Photoinduced C(sp3)?N Bond Cleavage Leading to the Stereoselective Syntheses of Alkenes

Article abstract of DOI:10.1002/chem.201900886

Herein we report a versatile Mizoroki–Heck-type photoinduced C(sp³)?N bond cleavage reaction. Under visible-light irradiation (455 nm, blue LEDs) at room temperature, alkyl Katritzky salts react smoothly with alkenes in a 1:1 molar ratio in the presence of 1.0 mol % of commercially available photoredox catalyst without the need for any base, affording the corresponding alkyl-substituted alkenes in good yields with broad functional-group compatibility. Notably, the E/Z-selectivity of the alkene products can be controlled by an appropriate choice of photoredox catalyst.

Full text of DOI:10.1002/chem.201900886

A Journal of
Accepted Article
Title: Photo-Induced C(sp3)–N Bond Cleavage Leading to
Stereoselective Syntheses of Alkenes
Authors: Chao Wang, Masanobu Uchiyama, Ze-Kun Yang, and Ning-
Xin Xu
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
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content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201900886
Link to VoR: http://dx.doi.org/10.1002/chem.201900886
Supported by

10.1002/chem.201900886
Chemistry - A European Journal
COMMUNICATION
Photo-Induced C(sp3)–N Bond Cleavage Leading to
Stereoselective Syntheses of Alkenes
Ze-Kun Yang,[ab+] Ning-Xin Xu,[a+] Chao Wang,*[ab] and Masanobu Uchiyama.*[ab]
Abstract: Here we report a versatile Mizoroki-Heck type photo-
induced C(sp3)–N bond cleavage reaction. Under visible light
irradiation (455 nm, blue LEDs) at room temperature, alkyl Katritzky
salts react smoothly with alkenes in 1 : 1 molar ratio in the presence
of 1.0 mol% of commercially available photoredox catalyst without
the need for any base, affording corresponding alkyl-substituted
alkenes in good yields with broad functional group compatibility.
Notably, the E/Z-selectivity of the alkene products can be controlled
by appropriate choice of the photoredox catalyst.
acids, have become available as alkyl radical precursors for the
photo-redox SET route to form a C(sp3)–C(sp2) bond with
alkenes, expanding the scope of the M-H reaction.
On the other hand, cross-coupling protocols with
amines/anilines and their derivatives,[9-10] especially ammonium
salts[11] as halide analogs, have also been well developed
recently.[12-14] Amine groups occur in many biologically essential
compounds and are widely used in industry for the preparation
of pharmaceuticals and functional materials. The high stability of
amino C–N bonds makes them very resistant to cleavage
reactions.[9] Ammonium salts can be easily prepared from
various amines/anilines, and such C–N bonds exhibit higher
reactivity. However, while aryl ammoniums have proved highly
reactive with transition metal catalysts,[12-13] most alkyl
ammoniums are quite inert with low-valence metal catalysts,[14]
because alkyl C–N species are weak acceptors for an electron
pair or a single electron (SE) from transition metals. In contrast,
owing to the low-lying aromatic π*-orbital, pyridinium salts are
excellent electron acceptors.[15] Pyridinium salts can easily
accept SE to form a neutral radical species, and this reactivity
has been utilized in the development of organic photo-redox
catalysts.[6b] Since 2017, several groups have further extended
the utility of pyridinium salts[15-16] from SE-acceptor to alkyl
radical source, by employing either transition metal catalysis[17]
or photochemical processes.[18] These impressive achievements
indicate that the alkyl radical generation protocol via C–N
cleavage can open up conceptually new synthetic routes. As the
latest development in our work on C–N bond cleavage
protocols,[13] we herein report our results on C(sp3)–N bond
cleavage type M-H reaction with alkyl Katritzky salts via a photo-
redox catalytic process, affording alkyl-substituted alkenes with
high yield and selectivity.[19]
Alkenes are essential building blocks for organic synthesis, and
are ubiquitous in the fields of life science, drug discovery, and
material science. The different configurational isomers (E and Z)
of alkenes usually display distinct physicochemical properties
and physiological activities,[1] and so stereoselective synthesis of
alkenes has long been of great interest to synthetic chemists.
