Electrochemical ruthenium-catalyzed alkyne annulations by C-H/Het-H activation of aryl carbamates or phenols in protic media

Article abstract of DOI:10.1039/C8CC07732K

Electrooxidative peri-C-H activation was accomplished by versatile ruthenium(ii) catalysis in terms of C-H/N-H and C-H/O-H functionalization. Thus, alkyne annulations proved viable with ample scope by organometallic C-H activation. The sustainable electrocatalysis exploited electricity, thereby avoiding the use of toxic transition metals as sacrificial oxidants. The robust ruthenium(ii)-electrocatalysis was operative in a protic alcohol/H₂O reaction medium with excellent levels of position-, regio- and chemo-selectivity.

Full text of DOI:10.1039/C8CC07732K

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Electrochemical ruthenium-catalyzed alkyne
annulations by C–H/Het–H activation of aryl
carbamates or phenols in protic media†
Cite this: Chem. Commun., 2018,
54, 12879
Received 26th September 2018,
Accepted 19th October 2018
Ruhuai Mei, Julian Koeller and Lutz Ackermann
*
DOI: 10.1039/c8cc07732k
rsc.li/chemcomm
Electrooxidative peri-C–H activation was accomplished by versatile
ruthenium(II) catalysis in terms of C–H/N–H and C–H/O–H func-
tionalization. Thus, alkyne annulations proved viable with ample
scope by organometallic C–H activation. The sustainable electro-
catalysis exploited electricity, thereby avoiding the use of toxic
transition metals as sacrificial oxidants. The robust ruthenium(II)-
electrocatalysis was operative in a protic alcohol/H2O reaction medium
with excellent levels of position-, regio- and chemo-selectivity.
Fig. 1 Electrochemical C–H/Het–H activation with alkynes.
Transition metal-catalyzed oxidative C–H activation1 has been
recognized as a powerful tool for the assembly of p-conjugated electricity as the terminal oxidant, and (d) mechanistic insights
heterocycles, with major potential for molecular syntheses and into electrochemical peri C–H activation by experiments. It is
material sciences.2 Despite of considerable progress, these furthermore noteworthy that our electrooxidative strategy also
oxidative C–H functionalizations heavily rely on stoichiometric set the stage for the first ruthenium-catalyzed C–H/N–H activation/
amounts of expensive and toxic metal salts as the sacrificial alkyne annulation of naphthylcarbamates.
oxidants.3 Electrosynthesis4 has emerged as an increasingly
At the outset of our studies, we tested various reaction conditions
viable platform for sustainable transformations, which enables for the envisioned electrooxidative annulation of alkyne 2a by easily-
the use of inexpensive electricity as the terminal oxidant.5 In this accessible ethyl naphthalen-1-ylcarbamate (1a) (Table 1 and Table S-1
context, major advances were achieved, exploiting transition- in the ESI†).18 Among a set of representative solvents, DMF and
metals based on inter alia palladium,6 cobalt,7 ruthenium,8 t-AmOH furnished promising results (entries 1 and 2), while a
rhodium,9 copper,10 or iridium.11
solvent mixture of t-AmOH and H2O,19 along with KOAc as the
Recently, we have introduced a versatile ruthenium12 catalyst additive, proved to be ideal (entries 3–6). The catalytic efficacy could
for oxidative C–H/O–H annulation of alkynes13 by 1-naphthols to be further improved when the electrolysis was conducted at a
access fused pyran derivatives.14 Despite considerable experi- constant current regime of 1.5 mA (entries 7–9). Control experiments
mentation, these transformations were restricted to the use of demonstrated the outstanding performance of the ruthenium(II)
anti-bacterial copper(II) oxidants. Within our program on sustain- carboxylates (entries 9–11), while typically used rhodium(III) catalysts
able C–H activation,15 we have now developed the first electro- fell short in delivering the desired product 3aa (entry 12).
chemical, organometallic peri C–H activation with synthetically
With the optimized ruthenium electrocatalysis being estab-
meaningful arylcarbamates,16 on which we report herein (Fig. 1). lished, we explored its versatility with a set of representative
Notable features of our finding include (a) the first electro- internal alkynes (Scheme 1). Thus, the broadly applicable
oxidative ruthenium-catalysed peri C–H activation, (b) C–H/N–H ruthenium(II) catalyst enabled the efficient conversion of diaryl-
annulation by electrooxidative ruthenium catalysis, (c) weakly and dialkyl-substituted alkynes 2a–2i. The robust ruthenium-
coordinating17 naphthol for C–H/O–H alkyne annulations with electrocatalysis displayed a remarkable tolerance of valuable
functional groups, such as ester, fluoro, chloro, or bromo
substituents, setting the stage for further late-stage diversifica-
tions. Unsymmetrical alkyne 2j delivered the desired product 3aj
¨
Institute for Organic and Biomolecular Chemistry, Georg-August-Universitat
¨
¨
