Visible light-mediated gold-catalysed carbon(sp2)-carbon(sp) cross-coupling

Article abstract of DOI:10.1039/c5sc03025k

A dual photoredox and gold-catalysed cross-coupling reaction of alkynyltrimethylsilanes and aryldiazonium tetrafluoroborates is described. The reaction proceeds through visible-light mediated oxidative addition of aryldiazoniums, transmetalation of alkynyltrimethylsilanes and aryl-alkynyl reductive elimination. Exclusive selectivity for silyl-substituted alkynes is observed, with no reactivity observed for terminal alkynes.

Full text of DOI:10.1039/c5sc03025k

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Visible light-mediated gold-catalysed carbon(sp )–
carbon(sp) cross-coupling†
Cite this: DOI: 10.1039/c5sc03025k
Suhong Kim, Jaime Rojas-Martin and F. Dean Toste*a
a
ab
Received 14th August 2015
Accepted 26th October 2015
A dual photoredox and gold-catalysed cross-coupling reaction of alkynyltrimethylsilanes and aryldiazonium
tetrafluoroborates is described. The reaction proceeds through visible-light mediated oxidative addition of
aryldiazoniums, transmetalation of alkynyltrimethylsilanes and aryl–alkynyl reductive elimination. Exclusive
selectivity for silyl-substituted alkynes is observed, with no reactivity observed for terminal alkynes.
DOI: 10.1039/c5sc03025k
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aryldiazoniums has emerged as a method for the generation of
Introduction
the requisite gold(III) intermediates via photoredox catalysis,
4
For over a decade, homogeneous gold catalysis has been thereby obviating the need for sacricial oxidants. These
investigated because it provides access to novel modes of gold(III) intermediates have been intercepted by a variety of
reactivity and enables rapid generation of complex molecular nucleophiles in dual catalytic photoredox–gold reactions
1
architectures. However, in contrast to other low-valent late (Scheme 1B).
transition metal catalysts, the majority of gold(I) complexes are
Although aryldiazoniums and photoredox catalysts provide
unreactive towards the oxidative addition of aryl and vinyl an efficient method to generate gold(III) intermediates, several
2
halides and pseudohalides. Consequently, most gold-catalysed challenges must be addressed in order to facilitate carbon–
cross-coupling reactions have required sacricial oxidants to carbon cross-coupling via these species. First, aryldiazonium
3
access the +3 oxidation state. For example, this reactivity plat- salts are highly electrophilic and reactive towards many classes
form has been exploited in a gold-catalysed oxidative coupling of nucleophilic coupling partners. Aryldiazoniums are generally
of organosilanes and 1,2-alkene functionalizations (Scheme 1A). decomposed under Kumada and Negishi coupling conditions
As an alternative, visible light-mediated oxidative addition of and do not tolerate ligand additives and stoichiometric bases
employed in the majority of Suzuki, Sonogashira and Hiyama
5
coupling reactions. Second, as visible light-mediated oxidative
addition of aryldiazoniums is proposed to proceed through
radical intermediates, nucleophilic coupling partners that can
participate in single electron transfer, such as organotin and
6
organotriuoroborates compounds, are problematic. Inspired
by the oxidative coupling of organosilanes, we envisioned that
the gold(III) complexes generated via photoredox catalysis might
undergo transmetalation with organosilanes, generating an
intermediate poised for carbon–carbon bond formation
7,8
through reductive elimination.
Results and discussions
While aryldiazonium tetrauoroborates have been shown to
react with halo-, azido-, allyl- and thiotrimethylsilanes, their
reactions with alkynyltrimethylsilanes has not been previously
I
III
Scheme 1 Photoredox catalyst and visible light-mediated Au /Au
catalysis.
9
reported. Additionally, previous reports of organosilane trans-
metallation with gold lead us to hypothesize that the trans-
metallation of alkynyltrimethylsilanes to gold(III) intermediates
might result in productive cross-coupling. On the basis of this
hypothesis, we examined the combined gold/photoredox
coupling of 1 equivalent of aryldiazonium salt 1a and 1 equiv-
alent of alkynyltrimethylsilane 2.
a
Department of Chemistry, University of California, Berkeley, CA 94720, USA. E-mail:
fdtoste@berkeley.edu
b
Departamento de Qu ´ı mica Org a´ nica (M ´o dulo 01), Universidad Aut ´o noma de Madrid,
C/Francisco Tom a´ sy Valiente 7, Cantoblanco, 28049 Madrid, Spain
†
Electronic supplementary information (ESI) available. See DOI:
0.1039/c5sc03025k
1
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Evaluation of reaction conditions showed that the combi- Table 2 Scope of aryldiazonium tetrafluoroborates
nation of Ar PAuCl and Ru(bpy) (PF ) , in acetonitrile gave the
3
3
6 2
highest yield of aryl alkyne 3a (Table 1). Changing either the
solvent or the photoredox catalyst proved detrimental to the
yield of the desired product. With respect to the ligands on the
gold catalyst, both electronic and steric factors impacted the
efficiency of the cross-coupling. For example, electron-decient
triarylphosphine ligands resulted in signicantly lower yield of
