Diazo compounds as electrophiles to react with 1,4-dilithio-1,3-dienes: Efficient synthesis of 1-imino-pyrrole derivatives

Article abstract of DOI:10.1021/ol401878q

1-Imino-pyrrole and indole derivatives were synthesized in high yields from the reaction of diaryl diazomethanes with 1,4-dilithio-1,3-dienes. Diaryl diazomethanes reacted as electrophiles in this reaction. An unprecedented Zn-complex was formed via trans

Full text of DOI:10.1021/ol401878q

ORGANIC
LETTERS
2013
Vol. 15, No. 16
4182–4185
Diazo Compounds as Electrophiles To
React with 1,4-Dilithio-1,3-dienes: Efficient
Synthesis of 1‑Imino-pyrrole Derivatives
Ming Zhan,† Shaoguang Zhang,† Wen-Xiong Zhang,† and Zhenfeng Xi*,†,‡
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, and State Key Laboratory of
Organometallic Chemistry, Shanghai Institute of Organic Chemistry, CAS, Shanghai
200032, China
zfxi@pku.edu.cn
Received July 4, 2013
ABSTRACT
1-Imino-pyrrole and indole derivatives were synthesized in high yields from the reaction of diaryl diazomethanes with 1,4-dilithio-1,3-dienes. Diaryl
diazomethanes reacted as electrophiles in this reaction. An unprecedented Zn-complex was formed via transmetalation of the above reaction
intermediate with ZnCl2 and was structurally characterized. The trans-μ2-η1:η1 coordination mode in the solid state for this azaallylzinc compound
was observed.
Diazo compounds are a class of important building
blocks in synthetic chemistry.1 Among various reaction
patterns, diazo compounds are usually known to act as
metal carbene precursors,2 1,3-dipoles,3 and nucleophiles.4
However, as demonstrated in Scheme 1, although it is
fundamental and straightforward that diazo compounds
behave as electrophiles to react with organometallic
reagents, such a reaction type is very rare, mainly due to
the high reactivity (instability) of the generated diazo
organometallic intermediates.5,6 Therefore, a way to sta-
bilize such reactive species is highly demanded to synthet-
ically utilize this fundamental reaction.
In recent years, we have studied the synthesis, reaction
chemistry, and synthetic applications of 1,4-dilithio-1,3-
† Peking University.
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C.; Lin, L.; Feng, X. J. Am. Chem. Soc. 2011, 133, 15268.
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Wei, J.; Zhan, M.; Luo, Q.; Wang, C.; Zhang, W.-X.; Xi, Z. J. Am.
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‡ Shanghai Institute of Organic Chemistry.
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Mckervey, M. A. Chem. Rev. 1994, 94, 1091. (b) Doyle, M. P.; Mckervey,
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Tetrahedron 2008, 64, 6577. (d) Xiao, Q.; Zhang, Y.; Wang, J. Acc.
Chem. Res. 2012, 46, 236.
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r
10.1021/ol401878q
Published on Web 08/07/2013
2013 American Chemical Society

