Hydride-Induced novel cyclization of dienedinitriles leading to multifunctionalized cyclopentadienes

Article abstract of DOI:10.1021/ol901840c

By treatment with LIAIH₄,1,4-dicyano-1,4-bis(trimethylsilyl)-1, 3-dienes underwent a novel hydride-induced nucleophilic intermolecular 1,4-addltion to the α,β-unsaturated nitrile moiety, followed by an Immediate nucleophilic Intramolecular 1,2-

Full text of DOI:10.1021/ol901840c

ORGANIC
LETTERS
2009
Vol. 11, No. 19
4458-4461
Hydride-Induced Novel Cyclization of
Dienedinitriles Leading to
Multifunctionalized Cyclopentadienes
Hui-Jun Zhang,†,‡ Tianhao Meng,§ Bernard Demerseman,‡ Christian Bruneau,*,‡
and Zhenfeng Xi*,†
Beijing National Laboratory for Molecular Science (BNLMS), Key Laboratory of
Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of
Chemistry, Peking UniVersity, Beijing 100871, China, Science Chimiques de Rennes,
UMR 6226 CNRS-UniVersite´ de Rennes 1, Catalyse et Organome´talliques, UniVersite´
de Rennes 1, 35042 Rennes Cedex, France, and Institute of Chemistry, Chinese
Academy of Science, Beijing 100190, China
zfxi@pku.edu.cn
Received August 7, 2009
ABSTRACT
By treatment with LiAlH4, 1,4-dicyano-1,4-bis(trimethylsilyl)-1,3-dienes underwent a novel hydride-induced nucleophilic intermolecular 1,4-addition to
the r,ꢀ-unsaturated nitrile moiety, followed by an immediate nucleophilic intramolecular 1,2-addition to the remaining CN group, to afford multiply
functionalized cyclopentadienes in high isolated yields. These multifunctional (-CN, -NH2, -SiMe3, -H) cyclopentadienes are of a rich and interesting
reaction chemistry as preliminarily demonstrated by their reaction with ArNCO involving both the substituent and the ring.
Cyclopentadienes are among the most useful and the most
frequently applied organic compounds in many aspects
including organic synthesis and organometallic chemistry.1-3
Therefore, the development of efficient synthetic approaches
to cyclopentadienes, especially the functionalized ones,3,4 has
been in great demand. In this paper, we report a convenient
and efficient synthesis of novel multiply functionalized
cyclopentadienes concomitantly bearing cyano, amino, and
(3) For the synthesis of multisubstituted Cp ligands, see: (a) Venier,
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2163–2164. (c) Xi, Z. Top. Catal. 2005, 35, 63–71, and references therein.
(d) Enders, M.; Baker, R. W. Curr. Org. Chem. 2006, 10, 937–953. For
synthesis of functionalized Cp-metal complexes, see: (e) Poli, R. Chem.
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(h) Siemeling, U. Chem. ReV. 2000, 100, 1495–1526. (i) Butenscho¨n, H.
Chem. ReV. 2000, 100, 1527–1564. (j) Enders, M.; Kohl, G.; Pritzkow, H.
Organometallics 2004, 23, 3832–3839. (k) Stoll, A. H.; Mayer, P.; Knochel,
P. Organometallics 2007, 26, 6694–6697.
† Peking University.
‡ Universite´ de Rennes 1.
§ Institute of Chemistry, CAS.
(1) (a) Corey, E. J.; ChengX.-M. The Logic of Chemical Synthesis;
Wiley: New York, 1989; Chapter 7, p 249. (b) Winterfieldt, E. Chem. ReV.
1993, 93, 827–843. (c) Walters, M. A.; Arcand, H. R. J. Org. Chem. 1996,
61, 1478–1486. (d) Corey, E. J. Angew. Chem., Int. Ed. 2002, 41, 1650–
1667. (e) Leach, A. G.; Goldstein, E.; Houk, K. N. J. Am. Chem. Soc. 2003,
125, 8330–8339. (f) Payette, J. N.; Yamamoto, H. J. Am. Chem. Soc. 2007,
129, 9536–9537
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Chem. (Engl. Transl.) 2000, 36, 609–637. (b) Banert, K.; Ko¨hler, F.; Meier,
B. Tetrahedron Lett. 2003, 44, 3781–3783. (c) Kuninobu, Y.; Nishina, Y.;
Matsuki, T.; Takai, K. J. Am. Chem. Soc. 2008, 130, 14062–14063.
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Organometallic Chemistry II; Elsevier: Oxford, U.K., 1995; Vols. 3-9.
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10.1021/ol901840c CCC: $40.75
Published on Web 09/02/2009
 2009 American Chemical Society

