Synthesis ofN-aryl amines enabled by photocatalytic dehydrogenation

Article abstract of DOI:10.1039/d0sc04890a

Catalytic dehydrogenation (CD)viavisible-light photoredox catalysis provides an efficient route for the synthesis of aromatic compounds. However, access toN-aryl amines, which are widely utilized synthetic moieties,viavisible-light-induced CD remains a significant challenge, because of the difficulty in controlling the reactivity of amines under photocatalytic conditions. Here, the visible-light-induced photocatalytic synthesis ofN-aryl amines was achieved by the CD of allylic amines. The unusual strategy using C₆F₅I as an hydrogen-atom acceptor enables the mild and controlled CD of amines bearing various functional groups and activated C-H bonds, suppressing side-reaction of the reactiveN-aryl amine products. Thorough mechanistic studies suggest the involvement of single-electron and hydrogen-atom transfers in a well-defined order to provide a synergistic effect in the control of the reactivity. Notably, the back-electron transfer process prevents the desired product from further reacting under oxidative conditions.

Full text of DOI:10.1039/d0sc04890a

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Synthesis of N-aryl amines enabled by
photocatalytic dehydrogenation†
Cite this: DOI: 10.1039/d0sc04890a
a
*
All publication charges for this article
have been paid for by the Royal Society
of Chemistry
Jungwon Kim,
Siin Kim,abc Geunho Choi,a Geun Seok Lee,a Donghyeok Kim,abc
abc
abc
a
*
*
Jungkweon Choi,
Hyotcherl Ihee
and Soon Hyeok Hong
Catalytic dehydrogenation (CD) via visible-light photoredox catalysis provides an efficient route for the
synthesis of aromatic compounds. However, access to N-aryl amines, which are widely utilized synthetic
moieties, via visible-light-induced CD remains a significant challenge, because of the difficulty in
controlling the reactivity of amines under photocatalytic conditions. Here, the visible-light-induced
photocatalytic synthesis of N-aryl amines was achieved by the CD of allylic amines. The unusual strategy
using C6F5I as an hydrogen-atom acceptor enables the mild and controlled CD of amines bearing
various functional groups and activated C–H bonds, suppressing side-reaction of the reactive N-aryl
amine products. Thorough mechanistic studies suggest the involvement of single-electron and
hydrogen-atom transfers in a well-defined order to provide a synergistic effect in the control of the
reactivity. Notably, the back-electron transfer process prevents the desired product from further reacting
under oxidative conditions.
Received 4th September 2020
Accepted 23rd November 2020
DOI: 10.1039/d0sc04890a
rsc.li/chemical-science
Introduction
Catalytic dehydrogenation (CD) offers a useful strategy for
constructing unsaturated systems from readily available sp3
carbon-rich scaffolds.1 For example, the CD of hydrocarbons
provides valuable olen feedstocks,1c and alcohol dehydroge-
nation can promote the formation of carbonyl functional
groups.1a By exploiting the thermodynamic preference towards
aromatization, a number of transformations to obtain various
aromatic compounds have been developed.2 Nevertheless,
despite the signicant advances in the CD process, the
requirement for harsh reaction conditions, such as high reac-
tion temperatures and the use of strong oxidants still limits the
practical application of the strategy.
Utilization of visible-light in organic transformations via
photoredox catalysis has led to novel and practical synthesis of
target molecules under relatively mild reaction conditions.3
Visible-light photoredox catalysis has also been applied to CD
reactions (Scheme 1).4 Since the initial development of a pho-
tocatalyst and the use of an external oxidant such as O2,4a tert-
aDepartment of Chemistry, Korea Advanced Institute of Science and Technology
(KAIST), Daejeon 34141, Republic of Korea. E-mail: kikj11@snu.ac.kr; hyotcherl.
ihee@kaist.ac.kr; soonhyeok.hong@kaist.ac.kr
bKI for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST),
Daejeon 34141, Republic of Korea
cCenter for Nanomaterials and Chemical Reactions, Institute for Basic Science,
Daejeon 34141, Republic of Korea
† Electronic supplementary information (ESI) available: Detailed experimental
procedures, computational details, and spectroscopic data for all new
compounds. See DOI: 10.1039/d0sc04890a
Scheme 1 Visible-light-induced catalytic dehydrogenation.