Table 1. Synthesis of 1-Imino-pyrrole and Indole Derivatives
from 1,4-Dilithio-1,3-dienes and Diphenyldiazomethane
Scheme 1. Diazo Compounds As Electrophiles
dienes 1 (dilithio reagents for short).7a,b,8 Because the two
Liatoms are bridged bya butadiene moiety and are in close
proximity, these dilithio reagents have demonstrated re-
markable cooperative effects including cooperative stabili-
zation.7a,b,8 As illustrated in Scheme 1, we envisioned that
the reaction between a dilithio reagent and one or two
diazo compounds would form the intermediate 2 or 20,
which might be stabilized through the intramolecular
coordination. Herein we report our preliminary results
on the reaction between the dilithio reagents 1 and diazo
compounds, in which diazo compounds acted as electro-
philes. Multiply substituted 1-imino-pyrrole and indole
derivatives were obtained in good to excellent isolated
yields.9,10 Synthetic methods for N-imino pyrrole and
indole derivatives are very limited.10 A mechanistic inves-
tigation revealed that two diazo compounds reacted with
one dilithio reagent affording the intermediate 2. Further-
more, an unprecedented Zn-complex was obtained via
transmetalation of the intermediate 2 with ZnCl2. In this
Zn-complex, the trans-μ2-η1:η1 coordination mode in the
solid state was observed.
corresponding 1-imino-pyrrole or indole derivatives. The
structure of 3e was determined by single-crystal X-ray
structural analysis (Figure 1).
1,4-Dilithio-1,3-dienes 1 (dilithio reagents for short)
were quantitatively generated from their corresponding
1,4-diiodo-1,3-dienesandt-BuLiatꢀ78°C for 1 h.7b When
the in situ generated dilithio reagent 1a (R = Et) was
treated with 1.0 equiv of diphenyldiazomethane, the multi-
ply substituted 1-imino-pyrrole derivative 3a was obtained
in 41% isolated yield upon quench of the reaction mixture
with H2O in air. The unreacted 1a changed into its
corresponding diene after quenching. When 2.2 equiv of
diphenyldiazomethane were used, 3a was obtained in 86%
isolated yield. Given in Table 1 are representative results.
In addition to those symmetrically substituted dilithio
reagents (1aꢀc), the unsymmetrically substituted dilithio
reagents (1d,e) and the vinylphenyl dilithio reagents (1f,g)
could all react with diphenyldiazomethane to afford their
Figure 1. ORTEP drawing of 3e with 35% thermal ellipsoids.
Hydrogen atoms are omitted for clarity. Selected bond lengths
˚
[A]: C(3)ꢀN(2) 1.381(4), C(3)ꢀC(4) 1.359(5), C(4)ꢀC(7) 1.425(5),
C(7)ꢀC(14) 1.370(5), C(14)ꢀN(2) 1.397(4), N(1)ꢀN(2) 1.428(4),
C(21)ꢀN(1) 1.293(4).
Given in Figure 2 are representative results obtained
from the reaction of the dilithio reagent 1awithother diazo
compounds, following the reaction conditions shown in
Table 1.
For those cases with lower yields (3d, 3f, 3i, 3j), both
their corresponding dienes and decomposition of diazo
compounds were observed. The lower reactivity of those
dilithio reagents and diazo compounds with different
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L.; Hierso, J.-C. Chem. Soc. Rev. 2012, 41, 3929. (b) Inman, M.; Moody,
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Org. Lett., Vol. 15, No. 16, 2013
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Scheme 3. Reaction Mechanism
Figure 2. 1-Imino-pyrrole derivatives obtained from the dilithio
reagent 1a and other diazo compounds.
structures is considered the major reason for the lower
product yields.
When cyclic dilithio reagents (1h,i, Scheme 2) were
treated with 2.2 equiv of dipenyldiazomethane, their cor-
responding N-imino tetrahydro iso-indole derivatives 3k
and 3l were obtained. However, in the case of the dilithio
reagent 1j (R = Ph), the unexpected bis(diazo) compound
4 was obtained in 83% isolated yield. Formation of its
corresponding tetrahydroisoindole derivative was not
observed.
Scheme 4. Synthetic Application of 2a
Scheme 2. Reaction of Cyclic Dilithio Reagents with Diphen-
lydiazomethane
Furthermore, as a demonstration of the formation and
synthetic application of 2, transmetalation of 2a with
ZnCl2 was performed. An unprecedented organozinc com-
pound 7was thus obtained in 87% isolated yield (Scheme 4).12
The structure of 7 was identified by single-crystal X-ray
structural analysis (Figure 3).
(12) For reports on structures of organozinc compounds, see: (a)
Uchiyama, M.; Matsumoto, Y.; Nobuto, D.; Furuyama, T.; Yamaguchi,
K.; Morokuma, K. J. Am. Chem. Soc. 2006, 128, 8748. (b) Wooten, A.;
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Angew. Chem., Int. Ed. 2007, 46, 3802. (e) Sarazin, Y.; Wright, J. A.;
Harding, D. A. J.; Martin, E.; Woodman, T. J.; Hughes, D. L.; Bochmann,
M. J. Organomet. Chem. 2008, 693, 1494. (f) Merkel, S.; Stern, D.; Stalke,
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The reaction mechanism between the dilithio reagent
and diazo compounds was investigated (Scheme 3). First,
we isolated the imtermediate 2a and obtained its NMR
data. The peak at 152.6 ppm in its 13C NMR spectrum
shows that an imine carbon exists in its structure. Then,
this intermediate was quenched with H2O under N2, and
the product 5 was formedand structurally characterized by
single-crystal X-ray analysis (see Supporting Information
for details). When 5 was dissolved and stirred in THF in
air, it was oxidized to afford the product 3b and the diazo
compound 6.11
€
29, 2063. (i) Schmidt, S.; Schulz, S.; Blaser, D.; Boese, R.; Bolte, M.
Organometallics 2010, 29, 6097. (j) Zhou, Y.; Zhang, W.-X.; Xi, Z.
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ꢀ
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Organometallics 2013, 32, 2625.
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Org. Lett., Vol. 15, No. 16, 2013

