Acetal Addition to Electron-Deficient Alkenes with Hydrogen Atom Transfer as a Radical Chain Propagation Step

Article abstract of DOI:10.1021/acs.joc.0c03044

We describe a visible-light-promoted addition of a hydrogen atom and an acetal carbon toward various electron-deficient alkenes. 1,3-Dioxolane is converted to its radical species in the presence of persulfate and an iridium catalyst upon visible light irradiation, which then reacts with electron-deficient alkenes. The reaction operates via a radical chain mechanism, a less commonly observed pathway for this class of transformation. Hydrogen atom transfer from 1,3-dioxolane to α-malonyl radicals is corroborated by experimental and density functional theory studies.

Full text of DOI:10.1021/acs.joc.0c03044

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Note
Acetal Addition to Electron-Deficient Alkenes with Hydrogen Atom
Transfer as a Radical Chain Propagation Step
Wei Chuen Chan, Jincy K. Vinod, and Kazunori Koide*
Cite This: J. Org. Chem. 2021, 86, 3674−3682
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ABSTRACT: We describe a visible-light-promoted addition of a
hydrogen atom and an acetal carbon toward various electron-
deficient alkenes. 1,3-Dioxolane is converted to its radical species in
the presence of persulfate and an iridium catalyst upon visible light
irradiation, which then reacts with electron-deficient alkenes. The
reaction operates via a radical chain mechanism, a less commonly
observed pathway for this class of transformation. Hydrogen atom
transfer from 1,3-dioxolane to α-malonyl radicals is corroborated
by experimental and density functional theory studies.
he radical hydrofunctionalization of alkenes is a useful
trapping with a second radical acceptor,11 or atom transfer
reactions, for example, HAT.16,13,17 Among the three possible
pathways, HAT is less commonly observed, specifically in a
radical-chain mechanism.18,19,12 Here, we report the visible-
light-induced addition of a hydrogen atom and acetal carbon to
electron-deficient alkenes via a radical chain mechanism
enabled by HAT as a propagating step (Scheme 1e), the
transformation previously demonstrated by the Tomioka group
under distinct reaction conditions.20,21
T
transformation in organic synthesis.1,2 For example, the
addition of a hydrogen and acetal carbon across a carbon−
carbon double bond is an expedient route to protected
complex aldehydes. 1,3-Dioxolane is a commercially available
and inexpensive solvent and has recently been used as a
surrogate formylating reagent. 1,3-Dioxolane has been used as
a C−H donor in the formal formylation of arenes and N-
heteroarenes.3,4 The successful generation and incorporation
of the dioxolanyl moiety relies on a hydrogen atom transfer
(HAT) from the C-2 position of 1,3-dioxolane to suitable
radicals. With the advances in photochemistry,5−7 several of
these transformations can be achieved under mild conditions.
For example, Doyle et al. reported the Ir/Ni co-catalyzed
cross-couplings of chloro-N-heteroarenes and 1,3-dioxolanes to
furnish dioxolane derivatives (Scheme 1a).8,9 They proposed
HAT from 1,3-dioxolane to chlorine radicals and that requisite
chlorine radicals were generated via the homolysis of
ArNi(III)Cl intermediate. The dioxolane products could be
deprotected to give Minisci-type products.
Besides C−H formylation of (N-hetero)arenes, 1,3-
dioxolane also undergoes additions across carbon−carbon
and carbon−nitrogen double bonds. For example, Ooi et al.
disclosed the formal hydroformylation of cinnamic acids
(Scheme 1b).10 They proposed a direct HAT to the excited
thioxanthone photocatalyst. Su et al. reported dioxolanylation-
triggered cascade cyclizations, in which α,α-disubstituted
acrylamides were employed to generate indoline products
(Scheme 1c).11 Gong and Lu reported the radical-chain
formylation of imines; HAT initially occurred via O-centered
radical derived from N-hydroxysuccinimide and 2,3-butadione
(Scheme 1d).12,13
We reasoned that a nucleophilic dioxolan-2-yl-radical22
could react with electron-deficient radical acceptors. Based
on literature precedents,23,24,4,9,25 we chose the combination of
soluble persulfate (n-Bu4N)2S2O8, Ir(III) photocatalyst, and
1,3-dioxolane to generate the desired dioxolan-2-yl radicals.