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butyl peroxybenzoate,4b and sulfonyl chloride,4h the combina- transferred to the target cyclic system to selectively achieve the
tion of a visible-light photocatalyst (Ir, Ru, organocatalyst) and desired dehydrogenation reaction. Moreover, the produced N-
a hydrogen-evolution metal catalyst (Co, Pd) has afforded the aryl amine would become a competing and more reactive
aromatization of saturated N-heterocycles such as tetrahy- substrate in the course of the reaction. This has the potential to
droquinoline and indoline via an acceptorless CD process to transform N-aryl amine products into unwanted a-amino
efficiently produce the corresponding aromatic heterocycles radical, iminium, and enamine species under visible-light
(Scheme 1A).4c–f,i–k,m Further elaboration of CD strategies using photoredox catalysis (Scheme 1B).5,6 Very recently, Leonori
an additional hydrogen-atom transfer (HAT) catalyst enabled and co-workers successfully overcame the above-mentioned
direct access to more challenging substrates. For example, hurdles via photocatalytic dehydrogenation of in situ gener-
Kanai designed a triple hybrid catalysis (photoredox, HAT, and ated enamines with photoredox/cobalt dual catalytic system.7
metal catalysts) to achieve the acceptorless photoredox CD of
Herein, we demonstrate the synthesis of N-aryl amines from
tetrahydronaphthalene derivatives (Scheme 1A).4e,g Very a 2-cyclohexenyl amine precursor via visible-light photoredox
recently, the developed strategies were applied to CD of acyclic CD (Scheme 1C). The use of peruoroarene as a hydrogen-atom
alcohols or secondary amines, providing carbonyl or imine acceptor is key to achieving selective aromatization on the
compounds.4l,n,o
cyclohexenyl moiety, and wide ranges of functional groups and
Despite these advances, the synthesis of functionalized bioactive motifs are tolerated under the reaction conditions.
benzenes, such as N-aryl amines, has been challenging, despite The operating mechanism was revealed to involve the syner-
the widespread use of these moieties in organic, materials, and gistic relay of SET and HAT processes mediated by the organic
biological chemistries. Direct access to N-aryl amines via visible- photoredox catalyst and
a pentauorophenyl radical, in
light photocatalytic dehydrogenation is difficult (Scheme 1B) combination with the protective back-electron transfer (BET)
because the strategy previously applied in photocatalytic dehy- process, based on the nature of the amine substrates.
drogenation relies on the single-electron transfer (SET) of
a nitrogen atom to produce reactive amine radical cation
species.5 Saturated N-heterocyclic systems, which contain
Results and discussion
nitrogen atoms inside the ring system, allow control of the The 2-cyclohexenyl amine A1 was initially selected as a model
reaction to promote the desired dehydrogenation; however, substrate to explore the target reaction. Aer extensive
systems with an exo-nitrogen functionality are more prone to screening (Tables S1–S5†), 3DPAFIPN was identied as the
unwanted side-reactions (Scheme 1B).6 These possibilities raise photocatalyst, iodopentauorobenzene (C6F5I) as the hydrogen-
the question of how the reactivity of the exo-nitrogen atom is atom acceptor, and K2CO3 as the base to induce the desired
oxidative aromatization in high yield (95%). It is noteworthy
Table 1 Variation of the reaction conditionsa
Entry
Variation of reaction conditions
Yield B1b (%)
1
None (standard)