Currently, the Mizoroki-Heck (M-H) reaction,[2] which is a Pd-
catalyzed cross-coupling reaction between alkenes and
aryl/vinyl halides, is regarded as one of the most useful
protocols for the selective synthesis of substituted alkenes.[3]
However, despite the high efficiency and applicability of the Pd-
catalyzed reaction, it has some some limitations. For example,
methodology for cross-coupling by using aliphatic halides,
especially those possessing β-hydrogen, is still limited due to the
occurrence of rapid β-H elimination as a side reaction. Further,
the configuration of the formed C=C bond is determined by the
transition structure at the syn-extrusion step (periplanar -Pd–C–
C–H- 4-membered ring), and hence external control of the E/Z
selectivity by changing the catalyst or ligand is difficult. Thus,
although elegant examples of the Pd-catalyzed reaction
involving alkyl halides have been reported,[4-5] there is still a
need for mechanistically new transformations employing sp3-
hybridized substrates other than halides.
Z-selectivity
Ph
The dramatic advances in photo-redox catalysis in recent
years[6] mean that many single electron-transfer (SET) reactions
that previously required harsh conditions, or afforded low yield or
selectivity, can now be accessed in a mild, efficient and/or
selective manner. Also, in addition to the use of alkyl halides,[7]
new types of aliphatic coupling partners,[8] such as carboxylic
fac-Ir(ppy)3
R1
H
1.0 mol%
R2
R2
Ph
R1
Ph
BF4
Ph
H
H
Ph
O
1.1 eq.
NH2
N
blue LEDs
R1
without
H
facile preparation
BF4
external base
R2
Ph
R1
[Ru(bpy)3](PF6)2
1.0 eq.
1.0 mol%
E-selectivity
Scheme 1. Outline of the current reaction.
[a]
[b]
[+]
Z.-K. Yang,[+] N.-X Xu,[+] Dr. C. Wang, Prof. Dr. M. Uchiyama
Graduate School of Pharmaceutical Sciences, The University of
Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
E-mail: chaowang@mol.f.u-tokyo.ac.jp (C.W.);
Our basic concept was as follows. First, Katritzky salts 1 would
react with the excited photo catalyst (PC) through an SE-redox
process,[18] releasing alkyl radical A and 2,4,6-triphenylpyridine
(through aromatizing homolysis of the C–N bond), together with
oxidized PC•+ species. Alkyl radical A would then add to alkene
2, affording new radical species B that is thermodynamically
more stabile.[7-8] Next, radical B, as a SE reducing agent, would
react with PC•+, to give cation species C with regeneration of PC.
E-mail: uchiyama@mol.f.u-tokyo.ac.jp (M.U.)
Z.-K. Yang,[+] Dr. C. Wang, Prof. Dr. M. Uchiyama
Cluster for Pioneering Research (CPR), Advanced Elements
Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama
351-0198, Japan
These authors contributed equally to this work.
Supporting information for this article is given via a link at the end of
the document.
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10.1002/chem.201900886
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COMMUNICATION
[7h, 18a]
Cation intermediate C then undergoes elimination to form
various electro-donating functional groups, such as OMe (2a-b),
SMe (2c), tBu (2d), and even OH (2e-f) or NH2 (2g) that have an
active proton, were compatible with the phenyl ring of styrene.
