Photocatalytic carbanion generation-benzylation of aliphatic aldehydes to secondary alcohols

Article abstract of DOI:10.1039/c9sc01356c

We present a redox-neutral method for the photocatalytic generation of carbanions. Benzylic carboxylates are photooxidized by single electron transfer; immediate CO₂ extrusion and reduction of the in situ formed radical yields a carbanion capable of reacting with aliphatic aldehydes as electrophiles giving the Grignard analogous reaction product.

Full text of DOI:10.1039/c9sc01356c

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DOI: 10.1039/C9SC01356C
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Photocatalytic Carbanion Generation – Benzylation of Aliphatic
Aldehydes to Secondary Alcohols
Karsten Donabauer,a Mitasree Maity,a Anna Lucia Berger,a Gregory S. Huff,a Stefano Crespia and
Received 00th January 20xx,
Accepted 00th January 20xx
Burkhard König*a
DOI: 10.1039/x0xx00000x
www.rsc.org/
We present
a redox-neutral method for the photocatalytic
generation of carbanions. Benzylic carboxylates are photooxidized
by single electron transfer; immediate CO2 extrusion and reduction
of the in situ formed radical yields a carbanion capable of reacting
with aliphatic aldehydes as electrophiles giving the Grignard
analogous reaction product.
Photocatalysis is a fast growing field in chemistry, enabling
novel transformations previously unattainable under thermal
conditions.[1] The formation of carbon–carbon bonds is at the
core of organic synthesis[2] and many photocatalytic methods
have been reported over the last two decades, the majority of
which involve the generation of one or more radical species as
key intermediates.[3] In contrast, photocatalytic C–C bond
formations involving anionic species as key intermediates are Scheme 1 (a) Photocatalytic carbanion generation via two consecutive SETs.
rare,[4] although the reaction between a carbanion and a carbon
electrophile, e.g. the Grignard reaction,[5] is the most typical C–
(b) Redox-neutral carbanion generation followed by intramolecular SN2
reaction. (c) Envisioned catalytic cycle.
C bond forming reaction. Thus, photocatalytic methods to
generate und utilize carbanion intermediates are desired in
order to expand the limits of photocatalytic transformations
from open shell to closed shell reactivity.
Commonly used photocatalysts, however, are only known to
transfer a single electron to a substrate at once (SET), forming
the corresponding radical and are not able to transfer two
electrons in one step to generate the corresponding
carbanion.[3] Thus, the most intuitive way to photocatalytic
carbanion generation is by two subsequent SETs, i.e. a
consecutive two-fold reduction.[6] There are a few literature
aromatic aldehydes (Scheme 1a).[4b] The latter transformation
reported by Yu et al. is especially interesting, as it is similar to
the commonly used Grignard reaction. However, this method
seems to be limited to aromatic aldehydes.
Beside the generation of a carbanion via a consecutive two-fold
reduction, redox-neutral carbanion formations are proposed in
several reports as well, typically by the reduction of a radical
intermediate during the regeneration of the photocatalyst.
However, this carbanion is in most cases simply protonated[7]
and examples where it is synthetically used are scarce.[4c-i, 8]
examples illustrating the synthetic applicability of this
These include the formation of
a
C–S bond with
4b]
strategy.[4a,
These include the carbanion formation from
benzenesulfonothioates as electrophiles[4e] and intramolecular
ring closures via an SN2 reaction (Scheme 1b).[4f-i]
1,2-dibromomalonates giving cyclopropanes after addition to
electron poor alkenes[4a] and the carbanion formation from
tetraalkyl ammonium salts followed by their addition to
To the best of our knowledge, there is so far no report for a
redox-neutral photocatalytic carbanion generation followed by
its intermolecular reaction with an aliphatic aldehyde or ketone
as electrophile (Scheme 1c). As mentioned above, aldehydes
and ketones are in this regard especially interesting
electrophiles, as the corresponding transformation is analogous
to the widespread Grignard reaction. Additionally, substituted
a.Institute of Organic Chemistry, Faculty of Chemistry and Pharmacy, University of
Regensburg, Universitätsstraße 31, 93053 Regensburg.
