Photoinitiated carbonyl-metathesis: Deoxygenative reductive olefination of aromatic aldehydes: Via photoredox catalysis

Article abstract of DOI:10.1039/c9sc00711c

Carbonyl-carbonyl olefination, known as McMurry reaction, represents a powerful strategy for the construction of olefins. However, catalytic variants that directly couple two carbonyl groups in a single reaction are less explored. Here, we report a photoredox-catalysis that uses B₂pin₂ as terminal reductant and oxygen trap allowing for deoxygenative olefination of aromatic aldehydes under mild conditions. This strategy provides access to a diverse range of symmetrical and unsymmetrical alkenes with moderate to high yield (up to 83%) and functional-group tolerance. To follow the reaction pathway, a series of experiments were conducted including radical inhibition, deuterium labelling, fluorescence quenching and cyclic voltammetry. Furthermore, NMR studies and DFT calculations were combined to detect and analyze three active intermediates: a cyclic three-membered anionic species, an α-oxyboryl carbanion and a 1,1-benzyldiboronate ester. Based on these results, we propose a mechanism for the CC bond generation involving a sequential radical borylation, "bora-Brook" rearrangement, B₂pin₂-mediated deoxygenation and a boron-Wittig process.

Full text of DOI:10.1039/c9sc00711c

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DOI: 10.1039/C9SC00711C
ARTICLE
Photoinitiated Carbonyl‐Metathesis: Deoxygenative Reductive
Olefination of Aromatic Aldehydes via Photoredox Catalysis
Shun Wang,a N. Lokesh,a Johnny Hioe,a Ruth Gschwind*a and Burkhard König*a
Received 00th January 20xx,
Accepted 00th January 20xx
Carbonyl‐carbonyl olefination, known as McMurry reaction, represents a powerful strategy for the construction of olefins.
However, catalytic variants that directly couple two carbonyl groups in a single reaction are less explored. Here, we report
a photoredox‐catalysis that uses B2pin2 as terminal reductant and oxygen trap allowing for deoxygenative olefination of
aromatic aldehydes under mild conditions. This strategy provides access to a diverse range of symmetrical and
unsymmetrical alkenes with moderate to high yield (up to 83%) and functional‐group tolerance. To follow the reaction
pathway, a series of experiments were conducted including radical inhibition, deuterium labelling, fluorescence quenching
and cyclic voltammetry. Furthermore, NMR studies and DFT calculations were combined to detect and analyze three active
intermediates: A cyclic three‐membered anionic species, an α‐oxyboryl carbanion and a 1,1‐benzyldiboronate ester. Based
on these results, we propose a mechanism for the C=C bond generation involving a sequential radical borylation, “bora‐
Brook” rearrangement, B2pin2‐mediated deoxygenation and a boron‐Wittig process.
DOI: 10.1039/x0xx00000x
Introduction
Alkenes are omnipresent in natural compounds and essential
functional groups for many chemical transformations. Among
many methods that have been developed for the generation of
alkenes, olefination and metathesis reactions converting two
functional groups into one alkene are particularly useful for the
synthesis of complex molecules. The classic Wittig olefination
uses phosphonium ylide reagents (Scheme 1A, Equation 1)1 and
many related carbonyl olefination processes, such as the
Horner‐Wadsworth‐Emmons,1b Peterson2, Julia3 and Tebbe4
reactions utilizing different ylide or carbene precursors have
been developed. Olefin cross‐metathesis reactions catalyzed by
metal alkylidenes allow the exchange between two olefins to
form a pair of distinct alkenes (Scheme 1A, Equation 2).5 The
related catalytic olefin‐carbonyl metathesis strategy for the
synthesis of alkenes was discovered just recently (Scheme 1A,
Equation 3).6
Contrary to these olefination and metathesis processes,
catalytic bicarbonyl olefination reactions remain less
developed. The McMurry reaction provides an attractive route
to alkenes from two carbonyl groups (Scheme 1B).7 The net
result of such a carbonyl‐carbonyl olefination could be viewed
as a “metathesis” process although the oxygen atom is generally
not released as oxygen gas, but bounded to reagents. Classic
McMurry protocols use titanium salts in combination with a
Scheme 1 Divergent functionalization of carbonyl
aFaculty of Chemistry and Pharmacy, University of Regensburg, D‐93040
Regensburg, Germany.
