Unusual transposition of allenic framework in intramolecular cyclization of acetal-tethered (allenylmethyl)silanes

Article abstract of DOI:10.1021/ol901780d

Treatment of acetal-tethered (allenylmethyl)silanes, which were obtained from the corresponding 3-bromo-5-silyl-1,3-pentadienes by a Pd-catalyzed reaction with an acetal-tethered malonate, with TiCl₄ gave not only vinylcyclohexene derivatives v

Full text of DOI:10.1021/ol901780d

ORGANIC
LETTERS
2009
Vol. 11, No. 18
4240-4243
Unusual Transposition of Allenic
Framework in Intramolecular Cyclization
of Acetal-Tethered (Allenylmethyl)silanes
Masamichi Ogasawara,* Atsushi Okada, Hidetoshi Murakami, Susumu Watanabe,
Yonghui Ge, and Tamotsu Takahashi*
Catalysis Research Center and Graduate School of Life Science, Hokkaido UniVersity,
Kita-ku, Sapporo 001-0021, Japan
ogasawar@cat.hokudai.ac.jp; tamotsu@cat.hokudai.ac.jp
Received August 2, 2009
ABSTRACT
Treatment of acetal-tethered (allenylmethyl)silanes, which were obtained from the corresponding 3-bromo-5-silyl-1,3-pentadienes by a Pd-
catalyzed reaction with an acetal-tethered malonate, with TiCl4 gave not only vinylcyclohexene derivatives via a standard SE2′ pathway but
also unusual allenylcyclopentane species via cyclization at the δ-position. Deuterium-labeling experiments revealed participation of a 1,2-
hydride shift in a carbocation intermediate for the formation of the latter products.
Allenes are an important class of compounds and have gained
increasing attraction as interesting building blocks in syn-
thetic organic chemistry.1,2 Substitution reactions of allenic
substrates/reagents are often accompanied by concurrent
reorganization/relocation of the carbon-carbon multiple
bonds.3 For example, reactions of allenylmetal reagents with
an appropriate electrophile proceed in an SE2′ fashion to give
the corresponding propargylic products (eq 1).4 Substitution
reactions of allenylmethyl halides afford conjugate dienes
via an SN2′ pathway (eq 2).5
In this paper, we describe an unprecedented mode of
allenic substitution reactions. Lewis acid promoted intramo-
lecular electrophilic substitution/cyclization of an acetal-
tethered (allenylmethyl)silane gives rise to an unusual
(1) (a) Taylor, D. R. Chem. ReV. 1967, 67, 317. (b) Pasto, D. J.
Tetrahedron 1984, 40, 2805. (c) Rutledge, T. F. Acetylenes and Allenes;
Reinhold: New York, 1969. (d) Patai, S., Ed. The Chemistry of Ketenes,
Allenes, and Related Compounds; Wiley: Chichester, 1980. (e) Landor, S. R.,
Ed. The Chemistry of the Allenes; Academic Press: London, 1982. (f)
Coppola, G. M.; Schuster, H. F. Allenes in Organic Synthesis; Wiley: New
York, 1984. (g) Krause, N., Hashmi, A. S. K., Eds. Modern Allene
(3) (a) Landor, S. R. In The Chemistry of the Allenes; Landor, S. R.,
Ed.; Academic Press: London, 1982; p 235. (b) Zimmer, R.; Reissig, H.-
U. In Modern Allene Chemistry; Krause, N., Hashmi, A. S. K., Eds.; Wiley-
VCH: Weinheim, 2004; p 847.
(4) (a) Fleming, I.; Barbero, A.; Walter, D. Chem. ReV. 1997, 97, 2063.
(b) Marshall, J. A. Chem. ReV. 2000, 100, 3163. (c) Marshall, J. A. In Lewis
Acids in Organic Synthesis; Yamamoto, H., Ed.; Wiley-VCH: Weinheim,
2000; p 453. (d) Marshall, J. A.; Gung, B. W.; Grachan, M. L. In Modern
Allene Chemistry; Krause, N., Hashmi, A. S. K., Eds.; Wiley-VCH:
Weinheim, 2004; p 493. (e) Marshall, J. A. J. Org. Chem. 2007, 72, 8153.
