Carbon Nitride-Catalyzed Photoredox Sakurai Reactions and Allylborations

Article abstract of DOI:10.1002/adsc.201400551

Within the last couple of years, the photocatalytic, oxidative C-C coupling has grown to a well-established methodology, especially for the modification of aryl-substituted tetrahydroisoquinoline derivatives. However, until now, this reaction is mainly restricted to the usage of strong nucleophiles like nitroalkanes, cyanides, enamines, phosphonates and malonates. Within this publication we present an extension of such a method towards the application of weaker nucleophiles, namely allylstannanes, allylsilanes and allylboranes. Therefore, a very simple protocol was invented, using heterogeneous mesoporous graphitic carbon nitride (mpg-C₃N₄) as catalyst and air as oxidizing agent, leading to high yields for a broad range of substrates.

Full text of DOI:10.1002/adsc.201400551

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DOI: 10.1002/adsc.201400551
Carbon Nitride-Catalyzed Photoredox Sakurai Reactions and
Allylborations
Lennart Mçhlmanna and Siegfried Blecherta,*
a
Institute of Chemistry, Technical University Berlin, Strasse des 17. Juni 135, 10623 Berlin, Germany
Fax : (+49)-30-314-29745; phone: (+49)-30-314-22255; e-mail: blechert@chem.tu-berlin.de
Received: June 4, 2014; Revised: July 9, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400551.
Abstract: Within the last couple of years, the photo-
catalytic, oxidative C C coupling has grown to
ence of a suitable nucleophile.[5] Various types of pho-
tosensitizers, for example, organic dyes, metal com-
plexes like RuACTHNGUTERN(NUG bpy)3 and more recently mesoporous
À
a well-established methodology, especially for the
modification of aryl-substituted tetrahydroisoquino-
line derivatives. However, until now, this reaction is
mainly restricted to the usage of strong nucleophiles
like nitroalkanes, cyanides, enamines, phosphonates
and malonates. Within this publication we present
an extension of such a method towards the applica-
tion of weaker nucleophiles, namely allylstannanes,
allylsilanes and allylboranes. Therefore, a very
simple protocol was invented, using heterogeneous
mesoporous graphitic carbon nitride (mpg-C3N4) as
catalyst and air as oxidizing agent, leading to high
yields for a broad range of substrates.
graphitic carbon nitride (mpg-C3N4), a heterogeneous,
metal-free and recyclable semiconductor, have proven
to deliver high yields even at room temperature
(Scheme 1).[6] Hence, the attempt to adopt this highly
effective methodology for photoinduced Sakurai-type
transformations is obvious.
However, to the best of our knowledge, until now
the coupling is mainly restricted to nitroalkanes, cya-
nides, enamines, phosphonates and malonates. With
regard to the logarithmic nucleophilicity scale devel-
oped by Mayr et al., in which various nucleophiles
are compared and sorted based on their reactivity to-
wards certain electrophiles, these compounds belong
to the strongest nucleophiles with a nucleophilicity
value (N) above 15.[7]
Keywords: aerobic oxidation; allylation; carbon ni-
tride; photoredox catalysis; Sakurai reaction
Weaker nucleophiles (N<15) are more challenging,
due to the formation of the hydroperoxide anion
within the catalytic cycle. This anion is a nucleophile
by itself (N=15.4)[8] and can react with the generated
À
Considered to belong to the most efficient C C bond iminium ion to afford the corresponding amide as
formations, the Sakurai reaction and allylboration de- product.[9] With strong nucleophiles, hydrogen perox-
scribe the direct allylation of imines or carbonyl moi- ide is formed, which can act as an additional oxidizing
eties via allyl nucleophiles such as allylstannanes, al- agent. However, the nucleophilicity of common allyl
lylsilanes or allylboranes.[1] The products derived by transfer agents, as illustrated in Scheme 1, is relatively
this process are valuable intermediates in the synthe- low (N <10) which makes a selective reaction process
sis of drugs and natural products.[2] The ongoing inter- difficult.
est in the development of novel, efficient and mild
Recently Stephenson et al. published a protocol
avoiding this amide formation by using BrCCl3 as the
procedures reflects the importance of this reaction.
À
Recently, a new approach for selective C C bond terminal oxidizing agent instead of molecular oxygen
formations has taken the focus of interest: the photo- in combination with Ru
(bpy)3 as the photoredox cata-
catalytic, oxidative C C coupling of amines has lyst.[10] Following this method, moderate to excellent
become a rapidly growing field in organic chemistry yields could be achieved for a broad scope of nucleo-
because of its generally mild conditions and environ- philes and, with limitations, also allylations were real-
mental sustainability.[3,4] Thereby a photosensitizer is ized. Besides the replacement of oxygen as a cheap
used to reduce oxygen under irradiation of visible and sustainable oxidation source by BrCCl3 a further
light. This reduction initiates the oxidation of the drawback of this reaction is the need for a two-step
amine substrate to the corresponding iminium ion process. Only after the oxidation is completed, the nu-
À
À
which is capable of C C bond formation in the pres- cleophile is added and the light radiation stopped.
