Metal-free, visible-light-mediated, decarboxylative alkylation of biomass-derived compounds

Article abstract of DOI:10.1039/c6gc01101b

This work describes a mild, environmentally friendly method to activate natural carboxylic acids for decarboxylative alkylation. After esterification of biomass-derived acids to N-(acyloxy)phthalimides, the active esters are cleaved reductively by photocatalysis to give alkyl radicals, which undergo C-C bond formation with electron-deficient alkenes. This reaction is catalyzed by the organic dye eosin Y and green light (535 nm) and the scope of acids includes abundant amino acids, α-oxy acids and fatty acids which are available from renewable resources.

Full text of DOI:10.1039/c6gc01101b

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DOI: 10.1039/C6GC01101B
Journal Name
ARTICLE
Metal-Free, Visible-Light-Mediated, Decarboxylative Alkylation of
Biomass-Derived Compounds†
Johanna Schwarz and Burkhard Königa
Received 00th January 20xx,
Accepted 00th January 20xx
This work describes a mild, environmentally friendly method to activate natural carboxylic acids for decarboxylative
alkylation. After esterification of biomass-derived acids to N-(acyloxy)phthalimides, the active esters are cleaved reductively
by photocatalysis to give alkyl radicals, which undergo C–C bond formation with electron-deficient alkenes. This reaction is
catalyzed by the organic dye eosin Y and green light (535 nm) and the scope of acids includes abundant amino acids, α-oxy
acids and fatty acids which are available from renewable resources.
DOI: 10.1039/x0xx00000x
www.rsc.org/
which are generated from carboxylic acids upon extrusion of
CO2 react with activated alkenes, typically Michael acceptors.
The alkyl radicals can either be formed by esterification of
carboxylic acids and subsequent reductive cleavage of the ester
bond (Scheme 1a)17c, 18 or by oxidative cleavage of the acid itself
(Scheme 1b).17a These methods have already been reported by
different groups, but expensive and toxic transition metal
catalysts are needed in all cases and the scope of carboxylic
acids is limited.
Introduction
Carboxylic acids are among the most abundant, renewable
feedstocks on our planet. They are non-toxic, stable and
inexpensive and therefore valuable starting materials for “green
chemistry”.1 Due to shortage of fossil resources and rising
energy demand, alternative sources of raw materials gain in
importance.2 In order to generate platform chemicals and high-
value chemicals like pharmaceuticals from biomass-derived
compounds, the carboxy group can be targeted as chemo- and
regioselective leaving group for C–C bond formation reactions.3
In principle, decarboxylative reactions are known for a long
time, but old protocols (e.g. according to Hunsdiecker4, Barton5
and Kolbe6) are not suitable for cross-coupling reactions
between acids and other substrates under benign conditions.
Over the last two decades, many transition metal-catalysed,
decarboxylative C–C and C–X coupling methods were reported
by Gooßen,7 Myers8 and many others.9 Even though these
methods are versatile in application and often compatible with
multiple step reactions, they require high temperatures as well
as palladium or copper reagents. Moreover, they are usually
Herein, we report for the first time a metal-free, photo-
catalytic, decarboxylative alkylation which is applicable for a
broad variety of natural carboxylic acids involving amino acids,
α
-oxy acids and fatty acids (Scheme 2). Therefore, N-(acyloxy)-
phthalimides were synthesized from the corresponding acid
19
according to a simple method developed by Okada,18b,
analogously to Overman´s approach. These active esters
undergo C–C bond formation with electron-deficient alkenes
under irradiation with green light in the presence of DIPEA and
the organic, non-toxic and cheap dye eosin Y. Thus, valuable
chemicals can be obtained from renewable biomass under eco-
friendly and mild conditions.
limited to decarboxylation of Csp –COOH or Csp–COOH bonds.