*Email: ruth.gschwind@ur.de
*Email: burkhard.koenig@ur.de
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
reducing reagent under heating. The whole process is driven
thermodynamically by the formation of strong Ti‐O bonds.
Despite being very effective and widely used, this system
generally requires relatively harsh reaction conditions, such as
the use of stoichiometric amounts of the titanium reagent and
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strong reductants at high temperature, lowering the overall Table 1. Screening of Reaction conditions
functional group tolerance.7‐8 Therefore, several milder and
View Article Online
DOI: 10.1039/C9SC00711C
catalytic methods were developed. A variant using only catalytic
amounts of titanium with an excess of chlorosilane was
developed by Fürstner and co‐workers.9 Wagner used
hexachlorodisilane at high temperature (160 oC) for converting
Entry
Change from standard
conditions
Yield of 2a
(Z and E)
[%]
Z/E[b]
diarylmethanones into tetraarylethylenes.10 More recently, Ott
et al. reported the stereoselective preparation of E‐alkenes
from two aldehydes by using phosphanylphosphonate.11 After
that, Li described a stepwise Ru‐catalyzed carbonyl‐carbonyl
olefination method wherein hydrazine was employed as the
mediator to transform one carbonyl into its carbanion
equivalent.12 Despite these advances, the direct catalytic
carbonyl‐carbonyl olefination in one‐step and under mild
reaction conditions remains a challenge.
1
2
none
without thiol
87
2.6/1
trace
0
‐
3
without B2in2
‐
4
without Cs2CO3
Na2CO3 instead of Cs2CO3
CsF instead of Cs2CO3
DMF (1 mL)
trace
trace
trace
77
‐
In recent years, photoredox catalysis has evolved into an
attractive alternative to traditional strategies for generating
radical intermediates.13 For instance, ketyl radicals are easily
accessed from carbonyl compounds by using a photoredox‐
mediated single‐electron reduction strategy.14 The obtained
ketyl radicals have been used in C‐C bond formation by addition
to π systems or radical‐radical coupling (Scheme 1C). However,
a photoredox catalyzed reductive coupling of carbonyls
followed by deoxygenation yielding a carbon‐carbon double
bond has not been achieved so far. Herein, we report the first
deoxygenative olefination coupling of aromatic aldehydes
enabled by the cooperative action of bis(pinacolato)diboron
and a photoredox catalytic system (Scheme 1D).
The anticipated deoxygenative olefination process requires a
four‐electron reduction and an efficient oxygen acceptor.
Moreover, a careful design of the catalytic system is required to
suppress the competing pinacol coupling.15 With these
mechanistic challenges in mind, we envisioned the possibility of
combining the photocatalytic carbonyl reduction system with a
diboron reagent allowing an efficient McMurry‐type process
based on the following considerations: 1) the Lewis acidity of
the boron atom of the diboronate compounds could potentially
activate the carbonyl groups thus facilitating the single electron
reduction process.16 2) the formation of a strong B‐O bond
would provide a significant thermodynamic driving force for the
deoxygenation process.16b,17
5
‐
6
‐
7
2.5/1
2.4/1
‐
8
DMF (0.4 mL)
68
9
without light
0
10
without photocatalyst
17
3.5/1
entry 3‐4). As the formation of the product does not require an
additional electron donor, we reasoned that B2Pin2 may serve
as the terminal reductant and the oxygen acceptor in this
reaction. Next, we explored the effect of another co‐catalyst,
which could potentially shuttle electrons from the boron
species to the photocatalytic system.18 To our delight, a
significant increase in yield (39%, Table S1, entry 6) was
observed upon adding benzyl thiol (10 mol%) as co‐catalyst,
whereas quinuclidine proved ineffective (Table S1, entry 5).
