Visible-Light Photoredox-Catalyzed α-Allylation of α-Bromocarbonyl Compounds Using Allyltrimethylsilane

Article abstract of DOI:10.1002/bkcs.12219

The development of a greener allylation reagent for α-allylation of carbonyl compounds is of great necessity. Here we present allyltrimethylsilane as a novel allylation reagent in the photoredox-catalyzed α-allylation of carbonyl compounds such as ketones, esters, and amides. The reaction process shows good functional group tolerance and generates a good yield of the product. The reaction mechanism is a radical-mediated reaction by photo-induced single electron transfer.

Full text of DOI:10.1002/bkcs.12219

Communication
DOI: 10.1002/bkcs.12219
BULLETIN OF THE
A. Gontala et al.
KOREAN CHEMICAL SOCIETY
Visible-Light Photoredox-Catalyzed α-Allylation of α-Bromocarbonyl
Compounds Using Allyltrimethylsilane
†
†
*
Arjun Gontala, Gwang Seok Jang, and Sang Kook Woo
Department of Chemistry, University of Ulsan, 93 Daehak-Ro, Nam-Gu, Ulsan 44610, South Korea.
*E-mail: woosk@uslan.ac.kr
Received December 12, 2020, Accepted January 1, 2021, Published online January 15, 2021
The development of a greener allylation reagent for α-allylation of carbonyl compounds is of great neces-
sity. Here we present allyltrimethylsilane as a novel allylation reagent in the photoredox-catalyzed
α-allylation of carbonyl compounds such as ketones, esters, and amides. The reaction process shows good
functional group tolerance and generates a good yield of the product. The reaction mechanism is a radi-
cal-mediated reaction by photo-induced single electron transfer.
Keywords: Allylation, α-Bromocarbonyl compounds, Visible-light, Photoredox catalysis, SET
Carbonyl and allylic groups are among the most important
functional groups in organic synthesis because they can
easily be converted to other functional groups and applied
in carbon–carbon bond-forming reactions.1 Thus, the
α-allylation of carbonyl compounds has been intensely
researched in organic chemistry.2 A common example of
classical allylation reactions is the allylation of enolates
with electrophilic allyl halides. As a matter of fact, enolate
chemistry is moisture sensitive and has scale-up limitations
due to the use of a strong base in generating enolate. Fur-
thermore, Pd-catalyzed allylation of nucleophiles with
allylic halides, acetates, and carbonates (Tsuji–Trost reac-
the α-carbonyl radicals with various alkenes have been well
studied.4b, 6
This study investigates the visible light photoredox-cata-
lyzed α-allylation of carbonyl compounds using α-halo-
carbonyl compounds as α-carbonyl radical precursors.
Allyltributyltin is a commonly used reagent for allylation in
classical radical reactions7 and UV-mediated photo-
chemistry (Scheme 1(b)).8 Recently, Reiser and coworkers
investigated the potential use of allyltributyltin in visible
light photocatalytic reactions.9 Despite reports on several
reagents from previous studies, the development of a novel
allylation reagent is still required due to toxicity. Recently,
Yasuda and coworkers developed allyltrifluoroborate as a
new-type allylation reagent for α-allylation of carbonyl
compounds using eosin Y as photocatalyst (Scheme 1
(b)).10 Our research group is interested in using orga-
nosilicon groups in photoredox catalysis and recently, we
developed organosilicon groups as radical precursors in
photocatalytic reactions.11 Also, we investigated the poten-
tial use of allyltrimethylsilane as a novel allylation reagent
for α-allylation of carbonyl compounds because of its neu-
tral, stable, and nontoxic nature. Reiser and coworkers
reported allyltrimethylsilane as an allylation reagent in pho-
toredox-catalyzed α-allylation of carbonyl compounds.12
However, their study only investigates three samples using
diethyl bromomalonate as α-carbonyl radical’s precursor.
Here we report the visible light photoredox-catalyzed
α-allylation of various carbonyl compounds using allyl-
trimethylsilane (Scheme 1(c)).
tion) has proved to be a mild method for α-allylation of car-
3
bonyl compounds (Scheme 1(a)).2a,
This method is
widely used due to its mild reaction conditions, wide sub-
strate range, and stereochemical control. However, this
reaction uses stabilized enolate such as an anion of
malonate, but enolates from ketones, esters, and amides are
rarely used.
An alternative strategy for α-allylation of carbonyl com-
pounds is a radical-mediated reaction. With respect to anion
chemistry, a radical-mediated reaction is less sensitive to
moisture, acidic proton, and electrophilic functional groups
but environmentally unsafe when toxic reagents such as
organotin or selenium are used. Recently, visible light pho-
toredox catalysis is an emerging research area in organic
chemistry because of its environmental sustainability.4 Visi-
ble photocatalysts can generate radical intermediates used
in carbon–carbon or carbon–heteroatom bond formation
reactions via electron transfer mechanisms. The radical in
the α-position of the carbonyl group is electrophilic5 and is
highly reactive with electron-rich alkenes. The generation
of radical intermediates from α-halocarbonyl compounds
using a visible light photocatalyst and addition reactions of
In the initial study, we conducted α-allylation of 2-