2
Recently, first photoredox-mediated processes were
developed for the activation of the carboxy group. The usage of
photocatalysts and visible light enables reactions under mild
conditions and low energy consumption. During the last years,
photocatalytic, decarboxylative reactions like arylations,10
vinylations,11 allylations,12 alkynylations,13 fluorinations14 and
hydrodecarboxylations15 have been reported by MacMillan and
other groups.16 Also different methods for decarboxylative
alkylations have already been investigated.17 Here, alkyl radicals
17c
according
Reductive decarboxylation
to Overman et al.
a)
R2
R1
R3
O
O
R1
R3
R1
OH-NPhth
COOH
DCC
Ru(bpy)3(PF6)2
R2
R2
ν
h
NPhth
R3
tertiary
carboxylic acids
17a
according
to MacMillan
Oxidative decarboxylation
R1
et al.
b)
Ir[dF(CF3)ppy]2(dtbbpy)+
R1
COOH
ν
h
R2
R2
amino acids
a. Institute of Organic Chemistry, University of Regensburg, Universitätsstraße 31,
93053 Regensburg, Germany
E-mail: Burkhard.Koenig@chemie.uni-regensburg.de; Phone: (+49)-941-943-4575.
α
-oxy
secondary
acids
all
cylic
carboxylic acids
†
Electronic Supplementary Information (ESI) available: synthesis of starting
1 Photocatalytic
of alkyl radicals from carboxylic acids
Scheme
generation
materials, spectroscopic investigations, analytical data and 1H- and 13C-NMR
spectra. See DOI: 10.1039/x0xx00000x
for
with electron-deficient alkenes.
subsequent coupling
This journal is © The Royal Society of Chemistry 20xx
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ARTICLE
Journal Name
EWG
R5
R5
View Article Online
EWG
R1
R3
O
O
O
R
DOI: 10.1039/C6GC01101B
1
R1
R2
R4
R2
eosin
Y
R1
R3
OH-NPhth
R2
COOH
N
R2
R3
R4
DCC, DMAP
2
DIPEA
R3
-
ν,
h
CO2
O
3
amino acids
alkyl radical
active ester 1
α
-oxy
and
3° acids
acids
1°, 2°
N
-(acyloxy)phthalimide
fatty acids
.
work:
2 Our
for the decarboxylative
of natural
reductive cleavage of N
1
-(acyloxy)phthalimide
Scheme
general approach
compounds
by
alkylation
almost every solvent (except DMF: Table 1, entries 2 and 7). As
[Ru(bpy)3]Cl2 is known to be a stronger reductant than
eosin Y,21 the reason for the better performance of the metal-
Results and discussion
Synthesis and scope
free catalyst
these solvents. Decomposition of
of the reaction mixtures after several minutes. The best product
yield of 96% was obtained with photocatalyst and CH2Cl2 as
A
is probably its better solubility and stability in
For investigation of the reaction conditions of the
decarboxylative alkylation, the N-(acyloxy)phthalimide of
N-Boc-protected proline (1a) and n-butyl acrylate (2a) served as
test substrates. A mixture of both compounds, the base DIPEA
and a homogeneous photocatalyst was irradiated with LEDs
under nitrogen atmosphere. For this reaction, no
heterogeneous catalysts have been investigated, although an
application would be conceivable.20 First, the catalytic activity
B
was indicated by darkening
A
solvent (Table 1, entry 9). For further optimization, different
reaction conditions and control reactions were investigated
(Table 2). Reducing the amount of catalyst to 5 mol% (Table 2,
entry 1) or the amount of alkene from 5 to 2 eq. (Table 2,
entry 4) resulted in lower yields of about 85%. Also a shorter
reaction time (Table 2, entry 2) or the use of less base (Table 2,
entry 3) had a clearly negative impact. However, running the
reaction in the presence of air (Table 2, entry 5) gave the same
yield as after degassing the reaction mixture (Table 1, entry 9).
Measuring the oxygen concentration during the non-degassed
reaction showed that the oxygen was consumed within two
hours (see Supporting Information). Control experiments
without light, DIPEA or catalyst led to no product formation at
all, independent if oxygen was present or not (Table 2, entry 6
to 11).
of the photocatalysts eosin Y (
different solvents was screened (Table 1). The inexpensive
A) and [Ru(bpy)3]Cl2 (B) in
organic dye
A
enabled higher yields than metal catalyst B in
a
and
Table 1 Evaluation of catalyst
solvent.
