Effect of solvent and temperature on the lithium?bromine exchange of vinyl bromides: Reactions of n -butyllithium and t -butyllithium with (E)-5-bromo-5-decene

Article abstract of DOI:10.1021/jo100303q

The outcome of reactions of (E)-5-bromo-5-decene (1), a representative vinyl bromide, with t-BuLi or n-BuLi at 0 °C and room temperature, respectively, in a variety of solvent systems has been investigated. Vinyl bromide 1 does not react with t-BuLi in pure heptane; however, the presence of even small quantities of an ether in a predominantly heptane medium resulted in virtually complete consumption of 1 at 0 °C, resulting in nearly the same distribution of products, including 60?80% of (Z)-5-decenyllithium, regardless of the solvent composition. Vinyl bromide 1 reacts slowly with n-BuLi at room temperature in a variety of ether and heptane-ether mixtures to afford a mixture of products including significant quantities of recovered starting material. The results of these experiments demonstrate that lithium?bromine exchange between a vinyl bromide and either t-BuLi or n-BuLi at temperatures significantly above ?78 °C is not an efficient method for the generation of a vinyllithium.

Full text of DOI:10.1021/jo100303q

pubs.acs.org/joc
Effect of Solvent and Temperature on the Lithium-Bromine Exchange
of Vinyl Bromides: Reactions of n-Butyllithium and t-Butyllithium
with (E)-5-Bromo-5-decene
William F. Bailey,* Mark R. Luderer, Daniel P. Uccello, and Ashley L. Bartelson
Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060
william.bailey@uconn.edu
Received February 17, 2010
The outcome of reactions of (E)-5-bromo-5-decene (1), a representative vinyl bromide, with t-BuLi or
n-BuLi at 0 °C and room temperature, respectively, in a variety of solvent systems has been
investigated. Vinyl bromide 1 does not react with t-BuLi in pure heptane; however, the presence of
even small quantities of an ether in a predominantly heptane medium resulted in virtually complete
consumption of 1 at 0 °C, resulting in nearly the same distribution of products, including 60-80% of
(Z)-5-decenyllithium, regardless of the solvent composition. Vinyl bromide 1 reacts slowly with
n-BuLi at room temperature in a variety of ether and heptane-ether mixtures to afford a mixture of
products including significant quantities of recovered starting material. The results of these
experiments demonstrate that lithium-bromine exchange between a vinyl bromide and either
t-BuLi or n-BuLi at temperatures significantly above -78 °C is not an efficient method for the
generation of a vinyllithium.
Introduction
The products of reactions of the aryl bromide with n-BuLi
varied considerably with changes in solvent composition: there
was no reaction with n-BuLi in pure heptane; the slow exchange
reaction in diethyl ether was virtually quantitative in heptane
containing a small quantity of THF; and the reaction with
n-BuLi in THF resulted in considerable coupling. On the other
hand, lithium-bromine exchange was found to be the exclusive
outcome of reactions of the aryl bromide with t-BuLi at 0 °C
in every solvent studied except pure hydrocarbons.2
We have been interested for some time in the effects of
solvent and temperature on the outcome of lithium-halogen
exchange reactions of organohalides with n-butyllithium
(n-BuLi) or t-butyllithium (t-BuLi).1 Several years ago,
we reported the results of a study of the reactions of a
representative aryl bromide, 1-bromo-4-t-butylbenzene, with
n-BuLi or t-BuLi at 0 °C in a variety of solvent systems.2
Prompted by the results of this study, we have extended the
investigation to assess the effect of solvent and temperature
on the outcome of the reactions of a representative vinyl
bromide, (E)-5-bromo-5-decene (1), with t-BuLi and n-BuLi.
As detailed below, the behavior of the vinyl bromide when
treated with an alkyllithium at temperatures near ambient is
considerably more complex than is the behavior of an aryl
bromide. The results of this study imply that a vinyllithium
can not be generated cleanly from a vinyl bromide by
lithium-bromine exchange at temperatures significantly
above -78 °C.
