Visible-light-mediated addition of α-aminoalkyl radicals generated from α-silylamines to α,β-unsaturated carbonyl compounds

Article abstract of DOI:10.1039/c2cc32745g

Visible-light-mediated addition of α-aminoalkyl radicals generated from α-silylamines to α,β-unsaturated carbonyl compounds using a photoredox catalyst is developed. We also succeeded in the isolation of a silyl enol ether as a primary product of the photochemical reaction.

Full text of DOI:10.1039/c2cc32745g

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COMMUNICATION
Visible-light-mediated addition of a-aminoalkyl radicals generated from
a-silylamines to a,b-unsaturated carbonyl compoundsw
Yoshihiro Miyake, Yuya Ashida, Kazunari Nakajima and Yoshiaki Nishibayashi*
Received 18th April 2012, Accepted 16th May 2012
DOI: 10.1039/c2cc32745g
Visible-light-mediated addition of a-aminoalkyl radicals generated
from a-silylamines to a,b-unsaturated carbonyl compounds using a
photoredox catalyst is developed. We also succeeded in the isolation
of a silyl enol ether as a primary product of the photochemical
reaction.
Oxidative transformation of amines is one of the most important
methods for conventional synthesis of nitrogen-containing
compounds, which are useful building blocks in various
bioactive compounds and electronic materials.1 a-Aminoalkyl
radicals formed by single electron oxidation of amines are
considered to be reactive intermediates,2–4 but their synthetic
Scheme 1 Photocatalytic addition of a-aminoalkyl radicals generated
from a-silylamines to a,b-unsaturated carbonyl compounds.
a-aminoalkyl radicals using a transition metal polypyridyl
complex as a photoredox catalyst.15 In fact, we have found
the visible-light-mediated addition of a-aminoalkyl radicals
generated from a-silylamines to a,b-unsaturated carbonyl
compounds and have also succeeded in the isolation of a silyl
enol ether as a primary product of the photochemical reaction
(Scheme 1). Preliminary results are described here.
utilization has been quite limited because the rapid oxidation
of a-aminoalkyl radicals to iminium ions is more favorable
under thermal conditions.5
In sharp contrast, single electron oxidation of amines via
photoinduced electron transfer is expected to be a suitable
method for generation and synthetic use of a-aminoalkyl
radicals.2a,6–12 Recently we have reported visible-light-mediated
addition of a-aminoalkyl radicals to electron deficient alkenes
and have also found that this reaction proceeds via a sequential
redox pathway.6 On the other hand, a-silylamines are known to
be oxidized readily rather than conventional amines13 and are
alternative candidates for generating a-aminoalkyl radicals
along with desilylation.10,14 Since Mariano’s group reported
addition of a-aminoalkyl radicals generated from a-silylamines
to a,b-unsaturated ketones under UV irradiation,10f,g the
utilization of a-silylamines for addition to alkenes has been
extensively studied.10–12 When 9,10-dicyanoanthracene (DCA)
and 1,4-dicyanonaphthalene (DCN), which absorb longer UV
to visible-light, were used as photosensitizers, addition reactions to
alkenes were found to proceed smoothly, but, applicable substrates
were limited to trialkylamines10a,c,d,11 and dialkylamides12 in
these reaction systems. As an extension of our study on the
visible-light-mediated utilization of a-aminoalkyl radicals,
we have now envisaged use of a-silylamines as precursors for
At first, we carried out the reaction of diphenyl(trimethyl-
silylmethyl)amine (1a) with 1.5 equiv. of 2-cyclohexenone (2a)
(Scheme 2). When a solution of 1a with 2a in the presence of
1 mol% of the iridium complex [4a][BF4] in dichloromethane
was illuminated with a 14 W white LED at 25 1C for 18 h,
3-(diphenylaminomethyl)cyclohexanone (3a) was obtained in
90% isolated yield after aqueous work up. Use of similar
Ir complex [4b][BF4] and [Ru(bpy)3][BF4]2 as photocatalysts
decreased the yield of 3a. Interestingly, when DCA was
used in place of [4a][BF4], no formation of 3a was observed.
Institute of Engineering Innovation, School of Engineering,
The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, 113-8656, Japan.
E-mail: ynishiba@sogo.t.u-tokyo.ac.jp; Fax: +81 3-5841-1175;
Tel: +81 3-5841-1175
w Electronic supplementary information (ESI) available. CCDC
877717. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c2cc32745g
Scheme 2 Photocatalytic reaction of diphenyl(trimethylsilylmethyl)-
amine (1a) with 2-cyclohexenone (2a).
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It is noteworthy that the alkylated product having a trimethylsilyl
group (5) was not observed at all, while the cleavage of a C–H
bond at the a-position in the amines often takes place to give the
alkylated products such as 5 in the previously reported system.10f,g
When methyldiphenylamine was used in place of 1a, no reaction
occurred at all (eqn (1)). These results indicate that C–Si bonds in
the amines can be functionalized selectively in this reaction
system. Separately, we confirmed that no formation of 3a was
observed in the absence of a photocatalyst or visible light.
ð1Þ
Scheme 4 Photocatalytic reactions of a-silylamines (1) with 2-cyclo-
hexenone (2a).
Reactions of 1a with a variety of a,b-unsaturated carbonyl
compounds were investigated by using [4a][BF4] as a photo-
catalyst. Typical results are shown in Scheme 3. The reactions
with 2-cyclopentenone and 2-methyl-2-cyclopentenone in
place of 2a proceeded smoothly to give the corresponding
products (3b and 3c) in 79 and 63% yield, respectively. Acyclic
ketones were also applicable to this reaction system, giving the