Testing the reaction with other bases resulted in lower yields
(Table S1 entry 7‐15). Further evaluation of other thiols
revealed that only benzyl thiol (20 mol%) and 4‐Me‐benzyl thiol
(20 mol%) gave comparably good yields (Table S2, entry 6 and
entry 14). A variety of photocatalysts were tested for this
transformation; using
a
slightly modified catalyst
[Ir(FCF3ppy)2dtbbpy]PF6 increased the yield to 74% (Z/E =
2.2/1). Screening of the solvents revealed that DMF was the
optimal solvent for this reaction (Table S3). Better yield and Z/E
selectivity were achieved by employing a combination of
[Ir(FCF3ppy)2dtbbpy]PF6 with 4‐Me‐benzyl thiol (Table S4, entry
3). Subsequently, the effect of concentration was examined,
subtle varying the concentration to 0.33 M increased the yield
to 87% with a better Z/E selectivity of the product (Z/E = 2.6/1)
(Table S5, entry 3). Interestingly, small amounts of product 2a
(17%, Table 1, entry 10) were also detected in the absence of
Results and discussion
Optimization of reaction contition
To examine the feasibility of our hypothesis, we chose para‐
tolualdehyde 1a as the model substrate in combination with
bis(pinacolato)diboron (B2pin2) as the oxygen acceptor. A
promising result was obtained when irradiating a mixture
containing 1a, B2pin2, DIPEA, Cs2CO3, [Ir(dFCF3ppy)2dtbbpy]PF6
(1 mol%) and DMF with a blue LED lamp giving trace amounts
of alkene 2a (see Supplementary Information Table S1, entry 1).
Interestingly, removing the electron donor DIPEA from the
system also yielded the product in 6% yield with full conversion
of 1a (Table S1, entry 2). Moreover, the alkene 2a was not
detected in the absence of either Cs2CO3 or B2pin2 (Table S1,
the photocatalyst. Presumably,
a
small amount of
benzaldehyde is excited by visible light in the presence of B2pin2
to form ketyl radicals that lead to the formation of product.
However, further control experiments confirmed that both the
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isomers. bEthyl 2‐mercaptopropionate (0.04 mmol) was used in place of 4‐MeBnSH.
photocatalyst and light were crucial for an efficient
transformation (Table 1, entry 9 and 10).
View Article Online
cIsolated yield, average of two parallel reactions.
DOI: 10.1039/C9SC00711C
benzofuran (1w) as well as indole (1x) performed well in this
transformation. However, aliphatic aldehydes and aromatic
ketones gave only trace amounts of products with low
conversions, presumably due to their higher reduction
potentials and steric hindrance, respectively.
S
ynthetic scope
With the optimized reaction conditions in hand, we then
investigated the scope of this reaction with substituted
aromatic aldehydes as substrates. A broad range of aromatic
aldehydes bearing para‐(1a‐1g), meta‐(1h‐1p) or ortho‐(1q‐1s
)
substituents reacted smoothly to afford the corresponding
alkenes. Many synthetically useful functional groups including
alkyl (1a, 1c and 1q), alkoxyl (1d‐e
silyl 1m), boronic ester 1n
transformation.
Importantly, the presence of acidic protons in amides (1f‐g
,
)
1h, 1r and 1t), acetal (1u),
are tolerated in this
(
(
,
and 1i) and amines (1j) did not interfere with the reaction,
giving yields of the isolated alkenes ranging from 47% to 63%.
Aromatic substituents, such as phenyl (1k
1l furnished alkene products, albeit in lower yields.
, 1s) and thiophenyl
(
)
Furthermore, the reaction was compatible with halogen
substituents on the benzaldehydes and gave the chloro‐ and
fluoro‐substituted alkenes in 40% and 32% yield, respectively
(
1o‐p). However, benzaldehydes possessing strong electron‐
Fig. 2 Scope of aldehydes for the cross‐coupling deoxygenative olefination.a aReaction
conditions: 1 (0.1 mmol), 3 (0.15 mmol), [Ir(FCF3ppy)2dtbbpy]PF6 (0.004 mmol), B2pin2
(0.24 mmol), Cs2CO3 (0.24 mmol), 4‐Me‐BnSH (0.04 mmol) in anhydrous DMF (1 mL),
withdrawing groups, such as nitro or nitrile, were not tolerated.
