Sequential base-promoted annulation/palladium-catalyzed domino 1,5-enyne arylation and vinylation of α-propargylaminohydrazones

Article abstract of DOI:10.1002/1521-3773(20020415)41:8<1400::AID-ANIE1400>3.0.CO;2-3

Stereoselective dominos: Cascade reactions of easily accessible α-propargylaminohydrazones 1 represent a simple and efficient method for the preparation of pyrazolones 3.

Full text of DOI:10.1002/1521-3773(20020415)41:8<1400::AID-ANIE1400>3.0.CO;2-3

COMMUNICATIONS
aminohydrazones. Here we report a new, efficient synthetic
methodology for the preparation of (Z)-6-arylidene/vinyl-
idene-6a-methyl-1,5,6a-tetrahydro-2H-pyrrolo[3,2-c]pyrazol-
Sequential Base-Promoted Annulation/
Palladium-Catalyzed Domino 1,5-Enyne
Arylation and Vinylation of a-
3
-ones (for example, 3a ± h) through remarkable sequential
Propargylaminohydrazones
base-promoted annulation/palladium-catalyzed, domino 1,5-
enyne arylation and vinylation reactions.
The treatment of 1a ± c with anhydrous piperidine in the
presence of aryl iodide/triflate derivatives 2a ± h and
Elisabetta Rossi,* Antonio Arcadi,* Giorgio Abbiati,
Orazio A. Attanasi, and Lucia De Crescentini
1,2-Diazabuta-1,3-dienes represent versatile building
Pd(OAc) /DPPF (Ac ˆ acetyl; DPPF ˆ 1,1'-bis(diphenyl-
2
blocks in organic synthesis because they offer easy access to
a wide variety of heterocyclic compounds by 1,4-conjugate
addition and subsequent cyclization reactions.[ Moreover,
Michael reaction adducts of the 1,2-diazabuta-1,3-diene
phosphanyl)ferrocene) catalytic system gave 3a ± h in good
yields (Scheme 1, Table 1). The structure of compounds 3 was
1]
1
13
confirmed by one- ( H, C) and two-dimensional (COSY,
HETCOR, NOESY) NMR spectral analysis, and by mass
spectroscopy. NOESY experiments clearly demonstrate that
the geometry of the exocyclic double bond is Z for all
[2]
system may act as nitrogen ligands for transition metal
catalysts, which leads to unusual reaction pathways.[ In
common with other Michael additions, 1,2-diazabuta-1,3-
dienes undergo divergent copper-promoted annulation reac-
tions to form functionalized imidazolines/imidazoles under
regiocontrol, whereas the base-promoted cyclization provides
both 1-substituted and 1-unsubstituted 4-aminocarbonyl-1H-
pyrazol-5(2H)-ones.[
3]
1
13
compounds 3a ± h. Moreover, H and C NMR signals arising
from the vinyl substituted pyrazolones 3e ± h are split because
of the presence of multiple isomers.
4]
A variety of metal-catalyzed reactions of enynes, which
involve a broad range of early and late transition metals, are
of interest in the synthesis of functionalized carbo/hetero-
cycles.[ The classes of reaction that involve the metal-
catalyzed functionalization of enynes include cycloisomeriza-
5]
tion,[ reductive cyclization, bismetallative cyclization,
6]
[7]
[8]
Scheme 1. Reagents and conditions: 1) Pd(OAc)
4 h. Spectroscopic data of new compounds can be found in the Supporting
Information.
2
, DPPF, piperidine, RT,
2
[9]
[10]
carbonylative cyclizations, and dimerization/cyclization.
One-pot domino reactions of enynes provide a valuable
procedure for easy access to five- and six-membered hetero-
cycles containing a 1,3-diene structure, which can lead to
bicyclic compounds through in situ Diels ± Alder reactions.[11]
Domino reactions are emerging as powerful strategies in
modern synthetic organic chemistry, and the discovery of new
reaction sequences able to produce functional compounds
constitutes a challenge both from the academic and industrial
points of view.[
The a-propargylaminohydrazone adducts 1a ± c (Scheme 1,
Table 1), which contain a 1,4-diazo-1,6-azenyne system,
turned out to be useful substrates for further metal-catalyzed
processes. In this context, we investigated the palladium-
catalyzed arylation and vinylation reactions of a-propargyl-
The absence of nuclear Overhauser enhancement (NOE)
interactions between the olefinic protons on the exocyclic
double bond and on the cyclohexene ring in 3e was explained
[13]
[14]
by the results of a conformational search at the AM1
semiempirical level to evaluate the conformational energies
of 3e. The results show that the conformers with lower steric
energies have spatial arrangements which are in agreement
with the observed NOE interactions. Moreover, the analysis
of all the observed minima show that there is only one local
minimum, with a spatial arrangement compatible with a NOE
interaction between the two olefinic protons (<3 ä apart),
12]
however the steric energy of this minimum is about
À1
1
0 kJmol higher than that of the global minimum structure.
