methyl]lithium were
previously reported, they are not as high as ours or not sited in the literature;
see: (a) Sakurai, H.; Nishiwaki, K.; Kira, M. Tetrahedron Lett. 1973, 4193.
(b) Gro¨bel, B.-T.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1974, 13, 83.
(c) Hartzell, S. L.; Rathke, M. W. Tetrahedron Lett. 1976, 2737. (d) Sachdev,
K. Tetrahedron Lett. 1976, 4041. (e) Carter, M. J.; Fleming, I. J. Chem.
Soc., Chem. Commun. 1976, 679. (f) Seyferth, D.; Lefferts, J. L.; Lambert,
R. L., Jr. J. Organomet. Chem. 1977, 142, 39. (g) Seebach, D.; Bu¨rstinghaus,
R.; Gro¨bel, B.-T.; Kolb, M. Liebigs Ann. Chem. 1977, 830. (h) Gro¨bel,
B.-T.; Seebach, D. Chem. Ber. 1977, 110, 852. (i) Isobe, M.; Kitamura,
M.; Goto, T. Tetrahedron Lett. 1979, 3465. (j) Fleming, I.; Pearce, A. J.
Chem. Soc., Perkin Trans. 1 1980, 2485. (k) Carter, M. J.; Fleming, I.;
Percival, A. J. Chem. Soc., Perkin Trans. 1 1981, 2415. (l) Sato, Y.;
Takeuchi, S. Synthesis 1983, 734. (m) Ager, D. J. J. Org. Chem. 1984, 49,
168. (n) Takeda, T.; Ando, K.; Mamada, A.; Fujiwara, T. Chem. Lett. 1985,
1149. (o) Boeckman, R. K., Jr.; Chinn, R. L. Tetrahedron Lett. 1985, 26,
5005. (p) Ager, D. J.; East, M. B. J. Org. Chem. 1986, 51, 3983. (q) Inoue,
S.; Sato, Y. Organometallics 1986, 5, 1197. (r) Terao, Y.; Aono, M.;
Takahashi, I.; Achiwa, K. Chem. Lett. 1986, 2089. (s) Marchand, A. P.;
Huang, C.; Kaya, R.; Baker, A. D.; Jemmis, E. D.; Dixon, D. A. J. Am.
Chem. Soc. 1987, 109, 7095. (t) Kira, M.; Hino, T.; Kubota, Y.; Matsuyama,
N.; Sakurai, H. Tetrahedron Lett. 1988, 29, 6939. (u) Bates, T. F.; Thomas,
R. D. J. Org. Chem. 1989, 54, 1784.
Org. Lett., Vol. 2, No. 9, 2000
1301

Scheme 3
Scheme 4
In conclusion, we have developed the facile generation
and reactions of (2-PyMe2Si)2CHLi with a variety of
aldehydes and ketones, affording the corresponding vinyl-
silanes and dienylsilanes in extremely high yields with
complete stereoselectivities. This expeditious and versatile
protocol will find use in many organic reactions using
vinylsilanes and dienylsilanes.11
stereoisomers (E and Z) strongly denotes that the addition
process is nonselective, giving the two diastereomeric
intermediates. Moreover, it should be noted that the
2-PyMe2Si-substitued styrene was not observed at all in this
reaction. This observation underscores the greater elimination
aptitude of the 2-PyMe2Si group, and we assume the
following as plausible explanations: (i) the coordination of
the pyridyl group may force the conformation as in C or D
(Figure 1), thereby making the 2-PyMe2Si group eliminate
and (ii) the greater electrophilicity of the 2-PyMe2Si group
facilitates the alkoxide attack more readily.8u
Although the 2-pyridyl-substituted vinylsilane itself can
be expected to exert interesting reactivity, its conversion to
other vinylsilanes is also viable (Scheme 4). By using a
recently developed protocol, the 2-Py-Si bond can be
cleaved in a KF/MeOH system to afford methoxy(vinyl)-
silane.9 The resultant methoxysilane can be further allowed
to react with a Grignard reagent such as PhMgBr to give
the corresponding vinylsilane.10
Acknowledgment. This research was supported by a
Grant-in-Aid for Scientific Research from the Ministry of
Education, Science, Sports and Culture, Japan, and in part
by the Mitsubishi Foundation.
Supporting Information Available: Experimental pro-
cedures and characterization data for all compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL005735N
(10) For example, aryl(vinyl)silane (R ) 2,4,6-Me3C6H2, R′ ) Ph) can
be prepared in 57% overall yield.
(11) (a) Fleming, I.; Dunogue`s, J.; Smither, R. Org. React. 1989, 37,
57. (b) Larson, G. L. J. Organomet. Chem. 1992, 422, 1. (c) Fleming, I.;
Barbero, A.; Walter, D. Chem. ReV. 1997, 97, 2063.
(9) Itami, K.; Mitsudo, K.; Yoshida, J. J. Org. Chem. 1999, 64, 8709.
1302
Org. Lett., Vol. 2, No. 9, 2000