ortho‐Substituted 2‐methyl benzaldehyde gave an excellent Z/E
selectivity (Z/E:16/1) and good yield (60%). More sterically irradiation with 3 W blue LED for 24 h at room temperature, isolated average yield of
two parallel reactions. Yields refer to the combined yield of Z and E isomers. bYields and
hindered groups such as methoxy (1r) and phenyl (1s) at the
ortho‐position showed a similarly high Z/E selectivity up to
Z/E ratio values were determined with 1H NMR using 1,3,5‐methoxybenzene as internal
standard; based on the amount of aldehyde 1. cYields and Z/E ratio values were
determined with 1H NMR using 1,3,5‐methoxybenzene as internal standard; based on
the amount of aldehyde 3.
(39:1), albeit a decreased yield. This significant increase in Z/E
selectivity may be attributable to the increase in triplet energy
of the Z isomers caused by a larger twisting angle in the
presence of an ortho‐substitution, while a small increase in
triplet energy in the less‐congested E isomer is expected.19
Additionally, heteroarenes including benzothiophene (1v),
After having established the scope of aldehydes in homo‐
coupling reactions, we turned our attention to more challenging
cross‐coupling reactions between two different aldehydes. As
Shown in Figure 2, using slightly modified reaction conditions,
the coupling between two different aldehydes proceeds well to
give a range of unsymmetrical alkenes. Aldehydes bearing
amides and amine groups at the aromatic ring react smoothly
with para‐tolualdehyde to give the corresponding alkenes in
moderate to good yields (5a‐5c). Aldehydes carrying alkoxy
groups at the phenyl ring were tolerated under our reaction
conditions, affording the alkenes in modest to good yields with
modest Z/E selectivity (5d‐5f). However, this cross‐coupling
reaction is sensitive to steric hindrance and ortho‐substituents
O
[Ir(FCF3ppy)2dtbbpy]PF6 (1 mol%)
B2Pin2 (1.2 eq), Cs2CO3 (1.2 eq)
R
R
H
R
R
R
4-Me-BnSH (20 mol%)
DMF (0.6 mL)
blue LED, 25 oC
1
E-2
Z-2
CHO
R
CHO
R
CHO
R
1h R = OMe: 35% (Z/E = 1.4/1)
1i R = NHBoc: 60% (Z/E = 1.5/1)
1j R = NHPh: 63% (Z/E = 2.1/1)
1k R = Ph: 30%(Z/E = 1/1.4)c
1l R = thiophenyl: 34% (Z/E = 1.85/1)c
1m R = TMS: 47% (Z/E = 1.3/1)
1n R = Bpin: 33% (Z/E = 1/1.6)c
1o R = Cl: 40% (Z/E = 1/1.7)b,c
1p R = F: 32% (Z/E = 1.7/1)b,c
1a R = Me: 83% (Z/E = 2.6/1)
1b R = H: 70% (Z/E =1.9/1)
1q R = Me: 60% (Z/E = 16/1)
1r R = OMe: 27% (Z/E = 7.7/1)
1s R = Ph: 39% (Z/E = 39/1)
1c R = tBu: 60% (Z/E = 1/1.3)
1d R = OMe: 66% (Z/E = 3.4/1)
1e R = OtBu: 42% (Z/E = 1/1.2)
1f R = CH2NHBoc: 47% (Z/E = 1.7/1)
1g R = NHAc: 63% (Z/E = 2.0/1)
led to
a decreased reactivity (5e). The reaction of
heteroaromatic aldehydes furnished a heterocycle‐containing
stilbene (5g). Coupling between benzaldehyde and 3,5‐
dimethoxybenzaldehyde afforded the alkene in 57% yield with
good selectivity (Z/E = 1/3.5).20
CHO
O
CHO
O
S
OHC
OHC
O
MeO
OMe
1w, 67% (Z/E = 1.65/1)
1t, 61% (Z/E = 1/1.2)c
1v, 54% (Z/E = 1/1)
1u, 60% (Z/E = 1.9/1)
Mechanistic investigation
OHC
N
To gain insights into the reaction mechanism, a series of
chemical experiments, spectroscopic investigations and in situ
illumination NMR experiments21 were conducted.