N
Ru
N
COOH
N
N
N
N
Br
Br
Cl2
HO
O
O
Br
Br
eosin
2
reaction
conditions.
of
Table
Y A
Optimization
ONPhth
(
)
B
( )
[Ru(bpy)3]Cl2
A
mol%)
(10
DIPEA
DIPEA
photocat.,
(2 equiv.)
O
O
ONPhth
N
dry solvent, LEDs,
N2 rt, 18 h
,
N
CH2Cl
535
2 (dry),
nm,
N2 rt, 18 h
,
N
N
O
O
O
O
Boc
Boc
Boc
Boc
2a
(5 equiv.)
O
O
3a
1a
3a
1a
equiv.)
(1
Entry
Modification
Yield [%]a
2a
Entry
Photocatalytic system
Solvent Yield [%]b
1
2
3
4
5
6
7
8
9
5 mol%
A
85
64
26
83
96
0
0
0
0
0
9 h irradiation time
1 equiv. DIPEA
2 equiv. 2a
Air atmosphereb
No base
1
2
3
4
5
6
7
8
9
[Ru(bpy)3]Cl2 (2 mol%, 455 nm)
[Ru(bpy)3]Cl2 (2 mol%, 455 nm)
[Ru(bpy)3]Cl2 (2 mol%, 455 nm)
[Ru(bpy)3]Cl2 (2 mol%, 455 nm)
[Ru(bpy)3]Cl2 (2 mol%, 455 nm)
Eosin Y (10 mol%, 535 nm)
Eosin Y (10 mol%, 535 nm)
Eosin Y (10 mol%, 535 nm)
Eosin Y (10 mol%, 535 nm)
Eosin Y (10 mol%, 535 nm)
DMSO
DMF
CH3CN
CH2Cl2
THF
30
47
60
18
7
No light
DMSO
DMF
CH3CN
CH2Cl2
THF
30
37
65
96
53
No photocatalyst
Air atmosphere, no base
Air atmosphere, no light
10
11
Air atmosphere, no photocatalyst
0
10
a Determined by GC analysis using naphthalene as internal standard.
a Reactions were performed using 1 equiv. 1a, 5 equiv. 2a and 2 equiv. DIPEA.
b Determined by GC analysis using naphthalene as internal standard.
2 | J. Name., 2012, 00, 1-3
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Table 3 Scope of electron-deficient alkenes.
cross-coupling reaction works on the one hand for primary (1c
,
View Article Online
DOI: 10.1039/C6GC01101B
1k,
1n-
s), secondary (1b
,
1c
-j
,
1l) as well as for tertiary carboxylic
A
mol%)
R2
(10
DIPEA
(2 equiv.)
ONPhth
EWG
acids (1l) and on the other hand for different substrate classes
like amino acids (1b-g), -oxy acids (1h ) and even fatty acids
1n-s).
The active esters of simple, Boc-protected, secondary amino
EWG
R1
+
CH2Cl
535
N
N
2 (dry),
α
-j
R2
nm,
air, rt, 18 h
R1
O
Boc
Boc
(
2
3
1a
equiv.)
(5
(isolated yield)
O
equiv.)
(1
acids proline (1a, Table 3), alanine (1b) or valine (1d) gave the
highest yields (68-89%). The N-(acyloxy)phthalimide of the
primary amino acid glycine showed slightly less product
formation (4c, 62%). Also amino acid derivatives with aromatic
side chains like phenylalanine (1e) or benzyl-protected serine
O
O
N
N
N
O
O
Boc
Boc
Boc
3a
3c
(76%)
(80%)
3b
(78%)
(
1f) and aspartic acid (1g) yielded the corresponding products
O
O
O
O
4e-g in about 60%. As a typical natural -hydroxy acid, lactic
α
N
N
Boc
N
O
acid with different protecting groups was investigated. Here,
the phenoxy- (1i) and methoxy-protected derivatives (1j) gave
with 50 and 58% yield, respectively, less coupling product than
Boc
Boc
3f
3e
3d
(59%)
(73%)
(73%)
cyclic
Applying active esters of simple carboxylic acids without any
heteroatom in -position to the carboxy moiety also resulted in
product formation, although the yields decreased to 30-45%
4k ). This decline in efficiency indicates that the stability of the
alkyl radical generated after decarboxylation is the decisive
point for successful product formation. In the case of amino and
α-oxy compounds, the radical is stabilized by electron-donation
α-oxy starting material 1h (72%).