Initial screenings with trans-chalcone as the radical acceptor
gave low and irreproducible yields (Table S1, Supporting
Information). We speculated that the insufficient electro-
philicity of the alkenes might be a reason for low yields and
chose the more electrophilic alkene 16a as the model substrate
for reaction optimizations.26 Gratifyingly, the desired product
18aa was formed in 77−93% yields (Table 1, entries 1−5),
with Ir-1 as the optimal catalyst. Control experiments
indicated that the persulfate was required (entry 6). The
reaction gave 18aa in 76% yield in the absence of the
photocatalyst (entry 7), suggesting that the major pathway of
the reaction might involve the homolysis of persulfate (vide
infra). In the absence of light,24 the starting material
Received: December 28, 2020
Published: February 4, 2021
Mechanistically, a dioxolanyl moiety adds to an electrophilic
acceptor. After the first radical addition step, the resulting
radical may undergo single-electron transfer (SET),14,10,15
https://dx.doi.org/10.1021/acs.joc.0c03044
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Scheme 1. Dioxolanylations of alkenes or imines
Table 1. Optimization of Reaction Conditions
entry
changes from standard conditions
yieldsa (%)
1
2
3
4
5
6
7
8
fac-Ir(ppy)3, Ir-1
Ir(dFppy)3, Ir-2
Ir(dtbbpy)(ppy)2PF6, Ir-3
Ir[dF(CH3)ppy]2(dtbbpy)PF6, Ir-4
Ir[dF(CF3)ppy]2(dtbbpy)PF6, Ir-5
no [O]
93
89
87
85
77
NR
76
dec
no [Ir]
no hν
Radical acceptors containing a sulfone or sulfonyl
fluoride27,28 were competent reactant partners (18an and
18ao). Sulfonyl fluoride 18an may be useful for SuFEx
chemistry.29,30 Despite the potential formation of C2- and C4-
regioisomers of 1,3-dioxolane,4,9 only 18an and 18ao were
formed as regioisomeric mixtures. Chromones31 were com-
petent radical acceptors under our reaction conditions (18ap);
carboxylic acid 16q underwent radical addition with
concomitant decarboxylation to form 18ap.
We then tested other radical donors; benzo-1,3-dioxole32
afforded 82% yield of 18ba. Trioxane25 did not afford any
desired product under photolytic conditions; heating the
reaction mixture to 90 °C gave 18ca in 38% yield.
Because previous works4,9 on N-heterocyclic substrates
focused on Minisci-type reactivity, we studied for orthogonal
reactivity under our reaction conditions (Scheme 2b). The 2-,
3-, and 4-pyridinyl substrates reacted with no observable
Minisci-type side products (18ar−18at). 4-Chloropyridinyl
substrate reacted efficiently (18au). Quinolinyl substrate also
performed well in the reaction (18av). A lower persulfate
loading (0.50 equiv) helped to isolate several water-soluble
products.
Unlike literature precedents, our reaction failed to work
when one or more electron-withdrawing groups was a nitrile
group26,16 (see the SI). The sterically hindered olefin 19
(Scheme 2c) was unreactive. Dienoate 20 failed to react due to
instability under our reaction conditions. The less electron-
deficient indole-derived alkene 21 was not a suitable substrate
(see Figure S3 for all unsuccessful substrates). Unlike literature
precedents, 2-vinylpyridine 2216 was unreactive. Acetal 18aa
could be converted to lactone 23 with Et3SiH and water in
trifluoroacetic acid in 99% yield (Scheme 2d).
Subsequently, we investigated the mechanism (Scheme 3).
Addition of TEMPO resulted in no conversion, supporting the
radical intermediacy (Scheme 3a). Unlike literature prece-
dents,4,25 we found that 0.25 equiv of persulfate worked
equally well (Scheme 3b, 97% yield). Additionally, a lights-on/
lights-off experiment suggested a closed catalytic cycle was not
operative (Figure S2). With only 0.050 mol % of [Ir], products
18aa, 18as, and 18af were produced in 72, 77, and 80% yields,
respectively (Scheme 3b).
underwent decomposition to unidentifiable side products
(entry 8).
Scheme 2 shows the substrate scope. Arylidenemalonates
with different substituents on the aryl ring were tolerated;
fluoro-, chloro-, and bromo- on the o-, m-, and p-positions,
respectively, underwent the desired reaction smoothly (18ab−
18ad). Additional steric hindrance on the aryl group did not
affect the reaction efficiency (18ae). Electron-donating
substituents were also compatible (18af and 18ag). Trifluor-
omethylthio- and trifluoromethyl substrates also reacted
efficiently (18ah and 18ai). Trans-chalcone afforded a
significantly diminished yield (18aj). Primary and secondary
alkylidenemalonates participated in the reaction successfully
(18ak and 18al). Sulfone 18am was produced in 92% yield as
a mixture of diastereomers.
Nishibayashi’s work inspired us to probe whether α-malonyl
radicals undergo HAT and propagate the radical chain.26 The
34
combination of Ir-5 (ET = 61 kcal mol−1
)
and
bromomalonate 24, a known source of α-malonyl radical,33
in dioxolane reacted with 16a to form 18aa in 93% yield
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Note
a
Scheme 2. Substrate Scope
a
General reaction conditions: Alkene (1.0 equiv, 0.20 mmol), (n-Bu4N)2S2O8 (1.0 equiv, 0.20 mmol), degassed 1,3-dioxolane (3.0 mL), fac-
b
Ir(ppy)3 (0.50 mol %), irradiated with household LEDs (15W × 4) for 24 h, external temp = 30 °C. 0.50 equiv of (n-Bu4N)2S2O8 was used; 0.10
c
d
mmol scale. Yield was determined by 1H NMR spectroscopy using mesitylene as standard. dr was determined by 1H NMR spectroscopy, PMP =
e
f
1
p-methoxyphenyl. Inseparable mixture of C-2/C-4, rr = regioisomeric ratio, determined by H NMR spectroscopy. Alkene (1.0 equiv, 0.20
mmol), (n-Bu4N)2S2O8 (1.0 equiv, 0.20 mmol), degassed MeCN (2.7 mL), fac-Ir(ppy)3 (0.50 mol %), irradiated with household LEDs (15W × 4)
g
for 24 h, external temp = 30 °C. (n-Bu4N)2S2O8(0.25 equiv, 0.05 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6, (0.50 mol %)
(Scheme 3c). We explored the substrate scope with this set of
conditions. However, the new conditions did not yield any
product with less successful and unsuccessful substrates
(Scheme 2 and Figure S3), which led us to conclude that
persulfate as the radical initiator works well with limited scope.