3a (Table 1, entry 10). The sterics of the ligand showed an even
more dramatic effect on reaction yield. The reaction conducted
with (p-tol) PAuCl provided 72% yield of the desired product,
3
while the much more hindered (o-tol) PAuCl-catalysed reaction
3
only provided 17% yield of 3a (Table 1, entry 11 and 12). The
yield of product was lower when tricyclohexylphosphinegold(I)
chloride was used as catalyst instead of triphenylphoshine-
gold(I) chloride (Table 1, entry 13). Gold(I) complexes of dia-
lkylbiarylphosphine were also examined, but all showed less
than 5% yield due to the combined effect of dialkyl groups and
the steric effect of biaryl groups. Finally, no coupling product
was observed in the absence of the ruthenium catalyst (entry 14)
or when the reaction was conducted in the dark (entry 15).
With an optimized catalyst system in hand, the scope with
respect to the aryldiazonium coupling partner was examined
Reaction conditions: 1a–l (0.24 mmol, 1.2 equiv.), 2 (0.2 mmol, 1.0
(Table 2). The yields of alkynylation reactions of electron-poor
3 3 6 2
equiv.), Ph PAuCl (10 mol%), Ru(bpy) (PF ) (2 mol%), acetonitrile
aryldiazonium salts were generally higher than those of reac- (2 mL), N
tions with electron-rich aryldiazonium coupling partners. It
should be noted that the intrinsic instability of ortho-
2
atmosphere, visible light, rt for 3 h. Isolated yields.
substituted aryldiazonium salts limited their use in this trans- were preserved during the coupling reaction. Bromo- and
formation (Table 2, entry 3k and 3l). It is also noteworthy that all iodoaryldiazonium salts were readily coupled and leaving
halogen substitutions on the aryldiazonium coupling partner halides intact for use in further reactions (Table 2, 3b and 3j);
this chemoselectivity is challenging under typical palladium-
10
catalysed Sonogashira coupling reactions.
Table 1 Optimization of reaction conditions
The difference in reactivity of electron-rich and -poor aryl-
diazoniums may be the result of competing reaction pathways.
Oxidative addition is believed to proceed through single elec-
tron reduction of aryldiazoniums and this process is preferred
4
with electron-poor aryldiazonium salts. On the other hand, the
generation of aryl cations, through loss of dinitrogen, is facile
with electron-rich aryldiazoniums. Correspondingly, we
observed trace amount of desired product when benzenedia-
a
Entry
Gold cat.
Photoredox cat.
Solvent
Yield
1
2
3
4
5
6
7
8
9
Ph
3
Ph
3
Ph
3
Ph
3
Ph
3
Ph
3
Ph
3
Ph
3
PAuCl
PAuCl
PAuCl
PAuCl
PAuCl
PAuCl
PAuCl
PAuCl
Ru(bpy)
Ru(bpy)
Ru(bpy)
Ru(bpy)
Ru(bpy)
Ru(bpy)
3
3
3
3
3
3
(PF
(PF
(PF
(PF
(PF
(PF
6
6
6
6
6
6
)
2
)
2
)
2
)
2
)
2
)
2
CH
Acetone
CH NO
3
CN
70
39
15
10
18
4
21
45
73
43
72
17
48
0
ꢀ
zonium tetrauoroborate was heated at 60 C for 9 hours in the
3
2
presence of 1-trimethylsilyl-2-(4-methoxy)phenylacetylene;
however the same reactivity was not observed with 4-uo-
rophenyldiazonium salts on the same conditions.
DMF
MeOH
EtOH
The scope of alkynyltrimethylsilanes was also investigated
(Table 3). Both aryl- and alkylethynyltrimethylsilanes were coupled
with modest to high product yields. o-Isopropylphenyl, biphenylyl
and naphthylalkynyltrimethylsilanes participated in the gold-cat-
alysed coupling (Table 3, 3m, 3n and 3o). Potentially sensitive
benzylic and propargylic C–H and C–X bonds were well tolerated
under the reaction conditions (Table 3, 3q, 3aa and 3s–v). Addi-
tionally, alkynyltrimethylsilane 3w was prepared in 78% yield
from the coupling of aryldiazonium salt 1d and bis(trimethylsilyl)
Ir(ppy)
Ir(ppy)
3
CH
CH
CH
CH
CH
CH
CH
CH
CH
3
3
3
3
3
3
3
3
3
CN
CN
CN
CN
CN
CN
CN
CN
CN
2
(dtbbpy)PF
6
(p-MeOPh)
(p-CF Ph) PAuCl
(p-tol)
(o-tol)
Cy
3
PAuCl
Ru(bpy)
Ru(bpy)
Ru(bpy)
Ru(bpy)
Ru(bpy)
—
3
3
3
3
3
(PF
(PF
(PF
(PF
(PF
6
6
6
6
6
)
2
)
2
)
2
)
2
)
2
1
1
1
1
1
1
0
1
2
3
4
5
3
3
3
PAuCl
PAuCl
3
3
PAuCl
Ph
Ph
3
PAuCl
PAuCl
b
3
Ru(bpy)
3
(PF
6
)
2
0
Reaction conditions: 4-uorobenzenediazonium tetrauoroborate 1a
(
0.2 mmol, 1 equiv.), 1-trimethylsilyl-2-phenylacetylene 2 (0.2 mmol, 1 acetylene, providing a compliment to using trimethylsilylacetylene
equiv.), gold catalyst (5 mol%), photoredox catalyst (1 mol%), solvent
a
b
in a traditional Sonogashira coupling (Table 3, 3w).
Another interesting feature of this reaction is the effect of the
silyl group on yield (Table 4). When trimethylsilylacetylene was
(
2 mL), N
2
atmosphere, visible light, rt for 6 h. GC yields. The
0
reaction was run in the dark. bpy ¼ 2,2 -bipyridine, ppy ¼ 2-phenylpyridine,
0
0
dtbbpy ¼ 4,4 -di-tert-butyl-2,2 -bipyridine.
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Table 3 Scope of alkynyltrimethylsilanes
Scheme 2 Reaction with allenyltrimethylsilanes.
reaction conditions, the silyl group plays a critical role in the
coupling. To investigate this role, a set of reactions was per-
formed by varying counteranions of aryldiazonium salts and
silyl group identities of alkynylsilanes. The yield of coupling
product was diminished as the steric hindrance of silyl group
was increased (Table 4, entry 1 and entries 4–7). While both
tetrauoroborate and tosylate diazonium salts proved efficient
coupling partners, the yield was diminished when hexa-
1
1

