Visible-light-promoted C-C bond cleavage: Photocatalytic generation of iminium ions and amino radicals

Article abstract of DOI:10.1002/anie.201202880

Photoscissors: Structurally variable and synthetically robust iminium ions and amino radicals species could be simultaneously generated by visible-light-promoted photoredox cleavage of the C-C bonds in simple vicinal diamine precursors under very mild reaction conditions. Copyright

Full text of DOI:10.1002/anie.201202880

Angewandte
Chemie
DOI: 10.1002/anie.201202880
Redox Chemistry
À
Visible-Light-Promoted C C Bond Cleavage: Photocatalytic
Generation of Iminium Ions and Amino Radicals**
Shunyou Cai, Xinyang Zhao, Xinbo Wang, Qisong Liu, Zigang Li,* and David Zhigang Wang*
Although the use of photons as reagents has enjoyed an
incredibly rich history,[1] the use of photons of red-shifted
wavelengths, particularly those extending into what is known
as the visible region (i.e., wavelengths ranging from 380 nm to
750 nm), in the context of promoting synthetically attractive
organic transformations has attracted considerable attention
only very recently.[2] Thanks to the pioneering work from the
groups of MacMillan,[3] Yoon,[4] Stephenson,[5] and others,[6]
this field has already demonstrated outstanding accomplish-
ments and holds promise for uncovering new catalysis
concepts and synthetic applications. Such efforts would most
likely be fueled and accelerated in the future by the increasing
demand for developing environmentally benign chemical
processes with reduced energy consumption, as well as by the
latest advancements in commercializing green light sources
such as organic light-emitting diodes (OLEDs).[7] Not surpris-
ingly, as organic compounds generally cannot absorb visible-
light, the use of visible light as an effective means to initiate
organic reactions must require a photosensitization strategy.
Such sensitizers function as useful photocatalysts, the most
widely employed example being a ruthenium(II)–polypyri-
dine complex such as [Ru(bpy)3Cl2] (bpy = bipyridine).[8] As
photocatalysts with suitable photoredox potentials and their
commercial availabilities are both highly limited, it is thus
readily recognizable that the success of unlocking the full
potential of visible-light photocatalysis for synthetic reactions
of broad utility lies in the identification of efficient method-
ologies for the convenient photocatalytic generation of some
of the most versatile reactive species, but with the aid of only
a few known sensitizers.
production of structurally robust iminium ion or radical
intermediates, and preferably, in a one-pot and controllable
fashion. We believe that the ability of accessing such
intermediates having variable substituents or structurally
editable functionalities would ensure the “freedom-of-oper-
ation” to be conveniently practiced while merging them into
intended catalysis cycles. In this context, it should be high-
lighted that the groups of Stephenson, Xiao, and Rueping
À
have described significant examples of oxidative C H func-
tionalizations through in situ generation of iminium ions
under visible-light photoredox conditions (Scheme 1).[5b,d,6]
Among the synthetic chemistsꢀ arsenal, iminium ions[9]
and radicals[10] clearly stand out as reactive intermediates of
major significance. The goal that considerably motivates us is,
thus, to devise and possibly implement new visible-light-
promoted photocatalysis strategies which would allow facile
Scheme 1. Design concept for visible-light-promoted photocatalytic
À
C C bond cleavage of the substituted the 1,2-diamine A which leads
to simultaneous generation of the structurally variable iminium ion C
and amino radical D as reactive intermediates. [O] denotes an oxidant,
and * denotes a photoexcited state.
[*] S. Y. Cai, X. Y. Zhao, X. B. Wang, Q. S. Liu, Prof. Dr. Z. G. Li,
Prof. Dr. D. Z. Wang
However, in nearly all of these reported cases, the reactivities
appeared to be closely associated with N-aryl tetrahydroiso-
quinolines and their structurally related substrates. In the
outlined mechanisms, the formation of putative iminium ions
from these structures apparently benefited from the stabili-
zation effects of the aryl substituents, in which the loss of
a hydrogen atom from the corresponding amine radical cation
precursor is significantly driven by charge delocalization
Key Laboratory of Chemical Genomics
School of Chemical Biology and Biotechnology
Shenzhen Graduate School of Peking University
Shenzhen University Town, Shenzhen, 518055 (China)
E-mail: zgli@pkusz.edu.cn
dzw@pkusz.edu.cn
[**] We thank the National Natural Science Foundation of China (Grants
20872004 and 20972008 to D.Z.W. and 21102007 to Z.G.L.), the
national “973 Project” of the State Ministry of Science and
Technology, the Shenzhen Bureau of Science and Technology, and
the Shenzhen “Shuang Bai Project” for financial support.