95
2
3
4
5
6
7
8
9
[Ir(dF(CF3)ppy)2(dtbbpy)](PF6) instead of 3DPAFIPN
C6F5Br instead of C6F5I
CH3CN instead of CH2Cl2
THF instead of CH2Cl2
1,2-DCE instead of CH2Cl2
K3PO4 instead of K2CO3
Triethylamine instead of K2CO3
18 h reaction time
52
N. D.
3
12
91
4
N. D.
49
10
11
12
13
No 3DPAFIPN
No C6F5I
No K2CO3
Dark condition
4
N. D.
32
N. D.
a
Reaction conditions: A1 (0.2 mmol), 3DPAFIPN (0.012 mmol), C6F5I (0.8 mmol), K2CO3 (0.6 mmol), CH2Cl2 (1 mL) in a 4 mL reaction vial,
b
irradiated with a 34 W Kessil blue LED for 24 h under fan cooling. Determined by GC using dodecane as an internal standard. THF ¼
tetrahydrofuran. N. D. ¼ not detected.
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that no imine compounds derived from either A1 or B1 were obtaining a high yield of the product (entries 7, 8, 12), and
observed, although the CD of secondary amines under visible- a control experiment under dark conditions (entry 13) proved
light photoredox catalytic conditions was reported in the that the reaction proceeded under visible-light irradiation.
synthesis of imines.4o Further variation of the standard reaction
With the optimal conditions in hand, the substrate scope of
conditions was implemented to check the effect of each the reaction was evaluated (Table 2). Several benzylamine
component (Table 1). Changing the photocatalyst to a well- derivatives were initially tested for this reaction. Notably,
known iridium photocatalyst ([Ir(dF(CF3)ppy)2(dtbbpy)](PF6)) various functional groups, including halides (B3, B4, B8), ester
signicantly decreased the reactivity (52%, entry 2), and (77%, B5), triuoromethyl (61%, B6), and boronate ester (44%,
photocatalyst-free conditions yielded only a small amount of B7), were tolerated under the reaction conditions and gave the
the desired product (4%, entry 10). Replacing C6F5I with C6F5Br desired N-aryl amines in good yields. A piperonylamine deriv-
(entry 3) completely shut down the reaction, although it was ative (77%, B9) and other heteroaromatic methyl amine deriv-
previously reported that C6F5Br can be converted to a penta- atives (85%, B10 and 32%, B11) were reactive under the reaction
uorophenyl radical under visible-light irradiation in the pres- conditions. Other secondary amine precursors, such as a-
ence of Eosin Y.8 In addition, no pentauorophenylation of the methyl benzylamine (84%, B12), linear (70%, B14), or cyclic
aniline aromatic ring as a side reaction was observed in all (70%, B15) aliphatic amines, and even a sterically bulky 1-ada-
entries. The developed reaction is highly sensitive to the solvent mantylamine derivative (74%, B16) could be applied in the
(entries 4–6, Table S3†), and dichloromethane can only be reaction. Notably, the cyclohexyl ring of B15 remains intact
replaced with 1,2-dichloroethane (1,2-DCE) without loss of the under the dehydrogenative conditions, implying the necessity
reactivity (91%, entry 6). Potassium carbonate was essential for of an allylic a-amino C–H bond for the desired reaction. The
Table 2 Evaluation of the substrate scopea
a
Reaction conditions: A (0.2 mmol), 3DPAFIPN (0.012 mmol), C6F5I (0.8 mmol), K2CO3 (0.6 mmol), CH2Cl2 (1 mL) in a 4 mL reaction vial, irradiated
with a 34 W Kessil blue LED for 24 h under fan cooling. Yields of the isolated products were described. b 36 h. c 48 h.
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Table 3 Utilization of bioactive aminesa
a
Reaction conditions: A (0.2 mmol), 3DPAFIPN (0.012 mmol), C6F5I (0.8 mmol), K2CO3 (0.6 mmol), CH2Cl2 (1 mL) in a 4 mL reaction vial, irradiated
with a 34 W Kessil blue LED for the indicated time under fan cooling. Yields of the isolated products were described.
