Visible-light-induced hydroalkoxymethylation of electron-deficient alkenes by photoredox catalysis

Article abstract of DOI:10.1039/c3cc42695e

Hydroalkoxymethylation of electron-deficient alkenes using alkoxymethyltrifluoroborates by photoredox catalysis has been developed. Highly reactive alkoxymethyl radicals can be easily generated from oxidation of alkoxymethyltrifluoroborates via a visible-light-induced SET process.

Full text of DOI:10.1039/c3cc42695e

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Visible-light-induced hydroalkoxymethylation of
electron-deficient alkenes by photoredox catalysis†
Cite this: Chem. Commun., 2013,
49, 7249
Kazuki Miyazawa, Yusuke Yasu, Takashi Koike* and Munetaka Akita*
Received 12th April 2013,
Accepted 18th June 2013
DOI: 10.1039/c3cc42695e
www.rsc.org/chemcomm
Hydroalkoxymethylation of electron-deficient alkenes using alkoxy-
methyltrifluoroborates by photoredox catalysis has been developed.
Highly reactive alkoxymethyl radicals can be easily generated from
oxidation of alkoxymethyltrifluoroborates via a visible-light-induced
SET process.
Photoredox catalysis with well-defined ruthenium(II) polypyridine
complexes (e.g. [Ru(bpy)3]2+) and the relevant cyclometalated
iridium(III) derivatives has become a useful tool for redox reactions
in synthetic chemistry, because they can efficiently mediate single-
electron-transfer (SET) under visible light irradiation.1,2 In particular,
Ru- or Ir-catalyzed functionalization at the positions adjacent to a
nitrogen atom has been well developed in this area.1f,g In most of
the reactions, iminium derivatives3 or aminoalkyl radicals,4 which
are usually formed from oxidation of electron-rich tertiary amines,
are involved as key intermediates. On the other hand, functionali-
zation of ethers by photoredox catalysis is limited.
In 2011, the group of Stephenson reported photocatalytic depro-
tection of p-methoxybenzyl (PMB) ethers via oxonium species formed
from a 2e-oxidation process (Scheme 1a).5 In contrast, oxidative
generation of alkoxymethyl radicals6 via a photoredox process has
not been reported yet. Recently, we found that cyclic organo(triol)-
borates and organotrifluoroborates can serve as C-radical precursors
by the action of photoredox catalysis.2e On the other hand, Molander
and co-workers have been developing a number of transition-metal-
mediated reactions using alkoxymethyltrifluoroborates, which are
easily accessible and stable to moisture and air.7,8 These results
stimulated us to explore facile generation of alkoxymethyl radicals
from alkoxymethyltrifluoroborates based on a SET photoredox process.
Herein we first report photoredox-catalyzed addition of alkoxymethyl
radicals, generated from 1e-oxidation of alkoxymethyltrifluoroborates,
to electron-deficient alkenes (Scheme 1b). This visible-light-induced
photocatalytic reaction provides us with a new method for C–C
coupling at a carbon atom adjacent to an oxygen atom.6,9
Scheme 1 Photoredox-catalyzed oxidative transformation of ethers.
We initially examined the photocatalytic reaction of potassium
(p-methoxyphenoxy)methyltrifluoroborate 1a (1.2 equiv.)10 with
2-cyclopentenone 2a using the photocatalysts 4–7 (2 mol%) in a
mixture of acetone-d6 and MeOH-d4 (1/1) under visible light irradia-
tion (blue LEDs: lmax = 425 nm) for 24 h (entries 1–4 in Table 1). The
hydroalkoxymethylated product 3aa was formed in every entry;
however, the choice of the photocatalyst turned out to be crucial
for the yield. The Ir photocatalyst 4 afforded the product 3aa in 99%
1
yield as determined using H NMR spectroscopy (entry 1). In the
present photocatalytic reaction, solvent affected efficiency of the
reactions (entries 5–8). The mixed solvent system using acetone and
MeOH resulted in the best efficiency. Notably, product 3aa was
obtained neither in the dark nor in the absence of a photocatalyst
(entries 9 and 10), strongly supporting that the photoexcited species
of the photoredox catalyst are involved in the reaction.