(1) (a) Bailey, W. F.; Gagnier, R. P.; Patricia, J. J. J. Org. Chem. 1984, 49,
2098. (b) Bailey, W. F.; Patricia, J. J.; Nurmi, T. T.; Wang, W. Tetrahedron
Lett. 1986, 27, 1861. (c) Bailey, W. F.; Patricia, J. J.; Nurmi, T. T. Tetra-
hedron Lett. 1986, 27, 1865. (d) Bailey, W. F.; Ovaska, T. V. Mechanisms of
Importance in Synthesis. In Advances in Detailed Reaction Mechanisms; Coxon,
J. M., Ed.; JAI Press: Greenwich, CT; Vol. 3, 1994, p 251. (e) Wiberg, K. B.;
Sklenak, S.; Bailey, W. F. J. Org. Chem. 2000, 65, 2014. (f) Bailey, W. F.;
Brubaker, J. D.; Jordan, K. P. J. Organomet. Chem. 2003, 681, 210. (g) Bailey, W.
F.; Rathman, T. L. In Process Chemistry in the Pharmaceutical Industry:
Challenges in an Ever Changing Climate; Gadamasetti, K., Braish, T., Eds.;
CRC Press: Boca Raton, FL, 2008; Vol. 2, p 205. (h) Rathman, T. L.; Bailey, W. F.
Org. Process Res. Dev. 2009, 13, 144.
(2) Bailey, W. F.; Luderer, M. L.; Jordan, K. P. J. Org. Chem. 2006, 71,
2825.
DOI: 10.1021/jo100303q
r
Published on Web 03/22/2010
J. Org. Chem. 2010, 75, 2661–2666 2661
2010 American Chemical Society

Bailey et al.
JOCArticle
Results and Discussion
SCHEME 1
Isomerically pure (E)-5-bromo-5-decene (1) was obtained
by DIBALH reduction of 5-decyne and quench with bro-
mine, as illustrated in Scheme 1;3 (E)-5-iodo-5-decene and
(Z)-5-decene (2) were prepared in analogous fashion.3 At the
outset it should be noted that (E)-5-bromo-5-decene (1) was
observed to isomerize slowly to an approximately 90:10
mixture of the E- and Z-isomers on standing in ambient
light at room temperature or upon distillation. This slow loss
of stereochemical integrity was not unexpected; some time
ago, Dreiding and Pratt noted that isomerically pure samples
of vinyl bromides isomerize to an equilibrium mixture upon
exposure to ambient light.4 Consequently, samples of 1 are
best stored in a dark refrigerator. Nonetheless, the isomeric
composition of the 5-bromo-5-decene used in this study
ranged from E/Z = 99:1 to 89:11, and the results of the
experiments discussed below were corrected, where appro-
priate, to reflect the differing isomeric compositions of the
vinyl bromide substrate.
protocol, depicted below,8 (E)-5-bromo-5-decene (1) was
converted to pure (Z)-5-decene in essentially quantitative
yield upon treatment with 2.2 equiv of t-BuLi in diethyl ether
at -78 °C followed by quench with methanol.
Several procedures have been developed for the prepara-
tion of vinyllithiums by lithium-halogen exchange. Peterson
and Polt,5 as well as Utimoto and co-workers,6 have reported
that vinyllithiums may be generated stereospecifically and in
high yield at room temperature by lithium-iodine exchange
between a vinyl iodide and either t-BuLi or n-BuLi in a
hydrocarbon solvent. Indeed, this is an excellent, experimen-
tally straightforward method for the preparation of vinyl-
lithiums with retention of configuration: isomerically pure
(Z)-5-decene (2) was obtained in virtually quantitative yield,
as shown below, upon treatment of (E)-5-iodo-5-decene with
either t-BuLi or n-BuLi in heptane at þ23 °C followed by
quenching of the vinyllithium with aqueous acid. In this
connection, it might be noted that Utimoto and co-workers
observed that vinyl bromides afforded low yields of vinyl-
lithium when treated with n-BuLi at room temperature in
hydrocarbon solution but the products of such reactions
were not reported (vide infra).6
In short, lithium-bromine exchange between a vinyl
bromide and an alkyllithium is a rapid and clean reaction
when conducted at low temperature (e78 C) in an ethereal
solvent, but it is a slow and ineffective process when con-
ducted at room temperature in a hydrocarbon solvent. It
occurred to us that it might be possible to prepare vinyl-
lithiums at temperatures significantly higher than -78 °C by
conducting the lithium-bromine exchange in a hydrocarbon-
ether solvent system. To this end, the effect of solvent
variation on the course of reactions of (E)-5-bromo-5-decene
(1) with t-BuLi and with n-BuLi were explored at 0 °C and at
room temperature, respectively.
