Unique reactivity of a 1,4-dilithiobutadiene with methyl iodide

Article abstract of DOI:10.1016/j.tetlet.2006.03.067

Reactions of 1,4-dilithiobutadiene 5 with MeI in THF gave predominantly methyl iododiene 6. Monolithio monoiodo intermediate 8 was shown not to be involved in the formation of 6, but the results were consistent with the involvement of monolithio monomethyl intermediate 11, which could lead to 6 by metal-halogen exchange. Several other lithioalkenes also reacted with MeI to give alkenyl iodides.

Full text of DOI:10.1016/j.tetlet.2006.03.067

Tetrahedron Letters 47 (2006) 3427–3430
Unique reactivity of a 1,4-dilithiobutadiene with methyl iodide
Paul F. Hudrlik,* Donghua Dai and Anne M. Hudrlik
Department of Chemistry, Howard University, Washington, DC 20059, USA
Received 17 January 2006; revised 10 March 2006; accepted 10 March 2006
Available online 31 March 2006
Abstract—Reactions of 1,4-dilithiobutadiene 5 with MeI in THF gave predominantly methyl iododiene 6. Monolithio monoiodo
intermediate 8 was shown not to be involved in the formation of 6, but the results were consistent with the involvement of mono-
lithio monomethyl intermediate 11, which could lead to 6 by metal–halogen exchange. Several other lithioalkenes also reacted with
MeI to give alkenyl iodides.
Ó 2006 Elsevier Ltd. All rights reserved.
1,4-Dilithiobutadienes are of considerable theoretical
interest,1 and their unique reactivity has recently been
studied for synthetic applications.2 1,4-Dimetallobuta-
dienes have also been widely used for preparing siloles
and other metalloles.3 In the course of using 1,4-dilithio-
butadienes for the preparation of siloles, we attempted
to characterize these intermediates by trapping reac-
tions. When dibromide 14a and diiodide 44b,c were each
treated with t-BuLi in THF (to generate the correspond-
ing dilithio compounds, 2 and 5), followed by Me3SiCl/
Et3N,5 siloles were formed instead of the expected disilyl-
ated compounds.6 We therefore investigated the reac-
tions with MeI. In the case of dibromide 1, the expected
dimethylated compound 37 was obtained in 87% yield
(Eq. 1). However, in the case of diiodide 4, there was
no evidence for the analogous dimethylated diene (7).
Instead, the methyl iododiene 67 was obtained in 81–
87% yields (Eq. 2).
The reaction of 5 with MeI (in THF, ca. ꢀ60 °C!rt)
was carried out a number of times. In some cases, espe-
cially when only ca. 2 equiv of MeI was used, significant
amounts of compounds 9 (below) and 108 were formed
in addition to 6.9 A series of reactions in which excess
MeI was added at various temperatures showed little
reaction after 10 min at ꢀ70 °C (major product after
Me
Br
excess
4 t-BuLi
ð1Þ
MeI
THF
Br
Me
Li Li
1
2
3
Et
Et
Et
Et
Et
Et
Et
Et
excess
4 t-BuLi
Et
Et
Et
Et
Et
Et
Et
Et
NOT
ð2Þ
THF
I
I
MeI
Li Li
Me
I
Me Me
4
6
7
5
Keywords: Alkenyllithium; Dilithiobutadiene; Methyl iodide; Metal–halogen exchange.
*
Corresponding author. Tel.: +1 202 806 4245; fax: +1 202 806 5442; e-mail: phudrlik@fac.howard.edu
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.03.067

