Photochemical Activation of a Hydroxyquinone-Derived Phenyliodonium Ylide by Visible Light: Synthetic and Mechanistic Investigations

Article abstract of DOI:10.1021/acs.joc.0c02592

We have identified and extensively investigated the photochemical activation and reaction of a hydroxyquinone-derived phenyliodonium ylide in the presence of visible light using experiment and theory. These studies revealed that in its photoexcited state this iodonium is capable of facilitating a range of single-electron transfer (SET) processes, including hydrogen atom transfer (HAT), a Povarov-type reaction, and atom-transfer radical addition chemistry. Where possible, we have employed density functional theory (DFT) to develop a more complete understanding of these photoinduced synthetic transformations.

Full text of DOI:10.1021/acs.joc.0c02592

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Article
Photochemical Activation of a Hydroxyquinone-Derived
Phenyliodonium Ylide by Visible Light: Synthetic and Mechanistic
Investigations
Mona Jalali, Curtis C. Ho, Rebecca O. Fuller, Nigel T. Lucas, Alireza Ariafard,* and Alex C. Bissember*
Cite This: J. Org. Chem. 2021, 86, 1758−1768
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ABSTRACT: We have identified and extensively investigated the
photochemical activation and reaction of a hydroxyquinone-
derived phenyliodonium ylide in the presence of visible light
using experiment and theory. These studies revealed that in its
photoexcited state this iodonium is capable of facilitating a range of
single-electron transfer (SET) processes, including hydrogen atom
transfer (HAT), a Povarov-type reaction, and atom-transfer radical
addition chemistry. Where possible, we have employed density
functional theory (DFT) to develop a more complete under-
standing of these photoinduced synthetic transformations.
and excited-states and explore the viability of phenyliodonium
1a to promote single electron-transfer processes induced by
visible light.
INTRODUCTION
■
Zwitterionic hydroxyquinone-derived phenyliodonium ylides,
such as molecules 1, are an established class of compounds that
are air-stable, both in solution and the solid state (Figure
1).1−3 The X-ray crystallographic characterization of lawsone
derivative 1b confirms that this structure is zwitterionic
consisting of a positively charged iodine atom and a negative
charge delocalized across three contiguous carbon centers.3
These hydroxyquinone-derived iodoniums can engage in
synthetically useful bimolecular reactions, such as transition-
metal-catalyzed cross-couplings with organometallic nucleo-
philes, other C−C bond-forming reactions, and formal
cycloadditions.4 However, ylides such as compound 1a are
particularly susceptible to thermally promoted intramolecular
rearrangements.2 These processes furnish cyclopentenediones
via putative cyclic ketenes (Figure 1A). Although highly
reactive ketenes, such as species 2a, have not been isolated,
their existence is supported by both experiment and
theory.2b,5,6
We recognized that hydroxyquinone-derived phenyliodo-
nium ylides 1 represent a relatively underutilized class of
compounds in synthesis. In response, we sought to explore and
extend the synthetic applications of these types of molecules
accordingly. Specifically, we wanted to investigate the capacity
for visible light to activate these systems and further unlock
their potential. It was recently reported that β-dicarbonyl-
derived iodonium ylides, such as 1d, engage in cyclo-
propanation reactions with olefins in the presence of visible
light (Figure 1B),7 which contrasts with the formation of
dihydrofuran products when UV irradiation is employed.8 In
this work, we employ experiment and theory to study the
fundamental reactivity of related molecule 1a in the ground-
RESULTS AND DISCUSSION
■
First, we prepared hydroxyquinone-derived phenyliodonium
ylide 1a on an 11-g scale (72% yield) from commercially
available 1,2,4-trihydroxybenzene in one step (Figure 2A).2b
We also confirmed the structure of compound 1a by single
crystal X-ray crystallography for the first time (Figure 2B).
This established that the structure of molecule 1a is consistent
with that of lawsone-derived phenyliodonium 1b.3 We
observed that the asymmetric unit contains two crystallo-
graphically independent molecules that differ insignificantly in
their geometric parameters. The molecules display biaxial
noncovalent interactions between the iodine atom of one
molecule and the carbonyl oxygen atoms of another (I1···
O4,O5 2.828, 3.132 Å).
The traditional approach of using close contacts to elucidate
packing and structural features can be greatly enhanced
through the visualization of the electrostatic potential
distribution for the determined crystallographic structure.9
We mapped the electrostatic potential at HF 3-21G onto an
electron density isosurface in which areas of blue are associated
Received: October 30, 2020
Published: December 30, 2020
https://dx.doi.org/10.1021/acs.joc.0c02592
© 2020 American Chemical Society
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Figure 1. (A) Representative hydroxyquinone-derived phenyliodo-
nium ylides and thermally promoted formation of cyclopentenedione
3a from phenyliodonium 1a. (B) Reported photoinduced cyclo-
propanation of phenyliodonium 1d.7
with positive regions of the surface with red assigned as
negative electrostatic potential (Figure 2C). This highlights
that these close contacts are likely to involve the electropositive
region of the iodine and neighboring negative potential of the
oxygen atoms. The biaxial coordination of the neighboring
iodonium compound appears to primarily arise from the
electrostatic complementarity of the neighboring molecules.10
The most positive part of the surface is associated with the
phenyl group of the adjacent molecule. Notably, we could not
find evidence of a binding mode consistent with a halogen
bond donor/acceptor pair. Such interactions have recently
been invoked for germane supramolecular structures compris-
ing hypervalent iodine(III) molecules and chelating Lewis
bases.11
Figure 2. (A) Synthesis of phenyliodonium ylide 1a; PIDA =
(diacetoxyiodo)benzene. (B) Structural representation of molecule 1a
with thermal ellipsoids drawn at the 50% probability level and
hydrogen atoms are omitted for clarity: Selected bond lengths (Å)
and angles (deg): I1−C1,C7 2.076(5), 2.117(5), C1−C2,C6
1.383(7), 1.432(8), C2−O1,C3 1.261(6), 1.549(7), C3−O2,C4
1.223(7), 1.461(8), C4−C5 1.327(8), C6−O3,C5 1.230(7),
1.491(8), C1−I1−C7 94.9(2). (C) Electrostatic complementarity
for neighboring phenyliodonium molecules 1a interpreted via the
mapping of the electrostatic potentials on 0.002 au isosurfaces of the
electron density calculated with HF 3-21G wave functions. Values
between −0.05 au (red) and +0.05 au (blue) have been mapped; 1 au
= 2627.21 kJ/mol.