Reactions with t-BuLi. Experiments were conducted at
0 °C in solvent systems composed of heptane-dialkyl ethers
in various proportions.9 As detailed in the Experimental
Section, 2.2 mol equiv of t-BuLi in heptane was added
dropwise at 0 °C to solutions of 1 in the appropriate solvent,
and the resulting 0.1 M reaction mixtures were allowed to
stand under argon at 0 °C for an additional 15 min before
quench with MeOH. Control experiments involving an
“inverse addition” demonstrated that adding solutions of 1
in heptane-dialkyl ethers to t-BuLi in heptane afforded
identical results. Thus, the mode of addition of t-BuLi and
vinyl bromide is inconsequential to the outcome of reactions.
Crude product mixtures were analyzed by capillary GC and
by GC-MS, affording baseline separation of the five pro-
ducts (2-6), illustrated in Scheme 2, that accounted for
essentially the total material balance.10 The (Z)-5-decene
(2), (E)-5-decene (3), 5-decyne (5), and 5-t-butyl-5-decanol
(6) were identified by comparison of their retention times and
A widely used method for the preparation of vinyl-
lithiums, developed by Seebach and Neumann,7 involves
low-temperature lithium-halogen exchange between a vinyl
bromide or iodide using 2 mol equiv of t-BuLi in an ethereal
solvent. Following a slightly modified Seebach-Newman
(3) (a) Zweifel, G.; Whitney, C. J. Am. Chem. Soc. 1967, 89, 2753.
(b) Zweifel, G.; Steele, R. B. J. Am. Chem. Soc. 1967, 89, 2754.
(4) Dreiding, A. S.; Pratt, R. J. J. Am. Chem. Soc. 1954, 76, 1902.
(5) Peterson, M. A.; Polt, R. Synth. Commun. 1992, 22, 477.
(6) (a) Shinokubo, H.; Miki, H.; Yokoo, T.; Oshima, K.; Utimoto, K.
Tetrahedron 1995, 51, 11681. (b) Yokoo, T.; Shinokubo, H.; Oshima, K.;
Utimoto, K. Synlett 1994, 645.
(7) Neumann, H.; Seebach, D. Chem. Ber. 1978, 111, 2785.
(8) Bailey, W. F.; Wachter-Jurcsak, N. M.; Pineau, M. R.; Ovaska, T. V.;
Warren, R. R.; Lewis, C. E. J. Org. Chem. 1996, 61, 8216–8228.
(9) Given the fairly rapid consumption of t-BuLi by proton abstraction
from various ethers at 0 °C, the exchange reaction between 1 and t-BuLi in
solvent containing more than 10% by vol of an ether was not investigated.
The half-life of t-BuLi in various solvents has been reported: see Stanetty, P.;
Mihovilovic, M. J. Org. Chem. 1997, 62, 1514.
(10) The second equivalent of t-BuLi used in these reactions consumes the
t-BuBr cogenerated in the exchange to give isobutane, isobutylene, and LiBr;
no attempt was made to quantitate these products: see (a) Bailey, W. F.;
Punzalan, E. R. J. Org. Chem. 1990, 55, 5404. (b) Seebach, D.; Neumann, H.
Chem. Ber. 1974, 107, 847.
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Bailey et al.
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SCHEME 2
a rather modest 60-80% for all of the reactions studied
(Table 1). Clearly, lithium-bromine exchange is not an
efficient process in hydrocarbon-ether mixtures at 0 °C.
The rather high proportion of (E)-5-decene (3) in the product
mixtures was unanticipated. Were the lithium-bromine
exchange to proceed with retention of configuration, via a
10-Br-2-ate intermediate or transition state,15 (Z)-5-decenyl-
lithium would result and the product, following quench with
MeOH, would be (Z)-5-decene (2). Given that a vinyllithium
generated under the conditions used for the reactions summar-
ized in Table 1 (15 min at 0 °C) is expected to be configura-
tionally stable,16 it would seem that lithium-bromine exchange
with retention of configuration is not the exclusive route
followed in these reactions. The results are consistent with an
exchange that proceeds, at least in part, via single-electron
transfer (SET) from the t-BuLi to the vinyl bromide substrate
to give a vinyl radical intermediate17 (Scheme 3). Vinyl radicals
are known to invert rapidly18 and, for this reason, an exchange
proceeding by SET would be expected to result in at least
partial isomerization of the vinyllithium product. The fact that
the relative proportions of (Z)-5-decene (2) and (E)-5-decene
(3) are roughly constant (viz. 2/3∼4) for all reactions except for
those conducted in a medium containing significant amounts of
2-methyltetrahydrofuran (Table 1, entries 9 and 10; 2/3 ∼ 9) is
consistent with this rationale.