Halogens such as F (2h), Cl (2i), and Br (2j), were tolerated as
either a meta- or an ortho-substituent. In most cases, the alkene
products 3aa-3aj were obtained in good yields (up to 99%).
alkene products 3 with the kinetically and thermodynamically
favored E-configuration. Here, the C–C bond-forming step
involves a radical addition step rather than a transition metal-
mediated insertion/extrusion process, thus avoiding the
undesired β-H elimination. On the other hand, although E-
alkenes are thermodynamically more stable than their Z-isomers, Unsubstituted styrene 2k and styrene derivative 2l with a bulky
the uphill E-to-Z isomerization can be efficiently realized
photochemically. Taking account especially of the recently
reported photo-catalytic orthogonal E-to-Z approaches,[20] we
also considered that the E-alkene product might be isomerized
in situ to the Z-form in the presence of a suitable photo-catalyst,
thus enabling control of the E/Z selectivity.
aryl ring could be employed in this reaction without difficulty
(3ak-3al). Further, 1,1- or 1,2-disubstituted alkenes 2m-q proved
to be available for this protocol, providing the tri-substituted
alkene products 3am-3aq in moderate to good yield. Secondly,
the current protocol offers high and controllable stereoselectivity.
When the reactions were carried out in the presence of fac-
Ir(ppy)3 catalyst, Z-isomers of 3 were obtained as the major
products in most cases. Indeed, the Z-selectivity was over 80%
in the reactions of 2c, 2f, 2l, and 2k, and was higher than 90%
when 2a and 2b were used. Notably, when [Ru(bpy)3](PF6)2 was
utilized as the PC, all reactions were E-selective, and only the E-
isomers of 3 were observed in all cases. Interestingly, styrene 2l
with a bulky mesityl group and 1,2-disubstituted alkene 2m
afforded only E-alkene products under both conditions. These
results suggest that the alkenylation step of either fac-Ir(ppy)3 or
[Ru(bpy)3](PF6)2 should afford the E-isomer as the initial product,
and the subsequent E-to-Z isomerization step may be blocked if
the substrates are highly sterically demanding. Under the current
conditions, reactions of aliphatic alkenes (1-hexene, 2-n-butyl-1-
hexene, Z-or E-5-decene, etc.), as well as tri-substituted alkenes
(e.g., triphenylethene), were sluggish. We are now trying to find
suitable conditions to increase the reactivity of these substrates.
H+
Ph
N
H
visible
light
R2
R2
R1
R1
R1
PC*
PC
Ph
C
E-3
Ph
1
photo-induced
isomerization
e
e
PC+
Ph
N
R1
H
PC = Photoredox Catalyst
Ph
R2
R2
R1
R1
Ph
B
A
Z-3
R2
H
2
Scheme 1. Proposed mechanism of the current protocol.
To test this approach, we first focused on the reaction of
Katritzky salt 1a (readily synthesized from phenylalanine) as a
model substrate with p-methoxystyrene 2a (Table 1). The
reaction of 1a (1.0 eq.) with an excess of 2a (2.0 eq.) proceeded
smoothly in the presence of several types of PC (2.5 mol%) in
DMA under visible light irradiation (λmax = 455 nm, blue LEDs) at
room temperature for 12 h, affording 2-alkylstyrene derivative
3aa in good yield. When iridium complexes were used as PCs,
Z-3aa was obtained as the main product (Entries 1-4). In
particular, fac-Ir(ppy)3 delivered Z-selectivity as high as 92% with
87% total yield (Entry 1). Remarkably, the reaction with
[Ru(bpy)3](PF6)2 as the PC gave E-3aa as the sole product in 86%
yield (Entry 4). Next, we evaluated the catalytic reactivity of PCs
in different solvents and found that DMSO was the best for both
fac-Ir(ppy)3 (Entries 5-8) and [Ru(bpy)3](PF6)2 (Entries 9-10).
Performing the reaction in the dark did not afford any product
(Entries 11-12), and only a trace of product was observed in the
absence of PC (Entry 13). Moreover, the reaction of 1a
proceeded with the same high efficiency and selectivity even
when a stoichiometric amount of 2a (1.1 eq.) and a lower PC
loading (1.0 mmol%) were used (Entries 14-15, optimal
conditions). In the case of [Ru(bpy)3](PF6)2, the reaction was
complete within 2 hours (Entries 14). It is also noteworthy that
no external base is needed for this reaction.
Table 1. Screening of reaction conditions.