Thermal Activation of Ylide 1a. Next, we resolved to use
theory and experiment to better understand the thermally
promoted transformation of iodonium 1a to ketene 2a. By
1
monitoring the consumption of substrate 1a via H NMR
spectroscopy, we observed that phenyliodonium 1a does not
undergo reaction in acetonitrile at ambient temperature in the
dark over 24 h (Table 1, entry 1).12 This reaction proceeds
relatively slowly at 40 °C (entries 2 and 3) and much faster at
60 and 80 °C as one might expect (entries 4 and 5). The
consumption of molecule 1a is faster in chloroform (entries 6−
8), a nonpolar solvent, and was not inhibited by the presence
of TEMPO (entry 9). These observations are consistent with
the absence of SET processes under these conditions. We
attempted to trap ketene 2a as its corresponding (dppf)nickel-
(ketene) adduct;13 however, despite considerable experimen-
tation, all efforts to isolate such a complex were not successful.
In 2008, a DFT study employing B3LYP level of theory in
the gas phase proposed that this transformation proceeds via a
concerted mechanism involving a 4-membered [1.1.0] cyclic
transition state (1a → 2a: ΔG‡ = 11.6 kcal/mol).6,14 These
calc
calculations, which suggest an extremely low activation energy
barrier for this process, appear inconsistent with many of the
results shown in Table 1 and previous experiments reporting
the thermal reaction of phenyliodonium 1a.2b We noted that in
a recent study exploring the mechanism of an IBX-mediated
oxidation reaction it was determined that the M06-2X
functional predicts energies of hypervalent iodine species
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Table 1. Thermal Reaction of Phenyliodonium 1a: Influence
of Reaction Parameters
Table 2. Free Energies of Activation (ΔG‡) and Reaction
(ΔGrxn) Calculated at Different Levels of Theory and
a
a
Solvents for Transformation of 1a → 2a
b
entry
variation
24 °C
40 °C
40 °C
60 °C
time (h)
yield (%)
1
2
3
4
5
6
7
8
24
1
2
0 (0)
21 (37)
41 (45)
97 (100)
90 (100)
17 (20)
39 (44)
80 (87)
40 (45)
1
80 °C
0.25
0.5
1
2
2
in CDCl3, 40 °C
in CDCl3, 40 °C
in CDCl3, 40 °C
40 °C
c
9
a
Reactions were performed in the dark employing 12.3 μmol 1a,
b
[0.03 M]. Yield of 3a determined by 1H NMR spectroscopy with the
aid of a calibrated internal standard (average of 2 experiments).
Performed in the presence of TEMPO (2 equiv); consumption of 1a
is shown in parentheses.
optimization method single point method
solvent
ΔG‡
ΔGrxn
−41.8
c
SMD/B3LYP-D3/
BS1
SMD/B3LYP-D3/
BS2
CD3CN
18.4
CDCl3
CD3CN
20.6
27.0
−42.1
−41.3
more accurately than other DFT methods, including B3LYP.15
Consequently, we investigated the transformation of 1a → 2a
using the M06-2X functional while also accounting for the role
of solvent in this reaction.16 The respective free energies of
activation for the thermal process starting from iodonium 1a
determined via this approach were higher than equivalent
results obtained at the B3LYP level (Table 2). Specifically,
these data suggest that the activation energy barriers are
underestimated by the B3LYP level of theory. We determined
that ΔG‡ = 27.5 kcal/mol for 1a → 2a in CD3CN using SMD/
CCSD(T)/BS2//SMD/M06-2X-D3/BS1 calculations and this
further supports the higher accuracy of the M06-2X method in
predicting the barrier height. Our calculations also reveal that
formation of ketene 2a from 1a is exergonic (ca. −40 kcal/
mol), which is consistent with the irreversible nature of the
process.
Although formation of molecule 2a from iodonium 1a is
thermodynamically favorable, our DFT calculations are
consistent with ketene 2a being particularly sensitive to
moisture (Figure 3).17 Specifically, the addition of a water
molecule to ketene 2a requires minimal free energy of
activation (ΔG‡ = 8.5 kcal/mol) and affords enol B in an
exergonic fashion (ΔG = −9.0 kcal/mol). Intermediate B is
predicted to be in equilibrium with zwitterion D. The reaction
of the latter with a water molecule then produces species F.
This is followed by the rate-determining decarboxylation step
that likely affords species G (ΔG‡ = 24.4 kcal/mol).
Surmounting this relatively high activation energy barrier is
consistent with the need to heat the reaction above ambient
temperature to facilitate an efficient reaction (Table 1). Finally,
we propose that product 3a is obtained from intermediate G
following another proton transfer step involving water.
