Organocatalyzed Birch Reduction Driven by Visible Light

Article abstract of DOI:10.1021/jacs.0c05899

The Birch reduction is a powerful synthetic methodology that uses solvated electrons to convert inert arenes to 1,4-cyclohexadienes - valuable intermediates for building molecular complexity. Birch reductions traditionally employ alkali metals dissolved in ammonia to produce a solvated electron for the reduction of unactivated arenes such as benzene (Ered < -3.42 V vs SCE). Photoredox catalysts have been gaining popularity in highly reducing applications, but none have been reported to demonstrate reduction potentials powerful enough to reduce benzene. Here, we introduce benzo[ghi]perylene imides as new organic photoredox catalysts for Birch reductions performed at ambient temperature and driven by visible light from commercially available LEDs. Using low catalyst loadings (<1 mol percent), benzene and other functionalized arenes were selectively transformed to 1,4-cyclohexadienes in moderate to good yields in a completely metal-free reaction. Mechanistic studies support that this unprecedented visible-light-induced reactivity is enabled by the ability of the organic photoredox catalyst to harness the energy from two visible-light photons to affect a single, high-energy chemical transformation.

Full text of DOI:10.1021/jacs.0c05899

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Article
Organocatalyzed Birch Reduction Driven by Visible Light
Justin Cole, Dian-Feng Chen, Max Kudisch, Ryan Pearson, Chern-Hooi Lim, and Garret M. Miyake
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 14 Jul 2020
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Organocatalyzed Birch Reduction Driven by Visible Light
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Authors: Justin P. Cole1,3, Dian-Feng Chen1,3, Max Kudisch1, Ryan M. Pearson1, Chern-Hooi
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Lim2, Garret M. Miyake1*
1Colorado State University, Department of Chemistry, Fort Collins, CO 80523 USA. 2New
Iridium Inc. Boulder, CO 80303 USA. 3These authors contributed equally to this work.
*Correspondence to: garret.miyake@colostate.edu
Abstract
The Birch reduction is a powerful synthetic methodology that uses solvated electrons to
convert inert arenes to 1,4-cyclohexadienes—valuable intermediates for building molecular
complexity. Birch reductions traditionally employ alkali metals dissolved in ammonia to produce
a solvated electrons for the reduction of unactivated arenes such as benzene (Ered < -3.42 V vs.
SCE). Photoredox catalysts have been gaining popularity in highly-reducing applications, but none
have been reported to demonstrate reduction potentials powerful enough to reduce benzene. Here,
we introduce benzo[ghi]perylene imides as new organic photoredox catalysts for Birch reductions
performed at ambient temperature and driven by visible light from commercially available LEDs.
Using low catalyst loadings (<1 mole percent), benzene and other functionalized arenes were
selectively transformed to 1,4-cyclohexadienes in moderate to good yields in a completely metal-
free reaction. Mechanistic studies support that this unprecedented visible light induced reactivity
is enabled by the ability of the organic photoredox catalyst to harness the energy from two visible
light photons to affect a single, high energy chemical transformation.
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Introduction
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Visible light photoredox catalysis has transformed the synthesis of small molecules and
materials through the conversion of photochemical energy to chemical potentials enabling unique
reactivity under mild conditions.1-5 However, the scope of accessible chemical transformations
using these catalytic platforms is fundamentally confined by the energetics of a visible photon. For
example, a 400 nm photon provides 3.1 eV of energy, defining the upper limit for the
thermodynamic driving force for transformations using visible light. Thus, the low electron affinity
of inert substrates such as benzene render it unreactive and difficult to reduce by single electron
transfer requiring a reduction potential of -3.42 V vs SCE,5 while the high triplet energy of benzene
(3.6 eV) prevents triplet energy sensitization.6 As such, the reduction of benzene requires harsher
conditions than accessible by current visible light photoredox catalyst systems. The Birch
reduction—the prototypical example being the overall 2e-/2H+ reduction of benzene to 1,4-
cyclohexadiene—represents one of the most demanding reductions in organic synthesis and
traditionally employs solvated electrons as the reductant, generated using lithium or sodium metal
under cryogenic liquid ammonia conditions (Fig. 1a-b).7,8 Several variations of Birch reductions
have been develeloped, including ammonia-free,9 electrochemical10,11, and photochemical12, each
of which has increased the safety of performing Birch reductions. Despite these advances, the
development of a mild, metal-free, visible light-driven Birch reduction is highly desirable.