TABLE 1. Reactions of (E)-5-Bromo-5-decene (1) with t-BuLi at 0 °C in
Various Solvents (Scheme 2)
products,a %
entry
solvent
2
3
4
5
6
1
1
heptane
2.3 tr
1.3 0.5 95.1
2
heptane-Et2O (99:1 by vol)
heptane-Et2O (19:1 by vol)
heptane-Et2O (9:1 by vol)
heptane-THF (99:1 by vol)
heptane-THF (19:1 by vol)
heptane-THF (9:1 by vol)
72.9 16.0 8.0 1.8 1.3
71.3 17.0 6.3 2.2 2.8 tr
66.8 17.5 8.3 1.7 1.4
72.7 17.2 6.7 1.6 2.0
69.0 17.5 6.9 1.5 1.5
66.0 20.2 7.6 1.9 3.2
3
4
5
6
7
8
heptane-MeTHFb (99:1 by vol) 83.8 10.6 2.5 1.3 0.8 tr
heptane-MeTHFb (19:1 by vol) 80.8 8.0 6.9 1.5 1.8 tr
heptane-MeTHFb (9:1 by vol) 77.4 9.6 7.4 1.7 2.2 tr
9
10
11
12
13
heptane-MTBE (99:1 by vol)
heptane-MTBE (19:1 by vol)
heptane-MTBE (9:1 by vol)
71.1 16.5 6.6 1.6 tr
2.4
67.7 21.9 4.9 2.6 1.3 tr
62.0 27.2 4.6 2.6 3.4
aYields were determined by capillary GC; tr indicates that a trace
(viz. < 0.2%) of material was detected. b2-Methyltetrahydrofuran.
mass spectra to those of authentic samples; (Z)-4-decene (4)
was identified on the basis of its reported GC retention time
and EI mass spectrum.11 It might be noted that the allene,
4,5-decadiene, whose mass spectra has been reported,12 was
not observed as a product of any of the reactions. The results
of these experiments are summarized in Table 1.
The formation of small quantities of alkyne 5 in these
reactions is almost certainly the result of an elimination of
HBr from the vinyl bromide substrate. The observation of
minor but non-negligible quantities of (Z)-4-decene (4) as a
product of these reactions is more problematic. The fact that
only the Z- isomer is observed (a control experiment, using a
commercial sample containing both (Z)-4-decene and (E)-4-
decene, demonstrated that both isomers could be detected by
the GC method used for analysis of reaction mixtures) suggests,
as illustrated in Scheme 4, that (Z)-4-decene (4) was generated
by protonation of an allyllithium intermediate: the U-shaped
geometry of the 1,3-dialkylallyl anion depicted in Scheme 4 is
Inspection of the data presented in Table 1 reveals that
t-BuLi in heptane is, for all intents and purposes, unreactive;
95% of the starting bromide (1) is recovered (Table 1, entry
1). Given that t-BuLi is known to exist as a tetrameric
aggregate in hydrocarbon solvent,13 it would appear that
the tetrameric species does not participate effectively in the
lithium-bromine exchange. However, the presence of even
small quantities (viz, 1% by vol) of an ether (Et2O, THF,
2-methyltetrahydrofuran,14 or MTBE) in a predominantly
heptane medium resulted in virtually complete consumption
of the vinyl bromide (Table 1, entries 2, 5, 8, and 11).
Moreover, and somewhat surprisingly, addition of any of
the ethers used in this study, in any proportion from 1 to 10%
by volume, led to nearly the same product distribution. The
yield of (Z)-5-decenyllithium, assayed as (Z)-5-decene (2), is
(15) Wiberg, K. B.; Sklenak, S.; Bailey, W. F. Organometallics 2001, 20,
771.
€
(16) (a) Knorr, R.; Lattke, E.; Rapple, E. Chem. Ber. 1981, 114, 1581.
(b) Lattke, E.; Knorr, R. Chem. Ber. 1981, 114, 1600. (c) Knorr, R.; Lattke, E.
Chem. Ber. 1981, 114, 2116. (d) Walborsky, H. M.; Banks, R .B. Bull. Soc.