The initial Stern‐Volmer luminescence quenching
experiments revealed that phenylmethanethiolate quenches
the excited state of the photocatalyst much more efficiently
1x, 40% (Z/E = 5.2/1)
Fig. 1 Scope of aldehydes for the homo‐coupling deoxygenative olefination.a aReaction
conditions: 1 (0.2 mmol), [Ir(FCF3ppy)2dtbbpy]PF6 (0.002 mmol), B2pin2 (0.24 mmol),
Cs2CO3 (0.24 mmol), 4‐MeBnSH (0.04 mmol) in anhydrous DMF (0.6 mL), irradiation with
3 W blue LED for 24 h at 25 oC, isolated yields. Yields are the combined yield of Z and E
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than the corresponding thiol, while the aldehyde and B2pin2 do following only the 13C signals of the labelledViecwaArbrtioclne Onalirnee
DOI: 10.1039/C9SC00711C
not quench at all (see Supplementary Information, Figure S6). discussed.
This indicates a potential electron transfer from the sulfur anion
On irradiation (455 nm, blue LED) of the reaction mixture,
to the excited state of the photocatalyst. This reduced besides starting material and product resonances, several new
III/II
[Ir(FCF3ppy)2dtbbpy]PF6 (II) (Ir0
= ‐1.38V vs SCE in DMF, 13C signals are detected, indicating the generation of possible
1/2
Figure S1) catalyst causes the single electron reduction of 1a
.
reaction intermediates. Figure 3A shows the in situ 1H
Even though the Ered of 1a is higher (Ered = ‐2.07 V vs SCE in DMF, decoupled 13C spectrum of the reaction mixture after 18 hours
Figure S3), the decrease of reduction potential of aldehyde 1a of irradiation. Besides benzaldehyde, the two products (P and P'
on addition of Lewis acidic B2pin2 (Figure S4 and S5) facilitates in Figure 3A), and the by‐products S4 and S5, several additional
this single‐electron reduction.
Next, the presence of radical species in the catalytic cycle was assigned, which are marked with
peaks appeared. Among them three intermediates were
and and highlighted
G,
F
H
tested by addition of 2,2,6,6‐tetramethylpiperidin‐1‐oxyl with different colors in Figure 3A. To identify and characterize
(TEMPO, 1.0 eq.) to the mixture, which shows a dramatic drop the intermediates, a combined approach of chemical exchange
in product yield (down to 8 % see Supplementary Information). information from 13C CEST (chemical exchange saturation
This was also evidenced in the 13C NMR spectrum, which shows transfer), chemical shift information and multiplicity pattern
a line broadened signal for the carbonyl of the benzaldehyde accessed from 1H coupled 1D 13C spectra was applied.
(see Supplementary Information Figure S9), possibly due to Furthermore, theoretical calculations and spectra of
exchange of the radical species (ketyl radical) with individually synthesized intermediates were used to
benzaldehyde.
Subsequently, a series of control experiments were
corroborate the assignment.
To identify the next intermediate formed from benzaldehyde,
performed to identify key intermediates. 1,2‐Diol, benzyl the spectra are scanned by 13C CEST NMR (detailed information
alcohol and 1,2‐diketone were excluded as intermediates, since about CEST is given in Supplementary Information ).24 In case
using them in place of benzaldehyde did not lead to alkene there is any chemical exchange on the ms time scale with
formation (Supplementary Information, Scheme S1). benzaldehyde, saturation can be transferred from the
Furthermore, benzylboronic esters S4 and benzyloxyborate exchanging intermediate onto benzaldehyde and hence the
ester S5 were identified as by‐products in the reaction (Figure intermediate becomes detectable. The most pronounced
S7). Most interestingly, control experiments in the presence of intensity drop observed for the benzaldehyde 13C=O signal at
D2O (10.0 eq.) quenched the reaction significantly, affording the 193 ppm is on saturation at 78.5 ppm (Figure 3B'). However, at
alkene in trace amounts along with the formation of deuterated 300 K, the peak at 78.5 ppm is very broad (blue, Figure 3B)
(at the benzylic position) boronic esters S4‐D and borate ester suggesting a transient nature of the intermediate. To
S5‐D (Scheme 2). In contrast, with only d7‐DMF as solvent, characterize this intermediate further, the temperature was
deuterium was not incorporated in the products or the boronic lowered to 270 K resulting in a considerable narrowing of this
ester S4 and borate ester S5. These findings suggest 13C signal. In addition, the 1H coupled 13C spectrum reveals a 13C‐
intermediate boron‐related species, such as an α‐oxyboryl H moiety by appearance of a doublet. From the literature, it was
carbanion22 and an α‐boryl carbanion23 in the reaction considered that the base might react with the diboron reagent
mechanism.
