1-Bromo-1-lithioethene: A practical reagent in organic synthesis

Article abstract of DOI:10.1021/jo051125v

A reliable preparative scale synthesis of 1-bromo-1-lithioethene is reported. This reagent undergoes clean 1,2-addition with a range of aldehydes and ketones at -110 °C to afford the corresponding 2-bromo-1-alken-3-ols in moderate to excellent yield. Trapping with other electrophiles (acylsilanes, chlorosilanes, tributyltin chloride, iodine) cleanly provides practically useful yields of various 1-substituted 1-bromoethene products. Unexpectedly high diastereoselectivities were observed during the addition of 1-bromo-1- lithioethene to α-siloxy aldehydes (typically 10:1, Felkin-Ahn control) and protected ketopyranose and ketofuranose sugars (> 10:1, addition from the less-hindered face). The title organolithium reagent possesses relatively low basicity at low temperature, and is compatible with a variety of common protecting groups. We believe that these unusual properties of 1-bromo-1-lithioethene may originate from the specific crystalline structure of the reagent in which lithium is coordinatively saturated and thus unavailable for chelation. 2005 American Chemical Society.

Full text of DOI:10.1021/jo051125v

1-Bromo-1-lithioethene: A Practical Reagent in Organic Synthesis
Yehor Y. Novikov* and Paul Sampson*
Department of Chemistry, Kent State University, Kent, Ohio 44242
yehor_novikov@yahoo.com; psampson@kent.edu
Received June 3, 2005
A reliable preparative scale synthesis of 1-bromo-1-lithioethene is reported. This reagent undergoes
clean 1,2-addition with a range of aldehydes and ketones at -110 °C to afford the corresponding
2-bromo-1-alken-3-ols in moderate to excellent yield. Trapping with other electrophiles (acylsilanes,
chlorosilanes, tributyltin chloride, iodine) cleanly provides practically useful yields of various
1-substituted 1-bromoethene products. Unexpectedly high diastereoselectivities were observed
during the addition of 1-bromo-1-lithioethene to R-siloxy aldehydes (typically 10:1, Felkin-Ahn
control) and protected ketopyranose and ketofuranose sugars (g10:1, addition from the less-hindered
face). The title organolithium reagent possesses relatively low basicity at low temperature, and is
compatible with a variety of common protecting groups. We believe that these unusual properties
of 1-bromo-1-lithioethene may originate from the specific crystalline structure of the reagent in
which lithium is coordinatively saturated and thus unavailable for chelation.
Introduction
3-buten-2-one;5f ene reaction of 2-bromoacrolein;9 or HBr
addition to terminal alkyn-3-ols.2,5b,c However, in a
number of cases, the yields of 2 were modest, and in some
cases, the separation of regioisomeric products was
required.2b
Prior to our work in this area, there were no reported
approaches to tertiary R-bromoallylic alcohols 2 (R1 and
R2 * H). However, a series of closely related acetate
ester10 and ether11 derivatives have been prepared, in
moderate to poor yield and with the derivative typically
being a component within a mixture of products, via the
Ag+-mediated opening of the corresponding gem-dibro-
mocyclopropane in the presence of acetic acid or an
alcohol. We considered that 1-bromo-1-lithioethene (1)
might offer a convenient synthetic entry to compounds
of general structure 2.
Bromoalkenes are important substrates for the con-
struction of C-C bonds in many modern organic reac-
tions.1 Recently, our attention was drawn to 1-bromo-1-
lithioethene (1) as a potential reagent for the convenient
one-pot preparation of various bromoalkenes. For ex-
ample, 2-bromo-1-alken-3-ols 2, which are formal adducts
of 1 with carbonyl compounds, have a considerable
potential utility as synthetic building blocks. Some
synthetic applications of 2 (R1 ) H) in Pd(0)-catalyzed
coupling2-4 as well as in a variety of other reactions5 have
already been demonstrated. The preparation of 2 (R1 )
H) has previously been achieved by 1,2-addition of
alkynyllithium,2a,b Grignard,5d,6 or enolate3,5e,7 nucleo-
philes to 2-bromoacrolein;8 Luche reduction of 3-bromo-
(R-Bromoethenyl)chlorodimethylsilane (3) has been
used as a building block in the construction of an
R-bromoethenyl silyl ether that underwent intramolecu-
lar radical cyclization chemistry.12 However, although
(1) (a) For examples of Pd(0)-catalyzed cross-coupling, see: Metal-
Catalyzed Cross-Coupling Reactions; de Meijere, A., Diederich, F., Eds.;
Wiley-VCH: Weinheim, Germany, 2004. Cross-Coupling Reactions -
A Practical Guide; Miyaura, N., Ed.; Topics in Current Chemistry;
Springer-Verlag: Berlin, 2002; Vol. 219. Handbook of Organopalla-
dium Chemistry for Organic Synthesis; Negishi, E., de Meijere, A., Eds.;
Wiley-Interscience: New York, 2002; Vol. 1 and 2. (b) For examples of
organocuprate coupling, see: Lipshutz, B. H.; Sengupta, S. Org. React.
1992, 41, 135-631. Modern Organocopper Chemistry; Krause, N., Ed.;
Wiley-VCH: Weinheim, Germany, 2002. Heaney, H.; Christie, S. In
Science of Synthesis; O’Neil, I. A., Ed.; Thieme Verlag: Stuttgart,
Germany, 2004; Vol. 3, pp 305-662. Organocopper Reagents; Taylor,
R. J. K., Ed.; IRL Press: Oxford, 1994. (c) For examples of Nozaki-
Hiyama-Kishi coupling, see: Wessjohann, L. A.; Scheid, G. Synthesis
1999, 1-36. Takai, K.; Nozaki, H. Proc. Jpn. Acad., Ser. B 2000, 76,
123-131. Furstner, A. Chem. Rev. 1999, 99, 991-1045. Avalos, M.;
Babiano, R.; Cintas, P.; Jiminez, J. L.; Palacios, J. C. Chem. Soc. Rev.
1999, 28, 169-177.
(2) For examples of Sonogashira coupling, see: (a) Dai, W.-M.; Wu,
J.; Fong, K. C.; Lee, M. Y. H.; Lau, C. W. J. Org. Chem. 1999, 64,
5062-5082. (b) Marshall, J. A.; Sehon, C. A. Org. Synth. 1999, 76,
263-270. (c) Marshall, J. A.; DuBay, W. J. J. Org. Chem. 1994, 59,
1703-1708. (d) Marshall, J. A.; DuBay, W. J. J. Org. Chem. 1993, 58,
3435-3443. (e) Marshall, J. A.; Sehon, C. A. Org. Synth. 1999, 76, 263-
270. (f) McDonald, F. E.; Schultz, C. C. J. Am. Chem. Soc. 1994, 116,
9363-9364.
(3) For an example of the intramolecular Heck reaction, see: Toyota,
M.; Nishikawa, Y.; Fukumoto, K. Tetrahedron 1994, 50, 11153-11166.
(4) For an example of bromohydroxylation/amination en route to
R-methylene-γ-lactams, see: Mori, M.; Chiba, K.; Okita, M.; Kayo, I.;
Ban, Y. Tetrahedron 1985, 41, 375-385.
10.1021/jo051125v CCC: $30.25 © 2005 American Chemical Society
Published on Web 11/05/2005
J. Org. Chem. 2005, 70, 10247-10259
10247

