Antimony/N-hydroxyphthalimide as a catalyst system for cross- dehydrogenative coupling reactions under aerobic conditions

Article abstract of DOI:10.1002/adsc.201200999

In the course of our investigations to find a novel catalyst for the cross-dehydrogenative coupling (CDC) reaction, it was discovered that antimony(V) serves as a co-catalyst with N-hydroxyphthalimide (NHPI) under aerobic conditions. This is a rare exampl

Full text of DOI:10.1002/adsc.201200999

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DOI: 10.1002/adsc.201200999
Antimony/N-Hydroxyphthalimide as a Catalyst System for Cross-
Dehydrogenative Coupling Reactions under Aerobic Conditions
Arata Tanoue,a Woo-Jin Yoo,a and Shu¯ Kobayashia,*
a
Department of Chemistry, School of Science, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Fax : (+81)-3-5684-0634; phone: (+81)-3-5841-4790; e-mail: shu_kobayashi@chem.s.u-tokyo
Received: November 13, 2012; Revised: January 14, 2013; Published online: February 1, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200999.
Abstract: In the course of our investigations to find
a novel catalyst for the cross-dehydrogenative cou-
pling (CDC) reaction, it was discovered that anti-
mony(V) serves as a co-catalyst with N-hydroxy-
ACHTUNGTRENNUNGphthalimide (NHPI) under aerobic conditions. This
is a rare example of a catalytic use of antimony for
an oxidative coupling reaction.
the Sb(V) counteranion can act as a catalyst for the
oxidative coupling reaction.
Although aminium radicals are known to serve as
stoichiometric single electron oxidants,[10] there are
only a few examples in which catalytic use of the ami-
nium radical cation were reported for an aerobic oxi-
dation reaction.[11] Initially, we examined the commer-
cially available tris(p-bromophenyl)aminium hexa-
chloroantimonate as a catalyst for the CDC reaction
(Scheme 1). Even though antimony is classified as
a semi-metal in the periodic table, we expected that
the replacement of the counteranion would be possi-
ble at a latter stage of our optimization process.
When N-phenyltetrahydroisoquinoline (1a) was react-
ed with nitromethane in the presence of tris(p-bromo-
Keywords: aerobic oxidation; antimony; CDC;
cross-dehydrogenative coupling; N-hydroxyphthali-
mide (NHPI)
Catalytic carbon-carbon bond forming reactions are phenyl)aminium hexachloroantimonate (5 mol%),
among the most valuable processes in synthetic or- and MS 4ꢀ[12] under oxygen atmosphere at room
ganic chemistry, since they can constitute key steps in temperature, the desired product was obtained in
the syntheses of complex molecules. Among these re- a low yield (Table 1, entry 1). We hypothesized that
actions, cross-dehydrogenative coupling (CDC) reac- the problem in its catalytic use for oxidation reactions
tions of amines have emerged as an attractive means is due to the difficulty in the hydrogen radical abstrac-
of forming carbon-carbon bonds,[1] because nitrogen- tion process. Therefore, we speculated that the addi-
À
containing compounds are ubiquitous in natural prod- tion of N-hydroxyphthalimide (NHPI) as an N O
ucts and pharmaceuticals, and their direct transforma- radical source for the hydrogen abstraction would fa-
tions into more complex compounds would be syn- cilitate the aerobic oxidation.[13,14] Gratifyingly, when
thetically useful.
we added NHPI (5 mol%), the cross-coupling product
After the pioneering work by Murahashi,[2] who re- was obtained in a good yield, accompanied with the
ported the ruthenium-catalyzed CDC reactions in formation of a small amount of amide 3 (entry 2). To
2003, and the subsequent development by Li using determine the best aminium radical catalyst, several
copper catalysts,[3] the CDC has emerged as the reac- aminium radical salts were examined. Although hexa-
tion of choice to examine new catalyst systems for ox- fluoroantimonate salt was an active catalyst (entry 3),
idative coupling reactions. Despite a large number of surprisingly, the catalytic activity of tetrafluoroborate
transition metal-catalyzed (V,[4] Mo,[5] Fe,[6] Ru,[7] Ir,[8]) and hexafluorophosphate salts was very poor (en-
CDC reactions reported to date, examples of metal- tries 4 and 5). Thus, we hypothesized that the counter-
free systems are still rare.[9]
anion must play an important role in the catalytic
Thus, we planned to explore the use of redox-active
organocatalysts to facilitate the aerobic oxidative cou-
pling reaction of amines with pronucleophiles. In the
course of our investigations into the use of aminium
radical cations as catalysts for the aerobic CDC reac-
tion, we found an interesting phenomenon in which Scheme 1. Aminium radical-catalyzed CDC reaction.
