Diverse reactivity of zirconacyclocumulenes derived from coupling of benzynezirconocenes with 1, 3-butadiynes towards acyl cyanides: Synthesis of indeno[2, 1-b]pyrroles or [3]cumulenones

Full text of DOI:10.1002/anie.200900951

Communications
DOI: 10.1002/anie.200900951
Synthetic Methods
Diverse Reactivity of Zirconacyclocumulenes Derived from Coupling
of Benzynezirconocenes with 1,3-Butadiynes towards Acyl Cyanides:
Synthesis of Indeno[2,1-b]pyrroles or [3]Cumulenones**
Xiaoping Fu, Jingjin Chen, Guangyu Li, and Yuanhong Liu*
The Group 4 metal complexes have attracted considerable
attention owing to their fascinating structural features, their
mediated sequence of cyclization and cross-coupling with aryl
iodides. We suggested that zirconacyclocumulenic intermedi-
ates were involved in our reactions.[5b] These original results
prompted us to study the chemistry of zirconacycles with a
cumulenic structure. We report herein an unprecedented
cycloaddition of carbamoyl cyanides to 1,3-butadiynes via
À
unique M C bonding, and their unusual capacity to induce
highly selective transformation reactions.[1] One of the most
ꢀ
extensively studied areas is the chemistry of diynes R(C C)2R
[2–4]
ꢀ
and polyynes R(C C)nR with metallocenes.
An extensive
investigation by Rosenthal and co-workers[2] was performed
using the metallocene source [Cp2M(L)(h -Me3SiC CSiMe3)]
(M = Ti, L = –; M = Zr, L = THF; Cp = C5H5) as a low-valent
seven-membered
zirconacyclocumulenes
to
form
À
2
2
ꢀ
dihydroindeno[2,1-b]pyrroles. It turns out that an sp C H
bond activation on the aromatic substituent of 1,3-butadiynes
takes place during the process. We also report the diverse
reactivity of the same zirconacycles towards aryl or alkyl acyl
cyanides, which provides a stereoselective route to cis-
[3]cumulenones (Scheme 1).
metal equivalent. These studies revealed a variety of inter-
À
esting reaction modes, such as complexation, C C single-
bond cleavage, and coupling reactions. The most notable
work was the discovery of the five-membered metallacyclo-
cumulenes [Cp2M(h4-1,2,3,4-RC4R)] (R = tBu, M = Zr, Ti; h4-
complexes), which formed
an equilibrium with a met-
allacyclopropene (h2-com-
plex) in some reactions.
Seven-membered zircona-
cyclocumulenes have also
been accessed through
homocoupling of butadiy-
nes[4c] or cross-coupling of
benzynezirconocenes with
butadiynes.[4a]
However,
the utilization of these com-
plexes in organic synthesis
has rarely been reported.
Scheme 1. Diverse reactivity of zirconacyclocumulenes.
Recently, we showed that
zirconium-mediated coupling of 1,3-butadiynes with alde-
hydes or ketones provides an efficient, general, one-pot
method for cis-[3]cumulenol formation.[5a] We also investi-
Meunier et al. reported that the coupling reaction of 1,4-
diphenyl-1,3-butadiyne 1a with benzynezirconocene [Cp2Zr-
(h2-C6H4)] occurs by heating 1a with diphenylzirconocene at
808C for several hours, furnishing a seven-membered zirco-
nacyclocumulene 2a (Table 1, Ar= Ph). Theoretical calcula-
tions revealed that an interaction between the dxy metal
atomic orbital with one terminal s orbital and with the in-
plane p orbital of the cumulene contribute to the remarkable
stability of 2a.[4a] In our continuing effort to explore the new
synthetic potential of functionalized zirconacycles towards
carbon electrophiles,[6] we found that treatment of zircona-
cycle 2a formed in situ with N,N-dimethylcarbamoyl cyanide
at 808C overnight afforded 1,8-dihydroindeno[2,1-b]pyrrole
3a in 74% yield after hydrolysis (Table 1, entry 1). The
structures of 3a and 3h were unambiguously confirmed by X-
ray crystallographic analysis,[7] which clearly showed the
pyrrole ring. The structure of 3h also indicated that the
phenyl group on the indenyl sp3 carbon atom is derived from
benzynezirconocene.
À
gated the C C bond formation reactions of a-alkynylzirco-
nacyclopentenes by cyclization or by a copper- and palladium-
[*] X.-P. Fu, J.-J. Chen, Prof. G.-Y. Li, Prof. Y.-H. Liu
State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences
345 Lingling Lu, Shanghai 200032 (China)
Fax: (+86)21-6416-6128
E-mail: yhliu@mail.sioc.ac.cn
[**] We thank the National Natural Science Foundation of China (Grant
No. 20672133, 20732008), Chinese Academy of Science, Science
and Technology Commission of Shanghai Municipality (Grant No.
07JC14063, 08QH14030), and the Major State Basic Research
Development Program (Grant No. 2006CB806105) for financial
support.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200900951.