Novikov and Sampson
is their thermal instability, which is especially pro-
nounced for compounds of general structure 4, in which
a hydrogen substituent is positioned trans to the halo
substituent.17,18
In this paper, we demonstrate that 1-bromo-1-lithio-
ethene (1) has sufficient thermal stability to serve as a
useful synthetic reagent. We describe the development
of a reliable preparative scale synthesis of 1 along with
an exploration of its synthetic utility as a 1-bromoethenyl
nucleophile for trapping a variety of electrophiles.19
reasonable yields and selectivities were observed with
this reagent, the preparation of 3 required a three-step
synthesis, and the utility of the method was limited by
the low hydrolytic stability of the intermediate silyl ether
required for its application in radical cyclization chem-
istry. We anticipated that a range of more stable R-bro-
moethenyl silane derivatives might be conveniently
accessed from 1-bromo-1-lithioethene (1).
Interestingly, little is known about the use of 1-halo-
1-lithioethenes (halo ) Cl, Br, I) as synthetic reagents.
To our knowledge, only two groups have reported the
preparation of 1-chloro-13 and 1-iodo-1-lithioethene14 as
a separate step. Other groups generated 1-chloro-1-
lithioethene15 and 1-bromo-1-lithioethene16 in the pres-
ence of an electrophile, which severely limited the
synthetic utility of the corresponding organometallic
reagent. Prior to our work in this area, it appears that
only a single example of trapping a 1-halo-1-lithioethene
with a carbonyl compound (halo ) I, 10% yield with
benzophenone) has been published.14 The apparent rea-
son for the limited usage of 1-halo-1-lithioethenes (and
other 1-halo-1-lithio-1-alkenes) in preparative synthesis
Results and Discussion
As was reported in our preliminary communication,19a
treatment of bromoethene with n-BuLi at -110 °C in the
Trapp solvent mixture20 in the presence of 0.2-0.5 equiv
of LiBr allowed the clean formation of 1-bromo-1-lithio-
ethene (1). Subsequent addition of carbonyl compounds
led to the clean formation of the corresponding 1,2-
addition adducts 2 in high yield (Table 1). These results
offer the first practical entry to tertiary R-bromoallylic
alcohols 2 (R1 and R2 * H).
Unexpectedly, no products were observed that origi-
nated from possible H2CdCHLi formation by a competing
halogen-metal exchange reaction of bromoethene. This
result seems to contradict earlier observations13,16 about
the relative rates of bromine-lithium exchange versus
deprotonation at an alkene sp2 carbon using n-butyl-
lithium. However, when bromoethene was treated with
tert-butyllithium under the same conditions, a 7:3 mix-
ture of H2CdCHLi and 1-bromo-1-lithioethene (1) was
obtained, and was further characterized by electrophilic
trapping with chlorotrimethylsilane (Scheme 1).
In an attempt to rationalize these observations, liquid-
phase ab initio HF6-31G*/SM5.42R calculations21 were
undertaken. To define the computational task, we as-
sumed that the base used (n-BuLi or t-BuLi) first
underwent partial dissociation induced by THF. This
assumption is partially supported by the observation that
bromoethene was essentially unreactive toward n-BuLi
at -110 °C in pentane solution. In addition, it was
observed that the presence of more than 0.7 equiv of LiBr
in the reaction mixture significantly decreased the rate
of the reaction between bromoethene and n-BuLi. This
was consistent with the participation of a relatively free
carbanion in the deprotonation step. This assumption
prompted us to examine direct reactions between ap-
propriate alkyl anions and bromoethene (Table 2). To
minimize complications resulting from the conforma-
(5) As a source of functionalized vinyllithium and vinylcuprate
reagents, see: Cloninger, M. J.; Overman, L. E. J. Am. Chem. Soc.
1999, 121, 1092-1093. (b) As a source of vinylstannanes, see: Han,
X.; Stoltz, B. M.; Corey, E. J. J. Am. Chem. Soc. 1999, 121, 7600-
7605. (c) For an example of methyldebromination with Me4CoLi2, see:
Kauffmann, T.; Stach, D. Chem. Ber. 1992, 125, 913-922. (d) For an
example of oxidation to R-bromo enones, see: Della, E. W.; Pigou, P.
E. Aust. J. Chem. 1983, 36, 2261-2268. (e) For examples of dehydra-
tion to 2-bromo dienes, see: Kozikowski, A. P.; Tueckmantel, W. J.
Org. Chem. 1991, 56, 2826-2837. Spangler, C. W.; Woods, G. F. J.
Org. Chem. 1963, 28, 2245-2248. (f) For an example of Mitsunobu
aminodehydroxylation, see: Murphy, J. A.; Scott, K. A.; Sinclair, R.
S.; Martin, C. G.; Kennedy, A. R.; Lewis, N. J. Chem. Soc., Perkin
Trans. 1 2000, 2395-2408. (g) For an example of hydrodebromination
to the corresponding allyl alcohol using Bu3SnH/AIBN, see: Chen, C.;
Crich, D. Tetrahedron 1993, 49, 7943-7954. (h) For examples of
dehydrobromination to the corresponding propargyl alcohol, see:
Lespieau, R. C.R. Hebd. Seances Acad. Sci. 1911, 152, 879-881.
Lespieau, R. C.R. Hebd. Seances Acad. Sci. 1910, 150, 113-114. Also
see ref 5c.
(6) (a) Chen, C.; Crich, D. Tetrahedron 1993, 49, 7943-7954. (b)
Nagasawa, K.; Ishihara, H.; Zako, Y.; Shimizu, I. J. Org. Chem. 1993,
58, 2523-2529.
(7) (a) Spangler, C. W.; Woods, G. F. J. Org. Chem. 1963, 28, 2245-
2248. (b) McDonald, F. E.; Schultz, C. C. J. Am. Chem. Soc. 1994, 116,
9363-9364.
(8) Smith, A. B.; Levenberg, P. A.; Jerris, P. J.; Scarborough, R. M.;
Wovkulich, P. M. J. Am. Chem. Soc. 1981, 103, 1501-1513.
(9) Barbero, A.; Cuadrado, P.; Fleming, I.; Gonzalez, A. M.; Pulido,
F. J.; Rubio, R. J. Chem. Soc., Perkin Trans. 1 1993, 1657-1662.
(10) For an example of an acetate ester derivative (R1 ) R2 ) Me;
50% yield), see: Sandler, S. R. J. Org. Chem. 1967, 32, 3876-3881.
(11) (a) R1 ) Me, R2 ) Me, Ph, cyclopropyl, -CHdCH2 (45-60%
yields), see: Molchanov, A. P.; Kostikov, R. R. Russ. J. Org. Chem.
1993, 29, 429-435. Sydnes, L. K.; Hemmingsen, T. H. Acta Chem.
Scand., Ser. B 1985, 39, 93-102. (b) R1 ) Me, R2 ) COOH (3% yield),
see: Svendsen, J. S.; Sydnes, L. K. Acta Chem. Scand. 1990, 44, 202-
204.
(17) Stang, P. J. Chem. Rev. 1978, 78, 383-405.
(18) Braun, M. Angew. Chem., Int. Ed. 1998, 37, 430-451.
(19) A preliminary account of some of these studies has appeared
in: Novikov, Y. Y.; Sampson, P. Org. Lett. 2003, 5, 2263-2266. (b)
Novikov, Y. Y.; Sampson, P. Presented at the 228th American Chemical
Society National Meeting, Philadelphia, PA, Aug 22-26, 2004; ORGN
595.
(20) The Trapp mixture is THF, ether, and pentane (4:1:1 by
volume). This mixture has a sufficiently low viscosity at -110 to -115
°C to provide a useful reaction medium.
(12) Tamao, K.; Maeda, K.; Yamaguchi, T.; Ito, Y. J. Am. Chem. Soc.
1989, 111, 4984-4985.
(21) Xidos, J. D.; Li, J.; Zhu, T.; Hawkins, G. D.; Thompson, J. D.;
Chuang, Y.-Y.; Fast, P. L.; Liotard, D. A.; Rinaldi, D.; Cramer, C. J.;
Truhlar, D. G. GAMESSPLUS, version 3.9; University of Minnesota:
Minneapolis, MN, 2003. Based on the General Atomic and Molecular
Electronic Structure System (GAMESS) as described in: Schmidt, M.
W.; Baldridge, K. K.; Boatz, J. A.; Elbert, S. T.; Gordon, M. S.; Jensen,
J. H.; Koseki, S.; Matsunaga, N.; Nguyen, K. A.; Su, S. J.; Windus, T.
L.; Dupuis, M.; Montgomery, J. A. J. Comput. Chem. 1993, 14, 1347-
1363.
(13) Ko¨brich, G.; Flory, K. Chem. Ber. 1966, 99, 1773-1781. Ko¨brich,
G. Angew. Chem., Int. Ed. 1967, 6, 41-52.
(14) Campos, P. J.; Sampedro, D.; Rodriguez, M. A. Organometallics
1998, 17, 5390-5396.
(15) Kasatkin, A.; Whitby, R. J. J. Am. Chem. Soc. 1999, 121, 7039-
7049.
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60, 777-778.
10248 J. Org. Chem., Vol. 70, No. 25, 2005

1-Bromo-1-lithioethene in Organic Synthesis
TABLE 1. Reaction of 1 with Simple Carbonyl Compounds R1C(dO)R2
entry
R1
R2
product
isolated yield (%)
1
2
3
4
5
6
7
Me
Me
Me
Me
2a
2b
2c
77
78
84
85
80
81
74
H2CdCH-
H2CdCH-CH2-CH2-
-CH2CH2-CH2-CH2-CH2-
2d
2ea
2f
-CHdCH-C(Me2)-CH2-CH2-
Ph
H2CdCH-
H
H
2ga
a No traces of 1,4-addition products were detected.
SCHEME 1. Reaction of Bromoethene with
Different Alkyllithium Bases
TABLE 2. Calculated Liquid-Phase Transition-State
Barriers for Deprotonation and Halogen-Metal
Exchange Reactions of Bromoethene in THF
FIGURE 1. Experimental setup used for the preparation (A)
and electrophilic trapping (B) of 1-bromo-1-lithioethene (1).
TS barrier
During our experimental work, we noticed that the
yield of the 2-bromo-1-alken-3-ol products 2 (Table 1) was
heavily dependent on the aggregation state of 1. Only if
1 existed as a solid phase could consistently high yields
be obtained in the subsequent trapping with an electro-
phile. We actually observed that a freshly prepared (at
-112 to -115 °C) solution of 1 was metastable; it could
spontaneously “crystallize” to produce a solid form of 1
as a white slurry. Fortunately, this phase transition did
not dramatically increase the reaction mixture viscosity,
so efficient stirring was still possible. Although 1 is not
very stable in solution (about 50% decomposition was
observed during 1 h at -115 °C), the crystalline form of
1 could be kept for 4 h at -112 to -115 °C without
noticeable degradation. When the solution was warmed,
a sharp phase transition usually took place over 2-5 min
at -105 to -104 °C, after which a clear solution was
formed. At this point, no 1-bromo-1-lithioethene (1) could
be detected in the resulting reaction mixture on the basis
of electrophilic trapping experiments.
entry
R-
reaction
deprotonation
(kcal/mol)a
1
2
3
4
methyl anion
methyl anion
10
16
5
halogen-metal exchange
tert-butyl anion deprotonation
tert-butyl anion halogen-metal exchange
5
a Activation energies calculated using liquid-phase ab initio
HF6-31G*/SM5.42R methods.21
tional freedom of n-butyl anion, we used methyl anion
as a surrogate nucleophile/base.
Computational results suggest that the formation of
1-bromo-1-lithioethene (1) is the kinetically favored
process when methyl anion is the nucleophile (Table 2,
entries 1 and 2). In contrast, the comparable calculated
activation energies for deprotonation (entry 3) and halo-
gen-metal exchange (entry 4) are consistent with the
formation of a mixture of products when tert-butyllithium
was allowed to react with bromoethene.
It is important to note that the bromine atom in 1
seems to originate almost entirely from the starting
bromoethene. It is well-known that 1-halo-1-lithioalkenes
are quite susceptible to nucleophilic substitution of the
halogen.17,22 However, we were not able to detect any
iodine-containing organic compounds when bromoethene
was deprotonated in the presence of 0.5 equiv of LiI, and
was then trapped by benzaldehyde. 1-Iodo-1-lithioethene
should be sufficiently stable to be trapped under these
conditions,14 indicating that no 1-iodo-1-lithioethene is
generated during this reaction.
It is important to note that all experimental results
presented above were reliably obtained when our original
glass reactor19 (Figure 1) was used to conduct the
deprotonation step. However, when the design of the
glass reactor was significantly modified (to allow the
option of adding 1 to an electrophile), the desired phase
transition did not always reproducibly occur under ap-
(22) Lucchini, V.; Modena, G.; Pasquato, L. J. Am. Chem. Soc. 1995,
117, 2297-2300.
J. Org. Chem, Vol. 70, No. 25, 2005 10249

Novikov and Sampson
TABLE 3. Addition of 1 to Carbohydrate-Derived Ketones
a Determined by 1H NMR analysis of the crude reaction mixture. b Attack of 1 from the less-crowded convex face of the ketone is
assumed. c Yield based on 1H NMR analysis of the crude reaction mixture. The reaction mixture also included 45% of 5c and 46% of
unreacted 5a. d CeBr3 (0.1 equiv) was used as an additive. e Major diastereomer structure was assigned using NOE studies. f Me3SiCl (1
equiv) was used as an additive. g An inseparable mixture of diastereomers was obtained. In this case, the isolated yield is for this mixture
of diastereomeric products.
parently identical conditions. We attempted to reoptimize
the solvent system as well as the concentrations of
reagents, but still could not achieve complete reproduc-
ibility of the crystallization. Attempts to modify the
solvent composition by changing from THF (mp -108 °C)
to THP (mp -45 °C) and/or from n-pentane (mp -130
°C) to n-heptane (mp -91 °C) resulted in significantly
lower yields of 1, even at -110 °C, and complete freezing
of the reaction mixture was frequently observed in these
cases.
To further explore these unexpected observations, we
carefully measured the temperature gradients in the
apparatus that afforded highly reproducible results
(Figure 1). We observed that the viscosity of methylcy-
clohexane (which was always used in conjunction with
liquid nitrogen as the external coolant, mp -127 °C)
significantly increased when the temperature dropped
below -110 °C. This caused a temperature difference of
ca. 15 °C along the height of the reactor, which did not
change appreciably with more efficient coolant stirring.
10250 J. Org. Chem., Vol. 70, No. 25, 2005