Adv. Synth. Catal. 2013, 355, 269 – 273
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Arata Tanoue et al.
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Table 1. Screening of the catalysts.[a]
nally, we confirmed that both the sodium antimonate
catalyst and NHPI work in a synergistic manner to fa-
cilitate the oxidative transformation. (entries 10 and
11).
Next, we examined the substrate generality of this
oxidative coupling reaction (Table 2). Under the opti-
mized reaction conditions, the oxidative aza-Henry
reaction of 1a at 308C provided the coupling product
in a high yield (entry 1). While electron-rich o- and p-
methoxyphenyl-substituted amines afforded high
yields, the m-methoxyphenyl-substituted substrate
Entry
Catalyst[b]
Yield [%][c]
2a
3
1[d]
2
3
4
5
6
7
8
9
Ar3NSbCl6
Ar3NSbCl6
Ar3NSbF6
Ar3NBF4
Ar3NPF6
Et4NSbCl6
Ph3CSbCl6
NaSbCl6(a-NaphNO2)
SbCl5
29
64
41
6
11
51
41
>95
53
3
24
6
<5
Table 2. Substrate generality.[a]
<5
<5
<5
<5
<5
6
<5
<5
10
–
11[d]
NaSbCl6(a-NaphNO2)
22
[a]
Reaction conditions: amine 1a (0.25 mmol), catalyst
(5 mol%), NHPI (5 mol%), MS 4A (50 mg) in MeNO2
(0.5 mL) under O2 (1 atm) at room temperature for 18 h.
Ar=p-Br-C6H4.
[b]
[c]
1
Yield based on 1a and determined by H NMR analysis
using 1,1,2,2-tetrachloroethane as an internal standard.
In the absence of NHPI.
[d]
cycle. When we tested this hypothesis by replacing
the countercation of the catalyst from the aminium
radical to tetraethylammonium or trityl cation, mod-
erate yields were obtained (entry 6 and 7). Thus, it
was most likely that the real active catalyst was not
the aminium radical cation, but the antimonate coun-
teranion.
Antimony oxide has been previously reported as
a catalyst for oxidation reactions, such as dehydrogen-
ation or selective oxidation of alkanes.[15,16] However,
in most cases, antimony served as an additive for
other transition metal catalysts (V, Mo, Fe, etc.) and
very high temperatures were required for these reac-
tions.[17] Although antimony is not strictly a non-
metal, we decided to investigate this catalyst further,
since the catalytic use of antimony for the CDC reac-
tions of tertiary amines has not been reported.[18] In
À
addition, the investigation of SbCl6 anion as an oxi-
dation catalyst would dispel the notion of these spe-
cies as just innocent non-coordinating counteranions.
After screening various antimonate salts, we found
that the a-nitronaphthalene-ligated sodium hexa-
[a]
Reaction conditions: amine
NaphNO2) (5 mol%), NHPI (5 mol%), MS 4 A (50 mg) in
1 (0.25 mmol), NaSbCl6(a-
MeNO2 (0.5 mL) under O2 (1 atm) at 308C.
[b]
[c]
NMR yields are based on 1 and determined by 1H NMR
analysis using 1,1,2,2-tetrachloroethane as an internal stan-
dard. Isolated yields are given in parentheses.
EtNO2 as a solvent.
ACHTUNGTRENNUNGchloroantimonate was the most active catalyst
(entry 8).[19] Although it would be desirable to employ
commercially available antimony pentachloride as
a catalyst, its activity was only moderate (entry 9). Fi-
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Antimony/N-Hydroxyphthalimide as a Catalyst System for Cross-Dehydrogenative Coupling Reactions
Table 3. Scope of nucleophiles.[a]
was slightly less reactive (entries 2–4). Also, a p-tolyl-
substituted compound reacted smoothly to afford the
desired product with an excellent yield (entry 5). On
the other hand, an electron-deficient p-chlorophenyl-
substituted substrate afforded only a moderate yield
(entry 6). In addition, when nitroethane was used as
a solvent, the corresponding product was obtained in
a
good yield and moderate diastereoselectivity
(entry 7). We also examined other amines such as tet-
rahydroisoquinoline, N-benzyltetrahydroquinoline,
and N,N-dimethyltoluidine as substrates, but the de-
sired products were obtained in very low yields.[20,21]
Then, the scope of nucleophiles was examined
(Table 3). Initially, we screened different solvents and
found acetonitrile was best at 408C in the presence of
3 equivalents of the pronucleophiles. While dimethyl
and diethyl malonates afforded the desired coupling
products in high yields (entries 1 and 2), the reactivity
of b-keto esters was surprisingly lower (entry 3). We
also examined sp2-hybridized nucleophiles such as
silyl enol ether 4d (entry 4) and N-methylindole
(entry 5) and found them to be viable substrates for
this aerobic oxidative coupling reaction. Similar to
the previous report by Li,[3b] the latter substrate re-
quired higher reaction temperature. In addition to the
carbon-based nucleophiles, phosphine nucleophiles
could also be applied. Methyl, ethyl and isopropyl
phosphites reacted smoothly with 1a (entries 6–8) to
afford the desired products in excellent yields.