Ph
Photocatalyst
Ph
(x mol% )
Ar
N
Ph
BF4
+
OMe
+
Ar
R
R
0.1 M in Solvent
MeO2C
blue LEDs, rt., 12 h
Ph
1a (1.0 eq.)
2a (n eq.)
3aa-E
3aa-Z
Entry
n (eq.)
PC (x mol%)e
Solvent
Yieldf
87%
E/Zf
1a
2a
3a
4a
5a
6a
7a
8a
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.1
1.1
[Ir]-1
[Ir]-2
[Ir]-3
[Ru]
[Ir]-1
[Ir]-1
[Ir]-1
[Ir]-1
[Ru]
[Ru]
[Ir]-1
[Ru]
-
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
1.0
1.0
DMA
8 / 92
11 / 89
24 / 76
DMA
79%
58%
86%
73%
89%
0%
DMA
DMA
100 / 0
9 / 91
9 / 91
-
DMF
DMSO
MeCN
MeOH
DMF
0%
-
9a
73%
93%
0 %
0 %
8%
100 / 0
100 / 0
-
10a
11b
12b
13c
14a
15a,d
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
-
100 / 0
14 / 86
100 / 0
[Ir]-1
[Ru]
87%
92%
We next set out to examine the scope of the current reaction.
Taking 1a as a model alkyl radical precursor, we tested a
variety of alkene substrates. To our delight, many were
available for this protocol (Scheme 3). Firstly, the reaction
shows excellent chemo-selectivity, with broad functional group
compatibility and high yield. Under the optimal conditions,
[a] Conditions: 1a (0.20 mmol), 2a (0.40 or 0.22 mmol) and PC (2.5 or 1.0
mol%), solvent (2 mL), irradiation with 36 W blue LEDs, rt., 12 h. [b] In the
dark. [c] Without PC. [d] Reaction was complete within 2 h. [e] [Ir]-1: fac-
Ir(ppy)3; [Ir]-2: [Ir(dtbbpy)(ppy)2](PF6); [Ir]-3: [Ir(dF(CF3)ppy)2(dtbbpy)]
(PF6); [Ru]: [Ru(bpy)3](PF6)2; [f] Determined by 1H-NMR analysis.
Mesitylene was used as an internal standard for determining the yield.
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COMMUNICATION
fac-Ir(ppy)3 (1.0 mol%)
or
[Ru(bpy)3](PF6)2 (1.0 mol%)
R2
R2
Ph
N
R2
R1
R1
Ph
MeO2C
Ph
R1
Ph
BF4
+
+
0.1 M in DMSO
blue LEDs, rt., 12 h
MeOOC
CO2Me
Ph
Ph
2 (1.1 eq.)
1a (1.0 eq.)
3–E
3–Z
tBu
2a
2b
2c
2d
MeOOC
1a
OMe
MeOOC
1a
MeOOC
1a
SMe
MeOOC
1a
Ph
3aa
Ph
3ab MeO
Ph
3ac
Ph
3ad
[Ir(III)]: yield: 82% (E / Z = 8 / 92)
[Ru(II)]: yield: 85% (E only)
[Ir(III)]: yield: 72% (E / Z = 4 / 96)
[Ru(II)]: yield: 74% (E only)
[Ir(III)]: yield: 95% (E / Z = 18 / 82)
[Ru(II)]: yield: 99% (E only)
[Ir(III)]: yield: 68% (E / Z = 39 / 61)
[Ru(II)]: yield: 94% (E only)
F
2j
2e
2f
2h
MeOOC
1a
OH
MeOOC
MeOOC
1a
NH2
MeOOC
1a
OMe
1a
Ph
3ae
3af
Ph
HO
Ph
3ag
Ph
3ah
[Ir(III)]: yield: 86% (E / Z = 46 / 54)
[Ru(II)]: yield: 66% (E only)
[Ir(III)]: yield: 93% (E / Z = 14 / 86)
[Ru(II)]: yield: 77% (E only)
[Ir(III)]: yield: 67% (E / Z = 30 / 70)
[Ru(II)]: yield: 57% (E only)
[Ir(III)]: yield: 95% (E / Z = 41 / 59)
[Ru(II)]: yield: 96% (E only)
Cl
Br
Me
2j
2i
2k
2l
MeOOC
1a
OMe
MeOOC
1a
OH
MeOOC
MeOOC
1a
Me
1a
3aj
Ph
Ph
Ph
3ak
Ph
3al
Me
3ai
[Ir(III)]: yield: 96% (E / Z = 20 / 80)
[Ru(II)]: yield: 89% (E only)
[Ir(III)]: yield: 74% (E / Z = 62 / 38)
[Ru(II)]: yield: 45% (E only)
[Ir(III)]: yield: 71% (E / Z = 15 / 85)