With iridium catalysts, we observed a correlation with the
catalyst’s triplet emission energy (ET) (see Table S2 for
catalyst screening). An Ir(III) photocatalyst with a large ET is
required to promote the reaction [BDE of C(sp3)−Br = 54−71
kcal mol−1]. Bromomalonate 24 might undergo homolysis
under this set of reaction conditions as an efficient radical
initiator. α-Bromomalonates are known to form malonyl
radicals via SET or an energy-transfer pathway.35−37 In the
energy-transfer pathway, bromine radicals are also formed; this
raised doubts about the actual radical abstracting hydrogen
from 1,3-dioxolane. In this regard, we performed a
stoichiometric experiment between bromomalonate 24 and
1,3-dioxolane, and malonate 27 was formed in only 45% yield
(unoptimized) (Scheme 3d). This supported the possibility of
direct HAT to an α-malonyl radical. Currently, the fate of 1,3-
dioxolane after HAT is unclear, warranting further inves-
tigations. Nevertheless, we tentatively propose a SET
mechanism of the dioxolanyl radical to the oxocarbenium
ion, followed by coupling with nucleophilic species. An
alternate pathway involving HAT by bromine radicals cannot
be excluded at this stage (Figure S4). Encouraged by the result
with bromomalonate 24, we also tested the reaction using
bromoester 28 as the initiator,38 affording 18aa in 93% yield
(Scheme 3e).
We propose a radical chain mechanism with three possible
initiation pathways (Scheme 4a). When a persulfate was used,
sulfate radical anions could be formed homolytically (BDE of
O−O = 28.7 kcal mol−1) via an energy transfer (path A, major)
or heterolytically via SET with Ir(III)* (path B, minor). When
bromide 25 was used as an initiator, it could form 26 and Br•
(path C). Thereafter, radical X• (sulfate radical anion, α-
malonyl radical 26, or Br•) abstracts a hydrogen atom from
1,3-dioxolane. In the propagation steps, nucleophilic dioxolanyl
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Scheme 3. Mechanistic Studies and Scale-Up Experiments
EXPERIMENTAL SECTION
■
General Information and Reagents. Commercially available
chemicals were purchased from Sigma-Aldrich, Alfa Aesar, Strem,
ACROS, or Oakwood and used without further purification, unless
otherwise indicated. Glasswares were either flamed-dried immediately
prior use or oven-dried (140 °C, overnight). Moisture-sensitive
reactions were performed under a nitrogen atmosphere with standard
Schlenk techniques unless otherwise stated. 1,3-Dioxolane was
purchased from ACROS Organics and freshly degassed before each
use. Acetonitrile (MeCN) and methanol (MeOH) were stored over 3
Å molecular sieves. 1,4-Dioxane was purchased from Acros Organics
and used as received. Solvents were degassed by sonication for 45 min
or sparging with nitrogen gas for 30 min immediately before use.
LEDs used are GE lighting Brightstik (15 W, 1600 lm, daylight).
Iridium photocatalysts were purchased from Strem or Sigma-Aldrich
and stored in amber secondary containers; the catalysts were used as
received. Tetrabutylammonium persulfate (n-Bu4N)2S2O8 was pre-
pared using a protocol reported by Yeung et al.25 and stored in a
scintillation vial wrapped with aluminum foil at room temperature for
up to 2 months. A sand bath with a mantle heater was used as the heat
source for reactions that required heating. Solvents used for NMR
spectroscopy were purchased from Cambridge Isotope Laboratories.
CDCl3 was stored over anhydrous K2CO3. All one- and two-
dimensional NMR spectra were recorded on Bruker AVANCE III
300, 400, and 500 MHz spectrometers and calibrated using either
tetramethylsilane or residual solvent peaks as the internal reference.
CDCl3 with 1% w/w CD3OD was used to characterize compounds
with exchangeable protons. NMR yields were determined by 1H
NMR spectra of the crude reaction mixtures using mesitylene as an
external standard. Isolated yields refer to chromatographically purified
materials, unless otherwise stated, that characterized by both NMR
spectroscopy and high-resolution mass spectrometry (HRMS). The
following abbreviations are used to indicate the multiplicities: s,
singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad; app,
apparent, or combinations thereof. HRMS data were obtained on a
GCT, Micromass UK Ltd. and Q-Tof Ultima API, Micromass UK
Ltd. X-ray data were collected on a Bruker X8 Prospector Ultra
diffractometer with an ImuS copper microfocus X-ray tube and an
Apex II CCD detector. Samples were coated in FluoroLube and
attached to Mitegen micromounts. Data were collected under cooled
nitrogen gas at 150 K. Reactions were monitored using thin-layer
radical 29 undergoes conjugate addition to alkene 16. α-
Malonyl radical 30 abstracts a hydrogen atom from a second
molecule of 1,3-dioxolane to generate another radical 29,
propagating the radical chain.