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Lennart Mçhlmann and Siegfried Blechert
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Scheme 1. Proposed mechanism for the oxidative C C coupling versus amide formation.
Motivated by our interest in aerobic oxidations by Table 1. Optimization of mpg-C3N4-catalyzed allylations.[a]
carbon nitride catalysis, a system which has proven to
be highly selective and efficient under mild condi-
tions, we decided to investigate the capture of imini-
um ions by weak nucleophiles, in particular, allyl
transfer agents, more in detail.
As our first trial we decided to test the reaction of
N-phenyltetrahydroisoquinoline 1a, a substrate which
was highly reactive towards previously reported C C
Entry Solvent
mpg-C3N4 [mg] Oxidant Yield [%]
À
coupling reactions, with allyltributylstannane 2 (N=
5.46). Allylation agent 2 has, compared with the com-
monly used allyltrimethylsilane (N=1.79), an en-
hanced nucleophilicity whereby a higher selectivity
was expected. The reaction was run under conditions
which have been proven to be preferential for
a broad scope of substrates and nucleophiles in our
laboratories: Acetonitrile was used as the solvent,
carbon nitride as the photocatalyst and an energy
saving bulb as light source under an oxygen atmos-
phere (Table 1). Unfortunately no product formation
could be observed but rather selective transformation
to the corresponding amide occurred (entry 1). There-
fore we decided to slow down the oxidation step by
reducing the amount of mpg-C3N4 catalyst (entry 2),
with the intention to keep the concentration of hydro-
peroxide anion and unreacted iminium ion as low as
possible during the reaction. As a result, traces of the
1
2
3
4
MeCN
MeCN
MeCN
acetone
NMP
15
5
O2
O2
air
air
air
air
air
air
air
N2
–
traces
41[d]
traces
–
5
5
5
5
5
5
6
7
C6H5CF3
MeOH
MeOH
MeOH
MeOH
50[d]
64
8[b]
9[b,c]
10[b,c]
5
72
5
93
5
–
[a]
Reaction conditions: room temperature, 0.25 mmol 1a,
0.5 mmol 2, 1 mL solvent, 1 bar oxidant, 5 mg mpg-C3N4,
60 W light bulb. The products were isolated by column
chromatography on SiO2.
4 mL of MeOH were used.
1 mmol of 2 was used.
[b]
[c]
[d]
1
Determined by H NMR.
desired product could be detected by NMR analysis, homoallyl product 3a could be increased significantly
however the amide formation was still dominating. To to 41%. An additional solvent screening demonstrat-
further decelerate the oxidation, air was used as the ed that methanol is superior for this reaction
terminal oxidation agent instead of oxygen (entry 3). (entry 7). Furthermore, lowering the concentration of
To our delight, the conversion to the corresponding the reaction mixture and increasing the excess of 2 to
2
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Carbon Nitride-Catalyzed Photoredox Sakurai Reactions
Table 2. mpg-C3N4-catalyzed coupling of various tetrahydro-
isoquinolines with allyl- and allenylstannanes.[a]
ther transformations, however to the best of our
knowledge, examples for oxidative homopropargyla-
tion reactions have not been reported yet.[11] The
product is relatively stable under the given reaction
conditions in the presence of an excess of 2c although,
after purification the neat compound is highly reac-
tive and must be stored at À188C under nitrogen in
order to prevent rapid decomposition.
ACHTUNGTRENNUNG
After demonstrating the versatile applicability of
allyl compounds for photoredox catalyzed Sakurai-
type reactions, we decided to go one step further and
test the capability of even less nucleophilic allylsilane
agents. Allyltrimethylsilane 5a, as a common allyltri-
butylstannane alternative, was tested first in combina-
tion with 1a as the model reaction. Unfortunately, no
product formation could be observed, instead, selec-
tive formation of the methanol adduct 6 took place.
Even the usage of established activators like CsF,
TBAF, TBAT and CuCl as well as the change to the
more reactive allyl tris(trimethylsilyl)silane did not
lead to the wanted transformation.[12] However, with
the more nucleophilic 2-methylallyltrimethylsilane 5b,
product 3f was formed when 5 mol% CuI was added
to the reaction mixture, leading to an excellent 87%
yield after work-up (Scheme 2).