bromoacetophenone 1a and allyltrimethylsilane 2a using
fac-Ir(ppy)3 as a photoredox catalyst in various solvents
under blue light emitting diodes (LEDs) irradiation. This
reaction produced a coupled ketone 3a with the best yield
in MeCN among several solvents (Table 1 entries 1, 5–7).
In the catalyst screening, we observed that other
†These authors contributed equally to this work.
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Table 1. Optimization of reaction conditions.a
nd, not detected.
Scheme 1. α-Allylation of carbonyl compounds.
a Reaction conditions: 1 a, 2 a, catalyst, solvent with 10 W blue LEDs
(452 nm) irradiated at room temperature for 24 h under argon
atmosphere in a pressure tube.
b Yield determined by 1H NMR (internal standard: methyl benzoate).
c Isolated yield by flash column chromatography.
photocatalysts did not produce the desired product 3a
(Table 1 entries 1–4). Furthermore, the results show that a
high concentration of acetonitrile provided better yields
than low concentrations (Table 1 entries 1, 8–9). Finally,
we observed that the optimization conditions of the reaction
of 2-bromoacetophenone 1a with three equivalents of
allyltrimethylsilane 2a in the presence of 1.0 mol% of fac-
Ir(ppy)3 in 0.5 M of acetonitrile at room temperature irradi-
ated at 10 W blue LEDs under an argon atmosphere pro-
duced the desired products 3a with 80% yield (Table 1,
entry 1). The control experiments revealed the essential role
of the visible light photoredox catalyst in the reaction
(Table 1, entries 10–11).
Using the optimized reaction conditions, we explored the
scope of α-allylation of carbonyl compounds employing
different α-halocarbonyl compounds (Table 2). Generally,
the reaction exhibited a broad substrate scope and good
functional group tolerance. Also, a series of aryl ketones
produced the corresponding allylation products in good
yields (3a-h). Functional groups such as alkyl (3b), aryl
(3c, h), alkoxy (3d), halogen (3e, f), and ester (3g) were
well-tolerated. Furthermore, the results showed no particu-
lar relationship between the electronic environment of the
ketone and the yield of the product. Also, the naphthene-
substituted ketone (3h) generates the corresponding product
in good yield. Additionally, the substrate scope was suc-
cessfully extended to α-bromoesters (1i, j) and
α-bromoamide (1k), in which the esters and amides showed
similar reactivity to ketones. Substrate investigations
showed that α-allylation of ketones, esters, and amides
were efficient in photoredox catalysis.
The reaction mechanism was also investigated. We
predicted the mechanism that governed the reduction of 2-
bromoacetophenone 1a, and the α-carbonyl radical was
generated by an excited photocatalyst. In literature, the
reduction potential of 2-bromoacetophenone 1a is −0.49 V
vs. SCE in MeCN,13 which implies that the excited
photocatalyst [fac-Ir(ppy)3*] can be reduced 1a.14 More-
over, Stern–Volmer fluorescence quenching experiments
were conducted with 2-bromoacetophenone 1a and
allyltrimethylsilane 2a. The results showed that only 1a
quenched the excited photocatalyst, whereas 2a did not
(Figure 1). Additionally, a radical trapping experiment
was conducted using 2,2,6,6-tetramethyl-1-piperidyloxy
(TEMPO) as a radical trapping reagent. No product was
observed in the presence of TEMPO except a radical-
coupled product 4a, thus indicating a radical-based pathway
(Scheme 2(a)).
Based on our control experiments and literature6c, 9, 12
we proposed the reaction mechanism depicted in Scheme 2
(b). The fac-Ir(ppy)3 was excited by irradiating with blue
LEDs and the excited photocatalyst reduces 2-
,
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Table 2. Substrate scope of various α-Bromocarbonyl
compounds.a
Figure 1. Luminescence quenching of fac-Ir(ppy)3 by 1a (left).
Stern–Volmer plot (right).
Scheme 2. Control experiment and proposed reaction.
catalyst cycle was completed via the oxidation of tri-
methylsilyl radical by the oxidized photocatalyst (IrIV).
In conclusion, we developed allyltrimethylsilane as a
novel allyl reagent in the photoredox catalytic α-allylation
of carbonyl compounds such as ketones, esters, and amides.
The developed allylation reaction generates products with
good tolerance and yields for different functional groups.
The reaction mechanism consists of the generation of α-car-
bonyl radicals and radical addition reaction by
photocatalyzed single electron transfer mechanism. This
study demonstrates the development of a new strategy for
the allylation of α-carbonyl compounds using allylsilanes.
a Reaction conditions as given in Table 1, entry 1; reported yields are
for isolated material. See Supporting information for details.
bromoacetophenone 1a. Subsequently, Br− was released
from the reduced 1a, thereby forming a α-carbonyl radical
intermediate I. The radical addition of an electrophilic
α-carbonyl radical I and an electron-rich alkene 2a pro-
duces 3a via the elimination of trimethylsilyl radical. The
Acknowledgments. This work was supported by the 2018
Research Fund of University of Ulsan.
Supporting Information. Additional supporting informa-
tion may be found online in the Supporting Information
section at the end of the article.
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