Pt-catalyzed tandem 1,2-acyloxy migration/intramolecular [3 + 2] cycloaddition of enynyl esters

Article abstract of DOI:10.1021/ja910346m

(Formula Presented) A platinum-catalyzed tandem reaction involving enynyl ester isomerization and subsequent intramolecular [3 + 2] cyclization has been developed. This strategy provides an efficient approach to five-, six-, or seven-membered cyclic polyfunctional compounds. Copyright

Full text of DOI:10.1021/ja910346m

Published on Web 01/25/2010
Pt-Catalyzed Tandem 1,2-Acyloxy Migration/Intramolecular [3 + 2]
Cycloaddition of Enynyl Esters
Huaiji Zheng, Jiyue Zheng, Binxun Yu, Qiang Chen, Xiaolei Wang, Yongping He, Zhen Yang, and
Xuegong She*
State Key Laboratory of Applied Organic Chemistry, Department of Chemistry, Lanzhou UniVersity,
Lanzhou 730000, P. R. China
Received December 14, 2009; E-mail: shexg@lzu.edu.cn
In recent years, utilization of Pt and Au catalysts to promote
reactions of enyne derivatives has attracted considerable attention in
modern catalysis.1,2 Among these reports, the propargylic carboxylate
is a unique class of substrates because of its significant reactivity pattern
involving Ct C triple-bond activation and O-ester rearrangement.3 As
shown in Scheme 1, the O-ester group undergoes an internal 1,3-shift
catalyzed by the transition metal, giving the rearranged allenic
intermediate D,4 wherein the computational calculation suggests that
1,3-acyloxy migration might also account for the double 1,2-acyloxy
migrations involving the in situ generation of synthetically valuable
1,3-dipole intermediate C.4a,5 To explore the diversity of reactivity of
enyne chemistry, we envisioned that the intermediate C, a metal-
involved 1,3-dipolar synthon, might experience cycloaddition with an
appropriate olefin to generate cycloaddition product E. To our
knowledge, this tandem transformation involving 1,2-acyloxy migration
of propargylic carboxylates followed by 1,3-dipolar cycloaddition has
not been reported previously. Herein, we present a cascade process
involving PtCl2-catalyzed 1,2-acyloxy migration of propargylic esters
and subsequent intramolecular [3 + 2] cycloaddition, giving access
to various functionalized cyclic compounds that are synthetically
interesting building blocks in the total synthesis of structurally relevant
natural products.
9-12). Simple Au catalysts such as AuCl3 and AuCl were ineffective
for this transformation, but interestingly, the cationic Au catalyst modified
with phosphines or N-heterocyclic carbene (NHC)-containing ligands6
promoted the formation of 3a, despite the low to moderate yield.
Table 1. Optimization of Reaction Conditions
entry
catalyst
solvent
T (°C)
time (h)
yield (%)a
1
2
3
4
5
6
7
8
PtCl2 (10% mol)
PtCl2 (10% mol)
PtCl2/CO (10% mol/1 atm) toluene
PtCl2/CO (10% mol/1 atm) toluene
PtCl2/CO (10% mol/1 atm) toluene
PtCl2/CO (10% mol/1 atm)
PtCl2/CO (10% mol/1 atm) THF
PtCl2/CO (10% mol/1 atm) MeCN
AuCl3 (5% mol)
AuCl (5% mol)
toluene
toluene
80
60
80
60
rt
60
60
60
60
60
rt
4
6
1
1
24
8
4
8
12
12
1
35
74
60
78
NR
71
61
NR
b
DCE
c
9
10
11
toluene
toluene
DCM
trace
trace
17
c
PPh3AuCl/AgSbF6
(5% mol/5% mol)
Au(IMes)Cl/AgSbF6
(10% mol/10% mol)
b
12
rt
2
58
DCE
a Isolated yields. b DCE ) 1,2-dichloroethane. c The remaining 1a was
recovered.
Scheme 1. Transition-Metal-Catalyzed Reactivity of Propargylic
Carboxylates
With optimized reaction conditions in hand, we then investigated a
series of enynyl esters under our PtCl2-catalyzed tandem protocol, and
various synthetically valuable multisubstituted pyrans were accessed
in good to excellent yields (Table 2). The ester group could be varied
from propargylic acetate to benzoate and pivaloate with satisfactory
yields (entry 1). Investigations of the substituent effects at the C6-C9
positions indicated that this tandem reaction has a wide range of
substrate scope. Substrates bearing various aryls at C6 afforded the
corresponding pyran adducts in good to excellent yields (entries 1-3).
The C6 alkenyl- and alkyl-substituted substrates were also suitable
for this reaction (entries 4-7). Substituents at C7 or C8 of the substrate
were also tolerated but gave the partially hydrolyzed dihydrofurans 3j
and 3k (entries 8 and 9), in which the related completely hydroxyl
diketones were not isolated. Contrarily, the C9 dimethyl-substituted
substrate 1l failed to undergo this transformation, and the fragmented
alcohol 4 was produced in 45% yield with the recovery of 1l in 52%
yield (entry 10). Surprisingly, substituents at the C1 position offered
