Palladium-catalyzed heck-type cascade cyclization of (Z)-1-iodo-1,6-dienes with N-tosyl hydrazones

Article abstract of DOI:10.1039/C8OB01821A

A palladium-catalyzed heck-type cascade cyclization of (Z)-1-iodo-1,6-dienes with N-tosyl hydrazones is reported. The alkylpalladium intermediate coupled with the diazo compound, generating the second alkylpalladium species bearing two β-H, which generate

Full text of DOI:10.1039/C8OB01821A

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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Palladium-Catalyzed Heck-Type Cascade Cyclization of (Z)-1-Iodo-
1,6-dienes with N-Tosyl Hydrazones
Jun Li,a Xiaochen Chi,a Long Meng,a Luyang Jiao,a Wenhui Shang,a Ping Wang,a Daopeng Zhang,a
Yunhui Donga, Qing Liu,*a and Hui Liu*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A palladium-catalyzed heck-type cascade cyclization of (Z)-1-Iodo- developed into a convenient carbenes precursor in numerous
1,6-dienes with N-tosyl hydrazones was reported. Alkylpalladium coupling reactions.[11] Wang group reported the cross-coupling
intermediate coupled with diazo compound generating the second of terminal alkynes with carbene precursors bearing β-H to
alkylpalladium species bearing two β-H, which generated terminal construct conjugated enynes (a, scheme 1).[8e] For the Csp2
alkene as major products in anti-Zaitsev way via the highly coupling with carbene precursors bearing β-H, polysubstituted
regioselective β-H elimination. It provided
a
new way to alkenes could be delivered (Scheme b).[8d,8f,9,10d-e,10j-o] Some
synthesize tetrahydropyridine derivates bearing terminal alkene.
strategies were also realized in the reaction of benzyl/allyl
halides and carbene precursors to afford styrene or 1,3-diene
derivatives (Scheme 1c).[5,7a,8a-b] Although Pd-catalyzed cross-
coupling reactions using N-tosyl hydrazones as carbene
precursors has been extensively investgated in the past years,
it is still rare on the reactions between alkylpalladium and
Diazo compounds have been found wide applications in
modern synthetic chemistry since Noyori reported the
asymmetric cyclopropanation of alkenes with diazo
compounds in the 1960s.[1] In particular, transition-metal
catalyzed transformations via active metal-carbene
intermediates, played an important role in the revolution of
modern organic synthetic methods.[2] Compared to the well-
established Rh, Cu, and Ru catalyzed reactions, palladium-
catalyzed transformations involving Pd-carbene intermediates
have received relative less attention, which might due to the
huge different reactivity of palladium-carbene species with the
corresponding Rh(II) and Cu(I) compounds.[3] The palladium
carbenes have been proposed as active intermediates in some
carbenes,[9f] which might be
construction of functionalized alkenes.
a new protocol for the
Our group has kept on developing new methodologies on
nondiazo
involved
reactions,[4]
however,
the
migration/insertion process was first demonstrated in the
palladium-catalyzed reaction of benzyl halides and
(trimethylsilyl)diazomethane by Van Vranken group in 2001.[5]
From then on, various elegant transformations have been
achieved in palladium carbene involved cross-couplings[6] by
Van Vranken,[7] Wang,[8] Barluenga and Valdés,[9] and others.[10]
So far, there are some procedures for the construction of
carbon-carbon double bond via palladium carbene
intermediates, among which N-tosyl hydrazones has been
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Heck-type reactions.[12] The key alkylpalladium intermediate screeninged several ligands, such as PCy3, P(2-furyl)3, dppe,
inspired us to study its reaction with carbene intermediates, dppp, dppf and BINAP, however, no better results were
which has rarely been explored.[7d] In 2013, Gu group reported obtained (entries 6-11). If the temperature was lowered down
o
a palladium-catalyzed Heck-type cascade reaction of organic to 50 C, the yield was decreased to 78% though the ratio was
halides with N-tosyl hydrazones via the alkylpalladium species a little better (entry 12). Finally, Pd(dba)2 (5 mol%), PPh3 (10
IV[13] bearing one β-H (d, scheme 1). (Z)-1-Iodo-1,6-dienes was mol%) and tBuOLi (3.0 equiv.) in MeCN at 80 oC under N2
a valuable block in constructing kinds of heterocycles reported atmosphere were chosen to the standard conditions (entry 5).
by Tong group.[14] To our interest, if vinyl iodide 1a reacts with
to generate the alkylpalladium intermediate , there will be
With the optimized conditions in hand, we then aimed to
2
V
two β-H to eliminate. Basing on the thermodynamic stability,
3aa-II was proposed to be the major products (e, scheme 1),
however, the kinetics determined terminal alkene 3aa-I was
obtained as the major product (f, scheme 1). Herein, we
reported our new research on palladium-catalyzed cascade
reaction of of (Z)-1-Iodo-1,6-dienes and N-tosyl hydrazones to
construct tetrahydropyridine derivatives possessing a terminal
alkene.
Initially, our study commenced with cascade reaction of (Z)-
N-(3-iodo-2-phenylallyl)-4-methyl-N-(2-methylallyl)benzene-
sulfonamide
1a
with