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To overcome the energetic constraints of a visible light photon, approaches to harness the
energetics of two photons into a single chemical event and access more challenging reactivity have
been developed.13 For example, under high photon flux conditions using a laser, an iridium (III)
complex underwent two successive photoexcitations allowing ionization to iridium (IV) and a
solvated electron;14 while promising, the practicality and utility of this system for Birch reductions
remains unknown. Efforts toward a Birch reduction driven by visible light utilized an iridium
complex that served as both a triplet sensitizer of the arene as well as a photoreductant in
conjunction with a sacrificial electron donor.15 However, this system was unable to reduce benzene
due to the high triplet energy of benzene and reactivity was restricted to arenes possessing lower
triplet energy.
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Fig. 1. Background and plausible mechanism of a visible light driven Birch reduction. (a)
Reaction conditions and considerations for traditional Birch reduction. (b) Mechanism of 2e-/2H+
reduction of benzene to afford 1,4-cyclohexadiene. (c) Plausible consecutive photoinduced
electron transfer (ConPET) catalytic cycle to merge the energetics of two photons to generate a
highly reducing solvated electron. D = electron donor (OH- or F- in this work).
In another approach to accessing more reducing power, the concept of consecutive
photoinduced electron transfer (ConPET) was applied with a perylene diimide (PDI) system.16,17
Here, the first photon generates an excited-state PDI that is reduced by a sacrificial electron donor
to yield a radical anion. Subsequently, the radical anion is photoexcited by a second photon,
generating a much stronger reducing species. This catalytic system was employed in the reduction
of aryl halides to generate aryl radicals that could be coupled with an appropriate trapping agent.
Similarly, reductive quenching of an acridinium PC was found to generate an acridine radical that
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could be photoexcited for the reduction of aryl chlorides and the reductive detosylation of
amines.18 However, reduction of the aromatic ring was not observed in any of these systems.
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Recently, replacing the first photoinduced electron transfer (PET) step to generate the
radical anion, electrochemical reduction of naphthalene imides19 or dicyanoanthracene20 catalysts
was reported. Electrochemical reduction of the catalyst afforded a stable radical anion that can be
subsequently photoexcited to a strongly reducing species capable of reducing aryl halides,
including aryl chlorides, to aryl radicals for subsequent coupling reactions. Although these systems
generate catalyst species with reactivity near Li0 and excited-state reduction potentials < -3 V vs
SCE, reduction of the arene ring was not observed. Thus, Birch reduction reactivity by a visible
light photoredox catalyst (PC) system remains elusive.
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Our interest in photoredox catalysis originated with the motivation to develop strongly
reducing organic PCs for organocatalyzed atom transfer radical polymerization (O-ATRP). Using
computationally accelerated discovery we have identified N,N-diaryl dihydrophenazines,21 N-aryl
phenoxazines,22 and N-aryl dimethyl-dihydroacridines23 as classes of strongly reducing organic
PCs. The most successful O-ATRP catalysts have impressively strong excited-state reduction
potentials, some possessing E0(PC•+/PC*) < -2 V vs SCE, representing some of the strongest single
photon visible light PC reductants known. This work has motivated us to identify even more
strongly reducing PC systems targeting the reduction of benzene and other arenes. Acknowledging
the limitations of single photon photoredox catalysis, we envisioned that through exploiting a
ConPET process we could realize a catalyst system for the reduction of benzene (Fig. 1c).
Results and Discussion
Our pursuit of a visible light photoredox catalyzed Birch reduction led to the investigation
of benzo[ghi]perylene monoimides (BPIs) as potential PCs.24 This class of molecules possesses a
computationally predicted high-energy lowest unoccupied molecular orbital (LUMO) [or in
equivalence, relatively low electron affinity at E0comp(PC/PC•-) ~ -1.3 V vs. SCE].25 This reduction
potential is significantly more negative than that reported for a PDI [E1/2(PDI/PDI•-) = -0.43 V vs.