1-Bromo-1-lithioethene in Organic Synthesis
SCHEME 2. Diastereoselectivity of
After a short time, the frozen coolant formed a bridge
between the bottom of the heat exchanger and the flask
wall (Figure 1B). This, in turn, caused the region of the
flask wall in contact with the frozen coolant to tempo-
rarily cool below -127 °C. This cold spot reproducibly
caused the crystallization of 1. Again, because the aver-
age temperature in the reaction flask was usually about
-115 °C during this process, the main bulk of the solvent
did not freeze. After this crystallization of 1, the resulting
slurry could safely be kept at -112 °C without noticeable
decomposition.
Interestingly, the sequence of temperature changes
described above occurs without variation because of the
intrinsic properties of the methylcyclohexane coolant. An
attempt to use n-pentane as the coolant decreased the
temperature gradients within the setup to ca. 2 °C (at
-120 °C), and instead of crystallization of 1, freezing of
the bulk solution was often observed. The experimental
procedure is rather simple, and except for the all-glass
reaction vessel itself, no custom-made equipment is
necessary. Further technical details are presented in the
Experimental Section.
Vinylmagnesium Bromide Addition to 12a
afforded a 1:1 mixture of diastereomeric adducts.24 More
highly diastereoselective (4:1) â-face addition reactions
were observed for the addition of 2-(trimethylsilyl)-
ethynyllithium to the corresponding â-anomer of 9a.23
Although the highly diastereoselective addition of vinyl-
magnesium bromide to the closely related â-anomeric
A-ulose sugar derivatives 12a has been reported25 (Scheme
2), these reactions afforded the epimeric adducts resulting
from an R-face attack at the ketone. The authors at-
tributed the high R-selectivity to Mg2+ chelation with the
C-4 carbonyl oxygen and oxygen centers within the C-3
protecting group,26 followed by nucleophilic attack from
the less-crowded equatorial direction.27
It appears that such chelation effects are not observed
with alkynyllithium or alkynyl Grignard reagents, or
with 1-bromo-1-lithioethene (1). This observation is
consistent with reactions of 1 with other sugar-derived
ketones (7a and 8a, Table 3, entries 4 and 5), in which
the major products formed are consistent with the
domination of steric factors over chelation effects.
These studies also demonstrated the remarkable
chemoselectivity of 1. For example, acetate and tosylate
moieties proved reasonably stable under the reaction
conditions used (Table 3, entries 5 and 7). Ketone 10a is
usually quite susceptible to E1cb elimination; indeed, 10a
could be completely converted to the corresponding R,â-
unsaturated ketone by treatment with DBU for 15 min
at room temperature.28 However, no traces of such
elimination byproducts could be detected in the crude
To evaluate the scope and limitations of the synthetic
utility of 1, we next examined more structurally complex
carbohydrate-derived ketones as electrophiles. Initial
studies were focused on the reaction of 1 with glucose-
derived ketone 5a. To our disappointment, only 9% (by
1H NMR analysis) of the desired bromoethenyl adduct
5b was formed (albeit as a single diastereomer; Table 3,
entry 1), accompanied by 46% of the starting ketone 5a
and 45% of the acetylenic adduct 5c. It is important to
note that 5c most probably did not originate from the
bromoethenyl adduct 5b. In a separate experiment, the
very similar adduct 9b exhibited no reaction when it was
subjected to a solution containing LDA or DBU, even at
room temperature. Instead, it seems likely that 5c was
formed via decomposition of 1 to ethynyllithium, followed
by nucleophilic addition to 5a.
After considerable experimentation, we found that
addition of CeBr3 (0.1 equiv) dramatically increased the
yield of 5b (from 5a) as well as 6b (from 6a) (Table 3,
entries 2 and 3). Further experimentation revealed that
Me3SiCl (0.5-1 equiv) also significantly improved the
yields of the desired 1-bromoethenyl adducts (Table 3,
entries 4-8). Regardless of the additive used, it was also
observed that a 1.5-2-fold excess of 1-bromo-1-lithioet-
hene (1) was necessary to obtain reproducible results.
Surprisingly high overall diastereoselectivities were
observed, even for ketones that do not possess an obvious
intrinsic facial bias. For example, ketone 9a (entry 6)
afforded a 95:5 mixture of diastereomeric products. In
contrast, reaction of 9a with 2-(trimethylsilyl)ethynyl-
lithium (THF, 0 °C) afforded only a 1.5:1 mixture of
diastereomeric propargyl alcohol products, with the major
diastereomer resulting from the same â-axial face attack
at the ketone.23 These authors found that the use of more
sterically demanding TBS protecting groups at C-3, C-4,
and C-6 allowed for completely diastereoselective axial
addition to the â-face. Similarly, addition of 1.2 equiv of
ethynylmagnesium bromide to ketone 9a (THF, 0 °C)
1
reaction mixture (by H NMR analysis) when 10a was
allowed to react with 1. No evidence for competing
enolization was seen in any of the reactions reported in
Table 3; the stereochemistry at each epimerizable ste-
reogenic center appeared unchanged after each reaction.
During our preliminary work,19 we observed that
reaction of simple conjugated aldehydes (benzaldehyde,
acrolein) with 1 gave good yields of the desired addition
products (see Table 1, entries 6 and 7). In contrast, simple
aliphatic aldehydes afforded only modest yields of 2-bromo-
1-alken-3-ol products on reaction with 1 (Table 4, entry
1). Yields dropped even further when protected R-hydroxy
aldehydes were used as electrophiles to trap 1. Attempts
to use various additives invariably led to even lower
yields of the desired adducts. In every case, unreacted
aldehyde was recovered as the major byproduct. Non-
(24) Norris, P. Youngstown State University, Youngstown, OH.
Personal communication, 2005.
(25) Thoma, G.; Schwarzenbach, F.; Duthalet, R. O. J. Org. Chem.
1996, 61, 514-524.
(26) Miljkovic, M.; Gligorijevic, M.; Satoh, T.; Miljkovic, D. J. Org.
Chem. 1974, 39, 1379-1384.
(27) Of course, the R-anomer would suffer increased steric crowding
on the R-face, which might have eroded this high stereocontrol;
unfortunately, no studies along these lines have been published.
(28) Davis, B. G.; Nash, R. J.; Watson, A. A.; Smith, C.; Fleet, G.
W. Tetrahedron 1999, 14, 4501-4520.
(23) Daly, S. M.; Armstrong, R. W. Tetrahedron Lett. 1989, 30,
5713-5716.
J. Org. Chem, Vol. 70, No. 25, 2005 10251

Novikov and Sampson
TABLE 4. Reaction of 1 with Aldehydes
a Determined by 1H NMR analysis of the crude reaction mixture after hydrolysis of the trimethylsilyl ether group. b Two equivalents
of Me3SiCl and three equivalents of 1 were used. c Isolated yield for the inseparable diastereomeric mixture. d Isolated yield for the major
diastereomer.
enolizable 4-trifluoromethylbenzaldehyde provided the
same low yield of adduct as n-heptanal (Table 4, entry
3), indicating that competing aldehyde enolization was
not the major problem during these reactions. A separate
experiment, in which the products derived from the
reaction of 1 with n-heptanal were quenched by a slight
excess of Me3SiCl followed by careful removal of the
solvent under anhydrous conditions, unexpectedly pro-
vided a 1:1 mixture (by 1H NMR analysis) of 1-bromo-1-
trimethylsilylethene (trapped unreacted 1) and 2-bromo-
3-trimethylsiloxy-1-nonene (15a) (trapped addition
product). No traces of silyl enol ethers derived from
trapping the n-heptanal enolate could be observed.
The above results are consistent with a competitive
trapping of the initially formed alkoxide adduct 13 by a
second molecule of aldehyde, with the facility of this
reaction depending on the electrophilicity of the aldehyde
substrate. Less-electrophilic conjugated aldehydes such
as benzaldehyde and acrolein presumably react more
sluggishly with 13, allowing efficient trapping of 1 by the
aldehyde (Table 1, entries 6 and 7). In contrast, more-
electrophilic aldehydes appear to compete effectively for
13, presumably eventually leading to the formation of
an aldehyde oligomerization product 14 (Scheme 3).
If this mechanism was indeed operating, we considered
that the competitive addition of 1 to an aldehyde in the
presence of Me3SiCl might lead to the preferential
silylation of the intermediate 13 before it could react with
a second molecule of the aldehyde. The success of this
approach would depend on the relative rates of silylation
for unreacted 1 and for the initially formed adduct 13.
Given the hard nature of the alkoxide anion 13, we
anticipated that Me3SiCl might react preferentially with
13 over 1. In practice, addition of a mixture of 2 equiv of
Me3SiCl and 1 equiv of n-heptanal to 3 equiv of 1 at -115
°C afforded a complex product mixture that contained
trimethylsilyl ether 15a as the major product, as well as
some other byproducts. This reaction mixture promptly
hydrolyzed upon contact with silica, precluding purifica-
tion of the silyl ether 15a. However, deliberate hydrolysis
of the silyl ether (aq CF3COOH in CH2Cl2) followed by
vacuum distillation afforded the desired allylic alcohol
16a in 74% yield (Table 4, entry 2). Similarly, reaction
of 4-trifluoromethylbenzaldehyde under these conditions
afforded allylic alcohol 16b in 77% yield (Table 4, entry
4).
To find the most efficient competitive trapping agent,
we surveyed several common silylating reagents. Inter-
10252 J. Org. Chem., Vol. 70, No. 25, 2005