The scope of this photocatalytic hydroalkoxymethylation is sum-
marized in Table 2. Under the optimized conditions, the reactions of
1a with 2a, 2-cyclohexenone 2b and 5,6-dihydro-2H-pyran-2-one 2c
smoothly afforded the corresponding hydroalkoxymethylated pro-
ducts (3aa–3ac) in 94%, 67%, and 62% yields, respectively. This
reaction could be applied to acyclic alkenes, acrylonitrile 2d, methyl
acrylate 2e, N,N-dimethylacrylamide 2f, methyl methacrylate 2g and
2-acetamidoacrylic acid methyl ester 2h. The corresponding hydro-
alkoxymethylated products (3ad–3ah) were obtained in moderate to
good yields (58–99% yields). However, remarkable hindrance due to a
Chemical Resources Laboratory, Tokyo Institute of Technology, 4259 Nagatsuta,
Midori-ku, Yokohama 226-8503, Japan. E-mail: koike.t.ad@m.titech.ac.jp,
makita@res.titech.ac.jp; Fax: +81-45-924-5230; Tel: +81-45-924-5230
† Electronic supplementary information (ESI) available: Experimental details and
spectral data. See DOI: 10.1039/c3cc42695e
c
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Table 1 Optimization of photocatalytic hydroalkoxymethylation of 2-cyclo-
pentenone 2aa
Table 2 Scope of the present photocatalytic hydroalkoxymethylationa
Entry
Photocatalyst
Solvent
Yield of 3aab/%
1
2
3
4
5
6
7
4
5
6
7
4
4
4
4
Acetone-d6/MeOH-d4 (1/1)
Acetone-d6/MeOH-d4 (1/1)
Acetone-d6/MeOH-d4 (1/1)
Acetone-d6/MeOH-d4 (1/1)
Acetone-d6
99
61
17
25
48
54
68
76
0
MeOH-d4
DMSO-d6/MeOH-d4 (1/1)
MeCN-d3/MeOH-d4 (1/1)
Acetone-d6/MeOH-d4 (1/1)
Acetone-d6/MeOH-d4 (1/1)
8
9c
10
4
None
0
a
PMP = p-methoxyphenyl. Reaction conditions: a reaction mixture of
alkoxymethylborate 1a (0.06 mmol), 2a (0.05 mmol), photocatalyst
(0.001 mmol) and solvent (0.5 mL) was irradiated by 3 W blue LEDs
b
(l = 425 ꢀ 15 nm) at room temperature for 24 h. Yields were
c
determined using 1H NMR spectroscopy. The reaction was conducted
in the dark.
Me group at the reaction site was observed for the reaction of ethyl
crotonate 2i (27% NMR yield). To expand this scope, alkenes bearing
two electron-withdrawing groups were examined. Ethylidenemalonic
a
Reaction conditions: a reaction mixture of organoborates 1 (0.24 mmol),
alkenes 2 (0.2 mmol), photocatalyst 4 (0.004 mmol), degassed acetone
acid diethyl ester 2j and 6-bromocoumarin-3-carboxylic acid ethyl (1 mL) and MeOH (1 mL) was irradiated by 3 W blue LEDs (l = 425 ꢀ 15 nm)
at room temperature for 24 h. Alkenes were completely consumed,
ester 2k readily reacted with 1a to give the corresponding coupling
products 3aj and 3ak in 76% and 50% yields, respectively.
unless otherwise noted. Isolated yields of some of the products are low
b
due to loss during the column purification process. The reaction was
In addition, 2-vinylpyridine 2l was applicable to this photocatalytic not completed under these reaction conditions. Yields were determined
using 1H NMR spectroscopy.
system. The corresponding hydroalkoxymethylated product 3al
was obtained in 70% yield. These results show that the present
photocatalytic reaction is highly tolerant to a wide variety of
functional groups.