SCE] that is structurally very similar to the PC used in the ConPET system above.26 Thus, we
hypothesized that by utilizing the more strongly reducing PC•- accessible with BPIs,
photoexcitationto PC•-* would access an even more reducing excited state that might be competent
for the reduction of benzene. To test this hypothesis, we synthesized a family of targeted PCs in
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two to four steps from commercial reagents, resulting in a series of BPI molecules possessing
electron neutral, withdrawing, and donating core-substituents on the 6-, 8-, and 11- core-positions
of the BPI (Fig. 1c). All these molecules exhibited strong visible light absorption (wavelength of
maximum absorption λmax > 400 nm and molar absorptivity εmax > 20,000 M-1cm-1), high-lying
LUMOs [E1/2,exp(PC/PC•-) < -1.2 V vs. SCE], and redox reversibility for single electron transfers
as determined by cyclic voltammetry (Table S5).
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To investigate the ability of these molecules to serve as PCs in a ConPET mechanism, we
first examined the light-induced reduction of the BPI by an electron donor to generate the PC
radical anion (PC•-). While commonly employed trialkyl amine electron donors failed to generate
the PC•-, we found that OH- and F- ions could reduce the PC upon light irradiation through taking
advantage of an association reaction analogous to that observed in the light-gated reduction of
naphthalene diimides (NDIs) with Cl- as the reductant (we note that the association reaction
observed here resulted in a different type of complexation; see below for a mechanistic
discussion).27 The lack of reactivity of trialkylamines likely results from both their inability to
associate with the PC and the lack of driving force for the electron transfer (E0*comp[3PC*/2PC•-] =
0.38 V vs. SCE; Ep/2[Et3N/Et3N•+ = 0.83 V vs. SCE).28 Our initial survey of the targeted photoredox
catalyzed Birch reduction implemented 2-phenylethanol as the substrate to produce the
cyclohexadiene product, 2-(cyclohexa-1,4-dien-1-yl)ethan-1-ol (1). Gratifyingly, using the
various BPI PCs (0.25 mol%), NBu4OH (2 equivalents) as the electron source,29 in mixed methanol
and tert-amyl alcohol as the solvent and H+ source, and irradiated with a 405 nm LED resulted in
conversion of the arene to the target product, albeit in low conversions (Table S2). The BPI
derivative possessing p-OMePh core-substituents outperformed the other PCs, resulting in 17%
conversion after 16 hours. Surveying potential reductants revealed that using the less sterically
hindered NMe4OH and increasing the loading to 10 equivalents resulted in an increase in
conversion to 42% after 48 hours.
The reaction still proceeded using a lower catalyst loading (0.1 mol%), but conversion did
not improve with increased catalyst loading (e.g. 1 mol%), presumably because of quenching of
the photoexcited PC (PC*) or the catalyst decomposing as an aromatic substrate in the reaction
(Table S2). We found that conversion slowed dramatically after 48 hours, so catalyst was added
to the reaction at intervals in order to drive the reaction to higher conversions. Excitingly, it was
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found that 88% conversion (70% isolated yield, 1 in Fig. 2b) could be achieved by adding a total
of 0.75 mol% of catalyst divided over three additions during the course of the reaction (96 h).
Control experiments revealed that the reaction did not proceed or resulted in minimal conversion
with omission of any single component (PC, OH-, H+ source, or light). While the reaction was not
•-
oxygen tolerant (PC•- can be quenched by O2, E0(O2/O2 ) ~ -1.0 V vs SCE)30 it was tolerant to
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water.