trimethylsilyl groups which are all directly bound to the
cyclopentadienyl ring via an unprecedented nucleophilic
domino intermolecular 1,4-addition/intramolecular 1,2-ad-
dition of dienedinitriles. The unique functionalized structure
containing an enaminonitrile moiety is of particular interest
as it provides valuable precursors for important heterocyclic
systems.5 Indeed, as preliminarily demonstrated by their
reaction with ArNCO, this type of multiply functionalized
cyclopentadienes does have interesting and useful properties.
The addition reaction of nucleophiles to R,ꢀ-unsaturated
nitriles (for examples acrylonitrile and derivatives) is a funda-
mental reaction in organic chemistry and of great synthetic
interest.6 We have recently developed an efficient synthetic
method for 1,4-dicyano-1,3-butadienes 1,7 which can be
considered as analogues of acrylonitrile derivatives, but they
should have much richer reaction chemistry because of their
unique conjugated structure. As shown in Scheme 1, when
treated with a nuchleophile, 1,4-dicyano-1,3-butadienes 1 should
have at least two reaction sites to be attacked by the nucleophile,
e.g., 1,4-addition fashion (I) and 1,2-addition fashion (II), in
the first step. When the substituents of 1 are alkyl groups, as
we previously noted,7 the 1,2-addition fashion (II) proceeded
exclusively to afford pyridine derivatives or pyrroles. Supris-
ingly, during our continuous investigation into the reaction
chemistry of various 1,4-dicyano-1,3-butadienes 1, we found
that a totally new structure of products was generated starting
from 1,4-dicyano-1,4-bis(trimethylsilyl)-1,3-butadienes via 1,4-
addition fashion (I) at the first nucleophilic attack.
with LiAlH4 affording their corresponding enaminonitrile
cyclopentadienes 2a-d in high isolated yields. Starting from
1a, the enaminonitrile cyclopentadiene 2a was formed in
quantitative yield (entry1, Table 1), and its structure was
confirmed by X-ray single-crystal analysis (Figure 1).
Figure 1. Single-crystal X-ray structure of 2a. Hydrogen atoms
are omitted for clarity.
Although complete conversion of 1b was also observed, the
enaminonitrile cyclopentadiene 2b was isolated in a lower
yield due to the undesired desilylation reaction during workup
(entry 2, Table 1). The noncyclic substrates 1c,d required a
longer reaction time to afford the enaminonitrile cyclopen-
tadienes in good yields of 71% and 74%, respectively (entries
3-4, Table 1). Of particular interest, similar cyclization
forming an indene derivative 2e in 84% isolated yield also
occurred starting from the analogous substrate 1e featuring
an aromatic ring (entry 5, Table 1). A similar cyclopentadiene
formation was also obtained from the reaction of 1a with
n-BuLi or MeLi (see the Supporting Information).
Scheme 1
.
Reaction Patterns of 1,4-Dicyano-1,3-butadienes 1
with Nucleophiles
The formation of 2a-e showed a cleavage of one
SiMe3-C bond besides the formation of the cyclopentadienyl
ring and the reduction of one nitrile group to NH2. To further
investigate the reaction mechanism, deuterated LiAlD4 was
applied, and d-2a was isolated in 95% yield with D
incoporation of more than 98% (Scheme 2).
On the basis of the above results, a plausible mechanism
was proposed as outlined in Scheme 3. First, the nucleophile
might selectively attack the ꢀ-carbon to CN (1,4-addition)
to form the intermediate A, which underwent a second
nucleophilic attack (intramolecular 1,2-addition) to form the
intermediates B and/or C.9 Then, hydrolysis of C completed
(6) (a) Rakita, P. E. In Handbook of Grignard Reagents; Silverman,
G. S., Rakita, P. E., Eds.; Marcel Dekker: New York, 1996; pp 381-389.
(b) Fleming, F. F.; Wang, Q.; Steward, O. W. Org. Lett. 2000, 2, 1477–
1497. (c) Fleming, F. F.; Shook, B. C. J. Org. Chem. 2002, 67, 3668–
3672, and references therein. (d) Ranu, B. C.; Das, A. Tetrahedron Lett.
2004, 45, 6875–6877.
As shown in Table 1, 1,4-dicyano-1,4-bis(trimethylsilyl)-
1,3-butadienes 1a-d, which can be readily prepared,8 reacted
(7) Wang, C. Y.; Wang, C.; Wang, Q.; Wang, Z.; Sun, H.; Guo, X.; Xi,
Z. Chem.sEur. J. 2007, 13, 6484–6494, and references therein.
(8) The dienedinitriles 1a-d were prepared through the substitution of
the iodine atoms of the corresponding 1,4-diiodo-1,4-bis(trimethylsilyl)-
1,3-dienes using CuCN (see the Supporting Information).
(5) (a) Robinson, J. M.; Brent, L. W.; Chau, C.; Floyd, K. A.; Gillham,
S. L.; McMahan, T. L.; Magda, D. J.; Motycka, T. J.; Pack, M. J.; Roberts,
A. L.; Seally, L. A.; Simpson, S. L.; Smith, R. R.; Zalesny, K. N. J. Org.
Chem. 1992, 57, 7352–7355. (b) Badia, L.; Ban˜os, J. E.; Camps, P.;
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Rodr´ıguez, T.; Torroba, T. E. Eur. J. Org. Chem. 2005, 5055–5066.
(9) (a) Baron, H.; Remfry, F. G. P.; Thorpe, Y. F. J. Chem. Soc. 1904,
85, 1726–1761. (b) Ziegler, K.; Eberle, H.; Ohlinger, H. Justus Liebigs
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1958, 80, 5483–5487. (d) Satoh, T.; Ota, D. Tetrahedron Lett. 1999, 40,
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275.
Org. Lett., Vol. 11, No. 19, 2009
4459

