Aerobic oxygenative cleavage of electron deficient C-C triple bonds in the gold-catalyzed cyclization of 1,6-enynes

Article abstract of DOI:10.1039/c4cc04153d

Gold-catalyzed aerobic oxygenative cleavage of triple bonds that occurs under the ambient pressure of air and at room temperature is reported; radical inhibition tests suggest that oxygenation occurs via a gold-bound metalloradical intermediate. This journal is

Full text of DOI:10.1039/c4cc04153d

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Aerobic oxygenative cleavage of electron
deficient C–C triple bonds in the gold-catalyzed
cyclization of 1,6-enynes†
Cite this: Chem. Commun., 2014,
0, 12722
5
Received 30th May 2014,
Accepted 25th August 2014
Dilip V. Patil, Hyun-Sub Park, Jaeyoung Koo, Jin Wook Han* and Seunghoon Shin*
DOI: 10.1039/c4cc04153d
www.rsc.org/chemcomm
a
Gold-catalyzed aerobic oxygenative cleavage of triple bonds that Table 1 Examination of reaction conditions
occurs under the ambient pressure of air and at room temperature
is reported; radical inhibition tests suggest that oxygenation occurs
via a gold-bound metalloradical intermediate.
Dioxygen has recently received a great deal of attention as an
ideal end-oxidant in transition metal-catalyzed oxidation and
b
b
oxygenation reactions because it does not generate noxious
Entry
Substrate
Solvent
Time (h)
2 (%)
3 (%)
1
by-products. Selective oxidations occurring under ambient
c
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
CH
2
Cl
2
4
4
4
4
4
4
4
4
12
2
87
86
74
66
25
—
7
—
—
—
—
11
conditions (ca. 0.2 atm of O and at RT) would be particularly
2
CH Cl2
2
appealing for larger-scale applications, considering operational
hazards associated with pressurized oxygen gas (or even air) at
CHCl
3
—
—
45
54
63
75
(73)
(82)
(86)
1,2-DCE
Toluene
THF
2
elevated temperature.
In oxidative transformations catalyzed by homogeneous gold
Et
2
O
3
–6
1,4-Dioxane
1,4-Dioxane
complexes, there has been an increasing use of dioxygen as a
d
7
d
reactant. In 2006, Y. Liu and coworkers reported the oxidative
1
0
C
CF
6
H
5
F
7
a
d
cleavage of C–C triple bond of (Z)-enynols. This process 11
3
CH
2
OH
1.5
involves Au(I)-catalyzed cyclization, followed by autoxidation of
a
Reaction conditions: 1 (0.1 mmol, 0.1 M), Au(SPhos)Cl (5 mol%) and
7b
b
electron-rich enolethers. A similar type of autoxidation was AgSbF
6
(5 mol%). Yields based on crude NMR spectra (1,3,5-
c
trimethoxybenzene) except noted otherwise. Au(PPh
was used. Isolated yield after chromatography in parenthesis.
3
)Cl and AgSbF
6
observed by Hashmi and coworkers in the cyclization of propargyl
amides into 2,5-disubstituted oxazoles having hydroperoxide
d
7c
functionality. Furthermore, R.-S. Liu and coworkers reported
the unique simultaneous cleavage of a single and a triple bond bicyclo[3.2.0]hept-6-enes, such as 2, in the presence of cationic
of propargyl ethers with the evolution of CO and CO
as C1 Au(PPh )SbF in CH Cl under a nitrogen atmosphere.
2 3 6 2 2
byproducts. We report herein that 1,6-enynes derived from Surprisingly, when the reaction was performed without rigorous
propiolamides deliver tricarbonyl products 3 through a novel triple exclusion of air (in a vial closed under ambient air), an
bond cleavage process. Remarkably, this transformation cleaves unexpected tricarbonyl compound 3a (11%) was co-isolated along
9
7d
8
electron-deficient triple bonds and proceeds efficiently under with 2a (entry 1, Table 1). With SPhos as the ligand, the ratio of 3a
ambient oxygen pressure (ca. 0.2 atm) and at room temperature.