A reasonable rationale for the production of 3 is depicted in
Scheme 2. The reaction involves the formation of the
-aminocarbonyl-1H-pyrazol-5(2H)-ones 4 derivatives ob-
[
*] Dr. E. Rossi, Dr. G. Abbiati
Istituto di Chimica Organica, Facolt a¡ di Farmacia
Universit a¡ di Milano
1
tained by the piperidine-promoted annulation reaction of
Via Venezian 21, 20133 Milano (Italy)
Fax : (‡39)02-5835-4476
[4b]
1
a ± c, according to our previous findings.
Solvolytic
cleavage at N-1 of 4 gives 5; ureas 6 were isolated as reaction
side products. Compounds 3a ± h are formed through the
palladium-catalyzed domino arylation or vinylation/carbocyc-
lization of 5. Thus, the regioselective syn addition of the s-
vinyl/aryl palladium complex on the triple bond of 7 affords
the s-vinyl palladium intermediate 8, which forms intermedi-
ate 9 by a carbocyclopalladation step. Finally, the elimination
of HPdX from 9 produces the Z pyrazolone derivatives 3
stereospecifically and regenerates the active catalyst. The
stereochemical outcome of the reaction is in agreement with
the sequence illustrated in Scheme 2 and with the results
E-mail: Elisabetta.Rossi@unimi.it
Prof. A. Arcadi
Dipartimento di Chimica Ingegneria Chimica e Materiali, Facolt a¡ di
Scienze, Universit a¡ di L×Aquila
Via Vetoio, Coppito Due, 67100 L×Aquila (Italy)
Fax : (‡39)08-6243-3756
E-mail: Arcadi@univaq.it
Prof. O. A. Attanasi, Dr. L. De Crescentini
Istituto di Chimica Organica, Universit a¡ di Urbino
Piazza della Repubblica 13, 61029 Urbino (Italy)
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
1400
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
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Angew. Chem. Int. Ed. 2002, 41, No. 8

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Table 1. Compounds 1 ± 3.
1
R
R1
2
a
Structure
3
a
Structure
Yield[a] [%]
67
a
Me
H
b
c
Et
H
b
c
d
e
f
b
c
d
e
f
68
67
64
62
66
64
65
Me
Ph
g
h
g
h
[
a] Yields refer to single runs and isolated products.
obtained in the bimetallic palladium-catalyzed cyclization of
enynes.[
Although the Pd -catalyzed intramolecular cyclization of
Experimental Section
8]
The appropriate halides or triflates 2a ± h (1 mmol), Pd(OAc)
2
(11.22 mg,
II
0
.05 mmol), and DPPF (27.72 mg, 0.05 mmol) were added to a nitrogen-
enynes has been utilized for the preparation of five-mem-
flushed solution of 1a ± c (1 mmol) in dry piperidine (6 mL). The reaction
mixture was stirred at room temperature for 24 h, poured into HCl (0.1m,
bered ring systems,[
6a, 15]
to our knowledge, the sequential
1
00 mL) and extracted twice with ethyl acetate. The organic layer was dried
palladium-catalyzed reaction reported here is the first exam-
ple of a domino, palladium-catalyzed, intermolecular aryl-
over Na SO , evaporated to dryness, and the crude product was purified by
2
4
flash chromatography on silica gel. Elution with petroleum ether/ethyl
acetate afforded pure 3a ± h.
