Ruthenium-catalyzed oxidative C-H alkenylation of aryl carbamates

Article abstract of DOI:10.1039/c2cc36196e

A cationic ruthenium(ii) catalyst enabled highly efficient oxidative alkenylations of electron-rich arenes bearing removable, weakly coordinating carbamates, and allowed for cross-dehydrogenative C-H bond functionalization in an aerobic manner. This journ

Full text of DOI:10.1039/c2cc36196e

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Ruthenium-Catalyzed Oxidative C–H Alkenylation of Aryl Carbamates
Jie Li, Christoph Kornhaaß and Lutz Ackermann*
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Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
First published on the web Xth XXXXXXXXX 200X
DOI: 10.1039/b000000x
5
A cationic ruthenium(II) catalyst enabled highly efficient
oxidative alkenylations of electron-rich arenes bearing
removable, weakly coordinating carbamates, and allowed for
cross-dehydrogenative C–H bond functionalization in an aerobic
Table 1 Optimization of oxidative alkenylationa
55
10 manner.
Palladium-catalyzed alkenylations of aryl (pseudo)halides
with alkenes, Mizoroki-Heck reactions, have matured to being
among the most reliable methods for the synthesis of
Entry
Catalyst
Solvent
Yield (%)
2
substituted styrenes.1, A more atom- and step-economical
15 strategy, however, relies on twofold functionalizations of
otherwise unreactive C–H bonds as latent functional groups.3
The vast majority of these cross-dehydrogenative
alkenylations was accomplished using palladium or rhodium
complexes, with notable recent progress being accomplished
1
2
---
DME
DMF
---
---
[RuCl2(p-cymene)2]
3
4
[RuCl2(p-cymene)2]
[RuCl2(p-cymene)2]
[RuCl2(p-cymene)2]
[RuCl2(p-cymene)2]
[RuCl2(p-cymene)2]
[RuCl2(p-cymene)2]
[Ru2Cl3(p-cymene)2][PF6]
PhMe
DCE
---
40
5
20 by among others Miura and Yu.4, On the contrary, less
5
t-AmOH
DME
48
expensive ruthenium complexes were only recently identified
as viable catalysts for environmentally benign twofold C–H
bond alkenylations. Thereby, carbonyl- and N-heteroaryl-
substituted, thus electron-deficient, arenes as well as anilides
25 were converted into the corresponding ortho-olefinated6
products.7 Contrarily, the use of air- and moisture stable
ruthenium complexes for challenging oxidative C–H bond
alkenylations with widely accessible phenol derivatives has
unfortunately thus far proven elusive. In the course of our
6
84
7
DME
86b
---c
---c
8
DME
9
DME
a
Reaction conditions: 1a (0.5 mmol), 2a (1.0 mmol), catalyst (2.5 mol
%), Cu(OAc)2·H2O (1.0 mmol), solvent (3.0 mL); isolated yields. b Under
60 air. c Without AgSbF6.
With an optimized catalytic system in hand, we tested the
influence of the N-substituents of phenyl carbamates 1 on the
reaction efficacy (Scheme 1). Thus, dialkyl-substituted
carbamates 1 furnished the desired products 3 in high yields,
65 with atom-economical N,N-dimethyl derivative 1b providing
the best results.
30 continuing
efforts
in
step-economical
C–H
bond
functionalizations,8 we devised reaction conditions for
ruthenium-catalyzed cross-dehydrogenative alkenylations of
aryl carbamates bearing removable directing groups, on which
we wish to report herein. Importantly, aryl carbamates are key
35 intermediates in organic synthesis, and serve as versatile
organic electrophiles in transition-metal-catalysis.9, 10
[RuCl2(p-cymene)]2
(2.5 mol %)
O
H
NR2
O
NR2
Preliminary studies with a naphthyl carbamate indicated that
the desired oxidative alkenylation was not viable with CsOAc
or KPF6 as the co-catalytic additive. However, satisfactory
40 results were gratifyingly achieved when employing 10 mol %
of AgSbF6. The desired olefination did not occur in the
absence of the ruthenium complex [RuCl2(p-cymene)2] (Table
1, entry 1). Among a set of representative solvents, DME
turned out to be optimal (entries 2–6), and the catalytic system
45 was found to be air-stable (entry 7). Notably, the cross-
dehydrogenative alkenylation failed to proceed in the absence
of AgSbF6 as the co-catalyst (entry 8), thus being suggestive
of the formation of a cationic ruthenium catalyst. Yet, the
preformed cationic complex [Ru2Cl3(p-cymene)2][PF6]7e
50 bearing the PF6-counteranion did not deliver the desired
product 3a under otherwise identical reaction conditions
(entry 9).
AgSbF6 (10 mol %)
H
+
CO2Et
O
Cu(OAc)2 H2O
DME, 110 °C, 24 h
O
2
3
1
CO2Et
O
NMe2
O
NEt2
O
N
O
O
O
CO2Et
3b: 68%
CO2Et
CO2Et
3d: 55%
3c: 67%
Scheme 1 Effect of N-substituents on oxidative C–H bond alkenylation.
70 Subsequently, we probed the scope of the optimized catalyst
in the twofold C–H bond functionalizations with moisture-
stable phenol derivatives
1 (Scheme 2). The cationic
ruthenium(II) catalyst proved broadly applicable and tolerated
This journal is © The Royal Society of Chemistry [year]
Chem. Commun., 2010, 46, 00–00 | 1