uorophosphate salts were used. Moreover, when the corre-
sponding terminal alkyne was used instead of
alkynyltrimethylsilanes, only 3% of the coupling product was
12
observed (Table 4, entry 8). Taken together, these results
suggests that transmetallation from the organosilane is critical
for high efficiency of the current coupling reaction.
Other organotrimethylsilanes were tested under the opti-
mized reaction conditions. While the reactions of aryl and
13,14
vinylsilanes were complicated by competing reactions,
the
Reaction conditions: 1d (0.24 mmol, 1.2 equiv.), 2m–aa (0.2 mmol, 1.0
gold/photoredox-catalysed coupling of allenyltrimethylsilane 4
3 3 6 2
equiv.), Ph PAuCl (10 mol%), Ru(bpy) (PF ) (2 mol%), acetonitrile
(
2 mL), N
2
atmosphere, visible light, rt for 3 h. Isolated yields. Ar ¼ p- provided propargylic compound 5 as the sole coupling product
a
nitrophenyl. b 5 equiv. of bis(trimethylsilyl)acetylene was used with 1
(
Scheme 2). The product from aryl–allenyl reductive elimination
equiv. of 1d. GC yields.
and the other aryl–propargylic coupling isomer were prepared
independently (Scheme 2, 6 and 7). We examined whether 6 was
an intermediate that underwent isomerization to 5 facilitated by
visible light and the photoredox catalyst. However, no isomer-
ization was observed of 6 to either 5 or 7 under the reaction
conditions. Therefore, the formation of 5 is best rationalized by
transmetalation of 4 to the gold(III) intermediate, followed by
coupled with 1d to generate terminal alkyne 3x, the yield was
15% with none of the corresponding silylacetylene 3w (Table 3).
This observation suggests that, under the current base free
Table 4 Effect of counteranion and silyl group
1,3-migration and aryl–propargyl reductive elimination.
Conclusions
In summary, we have demonstrated that trimethylsilylalkynes
and aryldiazonium tetrauoroborates can be coupled via dual
photoredox and gold catalysis strategy. The reaction proceeds
under mild conditions and shows excellent functional group
tolerance, including aryl halides that may be reactive under
traditional coupling conditions. This process compliments the
Sonogashira coupling, especially when aryl–alkynyl coupling is
required under non-basic conditions and may present an
advantage when TMS-alkynes are available rather than corre-
sponding terminal alkynes.
Counteranion
(X)
Silyl group
(Y)
a
Entry
Yield
4ꢁ
1
2
3
4
5
6
7
8
BF
TMS
TMS
TMS
TES
TBDMS
TIPS
TBDPS
H
70
68
24
61
10
10
1
ꢁ
TsO
ꢁ
PF
6
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
BF
4
BF
4
BF
4
BF
4
BF
4
3
Reaction conditions: aryldiazonium salt (0.2 mmol,
phenylethynylsilane (0.2 mmol, equiv.), Ph PAuCl (5 mol%),
Ru(bpy) (PF (a1 mol%), acetonitrile (2 mL), N atmosphere, visible
light, rt for 6 h. GC yields.
1 equiv.),
Acknowledgements
1
3
3
6
)
2
2
We are grateful for nancial support from the NIHGMS (RO1
GM073932). Jaime Rojas-Martin thanks MINECO for the EEBB-
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FPI fellowship. We thank Mark D. Levin, William J. Wolf and
Matthew S. Winston for helpful discussions.
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7
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W. J. Wolf, M. S. Winston and F. D. Toste, Nat. Chem., 2013,
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6
For
single-electron
transmetalation
of 14 In the case aryltrimethylsilanes, further optimization is
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