1
We also studied the propagation steps of the mechanism
using density functional theory (DFT) calculations; we chose
the conformationally rigid chromone 16p as the substrate
(Scheme 4b). Preliminary results obtained are in agreement
with previously reported computations of related systems.16
Our calculations show that HAT is likely the rate-determining
step.16 The reaction is overall exergonic, but the HAT step
might be reversible. Intrigued by whether the energetics for
chromone could be extrapolated to other electronically and
sterically different substrates in Scheme 2, we computed the
energetics of HAT of dioxolane by several radicals (Figure S5).
Highly electrophilic alkenes tend to react more effi-
ciently.39,40 Moreover, we predict that substrates with more
exergonic HAT would not necessitate a large excess of C−H
donors. Our hypotheses, however, still require experimental
validation. Taken together, our current data not only shed light
on the reactivity pattern of our substrates but may also serve as
predictive tools for designing radical additions to olefins that
operate by radical chain pathways.
chromatography (TLC) or H NMR spectroscopic analysis of crude
material. All reactions were monitored by TLC carried out on 0.25
mm Merck silica gel plates (60F-254) using UV light (254 nm) for
visualization or p-anisaldehyde in EtOH, 0.2% ninhydrin in EtOH,
2.4% phosphomolybdic acid/1.4% H3PO4/5% H2SO4 in water, or
alkaline KMnO4 solutions as developing agents and heat for
visualization as necessary. SilicaFlash P60 (230−400 mesh) was
used for flash chromatography.
General Procedure for Synthesis of Alkylidene Malonates.
Aldehyde (20 mmol, 1.0 equiv) and malonate (20 mmol, 1.0 equiv)
were dissolved in benzene (50 mL) in a 100 mL single-neck round-
bottom flask. A magnetic stir bar, piperidine (2.0 mmol, 0.10 equiv),
and acetic acid (4.0 mmol, 0.20 equiv) were added. Additional
benzene (10 mL) was added to wash the walls of the flask. A Dean−
Stark trap was attached, and additional benzene (15 mL) was added
to the trap. A condenser was attached, and the mixture was stirred at
reflux overnight. The solvent, piperidine, and AcOH were removed in
vacuo. The crude material was dissolved in EtOAc (100 mL) and
washed with saturated NaHCO3 (20 mL × 2) and brine. The organic
layer was dried over Na2SO4, filtered through a plug of cotton, and
concentrated in vacuo. Crude materials were purified using flash
column chromatography (SiO2, EtOAc in hexanes) to yield the
desired product. Spectroscopic data of known compounds matched
those reported in the literature.41−47
In conclusion, we have found the addition of a dioxolanyl
group and hydrogen atom to electron-deficient alkenes via a
radical chain mechanism. During our mechanistic investiga-
tions, we discovered that α-bromomalonate and α-bromoester
were competent radical initiators. These results open up the
possibility of several initiation pathways for our reaction.
Visible-Light-Mediated Dioxolane Addition. Method A.
Alkene 16 (0.20 mmol, 1.0 equiv), (n-Bu4N)2S2O8 (0.20 mmol, 1.0
equiv), and fac-Ir(ppy)3 (1.0 μmol, 0.50 mol %) were mixed in a 2
dram vial. Degassed 1,3-dioxolane (3.0 mL) was added using a
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Scheme 4. Proposed Mechanism with Diverse Initiation Pathways
syringe, and the vial was flushed with argon for 1 min and sealed. The
vial was stirred under household LED irradiation (15 W × 4) for 24 h.
The vial was placed ca. 5 cm from each LED and ca. 15 cm from the
fan. The reaction vial was shielded with an aluminum-foil wall to
maximize absorption. Upon completion of reaction as indicated by
TLC analysis, the solvent was removed in vacuo. The crude material
was dissolved in EtOAc (2 mL), the resulting mixture was poured into
DI water (5 mL), and the layers were partitioned. The aqueous layer
was extracted with EtOAc (2 mL × 2). The combined organic layers
were filtered through a plug of Na2SO4 and concentrated in vacuo.
The crude material was purified by flash column chromatography (3
mL of SiO2).
Method B. Alkene 16 (0.20 mmol, 1.0 equiv), (n-Bu4N)2S2O8
(0.10 mmol, 0.50 equiv), and fac-Ir(ppy)3 (1.0 μmol, 0.50 mol %)
were mixed in a 2 dram vial. Degassed 1,3-dioxolane (3.0 mL) was
added using a syringe, and the vial was flushed with argon for 1 min
and sealed. The vial was stirred under household LED irradiation
(15W × 4) for 24 h. The vial was placed ca. 5 cm from each LED and
ca. 15 cm from the fan. The reaction vial was shielded with an
aluminum-foil wall to maximize absorption. Upon completion of
reaction as indicated by TLC analysis, the solvent was removed in
vacuo. The crude material was directly purified using flash column
chromatography (3 mL of SiO2).
maximize absorption. Upon completion of reaction as indicated by
TLC analysis, the solvent was removed in vacuo. Mesitylene was
added as external standard (for accuracy, the mass of mesitylene was
recorded instead of volume). The NMR yield was determined by
comparing the peaks at δ 6.79 (aromatic C−H of mesitylene) and δ
5.14 (C2−H from dioxolanyl of product).
