Dual visible light photoredox and gold-catalyzed arylative ring expansion

Article abstract of DOI:10.1021/ja500716j

A combination of visible light photocatalysis and gold catalysis is applied to a ring expansion-oxidative arylation reaction. The reaction provides an entry into functionalized cyclic ketones from the coupling reaction of alkenyl and allenyl cycloalkanols with aryl diazonium salts. A mechanism involving generation of an electrophilic gold(III)-aryl intermediate is proposed on the basis of mechanistic studies, including time-resolved FT-IR spectroscopy.

Full text of DOI:10.1021/ja500716j

Communication
pubs.acs.org/JACS
Dual Visible Light Photoredox and Gold-Catalyzed Arylative Ring
Expansion
Xing-zhong Shu,†,⊥ Miao Zhang,‡ Ying He,†,⊥,§ Heinz Frei,*,‡ and F. Dean Toste*,†,⊥
†Department of Chemistry, University of California, Berkeley, California 94720, United States
⊥Chemical Sciences Divisions, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720, United States
‡Physical Biosciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720, United States
§Institute of Chemistry and BioMedical Sciences, Nanjing University, Nanjing 210046, P. R. China
S
* Supporting Information
(B) that subsequently reacts with the alkene to induce
ABSTRACT: A combination of visible light photo-
catalysis and gold catalysis is applied to a ring
expansion−oxidative arylation reaction. The reaction
provides an entry into functionalized cyclic ketones from
the coupling reaction of alkenyl and allenyl cycloalkanols
with aryl diazonium salts. A mechanism involving
generation of an electrophilic gold(III)−aryl intermediate
is proposed on the basis of mechanistic studies, including
time-resolved FT-IR spectroscopy.
intramolecular heteroarylation (eq 2). Inspired by recent
reports from the Gaunt laboratory,7 we hypothesized that
gold(III) species B might be a potent electrophile, capable of
engaging π-bonds and ultimately delivering a formal aryl
electrophile (eq 3). Herein, we describe application of this
hypothesis to the development of a gold-catalyzed arylative ring
expansion and experiments distinguishing these mechanistic
paths.
On the basis of this hypothesis, we reacted vinylcyclopro-
panol (1a) and phenyldiazonium 2a with 10% triphenyl-
phosphinegold(I) and 5% Ru(bpy)3(PF6)2 under visible light.8
Under these conditions, 1a underwent ring expansion9 and
coupling10 with 2a to afford cyclopentanone 3aa in 87% yield
(Scheme 1, 2a). Only a trace amount of product was detected
by NMR when the reaction was conducted in the absence of
light, photocatalyst, or gold catalyst (Table S3). The reaction
proceeded smoothly with diazonium salts having methyl
omogeneous gold catalysis has received great attention in
H
the past decade.1 The majority of reports rely on the π-
acidity of either gold(I) or gold(III) complexes to activate
multiple bonds toward nucleophilic attack, followed by
protodeauration. On the other hand, gold complexes, in
combination with a strong oxidant, have been shown to
catalyze oxidative functionalization reactions of unactivated
alkenes.2,3 In general, these reactions are proposed to proceed
through alkylgold(III) intermediates that undergo coupling
with nucleophiles such as arylsilanes and boronic acids.4
Recently, Glorius and co-workers proposed that aryl radicals,
generated by photoredox reaction of aryldiazonium salts, could
be employed to access analogous gold(III) species through
oxidation of an alkylgold(I) intermediate (A, eq 1).5 As an
a
Scheme 1. Reaction of 1a with Diazonium Compounds
a
Unless noted otherwise, method A was used: visible light, 1a (0.2
mmol), ArN2BF4 (3 equiv), Ph3PAuCl (10 mol%), Ru(bpy)3(PF6)2
(2.5 mol%), degassed MeOH/CH3CN (3:1, 5 mL) under N2 at rt.
Method B was used: Ph3PAuCl (10 mol%), Ir(ppy)3 (2.5 mol%).
