construct a 1,3,5-triene structure that minimizes the use of
special reagents, cost, time and steps remains highly desir-
able. Herein, we disclose a highly efficient method to con-
struct diverse 2,4-dihalo-1,3,5-trienes from propargylic
alcohols, providing quick access to multiple conjugated double
bonds with high selectivity in a single step (Scheme 1C). The
vinyl halogen moiety in the triene products can be easily
fuctionalized, thus making it a valuable synthon.8
As pioneered by Meyer, Schuster and Rupe,9 pro-
pargylic alcohols are versatile synthetic reagents in syn-
thetic organic chemistry. Apart from MeyerꢀSchuster and
Rupe rearrangement,10 many other elegant reactions have
utilization of propargylic alcohols as a practical and
versatile alkenylation reagent,14 in this work, we focus on
the possibility of constructing multisubstituted polyenes
using these readily available starting materials.
Our initial efforts were made to evaluate the palladium
catalysts for the nucleopalladation of 2-methylbut-3-yn-
2-ol (1a) to synthesize (E)-3,6-dibromo-2,7-dimethylocta-
2,4,6-triene (3a) with LiBr as the additive. As shown in
Table 1, Pd(II)-catalysts including Pd2(dba)3 and PdCl2
could afford the desired products, and Pd(OAc)2 proved
to be optimal (entries 1ꢀ3). The solvent was found to
have a dramatic impact on the efficiency of the reaction
(entries 3ꢀ8). Notably, HOAc was identified as the most
suitable medium for the formation of 3a (entry 3). Among
the various additives examined, LiBr gave the best result
(entry 3, 9, 10). Plus, the optimal reaction temperature
appeared to be 60 °C. Higher or lower reaction tempera-
tures just led to a decrease in the yield. However, there was
a significant increase in the yield when prolonging the
reaction time to 8 h, and the desired product was obtained
in 96% GC yield. The presence of phosphine ligands
inhibited this chemical process (entries 11ꢀ12). Thus, 1a
(0.5 mmol), Pd(OAc)2 (5 mol %), LiBr (1 mmol), and
HOAc (2 mL) as solvent at 60 °C were chosen as the
optimized conditions.
Scheme 1. Strategies for the Synthesis of Trienes
Under these optimized reaction conditions, the reaction
was applied to a range of substrates. A wide variety of tert-
propargylic alcohols successfully afforded the correspond-
ing 2,4-dibromo-1,3,5-triene derivatives (Scheme 2).
This transformation proceeded smoothly with high stereo-
selectivity and afforded the single E-type configuration
been developed.11 For instance, the SN20 displacement of
propargylic compounds with organometallic reagents (Au,
Rh, Zr, etc.) is one of the most commonly used methods to
prepare allenes.12 In analogy to this method, we have
reported a palladium-catalyzed method to prepare allenes
from propargylic alcohols,13 in which the allenes were
presumed to be generated directly through β-OH elimina-
tion. As part of our ongoing research program on the
Table 1. Optimization of Reaction Conditions for the Synthesis
of (E)-3,6-Dibromo-2,7-dimethy-locta-2,4,6,-triene from 1aa
entry
[Pd]
PdCl2
additive
solvent
yieldb (%)
1
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
LiBr
CuBr2
NH4Br
LiBr
LiBr
HOAc
HOAc
HOAc
Toluene
CH3CN
DMF
85
(8) (a) Kitamura, T.; Kobayashi, S.; Taniguchi, H. J. Am. Chem. Soc.
1986, 108, 2641. (b) Kabir, M. S.; Lorenz, M.; Cook, J. M. J. Org. Chem.
2010, 75, 3626. (c) Cohen, T.; Poeth, T. J. Am. Chem. Soc. 1972, 94, 4363.
(d) Chopa, A. B.; Dorn, V. B.; Badajoz, M. A.; Lockhart, M. T. J. Org.
Chem. 2004, 69, 3801.
(9) (a) Meyer, K. H.; Schuster, K. Chem. Ber. 1922, 55, 819. (b) Rupe,
H.; Glenz, K. Justus Liebigs Ann. Chem. 1924, 436, 195.
(10) (a) Rupe, H.; Kambli, E. Helv. Chim. Acta 1926, 9, 672.
(b) Rupe, H.; Kambli, E. Justus Liebigs Ann. Chem. 1927, 459, 215.
(c) Swaminathan, S.; Narayanan, K. V. Chem. Rev. 1971, 71, 431.
(11) (a) Ikeda, M.; Miyake, Y.; Nishibayashi, Y. Organometallics
2012, 31, 3810. (b) Hu, S. H.; Hager, L. P. J. Am. Chem. Soc. 1999, 121,
872. (c) Tian, G. Q.; Kaiser, T.; Yang, J. Org. Lett. 2010, 12, 288.
(d) Yuki, M.; Miyake, Y.; Nishibayashi, Y. Organometallics 2010, 29,
5994. (e) Inada, Y.; Nishibayashi, Y.; Hidai, M.; Uemura, S. J. Am.
Chem. Soc. 2002, 124, 15172.
(12) (a) Huang, W.; Shen, Q. S.; Wang, J. L.; Zhou, X. G. J. Org.
Chem. 2008, 73, 1586. (b) Marshall, J. A.; Wolf, M. A. J. Org. Chem.
1996, 61, 3238. (c) Riveiros, R.; Rodrıguez, D.; Sestelo, J. P.; Sarandeses,
´
L. A. Org. Lett. 2006, 8, 1403. (d) Zhu, Y. X.; Yin, G. W.; Hong, D.; Lu,
P.; Wang, Y. G. Org. Lett. 2011, 13, 1024. (e) Pu, X. T.; Ready, J. M.
J. Am. Chem. Soc. 2008, 130, 10874.
(13) Jiang, H. F.; Liu, X. H.; Zhou, L. Chem.;Eur. J. 2008, 14,
11305.
2
Pd2(dba)3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
80
3
96 (93)
37
4
5
trace
n.d.
n.d.
15
6
7
DMSO
Dioxane
HOAc
HOAc
HOAc
HOAc
8
9
79
10
11c
12d
12
56
18
a Reaction conditions: unless otherwise noted, all reactions were
performed with 1a (0.5 mmol), Pd-catalyst (5 mol %), LiBr (1 mmol) in
indicated solvent (2 mL) at 60 °C for 8 h. b Determined by GC using
dodecane as the internal standard. Data in parentheses are the yield of
isolated product. n.d. = not detected. c Phosphorus ligand dimethylbis-
diphenylphosphinoxanthene (10 mol %) was added. d Phosphorus
ligand 2-di-tert-butylphosphino-20,40,60-triisopropylbiphenyl (10 mol %)
was added, and 3-bromo-3-methylbut-1-yne was the main product.
B
Org. Lett., Vol. XX, No. XX, XXXX