efficiency of the reaction was maintained even with different tetrahydronaphthyl group remaining intact. This unique che-
types of tertiary allyl amines (B17–B21). To our delight, no moselectivity may be benecial for the synthesis of bioactive N-
oxidation at the benzyl,4o,9 tetrahydronaphthyl,4e,g,7 or a-amino10 aryl amines while maintaining a specic structure. Further
positions was observed (e.g., reactions with A22 or A23, high- elaborations with different cyclohexenyl moieties were con-
lighted in orange), demonstrating the advantage of the mild ducted using Mexiletine as a starting amine. As depicted in
reaction conditions compared to previously reported oxidative Table 3, the introduction of a simple phenyl group (B34) and
aromatization conditions.
substituted phenyl groups (48% for B35, 72% for B36) was
The cyclohexenyl scaffold was then varied and the synthesis realized under the standard reaction conditions with good
of ortho-/meta-/para-substituted N-aryl amines was achieved efficiency.
using the developed method, albeit with a reduced yield of the
The developed protocol for photocatalytic dehydrogenation
product in some cases (B24–B29). It is noteworthy that sulde provides a high degree of reactivity and selectivity for a wide
(A29) is compatible with the reaction, producing a sulfur- range of allylic amines. This raises fundamental questions
containing N-aryl amine in good yield (68%, B29), considering regarding the mechanism of the reaction (Fig. 1). First, the
that suldes are known to be readily oxidizable under oxidation origin of the selective dehydrogenation leading to aromatiza-
conditions and tend to inhibit transition metal-mediated CD.11 tion needs to be addressed to understand the underlying prin-
The developed method was further applied to bioactive ciple of the reaction. Several reactions with A containing
amines (Table 3). Amines containing polycyclic structures, a reactive benzylic position did not show any sign of activation
amino acid moieties, and terpenoid structures all remained of the benzylic position, which is in clear contrast to the re-
intact to form corresponding N-aryl amines in moderate to good ported functionalizations of benzylic amines.5,12 In addition, the
yields. Various types of reactive positions, such as benzylic role of C6F5I as a hydrogen-atom acceptor in the reaction must
(62%, B30), tertiary (67%, B32), and a-oxygen carbons (79%, be further investigated. Lastly, the preservation of the synthe-
B34), were tolerated under the developed reaction conditions. sized N-aryl amines under photocatalytic conditions (Eopx (B1) ¼
When the Sertraline derivative (A33) containing both cyclo- 0.88 V vs. SCE in CH3CN)13 is the most noticeable aspect of the
hexenyl and tetrahydronaphthyl groups was used, selective reaction, which enables controlled dehydrogenation with high
aromatization of the cyclohexenyl group was achieved to form efficiency.
the corresponding N-aryl amine (45%, B33) with the
To answer the questions about the mechanism of the
developed reaction, a number of control experiments were
conducted (Table 4). The reactions with C6F5Br as the sole
reagent did not provide the desired amine B1 (entry 2; Table 1,
entry 3), although C6F5Br can provide a C6F5 radical and
promote peruoroarylation under visible-light photocatalytic
conditions.8 Noticeably, the existence of both C6F5I and C6F5Br
exhibited a comparable reactivity, and the conversion of only
C6F5I to C6F5H was observed by 19F NMR spectroscopy (72%,
entry 3, see Fig. S2†). The effect of the counteranion was not
observed in either case (Table 4, entries 4 and 5), suggesting
that halide anions did not affect the reactivity. CV measure-
ments revealed that the single-electron reduction of C6F5I
(Erped ¼ ꢀ1.36 V vs. SCE in CH3CN) is more facile than that of
Fig. 1 Major mechanistic questions regarding the reaction.
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Table 4 Control experimentsa
Entry
Additive
Yield B1b (%)
1
2
3
4
5
6
7
C6F5I (4.0 equiv.)
C6F5Br (4.0 equiv.)
95
N. D.
72
C6F5I (4.0 equiv.) + C6F5Br (4.0 equiv.)
C6F5I (4.0 equiv.) + KBr (3.0 equiv.)
C6F5Br (4.0 equiv.) + nBu4NI (3.0 equiv.)
C6F5I (4.0 equiv.) + TEMPO (1.0 equiv.)
C6F5I (4.0 equiv.) + galvinoxyl (1.0 equiv.)