=
along the trans aryl–C N–aryl unit. In addition, MacMillan
an co-workers[3a] and Reiser and co-workers[6j] had reported
the generation of a-amino radicals from structurally related
À
N-aryl substrates for reactions involving C H arylations and
cyclizations, respectively.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201202880.
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With the objective of discovering new and broadly
applicable scenarios for efficient generation of structurally
variable iminium ions (and other useful reactive intermedi-
ates) with visible-light photoredox catalysis, as shown in
Scheme 1, we envisioned that a simple substituted 1,2-
diamine such as A might constitute a reasonable starting
point. The hypothesis is that in the presence of both visible
light and an external oxidant, the {Ru2+-[Ru2+]*-Ru1+} redox
cycle would catalytically abstract an electron from the
nitrogen lone pair in A, thus converting it into the radical
cation species B. The presence of a b-nitrogen heteroatom in
close proximity to the resultant N-centered radical cation
would subsequently induce reorganization of electron den-
Oxygen apparently functioned as the terminal oxidant as the
formation of 3 was inhibited when the reaction was run under
a nitrogen atmosphere.[11]
In addition, the amino radical pathway was directly
detected by visible-light-induced free-radical photopolymeri-
zation of 2-hydroxyethylacrylate (HEA; 4; Scheme 1) in the
presence of 0.1 mol% of the photocatalyst and 10 mol% of
TMEDA; a tube (20 mL) of the neat liquid monomer
solidified to form polymer 5 after 8 hours of exposure to
light. The dimethylamino radical attached to the polymer
chains showed NMR resonances at approximately d =
2.30 ppm.[12] It is significant that, unlike many other free-
radical polymerization systems which suffer severely from O2
inhibition effects, the open-flask protocol described herein
functioned effectively under an atmosphere of air. Photo-
polymerizations of olefinic monomers initiated by amino
radicals serve as the cornerstone of what is known as the UV-
curing industry,[13] thus a visible-light-enabled production of
such reactive species offers significant energy-saving and
environmental advantages over traditional methods which
employ high-pressure Hg lamps or metal halide lamps.
While the visible-light-promoted photopolymerization[14]
clearly warrants further studies, we decided to focus on
investigating the reactivities arising from iminium ion species.
As summarized in Scheme 3, a range of nitro substrates (6)
were found to undergo efficient electrophilic trapping by the
À
sities in B, and lead to the cleavage of the central C C bond as
well as concomitant formation of both the iminium ion C and
a-amino radical D. As a wide range of vicinal diamines A
bearing multiple substitutions, that is, R1 to R8, are readily
available, it could well be anticipated that this design concept,
if successful, would provide a highly robust and visible-light-
enabled entry to a plethora of new transformations associated
with electrophilic or nucleophilic properties of the reactive
species C and D.
Fortunately, this design scenario was indeed found to be
viable. As shown in Scheme 2, upon exposure to a household
LED bulb (36 W), the NO2-substituted substrate 1 reacted
=
Me2N CH2 iminium ion that was photocatalytically gener-
ated in situ from TMEDA (10 equiv) to give the correspond-
ing aza-Henry products 7 in good to excellent yields upon
isolation. The reaction setup, employing a cold light source
such as a household LED bulb at room temperature and
À
Scheme 2. Visible-light-promoted photocatalytic C C bond cleavage of
Me2NCH2CH2NMe2. a) Formation of an iminium ion for aza-Henry
reaction. b) Formation of an amino radical for photopolymerization.