(5) For recent examples, see: (a) Gharibian, H.; Palikyan, G.; Badanyan,
S. H.; Paulsen, K.; Melikyan, G. G. HelV. Chim. Acta 2000, 83, 3291. (b)
Shen, Q.; Hammond, G. B. Org. Lett. 2001, 3, 2213. (c) Brel, V. K.; Belsky,
V. K.; Stash, A. I.; Zavodnik, V. E.; Stang, P. J. Org. Biomol. Chem. 2003,
1, 4220. (d) Brel, V. K. Synthesis 2007, 2674.
Chemistry; Wiley-VCH: Weinheim, 2004
.
(2) (a) Marshall, J. A. Chem. ReV. 1996, 96, 31. (b) Wang, K. K. Chem.
ReV. 1996, 96, 207. (c) Yamamoto, Y.; Radhakrishnan, U. Chem. Soc. ReV.
1999, 28, 199. (d) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2000, 39, 3590.
(e) Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A. Chem. ReV.
2000, 100, 3067. (f) Lu, X.; Zhang, C.; Xu, Z. Acc. Chem. Res. 2001, 34,
535. (g) Ma, S.; Li, L. Synlett 2001, 1206. (h) Tius, M. A. Acc. Chem. Res.
2003, 36, 284. (i) Ma, S. Acc. Chem. Res. 2003, 36, 701. (j) Ma, S. Eur. J.
Org. Chem. 2004, 1175. (k) Brandsma, L.; Nedolya, N. A. Synthesis 2004,
735
.
10.1021/ol901780d CCC: $40.75
Published on Web 08/21/2009
 2009 American Chemical Society

transposition of the allenic substructure from the ꢀ,γ,δ-
position to the adjacent R,ꢀ,γ-position upon elimination of
the silyl group (eq 3). Scope and limitation of this novel
allenic substitution reaction as well as results of mechanistic
studies will be described in detail.
Table 1. Lewis Acid Promoted Intramolecular Cyclization of 1a
yield
(%) of 2/3c
cis/trans
in 3b
entry
1
Lewis acid conversionb (%)
1
2
3
4
5
6
7
8
9d
1a TiCl4
1a AlCl3
1a BF3·OEt2
1a Me3SiOTf
1b TiCl4
1c TiCl4
1d TiCl4
1e TiCl4
1f TiCl4
90
<10
15
75
85
80
80
90
100
50
32 (2a)/30 (3a)
n.d.
33/67
15 (2a)/0
72 (2a)/0
35 (2a)/23 (3a)
38 (2a)/14 (3a)
28 (2a)/28 (3a)
56 (2e)/24 (3e)
12 (2f)/trace
0/0
45/55
n.d.
8/92
31/69
An intermolecular reaction of an (allenylmethyl)silane with
an appropriate electrophile is generally regiospecific and
takes place in an SE2′ fashion to give the corresponding 1,3-
dien-2-yl products.6 By the use of scalemic δ-monosubsti-
tuted (allenylmethyl)silanes, which are axially chiral, unique
axial-to-central chirality transfer was realized with fair
success.7 In the reactions with δ-substituted (allenylmethyl)-
silanes, products were obtained as (E)-isomers predomi-
nantly,6b,7 and the stereoselectivity was explained by steric
repulsion between the δ-substituent and the incoming elec-
trophile in a transition state (Scheme 1).
10e 1g TiCl4
a The reaction was carried out with 1 (0.10 mmol) and Lewis acid (0.20
mmol) in dichloromethane (5.0 mL) at -78 °C for 3 h. b Determined by
1H NMR of the crude product. c Isolated yield by silica gel chromatography.
d Formation of poorly characterized oligomeric products were detected. e The
allene 4 was formed by elimination of acetal.
1a was consumed in 3 h. GC and NMR analyses revealed
that the reaction mixture contained three major products
(entry 1). One was a conjugated vinylcyclohexene 2a (32%
yield) derived by an intramolecular SE2′ pathway. The
formation of 2a was similar to the intermolecular process
shown in Scheme 1; however, the internal olefin in 2a
(the CγdCδ double bond) has a (Z)-configuration due to a
geometric requirement of the cyclohexenyl skeleton in
contrast to the (E)-configuration in intermolecular reaction
products.7b,9 The other two products from the intramolecular
reaction were a diastereomeric pair of allenylcyclopentane
derivatives, cis- and trans-3a (cis/trans ) 33/67),10 in 30%
combined yield. Formation of 3a was totally unpredictable,
and apparently, it was a result of an unprecedented allene-
to-allene rearrangement in the reaction. The allenic moiety
Scheme 1
Intramolecular variants of the electrophilic substitution
reactions of (allenylmethyl)silanes were examined by as-
sembling both an (allenylmethyl)silane and a proelectrophile
moieties into a single molecule. A series of acetal-tethered
(allenylmethyl)silanes 1 was prepared from the corresponding
3-bromo-5-silyl-1,3-pentadienes8 by the Pd-catalyzed reac-
tion according to our previous reports7b,9 (Scheme 2).