to generate sp3‐sp2 diboron species that participates in ketyl
radical borylation25 to give α‐boryl alkoxide. Furthermore,
theoretical calculations predict a 13C chemical shift of 70.4 ppm
for a cyclic three‐membered anionic species
open form of the α‐boryl alkoxide was found to be
energetically less favorable by theoretical calculations.
However we cannot distinguish experimentally between and
. Based on this evidence, the 13C peak at 78.5 ppm is assigned
F (Figure 3B). The
E
E
F
to the cyclic three‐membered species
F or to the α‐boryl
carbonyl peak of benzaldehyde indicate a fast chemical alkoxide
; thus, the above discussed line broadening of exchange with
Scheme 2 Deuteration experiments
E
the ketyl radical. In addition, CEST exchange saturation transfer
reveals a slow exchange of benzaldehyde with the cyclic three‐
membered anionic species F or E. Combining the experimental
observations we conclude that a sequential exchange process
takes place from benzaldehyde through a very short‐lived ketyl
radical to E or F.
Next, a systematic in situ illumination NMR study was
carried out to directly detect these reaction intermediates. To
monitor this unusual transformation from carbonyl groups to
double bonds and to boost sensitivity of otherwise insensitive
13C signals, benzaldehyde specifically 13C labelled at the
carbonyl position was used (see Figure 3A). This enabled us not
only to predominately track the chemical modulations at the
carbonyl position, but also to identify the number of protons
Next, the assignment of the α‐oxyboryl carbanion
intermediate G is discussed (see Figure 3C). In a “bora‐Brook”
1
rearrangement process this α‐oxyboryl carbanion
to be generated from the isomerization of α‐boryl alkoxide
G
was found
.22
bound to the carbon in several intermediate species by H
coupled 1D 13C experiments (see below); therefore, in the
E
Furthermore, Nozaki et al. proposed a three‐membered‐ring
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species similar to
ARTICLE
F
as the transition state of the C to O boryl reports and the oxophilicity of boron (B‐O bond BDE = 193
View Article Online
migration in the “bora‐Brook” rearrangement.22c Given these kcal/mol),26 such a carbon to oxygen boryl migration in the
DOI: 10.1039/C9SC00711C
Fig. 3 NMR Studies of the Reaction Intermediates. (A) In situ 13C spectrum of the reaction mixture after 18 hours of illumination, the observed intermediate peaks are marked with
respective colors and stable intermediates are directly compared to independently synthesized compounds. (B) Stabilization and characterization of transient intermediate F is
achieved at low temperature (270 K) and characterized from 1H decoupled and coupled 13C spectra. (B') 13C CEST spectra establishing initial chemical transformation between
benzaldehyde and primary key intermediate F. (C) Identification of α‐oxyboryl carbanion G from 13C and 1H chemical shifts (for HSQC see SI) and the multiplicity pattern of 13C at the
benzylic position. (D) Assignment of intermediate H from the multiplicity pattern of 13C at the benzylic position and 13C and 1H chemical shifts (for HSQC see SI). The 1H and 13
C
chemical shifts of independently synthesized H are given in green. The values inside brackets are calculated chemical shift values. Unless otherwise mentioned, all spectra were
measured at 300 K, in a 600 MHz NMR spectrometer
cyclic three‐membered anionic species
carbanion
is highly probable. The aforementioned control thermodynamically and kinetically favorable.27 Therefore, the
experiments, wherein deuterium‐trapped benzyloxyborate intermediacy of in our reaction process was examined with