[Ru(II)]: yield: 73% (E only)
[Ir(III)]: yield: 65% (E only)
[Ru(II)]: yield: 73% (E only)
MeOOC
1a
2m
OMe
MeOOC
1a
2n
with 1,2-disubstituted alkene
with styrene derivatives
Ph
3am
Ph
3an
Me
B
[Ir(III)]: yield: 88% (E only)
[Ru(II)]: yield: 55% (E only)
[Ir(III)]: yield: 68%
[Ru(II)]: yield: 77%
MeO
F3C
2p
2q
2o
MeOOC
1a
OMe
MeOOC
OMe
MeOOC
1a
OMe
with 1,1-disubstituted alkene
1a
B
3ap
Ph
3ao
Ph
Ph
3aq
[Ir(III)]: yield: 92%
[Ru(II)]: yield: 98%
[Ir(III)]: yield: 78% (E / Z = 63 / 37)
[Ru(II)]: yield: 78% (E / Z = 93 / 7)
[Ir(III)]: yield: 95% (E / Z = 42 / 58)
[Ru(II)]: yield: 89% (E / Z = 83 / 17)
Scheme 3. Reaction of Katritzky salt 1a with various alkene substrates 2.
Reactions of other alkyl Katritzky salts were also examined
(Scheme 4). With the use of styrene 2a, substrates synthesized
from amino acids such as alanine (1b), isoleucine (1c), valine
(1d), and glycine (1e) were successfully converted into the
corresponding products with Z- or E- selectivity (3ba-3ea).
Notably, Katritzky salt 1e prepared from glycine, which
generates a primary carbon radical, is available for this reaction.
Similarly, the reaction using Katritzky salt with lactone structure
1f or cyano group 1g also took place selectively, giving the
corresponding E- or Z-alkene product 3fa-3ga with good yield
and selectivity. Moreover, treatment of benzyl radical precursors
1h and 1i with 1,1-diphenylethylene 2q under the standard
conditions also proved to be effective, and tri-substituted
alkenes 3hq and 3iq were obtained, respectively, each in
around 70% yield. If the carbon radical has no electron-
withdrawing group at the α-position, the energy level of its
SOMO will be higher than those derived from 1a-g.[21] Hence,
such radicals are more nucleophilic and will interact more
strongly with electrophilic alkenes that have low-lying LUMOs.
Accordingly, we envisioned that the current catalytic cycle might
be further expanded (Scheme 5), that is, nucleophilic radical A
may first add to electron-deficient alkene 2’ to form a new
electrophilic radical A’. This radical species would then react
with alkene 2 to generate a more stabilized radical B’, which
would go through an SE-redox process with PC•+ to give cation
C’, finally leading to the three-component coupling product.
Gratifyingly, when we used [Ir(ppy)2(dtbbpy)](PF6) as the PC, the
anticipated three-component radical reaction proceeded
smoothly, affording tri-substituted alkenes 4 in moderate yields.
Such selective tandem C–C bond formation processes not only
provide solid support for the proposed mechanism, but also offer
another example of the potential synthetic utility of such photo-
redox reactions, due to their high reaction efficiency. We are
currently trying to further modify this transformation.