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
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carbonyl compounds are poor radical traps for an yield after 16 h (Table 1). Toluene (4a) was observed as a second
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intermolecular radical addition and forming the desired product product in 15% yield resulting from the reDaOctIi:o10n.1w03it9h/Cp9rSoCt0o1n3s56aCs
using established photocatalytic protocols for radical addition electrophile.
to double bonds is generally not successful.[9] An exception to To increase the reaction yield, several parameters were
this is the photocatalytic radical addition enabled by in situ optimized (Table 1, for the full optimization process see SI). A
Brønsted acid activation yielding 3-alkoxy alcohols as reaction slight improvement could be realized by using DMA as solvent.
products reported by Glorius et al.[10] Mainly aromatic carbonyl Interestingly, prior drying of the solvent over 4 Å molecular
compounds could be used as radical traps.
sieve did not improve the yield significantly (entries 2 and 3),
Inspired by the above mentioned reports, we envisioned a whereas the addition of H2O gave more toluene (4a) (entry 4).
photocatalytic cycle, in which a carbanion is formed from Control experiments confirmed that photocatalyst, light and
readily available carboxylic acids. Here, the in situ formed base (entries 5-7) are necessary for the reaction conversion.
carboxylate is oxidized to the corresponding radical. This However, the reaction can be performed in absence of base
intermediate is prone to CO2 exclusion, forming the carbon
centered radical, which may be converted to the corresponding
Table 2 Scope of the reactiona
carbanion by SET from the reduced photocatalyst. The desired
product is then formed by addition of the carbanion to an
aldehyde as electrophile (Scheme 1c). Herein we describe our
efforts to realize this catalytic cycle.
With the envisioned photocatalytic cycle in mind, the coupling
between phenylacetic acid (1a) and n-pentanal (2a) was chosen
as model reaction. Compound 1a was selected as carbanion
precursor, since the corresponding benzylic radical as well as
the desired carbanion intermediate are stabilized by the
aromatic moiety. As the photocatalyst is supposed to engage in
a single electron oxidation as well as reduction, employing a
catalyst with both a strong oxidation as well as reduction power
is crucial. 4CzIPN is an in this regard very attractive organic
photocatalyst, exhibiting an excited state redox potential of
E1/2(P*/P•-) = +1.35 V vs SCE and a ground state reduction
potential of E1/2red(P/P•–) = –1.21 V vs SCE in MeCN.[11] With
4CzIPN as catalyst and Cs2CO3 as base, the reaction proceeded
smoothly yielding the desired addition product 3a in 73% GC-
Table 1 Optimization of reaction conditionsa
Additive
(eq.)
Entry
Solvent
Yield 3ab [%]
Yield 4ab [%]
1
2
3
4
Dry DMF
Dry DMA
DMA
–
–
–
73
75
75 (63)c
34
15
11
12
55
DMA
H2O (3 eq.)
not detected
(n.d.)
n.d.
n.d.
64 (48)c
5d
DMA
–
n.d.
6e
7f
8g
DMA
DMA
DMA
–
–
–
n.d.
n.d.
12
a
Reactions were performed with
1 (150 μmol, 1 eq.) and 2 (3 eq.) in
degassed DMA (2 mL) under a nitrogen atmosphere. If not noted
otherwise, the numbers indicate isolated yields. b GC-yield of the
corresponding decarboxylated side-product
analysis with n-decane as internal standard. c Isolated yield of the
corresponding decarboxylated side-product
d Recovered starting
material
4 determined by GC-FID
a Reactions were performed with 1a (150 μmol, 1 eq.), 2a (3 eq.) and
Cs2CO3 (1 eq.) in degassed solvent (2 mL) under a nitrogen atmosphere.
b GC-Yield determined with n-decane as internal standard. c Isolated yield
in parentheses. d Reaction performed in absence of 4CzIPN. e Reaction
4
.