Photochemical Activation of Ylide 1a. We determined
that the absorption maximum for molecule 1a is 439 nm
employing UV−vis spectroscopy.18 This prompted us to
investigate the capacity for visible light to facilitate the
photochemical activation of this phenyliodonium. We
monitored the reaction of substrate 1a in the presence of
SMD/M062X-D3/
BS1
SMD/M062X-D3/
BS2
CDCl3
26.3
−42.3
a
Selected bond distances (green) and free energies are given in Å and
kcal/mol (referenced to compound 1a), respectively. BS1 =
LANL2DZ,6-31G(d) and BS2 = def2-TZVP.
1
visible light at 0 °C via H NMR spectroscopy and observed
the rapid consumption of this compound within 45 min (Table
3, entries 1−3). No reaction occurred in the absence of light,
the consumption of molecule 1a was much slower in a polar
solvent, and the consumption of 1a still occurred at −50 °C
(entries 4−8). Notably, in all of these experiments, product 3a
was not formed. However, dione 3a could be synthesized when
substrate 1a was irradiated in acetonitrile at 40 °C (entry 10).
Control experiments suggest that the formation of product 3a
occurs by both thermal and photochemical pathways under
these conditions (Table 1, entry 2 vs Table 3, entry 10).
Interestingly, while the consumption of substrate 1a decreased
in the presence of TEMPO and visible light, a similar yield of
dione 3a was obtained under these conditions (Table 3, entry
11).
We employed TD-DFT calculations at the CAM-B3LYP
level of theory to investigate the mechanism of photoactivation
for iodonium 1a and understand why irradiation with visible
light appears to accelerate the transformation 1a → 3a (Figure
4A). Although our studies revealed the existence of a band at
440 nm, the oscillator strength was negligible. However, the
second excitation at 380 nm was identified, which corresponds
to the transition of an electron from the HOMO to the LUMO
of substrate 1a (Figure 4B). Specifically, this involves the
transfer of an electron from the nonbonding lone pair on C1
atom to the C3C4 π* orbital (oscillator strength of f =
0.03).19 Due to the nature of this charge transfer, the
optimization of this excited state gives a structure in which
the I−C bonds are largely intact (see the structural parameters
for species 1a and 1a*; Figure 4A). The ensuing excited
structure was then used as an initial starting point for geometry
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Figure 3. A free energy profile for the conversion of 2a → 3a calculated by BS1 = LANL2DZ,6-31G(d) and BS2 = def2-TZVP. Free energies are
given in kcal/mol and referenced to compound 2a.
Table 3. Reaction of Phenyliodonium 1a in the Presence of
a
Visible Light: Influence of Reaction Parameters
b
entry
variation
time (min)
yield (%)
1
2
3
4
5
6
7
8
9
none
none
none
45
30
15
45
15
30
60
150
60
60
60
<1 (100)
<1 (90)
<1 (50)
0 (0)
no hν
in CD3CN
in CD3CN
in CD3CN
−50 °C
40 °C
in CD3CN, 40 °C
in CD3CN, 40 °C
<1 (9)
<1 (22)
<1 (38)
<1 (41)
<1 (100)
50 (100)
56 (73)
10
11
c
a
Reactions performed employing 12.3 μmol 1a, [0.03 M]; blue LED
b
1
λmax = 467 nm. Yield of 3a determined by H NMR spectroscopy
with the aid of a calibrated internal standard (average of 2
c
experiments). Performed in the presence of TEMPO (2 equiv);
consumption of 1a is shown in parentheses.
optimization of the triplet state and negligible change in the I−
C bond distances was observed upon moving from
intermediate 1a* to 1a*_T. The triplet structure was
determined to be 38.3 kcal/mol higher in energy than ground
state 1a. Notably, upon photoexcitation, the oxidation state of
the iodine center in the long-lived triplet structure 1a*_T
remains unchanged as negligible spin density resides on the
iodine center within triplet structure 1a*_T. This is because
Figure 4. (A) Simplified Jablonski diagram showing the photo-
chemical activation pathway leading to triplet structure 1a*_T
calculated by SMD/CAM-B3LYP/LANL2DZ,6-31G(d) in acetoni-
trile. Potential energies (blue) are given in kcal/mol and referenced to
compound 1a; selected bond distances (green) are given in Å. (B)
Spatial plots of the HOMO and the LUMO for compound 1a.
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Figure 5. Free energy profiles studying competition between pathway I (1a*_T → 1a) and pathway II (1a*_T → 2a + PhI) calculated by SMD/
M06-2X-D3/def2-TZVP/SMD/M06-2X-D3/LANL2DZ,6-31G(d) in acetonitrile. Spin densities derived from Mulliken population analysis of all
triplet structures (gray); NPA partial charge (pink); and selected bond distances (green; Å) for some optimized structures are included. Free
energies are given in kcal/mol and referenced to structure 1a*_T.
the presence of the CC bond, which is stabilized by the
conjugation with the carbonyl π system, leads to the
preferential population of the C3C4 π* orbital in favor of
the low-lying C−I σ* orbital. It is important to compare this
finding with the germane study investigating the photo-
excitation of related, but less conjugated, ylide 1d (Figure
1B).7 In the latter case, photoexcitation leads to the formal
reduction of iodine(III) to iodine(II) within ensuing excited
triplet structure 1d*_T due to the occupation of a C−I σ*
orbital by the excited electron.
