Cobalt-catalyzed, aminoquinoline-directed C(sp2)-H bond alkenylation by alkynes

Article abstract of DOI:10.1002/anie.201404579

A method for cobalt-catalyzed, aminoquinoline- and picolinamide-directed C(sp²)-H bond alkenylation by alkynes was developed. The method shows excellent functional-group tolerance and both internal and terminal alkynes are competent substrates for the coupling. The reaction employs a Co(OAc)₂·4 H₂O catalyst, Mn(OAc)₂ co-catalyst, and oxygen (from air) as a terminal oxidant.

Full text of DOI:10.1002/anie.201404579

Angewandte
Chemie
DOI: 10.1002/anie.201404579
À
C H Activation
2
À
Cobalt-Catalyzed, Aminoquinoline-Directed C(sp ) H Bond
Alkenylation by Alkynes**
Liene Grigorjeva and Olafs Daugulis*
Abstract: A method for cobalt-catalyzed, aminoquinoline-
We report herein a method for cobalt-catalyzed, aminoquino-
2
2
À
À
and picolinamide-directed C(sp ) H bond alkenylation by
line- and picolinamide-directed C(sp ) H bond coupling with
alkynes. The reaction is successful with terminal and internal
alkynes, tolerates a wide range of functional groups on the
alkyne and arene, and allows removal of the directing groups.
Furthermore, the first use of cobalt catalysis by employing
bidentate, monoanionic auxiliaries is demonstrated.
alkynes was developed. The method shows excellent func-
tional-group tolerance and both internal and terminal alkynes
are competent substrates for the coupling. The reaction
employs a Co(OAc)2·4H2O catalyst, Mn(OAc)2 co-catalyst,
and oxygen (from air) as a terminal oxidant.
In 2005, we introduced 2-aminoquinoline, picolinamide,
and 2-pyridinylmethylamine auxiliaries for palladium-cata-
À
D
uring the last decade transition-metal-catalyzed C H
2
3
[6a,b]
À
À
bond functionalization methodology has emerged as an
important chemistry tool which allows simplification and
shortening of synthetic schemes.[1] Within the last years,
lyzed C(sp ) H and C(sp ) H bond functionalization.
2
À
Subsequently, copper-catalyzed C(sp ) H bond sulfenylation,
amination, fluorination, and etherification was described.[6c–f]
Other groups have extensively used aminoquinoline, picolin-
amide, and other bidentate monoanionic directing groups for
À
applications of C H bond functionalization to the synthesis of
natural products and compounds of medicinal interest have
emerged, thus showing the maturity of the methodology.[2]
However, certain problems are still unsolved. For example,
a general functional-group-tolerant method for directed
coupling of non-acidic C(sp ) H bonds with alkynes has yet
palladium-, ruthenium-, iron-, nickel-, and copper-catalyzed
[7]
À
C H bond functionalization. The near-universal efficiency
À
of these directing groups for transition-metal-catalyzed C H
2
À
bond functionalization presumably arises from the substrate
acting as a tridentate, dianionic pincer which stabilizes high-
valent transition-metal intermediates (Figure 1).[6b,8]
2
À
to be described. Furthermore, most examples of C(sp ) H
bond coupling with alkynes feature second-row transition-
metal catalysis.[3a–n] Directed alkenylation by employing
alkenes is possible.[3o,p]
We speculated that 8-aminoquinoline and picolinic acid
auxiliaries would promote cobalt-catalyzed
2
À
Following the pioneering work of Murai and co-work-
ortho-alkenylation of C(sp ) H bonds since
2
ers,[3a] a number of groups have reported directed or non-
cobalt(III) is known to activate C(sp ) H
À
2
bonds[9] and carbon–carbon multiple-bond
À
directed reactions of C(sp ) H bonds with alkynes catalyzed
by second- or third-row transition metals.[3] The use of the
more available first-row transition metals has been rare.[4]
insertion into CoIII C bonds has been
À
demonstrated.[10]
Only a few examples describe nickel- or cobalt-catalyzed
We decided to use the readily available
cobalt(II) acetate catalyst in combination
2
À
alkyne/C(sp ) H bond coupling. Notably, following earlier
Figure 1. Amino-
quinoline direct-
ing group.
reports that low-valent cobalt species can activate and
with pivalate as a base. The reaction opti-
mization was carried out with respect to
solvent, reaction temperature, and cooxi-
dant (Table 1). The results in entries 1–3
show that the reaction is most efficient in
2
[5]
À
functionalize C(sp ) H bonds, Yoshikai and co-workers
has developed a versatile system for cobalt-catalyzed, imine-
2
À
and pyridine-directed alkenylation of C(sp ) H bonds with
internal alkynes.[4f–h,l] Nakao, Hiyama, and co-workers have
2
À
shown that [Ni(cod)2] catalyzes the coupling of C(sp ) H
trifluoroethanol as the solvent, presumably because of higher
solubility of the cobalt catalyst. The reaction is efficient at
temperatures as low as 608C (entry 4). Potassium persulfate
cannot be used as an oxidant (entry 6), but silver pivalate
(entries 1–5) and Mn(OAc)2 (entries 8–10, 12) work well.