O
O
O
N
N
N
α
O
O
O
Boc
Boc
Boc
3h
3g
3i
(85%)
(69%)
(92%)
(
-s
O
N
N
O
N
N
Boc
O
Boc
Boc
from the lone pair of the heteroatom to the single-occupied p
orbital of the neighboring radical centered carbon, which
explains the higher yields.22 Considering the decarboxylative
alkylation of N-(acyloxy)phthalimides of simple carboxylic acids,
3k
3j
(40%)
(55%)
3l 5%)a
(<
a Product not isolated. Yield estimated by 1H-NMR.
secondary (1l, 40%) or even more tertiary carboxylic acids (1m
45%) are more prone to decarboxylate than primary, linear
carboxylic acids (1k 1n ; all about 30%). Again, tertiary alkyl
radicals are more stable than secondary and especially primary
radicals, which is in good accordance with the observed
yields.22b Nonetheless, several fatty acids, which are
widespread in nature could be applied for this photocatalytic
,
With these optimized reaction conditions, the scope and
limitations of the decarboxlative alkylation were explored.
Therefore, the reaction of different electron-deficient alkenes
with active ester 1a was investigated (Table 3). The expected
cross coupling products were observed in moderate to excellent
,
-s
yields when
coupling partners. Unsubstituted or
Michael acceptors gave the desired products 3a
good yields of 73 to 80%. Benzylic, -unsaturated esters 2g
α
,
β
-unsaturated esters and ketones were used as
-methylated aliphatic
3b and 3e in
β
reaction. Saturated (1n-q), mono-unsaturated (1r) and di-
,
unsaturated (1s) fatty acid derivatives with different chain
lengths (12-18 C) all gave products 4n-s in about 30% yield. The
reaction with the active ester of cinnamic acid (1t) yielded no
product, because the vinylic radical intermediate, which is
formed upon decarboxylation is apparently not stable enough
to undergo further reactions. In summary, we could show that
cheap and abundant compounds from renewable biomass are
suitable starting materials for this cross-coupling reaction.
α,β
and 2h were suitable reaction partners in the same way. Also
reactions with cyclic ketones gave products 3d and 3e in about
75% yield. However, introduction of a phenyl ring at the
attacked carbon inhibited formation of product 3l almost
completely, presumably due to steric hindrance by the bigger
substituent in
positioned on the
β
-position. In contrast, if the phenyl ring was
-carbon of the Michael acceptor, the best
α
yield of 92% (3i) was observed. This result indicates that after
attack of the N-Boc proline fragment at the double bond, a
Mechanistic investigations
Based on the report by Overman et al.17c, the known
photochemistry of eosin Y23 and our own results, we propose
the following mechanism for the decarboxylative alkylation of
N-(acyloxy)phthalimides with electron-deficient alkenes
(Scheme 3): Irradiation of a photocatalyst (PC) with visible light
generates the excited catalyst PC*, which is reductively
quenched by the sacrificial electron donor DIPEA to give
DIPEA+•. Regeneration of the PC is presumably achieved by
reduction of N-(acyloxy)phthalimide 1a, which gives the
corresponding radical anion. Splitting of the N–O bond and
radical is formed at the
α-position, which is stabilized by an
adjacent phenyl ring in the case of 3i. Next to Michael acceptors,
also the electrophilic, heteroaromatic styrene derivative
vinylpyridine (2k) yielded the corresponding product 3k in 40%.
After establishing the scope of activated alkenes,
N-(acyloxy)phthalimide
1 was varied (Table 4). Here, benzyl
methacrylate 2h served as model alkene and again, the
optimized conditions of Table 2, entry 5 were applied. A broad
variety of esterified acids, including readily available, biomass-
derived compounds could be employed. This photocatalytic
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ARTICLE
Journal Name
Table 4 Scope of N
-(acyloxy)phthalimides.