82
N. D.
<2%
N. D.
a
Reaction conditions: A1 (0.2 mmol), 3DPAFIPN (0.012 mmol),
additive, K2CO3 (0.6 mmol), CH2Cl2 (1 mL) in a 4 mL reaction vial,
irradiated with a 34 W Kessil blue LED for 24 h under fan cooling.
b
Measured by GC using dodecane as an internal standard.
C6F5Br (Erped ¼ ꢀ1.64 V vs. SCE in CH3CN),14 which may account
for the difference in the reactivity of the two C6F5 radical
precursors. The addition of a radical scavenger ((2,2,6,6-
tetramethylpiperidin-1-yl)oxyl (TEMPO) or galvinoxyl) unam-
biguously hampered the reaction, indicating the involvement of
radical intermediates in the reaction (Table 4, entries 6 and 7).
Evaluation of the effect of 3DPAFIPN (Table 1, entries 1 and
10) indicated the formation of a radical intermediate by
photoexcited 3DPAFIPN. Stern–Volmer quenching experiments
with A1 and C6F5I (Fig. S6†) provided insight into the reductive
quenching process (Scheme 2A, le). In addition, the involve-
ment of HAT of the C6F5 radical was substantiated by the
observation of C6F5H aer the reaction (Fig. S1†). However, the
detailed aspects of HAT should be discussed by considering
a number of possible scenarios. In particular, the target of HAT
by the C6F5 radical should be addressed. First, it is possible for
the reactive C6F5 radical to abstract activated hydrogen-atom
from the neutral amine (A) (Scheme 2A, right). When amine
A1 deuterated at the allylic position (A1-D) was applied in the
reaction, only a trace amount of C6F5D was observed in the
reaction mixture (Scheme 2B, Fig. S7 and S8†), which is in clear
contrast with the results of signicant deuterium incorporation
in the hydrodeuorination of peruoroarene with an a-deuter-
ated aliphatic amine.15 This result strongly suggests that the
direct HAT of A1 by the C6F5 radical is not operative, consid-
ering that HAT with A1 would occur at an allylic a-amino C–H
bond due to the cumulative stabilization effect of the nitrogen
atom and the olen (Scheme S1†). Next, the standard reaction
was conducted with A1 using CD2Cl2 as the solvent (Scheme
Scheme 2 Mechanistic studies of HAT process.
radical, which undergoes HAT at the C4 position with the C6F5
radical to generate the cyclic dienamine intermediate (A1-diene)
(Scheme 2D). The involvement of A1-radcat as an intermediate
would result in selective functionalization of the allylic struc-
tures, which can provide a more stable allylic a-amino radical
(A1-rad) than the radical intermediate (A1-rad0) derived from
deprotonation of the benzylic position. Thꢀe1thermodynamic
preference of A1-rad to A1-rad0 in 3 kcal mol would result in
a >150 times higher concentration of A1-rad in equilibrium. The
same trend is expected in the corresponding transition states of
the deprotonation steps.17 The observed solvent effect in Table 1
could be derived from the thermodynamically preferred
deprotonation, which is favoured in dichloromethane, as
recently reported by Liu and Ready.17 The formation of double
bonds via HAT in radical species has been demonstrated with
a Co complex,18 a tert-butoxy radical,4b and TEMPO.19 Because
the reactive C6F5 radical can be generated only aer the initial
2
2C). Notably, no C6F5D was detected by H NMR spectroscopy,
suggesting that the formation of a dichloromethyl radical by
HAT between the C6F5 radical and CH2Cl2 does not occur in the
reaction mixture.16
From the experimental observations, together with the
reductive quenching between 3DPAFIPN and A1, it is expected
that the generated amine radical cation (A1-radcat) would expel
the allylic proton (deprotonation) to generate the a-amino
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reductive quenching of the photoexcited 3DPAFIPN by A1, such
a HAT event occurs in a highly selective manner between the
C6F5 radical and A1-rad. This order of the elementary steps
would be key to driving an array of oxidation steps toward the
desired aromatization process. HAT at the C6 position, which
provides a different type of diene (A1-diene0), is a thermody-
namically less favoured pathway (Scheme S2†), and SET
between the C6F5 radical and A1-radcat would not be viable,
based on the calculated SET barrier of the reaction
(31.8 kcal molꢀ1, Scheme S2†). Unfortunately, a number of
attempts to trap the proposed diene via Diels–Alder trapping
with dienophiles were not successful (Scheme S6†), presumably
due to the facile oxidation of A1-diene (Eox (calc.) ¼ 0.43 V vs.