Triplet intermediate 1a*_T may represent a branching point
for at least two pathways (Figure 5). For example, this
structure can undergo a redox process (ΔG‡ = 10.5 kcal/mol)
via TS1a*_T/T2 to give species 1a*_T2, from which triplet
organic intermediate 1a*_T3 may be formed following the loss
of iodobenzene. The resultant intermediate is prone to
cyclization to afford ketene 2a on the singlet surface by
crossing MECP2. We determined that this crossing point lies
only 0.6 kcal/mol above structure 1a*_T3. Alternatively,
triplet intermediate 1a*_T may undergo a quenching process
by passing through MECP1 to return starting material 1a.
MECP1 is computed to be 1.2 kcal/mol lower in energy than
TS1a*_T/T2, which suggests that both the quenching and redox
pathways are competitive.
compared to the equivalent bond within iodonium 1a.20 This
is supported by the longer I−C1 distance for intermediate
1a*_T relative to ground-state singlet structure 1a (2.089 vs
2.059 Å; Figure 5). Natural population analysis (NPA) reveals
that the electron density on the C1 atom decreases from
−0.649 (1a) to −0.217 (1a*_T). The greater electron density
on the C1 atom in 1a results in it coordinating more strongly to
the iodine(III) atom, making the iodine center in this structure
less reactive toward reduction. This is supported by our
calculations indicating that transition structure TS1a*_T/T2
occurs earlier than transition structure TS1a/2a, which is
consistent with the shorter I−C1 distance within TS1a*_T/T2
relative to the equivalent bond within TS1a/2a (2.239 vs 2.804
Å; Figure 5 and Table 2).
In practice, we found that cyclopentenedione 3a was most
efficiently prepared by heating iodonium 1a in acetonitrile at
60 °C (eq 1), which aligns with previous findings.2b
Our calculations indicate that the productive photochemical
pathway involving triplet structure 1a*_T requires a much
smaller activation energy barrier (ΔG‡ = 10.5 kcal/mol; Figure
5) relative to the thermal reaction via ground-state molecule 1a
(ΔG‡ = 27.0 kcal/mol; Table 2). These data are consistent
with our aforementioned experimental findings which demon-
strate that irradiation with visible light facilitates the formation
of dione 3a. The higher reactivity of the triplet structure can be
attributed to the weaker I−C1 bond within structure 1a*_T
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Bimolecular photochemical reactions with molecule 1a were
not particularly efficient. For example, reactions of phenyl-
iodonium 1a and styrene performed in the presence of visible
light gave a complex mixture of products. Furthermore, when
we reacted substrate 1a with phenylacetylene only low yields of
heterocycle 5 were obtained (eq 2). This is comparable to the
results of germane photochemical reactions employing UV
light to convert substrates 1 into furanoquinones and
furanonaphthoquinones.1,2b,4a In an effort to understand the
origins of the poor efficiency of this reaction of 1a, we
employed DFT calculations (Figure 6). The presence of a
Figure 7. Photoinduced, phenyiodonium-promoted C−H function-
alization of THF via HAT.
suggest that species 1a*_T is capable of abstracting a hydrogen
atom from THF and ensuing carbon-centered radical II adds
to azodicarboxylate ester 6 to afford nitrogen-centered radical
III. The latter is capable of abstracting a hydrogen atom from
THF leading to a radical chain process (Figure 7B).25
Figure 6. Free energy profiles studying competition between pathway
III (1a*_T → 5) and pathway II (1a*_T → 2a) calculated by SMD/
M06-2X-D3/def2-TZVP/SMD/M06-2X-D3/LANL2DZ,6-31G(d) in
acetonitrile. Free energies are given in kcal/mol and referenced to
structure 1a*_T.
The results shown in Figure 7 suggest that triplet species
1a*_T is sufficiently long-lived and reactive for it to serve as a
radical generator in this transformation. To further support this
hypothesis, we used DFT calculations to investigate the
reaction of 1a*_T with THF (Figure 8). Triplet 1a*_T
contains different reactive sites that have the capacity to
generate organic radicals. We determined that the C1 atom
within intermediate 1a*_T, which has the highest spin density,
is the most reactive site, and can produce a radical with the
lowest activation energy barrier. Specifically, species 1a*_T can
abstract a hydrogen radical from THF with activation barriers
comparable to those leading to ketene 2a (within 0.2 kcal/
mol). Thus, although 1a*_T is highly reactive toward the latter
pathway, the hydrogen atom transfer (HAT) reaction with
THF is competitive and viable.
We found that iodonium 1a also facilitates the photo-
induced, Povarov-type reaction between N,N-dimethylaniline
and N-phenylmaleimide (8) to afford tetrahydroquinoline 9,
albeit in moderate yield (eq 3). Our DFT calculations
exploring the activation of N,N-dimethylaniline are consistent
with species 1a*_T promoting this transformation.26 In
addition, we also determined that molecule 1a was capable
of promoting an atom-transfer radical addition reaction
between 1-octene (10) and bromotrichloromethane (eq 4).