With these reaction conditions established, we explored the general applicability of this
photoinduced Birch reduction (Fig. 2). The reduction of structurally similar 1-phenyl-2-propanol
(a secondary alcohol) also proceeded well to afford product 2 in 62% yield. Notably, additional
substituents on the phenyl ring affected reaction efficiency. For example, meta- and para-methyl
phenyl ethanol exhibited reduced reactivity and products 3 and 4 were isolated in 51% and 48%
yield, respectively. The introduction of a methyl group at the ortho-position significantly inhibited
the reactivity (5, 24% yield). Functional groups, such as carboxylic acid (6 and 7), amide (8),
carbamate (9 and 10), and strained cyclopropane (7) are well-tolerated. The reduction of feedstocks
benzene, toluene, and other simple mono- or di-substituted alkyl benzene derivatives were
successful as well, affording 11-14 in moderate to high yields (38-80%). Remarkably, the cyclic
ether motif was preserved in the high-yielding reduction of isochroman derivatives (15 and 16),
while exclusive benzyl C-O bond cleavage occurs under conventional Birch conditions using
lithium.31 Similarly, 1,3-dihydroisobenzofuran and 1,2,3,4-tetrahydroisoquinoline were
transformed to 17 and 18 in 82% and 40% yield, respectively. We also demonstrated that this Birch
reduction methodology was capable of generating products 1 and 17 on a larger scale. Performing
the reaction at 10 mmol (1.2 g) scale, we achieved 70% conversion (52% isolated yield) to product
1 and 98% conversion (91% isolated yield) to product 17. Scale-up required minimal optimization
as the same reactant stoichiometry was used in a larger reactor with using four 405 nm LEDs.
Under these prescribed reaction conditions this methodology proved less successful or ineffective
in the reduction of electron rich arenes as well as with substrates possessing alkenes, alkynes, alkyl
halides, unprotected amines, or nitrogen containing heterocycles (Fig. S1).
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Fig. 2. Synthesis of 1,4-cyclohexadienes by visible light driven Birch reduction of arenes. (a)
General reaction conditions. (b) Substrate scope; isolated yields are reported unless otherwise
indicated. 144 h reaction, otherwise 96 h. Yield determined by H NMR using 1,3,5-
trimethoxybenzene as the internal standard. cSee Supplementary Information for details. Scale: 0.5
mmol in arene unless otherwise indicated.
a
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Selective reduction of arenes containing multiple reactive unsaturated functional groups
could be achieved through modulation of the reaction conditions (Fig. 3). Interestingly, reduction
of one or both phenyl rings of diphenyl ether was observed (20 and 22), as well as the over-
reduction to afford vinyl ethers 21 and 23. Employing optimized conditions, benzophenone
proceeded through the tandem reductive deoxygenation and Birch reduction to afford 1-benzyl-
1,4-cyclohexadiene 25 in 42% yield. By manipulating the equivalents of NMe4OH and reaction
time, cinnamyl alcohol could be converted to either phenylpropanol 27 through alkene reduction
or 28 via both alkene and aromatic reductions. Similarly, trans-2-phenylcyclopropane-1-
carboxylic acid underwent a reductive ring-opening process to give 30 in 73% yield, while further
reduction provided 31 in 40% yield. Additionally, dehalogenation of the pharmaceutical loratadine
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was facile (33, 65% yield), although significant transesterification also occurred with the solvent
(34).
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Fig. 3. Selective reductions. Modulation of the reaction conditions enables selective reduction.
To investigate the mechanism underlying this reactivity, a combination of spectroscopic
studies and density functional theory (DFT) calculations were performed (Fig. 4). Overall, these
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results support a catalytic cycle involving two photon absorption steps in this photoredox catalyzed
Birch reduction (Fig. 4a). Prior to irradiation, a color change from orange to yellow was observed
upon OH- addition to an orange solution of the PC, suggesting dark reactivity between the PC and
OH- (Fig. 4b). To further investigate the nature of this interaction, a series of solutions were
analyzed by UV-visible spectroscopy (UV-vis) in which the molar ratio of OH- was increased
while the total volume of each solution was held constant. In this titration experiment, absorption
bands assigned to the PC (λabs,max = 353, 423, and 507 nm) decrease with increasing [OH-] in
conjunction with the appearance of new absorbance features (λabs,max = 312 and 412 nm).