(6) (a) Montury, M.; Psaume, B.; Gore´, J. Tetrahedron Lett. 1980, 21,
163. (b) Psaume, B.; Montury, M.; Gore´, J. Synth. Commun. 1982, 12, 409.
(c) Imai, T.; Nishida, S. J. Org. Chem. 1990, 55, 4849. (d) Hatakeyama,
S.; Sugawara, K.; Kawamura, M.; Takano, S. Tetrahedron Lett. 1991, 32,
4509. (e) Hatakeyama, S.; Sugawara, K.; Takano, S. Tetrahedron Lett. 1991,
32, 4513. (f) Hatakeyama, S.; Sugawara, K.; Takano, S. J. Chem. Soc.,
Chem. Commun. 1991, 1533. (g) Hatakeyama, S.; Kawamura, M.; Takano,
S. J. Am. Chem. Soc. 1994, 116, 4081. (h) Hatakeyama, S.; Yoshida, M.;
Esumi, T.; Iwabuchi, Y.; Irie, H.; Kawamoto, T.; Yamada, H.; Nishizawa,
M. Tetrahedron Lett. 1997, 38, 7887. (i) Yu, C.-M.; Yoon, S.-K.; Lee,
S.-J.; Lee, J.-Y.; Kim, S. S. Chem. Commun. 1998, 2749. (j) Luo, M.;
Matsui, A.; Esumi, T.; Iwabuchi, Y.; Hatakeyama, S. Tetrahedron Lett.
2000, 41, 4401. (k) Parsons, P. J.; Gold, H.; Semple, G.; Montagnon, T.
Synlett 2000, 1184. (l) Pacheco, M. C.; Gouverneur, V. Org. Lett. 2005, 7,
1267. (m) Berkheij, M.; Dijkink, J.; David, O. R. P.; Sonke, T.; IJzendoorn,
D. R.; Blaauw, R. H.; van Maarseveen, J. H.; Schoemaker, H. E.; Hiemstra,
H. Eur. J. Org. Chem. 2008, 914.
Scheme 2
(7) (a) Mentink, G.; van Maarseveen, J. H.; Hiemstra, H. Org. Lett. 2002,
4, 3497. (b) Ogasawara, M.; Ueyama, K.; Nagano, T.; Mizuhata, Y.;
Hayashi, T. Org. Lett. 2003, 5, 217.
(8) Roux, M.; Santelli, M.; Parrain, J.-L. Org. Lett. 2000, 2, 1701.
(9) (a) Ogasawara, M.; Ikeda, H.; Hayashi, T. Angew. Chem., Int. Ed.
2000, 39, 1042. (b) Ogasawara, M.; Ikeda, H.; Nagano, T.; Hayashi, T.
Org. Lett. 2001, 3, 2615. (c) Ogasawara, M.; Ikeda, H.; Nagano, T.; Hayashi,
T. J. Am. Chem. Soc. 2001, 123, 2089. (d) Ogasawara, M.; Ge, Y.; Uetake,
K.; Fan, L.; Takahashi, T. J. Org. Chem. 2005, 70, 3871. (e) Ogasawara,
M.; Nagano, T.; Hayashi, T. J. Org. Chem. 2005, 70, 5764.
Treatment of the acetal-tethered (allenylmethyl)silanes 1
with an appropriate Lewis acid (2 equiv to 1) at -78 °C in
dichloromethane promoted intramolecular electrophilic sub-
stitution (Table 1). With titanium(IV) chloride, ca. 90% of
Org. Lett., Vol. 11, No. 18, 2009
4241

in 3a consisted of the R,ꢀ,γ-carbons of the substrate 1a, while
the CdCdC framework comprised the ꢀ,γ,δ-carbons in 1a.