1-Bromo-1-lithioethene in Organic Synthesis
SCHEME 3. Possible Side Reactions of 1 with Highly Electrophilic Aldehydes
SCHEME 4. Reactions of 1 with Protected
tent with the smaller size of the benzyloxy and meth-
oxymethyloxy groups relative to that of the siloxy moieties
(entries 7-10). Somewhat surprising is the low level of
Felkin-Ahn selectivity seen for the t-BuPh2SiO-protected
substrate (Table 4, entry 8), whereas the corresponding
t-BuMe2SiO- and Et3SiO-protected R-hydroxy aldehydes
react with very high Felkin-Ahn control. We currently
have no explanation for these observations.
r-Hydroxy Aldehydes in the Presence of Me3SiCl
estingly, the initially chosen Me3SiCl provided the best
overall yields of the desired adducts. Me3SiI and Me3-
SiOTf were excessively reactive toward 1, resulting in
the predominant formation of 1-bromo-1-trimethylsi-
lylethene, whereas Et3SiCl and t-BuMe2SiOTf were not
sufficiently reactive to efficiently intercept 13.
To further explore the synthetic utility of 1 under these
in situ silylation conditions, we examined a series of
protected R-hydroxy aldehydes as electrophiles. These
reactions were complicated by the formation of bis-
protected diols (Scheme 4), which had to be carefully
hydrolyzed to afford the desired monoprotected diol
product. (Only traces of the corresponding addition
products were obtained without the Me3SiCl additive.)
From a practical standpoint, the t-BuMe2Si-protected
R-hydroxy aldehydes turned out to be the most useful
substrates because it was possible to selectively remove
the Me3Si group while the t-BuMe2Si group remained
intact, and then cleanly isolate the products 17 and 18
as single diastereomers by conventional flash chroma-
tography (Table 4, entries 7 and 9).
Since acylsilanes are often used as masked aldehydes,30
we thought it would be of some interest to examine
commercially available acetyltrimethylsilane as a trap-
ping reagent for 1. Somewhat discouragingly, it was
reported that reactions of R-substituted vinylmetals with
acylsilanes are not clean, and the expected products are
susceptible to Brook rearrangement.31 However, to our
surprise, acetyltrimethylsilane reacted cleanly with 1,
providing the R-silyl alcohol 19 in good yield (Scheme 6).
No evidence for any rearrangement products was ob-
served. Adduct 19 could be distilled and was stable in
THF solution as well as neat in the presence of traces of
tertiary amines. However, a solution of 19 in CH2Cl2
slowly rearranged at room temperature to produce the
unstable R-bromo-R-silyl ketone 2032 (Scheme 6). This
unusual rearrangement reaction was not appreciably
accelerated by the presence of acids (HCl gas, TsOH), and
was completely inhibited by weak bases (pyridine, Et3N)
and even THF. We are not aware of a precedent for this
rearrangement process.
Overall, the experimental data strongly suggest that
the lithium atom in 1 is not available for chelation during
the carbonyl addition reactions reported herein. Along
with the observation that 1 exists as a solid during the
reaction, it seemed likely that the lithium atoms were
tightly coordinated to THF molecules in a crystal and/or
formed a strong association with a bromo substituent in
an adjacent molecule of 1, thus forming a polymeric
structure. The narrow temperature range (2-3 °C) cor-
responding to the transition of the solid form of 1 into
Again, these results showed that a chelation mecha-
nism did not operate during the addition of 1 to variously
protected R-hydroxy aldehydes. In every case, the major
diastereomer of the deprotected product was the anti diol,
suggesting Felkin-Ahn control during the addition of 1
to the aldehyde.
The anti configuration of the products 17 and 18
(entries 7 and 9) was established after complete depro-
tection to the corresponding diols 17a and 18a, followed
by conversion to the cyclic acetonides 17b and 18b,
3
respectively. A comparison of the observed JH3-H4 cou-
pling constants with very closely related literature
compounds29 allowed for determination of the anti ster-
eochemistry (Scheme 5).
High levels of Felkin-Ahn diastereoselectivity were
seen with some R-siloxy aldehydes (e.g., Table 4, entries
7, 9, and 10). The much lower levels of stereocontrol
observed for the R-benzyloxy aldehyde and R-methoxym-
ethyloxy aldehyde (Table 4, entries 5 and 6) are consis-
(30) For reviews on the use of acylsilanes in organic synthesis, see:
(a) Ricci, A.; Deglinnocenti, A. Synthesis 1989, 647-660. (b) Bulman-
Page, P. C.; Klair, S. S.; Rosenthal, S. Chem. Soc. Rev. 1990, 19, 147-
195. (c) Bonini, B. F.; Franchini, M. C.; Fochi, M. Gazz. Chim. Ital.
1997, 127, 619-628. (d) Bonini, B. F.; Comes-Franchini, M.; Fochi,
M.; Mazzanti, G.; Ricci, A. J. Organomet. Chem. 1998, 567, 181-189.
(e) Patrocinio, A. F.; Moran, P. J. S. J. Braz. Chem. Soc. 2001, 12, 7-31.
(31) Kato, M.; Mori, A.; Oshino, H.; Enda, J.; Kobayashi, K.;
Kuwajima, I. J. Am. Chem. Soc. 1984, 106, 1773-1778.
(32) A very limited number of R-halo-R-silyl ketones have previously
been reported. (a) For an example of Hal ) Br, Cl, see: Berti, G.;
Canedoli, S.; Crotti, P.; Macchia, F. J. Chem. Soc., Perkin Trans. 1
1984, 1183-1188. (b) For an example of Hal ) F, see: Enders, D.;
Faure, S.; Potthoff, M.; Runsink, J. Synthesis 2001, 2307-2319.
(29) Pearson, W. H.; Lovering, F. E. J. Org. Chem. 1998, 63, 3607-
3617.
J. Org. Chem, Vol. 70, No. 25, 2005 10253

Novikov and Sampson
SCHEME 5. Establishing the Configuration of the Major Diastereomer Resulting from Trapping 1 with
Protected r-Hydroxy Aldehydes
SCHEME 6. Reactions of 1 with Acetyltrimethylsilane
solution, as well as literature data on related organo-
lithium species,14,18 might suggest that 1 has a crystalline
structure rather than a polymeric one. To further test
this hypothesis, liquid-phase ab initio HF6-31G*/SM5.42R
calculations were undertaken. Because only ground-state
structures were being considered, the balance between
the level of theory used and maximum complexity of the
structure being studied was shifted toward the latter.
Given the enormous amount of time33 required for even
a single geometry optimization of structures such as 21
(Figure 2), no attempts were made to locate global
minima.
On the basis of available literature data,35 our com-
putational results, and the sharp phase transitions
observed for 1, we presume that 1 most probably exists
as a regular monomeric crystalline solid rather than a
polymer. The low viscosity of the 1-bromo-1-lithioethene
(1) slurry at -112 °C might also support this conclusion.
Prior to our studies, it was known that 1-bromo-1-
lithioethene could be trapped with Me3SiCl.16 With a
potential one-step synthesis of small 1,1-difunctionalized
ethene building blocks in mind,12 we have examined the
use of several non-carbonyl electrophiles to trap 1-bromo-
1-lithioethene (1).
A traditional computational strategy was employed,
whereby the starting geometries of solvated dimers 21
and 22 were optimized until local minima were found (no
imaginary vibrations after the corresponding Hessian
calculations). The same procedures were then applied to
their monomeric fragments. Finally, the energetics of the
depolymerization reactions were evaluated (Figure 2).
In accordance with reported calculations for the 1-iodo-
1-lithioethene dimer,14 current calculations support the
notion that 1-bromo-1-lithioethene dimers might be less
energetically favorable than their monomers. In addition,
the optimized geometry at C1 seems significantly more
realistic for monomers than for dimers (Table 5). The
single related crystal structure34 determined by low-
temperature X-ray crystallography (compound 25) was
included in Table 5 for comparison.
The low degree of steric crowding in dichlorodimeth-
ylsilane resulted in bis-coupling with 1 to afford the bis-
ethenylsilane 27 in good yield (Table 6, entry 1). The
corresponding chloro-N,N-diethylaminodimethylsilane did
not react with 1 (entry 2), nor did the more crowded
dichlorodiphenylsilane (entry 3). It was possible to achieve
selective monocoupling with 1 using dichlorodiethylsilane
to afford the ethenylchlorosilane 28, albeit in low yield
(entry 4). Much more respectable yields of selective
monocoupling products were seen for the more crowded
dichlorodiisopropylsilane, leading to the isolation of 29
in 47% yield (entry 5). Compound 29 is a more crowded
variant of the bromoethenyl chlorosilane 3 initially
proposed by Tamao et al.12 as a source of a useful silyl
tether for efficient radical cyclization chemistry. In our
hands, 29 allowed for radical cyclization, to afford 34 in
the same yield as that reported by Tamao from the
corresponding chlorosilane precursor 3 (Scheme 7). How-
(33) A typical optimization took about 3 weeks on a desktop 2.4 GHz
Pentium 4 computer with 1 GB memory; this precluded the use of an
MP2 correlation correction as well as HF/DFT methods available
within the GAMESOL package.
(34) Maercher, A. Angew. Chem., Int. Ed. 1993, 32, 1023-1025.
(35) Braun, M. Angew. Chem., Int. Ed. 1989, 28, 896-989.
10254 J. Org. Chem., Vol. 70, No. 25, 2005

1-Bromo-1-lithioethene in Organic Synthesis
FIGURE 2. Computational attempts to delineate the possible structure of 1.
TABLE 5. Calculated Geometry Data for
SCHEME 7. Application of 29 in Construction of a
Silyl Tether for Radical Cyclization Chemistry
1-Bromo-1-lithioethene (1) Dimers and Monomers
C1-Hal bond
elongation C2-C1-Hal C2-C1-Li
source
of data
structure
(Å)
angle (deg) angle (deg)
25 (reference)
24 (monomer)
23 (monomer)
21 (dimer)
0.12a
0.31b
0.32b
1.00b
1.18b
112.6
107
108
104
98
137.1
148
X-ray
computation
computation
computation
computation
170
154
158
22 (dimer)
a Compared with that of 26. b Compared with the calculated
C-Br bond length for bromoethene (same basis set).
a Relative stereochemistry is supported by NOE studies.
chromatography, whereas the corresponding dimethyl-
silyl analogues of 33 and 34 are labile on silica.
TABLE 6. Trapping of 1 with Silicon- and Tin-Based
Electrophiles
As expected, chloromethyldimethylsilyl chloride reacts
cleanly with 1 at the silicon atom; treatment of the crude
product with NaI in anhydrous acetone allowed for the
isolation of the bromoethenyl iodomethylsilane 30 (Table
6, entry 6). We envisaged that 30 might serve as a useful
building block (analogous to 29) in the construction of a
siloxy tether for radical cyclization chemistry; however,
30 did not react with secondary alcohols under the
various conditions examined.
We also were interested in the preparation of bromo-
ethenylstannane 31 as a potential building block. No
examples of 1-haloethenylstannanes have previously
been reported, although the corresponding 2-haloethe-
nylstannanes have been prepared36 and, in one case, were
shown to be useful substrates for transmetalation and
Diels-Alder cycloaddition.37 Trapping 1 with Bu3SnCl
afforded 31 in moderate yield (Table 6, entry 7) along
with unreacted Bu3SnCl. During this experimental work
we noticed that fast addition (over 5-10 s instead of the
usual 5-25 min) of a precooled Bu3SnCl solution to a
slurry of 1 uniformly gave better yields of the desired
bromoethenylstannane 31 (Table 6, entry 7). Similar
improvements in the trapping of 1 by I2 were also
observed (Table 6, entry 8). Surprisingly, 1-bromo-1-
iodoethene has not previously been reported.38 However,
a Initially formed chloromethylsilane was not isolated but
instead converted into iodomethylsilane 30 by reaction with NaI/
acetone. b Range of yields observed for 5 runs. c Losses during
distillation limited the preparative yield.
(36) Barbero, A.; Cuadrado, P.; Fleming, I.; Gonzalez, A. M.; Pulido,
F. J.; Rubio, R. J. Chem. Soc., Perkin Trans. 1 1993, 1657-1662.
(37) Singleton, D. A.; Leung, S.-W.; Martinez, J. P.; Lee, Y.-K.
Tetrahedron Lett. 1997, 38, 3163-3166.
(38) The closely related 1-bromo-1-chloroethene was mentioned in
the literature (Havel, J. J.; Skell, P. S. J. Am. Chem. Soc. 1972, 94,
1792-1793. Agre, C. L.; Hilling, W. J. Am. Chem. Soc. 1952, 74, 3895-
3899), but it readily polymerizes and has not found utility as a
synthetic reagent. In contrast, 1,1-dichloroethene is an inexpensive
article of commerce, and has found some synthetic utility. For an
example, see: Qian, M.; Negishi, E. Org. Process Res. Dev. 2003, 7,
412-417.
ever, it should be noted that 29 has two advantages over
3: its preparation requires only one step (instead of 3
steps for 3) and all intermediates (e.g., 33 and 34) are
sufficiently stable to be isolated by conventional flash
J. Org. Chem, Vol. 70, No. 25, 2005 10255