Method D. Alkene (0.20 mmol, 1.0 equiv), (n-Bu4N)2S2O8 (0.10
mmol, 1.0 equiv), fac-Ir(ppy)3 (1.0 μmol, 0.50 mol %), and C−H
donors (10 equiv) were mixed in a 2 dram vial. Degassed MeCN (2.7
mL) was added using a syringe, and the vial was flushed with argon
for 1 min and sealed. The vial was stirred under household LED
irradiation (15W × 4) for 24 h. The vials are placed ca. 5 cm from
each LED and ca. 15 cm from the fan. The reaction vial was shielded
with an aluminum-foil wall to maximize absorption. Upon completion
of reaction as indicated by TLC analysis, the solvent was removed in
vacuo. The crude material was dissolved in EtOAc (2 mL) poured into
DI water (5 mL), and the layers were partitioned. The aqueous layer
was extrated with EtOAc (2 mL × 2). The combined organic layers
were filtered through a plug of Na2SO4 and concentrated in vacuo.
The crude material was purified by flash column chromatography (3
mL of SiO2).
Dimethyl 2-((1,3-Dioxolan-2-yl)(phenyl)methyl)malonate
(18aa). Colorless oil (54 mg, 91%), synthesized using Method A in
the general procedure. Rf = 0.20 (20% EtOAc in hexanes); IR (neat)
Method C. Alkene 16 (0.20 mmol, 1.0 equiv), (n-Bu4N)2S2O8
(0.10 mmol, 1.0 equiv), and fac-Ir(ppy)3 (1.0 μmol, 0.50 mol %) were
mixed in a 2-dram vial. Degassed 1,3-dioxolane (3.0 mL) was added
using a syringe, the vial was flushed with argon for 1 min and sealed.
The vial was stirred under household LED irradiation (15W × 4) for
24 h. The vials are placed ca. 5 cm from each LED and ca. 15 cm from
the fan. The reaction vial was shielded with an aluminum-foil wall to
1
2955, 2894, 1737, 1498, 1455, 1436 cm−1; H NMR (CDCl3, 500
MHz) δ 7.31−7.27 (m, 4H), 7.25−7.22 (m, 1H), 5.14 (d, J = 4.0 Hz,
1H), 4.08 (d, J = 11.0 Hz, 1H), 3.84−3.79 (m, 4H), 3.84−3.79 (m,
1H), 3.77 (s, 3H), 3.42 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
168.5, 167.8, 136.6, 129.2, 128.2, 127.4, 104.5, 65.1 65.0, 52.8, 52.6,
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52.3, 49.0; HRMS (ESI-TOF): m/z for [M + H]+ C15H19O6, calcd
295.1176, found 295.1162.
using Method A of the general procedure. Rf = 0.41(40% EtOAc in
1
hexanes); IR (neat) 1736, 1436, 1304, 1255 cm−1; H NMR (500
Dimethyl 2-((1,3-Dioxolan-2-yl)(2-fluorophenyl)methyl)-
malonate (18ab). Colorless oil (53 mg, 85%), synthesized using
Method A in the general procedure. Rf = 0.18 (20% EtOAc in
MHz, CDCl3) δ 7.58 (d, J = 8.0 Hz, 2H), 7.38 (d, J = 8.5 Hz, 2H),
5.14 (d, J = 3.5 Hz, 1H), 4.06 (d, J = 11.0 Hz, 1H), 3.88 (dd, J = 11.0,
3.5 Hz, 1H), 3.82 (dd, J = 1.5, 1.5 Hz, 1H), 3.81 (dd, J = 4.5, 3.0 Hz,
1H), 3.79 (dd, J = 2.0, 2.0 Hz, 1H), 3.77 (s 3H), 3.42 (s, 3H);
13C{1H} NMR (125 MHz, CDCl3) δ 168.2, 167.7, 139.9, 136.0,
1
hexanes); IR (neat) 2956, 2895, 1737, 1587, 1494, 1435 cm−1; H
NMR (CDCl3,500 MHz) δ 7.31 (app dt, J = 7.5, 1.5 Hz, 1H), 7.23
(app dq, J = 4.0, 2.0 Hz, 1H), 7.08 (app dt, J = 8.0, 1.5 Hz, 1H), 7.03
(ddd, J = 10.0, 8.0, 1.0 Hz, 1H), 5.20, (d, J = 4.0 Hz, 1H), 4.20 (d, J =
11.5, 4.5 Hz, 1H), 4.12 (app d, J = 11.0 Hz, 1H), 3.86 (dd, J = 6.0, 2.0
Hz, 1H), 3.85−3.81 (m, 3H), 3.78 (s, 3H), 3.47 (s, 3H); 13C{1H}
NMR (125 MHz, CDCl3) δ 168.3, 167.7, 161.0 (JCF = 245 Hz), 130.0
(JCF = 3.8 Hz), 129.0 (JCF = 8.8 Hz), 123.9 (JCF = 13.8 Hz), 123.8
(JCF = 3.8 Hz), 115.4 (JCF = 22.5 Hz), 103.9, 65.10, 65.0, 52.7, 52.4,
52.2, 41.9; HRMS (ESI-TOF) m/z for [M + H]+ C15H18O6F, calcd
313.1082, found 313.1068.