View Article Online
DOI: 10.1039/C6GC01101B
R1
O
A
mol%)
R2
R3
(10
DIPEA
R1
O
R2
R3
(2 equiv.)
N
O
O
+
O
CH2Cl
535
2 (dry)
O
O
O
nm,
air, rt, 18 h
2h
1
4
equiv.)
(5
equiv.)
(1
(isolated yield)
N
Product
Product
N
Product
N
-(acyloxy)phthalimide
-(acyloxy)phthalimide
-(acyloxy)phthalimide
PhO
OPh
ONPhth
C15H31
ONPhth
ONPhth
O
O
O
O
C14H29
BocHN
BocHN
O
O
O
O
O
acid-
OPh-lactic
acid-NPhth 1i
palmitic
4i
4p
4q
Boc-Ala-NPhth 1b
(31%)
4b
(50%)
(
)
(68%)
NPhth 1p
(
)
( )
OMe
MeO
ONPhth
C17H35
ONPhth
ONPhth
O
O
O
O
BocHN
C16H33
BocHN
O
O
O
O
O
stearic acid-
1c
OMe-lactic
acid-NPhth 1j
4j
(30%)
Boc-Gly-NPhth (
)
4c
(62%)
(58%)
NPhth 1q
(
)
(
)
C8H17
ONPhth
ONPhth
ONPhth
O
O
7
O
O
BocHN
O
BocHN
6
O
O
C8H17
O
oleic acid-
NPhth 1r
O
1k
4k
4d
Boc-Val-NPhth 1d
4r
(29%)
(89%)
(
)
(
)
(28%)
C5H11
O
ONPhth
O
O
6
ONPhth
ONPhth
O
O
7
BocHN
O
BocHN
O
Boc-Phe-NPhth 1e
O
O
1l
linoleic acid-
NPhth 1s
4s
(30%)
C5H11
4l
(40%)
4e
(
)
(57%)
(
)
OBzl
BzlO
ONPhth
ONPhth
O
O
ONPhth
O
O
O
BocHN
BocHN
O
O
O
O
cinnamic acid-
acid-
pivalic
NPhth 1m
4m
4t
Boc-Ser(Bzl)-NPhth
1f
(45%)
(0%)
4f
(55%)
NPhth 1t
(
)
(
)
(
)
COOBzl
ONPhth
BzlOOC
BocHN
ONPhth
C11H23
O
O
C10H21
O
O
O
BocHN
O
lauric acid-
4n
(31%)
Boc-Asp(OBzl)-NPhth
1g
NPhth 1n
4g (64%)
(
)
(
)
ONPhth
O
C13H27
O
O
O
ONPhth
O
O
C12H25
O
acid-
O
myristic
4o
(32%)
4h
1h
NPhth 1o
(72%)
( )
subsequent elimination of CO2 generates alkyl radical 1a•. This PC
radical can attack the double bond of Michael acceptor 2a to or
A
B
(eosin Y*/eosin Y•-: +0.83 V vs. SCE in CH3CN-H2O, 1:1)21b
(Ru2+*/Ru+: +0.77 V vs. SCE in CH3CN)25 and is a well
form the intermediate 3a•. It is assumed that hydrogen atom documented process in literature.21, 26 Furthermore, this step
abstraction from DIPEA+• or the solvent finally enables was confirmed by luminescence quenching experiments with
formation of product 3a
.
both photocatalysts. In the case of eosin Y, fluorescence
This mechanistic proposal was confirmed by several quenching could hardly be observed with DIPEA, N-(acyloxy)-
spectroscopic studies. Single electron transfer (SET) from DIPEA phthalimide 1a or alkene 2a (see Supporting Information for
to the excited PC should be exergonic according to the redox graphs and further details). This indicates that excited PC
A does
potentials of DIPEA (+0.72 V vs. SCE in CH3CN)24 and the excited rather react from the triplet than from the singlet state which
4 | J. Name., 2012, 00, 1-3
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ARTICLE
reaction mechanism
the
decarb-
photocatalytic,
Scheme 3
for
Figure 1 Fluorescence quenching of [Ru(bpy)3]Cl2 (B, 15.0 µM in CH3CN) upon
Proposed
View Article Online
of N
1a with
2a
titration with DIPEA (100 mM in CH3CN).