These results further support the involvement of SET
processes when molecule 1a undergoes photoactivation.
single electron on the C1 atom within biradical structure
1a*_T makes this species prone to react with the alkyne via
transition structure TS1a*_T/T4 which lies only 13.9 kcal/mol
above 1a*_T. Resultant triplet structure 1a*_T4 can then
cyclize on the singlet surface by overcoming the activation
energy barrier associated with the triplet to singlet spin flip via
MECP3 to form furanoquinone 5 exergonically. However,
while the ring closure is predicted to be kinetically favorable,
the barrier for the competing process that provides ketene 2a is
3.4 kcal/mol lower in energy. The low yield obtained for
heterocycle 5 may derive from this competition.21 It should be
noted this competing pathway is not operative in the
photochemical reaction of iodonium 1d with styrene which
proceeds in excellent yield (Figure 1B).7
Photoinduced Reactions Mediated by Ylide 1a. When
THF solutions containing azodicarboxylate esters 6 were
irradiated with visible light in the presence of iodonium 1a,
products 7 were synthesized in good to excellent yields (Figure
7A).22,23 Similar types of reactions of azodicarboxylate esters
have been reported using UV irradiation, transition-metal-
based photocatalysis, and N-hydroxyamide catalysts.24 Our
findings are consistent with molecule 1a serving as a free
radical initiator in its photoexcited state. Specifically, we
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understanding of hydroxyquinone-derived phenyliodonium
ylides, their photoactivation, and associated fundamental
reactivity may serve to broaden the scope and applications of
this interesting and relatively underutilized class of compounds
in synthesis.
EXPERIMENTAL SECTION
■
General Information. NMR spectroscopic experiments were
performed either on a Bruker Avance III NMR spectrometer
operating at 400 MHz (1H) and 100 MHz (13C) or on a Bruker
Avance III NMR spectrometer operating at 600 MHz (1H) and 150
MHz (13C). The deuterated solvents used were CDCl3, CD3CN, and
DMSO-d6. Chemical shifts were recorded in ppm. Spectra were
calibrated by assignment of the residual solvent peak to δH 7.26 and
δC 77.16 for CDCl3, δH 1.94 and δC 1.32 for CD3CN, and δH 2.50 and
δC 39.52 for DMSO-d6. Coupling constants (J) were recorded in Hz.
Infrared spectroscopy was performed on a Shimadzu FTIR 8400s
spectrometer, with samples analyzed as thin films on NaCl plates.
High resolution mass spectra (HRMS) were recorded on a either a
Shimadzu LCMS-9030 Q-TOF mass spectrometer using an electro-
spray ionization (ESI) source in either the positive or negative modes
or a Thermo Scientific Q-Exactive HF Orbitrap mass spectrometer
equipped with HESI interface. Photochemical experiments were
performed in either custom blue LED (λmax = 467 nm) photoreactor
#127 (maintained at 24 °C) or custom blue LED (λmax = 467 nm)
photoreactor #2 (maintained at 32 °C).28 Blue LED strips were
purchased from aliexpress.com. In each experiment, reaction vessels
were placed within 3−4 cm from the light source; light filters were not
used. All irradiation vessels were composed of borosilicate glass.
TLC was performed using Merck silica gel 60-F254 plates.
Developed TLC plates were visualized by UV absorbance (254 nm)
or through application of heat to a plate stained with cerium
molybdate {Ce(NH4)2(NO3)6, (NH4)6Mo7O24·4H2O, H2SO4, H2O}.
Flash column chromatography was performed with flash grade silica
gel (60 μm) and the indicated eluent in accordance with standard
techniques.29 THF, Et2O, CH2Cl2, PhMe, DMF, and CD3CN were
deaerated via a nitrogen sparge then dried using an Innovative
Technology solvent purification system. Unless otherwise specified all
reagents employed in these studies were used as received from Sigma-
Aldrich, AK Scientific, Combi-Blocks, and Oakwood. Previously
reported compounds 1b4a and 1c2b were prepared in accordance with
literature procedures.
Figure 8. Free energy profiles studying the competition between
conversions (a) 1a*_T + THF → II + I and 1a*_T → 2a in THF
calculated by SMD/M06-2X-D3/def2-TZVP//SMD/M06-2X-D3/
LANL2DZ,6-31G(d). Free energies are given in kcal/mol and
referenced to structure 1a*_T.
Computational Details. Gaussian 1630 was used to fully optimize
all the structures reported in this paper at the M06-2X level31 of
density functional theory (DFT). Grimme empirical dispersion was
added with the GD3 term on all the optimization calculations.32 For
all the calculations, solvent effects were considered using the SMD
solvation model for different solvents, including: CH3CN, CHCl3,
THF, and DMF.33 The effective core potential of Hay and Wadt with
a double-ξ valence basis set (LANL2DZ)34 was chosen to describe
iodine. Polarization functions were also added for I (ξd = 0.289).35
The 6-31G(d) basis set was used for other atoms.36 This basis set
combination will be referred to as BS1. Frequency calculations were
carried out at the same level of theory as those for the structural
optimization. Transition structures were located using the Berny
algorithm. Intrinsic reaction coordinate (IRC) calculations37 were
used to confirm the connectivity between transition structures and
minima. To further refine the energies obtained from the SMD/M06-
2X-D3/BS1 calculations, we carried out single-point energy
calculations using the M06-2X-D3 functional method38 for all the
structures with a larger basis set (BS2). BS2 utilizes def2-TZVP39
basis set on all atoms. Tight convergence criterion was also employed
to increase the accuracy of the single point calculations. All
thermodynamic data were calculated at the standard state (298.15
K and 1 atm).