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Table 1: Preparation of 1,8-dihydroindeno[2,1-b]pyrrole-2-carboxamide or -carboxylate.
smoothly underwent cycloaddition
reactions to yield pyrrole deriva-
tives with the formamide function-
ality CONR1R2 in 33–76% yields.
N,N-Diphenyl-substituted
carba-
moyl cyanide afforded the corre-
sponding pyrrole 3b in 74% yield,
indicating that the aryl substituents
on carbamoyl cyanides have little
influence on the cycloaddition reac-
tion (Table 1, entry 2). The addition
of cyclic carbamoyl cyanides simi-
larly gave 3d and 3e in 67 and 76%
Entry Butadiyne
Cyanide compound Product
Yield [%][a]
74
1
Me2NCOCN
3a
1a
R’=Me
yields,
respectively
(Table 1,
2
3
1a
1a
Ph2NCOCN
iPr2NCOCN
R’=Ph
R’=iPr
3b
3c
74
74
entries 4 and 5). The N-benzyl-N-
alkyl carbamoyl cyanide afforded
the corresponding product 3 f in
40% yield (Table 1, entry 6). Inter-
estingly, ethyl cyanoformate could
also be used for this reaction, and
the pyrrole 3g bearing an ester
functionality was obtained in 53%
yield (Table 1, entry 7). When bis-
4
1a
3d
67
5
1a
1a
3e
76
(thienyl)butadiyne
1d
was
6
7
3 f
40
53
employed, the corresponding prod-
uct 3j was formed in 33% yield
(Table 1, entry 10).
We tentatively propose the fol-
lowing plausible mechanism for this
cascade reaction (Scheme 2): first, a
seven-membered zirconacyclocu-
mulene 2 is produced in the reac-
tion mixture, which is assumed to be
in equilibrium with the five-mem-
bered a-alkynylzirconacyclopenta-
diene 4. An SE2’-type addition[11]
of carbamoyl cyanide to the zirco-
nacycle intermediate 4, presumably
via a cyclic transition state by coor-
dination of cyano group to zirco-
nium, gives a nine-membered aza-
zirconacycle 6 with a cumulenic
moiety. In this case, the cyanide
group is much more reactive than
the carbonyl group, as the elec-
1a
EtOCOCN
3g
1b, Ar=p-MeOC6H4
8
Me2NCOCN
3h
51
1c, Ar=p-(n-C5H11)C6H4
9
3i
3j
70
33
10
Me2NCOCN
1d
[a] Yield of isolated product. All reactions were carried out overnight at 808C.
It is interesting to note that in this novel transformation,
the reactions of benzene-fused zirconacyclocumulene 2
tronic delocalization over the O-C-N unit caused by reso-
nance of the nitrogen lone pair with the carbonyl p system
would decrease the reactivity of the carbonyl group. How-
proceeded selectively at the cumulenic zirconium moiety,
2
À
while the Zr C(sp ) bond at the side of benzene ring
ever, direct insertion of the cyano group into the cumulenic
2
À
remained intact. Most striking is the conversion of one of
the free phenyl groups on the butadiyne moiety into the fused
indene ring, which can be explained by the activation of the
Zr C(sp ) bond of 2 cannot be excluded. Intramolecular
attack of the nitrogen atom at the cumulenic double bond
results in the formation of a zwitterionic intermediate 7,
which immediately abstracts a hydrogen from the adjacent
phenyl ring to afford 8. Metal-assisted attack of the triene
double bond by oxygen or carbon nucleophiles has precedent
in the literature.[5b,12] Compound 8 undergoes ring closure and
subsequent 1,3-H shift to give intermediate 10. Hydrolysis of
10 affords the desired product 3.
À
C H bond at the ortho position of the phenyl ring.
Pyrroles are important heterocycles that widely occur as
key structural subunits in numerous natural products,[8] which
can find various applications in pharmaceuticals[9] and
materials science.[10] The tandem sequence described herein
allows the efficient synthesis of complex pyrrole derivatives.
As shown in Table 1, a variety of carbamoyl cyanides
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yields, respectively, with high stereoselectiv-
ity, as confirmed by X-ray crystallographic
analysis of 11i[7] (Table 2, entries 9 and 10).
Butadiyne 1g with an OPh group was also
compatible with this reaction, furnishing
11k in 72% yield (Table 2, entry 11). It
should be noted that cis–trans isomeriza-
tion[13] easily occurred during the workup of
11h and 11k. It turned out that if all of the
operations were carried out at room temper-
ature, isomerization could be minimized,
and cis/trans ratios of 91:9 (11h) and 90:10
(11k) were obtained.
These results indicated that aryl acyl
cyanides behaved differently than carba-
moyl cyanides. A plausible reaction mecha-
nism is shown in Scheme 4. In this scenario,
a carbonyl group instead of a CN group
À
reacts with the Zr C bond to form nine-
membered zirconacycle 12. Hydrolysis of 12
may afford cyanohydrin 13, which was
unstable and easily converted into the
Scheme 2. Proposed mechanism for the formation of indeno[2,1-b]pyrroles.
cumulenone 11 upon direct isolation by
column chromatography or treatment with
To support the proposed reaction mechanism, a deuter-
ated butadiyne 1,4-di(para-(n-pentyl)phenyl)buta-1,3-diyne
[D]1c was prepared (deuterium incorporation is 91%). The
coupling reaction with morpholine-4-carbonyl cyanide suc-
cessfully afforded the pyrrole [D]3i with 75% incorporation
of Da (Scheme 3). The result clearly indicates that one of the
Et3N prior to column separation. An attractive advantage of
this strategy is the stereoselective construction of cumulenic
compounds that are not easily available by other methods.