Dimethyl 2-((3-Chlorophenyl)(1,3-dioxolan-2-yl)methyl)-
malonate (18ac). Pale-yellow oil (55 mg, 84%), synthesized using
Method A in the general procedure. Rf = 0.39 (40% EtOAc in
hexanes); IR (neat) 2955, 2894, 1738, 1598, 1573, 1478, 1435 cm−1;
1H NMR (500 MHz, CDCl3) δ 7.32 (d, J = 1.0 Hz, 1H), 7.23−7.18
130.6, 104.1, 65.2, 65.1, 52.8, 52.6, 52.4, 48.7; HRMS (ESI-TOF) m/
z for [M + H]+ C16H16O6F3S, calcd 393.0614, found 393.0615.
Dimethyl 2-((1,3-Dioxolan-2-yl)(4-(trifluoromethyl)phenyl)-
methyl)malonate (18ai). Colorless oil (55 mg, 76%), synthesized
using Method A of the general procedure. Rf = 0.15 (20% EtOAc in
1
hexanes); IR (neat) 2958, 2896, 1740, 1621, 1436, 1423 cm−1; H
NMR (500 MHz, CDCl3) δ 7.55 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 8.5
Hz, 2H), 5.13 (d, J = 4.0 Hz, 1H), 4.10 (d, J = 11.0 Hz, 1H), 3.91
(dd, J = 11.0, 3.5 Hz, 1H), 3.82−3.79 (m, 4H), 3.78 (s, 3H), 3.46 (s,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 168.1, 167.6, 140.8, 129.8,
125.1, 125.0, 104.1, 65.2, 65.1, 52.8, 52.5, 52.4, 48.7; 19F NMR (471
MHz, CDCl3) δ − 63.6; HRMS (ESI-TOF) m/z for [M + H]+
C16H17O6F3, calcd 362.0972, found 362.0931.
3-(1,3-Dioxolan-2-yl)-1,3-diphenylpropan-1-one (18aj). White
solid (20 mg, 35%), synthesized using Method A of the general
procedure. X-ray crystals were obtained by slow evaporation in
EtOAc/hexanes. Rf = 0.33 (20% EtOAc in hexanes); mp = 88−90 °C;
IR (thin film) 3065, 2882, 1733, 1675, 1596, 1580, 1498, 1450 cm−1;
1H NMR (300 MHz, CDCl3) δ 7.94 (dd, J = 8.1, 1.2 Hz, 2H), 7.51
(m, 3H), 5.12 (d, J = 3.5 Hz, 1H), 4.05, (d, J = 11.5 Hz, 1H), 3.81−
3.79 (m, 5H), 3.77 (s, 3H), 3.48 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 168.24, 167.7, 138.7, 134.0, 129.5, 129.4, 127.7, 127.6,
104.2, 65.24, 65.15, 52.7, 52.6, 52.5, 48.6; HRMS (ESI-TOF) m/z for
[M + H]+ C15H18O6Cl, calcd 329.0786, found 329.0771.
Dimethyl 2-((4-Bromophenyl)(1,3-dioxolan-2-yl)methyl)-
malonate (18ad). Pale-yellow oil (69 mg, 92%), synthesized using
Method A in the general procedure. Rf = 0.13 (20% EtOAc in
(app dt, J = 8.1, 1.2 Hz, 1H), 7.43−7.41 (m, 2H), 7.38−7.35 (m, 2H),
7.32−7.28 (m, 3H), 7.26−721 (m, 1H), 5.10 (d, J = 3.6 Hz, 1H),
3.90−3.82 (m, 4H), 3.81−3.76 (m, 1H), 3.58 (dd, J = 16.8, 5.4 Hz,
1H), 3.37 (dd, J = 16.8, 8.1 Hz, 1H); 13C{1H} NMR (75 MHz,
CDCl3) δ 198.3, 139.8, 137.2, 132.9, 128.8, 128.5, 128.3, 128.1, 126.9,
106.0, 65.2, 65.0, 44.7, 38.8, 29.7; HRMS (ESI-TOF) m/z for [M +
H]+ C18H19O3 calcd 283.1329, found 283.1319.
1
hexanes); IR (neat) 2959, 2892, 1748, 1492 cm−1; H NMR (500
MHz, CDCl3) δ 7.42 (dd, J = 7.0, 2.0 Hz, 2H), 7.19 (dd, J = 6.5, 2.0
Hz, 2H), 5.10, (d, J = 3.5 Hz, 1H), 4.03, (d, J = 11.0 Hz, 1H), 3.81−
3.78 (m, 5H), 3.7 (s, 3H), 3.47 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 168.3, 167.7, 135.6, 131.3, 131.1, 121.6, 104.2, 65.22, 65.15,
52.7, 52.6, 52.5, 48.4; HRMS (ESI-TOF) m/z for [M + H]+
C15H18O6Br, calcd 373.02813, found 373.0266 and 376.0273.
Dimethyl 2-((1,3-Dioxolan-2-yl)(o-tolyl)methyl)malonate (18ae).
Colorless oil (48 mg, 78%), synthesized using Method A in the
general procedure. Rf = 0.38 (30% EtOAc in hexanes); IR (neat)
Dimethyl 2-(Cyclohexyl(1,3-dioxolan-2-yl)methyl)malonate
(18ak). Colorless oil (47 mg, 78%) using Method A of the general
procedure. Rf = 0.26 (20% EtOAc in hexanes); IR (neat) 2928; 2854,
1
1737, 1450, 1435 cm−1; H NMR (500 MHz, CDCl3) δ 5.14 (d, J =
4.5 Hz, 1H), 3.91−3.87 (m, 2H), 3.85−3.81 (m, 2H), 2.50 (ddd, J =
9.0, 7.0, 4.5 Hz, 1H), 1.74−1.72 (m, 4H), 1.65−1.60 (m, 2H), 1.26−
1.21 (m, 5H); 13C{1H} NMR (125 MHz, CDCl3) δ 169.6, 169.5,
103.3, 64.9, 64.5, 52.3, 49.7, 47.6, 37.9, 31.6, 29.9, 26.9, 26.7, 26.4;
HRMS (ESI-TOF) m/z for [M + H]+ C15H25O6, calcd 301.1646,
found 301.1634.