ester S5‐D was observed, further corroborates the existence of NMR. To identify the chemical shifts of H,
13C‐1H HSQC
. Indeed, we could detect a relatively broad peak of very small spectrum (see, Supplementary Information) of the pure
F to generate α‐oxyboryl benzyldiboronate ester H (for structure see Figure 3D) is
G
H
a
G
intensity at 102 ppm in the reaction mixture corresponding to independently synthesized intermediate
H was measured and
the benzylic carbon of α‐oxyboryl carbanion
G (Figure 3A and revealed a benzylic carbon at 21.5 ppm and the corresponding
3C). The 1H coupled 13C spectrum shows a doublet (Figure 3C) proton at 2.50 ppm. Indeed, careful observation of the 13C
indicating a 13CH group and the calculated chemical shifts (13C spectra of the reaction mixture revealed a very small peak of
H
1
108 ppm and H 6 ppm) are in good agreement with the at 21.5 ppm (Figure 3A and 3D). The assignment to
H
was
assignment to the benzylic carbon of α‐oxyboryl carbanion G.
confirmed by a doublet (‐13CH) in the 1H coupled 13C spectrum
Moreover, the essential role of DMF and Cs2CO3 in our reaction (Figure 3D) and HSQC spectra of the reaction mixture
is in line with the observation by Nozaki that the presence of a (Supplementary information). At present, we can only suggest
polar solvent and larger alkali metal cation could enhance the that
nucleophilicity of the anionic oxygen atom in such processes.22c B2pin2 followed by a deoxygenation step. A related mechanism
Overall, we conclude that the α‐oxyboryl carbanion is was proposed by Liu and Lan et al. for a borylation of an α‐
generated via a “bora‐Brook” rearrangement from the cyclic oxyboronic species, in which similar gem‐diboron compounds
three‐membered anionic species are generated via an oxoanion instead of a carbanion attacking
Previous theoretical calculations showed that the B2pin2.27
transformation of an α‐oxyboryl carbanion to a 1,1‐
H is formed via a nucleophilic attack of the carbanion G to
G
F
.
G
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5 for the reported
gem‐Diborylalkanes, such as intermediate H, treated with a mechanism depicted in Scheme
suitable base, are known to be deprotonated or mono‐ photocatalytic carbonyl‐carbonyl olefiDnOatI:io10n.103o9f/C9aSrCo0m07a1t1iCc
deborylated to boryl carbanions.23a,23b‐d, 23g The resulting α‐boryl aldehydes.
Initially, the photoexcited state of
anions react with carbonyl groups through a boron‐Wittig [IrIII(FCF3ppy)2dtbbpy]+ is reductively quenched by the sulfur
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pathway to give olefins. 23a,23b‐d, 23g Indeed, the olefinic product anion
A
, formed by the deprotonation of thiol by base, affording
III/II
could be obtained in an independent experiment treating sulfur radical
benzaldehyde 1d with 1,1‐benzyldiboronate ester
presence of Cs2CO3 (Scheme 3A). Moreover, we could trap the to benzaldehyde in the presence of B2pin2 gives the ground‐
α‐boryl anion as boronic esters S4‐D in the presence of D2O state Ir(III) and ketyl radical
. Subsequent radical borylation31
and anion or . The resulting
B
and [IrII(FCF3ppy)2dtbbpy] (Ir0
= ‐1.38V vs
1/2
H
in the SCE in DMF). Single electron transfer (SET) from the Ir(II) species
C
D
(10.0 eq) (Scheme 2). This is a strong hint that an α‐boryl of
carbanion is involved in our reaction pathway, although we
could not directly identify it via in situ NMR.
C
produces radical anion
E
F
2,2'‐Diphenyldicarboxaldehyde 1y was used to investigate a
potential intramolecular olefination reaction, but 9‐
phenanthrenol 2y’ was isolated as the main product (72%) with
only 3% of phenanthrene 2y (Scheme 3B; for more details, see
Supplementary Information).