Monitoring the emission of these same mixtures shows a progressive decrease in the intensity of
the PC fluorescence (λem,max = 563 nm) with the appearance of emission from a new species (λem,max
= 481 nm), supporting assignment of a 1:1 equilibrium binding model.32 Fitting the UV-vis data
to this 1:1 model yields the equilibrium constant for OH- association (Keq =920 M-1). It is relevant
to note that in the formation of a charge-transfer anion-π complex between iodide and NDIs a red-
shift was reported,as opposed to the blue-shift observed here, suggesting a fundamentally different
mode of complexation in this system.33 Interestingly, 13C NMR supports formation of a covalent
hydroxide adduct [PC-OH]- (Fig. 4b, SI Figs. S114-S116) rather than an anion-π type complex.27
A new signal emerges after the addition of 100 eq. of either OH- (δ = 173.9 ppm) or F- (δ = 173.0
ppm) which suggests a new covalent bond is formed in the proximity of the imide moiety.
Formation of [PC-OH]- is further supported by DFT calculations (Fig. 4a), which predict the
complex formation to be exergonic by 3.0 kcal mol-1 (Keq,comp =150 M-1) along with a qualitative
blue-shift in the predicted lowest energy UV-vis absorption (λabs,max,comp from 408 to 376 nm).
Thus, spectroscopic data and DFT computations support that OH- attacks the PC reversibly to form
[PC-OH]-, which comprises the majority species in the equilibrium mixture under reaction
conditions (i.e. OH-:PC molar ratio of 800-1333:1 in the reactions performed to determine scope
(Fig. 2 and Fig. 3)). Further, [PC-OH]- is stable in the dark such that thermally-induced electron
transfer does not occur and is predicted to be endergonic by 44.8 kcal mol-1, although such ground
state reactivity was observed with the structurally related PDIs and NDIs.34,35 Finally, control
experiments reveal that in the absence of OH-, the PC* is not quenched by either benzene or
alcohols, supporting that the catalytic cycle proceeds through [PC-OH]- (Fig. S18).
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Fig. 4. Mechanistic studies. (a) Proposed mechanism of ConPET proceeds through a covalent
[PC-OH]- complex; DFT predicted values are shown in purple and experimentally measured
values in turquoise; Electrochemical reference in V vs. SCE; Ar = p-OMePh. (b) Association of
the PC and OH- can be observed by absorption (left), fluorescence (middle), and 13C NMR (right)
spectroscopy; R = 2-ethylhexyl (c) The PC•- is stable and can be observed by absorption (left) and
EPR (middle) spectroscopy; Computational characterization of PC•- by visualization of spin
density and electrostatic potential (ESP)-mapped electron density depicting electron-rich “red” and
electron-poor “green” regions (right). (d) Nanosecond transient absorption spectroscopy of PC•-;
irradiation performed with a 405 nm LED (middle and right).
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With the dark speciation of the PC/OH- mixture driven towards [PC-OH]-, we next
investigated its reactivity under the influence of light (Fig. 4c). Upon photon absorption, we
propose that PET occurs intramolecularly from OH- to the imide moiety to form the radical anion
PC•- and OH•. While the fate of OH• (primarily O•- under basic conditions)36 is currently unknown,
we hypothesize that it may react with the methanol solvent to produce a hydroxymethyl radical
and OH-;37 further studies to elucidate the ultimate fate of these reactive species are ongoing in our
laboratory. This PET step is predicted by DFT to be exergonic by 11.5 kcal/mol and
thermodynamically driven by the lowest singlet excited state of the [PC-OH]- [E(S1)exp = 2.57 eV;
E(S1)comp = 2.44 eV] (Fig. 4a). Time-dependent DFT calculations suggest that the relevant
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absorption for [PC-OH]- under 405 nm LED irradiation is the HOMO–LUMO transition (Ecomp
=
3.29 eV, 376 nm, f = 0.709) which is of π-π* nature (Fig. S118).
