CuCl-mediated tandem CO insertion and annulation of 1,4-dilithio-1,3- dienes: Formation of multiply substituted cyclopentadienones and/or their head-to-head dimers

Article abstract of DOI:10.1039/b719007g

Mediated by CuCl, 1,4-dilithio-1,3-dienes reacted with carbon monoxide (CO) to generate multi-substituted cyclopentadienones and/or their head-to-head dimers, via tandem CO insertion and intra/intermolecular cycloaddition of organocopper compounds. The Ro

Full text of DOI:10.1039/b719007g

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CuCl-mediated tandem CO insertion and annulation of 1,4-dilithio-1,3-
dienes: formation of multiply substituted cyclopentadienones and/or their
head-to-head dimersw
Qian Luo,a Chao Wang,a Wen-Xiong Zhanga and Zhenfeng Xi*ab
Received (in Cambridge, UK) 10th December 2007, Accepted 8th February 2008
First published as an Advance Article on the web 25th February 2008
DOI: 10.1039/b719007g
Mediated by CuCl, 1,4-dilithio-1,3-dienes reacted with carbon
monoxide (CO) to generate multi-substituted cyclopenta-
dienones and/or their head-to-head dimers, via tandem CO
insertion and intra/intermolecular cycloaddition of organo-
copper compounds.
The insertion reaction of carbon monoxide (CO) into organo-
lithiums (RLi) to yield carbonyllithium species {R(CQO)Li} is
of significant importance because of the immediacy and
Scheme 1 Reaction protocols of 1,4-dilithio-1,3-diene with CO.
efficiency for introducing carbonyl functional groups into
organic molecules.1–4 Recently, we have reported a novel
1,1-cycloaddition protocol to give trans-3-cyclopenten-1-ones
by reaction of 1,4-dilithio-1,3-diene with CO, in which co-
operation of the two alkenyl C–Li bonds with CO was
regarded as the key driving force for this reaction (Scheme
1, a).5 As our continued interest in organo-bi-metallic re-
agents, we extended our research program from dilithiobuta-
dienes to other dimetallabutadienes, such as organo-di-copper
reagents. For example, upon treatment of the 1,4-dilithio-1,3-
diene 1 with two equiv. of CuCl, novel cyclodimerization took
place leading to the synthesis of substituted semibullvalenes,6
presumably via butadienylcopper intermediates. Since
organocopper reagents have played very important roles in
modern synthetic chemistry,7–9 we have tried to use various
substrates to trap the proposed butadienylcopper intermedi-
ates. When carbon monoxide (CO) was used to react with the
CuCl-mediated reaction mixture of 1,4-dilithio-1,3-butadiene
1, we were surprised to observe an unprecedented cycloaddi-
tion reaction forming cyclopentadienones 2 and/or their head-
to-head dimers 3 (Scheme 1, b). To the best of our knowledge,
this is the first example of tandem CO insertion and intra- or
intermolecular annulation of organocopper reagents. Herein
we report our preliminary results.
addition of 2 equiv. of CuCl and stirring at ꢀ78 1C for 0.5 h,
CO was bubbled into the reaction mixture. The tetrapropyl-
cyclopentadienone 2a and octapropyl substituted head-to-
head dimer 3a were obtained in 30% and 25% yields, respec-
tively. After many trials, we found that 3a was formed
predominately in 61% isolated yield when 2 equiv. of di-tert-
butyl peroxide (tBuOOtBu) were added as an additive to the
reaction mixture (Scheme 2).
Encouraged by the above result, we then tested reactions of
a variety of 1,4-dilithio-1,3-dienes 1 with CO in the presence of
t
2 equiv. of CuCl and BuOOtBu. Representative results are
summarized in Table 1.z The tetraalkyl-substituted dilithiums
1b,c could react in a similar way to give the octa-substituted
3b,c as major products in good isolated yields (Table 1, entries
1 and 2). Further, penta-ring-fused dimer 3d was readily
prepared in 55% isolated yield from cyclic dilithio reagent
1d and CO in the presence of 2 equiv. of CuCl and tBuOOtBu.