are almost perfectly delocalized. The ZnꢀC bond lengths
˚
(2.096ꢀ2.195 A) in 7 are elongated compared to the
corresponding values in zinc complexes with η1 bonded
allylic ligands (1.969ꢀ2.031 A).14 The ZnꢀN bond lengths
˚
˚
(2.006ꢀ2.008 A) in 7 are comparable with the reported
0
˚
ZnꢀN bond length (2.003 A) in the NCN chelating
binding mode.12i Thus, the azaallyl ligands of 7 are bonded
to the Zn(1) and Zn(2) atoms in a bridging trans-μ2-η1:η1
fashion. This is the first example of an azaallyl zinc
compound showing such a coordination mode.
In conclusion, an efficient synthesis of 1-imino-pyrrole
derivatives has been developed from the reaction between
1,4-dilithio-1,3-dienes and diaryl diazomethanes. It is a
rare example demonstrating that diaryldiazomethane acts
as an electrophile. The expected effect of cooperative
stabilization by 1,4-dilithio-1,3-dienes works well. The
azaallyl zinc compound 7 with the bridging trans-μ2-η1:η1
coordination mode, generated from the dilithio imtermedi-
ate 2a with ZnCl2, is of further synthetic interest.
Figure 3. ORTEP drawing of 7 with 30% thermal ellipsoids.
Hydrogen atoms are omitted for clarity. Selected bond lengths
˚
[A] for 7: Zn(1)ꢀCl(1) 2.2249(7), Zn(1)ꢀCl(2) 2.4163(7), Zn(1)ꢀ
Acknowledgment. This paper is dedicated to Professor
Teruaki Mukaiyama in celebration of the 40th anniversary
of the Mukaiyama aldol reaction. This work was sup-
ported by the Natural Science Foundation of China, and
the Major State Basic Research Development Program
(2011CB808700).
N(2) 2.008(2), Zn(1)ꢀC(16) 2.096(3), Zn(2)ꢀCl(2) 2.3778(8),
Zn(2)ꢀCl(3) 2.1841(7), Zn(2)ꢀN(3) 2.006(2), Zn(2)ꢀC(15)
2.195(2), N(1)ꢀN(2) 1.393(3), N(1)ꢀC(1) 1.294(4), N(2)ꢀC(14)
1.360(3), N(3)ꢀN(4) 1.415(3), N(3)ꢀC(17) 1.321(3), N(4)ꢀ
C(30) 1.288(4), C(14)ꢀC(15) 1.413(4), C(15)ꢀC(16) 1.535(3),
C(16)ꢀC(17) 1.447(4).
The Zn-complex 7 shows a rare azaallyl coordination
mode (μ2-η1:η1).13 The π-electrons within the azaallyl
N(3)ꢀC(17)ꢀC(16) and the azaallyl N(2)ꢀC(14)ꢀC(15)
Supporting Information Available. Experimental details;
X-ray data for 3e (CCDC-917412), 4 (CCDC-917411), 5
(CCDC 945229), and 7 (CCDC 945228); scanned NMR
spectra of all new products. This material is available free of
charge via the Internet at http://pubs.acs.org.
(14) (a) Yasuda, H.; Ohnuma, Y.; Nakamura, A.; Kai, Y.; Yasuka,
N.; Kasai, N. Bull. Chem. Soc. Jpn. 1980, 53, 1101. (b) Ernst, R. D.;
Freeman, J. W.; Swepston, P. N.; Wilson, D. R. J. Organomet. Chem.
1991, 402, 17.
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 16, 2013
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