vs. 2a was highly dependent on the solvents: in accordance with
Recently, Chung and coworkers reported cyclization of Chung’s report, the formation of bicyclo[3.2.0]hept-6-enes was
,6-enynes derived from propiolates or propiolamides into favored in chlorinated solvents (entries 1–4), whereas a predomi-
nant formation of tricarbonyl 3a was obtained in toluene or
1
Department of Chemistry and Institute for Natural Sciences, Hanyang University,
ethereal solvents (entries 5–9). Furthermore, we were pleased to
find that fluorinated solvents that are known to dissolve a larger
amount of oxygen accelerated the reaction giving an excellent
Seoul 133-791, Korea. E-mail: jwhan@hanyang.ac.kr, sshin@hanyang.ac.kr;
Fax: +82-2-2299-0762; Tel: +82-2-2220-0948
10
†
Electronic supplementary information (ESI) available: Optimization study,
experimental procedures and characterization data for new compounds. CCDC
33766. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c4cc04153d
isolated yield of 3b (86%) in 1.5 h at rt (entry 11). The structure of
the tricarbonyl product was unambiguously confirmed by X-ray
9
11,12
diffraction analysis of a related product 3e.
1
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To investigate the source of carbonyl O atoms, we performed patterns in 3k–p. Here, reactions of substrates with R sub-
1
8
18
the reaction in the presence of a H
2
O or
2
O environment, stitution were less effective, suggesting a developing strain in
1
3
18
1
employing 1b as a substrate. In the presence of H
15 equiv.) in 1,4-dioxane in an open flask, no O atom was (1p) also afforded tricarbonyl 3p as a major product. Notably,
incorporated into 3b. However, the reaction under an O2 the carbocyclic analogue 3q–t was formed smoothly without
balloon afforded 61% and 10% O atom incorporation at the any event. Unfortunately, however, homoallyl amide substrates
indicated positions (eqn (1)), confirming that dioxygen was the or ester-tethered substrates were unreactive. The net result
O
the transition state (3n–p). Those without R substitution
2
1
8
(
1
2
18
1
8
1
2,14
source of carbonyl oxygen.
of this triple bond cleavage is that the two Csp atoms of the
alkyne are added to alkenes, forming synthetically useful
1,4-dicarbonyl compounds. For example, the product 3r could
(1)
be converted into a fused pyrrole 4r via the Paal–Knorr syn-
thesis (eqn (2)).
The scope of the present method was next probed for a range
of substrates shown in Table 2. The reaction was conducted in
(2)
an open vial, employing Au(SPhos)Cl and AgSbF
6
(5 mol% each)
as catalysts in CF CH OH. Variations of electron-demand on the
3
2
(
(
3)
4)
arylalkyne moiety were well-tolerated providing 3a–g in good to
excellent yields. Different N-substituents were also well-tolerated,
including benzyl (3b), allyl (3i), alkyl (3e), phenyl (3h) and tosyl
1
2
(
3j) groups. Gratifyingly, different allyl moieties (R , R ) could
also be accommodated providing access to diverse substitution
a
Table 2 Investigation of the reaction scope
It is noteworthy that the reaction of 1m at a higher tem-
perature (60 1C) gave a predominantly metathesis type of
product (51%, eqn (3)) that could arise via s-bond reorganiza-
tion of II (Scheme 1). Surprisingly, the reaction of 1u unexpect-
edly provided dicarbonyl 5u as a major product in 1,4-dioxane
along with a small amount of 2u (25%). In CF
acetophenone derivative 6u was the only identifiable product
eqn (4)). At this point, the aberrant behavior of 1u is not clearly
3 2
CH OH, the
(
understood, but seems to be related to the stability of the
carbocationic II (Scheme 1).
To deduce a possible mechanistic model, the following experi-
ments were conducted. If the incorporation of triplet oxygen
occurs after the Au turnover (i.e. at III in Scheme 1), radical
inhibitors will not stop the conversion of the starting 1, unless
+
the cationic Au is decomposed by the radical inhibitors.
In contrast, if the oxygenation by O
stage (such as II/II ), the catalyst may be deactivated by the
2
occurs at the Au-bound
0
a
3 2
CF CH OH (0.1 M) as a solvent unless otherwise noted; isolated yield
b
after chromatography; reaction time in parentheses. 1,4-Dioxane as a
solvent. The product was obtained as a single diastereomer. 1p as a
mixture of E/Z (3 : 1) isomers was used.
c
d
Scheme 1 Proposed mechanism for the triple bond cleavage.