corresponding products (3d–3f) in good to high yields. Interestingly,
the reaction of methyl vinyl ketone also took place to give 3g
in 56% yield. Use of N-methyl-N-phenylbut-2-enamide as an
alkene gave a trace amount of the product, while the reaction
of the a,b-unsaturated amide bearing oxazolidinone groups
proceeded smoothly to give the corresponding product (3h) in
a high yield.
silyl group at the a-position of amines is an effective strategy
for generation of a-aminoalkyl radicals at the desired position
of amines to give monoalkylated amines selectively in sharp
contrast to the results in the case of direct C–H functionalization
of amines, where unselective formation of di- and tri-alkylated
amines is usually observed.3,4,6–9
To obtain information on the reaction pathway, the isolation of
a silyl enol ether was investigated. Treatment of 1a with 1.5 equiv.
of 2e under similar reaction conditions afforded the corresponding
silyl enol ether (6) in 94% yield without aqueous work up
(eqn (2)). This result clearly shows that the silyl enol ether is
the primary product in our visible-light-mediated reaction and
Next, we examined the photocatalytic reactions of various
a-silylamines. Typical results are shown in Scheme 4. Introduction
of a substituent such as methyl, fluoro or phenyl group at the
para-position in the benzene ring of 1a did not affect the yield
of 3i–k much. Dialkyl and trialkyl amines such as N-methyl-
N-trimethylsilylmethylaniline and N-trimethylsilylmethylmor-
pholine were also applicable to this reaction system and the
corresponding products 3l and 3m were obtained in good yields
without the formation of di- and tri-alkylated amines. The
reaction of N-ethyl-2-trimethylsilylpyrrolidine also proceeded
smoothly to give only the corresponding monoalkylated amine
3n in 48% yield. These results indicate that introduction of a
the corresponding carbonyl compounds
3 should form
after hydrolysis. In sharp contrast, Mariano’s group reported
similar reactions of a-silylamines with the a,b-unsaturated
ketones, where silyl enol ethers were not observed at all.10f,g
This is due to the contribution of the alcohol solvent assisted
desilylation and protonation mechanism, and also use of
alcohol solvents is important for providing the corresponding
addition products in their reaction systems.10,13 Additionally,
the quantum yield in the reaction of 1a with 2e was estimated
to be 0.68, which is less than 1 and is in the common range of
molecular transformations via photoinduced electron transfer
mediated by transition metal polypyridyl complexes.16
This result also suggests that the contribution of a photo-
independent process such as a radical chain process is negli-
gible in this system.6
ð2Þ
Considering the experimental results, a plausible reaction
pathway is shown in Scheme 5. This functionalization of C–Si
bonds in the amines is considered to proceed via a sequential
redox pathway similar to that of visible-light-mediated C–H
alkylation of the amines previously reported by our group.6
The initial step is the formation of the a-aminoalkyl radical A
from a single electron oxidation of 1 by the excited photocatalyst
(*cat) and subsequent desilylation. Addition of A to 2 results in the
formation of the alkyl radical species B. The reduction of B by the
Scheme 3 Photocatalytic reactions of diphenyl(trimethylsilylmethyl)-
amine (1a) with a,b-unsaturated carbonyl compounds (2).
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Scheme 5 Plausible reaction pathway.
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one electron reduced form of the photocatalyst (catꢀ) affords
the corresponding enolate and subsequent silylation occurs to
give the silyl enol ether C accompanied by regeneration of the
photocatalyst (cat). The reduction process of B is quite feasible
according to the reported redox potentials.17,18 The sequential
reduction and silylation step from B to C is in sharp contrast
to the previously reported reaction pathway.10–13 Finally, the
corresponding product (3) is obtained after hydrolysis of C.
Silyl enol ethers are known to be versatile building blocks in
organic synthesis and can be transformed into useful organic
compounds.19,20 We investigated a synthetic application of the
produced silyl enol ether 6. Oxidative transformation of 6 with a
stoichiometric amount of palladium acetate successfully proceeded
to give the corresponding a,b-unsaturated ketone 7 in 56% yield
(eqn (3)).20
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ð3Þ
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In summary, we have developed visible-light-mediated
functionalization of C–Si bonds in the a-silylamines via
a-aminoalkyl radicals. The use of visible-light instead of UV-light
is also supposed to realize the addition of a-aminoalkyl radicals
generated from a-silyldiarylamines to alkenes efficiently. The
reaction has been found to proceed in an atom economical
manner to afford silyl enol ethers in sharp contrast to previously
reported UV-light-mediated reactions.10f,g We believe that this
method described here is an alternative approach to C–H
functionalization of amines at the a-position and provides
a useful strategy for the synthesis of nitrogen-containing
compounds because a-silylamines are readily accessible.21
Further work is now in progress to functionalize C–Si bonds
of the a-silylamines via photoinduced electron transfer.
18 M. Rock and M. Schmittel, J. Chem. Soc., Chem. Commun., 1993,
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6968 Chem. Commun., 2012, 48, 6966–6968
This journal is The Royal Society of Chemistry 2012