Novikov and Sampson
given the utility of (E)-1-bromo-2-iodoethene as a syn-
thetic building block,39 we anticipate that 1-bromo-1-
iodoethene will be a useful 1,1-difunctionalized ethenyl
synthon.
step access to potentially useful small 1,1-difunctional-
ized ethene building blocks.
Experimental Section
It seems plausible that lithium halides, which were
formed along with the desired product in these reactions,
were crystallizing on the surface of the solid 1, thus
isolating the organolithium from the electrophile. On the
subsequent warm-up step, the rate of diffusion of the
electrophile through a crust of solid lithium salts might
be lower than the rate of thermal decomposition of
residual 1-bromo-1-lithioethene (1), resulting in incom-
plete trapping of the electrophile when it is slowly added
to the reaction mixture. Conversely, fast addition of the
electrophile caused the internal reaction temperature to
rise to -90 °C. At this temperature, 1 became soluble
and would be expected to decompose; however, the rate
of trapping of dissolved 1 with the added electrophiles
was apparently much faster than the rate of its thermal
decomposition, allowing for the generation of the adducts
31 and 32 in reasonable to good yields. We intend to
explore the synthetic utility of these two new synthetic
building blocks; results of these studies will be com-
municated in due course.
During our experimental work we have encountered
some limitations with the synthetic utility of 1-bromo-
1-lithioethene (1). We found that epoxides were com-
pletely unreactive toward 1 even in the presence of BF3‚
Et2O or CeBr3. In addition, crowded ketones such as 2,6-
dimethylcyclohexanone provided only traces of addition
product, independent of the conditions used. Finally,
attempts to conduct transmetalation reactions by using
derivatives of elements that are more electropositive than
Si or Sn (e.g., ZnCl2, ZnBr2, Zn(OTf)2, B(OMe)3, CeCl3,
CeBr3, ClTi(Oi-Pr)3, Cl2Ti(Oi-Pr)2, and BeCl240) under
various conditions have failed, to date, to afford any
synthetically useful results.
General Procedure A: Reaction of 1-Bromo-1-lithio-
ethene (1) with Acetone To Prepare 3-Bromo-2-methyl-
but-3-en-2-ol (2a). A solution of bromoethene (3.0 mL, 42.5
mmol), lithium bromide (0.23 g, 3.2 mmol), and the Trapp
mixture (THF:ether:pentane, 4:1:1 by volume, 20 mL) was
placed into the central flask of the low-temperature reactor
described in the Supporting Information. A mixture of anhy-
drous THF (19 mL) and anhydrous ether (7 mL) was placed
into the side tube. The reactor was cooled to -70 °C (methyl-
cyclohexane/liquid N2), and n-butyllithium (8.1 mL, 16.1 mmol,
2 M in pentane) was added to the side tube. The main bubbler
was temporarily stopped for ca. 10 s (argon started to bubble
through the side tube, mixing the contents of the side tube),
and the unit was then further cooled with liquid nitrogen to
-110 °C. At this point the auxiliary bubbler was stopped, and
the contents of the side tube were slowly transferred to the
main flask using argon pressure. (To achieve good yields, this
addition should be done over 15-30 min, and the temperature
should be in the -110 to -115 °C range.) After the addition,
the side tube was washed with the Trapp mixture (2 × 1.5
mL). Liquid nitrogen was added to the heat exchanger tube
until the bridge of the frozen coolant between the reactor and
the heat exchanger was formed (Figure 1B). This condition
was indicated by attempting to slightly move an outer Dewar
vessel. When the bridge is formed, the Dewar vessel cannot
be moved any more. At this moment, the crystallization of 1
had usually occurred. Addition of liquid nitrogen was ceased
until the bridge of the frozen coolant had melted (temperature
should not rise above -112 °C). This process was usually
completed in 20 to 40 min. The cloudy mixture was stirred for
30-40 min at -112-115 °C to complete the deprotonation of
bromoethene.
A solution of acetone (1.0 mL, 14 mmol) in the Trapp
mixture (10 mL) was placed into the side tube. After thermal
equilibration (usually 5-10 min), the contents of the side tube
were transferred as described above to the central flask over
2-15 min. (The time for this addition was not so critical.) The
reaction mixture was stirred at -110 to -105 °C for 30 min.
A solution of acetic acid (1.05 mL, 1.25 mmol) in the Trapp
mixture (15 mL) was placed into the side tube and, 5 min later,
it was transferred into the central flask. The cooling bath was
removed, and the contents were transferred to a separatory
funnel. The organic layer was washed with 4% aq NaHCO3
(10 mL), washed with brine (10 mL), dried (MgSO4), and
concentrated at atmospheric pressure. Vacuum distillation
gave 3-bromo-2-methylbut-3-en-2-ol (2a) (1.79 g, 77%) as a
colorless liquid which was 99.5% pure by GC, bp 53 °C at 17
mmHg. 1H NMR (300 MHz, CDCl3): δ 1.49 (s, 6H), 2.10 (br s,
Conclusion
1-Bromo-1-lithioethene (1) has proven to be a useful
practical reagent for the selective introduction of the
1-bromoethenyl group into various organic and organo-
metallic substrates. At -110 to -115 °C, 1 affords clean
1,2-addition to carbonyl compounds. It possesses low
basicity and is compatible with acetate, allyl ether, and
tosylate protecting groups. The addition of 1 to chiral
aldehydes and ketones proceeded under Felkin-Ahn
diastereocontrol, providing unusually high diastereomeric
ratios (88:12 to 92:8) of adducts in some cases. Among
simple protected R-hydroxy aldehydes, t-BuMe2Si-pro-
tected compounds provided the highest diastereoselec-
tivities (up to 93:7). For aliphatic aldehydes and protected
R-hydroxy aldehydes, Me3SiCl was necessary as an
additive to suppress undesirable side reactions. Epoxides
and crowded ketones were not sufficiently electrophilic
to react with 1. However, several dichlorosilanes, acetyl-
trimethylsilane, tributyltin chloride, and iodine proved
to be efficient electrophiles for trapping 1, providing one-
2
2
1H, OH), 5.49 (d, J ) 2.3 Hz, 1H), 5.89 (d, J ) 2.3 Hz, 1H).
13C NMR (75 MHz, CDCl3): δ 28.7, 74.1, 115.2, 142.7. Anal.
Calcd for C5H9BrO: C, 36.39; H, 5.50. Found: C, 36.67; H,
5.85.
2-Bromo-3-methylpenta-1,4-dien-3-ol (2b). 2b was pre-
pared according to General Procedure A from 3-buten-2-one
in 78% yield, bp 63 °C at 14 mmHg, and the GC purity was
98%. 1H NMR (400 MHz, CDCl3): δ 1.55 (s, 3H), 2.25 (s, 1H),
5.23 (dd, 3J1 ) 10.6 Hz, 2J2 ) 0.8 Hz, 1H), 5.40 (dd, 3J1 ) 17.2
2
2
Hz, 2J2 ) 0.8 Hz, 1H), 5.57 (d, J ) 2.3 Hz, 1H), 5.94 (d, J )
2.3 Hz, 1H), 6.01 (dd, J1 ) 17.3 Hz, J2 ) 10.7 Hz, 1H). 13C
NMR (100.6 MHz, CDCl3): δ 26.7, 76.1, 114.5, 116.6, 140.2,
141.5. Anal. Calcd for C6H9BrO: C, 40.71; H, 5.12. Found: C,
40.77; H, 5.25.
3
3
2-Bromo-3-methylhepta-1,6-dien-3-ol (2c). 2c was pre-
pared according to General Procedure A from 5-hexen-2-one
in 84% yield, bp 89-91 °C at 14 mmHg, a single peak by GC
analysis. 1H NMR (300 MHz, CDCl3): δ 1.46 (s, 3H), 1.73 (ddd,
(39) For examples, see: (a) Qian, M.; Huang, Z.; Negishi, E. Org.
Lett. 2004, 6, 1531-1534. (b) Haleh, G.; Antunes, L. M.; Organ, M. G.
Org. Lett. 2004, 6, 2913-2916.
(40) Krief, A.; Vos, M. J.; Lombart, S.; Bosret, J.; Couty, F.
Tetrahedron Lett. 1997, 38, 6295-6298.
3
3
2
2J1 ) 13.8 Hz, J2 ) 9.6 Hz, J3 ) 7.1 Hz, 1H), 1.89 (ddd, J1
10256 J. Org. Chem., Vol. 70, No. 25, 2005