The formation of PC•- is further supported by multiple independent experiments. First,
upon irradiation of [PC-OH]- with a 405 nm LED a color change from yellow to purple is observed
along with the appearance of several new absorption bands (λabs,max = 580 nm). In support that this
new species is the persistent radical PC•-, the same absorbance spectrum could be observed when
using F- as the electron source or through bulk electrolysis at an applied potential (Eapp = -2.26 V
vs SCE) (Fig. 4c). In addition, electron paramagnetic resonance (EPR) spectroscopy was used to
characterize the photogenerated PC•-. The experimental EPR spectrum could be reasonably
simulated38 and demonstrated delocalization of the unpaired electron on the benzo[ghi]perylene
monoimide core as indicated by its interactions with N (a = 1.985 G), two equivalent methylene
Hs adjacent to the N (a = 0.540 G), and seven non-degenerate Hs on the aromatic core (a values =
0.611, 0.612, 0.639, 0.644, 0.644, 0.645, and 0.645 G); other parameters used in the simulation
include gisotropic = 2.00171, linewidth = 0.666 G and lineshape = gaussian (Fig. S42). PC•- was
further characterized by visualization of the DFT-predicted spin density in which the unpaired
electron is localized on the imide moiety and to a lesser extent delocalized over the methylene
group adjacent to nitrogen and the aromatic system on the BPI core.
Although PC•- is a relatively strong reductant [E1/2,exp(PC/PC•-) = -1.24 V vs SCE; E0
comp
(PC/PC•-) = -1.30 V vs SCE], this reducing power is insufficient for a Birch reduction and
reactivity is not observed in the absence of light. Thus, we hypothesized that PC•- absorbs a second
photon to generate PC•-*, a much stronger reductant that can engage in Birch reduction (Fig. 4d).
Notably, PC•- is a persistent radical with sufficient lifetime for reversible CV and EPR analysis.
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This long-lifetime allows PC•- to absorb a photon using a practical LED setup as opposed to
requiring laser irradiation.14 The excited state properties of the PC•-* were predicted using time-
dependent DFT calculations to evaluate the thermodynamic feasibility of generating a solvated
electron or directly reducing the substrate. We determined that the first six doublet excited states
of PC•-* can be accessed with a 405 nm photon (3.06 eV) used in this study (Fig. S117). Excited
states 2 through 6 have enough energy for ionization of PC•-* by an electron transfer to the solvent
(kET,1) to form a solvated electron and the ground state PC. For efficient generation of a solvated
electron, kET,1 must be competitive with the internal conversion process (kIC) deactivating high-
lying excited states to the lowest doublet excited state of PC•-*, which is below the energy threshold
for both solvated electron formation and the direct PET to benzene. Solvated electron formation
has been observed to occur in as little as 11 ± 1 picoseconds in methanol, supporting the feasibility
of this competition.39 Further, electron transfer from the solvated electron to an aromatic substrate
(kET,2) for Birch reduction reactivity must also be facile relative to the unproductive back electron
transfer to the lowest excited state of PC•-* (kET,3).
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The photoexcitation of PC•- was investigated using nanosecond transient absorption
spectroscopy (Fig. 4d). Selective excitation of PC•- could be achieved through irradiation at 532
nm due to the minimal spectral overlap with PC or [PC-OH]-. Laser excitation produces a ground
state bleach feature (λmin = 580 nm) that matches the absorption of PC•- and thus can be assigned
to PC•-*. Kinetic monitoring of this signal reveals that the baseline is not recovered on the
millisecond timescale, indicating that PC•-* decomposes. Decomposition is consistent with either
direct PET to the substrate or the production of a solvated electron, as both processes yield the
neutral, closed-shell PC which lacks an absorption at λ = 580 nm. Since the photoionization event
to release a solvated electron is orders of magnitude faster than the time-resolution of our TA setup
(vide supra), the absorption signal of the solvated electron would be expected to appear in the TA
spectrum immediately following the laser pulse at t = 0 ns. However, we note that in THF the
solvated electron has been observed at λmax = 2120 nm, which is outside the range of our detector.40
We have attempted the measurement in MeOH where this absorption would fall within the visible
spectrum so far without success, likely due to the low solubility of the PC in MeOH and the
resulting challenge of generating high enough concentrations of PC•- for spectroscopic study.