Mn(OAc)2 was chosen as a cooxidant because of cost
considerations. At least 1 equivalent of Mn(OAc)2 is required
(entry 9 versus 12). Interestingly, reaction in a degassed
solvent affords only traces of the product, thus showing that
the presence of oxygen is essential (entries 9 versus 10). Low
conversion can be achieved without the Mn(OAc)2 co-catalyst
under an atmosphere of oxygen (entry 11). Cobalt(II) acetate
tetrahydrate can be used instead of the anhydrous salt without
a decrease in the reaction yield. No reaction was observed if
Co(OAc)2 was omitted.
bonds with disubstituted acetylenes,[4d] and Chatani and co-
workers has described the nickel-catalyzed reaction of
benzoic acid 2-pyridinylmethylamides with internal alk-
ynes.[4e] However, directed coupling of both internal and
2
[4m]
À
terminal alkynes with C(sp ) H bonds is exceedingly rare.
[*] Dr. L. Grigorjeva, Prof. O. Daugulis
Department of Chemistry, University of Houston
Houston, TX 77204-5003 (USA)
E-mail: olafs@uh.edu
[**] We thank the Welch Foundation (Grant No. E-1571), NIGMS (Grant
No. R01GM077635), and the Camille and Henry Dreyfus Founda-
tion for supporting this research.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201404579.
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Table 1: Optimization of reaction conditions.[a]
Table 2: Reaction scope with respect to arylamides.[a]
Entry
1
Ar
Product
Yield [%]
78
C6H5
Entry
T [8C]
t [h]
Solvent
Cooxidant
2/1
1[b,c]
2[b,c]
3[b,c]
4
150
150
150
60
25
60
60
60
80
80
12
12
12
12
12
12
2
16
2
12
18
2
DMF
o-Cl2C6H4
AgOPiv
AgOPiv
AgOPiv
AgOPiv
AgOPiv
K2S2O8
PhI(OAc)2
Mn(OAc)2
Mn(OAc)2
Mn(OAc)2
O2
<1:99
1:2 (33%)[h]
CF3CH2OH
CF3CH2OH
CF3CH2OH
CF3CH2OH
CF3CH2OH
CF3CH2OH
CF3CH2OH
CF3CH2OH
CF3CH2OH
CF3CH2OH
>99:1 (63%)[h]
>99:1 (65%)[h]
1:4 (16%)[h]
<1:99
5[b]
6
2
4-CF3C6H4
4-BrC6H4
4-NO2C6H4
2-MeC6H4
3-IC6H4
70
73
78
86
84
74
81
86
7[d]
8
1:1 (11%)[h]
5:1 (79%)[h]
1:2 (63%)[h]
<1:99
9[e]
10[e,f]
11[g]
12[d]
80
80
1:1 (50%)[h]
10:1 (87%)[h]
3
Mn(OAc)2
[a] Amide 0.1 mmol, solvent 0.7 mL. Conversions were determined by
1H NMR analysis. [b] Co(OAc)2 catalyst. [c] Cooxidant: 0.8 equiv.
[d] Cooxidant: 1 equiv [e] Cooxidant: 0.5 equiv. [f] Deoxygenated solvent.
[g] Reaction vessel pressurized with O2. [h] Yield of 2 determined by
NMR spectroscopy using 1,1,2-trichloroethane as an internal standard in
parentheses. DMF=N,N-dimethylformamide, Piv=pivalate.
4
The reaction scope with respect to aminoquinoline amides
is presented in Table 2. The reactions are successful for both
electron-rich (entries 5 and 7) and electron-poor (entries 2–4,
and 6) amides. Various functionalities, such as bromide
(entry 3), nitro (entry 4), and iodide (entry 6) are tolerated.
Furanecarboxylic and thiophenecarboxylic acids are reactive
(entries 8 and 9), thus showing the compatibility of reaction
conditions with heterocycles. The reaction headspace volume
is important as 1 equivalent of O2 is consumed in the reaction.
The reaction scope with respect to alkynes is presented in
Table 3. The reaction is remarkably functional-group tolerant,
wherein a free alcohol moiety (entry 1), ester (entry 6), silyl
(entry 7), cyclopropyl (entry 8), and protected amine
(entry 9) are compatible with the reaction conditions. Termi-
nal alkynes with either aromatic (entry 3) or large substitu-
ents (entries 4 and 7) afford products as single regioisomers.