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a
Table 3 Effect of radical inhibitors
and deauration of II via V would lead to 2. For the formation of 3,
0
a pathway involving Au(I) turnover from II to form metal-free III
18
and then oxygenation to 1,2-dioxetane IV was first considered.
However, such a pathway should go through a highly strained
19
trans-cycloheptenoid (III), and furthermore, the liberated Au(I)
should continue to consume 1. To explain the catalyst deactiva-
tion (entry 2, Table 3), an alternative mechanism has been
Product
0
proposed that involves the reaction of II/II with a triplet oxygen
1
b
2b 3b
Time (h) (%) (%) (%)
to form a metalloradical VI through a single electron transfer
Entry Conditions
Solvent
5
d,e,20
from Au(I) to O
2
.
Catalyst poisoning by BHT most likely
1
2
3
4
Open vial, no additive 1,4-Dioxane 12
Open vial, BHT (10%) 1,4-Dioxane 15
Under Ar, no additive CH
Under Ar, BHT (10%) CH
—
94
—
—
—
—
85
84
73
—
—
—
occurs at this stage. The following radical fragmentation via
VII can lead to 3. The observation of 5u and 6u may be
explained by the addition of trace amount of extraneous water
2
Cl
Cl
2
6
6
2
2
a
NMR yield based on an internal standard; BHT: 2,6-di-tert-butylcresol. into cationic II stabilized by the electron-richer aryl groups.
The following retro-aldol or [2+2] cyclo-reversion can generate
5
u and 6u, respectively.
In summary, we have reported herein the cyclization of
presence of radical inhibitors. The effect of BHT as a radical
inhibitor for the formation of 2b and 3b from 1b is summarized
in Table 3. The formation of 3b in 1,4-dioxane (under air) was
completely blocked in the presence of catalytic amounts of BHT
and the starting 1b was recovered (entries 2 vs. 1). In sharp
1,6-enynes with the cleavage of C–C triple bonds into 1,4-diketones.
The cleavage of an electron-deficient C–C triple bond is uncommon
and the salient features of this reaction are that the reaction
occurs efficiently at room temperature and under the atmo-
spheric pressure of air (0.2 atm of O ). Experiments indicated
2
that the oxygenation product formed via the Au-bound inter-
mediate, and not through metal-free autoxidation.
2 2
contrast, the formation of 2b in CH Cl (under Ar) was not
inhibited at all by the BHT (entries 4 vs. 3). These experiments
suggest that oxidation by O2 occurs via metallo-radical inter-
mediates, unlike previous metal-free autoxidation of electron-
7
b
This work was supported by a National Research Founda-
tion of Korea (NRF) grant funded by the Korean Government
rich intermediates in the reactions of (Z)-enynols or propargyl
7c
amides.
(2014-011165, 2012-015662 and 2012M3A7B4049653).
Notes and references
(
(
5)
6)
1
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3 2 2
Exposure of 2b in CF CH OH to air or O (1 atm) in the
presence or absence of the Au-catalyst resulted only in a near
quantitative recovery of the starting 2b (eqn (5)), suggesting
that 2b is not a precursor of 3b. In a d-labelling study, the
reaction of (E)-d-1b under anaerobic condition gave d-2b with
a slight loss of deuterium at the methylene position of 1b.
In contrast, under an atmosphere of air, d-3b was obtained
with no loss of D-atoms (eqn (6)). This indicates that the
oxygenation does not occur via allylic H-abstraction by peroxy
radicals from ether solvents or via an ene-reaction with
4 Outer sphere oxidation of alkynes (reviews): (a) H. S. Yeom and
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5
Inner sphere oxidation of Au(I): (a) H. A. Wegner, S. Ahles and
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5
7
c
(
2
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1
6
2
singlet O .
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7
0
9
heptane II/II (Scheme 1). The formation of 2 was computa-
(
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9
a
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1
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1
2724 | Chem. Commun., 2014, 50, 12722--12725
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6
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1
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4
ꢀ
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1
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1
3 For oxidations involving H
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(
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18
1
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 12722--12725 | 12725