Gottingen, Tammannstr. 2, 37077 Gottingen, Germany.
with high levels of regio-control, placing the aromatic moiety in
E-mail: Lutz.Ackermann@chemie.uni-goettingen.de
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c8cc07732k proximity to the nitrogen heteroatom.
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Table 1 Establishing the electrochemical C–H/N–H activationa
Entry
[TM]
Solvent
Yield [%]
1
2
3
4
5
6
7
8
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
—
DMF
t-AmOH
35
51
61
t-AmOH/H2O (3/1)
DMF/H2O (3/1)
t-AmOH/H2O (3/1)
t-AmOH/H2O (3/1)
t-AmOH/H2O (3/1)
t-AmOH/H2O (3/1)
t-AmOH/H2O (3/1)
t-AmOH/H2O (3/1)
t-AmOH/H2O (3/1)
t-AmOH
28
57b
65c
36c,d
77c,e
82c, f
31c,g
o5c, f
o5
9
10
11
12
[Cp*RhCl2]2
Scheme 2 Electrochemical C–H/N–H activation with amides 2.
a
General reaction conditions: 1a (0.60 mmol), 2a (0.30 mmol), [TM]
(10 mol %), KOAc (0.60 mmol), n-Bu4NPF6 (0.18 mmol), solvent (4.0 mL),
100 1C, 16 h, under N2, constant current electrolysis (CCE) at 4.0 mA,
b
the extended aromatic substrate fluoranthen-3-ylcarbamate 1f was
(0.60 mmol) instead of KOAc. n-Bu4NClO4 (0.18 mmol) instead of smoothly converted to give the p-conjugated polyheterocycles 3fa,
undivided cell, RVC anode, Pt-plate cathode. Isolated yields. NaOPiv
c
d
e
f
g
n-Bu4NPF6. 10 mA, 2.5 h. 2.0 mA, 16 h. 1.5 mA, 24 h. Without
current, 24 h.
featuring unique fluorescence emission.
The ruthenium(II) electrocatalysis was not limited to C–H/N–H
activation with arylcarbamates 1. Indeed, highly effective annu-
lations of alkynes 2 proved to be viable with the weakly coordi-
nating17 naphthol derivatives 4 (Scheme 3, and Table S-2 in the
ESI†).18 Thus, a series of fluorescent pyrans were accessed in a
step-economical fashion via the chemo-selective C–H/O–H func-
tionalization, featuring electricity as the sacrificial oxidant.
Given the unique site- and regio-selectivity of the electro-
chemical ruthenium(II) catalysis, we became interested in its
modus operandi. To this end, a catalytic C–H transformation
in the presence of D2O employing an excess of substrate 1a
resulted in a significant H/D exchange in the peri-position of
the recovered starting material [D1]-1a (Scheme 4a). This obser-
vation provided strong evidence for a reversible, organometallic
C–H ruthenation step. In good agreement with this finding,
a kinetic isotope effect (KIE) was not observed, when comparing
Scheme 1 Electrochemical C–H/N–H annulation of alkynes 2.
Subsequently, a variety of arylcarbamates 1 were probed,
highlighting an outstanding selectivity for the peri C–H activa-
tion to deliver benzoquinoline derivatives 3 (Scheme 2). Ethyl
naphthalen-1-ylcarbamates 1 bearing either electron-withdrawing
or electron-donating groups on the naphthyl ring provided the
corresponding benzoquinolines 3 with high efficacy. It is worth
noting that the ruthenium(II) electrocatalysis was likewise applic-
able to heterocyclic substrate ethyl quinolin-5-ylcarbamate 1d,
selectively furnishing the annulated product 3da. Likewise, Scheme 3 Electrochemical C–H/O–H activation with naphtholes 4.
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Based on our mechanistic studies, we propose a plausible
catalytic cycle to commence by a facile organometallic C–H
activation (Scheme 5). Thereby, ruthena(II)cycle 7 is generated,
along with two equivalents of carboxylic acid. Thereafter, migratory
alkyne insertion furnishes the seven-membered ruthena(II)cycle 9,
which rapidly undergoes reductive elimination to deliver the
ruthenium(0) sandwich complex 10. The key reoxidation of the
thus-formed ruthenium(0) complex 10 is finally accomplished by
anodic oxidation, while cathodic reduction generates molecular
hydrogen as the sole stoichiometric byproduct.
In summary, we have reported on the first electrocatalytic
organometallic C–H activation with aromatic carbamates and
phenols. Hence, a versatile ruthenium(II) carboxylate catalyst
enabled electrooxidative C–H/N–H and C–H/O–H activation/alkyne
annulations with ample scope. The C–H activation employed
electricity as the sacrificial oxidant, which avoids the use of toxic
metals as terminal oxidants, generating molecular hydrogen as the
only byproduct. Mechanistic studies provided strong support
for an organometallic C–H ruthenation, along with an efficient
electro-reoxidation of the key ruthenium(0) intermediate by
environmentally-benign electricity that is amenable for renewable
forms of energy. The electrochemical C–H/Het–H activation was
operative in protic aqueous reaction media.
Generous support by the DFG (Gottfried-Wilhelm-Leibniz Award)
and CSC (fellowship to R. M.) is most gratefully acknowledged.
Conflicts of interest
Scheme 4 Summary of key mechanistic findings.
There are no conflicts to declare.
the initial rates of transformations with substrates 1a and [D7]-1a References
(Scheme 4b). Furthermore, we performed intermolecular compe-
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