1-Bromo-1-lithioethene in Organic Synthesis
) 13.8 Hz, 3J2 ) 9.6 Hz, 3J3 ) 6.2 Hz, 1H), 2.03-2.15 (m, 2H),
took 90 min. (The addition of n-BuLi was done in two steps
because of the insufficient volume of the side tube.) The slurry
of CeBr3 in the Trapp mixture (prepared as described earlier)
was added to the side tube. The main bubbler of the unit was
stopped for 3 min, which allowed for gentle bubbling of argon
through the contents of the side tube (this was necessary to
prevent the precipitation of cerium(III) bromide). The stopper
was then removed from the main bubbler, and was placed on
the auxiliary bubbler. The argon pressure developed in the
side tube (10-20 mmHg) transferred the tube’s contents to
the central flask in ca. 10 s. This addition should be done
quickly to avoid clogging of the capillary tube of the reactor.
No rise in reaction temperature was observed. The yellowish
mixture was stirred for 5 min, and a solution of the starting
ketone 5a19 (4.02 g, 15.5 mmol) in the Trapp mixture (20 mL)
was placed into the side tube. After thermal equilibration (5
min), the contents of the side tube were slowly added over ca.
5 min to the central flask at -110 °C. The side tube was
washed with the Trapp mixture (4 mL). The slurry was stirred
for 45 min at -110 to -108 °C, and then the reaction was
quenched by addition of a solution of acetic acid (3.5 mL, 62
mmol) in the Trapp mixture (25 mL). The cooling bath was
removed, and sat. aq NaHCO3 (25 mL) was added at -20 °C
to the flask. The mixture was stirred overnight, and then the
organic layer was separated, dried over anhydrous sodium
sulfate (5 g), and evaporated. Column chromatography (40 g
silica, petroleum ether:ethyl acetate, 6:1) gave the title com-
3
2.30 (br s, 1H, OH), 4.98 (dm, J ) 10.1 Hz, 1H), 5.05 (ddd,
2
4
2
3J1 ) 17.2 Hz, J1 ) 3.2 Hz, J1 ) 1.6 Hz, 1H), 5.56 (d, J )
2.1 Hz, 1H), 5.83 (ddt, 3J1 ) 16.9 Hz, 3J2 ) 10.3 Hz, 3J3 ) 6.7
Hz, 1H), 5.92 (dd, J1 ) 2.1 Hz, J2 ) 0.36 Hz, 1H). 13C NMR
(75 MHz, CDCl3): δ 27.2, 28.5, 39.4, 76.8, 115.2, 116.5, 138.5,
140.6. Anal. Calcd for C8H13BrO: C, 46.85; H, 6.39. Found:
C, 47.15; H, 6.51.
2
4
1-(1-Bromoethenyl)cyclohexanol (2d). 2d was prepared
according to General Procedure A from cyclohexanone in 85%
yield, bp 62 °C at 1 mmHg, and the GC purity was 98.8%. 1H
NMR (400 MHz, CDCl3): δ 1.20-1.30 (m, 1H), 1.54-1.72 (m,
2
2
5H), 1.74-1.82 (m, 5H), 5.57 (d, J ) 2.3 Hz, 1H), 5.91 (d, J
) 2.3 Hz, 1H). 13C NMR (100.6 MHz, CDCl3): δ 21.9, 25.4,
36.0, 74.4, 115.5, 143.6. Anal. Calcd for C8H13BrO: C, 46.85;
H, 6.39. Found: C, 47.08; H, 6.43.
1-(1-Bromoethenyl)-4,4-dimethylcyclohex-2-enol (2e).
2e was prepared according to General Procedure A from 4,4-
dimethylcyclohex-2-enone in 80% yield, bp 64-65 °C at 1
mmHg, and the GC purity was 96%. 1H NMR (400 MHz,
CDCl3): δ 0.99 (s, 3H), 1.03 (s, 3H), 1.45 (ddd, J1 ) 13.2 Hz,
J2 ) 9.7 Hz, J3 ) 3.3 Hz, 1H), 1.59 (ddd, J1 ) 14.3 Hz, J2 )
9.2 Hz, J3 ) 3.8 Hz, 1H), 1.74 (ddd, J1 ) 12.9 Hz, J2 ) 9.2 Hz,
J3 ) 2.8 Hz, 1H), 2.11 (ddd, J1 ) 12.6 Hz, J2 ) 8.6 Hz, J3 )
2
3.2 Hz, 1H), 2.26 (s, 1H), 5.50 (d, J ) 10.0 Hz, 1H), 5.60 (d,
2
2
2J ) 2.0 Hz, 1H), 5.68 (d, J ) 10.0 Hz, 1H), 5.91 (d, J ) 2.0
Hz, 1H). 13C NMR (100.6 MHz, CDCl3): δ 28.5, 28.8, 32.2, 33.3,
74.1, 118.0, 126.5, 140.6, 142.2. Anal. Calcd for C10H15BrO:
C, 51.97; H, 6.54. Found: C, 52.13; H, 6.74.
1
pound 5b as a white solid (4.76 g, 84%), mp 113-115 °C. H
NMR (400 MHz, CDCl3): δ 1.35 (s, 3H), 1.41 (s, 3H), 1.45 (s,
3H), 1.63 (s, 3H), 3.28 (s, 1H), 3.96 (d, J ) 7.5 Hz, 1H), 4.00
(dd, J1 ) 8.5 Hz, J2 ) 5.8 Hz, 1H), 4.09 (dd, J1 ) 8.5 Hz, J2 )
6.1 Hz, 1H), 4.26 (dt, J1 ) 7.5 Hz, J2 ) 5.9 Hz, 1H), 4.55 (d, 3J
) 3.9 Hz, 1H), 5.86 (d, 2J ) 1.7 Hz, 1H), 5.97 (d, 3J ) 4.0 Hz,
1H), 6.34 (d, 2J ) 1.8 Hz, 1H). 13C NMR (100.6 MHz, CDCl3):
δ 25.5, 26.56, 26.65, 26.8, 67.1, 73.6, 81.7, 83.0, 83.9, 105.4,
109.5, 112.9, 120.6, 127.9. Anal. Calcd for C14H21BrO6: C,
46.04; H, 5.80. Found: C, 46.25; H, 5.68.
2-Bromo-1-phenylprop-2-en-1-ol (2f).41 2f was prepared
according to General Procedure A from benzaldehyde in 81%
yield, bp 87-88 °C at 0.6 mmHg, and the GC purity was 99.5%.
1H NMR (400 MHz, CDCl3): δ 2.74 (br s, OH, 1H), 5.20 (s,
1H), 5.64 (d, J ) 2.0 Hz, 1H), 6.00 (ddd, J ) 1.9, 1.1, 0.2 Hz,
1H), 7.30-7.38 (m, 5H). 13C NMR (100.6 MHz, CDCl3): δ 78.0,
117.9, 126.9, 128.6, 128.7, 135.8, 139.9.
2-Bromopenta-1,4-dien-3-ol (2g). 2g was prepared ac-
cording to General Procedure A from acrolein in 74% yield,
bp 67 °C at 14 mmHg, and the GC purity was 98.6%. 1H NMR
(400 MHz, CDCl3): δ 2.15 (s, 1H), 4.68 (s, 1H), 5.32 (dt, 3J1 )
10.4 Hz, J2 ) 1.2 Hz, 1H), 5.43 (dt, 3J1 ) 17.2 Hz, J2 ) 1.2 Hz,
1H), 5.61 (d, 2J ) 2.0 Hz, 1H), 5.91 (ddd, 3J1 ) 17.2 Hz, 3J2 )
3-C-(1-Bromoethenyl)-5-O-tert-butyldiphenylsilyl-1,2-
O-(1-methylethylidene)-â-L-lyxofuranose (6b). 6b was
obtained from 6a19 (1.0 g, 2.34 mmol) using General Procedure
B, with the exception that the addition of n-butyllithium was
done in a single step because of smaller loading. Column
chromatography (silica, petroleum ether:diethyl ether, 6:1)
gave the title compound 6b (0.838 g, 67%) as a colorless oil.
1H NMR (400 MHz, CDCl3): δ 1.05 (s, 9H), 1.45 (s, 3H), 1.58
(s, 3H), 3.63 (s, 1H), 3.87 (dd, J1 ) 11.1 Hz, J2 ) 6.0 Hz, 1H),
4.00 (dd, J1 ) 11.0 Hz, J2 ) 5.0 Hz, 1H), 4.39 (t, J ) 5.5 Hz,
3
2
4
10.4 Hz, J3 ) 5.6 Hz, 1H), 5.96 (dd, J1 ) 2.1 Hz, J2 ) 1.0
Hz, 1H). 13C NMR (100.6 MHz, CDCl3): δ 76.6, 117.4, 117.6,
135.2, 136.8. Anal. Calcd for C5H7BrO: C, 36.84; H, 4.33.
Found: C, 36.59; H, 4.48.
General Procedure B: 3-C-(1-Bromoethenyl)-1,2:5,6-
bis-O-(1-methylethylidene)-r-D-allofuranose (5b). Anhy-
drous CeBr3 (0.588 g, 1.55 mmol) was stirred in the Trapp
mixture (14 mL) for 4 h at room temperature. Bromoethene
(5.45 mL, 77.4 mmol), lithium bromide (0.35 g, 4.2 mmol), and
the Trapp mixture (18 mL) were placed into the central flask
of the low-temperature reactor (described above). Anhydrous
ether (10 mL) and anhydrous THF (10 mL) were placed into
the side tube. The low-temperature reactor was cooled to -60
°C (methylcyclohexane/liquid nitrogen was used as the cool-
ant), and the first aliquot of n-butyllithium (9.7 mL, 19.4 mmol,
2.0 M in pentane) was added into the side tube. The reactor
was further cooled with liquid nitrogen to -110 °C, and the
contents of the side tube were displaced into the central flask
over 25 min. Anhydrous ether (10 mL), anhydrous THF (10
mL), and the second aliquot of n-butyllithium (9.7 mL, 19.4
mmol, 2.0 M in pentane) were then placed into the side tube.
After thermal equilibration (5 min), the contents of the side
tube were again displaced into the central flask. The side tube
was washed with the Trapp mixture (4 mL). Liquid nitrogen
was added into the heat exchanger until a frozen coolant bridge
was formed, and then the temperature of the reaction mixture
was allowed to rise to -112 °C. The whole process of addition
2
1H), 4.81 (d, J ) 4.2 Hz, 1H), 5.63 (d, J ) 1.8 Hz, 1H), 5.81
2
(d, J ) 4.2 Hz, 1H), 6.20 (d, J ) 1.9 Hz, 1H), 7.35-7.45 (m,
6H), 7.65-7.70 (m, 4H). 13C NMR (100.6 MHz, CDCl3): δ 19.1,
26.8, 27.6, 27.7, 62.4, 79.2, 83.3, 85.1, 104.8, 116.1, 118.3, 127.7,
129.7, 133.2, 133.4, 133.6, 135.7, 135.7. Anal. Calcd for C26H33-
BrO5Si: C, 58.53; H, 6.23. Found: C, 58.58; H, 6.43.
General Procedure C: (2S,3R,3aS,9aS)-3-(1-Bromo-
ethenyl)-5,5,7,7-tetraisopropyl-2-methoxy-1,4,6,8-tetra-
oxa-5,7-disilabicyclo[6.3.0]undecan-3-ol (7b). This proce-
dure used the same approach as described in General Proce-
dure A, except that a solution of ketone 7a42 (1.2 g, 3.74 mmol,
1 equiv) and Me3SiCl (0.47 mL, 3.74 mmol, 1 equiv) in the
Trapp mixture was slowly added to the preformed slurry of 1
(2 equiv) over 5-10 min at -112 °C. Column chromatography
(silica, petroleum ether:ethyl acetate, 10:1) gave the title
compound 7b (1.01 g, 63%, colorless oil) as an inseparable 89:
11 mixture of diastereomers. Data given are for the major
diastereomer. 1H NMR (400 MHz, CDCl3): δ 0.90-1.00 (m,
2H), 1.02-1.15 (m, 24H), 3.25 (s, 1H), 3.51 (s, 3H), 3.85 (dd,
J1 ) 11.1 Hz, J2 ) 7.6 Hz, 1H), 3.98 (dd, J1 ) 6.8 Hz, J2 ) 3.4
Hz, 1H), 4.03 (dd, J1 ) 11.0 Hz, J2 ) 3.4 Hz, 1H), 4.38 (d, J )
6.7 Hz, 1H), 4.90 (s, 1H), 5.84 (d, 2J ) 1.8 Hz, 1H), 6.29 (d, 2J
(41) Mori, M.; Chiba, K.; Okita, M.; Kayo, I.; Ban, Y. Tetrahedron
1985, 41, 375-385.
(42) Batch, A.; Czernecki, S. J. Carbohydr. Chem. 1994, 13, 935-
940.
J. Org. Chem, Vol. 70, No. 25, 2005 10257