Scheme 3
Table 1. Reaction of Different
1,4-Dicyano-1,4-bis(trimethylsilyl)-1,3-butadienes with LiAlH4
2 was strongly polarized. The unique reactivity of these new
cyclopentadienes is demonstrated by the direct reaction of
2a with aryl isocyanates11 (Scheme 4). The attack of two
aryl isocyanate molecules on both the amino group and the
carbon atom adjacent to CN group led to the formation of
bis-addition products 3 with high selectivity. Moreover, the
reaction proceeds smoothly without any base or other
additives.
Scheme 4
the formation of enaminonitrile cyclopentadienes. Here, a
steric effect and the R-anion-stabilizing effect of the trim-
ethylsilyl group10 is supposed to be essential for the
formation of intermediate A.
Scheme 2
Interestingly, with normal workup of the reaction mixture
with aqueous 3 N HCl, C-C bond cleavage was observed.
Then starting from 3a,b, optimized hydrolysis condition with
aqueous 3 N HCl in 1,4-dioxane at room temperature
afforded the unexpected ring-opening products 4 in good
yields, with survival of the cyano group. The structures of
3a and 4b were identified by single-crystal X-ray structral
analysis (Figure 2).
Because of the introduction of cyano, amino, and trim-
ethylsilyl groups, the cyclopentadienyl ring of compounds
Shown in Scheme 5 is a proposed mechanism for the
unexpected reaction of 2 with aryl isocyanates. First, the
amino group of 2a reacted with one aryl isocyanate molecule
(10) (a) Bassindale, A. R.; Taylor. P. G. The Chemistry of Organic
Silicon Compounds; Patai, S., Rappoport, Z., Eds.; Wiley: New York, 1989;
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7805.
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57, 47–76. (b) Ozaki, S. Chem. ReV. 1972, 72, 457–496.
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Org. Lett., Vol. 11, No. 19, 2009

Scheme 5
and interesting reaction chemistry. This new strategy high-
lights a novel highly selective 1,4-addition of hydride to the
conjugated bis(trimethylsilyl) dienedinitriles. Moreover, the
resulting new cyclopentadienes also exhibited an unexpected
reactivity toward aryl isocyanates.
Acknowledgment. This work was supported by the
Natural Science Foundation of China, the Major State Basic
Research Development Program (2006CB806105), and the
international joint supervision of Ph.D. grant from the
Ambassade de France in China. Qiu Shi Science & Tech-
nologies Foundation, BASF, Eli Lilly China, and Dow
Corning Corp. are gratefully acknowledged.
Figure 2. Single-crystal X-ray structures of 3a (up) and 4b (down).
Hydrogen atoms are omitted for clarity.
Supporting Information Available: Experimental details,
spectroscopic data for synthetic compounds, and X-ray
crystallographic data (CIF) for compounds 2a, 3a, and 4b.
This material is available free of charge via the Internet at
http://pubs.acs.org.
to form the corresponding urea derivative D. Then the
addition of ꢀ-carbon of the tautomeric enamine to another
aryl isocynate molecule gave rise to 3.
In conclusion, we have developed an unprecedented
efficient method for the preparation of a variety of multi-
functionalized cyclopentadienes of unique substituted patterns
OL901840C
Org. Lett., Vol. 11, No. 19, 2009
4461