Both 3a and 3d were structurally characterized by crystal
X-ray analyses.y The ORTEP drawing of 3a is shown in
Fig. 1. The single crystal structural data of 3d is given in the
ESI.w The two cyclopentadienone moieties are linked head-to-
head by C4, C5, C6, and C10 in a syn-trans fashion to the
cyclobutane ring. This type of head-to-head dimer with less
substituents could be prepared generally by [2þ2] photodimer-
ization of two molecules of cyclopentadienones,10 or by Lewis
acid-induced rearrangement of the Diels–Alder dimer of
1,2,3,4-Tetrapropyl-1,4-dilithio-1,3-diene 1a in a solution of
diethyl ether was generated in situ from its corresponding
1,4-diiodo-1,3-diene and t-BuLi at ꢀ78 1C for 1 h.5,6 After
a Beijing National Laboratory for Molecular Sciences (BNLMS), Key
Laboratory of Bioorganic Chemistry and Molecular Engineering of
Ministry of Education, College of Chemistry, Peking University,
Beijing 100871, China. E-mail: zfxi@pku.edu.cn; Fax: +86 10
62759728; Tel: +86 10 62759728
b State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai, 200032, China
w Electronic supplementary information (ESI) available: Experimental
details, NMR spectra of all new products, and X-ray data for 3a and
3d. CCDC 668730 and 668731. See DOI: 10.1039/b719007g
Scheme 2 CuCl-mediated reaction of 1,2,3,4-tetrapropyl-1,4-dilithio-
1,3-diene with CO with or without di-tert-butyl peroxide as an
additive.
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Table 1 CuCl-mediated reactions between 1,4-dilithio-1,3-diene 1
and COa
Entry Dilithium 1 Cyclopentadienone 2 Head-to-head dimer 3
1
Fig. 1 ORTEP drawing of 3a with 30% thermal ellipsoids. Hydrogen
atoms omitted for clarity.
It was very interesting to find out that formation of either
cyclopentadienones 2 or their head-to-head dimers 3 was
highly depending on the substituents of dilithiobutadiene
reagents 1. Thus, the CuCl-mediated reaction of phenyl or
TMS substituted 1,4-dilithio-1,3-dienes 1e–i with CO yielded
exclusively 2d–h in good isolated yields (Table 1, entries 4 to
8).13 These results were in striking contrast with what was
observed previously for the reaction of 1,4-dilithio-1,3-diene
with CO in the absence of CuCl to yield trans-3-cyclopenten-
1-ones.5
2
3b
Cyclopentadienones with three or less substituents, such as
3-arylindenones can undergo [2þ2] photodimerization to af-
ford its corresponding head-to-head dimer.10 However, when
2a was exposed to light irradiation, no formation of its [2þ2]
dimer 3a was observed (Scheme 3). Instead, a [4þ2] adduct 4
was readily formed in a quantitative yield.13 Further, no
reaction was detected when pure 2a was treated with 2 equiv.
of CuCl and tBuOOtBu. Interestingly, when pure 3a was
heated in toluene, carbon–carbon bond cleavage of the cen-
tered four-membered ring in 3a took place to afford 2a in a
quantitative yield (Scheme 3).
4
5
Based on the above results and observations, a possible
mechanism for the formation of 2 and 3 is proposed as shown
in Scheme 4. Dicopper intermediate A might be formed as the
first key intermediate. One molecule of CO may insert into the
carbon–copper bond of A to yield the acylcopper B. On one
hand, B may undergo intramolecular radical cyclization lead-
ing to the formation of 2. On the other hand, intermolecular
radical dimerization of B may afford diradical C, which
immediately undergoes intramolecular radical cyclization to
form 3. Observation of Cu mirror on the reaction tube
provided useful support for the radical reaction process. As
6
7
8
a
b
Isolated yield. Trace amount of cyclopentadienone was observed.
cyclopentadienones,11a or by photochemical rearrangement of
cyclobutane cage compounds.11b
There is only one report on the synthesis of octa-substituted
head-to-head dimers with aromatic substituents by
a
rhodium mediated cycloaddition of two molecules of
cyclopentadienones.12
Scheme 3 Interconversion between tetrapropylcyclopentadienone 2a
and its dimers.
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y Crystal data for 3a: C34H56O2, Mw ¼ 496.79 g molꢀ1, T ¼ 293(2) K,
orthorhombic, space group Aba2, a ¼ 19.655(4), b ¼ 20.326(4), c ¼
16.036(3) A, b ¼ 901, V ¼ 6407(2) A3, Z ¼ 8, rcalcd ¼ 1.030 Mg mꢀ3, m
¼ 0.061 mmꢀ1, reflections collected: 11 916, independent reflections:
2929 (Rint ¼ 0.0506), Final R indices [I 4 2sI]: R1 ¼ 0.0527, wR2
¼
0.1108, R indices (all data): R1 ¼ 0.1280, wR2 ¼ 0.1210. 3d: C34H52O,
Mw ¼ 492.76 g molꢀ1, T ¼ 293(2) K, monoclinic, space group C2/c, a
¼ 22.715(5), b ¼ 8.6051(17), c ¼ 16.731(3) A, b ¼ 109.25(3)1, V ¼
3087.4(11) A3, Z ¼ 4, rcalcd ¼ 1.060 Mg mꢀ3, m ¼ 0.063 mmꢀ1
,
¼
reflections collected: 7422, independent reflections: 2700 (Rint
0.0461), Final R indices [I 4 2sI]: R1 ¼ 0.0685, wR2 ¼ 0.1558, R
indices (all data): R1 ¼ 0.1758, wR2 ¼ 0.1757. There is a crystal-
lographical twofold symmetry in 3d. The C17 has its CH2 groups
disordered equally over two sides (only one of which is shown in Fig.