Novikov and Sampson
) 1.8 Hz, 1H). 13C NMR (100.6 MHz, CDCl3): δ 56.1, 65.2,
81.1, 81.7, 104.5, 120.4, 130.2 (resonances due to isopropylsilyl
groups are omitted). NOE (400 MHz): irradiation of the vinylic
proton (at 6.29 ppm) resulted in enhancement of the H1 proton
resonance (at 4.90 ppm). Anal. Calcd for C20H39BrO6Si2: C,
46.95; H, 7.68. Found: C, 46.73; H, 7.76.
11a45 (1.15 g, 5.74 mmol) using General Procedure C. Column
chromatography (silica, petroleum ether: ethyl acetate, 3:1)
gave the title compound 11b (1.23 g, 70%) as a colorless oil.
1H NMR (400 MHz, CDCl3): δ 1.30 (s, 3H), 1.52 (s, 3H), 3.59
(s, 1H), 3.69 (dd, J1 ) 7.9 Hz, J2 ) 5.8 Hz, 1H), 4.07 (dd, J1 )
5.8 Hz, J2 ) 3.0 Hz, 1H), 4.27 (d, J ) 8.0 Hz, 1H), 4.40 (t, J )
6.3 Hz, 2H), 5.26 (d, J ) 3.2 Hz, 1H), 5.79 (d, J ) 2.8 Hz, 1H),
6.08 (d, J ) 2.9 Hz, 1H). 13C NMR (100.6 MHz, CDCl3): δ 25.9,
26.2, 64.3, 73.1, 74.8, 75.0, 75.7, 99.2, 111.1, 120.4, 136.5. Anal.
Calcd for C19H25BrO8S: C, 46.26; H, 5.11. Found: C, 45.64;
H, 5.08.
2-C-(1-Bromoethenyl)-3-O-allyl-4-O-acetyl-6-tert-butyl-
diphenylsiloxy-r-D-methylglucopyranoside (8b). 8b was
obtained from 8a43 (0.90 g, 1.76 mmol) using General Proce-
dure C. Column chromatography (silica, petroleum ether:ethyl
acetate, 10:1) gave the title compound 8b (0.545 g, 50%) as a
1
General Procedure D: 2-Bromonon-1-en-3-ol (16a).
This procedure used the same approach as described in
General Procedure C, except that a solution of n-heptanal (1.05
g, 9.19 mmol) and Me3SiCl (2 equiv) in the Trapp mixture was
added to the preformed slurry of 1 (3 equiv) at -115 °C. The
crude mixture was hydrolyzed by vigorous stirring with a CH2-
Cl2/water/CF3COOH mixture (1:1:0.1 by volume) overnight at
30-35 °C. Column chromatography (silica, petroleum ether:
ethyl acetate, 20:3) gave the title compound 16a (1.50 g, 74%)
colorless oil. H NMR (400 MHz, CDCl3): δ 1.07 (s, 9H), 1.97
(s, 3H), 3.00 (s, 1H), 3.51 (d, nJ ) 6.0 Hz, 3H), 3.65-3.80 (m,
2H), 3.84 (ddd, J1 ) 9.9 Hz, J2 ) 4.8 Hz, J3 ) 2.9 Hz, 1H),
3.90 (d, J ) 9.1 Hz, 1H), 4.17 (ddt, J1 ) 13.0 Hz, J2 ) 5.6 Hz,
J3 ) 1.53 Hz, 1H), 4.39 (ddt, J1 ) 13.0 Hz, J2 ) 5.3 Hz, J3 )
1.5 Hz, 1H), 4.96 (s, 1H), 5.15 (dq, J1 ) 10.4 Hz, J2 ) 1.6 Hz,
1H), 5.25 (dq, J1 ) 17.2 Hz, J2 ) 1.7 Hz, 1H), 5.33 (t, nJ ) 9.5
Hz, 1H), 5.87 (ddt, J1 ) 17.2 Hz, J2 ) 10.5 Hz, J3 ) 5.3 Hz,
1H), 5.96 (d, 2J ) 2.6 Hz, 1H), 6.53 (d, 2J ) 2.6 Hz, 1H), 7.35-
7.45 (m, 6H), 7.65-7.75 (m, 6H). 13C NMR (100.6 MHz,
CDCl3): δ 19.2, 20.9, 26.7, 55.5, 62.9, 68.6, 71.5, 74.4, 78.0,
82.1, 101.0, 116.6, 124.0, 127.7, 129.66, 129.70, 131.9, 133.31,
134.7, 135.7, 169.4. NOE (400 MHz): irradiation of the vinylic
proton (at 6.53 ppm) resulted in enhancement of the H4 proton
resonance (at 5.33 ppm); irradiation of the OH group (at 3.00
ppm) resulted in enhancement of the H3 proton resonance (at
3.90 ppm).
1
as a colorless oil. H NMR (400 MHz, CDCl3): δ 0.90 (t, J )
6.8 Hz, 3H), 1.25-1.35 (m, 8H), 1.55-1.75 (m, 2H), 2.14 (s,
2
1H), 4.09 (t, J ) 6.5 Hz, 1H), 5.56 (d, J ) 1.9 Hz, 1H), 5.88
2
(d, J ) 1.1 Hz, 1H). 13C NMR (100.6 MHz, CDCl3): δ 14.1,
22.6, 25.1, 29.0, 31.7, 35.3, 76.1, 116.9, 137.7. Anal. Calcd for
C9H17BrO: C, 48.88; H, 7.75. Found: C, 49.08; H, 7.80.
1-(4-Trifluoromethylphenyl)-3-propen-1-ol (16b). 16b
was prepared according to General Procedure D from p-
trifluoromethylbenzaldehyde (1.22 g, 7.0 mmol). The crude
mixture was hydrolyzed by vigorous stirring with a CH2Cl2/
water/CF3COOH mixture (1:1:0.1 by volume) overnight at 30-
35 °C. Column chromatography (silica, petroleum ether:ethyl
acetate, 5:1) gave the title compound 16b (1.52 g, 77%) as a
4-C-(1-Bromoethenyl)-2,3,6-tri-O-benzyl-r-D-methyl-
glucopyranoside (9b). 9b was obtained from 9a44 (0.95 g,
2.05 mmol) using General Procedure C. Column chromatog-
raphy (silica, petroleum ether:ethyl acetate, 3:1) gave the title
1
compound 9b (0.805 g, 69%) as a colorless oil. H NMR (400
1
colorless oil. H NMR (400 MHz, CDCl3): δ 2.81 (s, 1H), 5.32
MHz, 80% C6D6 + 20% CDCl3): δ 3.18 (s, 3H), 3.60 (dd, J1 )
9.5 Hz, J2 ) 6.2 Hz, 1H), 3.64 (s, 1H), 3.79 (dd, J1 ) 9.4 Hz, J2
) 6.8 Hz, 1H), 4.08 (dd, J1 ) 10.1 Hz, J2 ) 3.9 Hz, 1H), 4.20
(d, J ) 8.9 Hz, 1H), 4.21 (s, 2H), 4.27 (t, J ) 6.5 Hz, 1H), 4.48
(d, J ) 11.9 Hz, 1H), 4.60 (d, J ) 3.9 Hz, 1H), 4.66 (d, J )
11.9 Hz, 1H), 4.86 (d, J ) 11.7 Hz, 1H), 4.97 (d, J ) 11.7 Hz,
(s, 1H), 5.72 (d, J ) 1.8 Hz, 1H), 6.06 (dd, J1 ) 2.1 Hz, J2 )
1.0 Hz, 1H), 7.54 (d, J ) 8.7 Hz, 2H), 7.64 (d, J ) 8.2 Hz, 2H).
13C NMR (100.6 MHz, CDCl3): δ 77.3, 118.5, 122.7, 125.45,
125.49, 127.0, 134.9, 143.6. Anal. Calcd for C10H8BrF3O: C,
42.73; H, 2.87. Found: C, 43.31; H, 2.94.
2
2
anti-2-Bromo-4-tert-butyldimethylsiloxyoct-1-en-3-ol
(17). 17 was prepared according to General Procedure D from
2-tert-butyldimethylsiloxyhexanal46 (1.61 g, 7.0 mmol). The
crude mixture was hydrolyzed by vigorous stirring with a CH2-
Cl2/water/CF3COOH mixture (1:1:0.1 by volume) overnight at
30-35 °C. Column chromatography (silica, petroleum ether:
ether, 93:7) gave the title compound 17 (1.18 g, 50%) as a
1H), 5.81 (d, J ) 1.8 Hz, 1H), 6.19 (d, J ) 1.8 Hz, 1H), 7.15
(m, 11H), 7.27 (d, J ) 6.7 Hz, 2H), 7.40 (d, J ) 6.7 Hz, 2H).
13C NMR (100.6 MHz, C6D6): δ 54.9, 69.9, 71.0, 73.2, 73.4, 75.7,
78.0, 79.17, 83.6, 98.6, 120.6, 127.44, 127.48, 127.67, 127.70,
128.18, 128.29, 128.31, 128.44. NOE (400 MHz): irradiation
of the OH proton (at 3.64 ppm) resulted in enhancement of
the H6 (at 3.79 ppm) and H5 (at 4.27 ppm) protons of the
carbohydrate backbone; irradiation of the vinylic proton (at
5.81 ppm) resulted in enhancement of the H2 proton resonance
(at 4.08 ppm).
1
colorless oil. H NMR (400 MHz, CDCl3): δ 0.11 (s, 3H), 0.12
(s, 3H), 0.92 (s, 9H), 1.20-1.55 (m, 6H), 2.63 (s, 1H), 4.01
(apparent quintet, J ) 3.1 Hz, 1H), 4.19 (br d, J ) 4.3 Hz,
1H), 5.62 (t, J ) 1.4 Hz, 1H), 6.06 (dd, J1 ) 1.6 Hz, J2 ) 1.2
Hz, 1H). 13C NMR (100.6 MHz, CDCl3): δ -1.83, -1.76, 15.9,
17.0, 24.2, 27.1, 28.6, 30.7, 71.5, 76.5, 114.1, 127.4. Anal. Calcd
for C14H29BrO2Si: C, 49.84; H, 8.66. Found: C, 50.38; H, 8.93.
anti-2-Bromo-4-tert-butyldimethylsiloxypent-1-en-3-
ol (18). 18 was prepared according to General Procedure D
from 2-tert-butyldimethylsiloxypropanal47 (1.32 g, 7.0 mmol).
The crude mixture was hydrolyzed by vigorous stirring with
a CH2Cl2/water/CF3COOH mixture (1:1:0.1 by volume) over-
night at 30-35 °C. Column chromatography (silica, petroleum
ether:ether, 93:7) gave the title compound 18 (1.01 g, 49%
yield) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 0.10 (s,
6H), 0.90 (s, 9H), 1.09 (d, J ) 6.1 Hz, 3H), 2.65 (d, J ) 2.0 Hz,
1H), 4.05 - 4.16 (m, 2H), 5.61 (dd, J1 ) 1.6 Hz, J2 ) 1.0 Hz,
1H), 6.02 (t, J ) 1.5 Hz, 1H). 13C NMR (100.6 MHz, CDCl3):
δ -5.0, -4.5, 16.8, 25.8, 68.9, 78.7, 117.6, 132.1. Anal. Calcd
for C11H23BrO2Si: C, 44.74; H, 7.85. Found: C, 45.24; H, 7.96.
4-C-(1-bromoethenyl)-2,3-O-(1-methylethylidene)-6-O-
tosyl-r-D-methyltalopyranoside (10b). 10b was obtained
from 10a28 (1.65 g, 4.27 mmol) using General Procedure C.
Column chromatography (silica, petroleum ether:ethyl acetate,
3:1) gave the title compound 10b (1.35 g, 64%) as a colorless
1
oil. H NMR (400 MHz, CDCl3): δ 1.35 (s, 3H), 1.54 (s, 3H),
2.43 (s, 3H), 3.01 (s, 1H), 3.39 (s, 3H), 4.08-4.17 (m, 2H), 4.18
(dd, J1 ) 11.1 Hz, J2 ) 2.6 Hz, 1H), 4.33 (dd, J1 ) 8.33 Hz, J2
) 2.7 Hz, 1H), 4.62 (d, J ) 6.4 Hz, 1H), 4.94 (s, 1H), 5.70 (d,
2
2J ) 1.8 Hz, 1H), 6.20 (d, J ) 1.8 Hz, 1H). 13C NMR (100.6
MHz, CDCl3): δ 21.6, 24.7, 25.9, 55.3, 67.8, 68.3, 72.2, 72.9,
73.5, 97.7, 109.9, 120.9, 128.0, 129.9, 130.9, 132.9, 144.9. NOE
(400 MHz): irradiation of the vinylic proton (at 6.20 ppm)
resulted in enhancement of the OMe resonance (at 3.39 ppm).
Anal. Calcd for C11H15BrO5: C, 43.02; H, 4.92. Found: C, 43.09;
H, 4.97.
4-C-(1-Bromoethenyl)-1,6-anhydro-2,3-O-(1-methyl-
ethylidene)-â-D-talopyranose (11b). 11b was obtained from
(45) Torrente, S.; Noya, B.; Branchadell, V.; Alonso, R. J. Org. Chem.
2003, 68, 4772-4783.
(43) The preparation of 8a is presented in the Supporting Informa-
tion.
(44) Ketone 9a was kindly provided by Dr. Peter Norris, Department
of Chemistry, Youngstown State University.
(46) Midland, M. M.; Koops, R. W. J. Org. Chem. 1990, 55, 5058-
5065.
(47) Lattanzi, A.; Sagulo, F.; Scettri, A. Tetrahedron: Asymmetry
1999, 10, 2023-2036.
10258 J. Org. Chem., Vol. 70, No. 25, 2005