SCE in CH3CN) by 3DPAFIPN for further transformations and
deconstruction of the catalytic cycle by the external dienophiles.
The reaction with in situ generated imine species (A1-imine)
gave only trace amount of B1,20 implying that the formation of
the imine intermediate from A1-rad via HAT or A1-radcat via
halogen-atom transfer and deprotonation is not operating in
this reaction.21 The synergistic SET and HAT processes could
proceed again on the generated A1-diene, performing deproto-
nation on C5 position and HAT on C6 position, to provide the
aromatized product (B1). The involvement of the proposed HAT
pathway was further supported by the reaction with A1-D3
(Scheme 2E), which provided about 1 : 1 ratio of C6F5H and
C6F5D as a result of sequential HAT processes on C4 position of
A1-D3 and C6 position of the corresponding diene intermediate.
The developed reaction provides an N-aryl amine as
a product, but over-reactions of the generated N-aryl amine,
such as the formation of corresponding imines, were not
observed. Because the proposed mechanisms involving SET and
HAT are also possible with N-aryl amines as reactants (Fig. S6†),
it was envisaged that an additional mechanism that discrimi-
nates the starting alkyl allyl amines (A) and the products (B) may
be operative in the reaction. Insight into this aspect of the
mechanism was gained from the reactivity of an aniline-derived
allylic amine substrate (A37), which has a lower oxidation
barrier (Eopx ¼ 0.88 V vs. SCE in CH3CN) than that of the model
amine substrate (A1, Epox ¼ 1.29 V vs. SCE in CH3CN) (Scheme
3A). The conversion of A37 and the formation of C6F5H were
very low under the optimized reaction conditions (Fig. S3†),
implying that the productive catalytic cycle (Scheme 3A, orange
arrow) did not operate efficiently. From the proposed mecha-
nism that includes deprotonation of the amine radical cation, it
was hypothesized that the stability of the amine radical cation
would affect the reaction kinetics. Specically, we focused on
the possibility of back-electron transfer (BET) between the
reduced form of 3DPAFIPN (PCcꢀ) and the amine radical cation
(Scheme 3A, green arrow).
Scheme 3 Involvement of back-electron transfer in the reaction.
conditions (K2CO3).23 However, in the case of the N-aryl amine
radical cation, which is known to have higher stability than the
aliphatic amine radical cation and hence undergoes slower
deprotonation,24 BET can regenerate the starting amine and
3DPAFIPN (Scheme 3A, green arrow). This unproductive cata-
lytic cycle clearly excludes the N-aryl substrate from the
productive cycle, while no consumption of any reagents or the
catalyst happens. The concept of BET in product protection is
well established in the photocatalytic oxygenation of benzene to
phenol, where the electron-rich phenol does not undergo
oxidation due to the facile BET between the aryl radical cation
and the photocatalyst.22a,22b
To verify the effect of the rate of deprotonation of various
amine radical cations on the reaction, an array of N-aryl amines
bearing ortho-substituents and N-substituents were prepared.
