Cobalt(III)-Catalyzed Directed C-H Allylation

Article abstract of DOI:10.1021/acs.orglett.5b01701

The cobalt(III)-catalyzed allylation was developed for amide-directed C-H activation of arenes, heteroarenes, and olefins. A variety of allyl sources can be employed to introduce this useful functional group.

Full text of DOI:10.1021/acs.orglett.5b01701

Letter
pubs.acs.org/OrgLett
Cobalt(III)-Catalyzed Directed C−H Allylation
†
†
‡
́ ́
Tobias Gensch, Suhelen Vasquez-Cespedes, Da-Gang Yu, and Frank Glorius*
̈ ̈
̈ ̈
Organisch-Chemisches Institut, Westfalische Wilhelms-Universitat Munster, Corrensstraße 40, 48149 Munster, Germany
*
S Supporting Information
ABSTRACT: The cobalt(III)-catalyzed allylation was developed for
amide-directed C−H activation of arenes, heteroarenes, and olefins. A
variety of allyl sources can be employed to introduce this useful functional
group.
he direct transformation of C−H bonds into useful
functional groups offers great value added per step
Scheme 1. Cobalt(III)-Catalyzed C−H Allylation
T
compared to conventional functional group interconversions.
In this context, many effective methods have been developed,
mainly using second- and third-row transition-metal catalyst
1
systems, most notably palladium, rhodium, and ruthenium. In
contrast, the ability of the first-row transition metals to undergo
C−H activation catalysis is just beginning to be explored. Their
abundance, low price, and potentially novel reactivity motivate
the research in catalysis using first-row transition-metal
2
compounds. Pioneered by the group of Matsunaga and Kanai,
Cp*Co(III) complexes have been introduced as catalysts for
directed C−H activation very recently and used to complement
3
Cp*Rh(III) catalysis.
We first pursued the introduction of substituted allyl moieties
using a variety of allyl carbonates with pyrimidylindole 1
The allyl moiety is an exceptionally versatile functional group,
offering a wealth of opportunities for further functionalizations.
In this context, allylarenes and 1,4-dienes (skipped dienes),
which can be seen as allylated olefins, are interesting due to their
(
Scheme 2). We found that substituents at the α-position of the
allyl carbonate are generally tolerated, giving linear 2-allylindoles
as mixtures of the E/Z isomers. Thus, excellent yields were
obtained when alkyl-substituted allyl carbonates were used under
equally mild conditions (3a−c). The more complex hexadienyl
carbonate 2d gave moderate yields with an increased catalyst
loading and temperature. Cyclohexenyl carbonate 2e and crotyl
carbonate 2f proved the applicability to terminally substituted
allyl substrates, yielding the cyclohexenyl-substituted product 3e
and the branched product 3f, respectively. Notably, no linear
product 3b was obtained from the reaction of 2f. We also
demonstrated the utility of a residue other than methyl on the
4
,5
synthetic value and can be found in a number of biologically
6
active molecules. Allyl arenes and skipped dienes are tradition-
ally prepared by rearrangements, electrophilic or nucleophilic
substitutions, or cross-coupling reactions. These methods can
suffer from competing formation of the conjugated double-bond
isomers, harsh reaction conditions, and limited reaction scope
and/or require syntheses of special, prefunctionalized sub-
7
strates. More recently, methods have been described for the
direct allylation of aromatic C−H bonds using transition-metal
8
catalysts. We previously reported the use of a Cp*Co(III)
t
carbonate, using tert-butyl hept-1-en-3-yl carbonate (2c- Bu).
catalyst for the direct functionalization of C−H bonds, including
While the product yield was not affected by the change of the
carbonate, the E/Z ratio was enhanced when using the tert-butyl
rather than the methyl carbonate. Presumably, the conformation
of the carbonate at the step of olefin insertion to the cobaltacycle
intermediate determines the relative configuration of cobalt and
carbonate in the following intermediate and thus the geometry of
the resulting olefin. We showed the excellent scalability of this
transformation in a gram scale reaction of 1 with 2a. Employing
the allylation of N-pyrimidylindoles with allyl carbonates as
3
g,r,s
reaction partners (Scheme 1).