Chim. Belg. 1980, 89, 849. (e) Hoedt, R. W. M. T.; Van Koten, G.; Noltes,
J. G. J. Organomet. Chem. 1979, 170, 131. (f) Seyferth, D.; Vaughn, L. G.
J. Organomet. Chem. 1963, 1, 201. (g) Hoedt, R .W. M. T.; Van Koten, G.;
Noltes, J. G. J. Organomet. Chem. 1978, 161, C13. (h) Curtin, D. Y.; Koehl,
W. J., Jr. J. Am. Chem. Soc. 1962, 84, 1967. (i) Panek, E. J.; Neff, B. L.; Chu,
H.; Panek, M. G. J. Am. Chem. Soc. 1975, 97, 3996. (j) Curtin, D. Y.; Crump,
J. W. J. Am. Chem. Soc. 1957, 80, 1922. (k) Seyferth, D.; Vaughn, L. G.
J. Am. Chem. Soc. 1964, 86, 883. (l) Knorr, R.; Lattke, E. Tetrahedron Lett.
1977, 18, 3969.
(11) National Institute of Standards and Technology Chemistry WebBook,
Standard Reference Database No. 69. http://webbook.nist.gov/chemistry
(accessed December 2009).
(12) Back, T. G.; Krishna, M. V.; Muralidharan, K. R. J. Org. Chem.
1989, 54, 4146.
(13) (a) Brown, T. L. Acc. Chem. Res. 1968, 1, 23. (b) Thomas, R. D.;
Clarke, M. T.; Jensen, R. M.; Young, T. C. Organometallics 1985, 5, 1851.
(14) 2-Methyltetrahydrofuran, which is only partially soluble in water,
has been used as a solvent for a variety of organometallic reactions; it reacts
more slowly with organolithium reagents than does THF: see (a) Aycock,
D. F. Org. Process Res. Dev. 2007, 11, 156. (b) Bates, R. J. Org. Chem. 1972,
37, 560.
(17) Bailey, W. F.; Patricia, J. J. J. Organomet. Chem. 1988, 352, 1.
(18) Fressenden, R. W.; Schuler, R. H. J. Chem. Phys. 1963, 39, 2147.
J. Org. Chem. Vol. 75, No. 8, 2010 2663

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SCHEME 3
SCHEME 4
with vinyl bromide 1 were very slow at 0 °C) in solvent
systems composed of pure heptane, Et2O, THF, 2-methylte-
trahydrofuran, or MTBE as well as in various heptane-
ether mixtures. As detailed in the Experimental Section,
1.2 mol equiv of n-BuLi in hexane was added dropwise at
room temperature to solutions of 1, and the resulting 0.1 M
solutions were stirred at room temperature for 30 min before
quenching with MeOH. Crude product mixtures were ana-
lyzed as described above. The results of these experiments are
summarized in Table 2.
consistent with the well-established preference for allylic anions
to adopt the Z-geometry.19 Such an allyllithium would be
formed upon proton abstraction (either by t-BuLi or a vinylli-
thium) from (Z)-5-decene (2) generated by inadvertent quench
of (Z)-5-decenyllithium by solvent or adventitious moisture.
The presence of minor amounts of alcohol 6 in some of the
reaction product mixtures has a more prosaic origin: dissolved
molecular oxygen. Typically, an organohalide substrate should
be rendered oxygen-free by freeze-thaw cycles or by sparging
with argon before conducting a lithium-halogen exchange
reaction; however, due to concerns about the potential config-
urational photolability of (E)-5-bromo-5-decene noted above,
the vinyl bromide was not deoxygenated before use in these
experiments. Consequently, the vinyllithium product is appar-
ently trapped by reaction with dissolved molecular oxygen
present in the reaction mixtures to give a lithium enolate.20
As illustrated below, addition of residual t-BuLi to the ketone
generated upon quench of reaction mixtures accounts for the
formation of small quantities of tertiary alcohol 6.