1
after complete reaction time. e Mixture of syn- and anti-
product was obtained. f trans-styrylacetic acid rather than
α-vinylphenylacetic acid was used as starting material. g Observed by
GC-MS, not isolated. h Acetone/DMA (1:1) was used as solvent.
performed in the dark. f Reaction preformed without base. g The
+
preformed NBu4 carboxylate salt (NBu4PA,
absence of Cs2CO3.
5) was used instead of 1a in
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when using the preformed NBu4+ carboxylate salt (
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5
) (entry 8), acetone (
6
) as co-solvent (1:1 mixture of DMA and acetone)
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DOI: 10.1039/C9SC01356C
suggesting that the base merely serves to generate the increased the yield and 3ag could be isolated in 32% (Table 2).
carboxylate.
Further, several electrophiles for an intermolecular SN2 reaction
The reaction proceeds with various carboxylic acids (Table 2) as were tested (Table S11, SI), however an efficient system could
carbanion precursors in moderate to good yields. Halogen not be found and only product traces were detected in some
or -CF3 substituted phenyl acetic acid derivatives give the cases.
desired products (3b-h). The presence of an additional methyl
or phenyl group on the aromatic ring (3i-l), extended aromatic Starting the mechanistic investigation, a photo-conversion of
systems (3m-n), a Boc-protected amine (3o) and methoxy (3p-r
functional groups or additional substituents on the benzylic (Figure S1, SI). The degradation product could be isolated and
carbon (3t-v) are tolerated. identified as 4CzBnBN (7a) by X-ray crystal structure analysis
)
4CzIPN was observed during the course of the reaction
The presence of a stabilizing aromatic moiety is necessary. (Scheme 2). Compound 7a is likely formed by radical addition of
Aliphatic and allylic carboxylic acids yield only traces of the the benzyl radical to the radical anion of 4CzIPN, followed by
desired product or none at all.
cyanide elimination similar to reactions reported by different
Aliphatic aldehydes bearing short or long chains (3z-ab) react groups.[13] 4CzBnBN seems to be significantly more photo-stable
well as electrophiles. The presence of an additional methyl and the product resulting from a second cyanide elimination
group at the α-carbon decreased the yield to 25% (3ac) and only could only be detected in traces. Performing the benzylation
traces of the product could be observed when pivalaldehyde reaction with 4CzBnBN as catalyst gave the desired product as
was employed (3ad). Substituents in the β-position (3ae) are well (Scheme S4, SI), showing that 4CzBnBN is contributing and
tolerated and even adding a second methyl group showed only likely the main active catalyst for the carbanion formation.
a minor effect (3af). Aromatic aldehydes, e.g. benzaldehyde Ground state potentials of E1/2ox(P•+/P) = +1.48 V vs SCE and
(
2i), gave the corresponding product as well, but a radical- E1/2red(P/P•–) = –1.72 V vs SCE in DMF were measured by CV.
radical cross coupling of the benzyl radical and the ketyl radical The first step in our mechanistic hypothesis is the oxidation of
similar to our previous report[12] instead of a carbanion the carboxylate followed by the extrusion of CO2 to generate a
generation cannot be excluded (Section 8, SI).
The formation of byproducts was investigated for selected with various photoredox catalysts.[14] Accordingly, the emission
examples (3a-b, 3l-n, 3p-s, 3w) and an almost complete mass of 4CzBnBN could be quenched upon addition of NBu4PA (
balance could be obtained in most cases when combining the resulting in a linear Stern-Volmer plot (Figure S7, SI), confirming
yield of the desired ( ) and the decarboxylated ( ) product the interaction between the excited photocatalyst and the
(Table 2). If this was not the case, e.g. for 3p, an incomplete substrate. The following CO2 elimination could be monitored by
conversion of was observed. Ketones, e.g. acetone ( ), yield in situ IR spectroscopy (Figure 1) together with the depletion of
benzyl radical. There are several reports describing this process
5
)
3
4
1
6
only small amounts of the tertiary alcohol (Table S9, SI). Using the aldehyde in course of the reaction.
Scheme 2 Isolation of 4CzIPN photo-conversion product 4CzBnBN (7a). The reaction was performed with 4CzIPN (30 μmol, 1 eq.) and 1a (4 eq.) in
degassed DMA (2 mL) under a nitrogen atmosphere.
