Visible light induced photocatalytic conversion of enamines into amides

Article abstract of DOI:10.1055/s-0034-1378205

A series of enamines were photocatalytically cleaved to produce amide products under simple visible-light irradiation from a 45 W household light bulb. Mechanistically, the reactions appear to involve photosensitized formation of a singlet oxygen intermediate and a subsequent [2+2] cycloaddition event. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0034-1378205

1626▌
LETTER
lVettiersible Light Induced Photocatalytic Conversion of Enamines into Amides
Photocatalytic Conversion of Enamines into Amides
Jing Li, Shunyou Cai, Jietao Chen, Yaohong Zhao, David Zhigang Wang*
Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University,
Shenzhen University Town, Shenzhen 518055, P. R. of China
Fax +86(755)26032702; E-mail: dzw@pkusz.edu.cn
Received: 22.03.2014; Accepted after revision: 04.05.2014
Abstract: A series of enamines were photocatalytically cleaved to
produce amide products under simple visible-light irradiation from
a 45 W household light bulb. Mechanistically, the reactions appear
to involve photosensitized formation of a singlet oxygen intermedi-
ate and a subsequent [2+2] cycloaddition event.
standard conditions
O
Ru(bpy)3Cl2⋅6H2O (2.5 mol%)
N
N
Cs2CO3 (1.00 equiv), O2 balloon
MeCN, r.t., 16 h, visible light
(45 W household bulb)
2
Key words: photochemistry, catalysis, enamines, amides
1
87% yield
O
O
There has been a recent increase in the appreciation of vis-
ible light induced photoredox catalysis by the chemical
community.1 Among the extensive range of reactivities
that have been described, most rely mechanistically on the
single-electron oxidant nature of the catalyst that is most
frequently used: tris(bipyridyl)dichlororuthenium hexa-
hydrate [Ru(bpy)3Cl2·6H2O]. This oxidant is capable of
initiating electron abstraction, thereby generating reactive
radical species that undergo subsequent synthetic events.2
Conceivably, if new reaction modes could be strategically
merged with visible-light photoredox catalysis, then the
range of synthetic applications of the latter would be sig-
nificantly broadened and enriched. In this context, we
were particularly motivated by the possibility of combin-
ing photoredox catalysis with the rich chemistry of singlet
oxygen chemistry3 to realize some new reactivities. It is
clear that a visible light induced entry to singlet oxygen
intermediates would represent a change in the convention-
al protocol, which uses UV radiation from, for example,
high-pressure mercury lamps,3 thereby providing unusu-
ally benign reaction conditions and an improvement in ef-
ficiency.
photosensitized
formation of 1O2
N
– acetone
A
Scheme 1 Visible light induced photocatalytic cleavages of enamine
1 to give formamide 2, and a possible [2+2] cycloaddition pathway in-
volving singlet oxygen
The possibility that the reaction might have proceeded
through a singlet oxygen (1O2)-initiated [2+2] cycloaddi-
tion via intermediate A emerged from a set of interesting
experimental observations outlined below (Scheme 2).
Although direct attempts to isolate or to intercept interme-
diate A failed in the enamine system described above, we
were able to identify the corresponding intermediate in the
protected silyl enol ether structure 3 when this was sub-
jected to the standard reaction conditions described above.
The reaction of 3 progressed cleanly in the presence of ce-
sium carbonate to give the enone product 5 in 77% isolat-
ed yield and, notably, no C=C bond-cleavage product was
found to be present. We surmised the involvement of a re-
gioisomeric mixture of ene-type allylic hydroperoxide
products B and C, formed through participation of singlet
oxygen, echoing a recent report in the literature on the for-
mation of singlet oxygen under visible-light stimulation,
and we probed this reaction by using 4-(N,N-dimethyl-
amino)pyridine as an alternative base or triethyl phosphite
as an alternative reductant in place of cesium carbonate.4
The reaction in the presence of 4-(N,N-dimethylami-
no)pyridine resulted in the formation of enone 5 in 43%
yield and the new enone 4 in 32% yield, whereas the reac-
tion in the presence of triethyl phosphite gave enone 5 in
41% yield together with allylic alcohol 6 in 30% yield.
Strikingly, the structural footprints of 4 and 6 are strongly
indicative of their formation from the corresponding allyl-
ic hydroperoxide precursor B, whereas the formation of
enone 5 appears to be directly attributable to the other pre-
cursor C. Furthermore, the reaction ceased to work when
1,4-diazabicyclo[2.2.2]octane (DABCO), known to be an
After numerous attempts, we discovered that the synergis-
tic action of 2.5 mol% of Ru(bpy)3Cl2·6H2O photocata-
lyst, one equivalent of cesium carbonate base, and visible
light irradiation from a 45 W household light bulb for 16
hours at room temperature in acetonitrile as the solvent
under an oxygen atmosphere supplied by a balloon (here-
after referred as the standard conditions), enamine 1
(Scheme 1) was smoothly converted into the formamide
product 2 in 87% yield (quantitative if determined by 1H
NMR spectroscopy with naphthalene as an internal refer-
ence). We confirmed that the reaction did not occur in the
absence of either visible-light irradiation or the photocat-
alyst, and was retarded when an atmosphere of dry air was
used in place of oxygen from the balloon.
SYNLETT 2014, 25, 1626–1628
Advanced online publication: 05.06.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0034-1378205; Art ID: St-2014-w0247-l
© Georg Thieme Verlag Stuttgart · New York