With the exception of reactions run in THF-rich solvent
(Table 2, entries 6 and 7), the six products depicted in
Scheme 5 accounted for virtually the entire material balance:
5-butyl-5-decene (7) was identified by comparison of its mass
spectrum to that reported for this alkene;21 and 5-butyl-5-
decanol (8) was identified by comparison of its retention time
and mass spectrum to that of an authentic sample.22 Reac-
tions conducted in heptane-THF (1:1 by vol) or in pure
THF (Table 2, entries 6 and 7) afforded, in addition to the
products illustrated in Scheme 5, a number of extraneous,
unidentified compounds likely derived from reactions of
organolithiums with THF or the products generated from
fragmentation of the THF upon reaction with n-BuLi.23
It is apparent that n-BuLi reacts more slowly with vinyl
bromide 1 than does t-BuLi; indeed, recovered starting
material is, by far, the major component in all reactions
except those run in THF or 1:1 by vol heptane-THF
(Table 2, entries 6 and 7). Use of THF-rich solvent systems
resulted in significant amounts (ca. 15%) of 5-butyl-5-decene
(7) from coupling of the vinyllithium product with 1-bromo-
butane cogenerated in the lithium-bromine exchange reac-
tion.24 The other products observed in these reactions are
entirely analogous to those observed in the t-BuLi initiated
exchanges discussed above. Plainly, as noted by Utimoto and
co-workers,6 lithium-bromine exchange between n-BuLi
and 1 is not a practical route to a vinyllithium.
Conclusions
Vinyllithiums may be prepared stereospecifically and in
virtually quantitative yield by two methods: (1) lithium-iodine
Reactions with n-BuLi. Experiments with n-BuLi in hexane
were conducted at room temperature (reactions of n-BuLi
(19) (a) Wilson, K. W.; Roberts, J. D.; Young, W. G. J. Am. Chem. Soc. 1950,
72, 215. (b) Felkin, H.; Frajerman, C.; Gault, Y. J. Chem. Soc., Chem. Commun.
1966, 75. (c) Schlosser, M.; Hartmann, J.; David, V. Helv. Chim. Acta 1974, 57,
1567. (d) Schlosser, M.; Hartmann, J. J. Am. Chem. Soc. 1976, 98, 4674.
(e) Bywater, S.; Worsfold, D. J. J. Organomet. Chem. 1978, 159, 229.
(f) Brownstein, S.; Bywater, S.; Worsfold, D. J. J. Organomet. Chem. 1980, 199, 1.
(20) Wakefield, B. J. The Chemistry of Organolithium Compounds;
Pergamon Press: New York, 1974.
(21) Gerar, J.; Hevesi, L. Tetrahedron 2001, 57, 9109.
(22) Church, J. M.; Whitmore, F. C.; McGrew, R. V. J. Am. Chem. Soc.
1934, 56, 176.
(23) (a) Jung, M. E.; Blum, R. B. Tetrahedron Lett. 1977, 3791. (b) Bates,
R. B.; Kroposki, L. M.; Potter, D. E. J. Org. Chem. 1972, 37, 560.
(24) No attempt was made to quantitate the amounts of butane,
1-bromobutane, 1-butene, or octane that may have been produced by
extraneous reactions of n-BuLi.
2664 J. Org. Chem. Vol. 75, No. 8, 2010

Bailey et al.
JOCArticle
TABLE 2. Reactions of (E)-5-Bromo-5-decene (1) with n-BuLi at Room Temperature in Various Solvents (Scheme 5)
product,a %
entry
solvent
2
3
4
5
7
8
1
1
2
3
4
5
6
7
8
heptane
∼100
98.0
88.0
86.0
84.0
heptane-Et2O (9:1 by vol)
heptane-Et2O (1:1 by vol)
Et2O
tr
2.5
4.3
5.7
56.7
56.8
2.8
26.3
29.9
8.0
tr
tr
tr
tr
0.7
0.6
tr
0.6
0.6
tr
tr
tr
tr
0.5
0.7
0.6
5.2
5.1
tr
2.4
2.2
0.9
1.2
2.4
2.4
2.7
0.5
5.9
6.0
1.8
13.7
13.0
0.8
3.5
4.0
0.5
0.7
tr
2.0
1.7
2.2
2.6
2.3
1.0
1.2
1.7
1.1
4.1
2.0
heptane-THF (9:1 by vol)
heptane-THF (1:1 by vol)
THF
15.3
16.1
0.8
1.2
1.6
0.7
0.8
0.8
heptane-MeTHF (9:1 by vol)b
heptane-MeTHF (1:1 by vol)b
MeTHFb
86.0
48.8
42.5
87.1
77.3
61.2
9
10
11
12
13
heptane-MTBE (9:1 by vol)
heptane-MTBE (1:1 by vol)
MTBE
11.2
25.9
tr
0.7
aYields were determined by capillary GC; tr indicates that a trace (viz. < 0.2%) of material was detected. b2-Methyltetrahydrofuran.