DOI: 10.1039/C6GC01101B
oxylative alkylation
-(acyloxy)phthalimide
DIPEA+
n-butylacrylate ( ).
DIPEA
SCE in CH3CN, see Supporting Information) showed that
reduction by the strongly reducing PC B
(Ru+/Ru2+: -1.33 V vs.
O
SCE in CH3CN)21a is thermodynamically feasible. Although redox
potentials are not directly comparable with each other in the
O
N
PC
N
Boc
case of PC
A
(eosin Y•-/eosin Y: -1.06 V vs. SCE in CH3CN-H2O,
O
O
PC*
1a
O
N
1:1),21b this catalyst is also known to be a powerful reductant.
Eosin Y shows an absorption maximum at 527 nm which
corresponds to an energy of 2.35 eV. After intersystem crossing
to its reactive triplet state, 1.89 eV are still available for
photocatalytic reactions.21b To confirm the formation of radical
3a• during the reaction, this intermediate was captured by the
O
O
visible
light
PC
O
O
N
N
N
O
O
Boc
O
Boc
persistent radical TEMPO giving product
5 (Scheme 3), which
-
CO2
was determined by LC-MS analysis (see Supporting
Information). Furthermore, the quantum yield of the
photocatalytic model reaction was determined (see Supporting
Information). The low value of Φ = 2.6 ± 0.5% corresponds to
the relatively long reaction times of 18 h and indicates that
efficient radical chain processes are very unlikely in this
mechanism.28 For further insight, the stability of the photo-
catalyst eosin Y has been investigated by measuring UV-vis
absorption spectra during the reaction (see Supporting
Information). Over the reaction time of 18 h, the catalyst slowly
degrades and a precipitate occurs, which slows down the
product formation after some hours (see Supporting
Information for the time course of the reaction). However, the
remaining photocatalytic active species is sufficient to reach
almost complete conversion within the reaction time.
O
O
3a
O
N
O
N
2a
Boc
Boc
DIPEA+
DIPEA+
TEMPO
1a
HAT
O
N
O
O
N
O
Boc
N
5
3a
O
Boc
was already shown by our group for another reaction.27 For
verification of this triplet reactivity, transient absorption
measurements were performed, due to the short triplet lifetime
of eosin Y (τT = 320 ± 10 ns).27a Performing fluorescence
Experimental
experiments with [Ru(bpy)3]Cl2 (
B) revealed that the emission
General procedure for the synthesis of N-(acyloxy)phthalimides 1
of * is quenched by the electron donor DIPEA, which proves
B
SET between both species (Figure 1). Upon titration of B* with
1a or 2a, no quenching was observed (see Supporting
Information).
Starting materials
1 were synthesized by a slightly modified
procedure based on Reiser et al.18a and Overman et al.17c The
respective carboxylic acid (8.00 mmol, 1.0 equiv.), N-hydroxy-
phthalimide (1.43 g, 8.80 mmol, 1.1 equiv.), N,N´-dicyclohexyl-
The next step of the catalytic cycle was assumed to be
regeneration of the PC by SET from PC•- to 1a. Cyclic
voltammetry measurements of the active ester 1a (-1.20 V vs.
carbodiimide (1.98 g, 9.60 mmol, 1.2 equiv.) and 4-dimethyl-
aminopyridine (0.98 g, 0.80 mmol, 0.1 equiv.) were mixed in a
flask with a magnetic stirring bar. Dry THF (40 mL) was added
and the orange reaction mixture was stirred for 15 h at rt. The
white precipitate was filtered off and the solution was
concentrated by evaporation of the solvent. Purification by
column chromatography on flash silica gel (CH2Cl2 or
CH2Cl2/CH3OH = 9:1) gave the corresponding product.