Method C was used: (4-CF3Ph)3PAuCl (10 mol%), Ru(bpy)3(PF6)2
b
(2.5 mol%). Isolated yields are given. Yields were calculated on the
1
basis of H NMR using internal standard.
alternative, we envisioned that these reactions might proceed
through a pathway in which photoredox catalysis6 occurs first,
providing an entry into a cationic arylgold(III) intermediate
Received: January 22, 2014
Published: April 14, 2014
© 2014 American Chemical Society
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Communication
substituted at each position of the aryl ring, giving good yields
of desired products 2b−d. However, a more electron-rich
substituent on the aryl ring gave low yield with the use of
Ph3PAuCl as catalyst. A strong electron-withdrawing group on
the ligand of the gold catalyst improved the yield of desired
product (2e, method A vs C). The arylation of electron-
deficient diazoniums also proceeded efficiently in the presence
of Ru catalyst (2f−j). In the case of Ir(ppy)3-catalyzed arylation
of 2d, a lower yield of desired product was obtained in 12 h,
and a significant amount of diazonium salt was recovered (2d,
method A vs B). However, improved results were obtained
when the Ir photocatalyst was employed to couple electron-
poor diazonium salts (2f and 2j, method A vs B).
presented in Table S5 and Figure S7). The kinetic behavior for
the formation of the final product 3ab (phenyl C−C mode at
1515 cm−1) displays an induction period relative to the kinetics
for consumption of the diazonium compound and suggests the
formation of an intermediate involved in the rate-limiting step.
As shown in Figure 1, the absorption band at 1488 cm−1 was
The reaction proceeded efficiently with various alkyl-
substituted alkenes (Table 1, entries 1−3). A substrate bearing
Figure 1. Temporal behavior of intermediate (1488 cm−1) and final
product (1515 cm−1) of arylation−ring expansion of vinylcyclobutanol
in liquid solution monitored by rapid-scan ATR FT-IR spectroscopy.
The panel on the right shows the temporal behavior on an expanded
absorbance scale for clarity. The band at 1730 cm−1 is the CO mode
of the expanded ring.
Table 1. Scope Studies of Vinylcyclobutanols and
Vinylcyclopropanols
a
entry
n
R
Ar
Ph
time (h) 3 (% yield)
identified to be associated with this intermediate, increasing
upon onset of the light pulse and decreasing concurrently with
the growth of the final product. The kinetic relevancy of this
intermediate was directly demonstrated by the matching rates
of its consumption and the rise of the product band at 1515
cm−1. The absorption band at 1730 cm−1, which is the ν(CO)
mode of the expanded ring, is also associated with this
intermediate. By simultaneous least-squares fitting of the
temporal behavior of the 1250 cm−1 reactant, the 1488 cm−1
intermediate, and the 1515 cm−1 final product bands according
to the model
1
2
3
4
5
2
2
2
2
2
2
2
2
2
1
1
n-hexyl (1b)
isopropyl (1c)
Bn (1d)
6
6
3ba (90)
3ca (81)
3da (83)
3ea (80)
3fa (34)
3fb (71)
3ga (67)
3ha (80)
3ia (32)
3ja (67)
3ka (51)
Ph
Ph
6
PhthN(CH2)3 (1e)
Ph (1f)
Ph
4
Ph
24
24
24
6
b
6
Ph (1f)
4-FPh
4-FPh
4-FPh
4-FPh
Ph
b
7
4-ClPh (1g)
4-MePh (1h)
2-MePh (1i)
Ph (1j)
b
8
b
9
24
15
6
10
11
Bn (1k)
Ph
k1
k2
a
Unless noted otherwise, method A was used (see Scheme 1, footnote
R → I → P
b
a). Isolated yields are given. Method D was used: 4-FPhN2BF4 (4
kinetic parameters were obtained, on the basis of which the
temporal behavior of the 1730 cm−1 CO stretch absorption
was simulated. As shown in Figure S8, excellent agreement of
the simulated curve with the experimental absorbance at 1730
cm−1 was obtained. The result confirms that both the
intermediate and the final product absorb at 1730 cm−1.
Notably, these bands were not observed when the experiment
was carried out in the absence of gold (Figure S7), strongly
suggesting that the gold catalyst is required for ring expansion
to occur. These observations are consistent with a kinetically
relevant intermediate that requires decomposition of the
diazonium compound for its formation and contains an
expanded five-membered-ring ketone (1730 cm−1), but has
yet to undergo reductive elimination to form the C−C bond
(methyl-substituted analogue of 11, see Scheme 2).
The stereochemical course of the gold-catalyzed ring
expansion−arylation reaction was probed with deuterium-
labeled alkenes (eq 4). In the presence of gold catalysts, the
ring expansion reaction occurred with high levels of stereo-
specificity.12 Moreover, the observed stereochemistry of the
corresponding products is consistent with the previously
observed anti-migration13 and carbon−carbon bond formation
with stereochemical retention from alkylgold(III)−phenyl
species.4a
equiv), Ir(ppy)3 (2.5 mol%), and (4-CF3Ph)3PAuCl (10 mol%).
a protected amine group was tolerated (entry 4). The Ru
catalyst was inefficient in promoting the reaction of aryl-
substituted substrates, and product 3faa was obtained in low
yield with significant decomposition (entry 5); however, use of
the Ir catalyst improved the reaction (entries 6−8).11 The
reactivity was decreased when a sterically hindered aryl group
was used (entry 9). Finally, good yields of cyclobutanones were
obtained from the ring expansion/coupling reaction of
vinylcyclopropanols (entries 10 and 11).