SCHEME 5
exchange between a vinyl iodide and either t-BuLi or n-BuLi
at room temperature in a hydrocarbon solvent;5,6 or (2) low-
temperature (viz. e 78 C) lithium-bromine exchange be-
tween a vinyl bromide and two molar equivalents of t-BuLi
in diethyl ether.7,8 The results presented above (Tables 1 and
2) demonstrate that, to the extent (E)-5-bromo-5-decene (1)
is representative of its class, lithium-bromine exchange at
temperatures significantly higher than -78 °C using either
t-BuLi or n-BuLi in hydrocarbon solution or in hydrocar-
bon-ether mixtures is not an efficient process for the gen-
eration of vinyllithiums.
addition of 50 mL of 10% aq HCl. The aqueous phase was
discarded and the organic layer was washed with 10% aq
sodium bisulfite, saturated, aq NaHCO3, water, and brine, dried
(MgSO4), and concentrated by rotary evaporation. Distillation
(Kugelrohr; bath temp. 35 °C (5 mm)) removed residual alkyne
and alkene; distillation (Kugelrohr) at a bath temp. of 75 °C
(5 mm; lit.26 bp 64-66 °C (0.9 mm)) gave 3.20 g (33%) of the title
compound. Significant decomposition was observed during
each distillation. GC analysis revealed that the isolated product
was a 98:2 mixture of E/Z isomers, respectively. Upon standing
at room temperature in ambient light, the mixture slowly
isomerized to give an E/Z ratio of 90:10; if stored at -2 °C or
below in the absence of light, no isomerization occurred. The
title compound displayed the following spectroscopic proper-
ties: 1H NMR (CDCl3) δ 0.88-0.96 (m, 6H), 1.21-1.44 (m, 6H),
1.47-1.61 (five-line pattern, J=7.9 Hz, 2H), 2.01 (q, J=7.4 Hz,
2H), 2.42 (t, J=7.4 Hz, 2H), 5.84 (t, J=7.6 Hz, 1H); 13C NMR
(CDCl3) δ 14.1, 14.2, 21.97, 22.4, 29.5, 30.5, 31.7, 35.4, 126.2,
132.6.
(E)-5-Iodo-5-decene. A solution of 45 mL of a 1.0 M solution
of DIBALH in hexane (45 mmol) and 6.00 g (43.4 mmol) of
5-decyne was stirred at 50 °C under argon for 24 h. The hexane
was removed by rotary evaporation, 22 mL of THF was added,
the resulting solution was cooled to -50 °C, and 28.4 mL of a
1.55 M solution of iodide in THF (44.0 mmol) was added via syringe
pump at a rate of 1 mL/h. The reaction mixture was worked up
as described above for the preparation of 1. Distillation of the
residue afforded 6.20 g (54%) of the title compound as a 99:1
mixture of E/Z isomers: bp 85 °C (6 mm; lit.27 bp 96 °C (18 mm));
1H NMR (CDCl3) δ 0.90-0.96 (m, 6H), 1.24-1.35 (m, 6H),
Experimental Section
The concentrations of t-BuLi in heptane (FMC) and n-BuLi
in hexane (FMC) were determined prior to use by the method of
Watson and Eastham.25 Anhydrous heptane was freshly dis-
tilled from sodium; anhydrous diethyl ether, THF, 2-methylte-
trahydrofuran, and MTBE were freshly distilled from a dark-
purple solution of sodium and benzophenone. A sample of
5-butyl-5-decanol (8) was prepared as described by Whitmore
and co-workers;22 (E)-5-decene (3) was a commercial sample.
(E)-5-Bromo-5-decene (1). A solution of 45 mL of a 1.0 M
solution of DIBALH in hexane (45 mmol) and 6.10 g (44.2 mmol)
of 5-decyne was stirred at 50 °C under argon for 24 h. The
hexane was removed by rotary evaporation under nitrogen,
20 mL of dry THF was added, the resulting solution was cooled
to -50 °C, and 37.5 mL of a 1.2 M solution of bromine in
dichloromethane (45 mmol) was added via syringe pump at a
rate of 1 mL/h. Upon complete addition, the solution was
allowed to warm and stir at room temperature for 1 h before
(26) Brown, H. C.; Bhat, N. G.; Rajagopalan, S. Synthesis 1986, 6, 480.
(27) Tamao, K.; Akita, M.; Maeda, K.; Kumada, M. J. Org. Chem. 1987,
52, 1100.
(25) Watson, S. C.; Eastham, J. F. J. Organomet. Chem. 1967, 9, 165.
J. Org. Chem. Vol. 75, No. 8, 2010 2665

Bailey et al.