Interestingly, the observed excited state PC•-* is several orders of magnitude longer-lived
than the doublet excited states of other aromatic imides and diimides.26 This observation suggests
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that the signal followed by TA can be tentatively assigned to the lowest quartet excited state 4PC•-
*
produced via intersystem crossing (ISC) from the doublet manifold, as has been observed to
occur upon excitation of other persistent organic radicals such as the enzyme DNA photolyase.41,42
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Comparing the kinetic traces at λprobe = 580 nm when the benzene substrate is present as a potential
4
quencher does not reveal a significant change in the lifetime of PC•-* (Fig. S15), suggesting that
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4PC•-* does not react efficiently with the substrate. Considering that the computed lowest doublet
state 2PC•-* is also unlikely to reduce benzene (insufficient by ~ 1.0 V vs. SCE, Fig. S117), direct
PET to the substrate appears to be thermodynamically unfavorable. One possibility to achieve
increased driving force involves the occurrence of PET from a higher lying excited state in an anti-
Kasha fashion, an unlikely prospect that is typically observed only in systems in which
intramolecular PET is possible.43 Although we do not see evidence by UV-vis for association of
[PC-OH]- or PC•- with benzene (Fig. S13), we are actively investigating the alternate hypothesis
that PC•- may form ground state π-stacking complexes or exciplexes with benzene to enable
intramolecular PET, potentially through an Anti-Kasha process. These considerations taken
together suggest the working hypothesis that PC•-* photoionizes with kET,1 competitive with kIC,
releasing a solvated electron that subsequently reduces the substrate. Overall, the initial
mechanistic experiments herein support the formation of [PC-OH]- and subsequent
photodissociation to form PC•-. Further experiments are currently ongoing to elucidate the role of
2PC•-*, 4PC•-*, and the competition between kET,1 and kIC.
Conclusion
In sum, a class of organic benzo[ghi]perylene imide photoredox catalysts were developed
for Birch reductions under mild benchtop conditions and visible light LED irradiation. This work
represents the first visible light photoredox catlysis system that is capable of engaging arenes such
as benzene that were previously out of reach due to their high triplet energies and extremely
negative reduction potentials. Despite this unprecedented reactivity, this platform requires further
development to realize its full synthetic potential. Initial mechanistic experiments support the
formation of the hydroxide adduct [PC-OH]- and its subsequent photodissociation to PC•-, which
we posit undergoes absorption of a second photon to release a solvated electron as the active
reductant. Future mechanistic studies are ongoing to test this hypothesis and to identify
mechanistically-guided PC design principles for more robust and active PCs to improve the scope
of photocatalyzed Birch reductions.
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Acknowledgments: This work was supported by Colorado State University and the National
Institutes of Health under Award Number R35GM119702. The content is solely the responsibility
of the authors and does not necessarily represent the official views of the National Institutes of
Health. This work used the Extreme Science and Engineering Discovery Environment (XSEDE),
which is supported by National Science Foundation Grant ACI-1548562.
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Competing interests: We have filed a provisional patent application on the work described here
Data and materials availability: Single-crystal X-ray diffraction data is deposited at the
Cambridge Crystallographic Data Center under CCDC 1912318 and is contained in the .CIF file
attached to this manuscript. All data is available in the main text or the supplementary materials.
The data that support the findings of this study are available from the corresponding author upon
reasonable request.
Supplementary Information:
Materials and Methods
Figures S1-S119
Tables S1-S7
Coordinates of Calculated Molecular Structures
X-Ray Crystallographic Data for PC 8
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Organocatalyzed Birch Reduction Driven by Visible Light
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Authors: Justin P. Cole1,3, Dian-Feng Chen1,3, Max Kudisch1, Ryan M. Pearson1, Chern-Hooi
Lim2, Garret M. Miyake1*
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1Colorado State University, Department of Chemistry, Fort Collins, CO 80523 USA. 2New Iridium
Inc. Boulder, CO 80303 USA. 3These authors contributed equally to this work. *Correspondence
to: garret.miyake@colostate.edu
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