To probe the mechanism of this dual catalysis, time-resolved
FT-IR spectroscopy in the attenuated total reflection (ATR)
mode was employed to detect intermediates under reaction
conditions. Catalysis in methanol/acetonitrile (3/1) solution
containing reactants 1a and 2b, catalyst (CF3Ph)3PAuCl, and
sensitizer Ru(bpy)3(PF6)2 held in a liquid cell was initiated with
a 458 nm laser pulse (150 mW, Ar ion laser) of 12 s duration.
Arrival of the laser pulse was synchronized with the acquisition
of rapid-scan FT-IR spectra over a period of 96 s. Reaction of
the phenyl radical generated by photoactivation of the sensitizer
was monitored by characteristic infrared absorptions of the
reactants and final cyclopentanone product, which were
identified by recording spectra of authentic samples (com-
pound 2b, 1583 cm−1, νAr(C−C); compound 1a, 1467 cm−1,
ν(CC) and 1250 cm−1, ν(C−O); additional spectral data are
The current ring expansion−arylation reaction appears to
begin with gold(III) or gold(I) coordination with the alkene.
However, Ph3PAuCl on its own does not promote additions to
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Journal of the American Chemical Society
Communication
propensity of vinylgold intermediates to undergo facile
protodeauration. In contrast, the mechanism outlined in
Scheme 2 implies that the gold(III)−aryl is formed directly
from the ring expansion event, and therefore reductive
elimination might become competitive with protodeauration.
In order to further probe this hypothesis and expand the scope
of the dual catalysis, the standard reaction conditions were
applied to allenes 12a−e (eq 6). These allene substrates were
more reactive than alkenes and generally gave moderate yields
of the ring-expanded products in shorter time.
alkenes, and employing Ph3PAuBF4 as catalyst produced
inferior results (eq 4 and Figure S6). The reaction of Ph3PAuCl
with phenyl radical could generate Ph3PAuPh,14 which would
catalyze the title reaction. However, employing the independ-
ently prepared phenylgold(I) compound as a catalyst produced
3aa in inferior yield (eq 5).
On the basis of these observations and the experimental
results described above, a possible mechanism is proposed in
Scheme 2. The reaction of PhN2BF4 with photoexcited
In conclusion, we have reported a ring expansion−oxidative
arylation reactions of small sized ring-substituted alkenes and
allenes. The reaction was promoted by dual visible light
photoredox catalysis and gold catalysis at ambient conditions.
The mechanism of the reaction was studied by time-resolved
FT-IR spectroscopy and is consistent with formal oxidative
addition of gold(I) to aryldiazonium salts to form gold(III)−Ar
species preceding the reaction with the alkene. These oxidized
intermediates react as potent electrophiles toward π-bonds and
ultimately provide an entry into formal electrophilic aryl
species.
Scheme 2. Proposed Mechanism for Photoredox-Promoted,
Gold-Catalyzed Ring Expansion−Arylation Reaction
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental procedures and 1H NMR spectra. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
hmfrei@lbl.gov
■
fdtoste@berkeley.edu
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge support from the Director, Office of Science,
Office of Basic Energy Sciences, Division of Chemical Sciences,
Geological and Biosciences, of the U.S. DOE under contract
DE-AC02-05CH11231. F.D.T. gratefully acknowledge
NIHGMS (RO1 GM073932) for financial support.
10
3+
Ru(bpy)32+* generates Ru(bpy)3
and phenyl radical, and
that reacts with the gold(I) catalyst to initially generate
gold(II)−aryl 8.15 This gold(II) intermediate is further oxidized
by RuIII, giving gold(III)−aryl 916 and regenerating the
photocatalyst.17 The proposed gold(III) intermediate 9
accounts for the formation of ligand and diazonium-derived
phosphonium salts ([Ph3P-Ph]+ in Scheme 2) after con-
sumption of alkene substrate or in the reaction without alkene
(Figure S1).18 The anti-ring expansion of complex 10 furnishes
alkylgold(III) intermediate 11, which undergoes a reductive
elimination to give the desired product 6 and regenerate the
gold(I) catalyst.
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