with methyl acrylate derivative 2m bearing a boronic acid ester
(C–Bpin) moiety proceeded only at the C–BF3K moiety to provide
the coupling product 3am retaining the Bpin unit in 56% isolated
yield. Furthermore, the reaction of potassium ((trimethylsilyl)-
methoxy)methyl-trifluoroborate 1g with 2a gave the product 3ga
bearing the a-silylether moiety. These results show that the
photocatalyst can discriminate a BF3K group from other possible
reaction sites such as TMS and Bpin groups, which are susceptible
to other oxidative treatments to generate C-radicals.12
Furthermore, various alkoxymethylborates were investigated. The
reactions of alkoxymethylborates (RO = phenoxy (1b), benzyloxy (1c),
PMBO (1d)) with 2a resulted in low yields of coupling products.
However, the reactions with 2d afforded products 3bd, 3cd and 3dd
in good yields (45–82%). In addition, sesamoxymethylborate 1e and
4-(3-thienyl)phenoxyborate 1f reacted with 2a to give products
(3ea and 3fa) in 78% and 47% yields, respectively. Notably, homo-
coupling products of alkoxymethyl radicals were not detected at all.11
This is a characteristic reactivity of an a-oxygenated alkyl radical
classified as a stabilized nucleophilic radical.
Certainly, site-specific generation of C-radicals is important
for modern radical reactions. The present photocatalytic hydro-
alkoxymethylation exhibited site-selective reactions at the C–BF3K
moiety. The present photocatalytic hydroalkoxymethylation of 1a
(1)
c
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Scheme 2 A plausible reaction mechanism.
It should be noted that the present photocatalytic system
can harness natural sunlight as a light source. To our surprise,
sunlight could induce the reaction more efficiently than blue
LEDs. The photocatalytic reaction of 1a with 2a under sunlight
was completed in 4 h (eqn (1)).
A plausible reaction mechanism is illustrated in Scheme 2.
First, the photocatalyst 4 (IrIII) is excited by visible light
irradiation (blue LEDs or sunlight) to generate the excited
species *IrIII, which undergoes SET from alkoxymethyltrifluoro-
borate 1 to generate an alkoxymethyl radical and convert into
IrII. Luminescent quenching experiments support this SET
process (see the ESI†). In addition, the cyclic voltammogram
for organoborate 1a exhibited irreversible broad oxidation
waves at around +0.48 V (vs. Cp2Fe in MeCN) (see the ESI†).
These data suggest that alkoxymethylborates can be oxidized by
photoexcited *IrIII (cf. oxidation potential of *IrIII = +0.48 V vs.
Cp2Fe).13 The generated alkoxymethyl radical reacts with
electron-deficient alkene 2 to afford the C–C coupling adduct
30. Reduction of 30 by IrII (path a) followed by protonation by
the solvent gives the hydroalkoxymethylated product 3 and
regenerates the ground state IrIII. There is an alternative pathway,
where 30 reacts with 1 to give an alkoxymethyl radical (path b),
leading to the product 3 (radical propagation).
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In conclusion, visible-light-driven photoredox catalysis pro-
vides a facile and efficient access to alkoxymethyl radicals via
1e-oxidation of alkoxymethyltrifluoroborates. The photocatalytic
hydroalkoxymethylation of electron-deficient alkenes has also
been developed. This new reaction is one of the methods for
functionalization of a carbon atom adjacent to the oxygen atom
of ethers. Further development of synthetically valuable photo-
catalytic radical transformations is a continuing effort in our
laboratory.
The financial support from the Japanese government
(Grant-in-Aid for Scientific Research: No. 23750174) is gratefully
acknowledged. Y. Y. also gratefully acknowledges financial
support from the GCOE program ‘‘Education and Research
Center for Emergence of New Molecular Chemistry’’.
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10 The present aryloxymethylation is regarded as hydroxymethylation
because the aryloxy group can be deprotected by treatment with
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K. Narasaka, Chem. Lett., 1999, 425.
11 Homocoupling products were apparently observed in photoredox-
catalyzed benzylation with benzylborates. To prevent this, an excess
amount of alkenes with respect to borates was used as in ref. 2e.
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´
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Notes and references
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c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 7249--7251 7251