CONCLUSIONS
■
We have extensively investigated the photochemical activation
and reaction of a hydroxyquinone-derived phenyliodonium
ylide in the presence of visible light. Our studies have revealed
that iodonium 1a can undergo an original photochemical
rearrangement. Furthermore, we have determined that, in its
photoexcited state, triplet 1a*_T is sufficiently long-lived and
reactive to promote various SET processes, including HAT, a
Povarov-type reaction, and atom-transfer radical addition
chemistry. We anticipate that by developing a more complete
In this work, the free energy for each species optimized by SMD/
M06-2X-D3/BS1 in solution was calculated using the formula: G =
E(BS2) + G(BS1) − E(BS1) + ΔG1atm→1M; where ΔG1atm→1M = 1.89
kcal/mol is the free-energy change for compression of 1 mol of an
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ideal gas from 1 atm to the 1 M solution phase standard state. An
additional correction to Gibbs free energies was made to consider
solvent (THF) concentration where a THF is directly involved in
transformations. In such a case, the free energy of a THF molecule is
photoreactor. The reaction mixture was then subjected to flash
column chromatography (silica gel, 0−5% EtOAc/hexanes elution) to
provide previously reported compound 5 as a red solid (10 mg, 15%
yield).47 1H NMR (600 MHz, CDCl3) δ 7.86 (d, J = 7.3 Hz, 2H),
7.54−7.44 (complex m, 3H), 7.07 (s, 1H), 6.77 (d, J = 10.3 Hz, 1H),
6.73 (d, J = 10.4 Hz, 1H) ppm. 13C{1H} NMR (150 MHz, CDCl3) δ
183.0, 174.4, 159.8, 149.7, 136.4, 130.31, 130.29, 129.1, 128.2, 125.5,
102.3 ppm.
General Procedure A: Synthesis of Compounds 7. In air, THF (5
mL) was added to a 20 mL screw-top vial containing compound 1a
(30 mg, 92 μmol), the azodicarboxylate ester 6 (613 μmol), and a stir
bar. The vial was then capped and placed in blue LED photoreactor
#1 (switched off) and magnetically stirred at 24 °C (Figure S1). The
vial was then irradiated. After 5 h, compound 1a (10 mg, 31 μmol)
was added and, after a further 5 h, compound 1a (10 mg, 31 μmol)
was added. After a further 14 h, the vial was removed from the
photoreactor. The reaction mixture was concentrated under reduced
pressure and the ensuing residue was subjected to flash column
chromatography.
described as G(THF) = E(BS2) + G(BS1) − E(BS1) + ΔG1atm→1M
+
RT ln (12.2); where the last term corresponds to the free energy
required to change the standard state of THF from 12.2 to 1 M.40 The
numerical correction value for THF was calculated to be 1.4 kcal/mol.
TD-DFT calculations were performed using the SMD/CAM-B3LYP/
BS1 level of theory in CH3CN, which is specifically designed for
investigating the nature of the excited states.41 Natural population
analysis (NPA) was carried out using NBO6 software integrated into
Gaussian 16.42 The respective minimum energy crossing points
(MECPs) between singlet structure 1a and triplet structure 1a*_T;
singlet structure 2a and triplet structure 1a*_T3; and singlet structure
5 and triplet structure 1a*_T4 were located using the code reported
by Harvey and co-workers.43
CrystalExplorer 17.5 was used to examine the arrangement
molecules of complex 1a.44
X-ray Crystallography. Data for compound 1a were collected at
100 K using Cu Kα radiation (microsource, mirror monochromated)
using an Agilent SuperNova diffractometer with Atlas detector. The
structures were solved by direct methods with SHELXT-2014, refined
using full-matrix least-squares routines against F2 with SHELXL-
2014,45 and visualized using OLEX2.46 All non-hydrogen atoms were
refined anisotropically. All hydrogen atoms attached to carbon were
placed in calculated positions and refined using a riding model with
fixed C−H distances of 0.95 Å (sp2CH). The thermal parameters of
hydrogen atoms were estimated as Uiso(H) = 1.2Ueq(C). CCDC-
2041504 contains the supplementary crystallographic data for
compound 1a. The data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via http://www.ccdc.cam.
ac.uk/data_request/cif. Crystal data for compound 1a: C12H7IO3, M
= 326.08, triclinic, a = 8.0768(3), b = 11.5213(4), c = 12.1793(4) Å, α
= 71.418(3), β = 87.592(3), γ = 88.719(3) °, U = 1073.27(7) Å3, T =
Diisopropyl 1-(tetrahydrofuran-2-yl)hydrazine-1,2-dicarboxylate
(7a). This reaction employed diisopropyl azodicarboxylate (DIAD)
and followed General Procedure A. The ensuing residue obtained
from the reaction mixture was subjected to flash column
chromatography (silica gel, 0−20% EtOAc/hexanes elution) to
provide previously reported compound 7a as a colorless amorphous
solid (155 mg, 92% yield).48 1H NMR (600 MHz, CDCl3) δ 6.60−
6.28 (m, 1H), 5.96 (br s, 1H), 4.91 (sept, J = 6 Hz, 2H), 3.95 (q, J =
6.9 Hz, 1H), 3.71 (q, J = 6.9 Hz, 1H), 2.11−1.77 (complex m, 4H),
1.21 (br s, 12H) ppm. 13C{1H} NMR (150 MHz, CDCl3) δ 156.4,
155.0, 87.0, 70.5, 69.8, 68.6, 28.2, 25.3, 22.0, 21.9 ppm.
Di-tert-butyl 1-(tetrahydrofuran-2-yl)hydrazine-1,2-dicarboxy-
late (7b). This reaction employed di-tert-butyl azodicarboxylate and
followed General Procedure A. The ensuing residue obtained from
the reaction mixture was subjected to flash column chromatography
(silica gel, 0−20% EtOAc/hexanes elution) to provide previously
reported compound 7b as a colorless amorphous solid (127 mg, 69%
yield).49 1H NMR (600 MHz, CDCl3) δ 6.18 (br s, 1H), 5.95 (m,
1H), 3.99 (m, 1H), 3.77 (m, 1H), 2.07−2.00 (m, 3H), 1.83 (m, 1H),
1.49 (br s, 18H) ppm. 13C{1H} NMR (150 MHz, CDCl3) δ 155.6,
154.3, 87.2, 81.8, 81.1, 68.5, 28.2, 25.3 ppm; 8 signals observed.