Although the reaction mechanism for the copper-
catalyzed aerobic and peroxide-mediated CDC reac-
tion has been recently clarified by Klussmann, the
roles of antimonate and NHPI in our system remain
unclear. However, since the reaction does not proceed
with only NHPI as a catalyst and that catalyst turn-
over is observed for the antimonate salt, we assume
that the antimony catalyst is responsible for the single
electron oxidation step and NHPI facilitates the hy-
drogen radical abstraction process (Scheme 2).[22] Ini-
tially, the reaction begins from a single electron oxida-
tion of the tertiary amine by high valent antimonyACTHNUTRGNEUNG(V
or IV). The resulting low valent antimony(IV or III)
is oxidized with molecular oxygen to regenerate
antimonyACHTUNGTRENNUNG(V or IV) and form an oxygen radical
[a]
[b]
Reaction conditions: amine 1a (0.25 mmol), nucleophile 4
(3 equiv), NaSbCl6(a-NaphNO2) (5 mol%), NHPI
(5 mol%), MS 4A (50 mg) in MeCN (0.5 mL) under O2
(1 atm) at 408C.
NMR yields are based on 1a and determined by
1H NMR analysis using 1,1,2,2-tetrachloroethane as an
internal standard. Isolated yields are given in parenthe-
ses.
anion.[23] Next, the oxygen radical anion abstracts the
hydrogen from NHPI to form PINO (phthalimide N-
oxide) radical and hydrogen peroxide anion. Hydro-
gen abstraction of aminium radical cation I by PINO
affords iminium intermediate II and subsequently, the
nucleophile, deprotonated by the hydrogen peroxide
anion, is trapped to furnish the aerobic oxidative cou-
pling product. It should be noted that both the high
valent antimony and PINO could be interchanged for
[c]
[d]
1.5 equivalents of the nucleophile were used.
808C.
either oxidation steps. We also performed the CDC reaction in the absence of the NHPI co-catalyst, the
reaction in the presence of a radical inhibitor and the most likely explanation is that a second antimonate-
desired product was still obtained, albeit with a low mediated two-electron oxidation pathway exists in
yield (21%).[24] Since the yield obtained parallels the our CDC reaction.
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Arata Tanoue et al.
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Acknowledgements
This work was partially supported by a Grant-in-Aid for Sci-
ence Research from the Global COE Program of the Japan
Society for the Promotion of Science (JSPS), The University
of Tokyo, the Ministry of Education, Culture, Sports, Science
and Technology (MEXT) Japan, the New Energy and Indus-
trial Technology Development Organization (NEDO) and
Japan Science and Technology Agency (JST).
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Experimental Section
Typical Procedure for the CDC Reaction of N-Aryl-
tetrahydroisoquinolines
To a dried 10-mL round-bottomed flask, equipped with an
oxygen balloon, was added MS 4 A (50 mg), MeNO2
(0.5 mL) and 1a (52.2 mg, 0.249 mmol). Then, NHPI
(2.0 mg, 0.0123 mmol) and NaSbCl6(a-NaphNO2) (6.8 mg,
0.0128 mmol) were successively added. After stirring the re-
action mixture for 4 h at 308C, the solvent was removed
under reduced pressure and the NMR yield was determined
with 1,1,2,2-tetrachloroethane (13 mL) as an internal stan-
dard (90% yield). The crude mixture was filtered through
silica gel, and the filtrate was concentrated under reduced
pressure. Flash chromatography on silica gel with hexane/
ethyl acetate (15:1) afforded 2a; yield: 56.6 mg (85%).
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Antimony/N-Hydroxyphthalimide as a Catalyst System for Cross-Dehydrogenative Coupling Reactions
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À
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