The reaction was sensitive to choices of Lewis acid
promoters. A reaction of 1a with AlCl3 was sluggish, and
its conversion was less than 10% in 3 h (entry 2). BF3·OEt2
and Me3SiOTf promoters afforded 2a exclusively, and no
3a was detected (entries 3 and 4).
With a bulkier silyl group in 1, the six-membered
product 2a became more dominant over the five-membered
3a in the reaction. The TES-substituted substrate 1b gave
2a and 3a in 35% and 23% yields, respectively (entry 5).
The TIPS analogue 1c afforded a mixture of 2a (38%)
and 3a (14%; entry 6). In the same way, the diethyl acetal
derivative 1e reacted with TiCl4 to give the vinylcyclo-
hexene 2e (56%) and the allenylcyclopentane 3e (24%),
respectively (entry 8).
Subsequent elimination of the silyl group from 8 affords the
allenylcyclopentanes 3. The selectivity between 2 and 3 in
the cyclization of 1 should be determined by nature of the
oxonium intermediate 5, which exists as an ion pair with an
anionic adduct between RO- and a Lewis acid. Since pairing
affinity between 5 and the anion depends on the Lewis acid
moiety in the anion, nature/reactivity of 5 also depends on
the Lewis acid. This can be attributed to the Lewis acid-
dependent selectivity in the present reaction.11
A key step in the pathway to the unusual products 3 is
the 1,2-hydride shift in 7. The validity of the proposed
reaction mechanism was justified by a deuterium-labeling
experiment. A partially deuterated (allenylmethyl)silane 1a-
d2 (95% deuterium incorporation) was prepared as shown
in Scheme 4. Treatment of 1a-d2 with TiCl4 as in entry 1 in
Formation of the unusual product 3 was unique to the
five-membered carbocycles. The (allenylmethyl)silane 1f,
which possesses an additional CH2 moiety in the acetal
tether, mainly produced poorly characterized oligomeric
products together with vinylcycloheptene 2f in 12% (entry
9). A reaction of 1g, that is with a shorter acetal tether,
facilitated elimination of the acetal group to give
Me3SiCH2CHdCdCHCH2CH(CO2Me)2 (4) in 34% yield,
and no cyclized products were detected (entry 10).
A plausible mechanism of the intramolecular cyclization
of 1 is shown in Scheme 3. A cationic intermediate 5, which
Scheme 4
Scheme 3
Table 1 provided a mixture of 2a-d2 and 3a-d2 with the same
yields and the same distribution within experimental errors.
1
2
The H- and D-NMR spectra of the products revealed that
the deuterium atoms were retained on the ꢀ- and δ-carbons
in 2a-d2. On the other hand, the deuterium atoms were
incorporated on the γ- and δ-carbons in cis- and trans-3a-
d2 as expected from the mechanism in Scheme 3. No other
extra deuteration was detected in all three products. These
results clearly support involvement of the 1,2-hydride shift
process in the formation of 3.
It was found that, however, the D-content at the γ-carbon
in cis-3a-d2 was significantly diminished to 14%. Despite
our best efforts,12 proton sources of the D-content reduction
in cis-3a-d2 could not be identified. The lower D-content
is generated in situ by Lewis acid promoted abstraction of
OR- from 1, reacts in two separate pathways. The electro-
philic oxonium moiety in 5 reacts primarily at the γ-carbon
of the (allenylmethyl)silane unit as reported in the intermo-
lecular reactions.6 Following elimination of the silyl group
from the ꢀ-silyl carbocation, intermediate 6 furnishes the
vinylcyclohexene 2. On the other hand, a nucleophilic attack
of the δ-carbon to the oxonium cation is competeing with
the γ-attack in certain cases. An initially formed vinyl cation
7 is transformed to 8 via an 1,2-hydride shift. Presumably,
stabilization of a positive charge in 8 by the ꢀ-silicon effect
is the main driving force to facilitate the hydride shift.
(11) Santelli, M.; Pons, J.-M. Lewis Acids and SelectiVity in Organic
Synthesis; CRC Press: New York, 1996; p 185 and references cited
therein.