Scheme 3 Further mechanistic studies
Next, we turned our attention to explore the origin of the Z/E
selectivity in the reaction. By NMR, we observed that the more
thermodynamically stable E isomer was formed dominantly at
the early stage of the reaction. Later, a E to Z isomerization
occurs, with the Z isomer being the major product (Table S8).
We rationalize the formation of E‐alkenes as the major
configuration at the early reaction stage as a consequence of a
syn boron‐oxygen elimination.23a, 28 Additional evidence for the
photo‐induced alkene isomerization process was obtained
when E‐alkene was subjected to the standard reaction
condition. The corresponding product was obtained in a similar
Z/E ratio (Z/E = 2.6/1, 96% yield) as in our reaction system.
(Scheme 4A).29 We also found that alkene E‐2a could be
obtained in one pot using the reported photo‐sensitized Z to E
isomerization strategy, giving alkene E‐2a in 77% (Scheme 4B).30
Scheme 5 Proposed reaction mechanism
radical anion
The three‐membered cyclic anion
rearrangement to form α‐oxyboryl carbanion
carbanion subsequently reacts with another molecule of
B2pin2 leading to the formation of 1,1‐benzyldiboronate ester
The base‐promoted mono‐deborylation of gives rise to the
formation of α‐boryl carbanion . After nucleophilic attack to the
carbonyl group of a second aldehyde, a four‐membered cyclic
intermediate is most probably formed, which affords E‐alkene
D
reduces the sulfur radical
undergoes a “bora‐Brook”
. The resulting
B back to the anion A.
F
G
G
H.
H
I
J
via a B‐O syn elimination. Finally, energy transfer from the
excited state of the photocatalyst to the E‐alkene produces a
mixture of Z and E isomers as the final product.
Conclusions
In summary, we have developed a photoredox‐catalyzed
reaction for reductive carbonyl‐carbonyl olefination of aromatic
aldehydes using B2pin2 as both the oxygen atom trap and the
terminal reductant. The reaction system provides a mild and
efficient method to prepare both symmetrical and
unsymmetrical diarylalkenes through intermolecular bicarbonyl
olefination and tolerates a broad range of functional groups.
Combining our in situ illumination NMR technique with a series
of mechanistic studies, α‐oxyboryl carbanion, α‐boryl carbanion
Scheme 4 Isomerization studies
Based on the above experimental evidence and mechanistic
pathways previously reported in literature, we propose the
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and 1,1‐benzyldiboronate esters were detected as key 12. W. Wei, X.‐J. Dai, H. Wang, C. Li, X. Yang and C.‐J.VLiei,wCAhrteicmle .OSnlcini.e,
intermediate species in the reaction. Furthermore, theoretical 2017, 8, 8193‐8197.
calculations corroborate the NMR observation of the cyclic 13. (a) J. M. R. Narayanam and C. R. J. Stephenson, Chem. Soc. Rev.,
DOI: 10.1039/C9SC00711C
three‐membered anionic species involved in the “bora‐Brook”
rearrangement. Mechanistic studies support the hypothesis
that the formation of the double bond is facilitated by a boron‐
Wittig process. This combination of photoredox catalysis with
boron chemistry constitutes a unique example of an Umploung
strategy to convert an aldehyde into a boryl‐functionalized
carbanion.
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Acknowledgements
This work was supported by the German Science Foundation
(DFG) (GRK 1626, Chemical Photocatalysis; KO 1537/18‐1). This
project has received funding from the European Research
Council (ERC) under the European Unions Horizon 2020
research and innovation programme (grant agreement No.
741623). S.W. thanks the China Scholarship Council (CSC) for a
predoctoral fellowship (CSC student number 201606280052).
N.L. acknowledges ERC for the funding. We are grateful to Dr.
Gregory S. Huff (University of Regensburg) for helpful
discussions and writing suggestions. We further thank Dr.
Rudolf Vasold (University of Regensburg) for his assistance in
GC‐MS measurements and Ms. Regina Hoheisel (University of
Regensburg) for her assistance in cyclic voltammetry
measurements.
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