Construction of octaalkyl-substituted and decasubstituted all-cis-octatetraenes via linear dimerization of 1,4-dicopper-1,3-butadienes and subsequent cross-coupling with halides

Article abstract of DOI:10.1021/ol400140n

Lithium iodide-assisted linear dimerization of 1,4-dicopper-1,3-butadienes and subsequent Pd-catalyzed cross-coupling reaction with halides provide an efficient way to construct octaalkyl-substituted and decasubstituted all-cis octatetraenes.

Full text of DOI:10.1021/ol400140n

ORGANIC
LETTERS
2013
Vol. 15, No. 6
1222–1225
Construction of Octaalkyl-Substituted and
Decasubstituted all-cis-Octatetraenes
via Linear Dimerization of 1,4-Dicopper-1,
3-butadienes and Subsequent
Cross-Coupling with Halides
Junnian Wei,† Zitao Wang,† Wen-Xiong Zhang,† and Zhenfeng Xi*,†,‡
Beijing National Laboratory of Molecular Sciences (BNLMS) and Key Laboratory of
Bioorganic Chemistry and Molecular Engineering of Ministry of Education,
College of Chemistry, Peking University, Beijing 100871, China, and
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, CAS, Shanghai 200032, China
zfxi@pku.edu.cn
Received January 16, 2013
ABSTRACT
Lithium iodide-assisted linear dimerization of 1,4-dicopper-1,3-butadienes and subsequent Pd-catalyzed cross-coupling reaction with halides
provide an efficient way to construct octaalkyl-substituted and decasubstituted all-cis octatetraenes.
Conjugated polyenes have received intense interest in
recent decades because of their unique electronic structures
and optoelectronic properties.1,2 The introduction of alkyl
† Peking University.
‡ Shanghai Institute of Organic Chemistry, CAS.
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Figure 1. Stereocontrolled all-substituted octatetraenes.
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to solve the insolubility, infusibility, and instability pro-
blems of such compounds. Therefore, it is of significant
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selective synthesis of substituted trans-tetraenes5a,b by oligo-
merization of alkynes. Wu et al. reported a nickel-catalyzed
r
10.1021/ol400140n
Published on Web 03/01/2013
2013 American Chemical Society

Scheme 1. Thermal DecompositionÀLinear Dimerization of
Scheme 2. CuCl/LiI-Mediated Dimerization of 1,4-Dilithio-1,
3-butadienes
Butadienyl Dicopper Compounds
tetramerization of arylacetylenes to construct trans-tetraenes
(Figure 1).5c Although many examples are known for the
synthesis of trans-substituted octatetraenes,4À6 there is no
report in the literature for the synthesis of fully substituted
all-cis octatetraenes, except for one case where they formed
as byproducts.7
We have been working on the synthesis and synthetic
applications of multiply substituted 1-lithio-1,3-butadienes
(I, Scheme 1)8 and 1,4-dilithio-1,3-butadienes (III).9 The
alkyl substituents on the butadienyl skeletons in I and
III are all-cis oriented. Inspired by the formation of
conjugated dienes via homocoupling of vinylic mono-
copper reagents,10,11 we envisioned that the 1,3-butadienyl
monocopper compounds (II), generated in situ from the
reaction between I and CuCl, could undergo a similar
thermal dimerization to provide a direct method to synthe-
size octaalkyl-substituted all-cis octatetraene derivatives 1.
However, the corresponding thermal dimerization did not
occur. Interestingly, 1,4-dicopper-1,3-butadienes (IV),12
generated in situ from the reaction between III and CuCl,
were found to undergo thermal decomposition-linear di-
merization, yielding the corresponding octatetraenyl di-
copper (V). The addition of lithium iodide was found very
effective for this thermal decomposition-linear dimeriza-
tion process. Hydrolysis of V afforded octa-alkyl substi-
tuted all-cis octatetraene derivatives 1 in excellent yields.
Subsequent Pd-catalyzed cross-coupling of V with halides
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Org. Lett., Vol. 15, No. 6, 2013
1223