(12) No deuterium introduction was detected in the reactions of 1a using
a deuterated solvent (CD2Cl2) and/or a deuterated quencher (a mixture of
CD3OD and D2O). A partially deuterated 1a, which is with a deuterated
acetal pendant -CH(OCD3)2, afforded the products which were deuterated
only in the -OCD3 substituents.
1
(10) The configurations of the cis- and trans-3 were determined by H
NMR NOE experiments.
4242
Org. Lett., Vol. 11, No. 18, 2009

postulates participation of an intermolecular process,13 which
is competing with the intramolecular pathway, in the
formation of cis-3a-d2.
reactions of (allenylmethyl)silanes with an electrophile
generally takes place in the same way as those of allylsilanes.
Thus, a usual intermolecular reaction of an (allenylmethyl)-
silane with an electrophile takes place at the allenic central
sp-carbon (the γ-carbon).6 In the cases of 1a-e, however,
reactions at the less nucleophilic δ-carbons were competing
with those at the γ-carbons due to constrained steric
requirements of the intramolecular process. As a conse-
quence, the (allenylmethyl)silanes showed the reaction mode
analogous to that of homoallylsilanes to give the unusual
allenic rearrangement products 3.
In summary, we have found out an unprecedented mode
of an allenic substitution reaction. The unusual transposition
of allenic frameworks was concomitant with the intramo-
lecular electrophilic substitution/cyclization of the acetal-
tethered (allenylmethyl)silanes. To the best of our knowledge,
this is the first demonstration that (allenylmethyl)silanes show
homoallylsilane-like ractivity in electrophilic substitutions.
Silicon atoms promote the formation of a positive charge
at the ꢀ-position, which is known as the ꢀ-silicon effect.14
High reactivity of carbon-carbon double bonds in allylsilane
derivatives toward electrophiles could be ascribed to the
effect. Silicon atoms are also capable of stabilizing a cation
at the γ-position in the same way (the γ-silicon effect), but
the γ-silicon effect is much weaker than the ꢀ-counterpart.15
Thus, synthetic applications of the γ-silicon effect have been
rather limited. It was reported that homoallylsilanes (3-
butenylsilanes) reacted with an electrophile at the δ-positions
to generate the corresponding γ-cation intermediates, which
were transformed to final products either by desilylative
cyclopropanation (path (a) in Scheme 5)16 or by the 1,2-
hydride shift/silicon elimination sequence (path (b)).16a,17
Acknowledgment. A part of this work was supported by
a Grant-in-Aid for Scientific Research on Priority Areas
“Advanced Molecular Transformations of Carbon Resources”
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
Scheme 5
Supporting Information Available: Detailed experimen-
tal procedures and compound characterization data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
An (allenylmethyl)silane possesses both an allylsilane and
a homoallylsilane substructure within a single molecule.
Whereas the ꢀ-silicon effect is dominant over the γ-effect,
OL901780D
(14) (a) Weber, W. P. Silicon Reagents for Organic Synthesis; Springer-
Verlag: Berlin, Heidelberg, 1983. (b) Colvin, E. W. Silicon Reagents in
Organic Synthesis; Academic Press: London, 1988. (c) Fleming, I. In
ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Paquette, L. A.,
Eds; Pergamon Press: Oxford, 1991; Vol. 2, p 563. (d) Fleming, I.;
Dunogue`s, J.; Smithers, R. Org. React. 1989, 37, 57.
(13) As a possible intermolecular process for the loss of D-content in
cis-3a-d2, the following route is postulated: initial deprotonation of the
intermediate cis-7-d2 gives the corresponding propargylsilane, which
undergoes successive protodesilylation to afford cis-3a-d2. Whereas the
reaction mixture must be protic due to inevitable partial hydrolysis of TiCl4,
this route gives cis-3a-d2 of the lower D-content at the γ-carbon. Neverthe-
less, the difference between cis- and trans-3a-d2 in the D-contents at the
γ-positions cannot be rationalized by this process.
(15) Sakurai, H.; Hosomi, A.; Kumada, M. J. Org. Chem. 1969, 34,
1764.
(16) (a) Sakurai, H.; Imai, T.; Hosomi, A. Tetrahedron Lett. 1977, 18,
4045. (b) Hatanaka, Y.; Kuwajima, I. Tetrahedron Lett. 1986, 27, 719.
(17) Masuya, K.; Tanino, K.; Kuwajima, I. Synlett 1999, 647.
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