Entry Subst. R1/Ar
Stannane Prod. Yield [%]
1
2
3
4
1a
1b
1c
1d
1e
1a
1b
1c
1d
1e
1f
1b
H/Ph
H/p-MeOC6H4 2a
H/p-t-BuC6H4 2a
H/p-Tol
MeO/Ph
H/Ph
H/p-MeOC6H4 2b
H/p-t-BuC6H4 2b
2a
3a
3b
3c
3d
3e
3f
3g
3h
3i
93
83
79
70
65
93
71
83
96
89
75
89
2a
2a
2b
5
6[b]
7[b]
8[b]
9[b]
10[b]
11[b]
12
H/p-Tol
2b
2b
2b
2c
MeO/Ph
H/p-BrC6H4
MeO/Ph
3j
3k
4b
Presumably, the copper salt catalyzes a “retro-Man-
nich” type transformation of 6 to the iminium ion
which can then be captured by 5b.[13] For 5a, however
slow conversion to the corresponding amide took
place under these conditions.
[a]
Reaction conditions: room temperature, 0.25 mmol sub-
strate, 1 mmol stannane, 4 mL methanol, air, 5 mg mpg-
C3N4, 60 W light bulb, reaction time: 6–26 h.
0.5 mmol of stannane was used.
[b]
1 mmol led to an excellent 93% isolated yield
(entry 9) after 6 h reaction time. A control experi-
ment under nitrogen atmosphere led to no conversion
of the starting material, demonstrating that oxygen is
indeed the terminal oxidation agent (entry 10).
Having the optimized conditions in hand, we next
À
tested the substrate scope of this aerobic C C cou-
pling reaction by varying both the substrates as well
as the nucleophiles (Table 2). Pleasingly, various aryl-
substituted tetrahydroisoquinoline derivatives were
capable of this transformation. Both electron-defi-
cient as well as electron-rich substrates led to the cor-
responding homoallyl products in good to excellent
yields at reasonable reaction times (6–26 h). Notably,
(2-methylallyl)-tributylstannane as the allylation
agent (entries 6–11) could be used in a smaller excess
(0.5 mmol), to achieve even higher yields in most of
the cases, presumably due to its slightly increased nu-
cleophilicity.[7] Remarkably, even tributylallenylstan-
nane 2c could be used as a nucleophile leading to the
formation of the corresponding homopropargylic
amine 4b in very good yield (entry 12). The introduc-
tion of unprotected triple bond moieties is a highly
Scheme 2. Oxidative Sakurai reaction using silanes as allyl
desired task due to the versatile possibilities for fur- transfer agents.
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Lennart Mçhlmann and Siegfried Blechert
The screening of other substrates led to comparable
yields and reaction times as for the use of allyltribu-
tylstannanes (Table 3) and demonstrates the generali-
ty of this protocol with the advantage of significantly
reduced toxicity.
In conclusion, we have demonstrated the first direct
photocatalytic oxidative allylation of tetrahydroiso-
quinolines using air as the sole oxidizing agent in
combination with visible light and polymeric graphitic
carbon nitride as the photocatalyst. The reaction is
not limited to stannanes, but also boranes and, with
limitations, silanes, could be used as the allylation
agent allowing high flexibility in its applications.
Scheme 3. Allylboration of tetrahydroisoquinoline 1a with
different boranes.
Experimental Section
Furthermore, we decided to investigate the suitabil- General Procedure
ity of allylborane compounds as another source for
Allylation agent (2–4 equiv.), substrate (0.25 mmol), mpg-
benign and environmentally harmless allyl transfer re-
agents. Allylboranes offer significant advantages such
as superior stability and ease of modification with
chiral ligands and unique selectivity, although till now
they have not been tested in photoredox catalysis.[14]
Gratifyingly, the initial experiment using allylbor-
onic acid MIDA ester 7a and 1a resulted in a good
65% yield of the homoallylamine 3a after 22 h
(Scheme 3). Employing the pinacol ester 7b the yield
could be further increased to 75% after reduced reac-
tion times of 6 h. Using chiral allylborane 7c reduced
the yield only slightly at a similar reaction time, al-
though a significant enantiomeric induction failed to
appear. Therefore pinacol ester 7b was used for fur-
ther investigations.
C3N4 (5 mg) and methanol (4 mL) were added into a 10-mL
Schlenk tube. The tube was covered with a septum which
was pierced with a needle in order to prevent an inflow of
air. The suspension was then shaken at room temperature
under irradiation with visible light using a Philips cool day-
light energy saving bulb (60 W) until all starting material
was consumed (TLC analysis). The mpg-C3N4 was removed
either by centrifugation or by filtration and the solvent was
distilled off under reduced pressure. The residue was puri-
fied by column chromatography on SiO2 to furnish the de-
sired product.
For more details, see the Supporting Information.
Acknowledgements
This work was supported by the “Light2Hydrogen” Project
of the BMBF (03IS2071D),
Table 3. Allylboration of various tetrahydroisoquinoline de-
rivatives.[a]
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6 Carbon Nitride-Catalyzed Photoredox Sakurai Reactions
and Allylborations
Adv. Synth. Catal. 2014, 356, 1 – 6
Lennart Mçhlmann, Siegfried Blechert*
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