[16]
ation/vinylation combined with an intramolecular carbo-
palladation process of a 1,5-enyne derivative, which leads to
fused heterocycles through a regioselective 5-endo-dig annu-
lation reaction, followed by b-hydride elimination with
cleavage of the NÀH bond. Only a few examples of s-aryl/
À1
3
a: M.p. 139.7± 141.9 8C ; IR (KBr): nÄ ˆ 3360, 3186, 1718, 1682, 1560 cm
;
1
H NMR (200 MHz, CDCl
3
, 258C): d ˆ 1.98 (s, 3H, CH
3
), 2.58 (s, 3H,
O-exchange, NH), 4.05 (dd, J(H,H) ˆ 15 Hz,
2
CH
3
CO), 2.93 (br s, 1H, D
2
4
2
4
J(H,H) ˆ 2 Hz, 1H, CH
2
), 4.35 (dd, J(H,H) ˆ 15 Hz, J(H,H) ˆ 2 Hz, 1H,
4
3
CH
2
), 6.70 (t, J(H,H) ˆ 2 Hz, 1H, ˆCH), 7.32 (d, J(H,H) ˆ 7.8 Hz, 2H,
vinyl palladium complexes involved in cascade[ carbopalla-
dation and domino palladium-catalyzed intermolecular ary-
lation/vinylation-intramolecular[ carbopalladation process-
es of 1,6- or 1,7-enynes have been reported.
17]
3
aromatic), 7.88 (d, J(H,H) ˆ 7.8 Hz, 2H, aromatic), 8.82 (br s, 1H, D
2
O-
13
exchange, NH); C NMR (75.4 MHz, CDCl
3
, 258C): d ˆ 13.9 (CH
3
), 26.9
14]
(CH CO), 54.9 (CH ), 78.2 (Csp3), 126.2 (Csp2H, 2C; aromatic), 129.3 (Csp2H,
3
2
2
C; aromatic), 134.6 (ˆCsp2H), 137.0 (Csp2), 137.2, (Csp2), 138.0, (Csp2), 164.1
‡
(
CˆN), 178.1 (CˆO), 197.8 (CˆO); MS (70 eV): m/z (%): 269 (100) [M ];
In conclusion, we have developed a new efficient Pd-
catalyzed ene-type carbocyclization and current efforts are
now focused on these and related substrates, to access the
synthetic potential of this procedure.
Elemental analysis calcd (%) for C17
found: C 73.79, H 5.57, N 14.85.
15 3
H N O: C 73.62, H 5.45, N 15.15;
Received: November 29, 2001 [Z18300]
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Angew. Chem. Int. Ed. 2002, 41, No. 8
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002

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The First Isolable 4-Silatriafulvene**
Kenkichi Sakamoto,* Jun Ogasawara, Yoshihiro Kon,
Tatsuya Sunagawa, Chizuko Kabuto, and Mitsuo Kira*
Among various silicon ± carbon doubly bonded compounds
1]
(
silaethenes),[ 4-silatriafulvenes have attracted much atten-
[2, 3]
tion because of their unique electronic properties;
the
intrinsic polarity of the SiˆC bond in 4-silatriafulvene (A) is
expected to be reduced by the significant contribution of
resonance structure B (Scheme 1).
R
R
R
δ− δ+ R'
R'
R'
Si
Si
R'
R
A
B
Scheme 1.
We recently generated the first 4-silatriafulvene derivative,
2]
1
,2-di-tert-butyl-4,4-bis(trimethylsilyl)-4-silatriafulvene (1a),[
as a reactive intermediate and demonstrated that 1a is much
less reactive toward tert-butyl alcohol
tBu
SiR3
than is usual for silaethenes and isomer-
izes to the corresponding silacyclobuta-
Si
SiR3
diene at high temperatures. Theoretical
calculations for 4-silatriafulvene deriva-
tives have predicted the fluxional nature
of the 4-silatriafulvene skeletons, which
are not planar around the SiˆC bond but
tBu
Scheme 2. A plausible catalytic cycle for the formation of 3.
1a, SiR3 = SiMe3
1
b, SiR3 = SiMe2tBu
[
1] O. A. Attanasi, P. Filippone, S. Santeusanio, Acc. Chem. Res. 2001, in
press.
[
[
2] B. M. Trost, S.-F. Chen, J. Am. Chem. Soc. 1986, 108, 6053.
3] A. Arcadi, O. A. Attanasi, L. De Crescentini, E. Rossi, F. Serra-
Zanetti, Tetrahedron 1996, 52, 3997.
trans-bent, with large bend angles and an energy difference of
only 1.0 kcalmol between the trans-bent and planar struc-
À1
[3d]
[
4] a) A. Arcadi, O. A. Attanasi, L. De Crescentini, E. Rossi, Tetrahedron
Lett. 1997, 38, 2329; b) G. Abbiati, A. Arcadi, O. A. Attanasi, L.