4-methyl-N'-(1-
phenylethylidene)benzenesulfonohydrazide 2a catalyzed by
PdCl2(PPh3)2 using 3.0 equivalent of tBuOLi as base in MeCN
under N2 (Entry 1, Table 1). As expected, a mixture with two
isomers terminal alkene 3aa-I and internal alkene 3aa-II were
obtained in 39% yield with a ratio of 78:22 (Entry 1). When
PdCl2(dppf) was used, the yield was not so good, but the ratio
of 3aa-I and 3aa-II was improved to 90:10 (Entry 2).
Delightfully, the yield could be increased to 53% by using
Pd(PPh3)4 with a ratio of 82:18 (entry 3). Interestingly, the
combination of Pd(OAc)2 and PPh3 gave product up to 88%
yield and 89:11 ratio (entry 4). Gratifily, the desired products
was obtained in 88% by using Pd(dba)2/PPh3, and the teminal
alkene selectivity was up to 88 to 12(entry 5). Furthermore, we
aReaction conditions: 1 (0.2 mmol, 1.0 equiv.), 2 (0.24 mmol,
1.2 equiv.), Pd(dba)2 (0.01 mmol, 5 mol%), PPh3 (0.02 mmol, 10
mol%), tBuOLi (0.6 mmol, 3.0 equiv.), solvent (2.0 mL).
bIsolated yields. C3-I:3-II is the ratio of terminal alkene and
internal alkene.
2 | J. Name., 2012, 00, 1-3
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survive very well under the standard condition, afford 5eb in
75% yield.
A plausible catalytic cycle for this cross-coupling reaction
was shown in Scheme 2. It might start with the oxidative
addition of the (Z)-N-(3-iodo-2-phenylallyl)-4-methyl-N-(2-
methylallyl)-benzenesulfonamide 1a to palladium(0) to
explore the substrate scope. It was found that the scope of the
generate the palladium(II) complex
insertion via 6-exo cyclization, alkylpalladium species
formed. Subsequently, the reaction of with carbene which
generated via dediazoniation of the in situ generated diazo
compound , produced the second alkylpalladium species
6. After the intramolecular
N-tosyl hydrazones
coupling with (Table 2). The aryl hydrazones bearing strong
electron-donating group such as methoxyl, provided the
desired product in good yield 3ab and 3ac). Halides
2 was expansive, allowing for efficient
7
was
1
7
(
9
8,
substitutions on the phenyl could survive very well (3ad-3ah).
Not only fluro and chloro, but also bromo and iodo could
afford the corresponding products in moderate to high yields.
It was worth mentioning that the products bearing active
bromo and iodo substitutions could be easily transferred to
more complex molecules via cross-couplings, which was
potential applied in synthsis (3af-3ah). The strong electron-
withdrawing group such as CN, could provide the product in
relative low yield (3ai). The reaction of substrates bearing alkyl
(e.g. ethyl, butyl and dodecyl) could afford the corresponding
bearing two β-hydride. The elimination of β-Ha delivered the
major product terminal alkene 3aa-I via anti Zaitsev way.
Considering on the structure of intermediate
8, Ha is less
hinder than Hb, so the dynamically stable product 3aa-I was
easy to be generated. Alternatively, the minor product was the
thermodynamically stable alkene 3aa-II formed via β-Hb
elimination.
Conclusions
terminal alkenes in good to excellent yields (3ba-3da). The
In conclusion, we developed a palladium-catalyzed heck-type
intramolecularly cyclization of (Z)-1-Iodo-1,6-dienes and
coupling with N-tosyl hydrazones. It provided a new way to
synthesize tetrahydropyridine derivates bearing terminal
alkene. The highly regioselective β-H elimination produced
dynamically stable terminal alkene as major product rather
than thermodynamic stable internal alkenes, which might due
reaction of 1a and N-tosyl benzaldehyde hydrazones 2j could
also give the internal alkenes 3aj in 87% yield. To investigate
the steric effect to regioselectivity, more bulky groups nBu and
Ph at the C=C bond of substrate
corresponding terminal alkenes
1
were tested and gave
3ea-3fa with better
(
)
selectivity. Notably, the substrate N-tosyl benzaldehyde
hydrazones 2k lead to corresponding product 3ak in 83% yields
with totally E selectivity, which was confirmed via the result of
NOESY spectra.
to the steric hindrance of β-H in palladium intermediate 8.
Investigation to the mechanism and further applications of this
methodology will be reported in due cause.
Subsequently, substrates containing oxygen tether were
also tested under the standard conditions (Table 3). Both
aromatic vinyl iodides bearing electron withdrawing/donating
group and alkyl iodides delivered the corresponding products
Conflicts of interest
There are no conflicts to declare.
in good yield (5aa-5ea). The bromo group on substrate b could
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Chen, H. Zhang, S. Xu, F. Ye, Y. Zhang, J. Wang, Org. Biomol.
Chem., 2016, 14, 3809.
Acknowledgements
We thank the Shandong Provincial Natural Science Foundation
(ZR2018MB008, ZR2018MB012), National Natural Science
Foundation of China (21671121), the CPSF (2016M590736), and the
Special Funding for Postdoctoral Innovation Project of Shandong
Province (201501002). The author would like to thank Dr Pingping
Zhao of Shandong University of Technology for her useful
suggestions and help to the paper.
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