Diethyl 2-(1-(1,3-Dioxolan-2-yl)ethyl)malonate (18al). A crude
oil (95%, NMR), synthesized using Method C from the general
procedure. The crude material was not purified due to difficulties in
purification using flash column chromatography.
1
2955, 2892, 1739, 1495, 1435 cm−1; H NMR (500 MHz, CDCl3) δ
7.24 (dd, J = 8.5, 2.0 Hz, 1H), 7.16−7.11 (m, 1H), 5.09 (d, J = 3.5
Hz, 1H), 4.18 (dd, J = 11.5, 4.0 Hz, 1H), 4.10 (d, J = 11.5 Hz), 3.83−
3.78 (m, 4H), 3.78 (s, 3H), 3.41 (s, 3H), 2.45 (s, 3H); 13C{1H} NMR
(125 MHz, CDCl3) δ 168.71, 167.94, 137.7, 135.3, 130.3, 127.4,
127.1, 125.7, 104.8, 65.2, 65.1, 53.0, 52.7, 52.3, 43.6, 20.1; HRMS
(ESI-TOF) m/z for [M + H]+ C16H21O6, calcd 309.1333, found
309.1318.
Methyl 3-(1,3-Dioxolan-2-yl)-2-((4-methoxyphenyl)sulfonyl)-3-
phenylpropanoate (18am). Pale-yelow solid, mixture of both
diastereomers (75 mg, 92%, dr = 1:1.2) using Method A from the
general procedure. Rf = 0.30 (40% EtOAc in hexanes), 0.21 (40%
EtOAc in hexanes); IR (neat) 2955, 2892, 1746, 1591, 1497, 1455
cm−1; 1H NMR (500 MHz, CDCl3) δ 7.85 (d, J = 9.0 Hz, 2H), 7.28
(dd, J = 9.0, 2.0 Hz, 2H), 7.25−7.13 (m, 9H), 7.00 (d, J = 9.0 Hz,
2H), 6.71 (d, J = 9.0 Hz, 2H), 5.73 (d, J = 2.5 Hz, 1H), 4.95 (d, J =
2.5 Hz, 1H), 4.80 (d, J = 10.5 Hz, 1H), 4.69 (d, J = 11.5 Hz, 1H),
3.90 (app d, J = 2.5 Hz, 1H), 3.88 (s, 3H), 3.85 (app d, J = 3.0 Hz,
1H), 3.82 (s, 3H), 3.81 (app s, 4H), 3.22−3.10 (m, 1H), 3.17 (s,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 166.1, 165.4, 164.2, 163.4,
134.8, 133.8, 131.5, 130.7, 130.4, 130.1, 129.4, 127.9, 127.8, 127.7,
127.6, 114.2, 113.8, 104.6, 102.6, 72.3, 71.4, 65.4, 65.3, 65.1, 65.0,
55.7, 55.6, 52.9, 52.3, 48.6, 47.7; HRMS (ESI-TOF) m/z for [M +
H]+ C20H21O7S, calcd 405.1003, found 405.0998.
Dimethyl 2-((1,3-Dioxolan-2-yl)(4-methoxyphenyl)methyl)-
malonate (18af). Pale-yellow oil (59 mg, 90%), synthesized using
Method A in the general procedure. Rf = 0.30 (40% EtOAc in
1
hexanes); IR (neat) 2955, 2896, 1738, 1613, 1515, 1435 cm−1; H
NMR (400 MHz, CDCl3) δ 7.23 (d, J = 8.8 Hz, 2H), 6.82 (d, J = 8.8
Hz, 2H), 5.11 (d, J = 3.6 Hz, 1H), 4.03 (d, J = 10.8 Hz, 1H), 3.83−
3.76 (m, 5H), 3.77 (s, 3H), 3.76 (s, 3H), 3.45 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 168.6, 167.9, 158.8, 130.2, 128.5, 113.6, 104.7,
65.13, 65.05, 55.1, 52.9, 52.6, 52.3, 48.2; HRMS (ESI-TOF) m/z for
[M + H]+ C16H21O7, calcd 325.1282, found 325.1267.
Dimethyl 2-((4-Acetamidophenyl)(1,3-dioxolan-2-yl)methyl)-
malonate (18ag). Yellow oil (53 mg, 76%), synthesized using
Method B in the general procedure. Rf = 0.13 (60% EtOAc in
hexanes); IR (neat) 3319 (br); 3123, 2955, 2926, 2854, 1737, 1671,
1
1602, 1632, 1436 cm−1; H NMR (500 MHz, CDCl3) δ 7.80 (br s,
1H), 7.43 (d, J = 8.5 Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H), 5.10 (d, J =
3.5 Hz, 1H), 4.05 (d, J = 11.0 Hz, 1H), 3.86−3.79 (m, 5H), 3.77 (s,
3H), 3.45 (s, 3H), 2.14 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
168.5, 168.47, 168.0, 137.4, 132.1, 130.5, 129.7, 119.4, 104.5, 65.1,
65.0, 52.8, 52.6, 52.4, 48.4, 24.4; HRMS (ESI-TOF) m/z for [M +
H]+ C17H22O7N, calcd 352.1391, found 352.1374.
