Platinum-catalyzed hydrogenative cyclization of yne-enones, yne-aldehydes, and yne-dienes

Article abstract of DOI:10.1002/ejoc.200901005

Pt complexes were used in the presence of phosphane ligands, SnCl ₂, and H₂ for coupling reactions of alkynes with electrophiles under environmentally benign hydrogenation conditions, providing five- and six-membered cycloreduction p

Full text of DOI:10.1002/ejoc.200901005

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200901005
Platinum-Catalyzed Hydrogenative Cyclization of Yne-Enones, Yne-Aldehydes,
and Yne-Dienes
Mahadev P. Shinde,[a] Xi Wang,[a] Eun Joo Kang,[b] and Hye-Young Jang*[a]
Keywords: Platinum / Cyclization / Hydrogenation / Alkynes / Enones / Aldehydes / Alkenes
Pt complexes were used in the presence of phosphane li-
gands, SnCl2, and H2 for coupling reactions of alkynes with
electrophiles under environmentally benign hydrogenation
conditions, providing five- and six-membered cycloreduction
products in moderate to good yield. Deuterium labeling stud-
ies suggested the occurrence of a catalytic cycle including
the diploar intermediate derived from hydrometalation of a
platinum–hydride complex to the alkyne.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
Introduction
Results and Discussion
Pt complexes are promising catalysts for the cyclizations
of enynes,[1] dienes,[2] diynes,[3] hydroxy alkenes,[4] amino al-
kenes,[5] and arene–alkyne substrates,[6] where the Pt com-
plex activates the alkynes (or the alkenes), facilitating the
intramolecular addition of a nucleophile to the Pt–alkyne
(alkene) complex. Although the Pt-catalyzed reaction of al-
kynes (and alkenes) with nucleophiles are a powerful strat-
egy for the synthesis of synthetically and biologically im-
portant building blocks, there has been relatively less inter-
est in the Pt-catalyzed reactions of alkynes (the alkenes)
with electrophiles. In particular, there are few reports on
the addition of a Pt–alkyne (alkene) complex to electro-
philes under hydrogenation conditions.[7] In the context of
the intramolecular addition of the Pt–alkene to the electro-
philes, we previously reported the Pt-catalyzed Michael and
aldol reaction under hydrogenation conditions.[8] As a pos-
sible mechanism, the LnPtH complex derived from PtCl2,
the ligands, and H2 is expected to coordinate with the acti-
vated alkene to perform the subsequent cyclization with the
α,β-unsaturated carbonyl compound (or the aldehyde).[9,10]
As part of an ongoing study aimed at developing the reac-
tion of a Pt–alkyne complex with electrophiles under hydro-
gen, this study examined the reaction mode of Pt catalysts
exhibiting high catalytic activity with the yne-enones, yne-
aldehydes, and yne-dienes. In addition to examples of the
cyclizations of the alkyne with enones, aldehydes and,
dienes, a plausible catalytic cycle is proposed to account for
the deuterium labeling results.
To optimize the reaction conditions, N-(E)-4-methyl-N-
(4-oxo-4-phenylbut-2-enyl)-N-(prop-2-ynyl)benzenesulfon-
amide (1a) was added to a solution containing PtCl2
(5 mol-%), P[2,4,6-(OMe)3C6H2]3 (5 mol-%), and SnCl2
(25 mol-%) under 1 atm of H2 to afford product 1b in 44%
yield (Table 1, Entry 1). In the previous Michael and aldol
