Lewis acid-promoted reactions of zirconacyclopentadienes with isocyanates. A one-pot three-component synthesis of multiply-substituted iminocyclopentadienes from one isocyanate and two alkynes

Article abstract of DOI:10.1039/b509142j

Multiply-substituted iminocyclopentadienes were formed from Lewis acid-promoted reactions of zirconacyclopentadienes and isocyanates via a one-pot three-component coupling process; the C=O double bond of the RN=C=O moiety in the isocyanate was cleaved, and the isocyanates behaved formally as a one-carbon unit with Lewis acid-dependent and substituent-dependent reactions being realized. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b509142j

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COMMUNICATION
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Lewis acid-promoted reactions of zirconacyclopentadienes with
isocyanates. A one-pot three-component synthesis of
multiply-substituted iminocyclopentadienes from one isocyanate and
two alkynes{
Jiang Lu,a Guoliang Mao,a Wenxiong Zhanga and Zhenfeng Xi*ab
Received (in Cambridge, UK) 30th June 2005, Accepted 2nd August 2005
First published as an Advance Article on the web 5th September 2005
DOI: 10.1039/b509142j
No reaction was observed when zirconacyclopentadienes 1 were
treated with isocyanates. As demonstrated in Scheme 2, after
addition of BF3?Et2O, reaction of zirconacyclopentadienes 1 with
isocyanates immediately took place to afford cyclopentadienyl
imines 2. Representative examples are given in Table 1.
Multiply-substituted iminocyclopentadienes were formed from
Lewis acid-promoted reactions of zirconacyclopentadienes and
isocyanates via a one-pot three-component coupling process;
the CLO double bond of the RNLCLO moiety in the isocyanate
was cleaved, and the isocyanates behaved formally as a one-
carbon unit with Lewis acid-dependent and substituent-
dependent reactions being realized.
2,3,4,5-Tetrasubstituted-1-zirconacyclopentadienes 1a (with
tetraalkyl substituents) and 1b (with tetraaryl substituents),12 and
zirconaindene 1c13 all reacted with aryl isocyanates in the presence
of BF3?Et2O to afford multiply-substituted iminocyclopentadiene
derivatives 2a–f and indenyl imines 2g–i, respectively, in good to
high isolated yields. This reaction is highly site selective; only the
CLO double bond in the RNLCLO moiety is cleaved to form the
iminocyclopentadienes. No cleavage of the CLN double bond is
observed. Iminocyclopentadiene and indenimine derivatives are all
interesting and useful intermediates for synthetic chemistry and
organometallic chemistry.14,15 The reaction reported here provides
an alternative practical method for the preparation of such
complex compounds, via a one-pot three-component procedure. It
should be noted that reactions of aliphatic isocyanates with
We have recently been interested in Lewis acid-mediated reactions
of organometallic compounds with organic substrates,1,2 since the
development of synthetic methods can be expected from a
combination of transition metal-mediated C–C bond-forming
reactions and Lewis acid-mediated organic transformations.1–10
This strategy has been proved to be efficient and useful by us,1,2
Tilley,3 Negishi4 and others.5–10 Zirconacyclopentadienes 1, which
can be easily prepared in situ from two alkyne molecules and low
valent zirconocene species, are generally inert towards most
organic substrates.11 Interestingly, as we have reported previously,
zirconacyclopentadienes 1 could react smoothly with aldehydes to
afford cyclopentadiene derivatives when a Lewis acid such as AlX3
or BF3 was present in the reaction mixture.1
Isocyanates (RNLCLO) are a class of important synthetic
intermediates. The site selectivities of these unsymmetrical hetero-
cumulenes toward nucleophiles are of great interest in heteroatom
chemistry and controlled synthetic chemistry. As part of our
continuous interest in the development of synthetically useful
methods by combining transition metal-mediated C–C bond
forming reactions with Lewis acid-mediated organic transforma-
tions, we investigated the reactions of 1 with unsymmetrical
heterocumulenes such as isothiocyanates (RNLCLS) and isocya-
nates (RNLCLO). Iminocyclopentadiene derivatives composed of
three different components were prepared in one pot in excellent
yields via cleavage of the CLO double bond of the RNLCLO
moiety (Scheme 1). Depending on the Lewis acids used and the