S2 (ESIw)). No allowance was made for the H atoms of both C16 and
C17. CCDC 668730 (3a) and 668731 (3d).
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Scheme 4 A possible mechanism for the formation of cyclopenta-
dienones 2 and diketones 3.
shown in entries 4–8 of Table 1, CuCl-mediated cycloaddition
of 1e–i with CO produced exclusively 2d–h, probably because
phenyl and TMS groups on the butadiene skeletons could
stabilize the carbon–copper bond of intermediate B and there-
fore intramolecular radical cyclization became more favored.
In summary, the first examples of tandem CO insertion and
intra- or intermolecular annulation of organocopper reagents
have been developed to afford cyclopentadienones and their
head-to-head dimers. Further investigation on the reaction
mechanism, scope and application are in process.
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This work was supported by the National Natural Science
Foundation of China and the Major State Basic Research
Development Program (2006CB806105). The Cheung Kong
Scholars Programme, Qiu Shi Science & Technologies Foun-
dation, Dow Corning Corporation, Eli Lilly China and BASF
are gratefully acknowledged.
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Chem. Soc., 2006, 128, 4564–4565; see also: C. Wang and Z. Xi,
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Notes and references
z A typical procedure for the preparation of cyclopentadienones and
their head-to-head dimers. To a 10 mL solution of 1,4-diiodo-1,3-diene
compound (1.0 mmol) in Et2O at ꢀ78 1C was added t-BuLi (4.0 mmol,
1.5 mol Lꢀ1 in pentane). After this reaction mixture was stirred at
ꢀ78 1C for 1 h, CuCl (2.0 mmol) was added and kept at ꢀ78 1C for
0.5 h. Then CO was bubbled into the vessel for 5 min, followed by
addition of tBuOOtBu (2.0 mmol) to this reaction mixture. After 1 h of
stirring at 0 1C, the reaction mixture was quenched with water and
extracted with Et2O. The extraction was washed with brine and dried
over MgSO4. The solvent was then evaporated in vacuo and the residue
was purified by column chromatography using silica gel (hexane :
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1
Et2O ¼ 20 : 1) to afford the final products. 2a: H NMR (300 MHz,
CDCl3, 25 1C): d ¼ 0.88 (t, J ¼ 7.2 Hz, 6H, CH3), 0.99 (t, J ¼ 7.2 Hz,
6H, CH3), 1.33–1.54 (m, 8H, CH2), 2.04 (t, J ¼ 7.5 Hz, 4H, CH2), 2.23
(t, J ¼ 7.5 Hz, 4H, CH2); 13C NMR (75 MHz, CDCl3, 25 1C): d ¼
14.23 (2 CH3), 14.43 (2 CH3), 22.52 (2 CH2), 22.85 (2 CH2), 24.91 (2
CH2), 28.30 (2 CH2), 125.78 (2 quat. C), 154.95 (2 quat. C), 204.94 (1
ketone CQO). 3a: 1H NMR (300 MHz, CDCl3, 25 1C): d ¼ 0.74 (t, J
¼ 7.2 Hz, 6H, CH3), 0.82 (t, J ¼ 7.5 Hz, 6H, CH3), 0.97 (t, J ¼ 7.2 Hz,
6H, CH3), 1.09 (t, J ¼ 7.2 Hz, 6H, CH3), 1.37–1.73 (m, 24H, CH2),
2.18–2.41 (m, 8H, CH2); 13C NMR (75 MHz, CDCl3, 25 1C): d ¼ 14.70
(2 CH3), 15.05 (2 CH3), 15.40 (2 CH3), 15.66 (2 CH3), 17.56 (2 CH2),
19.22 (2 CH2), 21.49 (2 CH2), 21.72 (2 CH2), 26.56 (2 CH2), 32.49
(2 CH2), 32.92 (2 CH2), 33.30 (2 CH2), 53.83 (2 quat. C),
60.85 (2 quat. C), 144.84 (2 quat. C), 173.41 (2 quat. C), 209.36
(2 ketone CQO).
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¨
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