aldehyde or ketone. Interestingly, however, very little is
generated a mixture of lithioethene and 1-bromo-1-lithio-
ethene (2), which was characterized by electrophilic trapping
with chlorotrimethylsilane (Scheme 2). Clearly, competitive
7
known about the use of 1-halo-1-lithioethenes (halo ) Cl,
8
9
Br, I ) as synthetic intermediates, presumably due to
concerns over the rearrangement and/or decomposition of
such metalated carbenoids.9
-11
Only a single report has
appeared on the preparation and electrophilic trapping of
Scheme 2. Reaction of Bromoethene with Different
8
1-bromo-1-lithioethene 2. We now report a reliable prepara-
Alkyllithium Bases
tive-scale synthesis of 2 and demonstrate its utility for the
efficient trapping of aldehydes and ketones en route to the
preparation of 2-bromo-1-alken-3-ols 1.
n-BuLi had been previously used by K o¨ brich for the
selective deprotonation of chloroethene at -110 °C to afford
-chloro-1-lithioethene.7 However, Shimizu reported that
a
1
attempted n-BuLi deprotonation of bromoethene was thwarted
by several competing processes that led them to use LDA/
8
Me SiCl for the R-deprotonation/silylation of bromoethene.
3
In stark contrast, we found that 1-bromo-1-lithioethene (2)
could be generated cleanly via reaction of n-BuLi with
commercially available bromoethene. The reproducible
preparation of 2 required strict temperature control, which
1
2
was achieved using a specially designed glass reactor.
Given its instability, 2 was immediately trapped with a
suitable aldehyde or ketone (Scheme 1). After some opti-
mization, it was found that the slow addition of n-BuLi to a
solution of bromoethene in the Trapp mixture13 at -110 °C
followed by addition of acetone gave 57% isolated yield of
the desired bromoallylic alcohol 1a (Table 1, entry 1).
halogen-metal exchange had dominated during the at-
tempted deprotonation step.
Carrying out the metalation step in the presence of
0.2-0.5 equiv of lithium bromide significantly increased the
yield of acetone-trapped adduct 1a (Table 1, entry 2). This
product did not contain even traces of 2-methyl-3-buten-2-
ol, indicating that deprotonation of bromoethene was not
complicated by side reactions involving halogen-metal
exchange under the reaction conditions employed.
When bromoethene was added to a low-temperature
solution of n-butyllithium (i.e., inverse addition), the yield
of 1a dropped dramatically (entry 3) but again no 2-methyl-
Table 1. Reaction of 1-Bromo-1-lithioethene with Aldehydes
and Ketones R C(O)R
1 2
entry R1
R2
product % yielda
1
2
3
4
5
6
7
8
9
0
1
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH2dCH-
1a
1a
1a
1b
1c
1d
1e
1f
57b
77
20c
78
84
85
80
46
50
81
74
3
-buten-2-ol was formed.
When the optimized conditions developed above for the
trapping of acetone (entry 2) were employed with a range
of other aldehydes and ketones, the desired bromoallylic al-
cohols 1 were obtained in moderate-to-excellent yield (entries
4-11). All ketones examined here afforded the desired ad-
ducts in high yield (entries 2, 4-7). R,â-Unsaturated ketones
and aldehydes cleanly gave 1,2-adducts 1b, 1e, and 1i (entries
CH2dCH-CH2-CH2-
-CH2CH2CH2CH2CH2-
-CHdCH-C(Me)2-CH2CH2-
CH3CH2
n-C6H13
Ph
H
H
H
H
1g
1h
1i
1
1
4
, 7, 11). While benzaldehyde and acrolein afforded high
CH2dCH-
yields of adducts 1h and 1i (entries 10, 11), lower yields
were obtained with simple aliphatic aldehydes (entries 8, 9).
No products originating from vinyllithium addition were de-
tected in any experiment. Throughout this study, it was ap-
parent that the chemical behavior of 1-bromo-1-lithioethene
at the reaction temperature was more similar to a simple
organolithium reagent rather than to a carbenoid-type species.
a
Isolated yields of product obtained in 95-99% purity (by GC) after
b
c
vacuum distillation. No LiBr was present. Bromoethene was added to
n-BuLi solution (inverse addition).
The choice of alkyllithium base proved to be important.
An attempt to deprotonate bromoethene with tert-butyllithium
(
7) 1-Chloro-1-lithioethene was prepared from chloroethene by K o¨ brich
(9) 1-Iodo-1-lithioethene was prepared from 1-iodoethene and LDA: it
was trapped by several electrophiles in very low yield (e.g., 10% for trapping
with Ph2CdO) due to its facile decomposition to ethyne even at -100 °C:
Campos, P. J.; Sampedro, D.; Rodriguez, M. A. Organometallics 1998,
17, 5390-5396.
more than 35 years ago and was successfully trapped with a limited range
of electrophiles that did not include aldehydes or ketones: (a) K o¨ brich, G.;
Flory, K. Chem. Ber. 1966, 99, 1773-1781. (b) K o¨ brich, G. Angew. Chem.,
Int. Ed. Engl. 1967, 6, 41-52. However, only one (moderate-to-poor-
yielding) synthetic application of 1-chloro-1-lithioethene has subsequently
appeared: (c) Kasatkin, A.; Whitby, R. J. J. Am. Chem. Soc. 1999, 121,
(10) Stang, P. J. Chem. ReV. 1978, 78, 383-405.
(11) (a) Liu, F. Jiegou Huaxue 2002, 21, 210-213. (b) Schoeller, W.
W. Chem. Phys. Lett. 1995, 241, 21-25. (c) Lucchini, V.; Modena, G.;
Pasquato, L. J. Am. Chem. Soc. 1995, 117, 2297-2300. (d) Wang, B. Z.;
Deng, C. H.; Xu, L. X.; Tao, F. G. Sci. China, Ser. B 1990, 33, 421-429.
(12) Design for this glass reactor is provided in Supporting Information.
(13) THF/ether/pentane 4:1:1 by volume: see ref 7b.
7
039-7049.
(8) 1-Bromo-1-lithioethene was generated from 1-bromoethene using
LDA and trapped in 60% yield with Me3SiCl (Shimizu, N.; Shibata, F.;
Tsuno, Y. Bull. Chem. Soc. Jpn. 1987, 60, 777-778), but no other
applications of this reagent have appeared.
2264
Org. Lett., Vol. 5, No. 13, 2003