These allylation reactions
proceeded with remarkable efficiency at room temperature, using
only 0.5 mol % of the catalyst. With an even lower catalyst
loading, we observed a turnover number (TON) of 2200. So far,
both the high turnover number and the mild reaction conditions
are unique for this catalyst. Intrigued by the exceptional reactivity
of Cp*Co(III) in the allylation of pyrimidyl indoles, we aimed to
achieve the allylation of more challenging (hetero)arenes and
olefins, exploring other directing groups (DG), as well as other
allyl reaction partners. Herein, we report the direct C−H
allylation of (hetero)arylamides and acrylamides using Cp*Co-
0
.25 mol % of the convenient precatalyst [Cp*CoI ] , we
2 2
obtained 98% (1.15 g) of 3a.
Received: June 10, 2015
(
III) catalysis (Scheme 1).
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b01701
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
a
Scheme 2. Scope of Allyl Carbonates
Scheme 3. Scope of Aryl- and Alkenylamides
a
1
Isolated yields are given. E/Z ratios were determined by H NMR.
For more detailed reaction conditions, see the Supporting
b
Information. 5 mmol scale, 0.25 mol % of [Cp*CoI ] was used.
2
2
c
t
d
tert-butyl hept-1-en-3-yl carbonate (2c- Bu) was used. 5 mol % of
[
h.
Cp*Co(CO)I ], 40 mol % of AgSbF , 20 mol % of HOPiv, 80 °C, 16
2
6
a
Isolated yields are given. For more detailed reaction conditions, see
b
c
Other heterocycles and benzamides can also be allylated using
the Supporting Information. 32 h. 110 °C.
Cp*Co(III) catalysis, albeit not with the exceptional efficiency of
the pyrimidylindoles. Increasing the catalyst loading to 5 mol %
and the amount of additives to 40 mol %, as well as changing the
solvent to 2,2,2-trifluoroethanol (TFE), gave the allylated
benzamide 5a in satisfactory yield. We found that [Cp*CoI2]2
We were interested in using other directing groups for the
selective 2-allylation of indole. While N-acetyl, N-diethylcarba-
moyl, and N-Boc indole failed to yield any desired reaction
product, we finally found the first example of an acyl-directed C−
H activation with the Cp*Co(III) catalyst when N-benzoylindole
(
2.5 mol %), AgBF , and HOAc are superior and convenient
4
replacements for [Cp*Co(CO)I ], AgSbF , and HOPiv,
2
6
(
6) was used, giving exclusively allylation at the 2-position of
respectively. Under these conditions, benzamides are allylated
in moderate to good yields, giving exclusively the γ-substituted
allyl compounds (Scheme 3). Secondary alkyl- or benzylamides
can be used as directing groups with similar utility (5a−d).
Electron-donating (5e,f) and -withdrawing substituents (5g) are
tolerated just as well as halides (5h,i). The effect of the position
of a substituent was explored using p-, m-, and o-methylbenza-
mides 4e, 4j, and 4k. We found that meta-substitution has only a
slight detrimental effect on the transformation, leading to
functionalization in the less hindered position para to the methyl
group (5j). Even a substituent ortho to the directing group led to
a reasonable conversion with only an increase of the reaction
time (5k).
Considering the importance of skipped dienes and the scarcity
of olefinic C−H activation using Cp*Co(III) catalysts, we next
explored the direct C−H allylation of acrylamides (Scheme 3).
When the reaction was carried out at elevated temperatures, the
allylation was found to proceed with acceptable yields for 2-
substituted secondary and tertiary acrylamides. Notably, besides
alkyl and phenyl substituents (5l,m,o), bromo (5n) and methoxy
indole. Functionalization of the phenyl was not observed (eq 1).
Under the acidic conditions employed in the allylation
2+
reactions, the hypothetical [Cp*Co] fragment should display
a high Lewis acidity. Thus, we performed a number of control
experiments to ascertain that a C−H metalation mechanism was
operational, as opposed to a Lewis acid catalyzed electrophilic
substitution (Table 1). When using other cobalt compounds
such as Co(II) salts or Co(acac) , or even another strong Lewis
3
acid such as Sc(OTf) , no reactivity was observed at all. The
3
presence of a silver salt for the abstraction of iodide from the
precatalyst was crucial, yet the Cp*Co complex introduced by
3h
the group of Ellman (see Table 1, entry 4) featuring very
weakly coordinating perfluorophenyl borate counterions proved
to be unsuitable for this reaction.
(5p) groups were tolerated in the reaction as well.