De Crescentini, E. Rossi, Tetrahedron 2001, 57, 2031.
5] a) K. K. D. Amarasinghe, S. K. Chowdhury, M. J. Heeg, J. Montgom-
ery, Organometallics 2001, 20, 370, and references therein; b) T. L.
Gilchrist, J. Chem. Soc. Perkin Trans. 1 2001, 2491, and references
therein.
tures at the MP2/6-311 ‡‡ G** ‡ ZPE level (Scheme 2).
[
[
6] a) M. Hatano, M. Terada, K. Mikami, Angew. Chem. 2001, 113, 255;
Angew. Chem. Int. Ed. 2001, 40, 249; b) J.-C. Galland, S. Dias, M.
Savignac, J.-P. Gen e√ t, Tetrahedron 2001, 57, 5137, and references
therein.
Scheme 2. Skeletal inversion of silatriafulvene.
[
[
[
7] C. H. Oh, H. H. Jung, R. Sung, J. D. Kim, Tetrahedron 2001, 57, 1723,
and references therein.
8] M. Mori, T. Hirose, H. Wakamatsu, N. Imakuni, Y. Sato, Organo-
metallics 2001, 20, 1907.
9] J. Adrio, M. R. Rivero, J. C. Carretero, Angew. Chem. 2000, 112, 3028;
Angew. Chem. Int. Ed. 2000, 39, 2906, and references therein.
Although Schumann et al. have reported the isolation of
[4]
stable 4-germa-, 4-stanna-, and 4-plumbatriafulvenes, no
stable 4-silatriafluvene has been synthesized to date.[ By use
of bulky tert-butyldimethylsilyl groups instead of trimethyl-
silyl groups in 1a, we synthesized the first stable 4-silatria-
5]
[
10] B. M. Trost, A. S. K. Hashmi, R. C. Ball, Adv. Synth. Catal. 2001, 343,
90.
11] L. Ackermann, C. Bruneau, P. H. Dixneuf, Synlett 2001, 397.
12] L. F. Tietze, Chem. Rev. 1996, 96, 115.
4
‡]
[
*] Prof. K. Sakamoto,[ Dr. J. Ogasawara, Y. Kon,
T. Sunagawa, Dr. C. Kabuto, Prof. M. Kira
Department of Chemistry,
[
[
[
13] Calculations were performed with the Hyperchem program (release
Graduate School of Science
6
.02), Hypercube, 1115 NW 4th Street, Gainesville, FL 32601 USA -
Tohoku University, Aoba-ku, Sendai 980-8578 (Japan)
Fax (‡81) 22-217-6589
http://www.hyper.com.
[
14] M. J. S. Dewar, E. G. Zoebish, E. F. Healy, J. J. P. Stewart, J. Am.
Chem. Soc. 1985, 107, 3902.
15] X. Xie, X. Lu, Synlett 2000, 707.
16] a) B. M. Trost, J. Dumas, Tetrahedron Lett. 1993, 34, 19; b) S. Brown, S.
Clarkson, R. Grigg, V. Sridharan, Tetrahedron Lett. 1993, 34, 157;
c) B. M. Trost, W. Pfrengle, H. Urabe, J. Dumas, J. Am. Chem. Soc.
E-mail: mkira@si.chem.tohoku.ac.jp
‡
[
] Concurrent office:
[
[
Photodynamics Research Center
The Institute of Physical and Chemical Research (RIKEN)
5
19-1399 Aoba, Aramaki, Aoba-ku, Sendai 980-0845 (Japan)
1
992, 114, 1923.
[**] This work was supported by the Japanese Ministry of Education,
Culture, Sports, Science, and Technology [Grant-in-Aid for Scientific
Research (B) No. 11440185].
[
17] a) R. Grigg, V. Loganathan, V. Sridharan, Tetrahedron Lett. 1996, 37,
3
399; b) Y. Zhang, E.-G. Negishi, J. Am. Chem. Soc. 1989, 111, 3454.
1402
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1433-7851/02/4108-1402 $ 20.00+.50/0
Angew. Chem. Int. Ed. 2002, 41, No. 8