with tetramethylethanediamine (TMEDA; 2) in the presence
of a catalytic amount (5 mol%) of the photocatalyst [Ru-
(bpy)3]Cl2·6H2O under a balloon of oxygen to give the aza-
Henry product 3, after 48 hours at room temperature, in 27%
yield upon isolation. The product yield and reaction efficiency
could be readily improved by employing the diamine 2 in
excess, thus 85% yield was obtained after 36 hours when
10 equivalents of 2 was used. The choice of solvent markedly
influenced the reaction, and MeCN was found to be optimal
in terms of achieving a high product yield. Other solvents
examined, such as DMF, CH2Cl2, EtOH, and NMP, produced
3 in much lower yields (25–40%) under otherwise identical
reaction conditions, while no reaction and decomposition
occurred when using 1,2-dichloroethane and trifluoroethanol,
respectively. Control experiments conducted in the absence of
either the photocatalyst or visible-light exposure showed no
reaction, thereby confirming the operation of a photoredox
catalysis cycle towards efficient iminium ion generation.
Scheme 3. Visible-light-promoted aza-Henry reactions by means of the
À
photocatalytic C C bond cleavage of Me2NCH2CH2NMe2. Yields are of
the isolated product.
2
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under neutral conditions, was both operationally simple and
environmentally benign. Substrate aryl rings bearing an
electron-donating substituent (7b and 7 f–h), electron-with-
drawing substituent (7c–d), more conjugation (7e), or
heteroatoms (7i–j) all gave the expected products with
comparable yields (61–91%), except in the case of 7d
(42%) wherein the presence of a strongly electron-with-
drawing NO2 group appeared to impact negatively on the
reaction efficiency. The purely aliphatic substrate 7k also
worked smoothly (68%). The increased steric size of the
benzylic R2 group in 7 f–h imposed little influence on the
reaction diastereoselectivities (1.3:1 to 1.5:1), but did some-
what slow down the reactions as similar product yields (84–
87%) were obtained with prolonged reaction times. Since the
NO2 group in 7 could be readily reduced to NH2 or oxidized to
a carbonyl group by conventional protocols,[15] the present
discovery serves as a useful methodology for the facile
preparation of functionalized vicinal diamines or a-amino
ketones.
was isolated was exclusively 16 (58%). These findings
collectively hint at the exciting possibilities for fine-tuning
of the reactivities, as well as selectivities of these synthetically
attractive intermediates.
In summary, by employing simple vicinal diamines as new
precursors of photoexcited radical cations, we were able to
record some fascinating examples of the visible-light-pro-
a
b
À
moted photoredox catalytic cleavage of strong C C bonds.
The discovery enables structurally versatile and synthetically
robust iminium ions and amino radical species to be simulta-
neously generated under exceptionally mild reaction condi-
tions, thereby bringing about practically useful reactivities in
such important contexts as aza-Henry condensations and
radical photopolymerizations. Given the established signifi-
cance of such reactive intermediates in modern synthetic
transformations,[14] it could well be anticipated that such
a visible-light-initiated photoredox catalysis approach would
allow reactions of much broader scope to be tackled in
a convergent and operationally simple manner.
With 8 as a representative substrate, similar reactions
proceeded with other iminium ion precursors such as 9 and 11
(5 equiv, Scheme 4), albeit with lower efficiency, thus gen-
erating the aza-Henry-type products 10 and 12, respectively,
Received: April 15, 2012
Revised: June 4, 2012
Published online: && &&, &&&&
À
Keywords: amines · C C activation · photochemistry · radicals ·
ruthenium
.
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À
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material.
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À
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Communications
Redox Chemistry
S. Y. Cai, X. Y. Zhao, X. B. Wang, Q. S. Liu,
Z. G. Li,* D. Z. Wang*
&&&& — &&&&
À
Visible-Light-Promoted C C Bond
Cleavage: Photocatalytic Generation of
Iminium Ions and Amino Radicals
À
Photoscissors: Structurally variable and
synthetically robust iminium ions and
amino radicals species could be simulta-
neously generated by visible-light-pro-
moted photoredox cleavage of the C C
bonds in simple vicinal diamine precur-
sors under very mild reaction conditions.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!