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Page 2 of 3
valuable functional groups, including aryl and alkyl fluorides,
Importantly, the double C–H bond functionalization was not
chlorides or bromides, the latter of which should prove 20 limited to the use of stoichiometric amounts of
valuable for a post-synthetic elaborations of products 3.
Additionally, both electron-deficient as well as electron-rich
arenes 1 were found to be suitable substrates, and delivered
Cu(OAc)2•H2O. Indeed, aerobic oxidative alkenylations
proved viable with Cu(OAc)2•H2O as the cocatalyst under an
atmosphere of ambient air (Scheme 4).
View Online
5
the corresponding styrenes
diastereoselectivities.
3
with excellent E-
25
Scheme 4 Aerobic oxidative C–H bond alkenylation.
Importantly, the carbamate directing group was easily
removed to deliver the desired phenol 4a (Scheme 5).
10 Scheme 2 Scope of oxidative C–H bond alkenylation.
Furthermore, we observed that intramolecular competition
experiments with meta-substituted substrates 1 proceeded with
high site-selectivities, furnishing products 3r–3ae as the sole
products (Scheme 3). The ruthenium(II) complex again
15 displayed a useful chemoselectivity, and allowed for the
effective conversion of various acrylic esters 2 as well.
30 Scheme 5 Removal of directing group.
Considering the remarkable activity and high selectivity of the
cationic ruthenium(II) catalyst, we became interested in
probing its mode of action. To this end, we conducted
intermolecular competition experiments with differently
35 substituted arenes 1, which revealed electron-rich substrates
to be preferentially converted (Scheme 6, and Scheme S-1 in
the Supporting Information).
Scheme 6 Intermolecular competition experiments.
40 Based on these mechanistic studies as well as our previous
findings with cationic ruthenium(II) catalysts7a,e we propose
the catalytic cycle to involve an initial base-assisted,
reversible cycloruthenation.11 Thereafter, coordinative
insertion of alkene 2 and β-hydride elimination deliver
45 product 3, while reductive elimination and reoxidation by
Cu(OAc)2•H2O regenerate the active cationic catalyst.
In conclusion, we have developed ruthenium-catalyzed
oxidative C–H bond alkenylations with electron-rich phenol
derivatives. Thus, a cationic ruthenium(II) complex set the
Scheme 3 Scope within intramolecular competition experiments.
2
| Chem. Commun., 2010, 46, 00–00
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stage for site-selective, broadly applicable olefinations of aryl
carbamates displaying removable directing groups, which also
55
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Acknowledgements
60
Financial support by the China Scholarship Council
(fellowship to J.L.), and the CaSuS Ph.D. program (fellowship
to C.K.) is gratefully acknowledged.
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Notes and references
10 Institut fuer Organische und Biomolekulare Chemie, Georg-August-
Universitaet, Tammannstrasse 2, 37077 Goettingen, Germany. Fax:+49
551 396777
E-mail: Lutz.Ackermann@chemie.uni-goettingen.de
# Electronic Supplementary Information (ESI) available: See
15 DOI: 10.1039/b000000x/
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This journal is © The Royal Society of Chemistry [year]
Chem. Commun., 2010, 46, 00–00 | 3