1.4x106
[Ru(bpy)3]Cl2 (B)
+ 30 µL DIPEA
+ 60 µL DIPEA
+ 100 µL DIPEA
1.2x106
1.0x106
+ 150 µL DIPEA
+ 250 µL DIPEA
+ 350 µL DIPEA
8.0x105
General procedure for the photocatalytic decarboxylative
alkylation
+ 650 µL DIPEA
+ 950 µL DIPEA
+ 1250 µL DIPEA
6.0x105
+ 1900 µL DIPEA
In a 5 mL crimp cap vial with a stirring bar, eosin Y (
0.03 mmol, 0.1 equiv.) and N-(acyloxy)phthalimide
(0.30 mmol, 1.0 equiv.) were added. After addition of DIPEA
(102 µL, 0.60 mmol, 2.0 equiv.), the corresponding olefin
A, 19.4 mg,
4.0x105
1
2.0x105
0.0
2
(1.50 mmol, 5.0 equiv.) and dry CH2Cl2 (4 mL), the vial was
capped to prevent evaporation. The reaction mixture was
stirred and irradiated through the vials´ plane bottom side using
500
550
600
650
700
750
800
λ [nm]
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Green Chemistry
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green LEDs (535 nm) for 18 h at rt. The reaction mixture of two
vials with the same content was combined and diluted with
saturated aqueous solution of NaHCO3 (20 mL). It was extracted
with EA (3 x 20 mL) and the combined organic phases were
washed with brine (20 mL), dried over Na2SO4 and concentrated
in vacuum. Purification of the crude product was performed by
8
9
8 (a) A. G. Myers, D. Tanaka and M. R. Mannion, J. Am.
Chem. Soc., 2002, 124, 11250-11251; (b) D. Tanaka, S.
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P. Romeril and A. G. Myers, J. Am. Chem. Soc., 2005, 127
,
10323-10333.
9 R. Shang and L. Liu, Sci. China Chem., 2011, 54, 1670-
1687.
automated flash column chromatography (PE/EA = 19:1 to 1:1) 10
yielding the corresponding product 3 or 4 as colorless oil.
10 (a) Z. Zuo and D. W. C. MacMillan, J. Am. Chem. Soc.,
2014, 136, 5257-5260; (b) Z. Zuo, H. Cong, W. Li, J. Choi,
G. C. Fu and D. W. C. MacMillan, J. Am. Chem. Soc., 2016,
138, 1832-1835; (c) Z. Zuo, D. T. Ahneman, L. Chu, J. A.
Terrett, A. G. Doyle and D. W. C. MacMillan, Science,
2014, 345, 437-440; (d) Y. Jin, M. Jiang, H. Wang and H.
Conclusions
In conclusion, we have developed a metal-free, photocatalytic
method for the decarboxylative alkylation of biomass-derived
compounds. The advantage of this procedure over other
methods reported in literature is the broad substrate scope
Fu, Scientific Reports, 2016, 6, 20068.
11
12
11 (a) A. Noble and D. W. C. MacMillan, J. Am. Chem.
Soc., 2014, 136, 11602-11605; (b) A. Noble, S. J.
McCarver and D. W. C. MacMillan, J. Am. Chem. Soc.,
2015, 137, 624-627.
including cheap and abundant α-amino acids, α-oxy acids and
fatty acids as well as primary, secondary and tertiary substrates.
In addition, the reactions can be carried out under mild,
environmentally friendly conditions with the metal-free,
organic dye eosin Y as photocatalyst. The carboxylic acids are
activated by esterification to N-(acyloxy)phthalimides and then
reductively cleaved upon irradiation with green light. This
generates alkyl radicals, which undergo cross-coupling with
electron-deficient alkenes. Thereby, largely new compounds for
the synthesis of pharmaceuticals or fine chemicals are
generated. The method contributes to the ongoing efforts
replacing fossil resources by renewable feedstocks in the
synthesis of chemical intermediates.
12 (a) C. Hu and Y. Chen, Org. Chem. Front., 2015, 2,
1352-1355; (b) S. B. Lang, K. M. O'Nele, J. T. Douglas and
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Comm., 2015, 51, 5275-5278; (b) F. Le Vaillant, T.
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14
15
Acknowledgements
We thank the German Science Foundation (DFG, GRK 1626,
Chemical Photocatalysis) for financial support for this work.
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