In summary, we have shown that cycloaddition of
carbamoyl cyanide compounds to zirconacyclocumulenes
derived from zirconium-mediated benzyne–1,3-butadiyne
coupling reactions afforded 1,8-dihydroindeno[2,1-b]pyrroles,
while the reactions of aryl or alkyl acyl cyanides provided
access to an efficient one-pot procedure for the
cis-selective synthesis of tetrasubstituted
[3]cumulenones. Clarification of the reaction
mechanism and further application of this
chemistry are in progress.
À
ortho C H bonds of the aromatic ring on the butadiyne
terminus was activated during the reaction.
Experimental Section
General procedure for the preparation of 1,8-
dihydroindeno[2,1-b]pyrrole-2-carboxamides or -car-
boxylate 3: PhLi (1.4 mmol, 2.0m in dibutyl ether,
Scheme 3. The reaction with a deuterated butadiyne.
0.7 mL) was added dropwise to a solution of [Cp2ZrCl2]
(0.19 g, 0.65 mmol) in toluene (5 mL) at 08C. After
stirring for 1 h at that temperature, 1,3-butadiyne 1
In light of the unusual reactivity of zirconacycle 2, we
proceeded to investigate the reactions of 2 with aryl acyl
cyanides. Interestingly, it was found that [3]cumulenone 11
was formed in good to high yields after hydrolysis. Repre-
sentative results are shown in Table 2. Functionalized aryl
acyl cyanides bearing a chlorine (88%), NO2 (91%), methyl
(85%), or heterocyclic group (83%) reacted very well with
zirconacycle 2a, leading to the corresponding products in high
yields (Table 2, entries 2–4, 6). An alkyl acyl cyanide such as
tBuCOCN could also be used; product 11g was formed in
66% yield, although a higher reaction temperature of 808C
was required (Table 2, entry 7). When alkyl-substituted
butadiynes 1e and 1 f were used, the reaction selectively
afforded cis-[3]cumulenones 11i and 11j in 69 and 74%
(0.5 mmol) was added, and the reaction mixture was warmed up to
808C and stirred for 6 h. The resulting orange-yellow solution was
allowed to return to room temperature, and carbamoyl cyanide or
ethyl cyanoformate (1.0 mmol) was added. Then the reaction mixture
was warmed up to 808C and stirred overnight. The reaction mixture
was allowed to return to room temperature, was quenched with
saturated aqueous NaHCO3 and extracted with diethyl ether. The
extract was washed with water and brine, and dried over anhydrous
MgSO4. The solvent was evaporated in vacuo, and the residue was
purified by column chromatography on silica gel to afford the desired
pyrrole products 3.
General procedure for the preparation of [3]cumulenones 11:
PhLi (1.4 mmol, 2.0m in dibutyl ether, 0.7 mL) was added dropwise to
a solution of [Cp2ZrCl2] (0.19 g, 0.65 mmol) in toluene (5 mL) at 08C.
After stirring for 1 h at that temperature, 1,3-butadiyne 1 (0.5 mmol)
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R2COCN
PhCOCN
Product Yield [%][a] cis/trans
1
11a
84
1a
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3
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1a
1a
1a
1a
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p-ClC6H4COCN
11b
88
91
85
90
p-NO2C6H4COCN 11c
p-MeC6H4COCN 11d
1-naphthyl-COCN 11e
2-furanyl-COCN
tBuCOCN
11 f
11g
83
66[b]
8
p-NO2C6H4COCN 11h
p-NO2C6H4COCN 11i
p-NO2C6H4COCN 11j
67
69
74
91:9
95:5
97:3
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was added, and the reaction mixture was warmed up to 808C and
stirred for 6 h. The resulting orange-yellow solution was allowed to
return to room temperature, and acyl cyanide (0.5 mmol) was added.
After stirring for 1 h, the reaction mixture was quenched with 3n HCl
and then extracted with diethyl ether three times. The extract was
washed with saturated aqueous NaHCO3, water, and brine and dried
over anhydrous MgSO4. The solvent was removed by rotary
evaporation and oil pump successively at room temperature to
minimize cis-trans isomerization, and the residue was purified by
chromatography on silica gel to afford the [3]cumulenone derivatives
11. When pivaloyl cyanide was used, the reaction was carried out
overnight at 808C and quenched with saturated NaHCO3 solution. In
some cases, several drops of Et3N were added to the extract of the
reaction mixture after workup and then the solution was stirred for ca.
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Published online: May 28, 2009
À
Keywords: C H activation · cumulenes · cycloaddition ·
synthetic methods · zirconium
.
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