reaction conditions, different types of products were formed.
Scheme 1
aKey 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: +86-10-62751708;
Tel: +86-10-62759728
bState Key Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032,
China
{ Electronic Supplementary Information (ESI) available: Experimental
details and copies of 1H and 13C NMR charts for all new compounds. See
http://dx.doi.org/10.1039/b509142j
Scheme 2
4848 | Chem. Commun., 2005, 4848–4850
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Table 1 Preparation of multi-substituted iminocyclopentadienes from BF3?Et2O-mediated reaction of zirconacyclopentadienes with isocyanatesa
Run
1
Zirconacyclopentadiene 1
Isocyanate Ar group
3,5-dichlorophenyl
Product 2
Yield of 2 (%)b
1a
2a
74
2
3
4
5
6
1a
1a
1a
1a
1b
2,4-dichlorophenyl
4-bromophenyl
4-fluorophenyl
2-chlorophenyl
2-chlorophenyl
2b
2c
2d
2e
2f
73
81
77
75
91
7
1c
2-chlorophenyl
2g
59
8
9
a
1c
1c
4-methoxyphenyl
4-methylphenyl
2h
2i
55
51
Reaction conditions: 2 equiv. of ArNCO, 4 equiv. of BF3?Et2O; the reaction mixture was stirred firstly at 0 uC for 1 h then at 80 uC for 1 h.
Isolated yields.
b
zirconacyclopentadienes and zirconaindenes under the same
determining the type of products obtained. 2,4-Dichlorophenyl
isocyanate (Table 2, run 1) and 2-chlorophenyl isocyanate (Table 2,
run 2) afforded 1,6-bisamide derivatives in high isolated yields
whilst 4-bromophenyl isocyanate (Table 2, run 3) gave the
monoamide product.16 Other aryl isocyanates such as 4-chloro-,
4-fluoro-, and 4-methyl- isocyanates afforded a mixture of bis- and
monoamide derivatives. Such dramatic Lewis acid-dependent and
substituent-dependent changes have not been observed in our
previous work. Transmetallation of the zirconium species to an
aluminium species is assumed to be essential for this reaction.
Further investigation is needed to explain this novel selectivity.
reaction conditions described above generally gave messy mixtures
of products. Messy mixtures of products were also obtained when
isothiocyanates, either aryl or aliphatic, were applied under the
same reaction conditions.
Other Lewis acids generally behaved differently from BF3. For
example, CsF, InCl3, CoCl2, VCl3, TiCl4 and CrCl3 did not
promote the above reactions. In the case of FeCl3 as the Lewis
acid, a messy mixture of reaction products was observed. When
AlCl3 and AlBr3 were used, the zirconacyclopentadienes 1 and
isocyanates disappeared, but did not result in formation of isolable
products. Very interestingly, when EtAlCl2 was used as the Lewis
acid, substituent-dependent and Lewis acid-dependent selectivities
were observed. Scheme 3 shows a representative example. Results
are given in Table 2. Treatment of 2,3,4,5-tetrapropyl-1-zircona-
cyclopentadiene 1a with ArNCO in the presence of BF3?Et2O
afforded their iminocyclopentadiene derivatives in high yields
(Table 1). However, on the contrary, different products were
obtained only by changing the Lewis acid from BF3 to EtAlCl2
(Table 2). No iminocyclopentadiene derivatives were obtained
when EtAlCl2 was used as the Lewis acid. Furthermore, the
substituent on the Ar ring played a very important role in
Table 2 EtAlCl2-mediated substituent-dependent reactions of zirco-
nacyclopentadiene 1d with isocyanatesa
Run
1
Isocyanate
Yield of 2 (%) Yield of 3 (%) Yield of 4 (%)
0
0
3a: 89
3b: 80
trace
2
0
3
4
0
0
0
0
0
4a: 54
4b: 30
4c: 40
4d: 21
3c: 23
3d: 26
3e: 34
5
6
a
Isolated yields
Scheme 3
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Notes and references
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Scheme 4
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Scheme 5
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For the formation of iminocyclopentadienes 2 from the BF3-
mediated reaction of zirconacyclopentadienes 1 with isocyanates, a
proposed reaction mechanism is given in Scheme 5. Metathesis in 6
is assumed to be a key process in the mechanism from 1 to 2.17
Detailed investigation to understand the scope, application and
reaction mechanisms is in progress.
This work was supported by the National Natural Science
Foundation of China (29825105, 20172003, 20232010) and the
Major State Basic Research Development Program
(G2000077502-D). The Cheung Kong Scholars Programme and
BASF are gratefully acknowledged.
4850 | Chem. Commun., 2005, 4848–4850
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