Table 2. Construction of Fully Substituted all-cis-Octatetraenes
Scheme 3. Cyclic Dimerization of Octatetraenyl Dicopper
Intermediates
Table 1. Optimization of Reaction Conditions
temp time
yield of
entry (°C) (h)
additive
solvent
Et2O
2ca (%)
a Isolated yields.
1
2
3
4
5
6
7
8
0
0
4
4
4
4
4
4
8
DMPU
DMPU
Et2O
Et2O
Et2O
rt
rt
rt
Pd(PPh3)4 5% Et2O
10
42
67
64
50
60
60
Pd(PPh3)4 5% THF/Et2O (2:1)
Pd(PPh3)4 5% THF/Et2O (2:1)
12 Pd(PPh3)4 5% THF/Et2O (2:1)
a Isolated yields.
constructed fully substituted all-cis octatetraene deriva-
tives 2.
As demonstrated in Scheme 2, we first used the isolated
purified 1,4-dilithio-1,3-butadiene IIIa as the starting ma-
terial. However, only cyclic products 3a and 4a were
observed. Surprisingly, when IIIa generated in situ from
its corresponding 1,4-diiodocompounds5awas used,13 the
all-cis-substituted octaethyl 1,3,5,7-tetraene 1a was ob-
tained in 41% isolated yield, along with cyclic products
3a and 4a. The only difference between these two reactions
was that in the second reaction 2 equiv of lithium iodide
was generated in situ. This observation indicated that
lithium iodide could promote the formation of the octate-
traenyl dicopper V intermediates and stabilize them.
Thus, additional LiI was added. As expected (Scheme 2),
when the dilithio compound III generated in situ was
treated with copper(I) chloride and extra lithium iodide,
the color of the mixture changed from yellow to dark
brownimmediately. Themixture was stirred at0 °C for 4 h,
and copper mirror was observed. During this process,
thermal decomposition and linear dimerization proceeded
smoothly to afford the proposed all-cis-alkyl-substituted
octatetraenyl dicopper V. Quenching of V with aqueous
3 N HCl afforded their corresponding tetraenes 1 in
Figure 2. Single-crystal X-ray structures of 2a (upper) and 2b
(down) with 20% thermal ellipsoids. Hydrogen atoms are
omitted for clarity.
excellent isolated yields, which represented an efficient
synthesis of all-cis-alkyl-substituted octatetraenes.
When the octatetraenyl dicopper Va generated in situ
was heated at 60 °C for 8 h (Scheme 3), no obvious further
linear dimerization took place. Instead, cyclic dimerization
occurred, affording the octaethyl-substituted cyclooctate-
traene 4a as a major product in 62% isolated yield.14
Based on the above results, we envisioned that V
could be further applied to introduce two more substitu-
ents via transition-metal-catalyzedcross-coupling reactions
(13) Song, Q.; Chen, J.; Jin, X.; Xi, Z. J. Am. Chem. Soc. 2001, 123,
10419.
(14) For a review on cyclooctatetraenes, see: Wang, C.; Xi, Z. Chem.
Commun. 2007, 48, 5119.
1224
Org. Lett., Vol. 15, No. 6, 2013

between the CÀCu bonds and electrophiles. Thus 1,8-
double phenylation of Vc was first attempted (Table 1),
aiming at the synthesis of 1,8-diphenyl octatetraene 2c,
which has an elongated π-conjugation. Optimal reaction
conditions were realized as follows: Pd(PPh3)4 (5 mol %),
in a mixed solvent (THF/Et2O = 2: 1), 60 °C, 8 h. Under
the optimal conditions (entry 7), the product 2c was
obtained in 67% isolated yield.
More examples of fully substituted all-cis-octatetraenes
2 are given in Table 2. In the cases of 2b and 2d, formation
of their corresponding cyclooctatetraenes was also observed.
The reported computational studies have indicated that
octatetraenes should exist in a nonplanar state.15 Single-
crystal X-ray structural analysis of 2a and 2b clearly show
their all-cis and nonplanar skeleton structures (Figure 2).
In summary, an efficient synthesis of octaalkyl-substi-
tuted and decasubstituted all-cis-octatetraenes has been
achieved via LiI-assiated thermal decomposition-linear
dimerization of 1,4-dicopper-1,3-butadienes and subse-
quent Pd-catalyzed cross-coupling between CÀCu bonds
and electrophiles. Further studies on a detailed reaction
mechanism and synthetic applications are in progress.
Acknowledgment. This work was supported by the
Natural Science Foundation of China and the 973 Pro-
gram (2011CB808700).
Supporting Information Available. Experimental de-
tails; X-ray data for 2a (CCDC-911652) and 2b (CCDC-
911651); scanned NMR spectra of all new products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(15) (a) Rao, B. K.; Darsey, J. A.; Kestner, N. R. J. Chem. Phys. 1983,
79, 1377. (b) Rao, B. K.; Darsey, J. A.; Kestner, N. R. Phys. Rev. B 1985,
31, 1187.
The authors declare no competing financial interest.
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