cyclization, the Pt–enolate was generated from the hydro-
metalation of the enone treated with the aldehyde or enone.
However, in the cyclization of yne-enones, the addition of
the Pt–enolate to the alkyne, which was expected to afford
six-membered ring product 1d, was not observed. To im-
Table 1. Optimization of reductive cyclization of 1a.
Entry Pt complex
(5 mol-%)
Ligand
(5 mol-%)
Additive
(25 mol-%)
Yield [%]
(1b/1c)
1
2
3
4
5
6
7
8
9
PtCl2
PtCl2
PtCl2
PtCl2
PtCl2
PtCl2
PtCl2
PtCl2
PtCl2
PtCl2
PtBr2
P[2,4,6-(OMe)3C6H2]3
P[2,4,6-(OMe)3C6H2]3
P[2,4,6-(OMe)3C6H2]3
P(p-OMeC6H4)3
PPh3
SnCl2
SnCl2
SnCl2
SnCl2
SnCl2
SnCl2
SnCl2
SnCl2
–
44 (1b)[a]
30(1b)[b]
35(1b)
51 (2.7:1)
74 (1.2:1)
68 (1:1.6)
80 (5.2:1)
28 (1b)
P(p-CF3C6H4)3
P(C6F5)3
[a] Division of Energy Systems Research, Ajou University,
Suwon 443-749, South Korea
–
P(C6F5)3
P(C6F5)3
P(C6F5)3
reduction
Fax: +82-31-219-1615
E-mail: hyjang2@ajou.ac.kr
10
11
SnCl2
SnCl2
N.R.[c]
[b] Department of Applied Chemistry, Kyung Hee University,
Yongin 449-701, South Korea
58 (1b)
[a] Dichloromethane, 40 °C, 18 h. [b] 60 °C, 8.5 h. [c] In the absence
of H2.
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200901005.
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M. P. Shinde, X. Wang, E. J. Kang, H.-Y. Jang
SHORT COMMUNICATION
prove the yield, the temperature was increased, but the yield often reported in the Pt-catalyzed cyclizations of enynes,
was still too low (Table 1, Entries 2 and 3). Next, a variety was observed (Table 1, Entry 10).[1] An alternative Pt cata-
of phosphane ligands were evaluated. Upon the addition of lyst, PtBr2, was used, affording compound 1b in 58% yield
relatively less electron-rich phosphanes, the yield increased (Table 1, Entry 11).
with the concomitant formation of isomerized product 1c,
A diverse range of substrates were evaluated employing
which was formed through isomerization of 1b (Table 1, En- a suitable set of reaction conditions using PtCl2 (5 mol-%),
tries 4–7).[11] In the absence of phosphane ligands, the reac- phosphane ligands (5 mol-%), and SnCl2 (25 mol-%) under
tion still proceeded to compound 1b in 28% yield (Table 1, 1 atm of H2 (Table 2). Depending on the substituent on the
Entry 8). The phosphane ligand is expected to modulate the substrate, either an electron-deficient or an electron-rich
reactivity of the catalyst. The critical role of SnCl2 in Pt- phosphane was needed to produce the cycloreduction prod-
catalyzed hydrogenations has been emphasized in previous uct in good yield. In comparison to compound 1a, oxygen-
reports.[12] It is likely that no cycloreduction proceeded in tethered substrate 2a, which is known to be unstable under
the absence of SnCl2 (Table 1, Entry 9). Interestingly, when transition-metal catalysis conditions, showed a diminished
hydrogen was omitted, neither the desired reductive cycliza- yield (51%). Compound 3a possessing an acetyl-substituted
tion product nor the cycloisomerization product, which is enone participated in the reaction in the presence of P(p-
Scheme 1. Deuterium labeling studies.
Scheme 2. A plausible catalytic cycle.
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Eur. J. Org. Chem. 2009, 6091–6094