Figure 1 In situ FT-IR studies. Irradiation of a solution containing NBu4PA
(5) (75 mM), 2a (75 mM) and 4CzBnBN (3.75 mM) in dry DMA lead to the
Scheme 3 Experiments supporting the formation of a reactive anionic
intermediate.
formation of CO2 (2338 cm-1) and the depletion of 2a (1722 cm-1).
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radical 14 by elimination of CO2. The radical anion of 4CzBnBN
is with a reduction potential of E1/2 (P/P ) = – 1.72 V vs SCE
not able to reduce aliphatic aldehydes (E1/2red(3-methylbutanal
2g) = –2.24 V vs SCE[15]) and hence transfers an electron to the
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DOI: 10.1039/C9SC01356C
red
•–
more easily reducible benzyl radical (E1/2red = – 1.43 V vs SCE[16]
to form carbanion 15. This species is capable of adding to
aldehydes ( ) forming the desired product after protonation
)
2
3
of the alcoholate.
Conclusions
Scheme 4 Proposed mechanism.
In summary, a redox-neutral procedure to benzylate aliphatic
aldehydes via the photocatalytic generation of a carbanion
intermediate is presented, rendering the desired Grignard
analogous products in moderate to good yields. The proposed
mechanism is supported by emission quenching, in situ UV/VIS
and in situ IR studies, while the presence of the reactive anionic
intermediate is shown by deuterium labeling, E1cb Elimination
and DFT calculation.
Next, deuterium labeling experiments were conducted to
support the formation of an anionic intermediate during the
later course of the reaction (Scheme 3a). With D2O as
electrophile, the corresponding deuterated decarboxylated
starting material was isolated (4v-d). As a control experiment,
the non-deuterated product (4v) was obtained when the
reaction was performed in deuterated DMF in absence of D2O.
Addition of D2O to a reaction mixture after completed
irradiation did not yield any 4v-d from 4v via base-induced
(Cs2CO3) H/D-exchange (Scheme S5, SI).
Acknowledgements
In addition to the incorporation of deuterium, a carbanion
intermediate is expected to engage in an E1cb elimination if an
appropriate leaving group is present in the homobenzylic
This work was supported by the German Science Foundation
(DFG, KO 1537/18-1). This project has received funding from the
European Research Council (ERC) under the European Union’s
Horizon 2020 research and innovation programme (grant
agreement No. 741623). We thank Dr. Rudolf Vasold for GC-MS
measurements, Nele Berg for in situ NMR-measurements, the
X-Ray department for crystal structure analysis and Regina
Hoheisel for CV measurements.
position. Hence, tropic acid (9) was subjected to the reaction
conditions (Scheme 3b). Indeed, styrene (10) together with the
decarboxylated byproduct (11) was detected. To exclude
styrene formation from 11 by a simple E2 elimination induced
by Cs2CO3, 11 was directly subjected to the applied reaction
conditions, yielding no styrene (Scheme S6, SI).
In order to thoroughly study the feasibility and selectivity of the
addition of the benzyl anion (15) to the electrophile, a
computational analysis was performed. The C=O addition and
the acid-base reaction of 15 and the C-H was proven at the
Conflicts of interest
There are no conflicts to declare.
SMD(DMF)-
the Supplementary Information). Indeed, the reaction of the
benzyl anion with the aldehydes results to be exothermal ( G =
-6.9 kcal/mol) and slightly kinetically favored ( G* = +6.2
kcal/mol) compared to the abstraction of the acidic proton in
the position ( G* = +6.8 kcal/mol). Ketones were found to be
less selective towards the C=O addition of the benzyl anion
compared to the aldehydes (see compound 3ag). As a
parallelism, the reaction of the benzyl anion with the ketonic
B97X-D/TZVP level of theory (see Section 7.9 in


Notes and references


1
M. H. Shaw, J. Twilton, D. W. MacMillan, J. Org. Chem. 2016,
81, 6898-6926.