LETTER
Photocatalytic Conversion of Enamines into Amides
1627
effective quencher of singlet oxygen,5 was deliberately amine 7a and its various analogues 7b–e bearing methyl
added to the system under otherwise identical conditions.6 substituents on each of the three regioisomeric α-, β-, and
Note that Friedrich7 and Turro8 and their respective co- γ-positions were converted into the corresponding for-
workers have previously demonstrated similar reaction mamides 8a–e in 79–89% yield. The lone pair on the ox-
pathways with a high-pressure mercury lamp as the UV ygen of the morpholine ring did not appear to impede the
source; the current discovery therefore represents a signif- reaction, as the morpholine derivative 8f was obtained in
icantly improvement in terms of operational safety and 83% yield. The pyrrolidine group, presumably because of
practical usefulness.
its allylic strain, showed a significantly reduced reactivity,
and the corresponding product 8g was obtained in 40%
yield. The presence of linear aliphatic groups in for-
mamides 8i and 8j appeared to be advantageous in com-
parison with the branched substitution in 8h, possibly as a
result of the difference in bulk.
regioisomeric ene intermediates
OTBS
TBSO
OOH
O
OTBS
OOH
Cs2CO3
(1 equiv)
1O2
Next, we applied the protocol to the ketone-derived en-
amine substrates 9a–d, and in each case we obtained the
corresponding amide 10a–d in high isolated yield (82–
99%) under the standard conditions. Both, the aliphatic
keto amide 10a and the aromatic keto amides 10b–d could
be used as substrates without loss of reaction efficiency.
These results, in conjunction with those shown in Scheme
3 illustrate the ability of this new method to provide a sim-
ple route for amide synthesis. Note that such transforma-
tions have previously relied on promotion by metal-based
oxidants.10
+
O
O
77%
Scheme 1
conditions
O
O
O
O
O
O
B
C
5
3
(EtO)3P
(2 equiv)
DMAP
(0.10 equiv)
32%
30%
41%
43%
O
OTBS
OTBS
O
OH
O
O
O
O
O
O
O
N
O
N
standard
conditons
5
6
4
Scheme 2 Experimental observations supporting the visible light
stimulated formation of singlet oxygen species
R4
R3
O
R3
9
10
Next, we examined the reaction of a range of enamines
7a–g under the standard conditions (Scheme 3). All un-
derwent smooth C=C bond-cleavage reactions to give the
corresponding formamides 8 in good isolated yields.9
Both the cyclic enamines 8a–g and the acyclic enamines
8h–j were suitable substrates. The piperidine-derived en-
O
N
O
O
N
O
N
N
O
O
O
O
Cl
10a: 86%
10b: 82%
10c: 83%
3 = 4-MeC6H4
R4 = H
10d: 99%
3 = 4-ClC6H4
R4 = H
R
R
3 = Et
R3 = Ph
R
R
4 = Me
R
4 = H
standard
R1
R1
R2
O
conditons
N
N
Scheme 4 Formations of amides by means of visible light enabled
R2
C=C bond cleavage of ketone-derived enamines
8
7
In summary, we have developed direct enamine-to-amide
conversion facilitated by visible-light photoredox cataly-
sis. The method is fairly simple and can be readily imple-
mented on widely available materials. It constitutes a very
useful formal functionality metathesis from a C=C bond
to a C=O bond, synthetically connecting significant en-
amine and amide structures. The transformation has been
shown to proceed through an interesting visible light sen-
sitized formation of a singlet oxygen species that subse-
quently initiates a [2+2] cycloaddition event and ring
fragmentation. Given the usefulness of this new method
and the importance of amide-bond formation, the work
should contribute to the arsenal of the practicing chemist.
O
O
O
O
O
O
N
N
N
N
N
8a: 82%
8b: 83%
N
8c: 79%
8d: 89%
8e: 79%
O
O
O
O
N
N
N
O
N
8f: 83%
8g: 40%
8h: 51%
8i: 89%
8j: 79%
Scheme 3 Formation of formamides by means of visible light in-
duced C=C bond cleavage of enamines
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1626–1628

1628
J. Li et al.
LETTER
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Acknowledgment
Financial support was generously provided by the National Science
Foundation of China (grants 20872004 and 20972008 to DZW), the
National 973 Project from the State Ministry of Science and Tech-
nology of China, the Shenzhen Bureau of Science, Technology and
Information, and the Shenzhen Shuang Bai Project.
Supporting Information for this article is available online
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