severe disadvantages to the expected reaction because of the steric
bulk of the two methyl groups (entry 11).7 In the case of substrate 1m,
the undesired conjugated diene 5 was obtained in 67% yield. Furthermore,
the scope of this reaction was expanded to enynyl esters 1n-r contain-
ing the homopropargylic moiety, and a series of structurally differantial
pyrans were smoothly produced in good yields (entries 12-16).
Initially, enynyl ester 1a was selected as a model substrate to
investigate this proposed tandem transformation. Pleasingly, the
reaction proceeded in the presence of PtCl2 (10 mol %) in toluene at
80 °C for 4 h, leading to the formation of 3a in 35% yield (Table 1,
entry 1), in which the instability of the resulting enol ether 2a enabled
rapid hydrolysis on silica gel. The yield was readily increased to 74%
within 6 h by lowering the temperature to 60 °C (entry 2). When the
reaction was carried out in toluene at 80 °C under an atmosphere of
CO (1 atm), 3a was obtained in 60% yield with a reduced reaction
time of 1 h (entry 3). The optimal result was further obtained in 78%
yield in toluene at 60 °C under an atmosphere of CO (entry 4). The
reaction also proceeded in 1,2-dichloroethane (DCE) or tetrahydrofuran
(THF) solvent (entries 6 and 7). When the reaction was carried out in
CH3CN at 60 °C or in toluene at room temperature under an
atmosphere of CO, no reaction was observed (entries 5 and 8). In
addition to PtCl2, several Au catalysts were also examined (entries
In order to demonstrate the synthetic utility of this tandem
reaction in the synthesis of non-pyran cyclic componds, three
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1788 J. AM. CHEM. SOC. 2010, 132, 1788–1789
10.1021/ja910346m  2010 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Pt-Catalyzed Tandem 1,2-Acyloxy Migration/
Scheme 3. PtCl2-Catalyzed [3 + 2] Cycloaddition of Enynes and
the Proposed Mechanism
Intramolecular [3 + 2] Cycloaddition Reaction of Enynyl Estersa
In conclusion, we have completed a platinum-catalyzed tandem
reaction involving enynyl ester isomerization and subsequent intramo-
lecular [3 + 2] cyclization. This strategy provides an efficient approach
to five-, six-, or seven-membered cyclic polyfunctional compounds.
This study permitted the details of a novel cycloisomerization mode
to be uncovered and, more generally, provided insight into mechanistic
aspects of the intricate cyclization mode of enynes bearing a propargylic
ester group. Further studies taking advantage of this tandem protocol
to address complex synthetic issues are ongoing.
Acknowledgment. We are grateful for the generous financial
support by the MOST (2010CB833200) and the NSFC (QT
Program, 20872054, 20732002).
Supporting Information Available: Experimental procedures,
compound characterization data, and CIF files for 3c, 3r, and 3u. This
material is available free of charge via the Internet at http://pubs.acs.org.
References
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Scheme 2. Modified Pt-Catalyzed Reaction of Enynyl Esters
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additional acyclic enynyl esters 1s-u were employed (Scheme 2).
It is worth mentioning that seven-membered-ring compound 3s can
also be generated under these conditions. For the full-carbon-chain
substrates 1,7-enynyl ester 1t and 1,6-enynyl ester 1u, the cyclo-
hexane derivative 3t and the fused cyclopentane derivative 3u were
obtained in 75 and 54% yield, respectively.
For products 3c, 3r and 3u, the corresponding structures and
relative configurations were further confirmed by X-ray crystal-
lography (for details, see the Supporting Information).
A rational mechanism for this Pt-catalyzed cascade transformation
is proposed in Scheme 3. Pt-promoted 1,2-acyloxy migration of the
propargylic ester leads to the formation of the Pt carbene intermediate
III via II. The Pt carbenoid then undergoes an intramolecular
nucleophilic addition of the carbonyl to give the 1,3-dipolar intermedi-
ate IV, which forms enol ketal 2 through [3 + 2] cycloaddition with
the release of the Pt catalyst for the next catalytic cycle. After hydrolysis
on silica gel, enol ketal 2 provides the desired product 3.
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(7) The formation of the conjugated diene 5 may involve 1,2-acyloxy migration
and 1,2-hydride migration, for which the proposed mechanism is shown below:
JA910346M
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