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10.1002/chem.201900886
Chemistry - A European Journal
COMMUNICATION
current reaction.[22] We also investigated the Z/E-selectivity of
this reaction. As shown in Scheme 6-b, pure E- and Z-isomers of
3aa were irradiated in the presence of fac-Ir(ppy)3 or
[Ru(bpy)3](PF6)2 under the standard conditions. After 12 hours,
90% of E-3aa had isomerized to the Z-form (with Ir-PC), while
no isomerization of Z-3aa occurred (with Ru-PC). Such E/Z
isomerizations proceed through triplet-triplet energy transfer
processes,[20] which require a sufficiently high triplet energy of
PC. In a recent report,[20f] Weaver and co-workers compared the
different emissive energies of excited state PC ([Ru(bpy)3]2+:
46.5 kcal/mol,[6d] Ir(ppy)3: 55.2 kcal/mol[23a]) with the triplet
energies of some styrene derivatives (ca. 51-53 kcal/mol);[23b]
the results indicated that Ru-catalyzed isomerization should be
rather endergonic and slow, while Ir-catalyzed isomerization is
energetically favorable. We next examined the time profile of
these reactions (Scheme 6-c).[24] The results suggested that
formation of 3aa peaked within 2 hours, and only fac-Ir(ppy)3
promoted the isomerization to the Z-isomer, which proceeded
gradually for about 10 hours. These results clearly explain how
the Z/E-selectivity is determined by the use of different PCs.
fac-Ir(ppy)3 (1.0 mol%)
or
[Ru(bpy)3](PF6)2 (1.0 mol%)
Ph
R1
R2
R
N
Ph
+
OMe
0.1 M in DMSO
blue LEDs, rt., 12 h
BF4
1 (1.0 eq.)
Ph
2a or 2q (1.1 eq.)
2a
2a
MeOOC
1c
OMe
MeOOC
OMe
1b
3ca
Me
3ba
Me
Me
[Ir(III)]: yield: 73% (E / Z = 25 / 75)
[Ru(II)]: yield: 78% (E only)
[Ir(III)]: yield: 67% (E / Z = 45 / 55)
[Ru(II)]: yield: 65% (E only)
2a
2a
MeOOC
1d
OMe
EtOOC
OMe
1e
Me
3da
Me
3ea
[Ir(III)]: yield: 61% (E / Z = 12 / 88)
[Ru(II)]: yield: 65% (E only)
[Ir(III)]: yield: 62% (E / Z = 11 / 89)
[Ru(II)]: yield: 27% (E only)
O
2a
2a
OMe
NC
1g
Ph
OMe
O
1f
3ga
3fa
[Ir(III)]: yield: 77% (E / Z = 11 / 89)
[Ru(II)]: yield: 89% (E only)
[Ir(III)]: yield: 83% (E / Z = 25 / 75)
[Ru(II)]: yield: 84% (E only)
MeO
MeO
Ph
(a)
TEMPO (2.0 eq.)
PC (1.0 mol% )
MeOOC
Ph
MeOOC
Ph
N
Ph
BF4
+
OMe
O
Me
0.1 M in Solvent
N
Me
blue LEDs, rt., 12 h
Ph
Me
Me
2q
2q
OMe
OMe
1a (1.0 eq.)
2a (1.1 eq.)
F
1h
1i
Detected by ESI-MS
[Ir(III)]: yield: 69%
[Ru(II)]: yield: 69%
[Ir(III)]: yield: 69%
[Ru(II)]: yield: 71%
PC: fac-Ir(ppy)3 or [Ru(bpy)3](PF6)2
3hq
3iq
3aa (Not Detected)
(b)
fac-Ir(ppy)3
no E/Z or Z/E isomerization
was observed without [Ir] or [Ru]
(5 mol%)
90% Z : 10% E
Scheme 4. Reaction of various Katritzky salts 1.