Terminal alkynes with smaller substituents (entries 6, 8, and
9) as well as unsymmetric internal alkynes (entry 5) form
regioisomeric mixtures. However, selectivities are reasonably
good, ranging from about 6:1 for ethyl propiolate (entry 6) to
14:1 for phenylmethylacetylene (entry 5).
5
6
7[b]
8[c]
9[d]
2-MeOC6H4
2-furyl
Furthermore, aminoquinoline vinylamides are reactive
(Scheme 1). Thus, cinnamic acid aminoquinoline amide was
treated with 2-butyne and the cyclization product was isolated
in 75% yield.
2-thienyl
The picolinamide directing group can be used (Scheme 2),
thus allowing functionalization of benzyl- and naphthylamine
derivatives. The picolinamide of 1-naphthylamine (5) was
reacted with 2-butyne in the presence of catalytic Co-
(OAc)2·4H2O to afford the noncyclized alkenylation product
[a] Amide 0.5 mmol, CF3CH2OH 5 mL, air. Yields are those of the isolated
products. Please see the Supporting Information for details. [b] Time:
18 h. [c] Time: 16 h. [d] Time: 20 h.
2
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Table 3: Reaction scope with respect to alkynes.[a]
Entry
R1
R2
Yield [%]
1
2
3
4
CH2OH
Me
H
H
Me
H
H
H
H
CH2OH
Me
Ph
tBu
Ph
CO2Et
TIPS
cyclopropyl
CH2NPhth
95
96
95
73
95
82
64
84
93
5[b]
6[c]
7
Scheme 3. Directing-group removal. CAN=ceric ammonium nitrate.
8[d]
9[e]
base hydrolysis of 8 removes picolinamide to give the
trimethylisoquinoline 9. The aminoquinoline directing group
can be removed by treatment with CAN at room temperature,
and cleavage of the directing group is accompanied by
oxidation of the double bond, thus affording the ketolactone
10 in moderate yield.
[a] Amide 0.5 mmol, CF3CH2OH 5 mL, alkyne 1.2 equiv, air. Yields are
those of isolated products. Please see the Supporting Information for
details. [b] Isolated as a 14:1 mixture of isomers. [c] Minor isomer (13%)
also isolated. [d] Isolated as a 13:1 mixture of isomers. [e] Isolated as
a 7:1 mixture of isomers; reaction time: 18 h. TIPS=triisopropylsilyl.
Based on the fact that the aminoquinoline ligand stabilizes
transition metals in high oxidation states, it is likely that the
reaction proceeds via the cobalt(III) intermediate 11, which is
formed by oxidation of Co(OAc)2 in the presence of amino-
quinoline amide ligand (Scheme 4). Insertion of the alkyne
Scheme 1. Cyclization with vinyl amide.
Scheme 4. Mechanistic considerations.
Scheme 2. Picolinamide directing group.
into the cobalt–aryl bond would provide 12. An alternative
mechanism with the cobalt acetylide intermediate is unlikely
since 1) internal alkynes are reactive, and 2) terminal alkynes
form an isomeric mixture of products. The compound 12
could directly reductively eliminate to give 13, or cobalt(III)
could be protonated to give 14 which could oxidatively cyclize
to give 13. Formation of 14 is plausible since the picolinamide
of 1-naphthylamine reacts to form the noncyclic 6 (Scheme 2).
To distinguish between those pathways, 14 was heated with
Co(OAc)2 and Mn(OAc)2 at 608C. A complex reaction
6 in moderate yield. Similarly, the 1-methylbenzylamine-
derived picolinamide 7 reacted with 2-butyne to give the
cyclized product 8 in 44% yield. As shown before,[6]
picolinamide-directed reactions are less efficient, thus afford-
ing lower yields of products, and requiring higher temper-
atures and longer reaction times.
The advantage of aminoquinoline and picolinamide
directing groups lies in the possibility of their removal,
which affords useful functionalized products (Scheme 3). The
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(OAc)2·4H2O catalyst, Mn(OAc)2 co-catalyst, and oxygen
(from air) as a terminal oxidant. Future directions of the work
involve mechanistic studies of the transformation and
attempts to isolate reaction intermediates.
Received: April 22, 2014
Published online: && &&, &&&&
À
Keywords: alkenes · alkynes · C H activation · cobalt ·
cyclization
.
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4
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À
C H Activation
L. Grigorjeva,
O. Daugulis*
&&&& — &&&&
Cobalt-Catalyzed, Aminoquinoline-
2
À
Directed C(sp ) H Bond Alkenylation by
Alkynes
In the air: Excellent functional-group
tolerance is observed in the title reaction,
and both internal and terminal alkynes
are competent substrates for the cou-
pling. The reaction employs Co-
(OAc)2·4H2O as the catalyst, Mn(OAc)2
as the co-catalyst, and oxygen (from air)
as the terminal oxidant. Piv=pivalate.
Angew. Chem. Int. Ed. 2014, 53, 1 – 5
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