Dinnocenzo and co-workers demonstrated the stereoelectronic
effect of N–Ar substituents in the deprotonation of N-aryl amine
radical cations.24c Incorporation of a substituent at the ortho-
position of the aryl group led to structural distortion through
the N–C1 bond, and the structurally-disfavoured conjugation
induced destabilization of the amine radical cation and thus
faster deprotonation (Scheme 3B).24c Inspired by this stereo-
electronic effect on the rate of deprotonation of amine radical
cations, the correlation between the amine reactivity and the
dihedral angle (:C2C1NRN) of the amine radical cation was
investigated with independently prepared N-aryl amine
substrates (Scheme 3C). Notably, aryl allyl amines with large
BET affects the reactivity of a number of visible-light pho-
toredox catalysis, and the control of this elementary step has
been elaborated to improve the reactivity and selectivity.22
When the triplet-state photoexcited 3DPAFIPN is quenched by
the amine substrate, the radical ion-pair is immediately
generated from two neutral species. Immediate and facile
deprotonation of the amine radical cation then occurs via the
desired catalytic cycle (Scheme 3A, orange arrow) under basic
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Fig. 2 Proposed mechanism.
dihedral angles in the corresponding amine radical cations Throughout the photoredox catalytic cycle, both the productive
(A38-Me and A39-Me) were reactive toward CD, producing N,N- pathway (Fig. 2B, black arrow) and the non-productive pathway
diaryl amines (B38-Me and B39-Me) in noticeable yields (28% (Fig. 2B, green arrow) are operative, leading to discriminatory
and 34%, respectively). These results support the involvement activity where the substrates react and the product is preserved in
of BET in the reaction by demonstrating that preventing BET the reaction media. The possibility of halogen bonding between the
could initiate the productive catalytic cycle (Scheme 3A, orange substrate amine (A) and C6F5I was excluded by the absence of
arrow). In the synthesis of N-aryl amines from aliphatic allylic noticeable interaction in the 19F NMR spectra of the mixture
amines, BET is highly advantageous for achieving the targeted (Fig. S15†),26 along with the UV-Vis observation of that the direct
synthesis in an efficient and selective manner by preventing SET via the donor–acceptor complexation and photoinduced elec-
further undesired transformation of the product B (Scheme 3D). tron transfer (PET) do not likely operate in the reaction (Fig. S16†).27
Based on mechanistic studies and previous literature, we
propose an overall mechanism for the photoredox CD of 2-cyclo-
hexenyl amines (Fig. 2A). Transformation of the allylic amine
Conclusions
substrate (A) is initiated by single-electron oxidation by the triplet-
state photocatalyst (3PC) to generate the amine radical cation (A-
radcat), which undergoes facile deprotonation to produce the a-
amino radical species (A-rad). The pentauorophenyl radical
In conclusion, the visible-light photoredox catalytic dehydro-
genation of allylic amines was developed to synthesize invalu-
able N-aryl amines. Synergistic single-electron transfer and
hydrogen-atom transfer enabled controlled dehydrogenation
of the 2-cyclohexenyl amines bearing several reactive sites, thus
affording a wide range of N-aryl amines under mild reaction
conditions. Notably, the protective back-electron transfer
pathway plays a crucial role in achieving the photoredox cata-
lytic dehydrogenation protocol for the synthesis of N-aryl
amines by preventing unwanted side-reactions.
ðC6Fꢁ Þ, which is generated by the subsequent reduction of C6F5I by
5
the reduced form of the photocatalyst (PCcꢀ), abstracts a hydrogen-
atom from another allylic position of A-rad, forming the diene-
amine intermediate (A-diene). With this intermediate, a similar
mechanistic scenario is possible, considering the redox potential of
the dienamine derived from amine A1 (A1-diene, Eox (calc.) ¼ 0.43 V
vs. SCE in CH3CN). The generated dienamine radical cation (A-
dieneradcat) undergoes the facile deprotonation at the C5 position
(DDG (C5 and C6) ¼ ꢀ6.5 kcal molꢀ1, Scheme S3†) to provide the
7p-enaminyl radical, as previously reported in the production of the
5p-enaminyl radical.25 Further HAT by the C6F5 radical of the highly
conjugated enaminyl radical intermediate (A-dienerad) provides an
aromatized product (B). The involvement of a chain-propagating
mechanism for the generation of radical intermediates was
excluded, based on the low quantum yield of 0.08 (Fig. 2B).
Conflicts of interest
There are no conicts to declare.
Acknowledgements
This work was gratefully supported by the National Research
Foundation of Korea (NRF-2019R1A2C2086875; NRF-
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