JOCArticle
1.38-1.51 (five-line pattern, J=7.8 Hz, 2H), 2.03 (q, J=7.2 Hz,
2H), 2.37 (t, J=7.3 Hz, 2H), 6.17 (t, J=7.5 Hz, 1H); 13C NMR
(CDCl3) δ 14.1, 14.2, 21.8, 22.4, 30.8, 31.5, 31.6, 38.4, 103.7,
141.6.
(CDCl3) δ 14.3, 14.4, 22.9, 24.0, 24.8, 26.8, 27.4, 33.2, 35.3,
35.5, 38.9, 77.6; HRMS-EI (m/z): [M - H2O]þ calcd for C14H28,
196.2211; found, 196.2191.
Reactions of (E)-5-Bromo-5-decene with t-BuLi or n-BuLi. A
flame-dried, septum-capped, 25-mL flask was charged under a
positive pressure of argon with an accurately weighed quantity
(ca. 0.5-1.0 mmol) of (E)-5-bromo-5-decene (1) and the appro-
priate quantity of heptane and ether needed to make a 0.1 M
solution of 1 in the desired solvent ratio. The solution was cooled
to 0 °C for reactions with t-BuLi or left at room temperature for
reactions with n-BuLi and then either 1.2 mol equiv of n-BuLi in
hexanes or 2.2 mol equiv of t-BuLi in heptane was added
dropwise. Upon completion of the addition, the mixture was
allowed to stir at 0 °C or room temperature for an additional 15
or 30 min, respectively, and then quenched with MeOH. The
organic layer was washed with water, dried (MgSO4), and the
crude products were analyzed by GC on a 30 m ꢀ 0.25 mm ꢀ
0.25 μm Chiraldex B-DM column and by GC-MS on a 25 m ꢀ
0.2 mm ꢀ 0.33 μm DB-5 cross-linked 5% phenyl methyl silicone
capillary column. The results are summarized in Tables 1 and 2.
(Z)-5-Decene (2). A solution of 36 mL of a 1.0 M solution
of DIBALH in hexane (36 mmol) and 4.70 g (34.0 mmol) of
5-decyne was stirred at 50 °C under argon for 24 h. The hexane
was removed by rotary evaporation, 18 mL of THF was added,
and the resulting solution was cooled to -50 °C before dropwise
addition of 25 mL of 10% aq HCl. The reaction mixture was
worked up as described above for the preparation of 1 and
concentrated by rotary evaporation to yield 3.90 g (82%) of
isomerically pure title compound:28 1H NMR (CDCl3) δ 0.92 (t,
J=7.2 Hz, 6H), 1.30-1.41 (m, 8H), 2.00-2.05 (m, 4H), 5.35 (dt,
J=3.3, J=1.2 Hz, 2H); 13C NMR (CDCl3) δ 14.2, 22.6, 27.1,
32.2, 130.1.
5-tert-Butyl-5-decanol (6). A solution of 3.25 g (20.8 mmol)
of 5-decanone in 40 mL of diethyl ether was cooled to 0 °C and
14.6 mL of 1.50 M solution of t-BuLi in pentane (21.8 mmol)
was added dropwise. After complete addition, the solution was
allowed to stir for 1 h at 0 °C before addition of 10 mL of
saturated, aq NH4Cl. The aqueous phase was discarded and the
organic phase was washed with water and brine, dried (MgSO4),
and concentrated by rotary evaporation. The residue was dis-
tilled to afford 1.83 g (41%) of the title alcohol as a clear oil: bp
89-90 °C (6 mm); 1H NMR (CDCl3) δ 0.85-0.99 [overlapping
patterns, i.e., 0.94 (s, 9H), 0.85-0.99 (m, 6H)], 1.05-1.20 (bs,
1H), 1.27-1.37 (m, 10H), 1.45-1.58 (m, 4H); 13C NMR
Acknowledgment. We are grateful to Dr. Christopher
Wolterman of FMC, Lithium Division, for generous gifts
of t-BuLi in heptane and n-BuLi in hexane. This work was
supported by a grant from the Process Chemistry Division,
H. Lundbeck A/S, Copenhagen, Denmark.
Supporting Information Available: NMR and mass spectra
of products. This material is available free of charge via the
Internet at http://pubs.acs.org.
(28) Campbell, E. J. Am. Chem. Soc. 1941, 63, 2684.
2666 J. Org. Chem. Vol. 75, No. 8, 2010