2
3
G. Brahmachari, RSC Adv. 2016,
(a) D. Ravelli, S. Protti, M. Fagnoni, Chem. Rev. 2016, 116
9850-9913; (b) J. Twilton, C. Le, P. Zhang, M. H. Shaw, R. W.
Evans, D. W. C. MacMillan, Nat. Rev. Chem. 2017, , 0052; (c)
6, 64676-64725.
,
C=O is almost thermoneutral (
competing acid-base reaction is exothermal (
kcal/mol), with comparable barriers ( G* ca. 10 kcal/mol). The

G = +1.5 kcal/mol). The
1

G = -12.1
C. K. Prier, D. A. Rankic, D. W. MacMillan, Chem. Rev. 2013,
113, 5322-5363; (d) N. A. Romero, D. A. Nicewicz, Chem. Rev.
2016, 116, 10075-10166; (e) L. Marzo, S. K. Pagire, O. Reiser,
B. König, Angew. Chem. Int. Ed. 2018, 57, 10034-10072; (f) I.
Ghosh, L. Marzo, A. Das, R. Shaikh, B. König, Acc. Chem. Res.
2016, 49, 1566-1577.
(a) Y. Zhang, R. Qian, X. Zheng, Y. Zeng, J. Sun, Y. Chen, A. Ding,
H. Guo, Chem. Commun. 2015, 51, 54-57; (b) L. L. Liao, G. M.
Cao, J. H. Ye, G. Q. Sun, W. J. Zhou, Y. Y. Gui, S. S. Yan, G. Shen,
D. G. Yu, J. Am. Chem. Soc. 2018, 140, 17338-17342; (c) Y.
Kumagai, T. Naoe, K. Nishikawa, K. Osaka, T. Morita, Y.
Yoshimi, Aust. J. Chem. 2015, 68, 1668; (d) V. R. Yatham, Y.

barriers for the reactions of 15 with DMA are higher compared
to the ones of aldehydes and ketones.
Considering the experimental observations, computational
results and cited literature reports, the following mechanism is
proposed (Scheme 4): Carboxylic acid 1a is deprotonated by the
4
ox
base (Cs2CO3) to give carboxylate 12. The carboxylate (E1/2
(NBu4PA 5
) = +1.27 vs SCE[14a]) can be oxidized by the excited
photocatalyst 4CzBnBN (E1/2ox(P*/P•–) = +1.21 V vs SCE) and the
generated radical species 13 is transformed to the benzylic
4 | J. Name., 2012, 00, 1-3
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COMMUNICATION
Shen, R. Martin, Angew. Chem. Int. Ed. 2017, 56, 10915-
10919; (e) W. Kong, H. An, Q. Song, Chem. Commun. 2017, 53
View Article Online
DOI: 10.1039/C9SC01356C
,
8968-8971; (f) J. P. Phelan, S. B. Lang, J. S. Compton, C. B. Kelly,
R. Dykstra, O. Gutierrez, G. A. Molander, J. Am. Chem. Soc.
2018, 140, 8037-8047; (g) J. A. Milligan, J. P. Phelan, V. C.
Polites, C. B. Kelly, G. A. Molander, Org. Lett. 2018, 20, 6840-
6844; (h) C. Shu, R. S. Mega, B. J. Andreassen, A. Noble, V. K.
Aggarwal, Angew. Chem. Int. Ed. 2018, 57, 15430-15434; (i) C.
Shu, A. Noble, V. K. Aggarwal, Angew. Chem. Int. Ed. 2019, 58
3870-3874.
,
5
6
(a) V. Grignard, C. R. Acad. Sci. 1900, 130, 1322-1324; (b) G. S.
Silverman, P. E. Rakita, Handbook of Grignard Reagents,
Marcel Dekker, Inc., New York, 1996
.
(a) K. Hironaka, S. Fukuzumi, T. Tanaka, J. Chem. Soc., Perkin
Trans. 2 1984, 1705-1709; (b) J.-M. Kern, J.-P. Sauvage, J.
Chem. Soc., Chem. Commun. 1987, 546-548; (c) D. Li, C.-M.
Che, H.-L. Kwong, V. W.-W. Yam, J. Chem. Soc., Dalton Trans.