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P. F. Hudrlik et al. / Tetrahedron Letters 47 (2006) 3427–3430
workup was diene 10), and significant reaction at
ꢀ30 °C (1:1 ratio of 6:10).10 Monomethyldiene 12 (see
below) was not observed.
Et
Et
Et
Et
Si
13
In order to learn more about this reaction, we generated
the monolithio intermediates 8 and 11, and treated them
with MeI. Intermediate 8 was generated by treating diio-
dide 4 with 1.5 equiv of t-BuLi; quenching with MeOH
gave the monoiododiene 9 as the major product, along
with some of the starting diiodide, and a small amount
of diene 10 (Eq. 3) (GC areas: 9:4:10 = 48:34:6; molar
ratio by 1H NMR 9:4:10 = 63:32:5). Column chromato-
graphy gave monoiododiene 97 in 49% yield, and
some recovered diiodide 4 (16%). When intermediate 8
was generated as above, and then treated with
excess MeI, the major product was diiodide 4 (Eq. 4)
(90% crude yield, 87% pure by GC).11 This result
shows that 8 is not an important precursor to methyl
iododiene 6.
The reactions of vinyllithium reagents with MeI to give
methyl-substituted alkenes are well known,12,13 and
there are also reports of such reactants giving alkenyl
iodides.13b,14 Neumann and Seebach found that the
product ratio can depend on solvent and on the number
of equivalents of MeI, and interpreted the results in
terms of a fast reversible metal–halogen exchange
between the alkenyllithium and the MeI.13b We decided
to study the reaction of a simple monolithioalkene with
MeI using our conditions. Iodoalkene 1415 (Z:E 93:7, by
1H NMR) was treated with t-BuLi in THF (Eq. 7). GC
analysis of an aliquot (aqueous workup) showed the
Et
Et
Et
Et
Et
Et
1.5 t-BuLi
MeOH
4
Et
Et
+
4
Et
Et
Et
Et
(3)
(4)
THF
H H
10
H
I
Li
I
9
8
excess MeI
4
Monolithio intermediate 11 was generated by treating
compound 6 with t-BuLi (2 equiv). Quenching with
MeOH gave monomethyldiene 127 (Eq. 5) (63% after
chromatography). When intermediate 11 was treated
with excess MeI, the major product was methyl iodo-
diene 6 (Eq. 6). (GC areas of the crude product were
87% 6 and 5% 12; column chromatography gave 6 in
71% yield.) These results demonstrate that lithio methyldi-
ene 11 could be a precursor to methyl iododiene 6 in Eq. 2.
absence of 14, and the major component (98%), having
a GC retention time very similar to the original starting
material 4-octyne, presumably trans-4-octene. Excess
MeI was added to the reaction mixture, and after work-
up, GC analysis of the crude sample showed 14 to be the
major product (89% of GC area). Iodide 14 was isolated
by Kugelrohr distillation in 80% yield with a GC purity
1
of 93%. H and 13C NMR, and GC/MS analyses also
showed the presence of the E isomer (Z:E = 93:7 by
Et
Et
Et
Et
Et
Et
2 t-BuLi
MeOH
(5)
(6)
Et
Et
Et
Et
Et
Et
Me
I
THF
Me H
Me Li
11
6
12
excess MeI
(+ 12 if short
reaction time)
6
The relative reactivity of MeI and Me3SiCl to the dilith-
iodiene 5 (generated from diiodide 4) was determined.
When 4 was treated with t-BuLi (in THF) followed by
(1) excess Me3SiCl/Et3N (ca. ꢀ64 °C, 10 min) and (2)
excess MeI (at ꢀ63 °C, and then warmed to rt), methyl
iododiene 6 was the major product, with none of the
silole 13 (see Ref. 6) (or a bis(trimethylsilyl) diene)
observed. These results show that MeI is more reactive
to the dilithiodiene intermediate 5 than is Me3SiCl.
1H NMR). As expected, the Z:E ratio was essentially
identical to that of the starting iodide.
Pr
Li
2 t-BuLi
Pr
I
excess
MeI
14
ð7Þ
Pr
Pr
THF
15
14
We have found one example of the reaction of a 1,4-
dilithiobutadiene with MeI (Eq. 8).16 The dilithio inter-
mediate 16 (in Et2O), generated from cyclooctyne and