OMe
DMSO (0.1M), blue LEDs, rt., 12 h
MeOOC
Ph
OMe
COOMe
EWG
Ar
E-3aa
Z-3aa
2’
2
EWG
Ph
[Ru(bpy)3](PF6)2
(5 mol%)
R
EWG
Ar
R
R
Ph
N
B’
A
A’
yield
(c)
100%
Ph
visible light
90%
80%
70%
60%
50%
40%
30%
20%
10%
Ph
e
e
PC
Ph
EWG
R
PC
3aa
R
N
Ph
BF4
Ar
[Ir]
[Ir]
total
Z
C’
Ph
1
[Ir]
E
H+
condition: [Ir(ppy)2(dtbbpy)](PF6) (2.0 mol%), DMSO (0.1 M), r.t., 48 h, blue LED
[Ru]
total
1j
1j
2s
1j
2t
1k
2t
2r
Me
CN
COOCH2Ph
COOEt
Ar
COOEt
Ar
0%
0
2
4
6
8
10
12
14
16
18
20
Ph
Ar
Ar
Ar
reaction time (h)
2q
2q
2q
2q
Ar
Ar
Ar
4jrq
yield: 51%
4jsq
yield: 58%
4jtq
yield: 53%
4ktq
yield: 61%
Scheme 6. Mechanistic study.
Scheme 5. Mechanistic design and experimental results for three-component
alkenylation reactions.
In summary, we have developed an efficient and selective
protocol for alkene synthesis via photo-redox-mediated C(sp3)–N
bond cleavage and C(sp3)–C(sp2) bond formation under mild
conditions, using commercially available PCs and alkene
substrates, as well as naturally abundant amines. The reaction
To further examine the radical mechanistic pathway, we
performed the reaction of 1a and 2a in the presence of TEMPO
under the standard conditions (Scheme 6-a). The formation of
3aa was completely suppressed, and the TEMPO-alkyl radical
adduct was detected, strongly suggesting that generation of the
alkyl radical intermediate took place in the initial step of the
proceeds through
a
photo-catalytic SET process, and,
importantly, the Z/E-selectivity of the alkene products can be
efficiently controlled simply by choosing the appropriate PC. The
current results not only provide a valuable complement to the
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original Mizoroki-Heck reaction, but also exemplify a promising
method for functionalization of the amino C–N bond without the
need for traditional TM catalysts. Work to extend the scope of
this reaction and to apply it for the synthesis of a range of
functional molecules is in progress.
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Acknowledgements
This work was supported by a JSPS Grant-in-Aid for Scientific
Research on Innovative Areas (No. 17H05430), JSPS KAKENHI
(S) (No. 17H06173) (to M. U.), and Grant-in-Aid for Scientific
Research (C) (No. 18K06544, C.W.).
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Keywords: C–N bond cleavage • alkene • amine • Mizoroki-
Heck reaction • photoredox catalysis
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(Scheme 6-a), indicating that oxidative quenching is the major route in
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Just before we were ready to submit our present manuscript, Xiao, Lu
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COMMUNICATION
fac-Ir(ppy)3
R1
Ze-Kun Yang, Ning-Xin Xu, Chao
Wang,* and Masanobu Uchiyama*
H
1.0 mol%
R2
R2
Z-selectivity
E-selectivity
Ph
R1
Ph
H
H
1.1 eq.
without
N
blue LEDs
H
BF4
Page No. – Page No.
external base
R2
Ph
R1
Ru(bpy)3(PF6)2
1.0 mol%
Photo-Induced C(sp3)–N Bond
Cleavage Leading to Stereoselective
Syntheses of Alkenes
1.0 eq.
Under visible light irradiation (455 nm, blue LEDs) at room temperature, alkyl
Katritzky salts react smoothly with alkenes in 1 : 1 molar ratio in the presence of 1.0
mol% of commercially available photoredox catalyst without the need for any base,
affording corresponding alkyl-substituted alkenes in good yields with broad
functional group compatibility. Notably, the E/Z-selectivity of the alkene products
can be controlled by appropriate choice of the photoredox catalyst.
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