1992, 3325-3329.
7
(a) H. Yokoi, T. Nakano, W. Fujita, K. Ishiguro, Y. Sawaki, J. Am.
Chem. Soc. 1998, 120, 12453-12458; (b) H. Huang, C. Yu, Y.
Zhang, Y. Zhang, P. S. Mariano, W. Wang, J. Am. Chem. Soc.
2017, 139, 9799-9802; (c) Y. Yasu, T. Koike, M. Akita, Adv.
Synth. Catal. 2012, 354, 3414-3420; (d) A. J. Musacchio, L. Q.
Nguyen, G. H. Beard, R. R. Knowles, J. Am. Chem. Soc. 2014,
136, 12217-12220; (e) R. Zhou, H. Liu, H. Tao, X. Yu, J. Wu,
Chem. Sci. 2017,
A. Ortega-Martínez, L. Mengozzi, F. Calcinelli, E. Matteucci, F.
Monti, N. Armaroli, L. Sambri, P. G. Cozzi, ACS Catal. 2017,
5357-5362; (g) X. Dong, P. Hu, W. Shen, Z. Li, R. Liu, X. Liu,
8, 4654-4659; (f) A. Gualandi, D. Mazzarella,
7
,
Polymers 2017, 9, 400; (h) A. Noble, R. S. Mega, D. Pflasterer,
E. L. Myers, V. K. Aggarwal, Angew. Chem. Int. Ed. 2018, 57
2155-2159.
,
8
9
S. B. Lang, R. J. Wiles, C. B. Kelly, G. A. Molander, Angew.
Chem. Int. Ed. 2017, 56, 15073-15077.
(a) A. Clerici, O. Porta, P. Zago, Tetrahedron 1986, 42, 561-
572; (b) A. Clerici, O. Porta, J. Org. Chem. 1989, 54, 3872-3878;
(c) S. Wilsey, P. Dowd, K. N. Houk, J. Org. Chem. 1999, 64
,
8801-8811; (d) C. Che, Z. Qian, M. Wu, Y. Zhao, G. Zhu, J. Org.
Chem. 2018, 83, 5665-5673.
10 L. Pitzer, F. Sandfort, F. Strieth-Kalthoff, F. Glorius, J. Am.
Chem. Soc. 2017, 139, 13652-13655.
11 J. Luo, J. Zhang, ACS Catal. 2016, 6, 873-877.
12 A. L. Berger, K. Donabauer, B. König, Chem. Sci. 2018, 9, 7230-
7235.
13 (a) T. Itou, Y. Yoshimi, T. Morita, Y. Tokunaga, M. Hatanaka,
Tetrahedron 2009, 65, 263-269; (b) M. T. Pirnot, D. A. Rankic,
D. B. Martin, D. W. MacMillan, Science 2013, 339, 1593-1596.
14 (a) L. Capaldo, L. Buzzetti, D. Merli, M. Fagnoni, D. Ravelli, J.
Org. Chem. 2016, 81, 7102-7109; (b) T. Patra, D. Maiti, Chem.
Eur. J. 2017, 23, 7382-7401; (c) J. Schwarz, B. König, Green
Chem. 2018, 20, 323-361; (d) H. Huang, X. Li, C. Yu, Y. Zhang,
P. S. Mariano, W. Wang, Angew. Chem. Int. Ed. 2017, 56, 1500-
1505.
15 D. Nicewicz, H. Roth, N. Romero, Synlett 2015, 27, 714-723.
16 (a) B. A. Sim, D. Griller, D. D. M. Wayner, J. Am. Chem. Soc.
1989, 111, 754-755; (b) D. D. M. Wayner, D. J. McPhee, D.
Griller, J. Am. Chem. Soc. 1988, 110, 132-137.
This journal is © The Royal Society of Chemistry 20xx
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N
N
Benzylic Carbanion
Intermediate
Grignard-analogous
Product
CN
N
Ph
N
O
H
H
R
OH
R
H
OH
O
Base
32 Examples
Mild Reaction Conditions
Redox-neutral Carbanion Generation