Dibenzyl 1-(tetrahydrofuran-2-yl)hydrazine-1,2-dicarboxylate
(7c). This reaction employed dibenzyl azodicarboxylate and followed
General Procedure A. The ensuing residue obtained from the reaction
mixture was subjected to flash column chromatography (silica gel, 0−
30% EtOAc/hexanes elution) to provide previously unreported
compound 7c as a colorless amorphous solid (215 mg, 95% yield).
1H NMR (600 MHz, CDCl3) δ 7.32 (br s, 10H), 6.55 (br s, 1H), 6.02
̅
100 K, space group P1 (no. 2), Z = 4, 18359 reflections measured,
4207 unique (Rint = 0.0788), 3694 > 4σ(F), R = 0.0391 (observed),
Rw = 0.1016 (all data).
Synthesis of Products. Compound 1a. A mixture of PIDA (32.0
g, 99.9 mmol) in CH2Cl2 (120 mL) was added to a magnetically
stirred solution of benzene-1,2,4-triol (6.00 g, 47.6 mmol) in CH2Cl2
(300 mL) maintained at 0 °C in air. After 0.25 h, the reaction mixture
was warmed to room temperature. After 2 h, the reaction mixture was
filtered and the red precipitate was collected. The filtrate was
concentrated to ca. one-third of its volume and hexanes were added
(100 mL) and the ensuing mixture was magnetically stirred. The red
precipitate was collected and the combined solids were dried under a
vacuum. This afforded the previously reported compound 1a (11.2 g,
72% yield) as a red powder.2 X-ray quality crystals were grown from
CH3CN/Et2O. 1H NMR (600 MHz, DMSO-d6) δ 7.81 (d, J = 7.7 Hz,
2H), 7.52 (t, J = 7.3 Hz, 1H), 7.40 (t, J = 7.7 Hz, 2H), 6.94 (d, J =
10.0 Hz, 1H), 6.62 (d, J = 10.0 Hz, 1H) ppm. 13C{1H} NMR (150
MHz, DMSO-d6) δ 182.2, 177.3, 168.9, 139.9, 133.2, 132.6, 131.1,
130.6, 114.1, 97.8 ppm.
(br s, 1H), 5.17 (br s, 4H), 3.95 (d, J = 6.6 Hz, 1H), 3.74 (q, J = 7.1
Hz, 1H), 2.19−1.77 (complex m, 4H) ppm. 13C{1H} NMR (150
MHz, CDCl3) δ 156.7, 155.6, 135.8, 128.8, 128.7, 128.6, 128.5, 128.4,
128.2, 88.0, 69.0, 68.6, 68.1, 28.6, 25.5 ppm; 15 signals observed. IR
(NaCl) 3286, 2956, 2359, 1722, 1493, 1223, 1092, 1044, 1016, 805
cm−1. HRMS (ESI) m/z [M + Na]+ Calcd for C20H22N2O5Na
393.1421, Found 393.1404.
2-Cyclopentene-1,4-dione (3a). CH3CN (200 mL) was added to a
250 mL round-bottomed flask containing compound 1a (2.00 g, 6.13
mmol) and a stir bar in air. The flask was fitted with a condenser and
the mixture was then heated at 60 °C. After 2 h, the reaction mixture
was concentrated under reduced pressure and the ensuing residue was
subjected to flash column chromatography (silica gel, 0−20% Et2O/
hexanes elution) to provide the previously reported compound (210
mg, 36% yield) as a colorless amorphous solid.2 1H NMR (600 MHz,
CDCl3) δ 7.30 (s, 2H), 2.90 (s, 2H) ppm. 13C{1H} NMR (150 MHz,
CDCl3) δ 199.7, 149.5, 40.5 ppm.
2-Phenylbenzofuran-4,7-dione (5). In a nitrogen-filled glovebox,
phenylacetylene (2 mL) was added to a 4 mL screw-top vial
containing compound 1a (100 mg, 307 μmol) and a stir bar. The vial
was then capped and removed from the glovebox, placed in blue LED
photoreactor #1 (switched off) and magnetically stirred. The vial was
then irradiated and, after 14 h, the flask was removed from the
Bis(4-chlorobenzyl) 1-(tetrahydrofuran-2-yl)hydrazine-1,2-dicar-
boxylate (7d). This reaction employed di-(4-chlorobenzyl)-
azodicarboxylate (DCAD) and followed General Procedure A. The
ensuing residue obtained from the reaction mixture was subjected to
flash column chromatography (silica gel, 0−30% EtOAc/hexanes
elution) to provide previously unreported compound 7d as a colorless
1
amorphous solid (245 mg, 91% yield). H NMR (600 MHz, CDCl3)
δ 7.24 (br s, 8H), 6.44 (br s, 1H), 5.92 (br s, 1H), 5.07 (br s, 4H),
3.89 (m, 1H), 3.68 (q, J = 7.2 Hz, 1H), 2.03−1.79 (complex m, 4H)
ppm. 13C{1H} NMR (150 MHz, CDCl3) δ 156.2, 155.2, 134.4, 134.3,
134.1, 134.0 129.5, 129.4, 128.8, 128.7, 87.8, 68.8, 67.6, 67.0, 28.3,
25.2 ppm. IR (NaCl) 3286, 2957, 1723, 1493, 1242, 1225, 1093,
1046, 1016, 806 cm−1. HRMS (ESI) m/z [M + Na]+ Calcd for
C20H20Cl2N2O5Na 461.0642, Found 461.0615.