P. F. Hudrlik et al. / Tetrahedron Letters 47 (2006) 3427–3430
3429
´
3. Dubac, J.; Guerin, C.; Meunier, P. In The Chemistry of
Organic Silicon Compounds; Rappoport, Z., Apeloig, Y.,
Eds.; Wiley: Chichester, 1998; Vol. 2, Part 3; pp 1961–
2036.
Li, was treated with excess MeI to give the iodo- and
methyl-substituted product 18 in 28% yield, while the
dimethyl-substituted product was not observed. Forma-
tion of MeLi was postulated based on detection of
Me4Si when Me3SiCl was added to the reaction mixture,
and the reaction was suggested to involve lithio iodo-
diene intermediate 17.16 Based on our results, the
involvement of 17 is unlikely.
4. (a) Liu, Y.; Stringfellow, T. C.; Ballweg, D.; Guzei, I. A.;
West, R. J. Am. Chem. Soc. 2002, 124, 49–57; (b) Freeman,
W. P.; Tilley, T. D.; Liable-Sands, L. M.; Rheingold, A. L.
J. Am. Chem. Soc. 1996, 118, 10457–10468; (c) Buchwald,
Me
MeI
MeI
ð8Þ
Li
I
Li Li
I
16
17
18
The simplest explanation of our results17 is that the di-
lithio intermediate 5 reacts with MeI by initial C-alkyl-
ation to give monolithio intermediate 11, and that this
undergoes metal–halogen exchange with MeI to give
methyl iododiene 6. The reverse process (metal–halogen
exchange followed by alkylation) is ruled out, since
monolithium intermediate 8 was shown to not be a pre-
cursor to 6. The reactions in which conversion to 6 is
incomplete suggest that 11 reacts faster with MeI than
does 5. Dilithio intermediates such as 5 are believed to
have a bridged structure, and to be somewhat stabi-
lized,1 but we are unaware of reactivity comparisons
between them and simple monolithio intermediates. It is
noteworthy that all of the monolithio alkenes we studied
(8, 11, and 13) react with MeI under these conditions to
give iodides, and only the dilithio compound 5 under-
goes alkylation. This is further evidence for the unique
reactivity of the 1,4-dilithiobutadienes.
S. L.; Nielsen, R. B. J. Am. Chem. Soc. 1989, 111, 2870–
2874.
5. We often use mixtures of Me3SiCl with Et3N for quench-
ing reactions. Et3N reacts with (and precipitates) traces of
HCl in the chlorosilane, and minimizes hydrolysis during
aqueous workup.
6. Hudrlik, P. F.; Dai, D.; Hudrlik, A. M. J. Organomet.
Chem. 2006, 691, 1257–1264.
7. Compound 3, methyl iododiene 6, monoiododiene 9, and
monomethyldiene 12 were identified by their IR, 1H
NMR, 13C NMR (with DEPT), and mass spectra. The 1H
13
and C NMR spectra of 318 and 919 were consistent with
those reported.
8. A sample of diene 1020 was prepared by treatment of
diiodide 4 in THF with t-BuLi (4 mol per mol of 4)
followed by hydrolysis.
9. GC areas: 6:10:9 = 65.5:16:7; assignments confirmed by
GC and GC/MS comparisons with the previously
prepared samples; molar ratio by 1H NMR: 6:10:9 =
76:15:9. No evidence for the monomethyldiene 12 was
obtained.
10. By GC and 1H NMR; a small peak at the retention time of
monoiododiene 9 (3%) was also observed by GC, but
negligible amount (<0.2%) at that of the monomethyldiene
12.
Acknowledgements
We are grateful to the National Science Foundation/
Chemical Instrumentation (CHE-0342500), for funding
for the Agilent 5973 inert GC/MS instrument used in
this work. We thank Professor Hans Reich, for helpful
discussions.
11. Small GC peaks corresponding to monoiododiene 9 (3%)
and methyl iododiene 6 (5%) were also visible, with no
significant peaks (>0.2%) for 10 or 12. In a separate
experiment, GC analysis of an aliquot (before addition of
MeI) worked up with water showed considerable amounts
of monoiododiene 9 as well as diiodide 4, with a smaller
amount of diene 10 (GC ratio 9:4:10 = 21:48:15). Excess
MeI was added to the reaction mixture, and after workup,
GC analysis showed diiodide 4 to be the major product
(72% of GC area). Small peaks corresponding in retention
time to 9 (4%), methyl iododiene 6 (7.5%) and mono-
methyldiene 12 (1%) were also visible.
12. Carey, F. A.; Sundberg, R. J. Advanced Organic Chemis-
try, Part B, Reactions and Synthesis, 4th ed.; Kluwer/
Plenum: New York, 2001; p 433.
13. (a) Curtin, D. Y.; Johnson, H. W., Jr.; Steiner, E. G. J.
Am. Chem. Soc. 1955, 77, 4566–4570; (b) Neumann, H.;
Seebach, D. Chem. Ber. 1978, 111, 2785–2812; (c) Krebs,
Supplementary data
The experimental procedure for methyl iododiene 6, and
1H and 13C NMR spectra for 6 and 12 are available.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.03.067.
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