1-Bromo-1-lithioethene in Organic Synthesis
3-Bromo-2-trimethylsilyl-3-buten-2-ol (19). 19 was ob-
tained according to General Procedure A from acetyltrimeth-
ylsilane (1.63 g, 14 mmol) as a colorless liquid (2.03 g, 65%),
bp 45-46 °C at 0.6 mmHg. (To prevent spontaneous rear-
rangement to 20, the distillation glassware was soaked in 40%
aq NaOH for 3 min, and then thoroughly rinsed with distilled
water prior to use; 1% (v/v) pyridine was added to the product
immediately after distillation to stabilize the purified product.)
1H NMR (300 MHz, C6D6): δ 0.18 (s, 9H), 1.37 (s, 3H), 5.41
(d, J ) 1.8 Hz, 1H), 5.67 (d, J ) 1.8 Hz, 1H). 13C NMR (75
MHz, C6D6): δ -3.2, 25.1, 72.0, 113.5, 141.3.
3-Bromo-3-trimethylsilylbutan-2-one (20). A solution of
19 in CH2Cl2 (ca. 1 M) was kept in a glass vessel under argon
for 72 h at room temperature. After the solvent was removed
(rt at 20 mmHg), the crude title compound 20 was obtained
as a 10:1 mixture with 19. 1H NMR (300 MHz, CDCl3): δ 0.17
(s, 9H), 1.81 (s, 3H), 2.38 (s, 3H). 13C NMR (75 MHz, CDCl3):
δ -3.0, 24.9, 61.6, 207.5.
(1-Bromoethenyl)-tri-n-butylstannane (31). 31 was pre-
pared using tributyltin chloride (4.56 g, 14 mmol) according
to General Procedure A, except that the addition of tributyltin
chloride was completed rapidly over 5-10 s, and a solution of
AcOH was not added prior to workup. The title compound was
obtained as a colorless liquid (4.71 g, 85%), bp 108-109 °C at
0.1 mmHg. 1H NMR (300 MHz, CDCl3): δ 0.92 (t, J ) 7.3 Hz,
9H), 1.06 (apparent t, J ) 8.1 Hz, 6H), 1.35 (sextet, J ) 7.7
Hz, 6H), 1.50-1.70 (m, 6H), 6.13 (d, J ) 1.9 Hz, 1H), 6.49 (d,
J ) 1.9 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 11.0, 13.9, 27.4,
28.9, 131.9, 137.6. Anal. Calcd for C14H29BrSn: C, 42.47; H,
7.38. Found: C, 42.83; H, 7.56.
1-Bromo-1-iodoethene (32). 32 was prepared using iodine
(3.55 g, 14 mmol) according to General Procedure A, except
that the addition of iodine was completed rapidly over 5-10
s, and a solution of AcOH was not added prior to workup. The
title compound was obtained as a colorless liquid (1.30 g, 40%),
bp 80-81 °C at 160 mmHg. 1H NMR (300 MHz, CDCl3): δ
6.72 (d, J ) 3.3 Hz, 1H), 6.92 (d, J ) 3.3 Hz, 1H). 13C NMR
(75 MHz, CDCl3): δ 55.3, 134.9. Anal. Calcd for C2H2BrI: C,
10.32; H, 0.87. Found: C, 11.52; H, 1.03.
2,2-Diisopropyl-4,6,6-trimethyl-3-methyleneoctahydro-
1,2-benzoxasilole (34). A solution of 33 (119 mg, 0.33 mmol),
tributyltin hydride (116 mg, 0.39 mmol), and triethylborane
(0.07 mL of a 1 M solution in hexanes) were stirred in benzene
(20 mL) at room temperature for 24 h. The mixture was
concentrated in vacuo. Purification of the crude product by
column chromatography (silica, pentane:ether, 20:1) gave the
title compound 34 (46 mg, 50%) as a colorless oil. 1H NMR
(400 MHz, CDCl3): δ 0.90 (d, J ) 3.1 Hz, 6H), 1.00-1.05 (m,
9H), 1.06-1.10 (m, 8H), 1.27 (d, J ) 7.3 Hz, 3H), 1.39 (t, J )
13.2 Hz, 1H), 1.51 (dq, J1 ) 13.4 Hz, J2 ) 0.8 Hz, 1H), 2.00-
2.10 (m, 1H), 2.78 (sextet, J1 ) 0.8 Hz, 1H), 4.19 (quintet, J )
6.3 Hz, 1H), 5.52 (t, J ) 2.7 Hz, 1H), 5.98 (t, J ) 2.6 Hz, 1H).
13C NMR (75 MHz, CDCl3): δ 12.7, 13.2, 17.3, 17.6, 17.7, 17.9,
20.0, 25.1, 30.2, 32.2, 33.2, 41.2, 45.0, 51.5, 76.5, 123.5, 147.4.
NOE (400 MHz): irradiation of the vinylic proton (at 5.52 ppm)
resulted in enhancement of the Me resonance (at 1.27 ppm).
Anal. Calcd for C17H32OSi: C, 72.79; H, 11.50. Found: C, 72.58;
H, 11.60.
Bis(1-bromoethenyl)dimethylsilane (27). 27 was pre-
pared according to General Procedure A (with the exception
that a solution of AcOH was not added) from dichlorodimeth-
ylsilane (1.81 g, 14 mmol) as a colorless liquid (1.21 g, 64%),
bp 86-88 °C at 16 mmHg. 1H NMR (400 MHz, CDCl3): δ 0.41
(s, 6H), 6.38 (d, J ) 2.0 Hz, 1H), 6.45 (d, J ) 2.0 Hz, 1H). 13
C
NMR (100.6 MHz, CDCl3): δ -3.7, 132.9, 133.5. Anal. Calcd
for C6H10Br2Si: C, 26.69; H, 3.73. Found: C, 26.68; H, 3.83.
General Procedure E: Preparation of (1-Bromoeth-
enyl)chlorodiethylsilane (28) from Dichlorodiethylsi-
lane. General procedure A was used but with a different
workup procedure: instead of the addition of an AcOH
solution, the reaction mixture was warmed and diluted with
a 3-fold excess (by volume) of anhydrous pentane. The lithium
salts were filtered off, and the solvents were removed from
the filtrate by distillation at atmospheric pressure. Vacuum
distillation of the residual oil gave title compound 28 as a
colorless oil (1.01 g, 26%), bp 72-74 °C at 17 mmHg. 1H NMR
(400 MHz, CDCl3): δ 0.96-1.10 (m, 10H), 6.48 (d, J ) 1.9 Hz,
1H), 6.56 (d, J ) 1.9 Hz, 1H). 13C NMR (100.6 MHz, CDCl3):
δ 6.5, 7.0, 130.2, 133.9.
(1-Bromoethenyl)chlorodiisopropylsilane (29). 29 was
prepared according to General Procedure E from dichlorodi-
isopropylsilane (2.59 g, 14 mmol) as a colorless liquid (1.68 g,
47%), bp 94-96 °C at 16 mmHg. 1H NMR (400 MHz, CDCl3):
δ 1.08-1.10 (m, 12 H), 1.41 (septet, J ) 7.4 Hz, 2H), 6.53 (d,
J ) 1.9 Hz, 1H), 6.59 (d, J ) 1.9 Hz, 1H). 13C NMR (100.6
MHz, CDCl3): δ 13.2, 16.7, 17.3, 128.5, 134.7.
Acknowledgment. Y.Y.N. acknowledges Kent State
University for a University Fellowship. We thank Larry
Mauer for his help with making the low-temperature
glass reactor, Dr. Mahinda Gangoda for his assistance
with NOE experiments, and Nataliya Chumachenko for
useful discussions. Dr. Peter Norris (Youngstown State
University) is gratefully acknowledged for providing a
sample of ketone 9a.
(1-Bromoethenyl)iodomethyldimethylsilane (30). 30
was prepared according to General Procedure E from chloro-
(chloromethyl)dimethylsilane (1.74 g, 12.2 mmol). The volatile
components were removed from the crude reaction product in
vacuo, and the residue was treated with a saturated solution
of sodium iodide in anhydrous acetone (10 mL) at reflux for
20 h. Water (20 mL) was added; the mixture was extracted
with petroleum ether (2 × 20 mL), and the combined organic
extracts were dried (MgSO4). Vacuum distillation gave the title
compound 30 as a colorless oil (1.22 g, 33%), bp 105-110 °C
at 17 mmHg. 1H NMR (400 MHz, CDCl3): δ 0.36 (s, 6H), 2.16
Supporting Information Available: General experimen-
tal procedures, design of the low-temperature glass reactor
used in these studies, details of the preparation of the ketone
precursor 8a, experimental details related to Table 4 (entries
5, 6, 8), and copies of 1H and 13C NMR spectra for compounds
2a-2g, 5b-11b, 16a, 16b, 17, 18, 17a, 18a, 17b, 18b, 19,
20, 28-34, 36, and 37. This material is available free of charge
via the Internet at http://pubs.acs.org.
(s, 2 H), 6.30 (d, J ) 2.1 Hz, 1H), 6.39 (d, J ) 2.1 Hz, 1H). 13
C
NMR (100.6 MHz, CDCl3): δ -16.1, -3.5, 131.7, 134.8. Anal.
Calcd for C5H10BrISi: C, 19.69; H, 3.30. Found: C, 20.69; H,
3.35.
JO051125V
J. Org. Chem, Vol. 70, No. 25, 2005 10259