5-Methyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]-
quinoline-1,3(2H)-dione (9). In air, compound 1a (28 mg, 86 μmol)
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was added to a 20 mL screw-top vial containing, N-phenylmaleimide
(100 mg, 577 μmol), PhNMe2 (140 mg, 1.15 mmol), DMF (2.5 mL),
and a stir bar. The vial was then capped and placed in a water bath
(suspended with Cu wire) maintained at 32 °C that was contained
within blue LED photoreactor #2 (switched off) and magnetically
stirred. The vial was then irradiated. After 5 h, compound 1a (9.5 mg,
29 μmol) was added and, after a further 5 h, compound 1a (9.5 mg,
29 μmol) was added. After a further 14 h, the vial was removed from
the photoreactor. The reaction mixture was concentrated under
reduced pressure and the ensuing residue was subjected to flash
column chromatography (silica gel, 0−20% EtOAc/hexanes elution;
0.5% NEt3 was present in the eluent) to provide a yellow solid.
Recrystallization from Et2O afforded previously reported compound 9
as a colorless solid (86 mg, 51% yield).50 1H NMR (600 MHz,
CDCl3) δ 7.54 (d, J = 7.9 Hz, 1H), 7.44 (t, J = 7.9 Hz, 2H), 7.36 (t, J
= 7.4 Hz, 1H), 7.31−7.22 (complex m, 3H), 6.92 (t, J = 7.9 Hz, 1H),
6.76 (d, J = 7.9 Hz, 1H), 4.17 (d, J = 9.7 Hz, 1H), 3.62 (dd, J = 11.5,
2.6 Hz, 1H), 3.54 (dt, J = 9.3, 3.0 Hz, 1H), 3.13 (dd, J = 11.5, 4.4 Hz,
1H), 2.85 (s, 3H) ppm. 13C{1H} NMR (150 MHz, CDCl3) δ 177.7,
175.8, 148.5, 132.0, 130.4, 129.0, 128.7, 128.5, 126.3, 119.7, 118.6,
112.6, 50.7, 43.6, 42.2, 39.5 ppm.
3-Bromo-1,1,1-trichlorononane (11). In a nitrogen-filled glovebox,
compound 1a (32.5 mg, 100 μmol) was added to a Schlenk flask
containing, 1-octene (112 mg, 1.00 mmol), BrCCl3 (397 mg, 2.00
mmol), CH2Cl2 (5 mL), and a stir bar. The flask was then stoppered
and removed from the glovebox, placed in blue LED photoreactor #1
(switched off) and magnetically stirred. The flask was then irradiated.
After 3 h, compound 1a (32.5 mg, 100 μmol) was added under a
stream of Ar and, after a further 3 h, compound 1a (32.5 mg, 100
μmol) was added was added under a stream of Ar. After a further 15
h, the flask was removed from the photoreactor. The reaction mixture
was exposed to air and concentrated under reduced pressure and the
ensuing residue was subjected to flash column chromatography (silica
gel, hexanes elution) to provide previously reported compound 11 as
a colorless oil (125 mg, 40% yield).51 1H NMR (400 MHz, CDCl3) δ
4.32 (m, 1H), 3.33 (ABq, J = 15.9 Hz, 2H), 1.98 (m, 2H), 1.54 (m,
2H), 1.32 (m, 6H), 0.89 (t, J = 6.7 Hz, 3H) ppm. 13C{1H} NMR
(100 MHz, CDCl3) δ 97.4, 62.9, 49.1, 36.7, 31.7, 28.6, 27.3, 22.7, 14.2
ppm.
Authors
Mona Jalali − School of Natural Sciences − Chemistry,
University of Tasmania, Hobart, Tasmania 7001, Australia
Curtis C. Ho − School of Natural Sciences − Chemistry,
University of Tasmania, Hobart, Tasmania 7001, Australia;
orcid.org/0000-0002-7555-0635
Rebecca O. Fuller − School of Natural Sciences − Chemistry,
University of Tasmania, Hobart, Tasmania 7001, Australia;
orcid.org/0000-0003-3926-8680
Nigel T. Lucas − Department of Chemistry, University of
Otago, Dunedin, Otago 9054, New Zealand; orcid.org/
0000-0002-4944-9875
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c02592
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge the University of Tasmania School
of Natural Sciences − Chemistry and an Australian Research
Council (ARC) Discovery Project Grant (DP200101714) for
funding, the University of Tasmania Central Science
Laboratory for providing access to NMR spectroscopy services,
and the generous allocation of computing time from the
Australian National Computing Infrastructure and University
of Tasmania. R.O.F.’s contributions were supported by an
ARC Discovery Early Career Research Award
(DE180100112). N.T.L. acknowledges financial support by
the MacDiarmid Institute for Advanced Materials and
Nanotechnology, and the Marsden Fund Council, managed
by the Royal Society Te Aparangi, New Zealand.
̅
REFERENCES
■
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ASSOCIATED CONTENT
■
sı
* Supporting Information
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Additional experimental information and compound
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Accession Codes
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AUTHOR INFORMATION
■
Corresponding Authors
Alireza Ariafard − School of Natural Sciences − Chemistry,
University of Tasmania, Hobart, Tasmania 7001, Australia;
orcid.org/0000-0003-2383-6380;
Email: alireza.ariafard@utas.edu.au
Alex C. Bissember − School of Natural Sciences − Chemistry,
University of Tasmania, Hobart, Tasmania 7001, Australia;
orcid.org/0000-0001-5515-2878;
Email: alex.bissember@utas.edu.au
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