Finally, we could demonstrate the applicability of the C−H
Further experiments were conducted to gain insight into the
reaction mechanism (Scheme 4). The kinetic isotope effect was
determined in parallel and competition experiments. While we
observed a large KIE of 6.4 in the latter experiment, the parallel
reactions resulted in a lower k /k of 2.0. The observed isotope
effect is more pronounced than in previously reported
mechanistic data for Cp*Co(III)-catalyzed C−H activation
allylation to other heteroarenes with amides as directing groups.
Tertiary amides of furan and thiophene were allylated in
satisfactory yields (5q,r) exclusively ortho to the directing
group. As expected, in the case of the 3-amidofuran 4q,
functionalization occurred in the more reactive 2- instead of
the 4-position.
H
D
B
DOI: 10.1021/acs.orglett.5b01701
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Table 1. Control Reactions
Scheme 5. Proposed Mechanism
a
entry
[M] =
% yield
b
1
2
3
4
5
6
7
8
9
[Cp*CoI2]2 (standard conditions)
77
20
0
b
[Cp*CoI2]2, allylic alcohol instead of 2a
b,c
[Cp*CoI2]2
Cp*Co(C H )[B(C F ) ]
6 5 4 2
c
0
6
6
none
0
Co(acac)3
0
Co(OAc) ·H O
0
2
2
CoCl2
0
Sc(OTf)3
0
a
b
c
Determined by GC-FID. 2.5 mol % of [Cp*CoI ] . No AgBF .
2
2
4
Scheme 4. Mechanistic Experiments
functional group by means of directed C−H activation. Besides
methyl carbonates, tert-butyl carbonates and even allylic alcohol
can serve as allyl sources. This transformation can also be applied
to substrates other than the privileged N-pyrimidylindoles, as the
amide directing group proved to be versatile for the allylation of
arenes and heteroarenes with low catalyst loadings. Notably, the
use of acrylamides allows for the synthesis of skipped dienes. We
showed the first example of an acyl directed C−H functionaliza-
tion using the Cp*Co(III).
ASSOCIATED CONTENT
Supporting Information
■
*
S
Experimental details, characterization data, and copies of NMR
spectra of new compounds. The Supporting Information is
available free of charge on the ACS Publications website at DOI:
1
0.1021/acs.orglett.5b01701.
AUTHOR INFORMATION
Corresponding Author
3
f,i,j,n,p
■
*
with phenylpyridine and -pyrazole.
The values indicate that
C−H activation likely occurs in the rate-limiting step of our
transformation. H/D scrambling was observed when deuterated
substrate 4a-D5 was subjected to the standard reaction
conditions in the absence of allyl carbonate, indicating the
reversibility of the C−H activation process. While single
regioisomers were obtained in the reactions using substituted
allyl carbonates, a 91:9 mixture of α:γ deuterium substitution was
observed in a reaction with γ-deuterated allyl carbonate 2a-D2.
Considering the complete regioselectivity in the substituted
products 3b−f, the ability of allylic alcohol to serve as allyl
E-mail: glorius@uni-muenster.de.
Present Address
‡
College of Chemistry, Sichuan University, 29#, Wangjiang Rd,
Chengdu 610064, China.
Author Contributions
†
T.G. and S.V.-C. contributed equally.
Notes
The authors declare no competing financial interest.
9
transfer reagent (see Table 1, entry 2), and a recent related
mechanistic analysis of cobalt catalyzed allylation, we propose
the mechanism shown in Scheme 5.
3s
ACKNOWLEDGMENTS
We thank Kathryne Chepiga, Mario Wiesenfeldt, and Roman
■
Formation of a catalytically active cobalt species I from the
precursors is followed by C−H activation to cobaltacycle II.
Olefin insertion leads to intermediate III that is stabilized by
intramolecular coordination. In this geometry, β-hydride
elimination is disfavored, and β-oxygen elimination leads to the
allylated product. Yet, considering the observed deuterium
distribution, we cannot rule out other pathways, possibly
involving the formation of π-allyl species from the allyl
precursors.
Honeker (WWU Mu
financial support by the European Research Council under the
European Community’s Seventh Framework Program (FP7
̈
nster) for helpful discussions. Generous
2
(
007-2013)/ERC Grant Agreement No. 25936 and the SFB 858
S.V.C.) is acknowledged.
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allyl carbonates can be employed to introduce this useful
C
DOI: 10.1021/acs.orglett.5b01701
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Organic Letters
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DOI: 10.1021/acs.orglett.5b01701
Org. Lett. XXXX, XXX, XXX−XXX