Hydrogenative Cyclization of Yne-enones, Yne-aldehydes, and Yne-dienes
CF3C6H4)3, affording compound 3b in 78% yield. In the tively in the presence of P(p-OMeC6H4)3, providing desired
case of the ester substituted substrate, compound 4a under- product 8b and 9b in 72 and 98% yield, respectively.
went cyclization to form the product in 39% yield due to
To probe the reaction mechanism, the cyclizations of
the low reactivity of the ester-substituted alkene as an elec- compound 1a, 5a, and 8a were carried out under D2, pro-
trophile.
viding deuterio-1b, deuterio-5b, and deuterio-8b as a mixture
of two stereoisomers in 63, 30, and 60% yield, respectively
(Scheme 1). In the case of compound 5a, deuterated pyrrole
derivative 5c was observed in 30% yield, along with de-
uterio-5b. During the reaction in the presence of D2, par-
tially deuterated 5b, 5c, and 8b were observed, which is at-
tributed to the formation of Pt–H during the catalytic reac-
tion. Although D2 was employed for reductive cyclization,
hydrometalation of Pt–D to the 1,3-diene functional group
of 5c and 8a might occur and subsequent β-hydride elimi-
nation is assumed to provide the Pt–H complex to account
for the incorporation of hydrogen in deuterio-5b, 5c, and
8b.[13]
Table 2. Examples of cycloreduction.
To rationalize the present outcomes of deuterium label-
ing studies, a dipolar mechanism involving metastable IЈ
was considered[14] (Scheme 2). The catalytic cycle begins
with the hydrometalation of LnPtD to the alkyne,[15] fol-
lowed by cis–trans isomerization between intermediates I
and IЈЈ. Subsequently, each intermediate undergoes cycliza-
tion, forming intermediate II, which reacts with another
molecule of deuterium to produce the cyclized products
with the regeneration of the LnPtD catalysts. The genera-
tion of intermediate I and the equilibrium to intermediate
IЈЈ can account for the formation of the two isomeric mix-
tures of deuterio-1b, 5b, and 8b (Scheme 1).
Conclusions
In summary, the cycloreductions of yne-enones, yne-al-
dehydes, and yne-dienes were explored by using a Pt cata-
lyst generated from PtCl2, SnCl2, phosphane, and H2. This
catalytic system produced five-and six-membered cyclore-
duction products in moderate to good yields by using nitro-
gen- and carbon-tethered substrates. In the case of nitrogen-
tethered yne-aldehyde substrate 5a, pyrrole derivative 5c
was formed by dehydration and migration of the double
bond of cycloreduction product 5b. On the basis of the deu-
terium labeling study, it was speculated that the diploar in-
termediate was generated after hydrometalation of the al-
kyne, rendering a cis–trans isomerization. The knowledge
gained from the Pt-catalyzed hydrogen-mediated cyclization
of yne-enones, yne-aldehydes, and yne-dienes is expected to
contribute to the design and development of efficient and
versatile Pt catalysts for a wide variety of reductive cou-
plings.
[a] P(C6F5)3. [b] P(p-CF3C6H4)3. [c] Pt(cod)Cl2 and P(p-OMeC6H4)3
were used. Compounds 8b and 9b were obtained as isomeric mix-
tures of ratio 2.4:1 and 1.5:1, respectively. Indicated stereoisomers
are major compounds.[15b] [d] The reaction was run at ambient tem-
perature.
In addition to α,β-unsaturated carbonyl compounds, the
aldehyde participated effectively in the reductive cyclization
with the alkyne. Nitrogen-tethered 1,5-alkynal 5a was sub-
jected to these reaction conditions, affording cyclized prod-
uct 5b and pyrrole 5c in 62% yield. Nitrogen-tethered 1,7-
alkynal 6a participated in the reductive cyclization, afford-
ing compound 6b in 52% yield. Carbon-tethered substrate
7a underwent the cyclization successfully but exo-methylene
cyclopentenol 7b isomerized to 7c during the catalytic reac-
tion. Both nitrogen-tethered yne-diene 8a and carbon-teth-
Experimental Section
Representative Experimental Procedure for Reductive Cyclization:
To a premixed solution of PtII (5 mol-%), phosphane (5 mol-%),
and SnCl2 (25 mol-%) under an atmosphere of H2 (1 atm) in
dichloroethane (0.1 ) was added each substrate under an atmo-
ered yne-diene 9a underwent reductive cyclization effec- sphere of H2 (1 atm) at room temperature. The resulting mixture
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Acknowledgments
This study was supported by the Korea Science and Engineering
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Received: September 3, 2009
Published Online: November 2, 2009
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