2-(1,3-Dioxolan-2-yl)ethane-1-sulfonyl fluoride (18an). Colorless
oil, as an inseparable mixture of regioisomers (70 mg, 95%, rr = 14:1),
synthesized using Method B from the general procedure. Rf = 0.35
(30% EtOAc in hexanes); IR (neat) 2959, 2897, 1738, 1404, 1365,
1
1256, 1198 cm−1; H NMR (400 MHz, CDCl3) δ 5.06 (dd, J = 3.6,
3.6 Hz, 1H), 3.99 (ddd, J = 11.2, 9.2, 6.4 Hz, 2H), 3.92 (ddd, J = 11.2,
9.2, 6.8 Hz, 2H), 3.53 (d, J = 8.0, 4.8 Hz, 1H), 3.51 (dd, J = 8.4, 4.8
Dimethyl 2-((1,3-Dioxolan-2-yl)(4-((trifluoromethyl)thio)phenyl)-
methyl)malonate (18ah). Pale-yellow oil (61 mg, 77%), synthesized
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Note
Hz, 1H), 2.34 (dd, J = 8.0, 3.2 Hz, 1H), 2.31 (dd, J = 4.4, 3.2 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ 100.7, 95.2, 72.6, 69.1,
65.3, 47.5, 47.3, 45.2, 45.0, 27.3; 19F NMR (376 MH, CDCl3) δ
−151.9; HRMS (ESI-TOF) m/z for [M + H]+ C5H10FO4S calcd
185.0284, found 185.0271.
104.5, 65.2, 65.1, 52.7, 52.5, 51.7, 50.4; HRMS (ESI-TOF) m/z for
[M + H]+ C14H17O6NCl, calcd 330.0739, found 330.0726.
Dimethyl 2-((1,3-Dioxolan-2-yl)(quinolin-2-yl)methyl)malonate
(18av). Yellow oil (51 mg, 74%), synthesized using Method B of
the general procedure. Rf = 0.13 (30% EtOAc in hexanes); IR (neat)
2954, 2894, 1756, 1737, 1600, 1505, 1434 cm−1; 1H NMR (500 MHz,
CDCl3) δ 8.08 (app d, J = 8.5 Hz, 1H), 8.00 (app d, J = 8.5 Hz, 1H),
7.77 (app d, J = 8.0 Hz, 1H), 7.65 (app dt, J 8.5, 1.5 Hz, 1H), 7.48
(app dt, J = 8.0, 1.0 Hz, 1H), 7.44 (d, J = 8.5 Hz, 1H), 5.38 (d, J = 5.5
Hz, 1H), 4.11 (dd, J = 10.5, 5.5 Hz, 1H), 3.92−3.88 (m, 2H), 3.86−
3.83 (m, 2H), 3.81 (app s, 4H), 3.53, (s, 3H) 13C{1H} NMR (125
MHz, CDCl3) δ 169.2, 168.7, 157.9, 147.6, 135.9, 129.3, 129.2, 127.5,
127.2, 126.2, 122.8, 105.1, 65.1, 65.0, 52.6, 52.4, 52.1, 51.2; HRMS
(ESI-TOF) m/z for [M + H]+ C18H20O6N calcd 346.1285, found
346.1269.
Dimethyl 2-(Benzo[d][1,3]dioxol-2-yl(phenyl)methyl)malonate
(18ba). White solid (56 mg, 82%), synthesized using Method D of
the general procedure. Additional note: The bulk of benzo-1,3-dioxole
could be removed by drying the crude material by high vacuum
overnight prior flash column chromatography. X-ray quality crystals
were obtained by slow evaporation in EtOAc/hexanes. IR (thin film)
2954, 2894, 1756, 1738, 1593, 1474, 1436 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.34−7.32 (m, 2H), 7.30−7.27 (m, 2H), 7.26−7.23 (m,
2H), 6.76−6.70 (m, 3H), 6.70−6.67 (m, 1H), 4.17 (d, J = 10.4 Hz,
1H), 4.08 (dd, J = 10.4, 4.0 Hz, 1H), 3.71 (s, 3H), 3.46 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 168.2, 167.4, 147.2, 147.1,
2-(2-(Phenylsulfonyl)ethyl)-1,3-dioxolane (18ao). Pale-yellow oil
as an inseparable mixture of regioisomers (40 mg, 83%, rr = 20:1),
1
synthesized using Method A from the general proceure. H NMR
(500 MHz, CDCl3) δ 7.91 (app d, J = 7.5 Hz, 2H), 7.67 (dd, J = 7.0,
1.0 Hz, 1H), 7.58 (m, 2H), 4.96 (app t, J = 4.0 Hz, 1H), 4.80 (s, 2H,
C4-isomer), 3.91 (ddd, J = 11.0, 9.0, 6.5 Hz, 2H), 3.83 (ddd, J = 11.0,
9.0, 7.0 Hz, 2H), 3.95 (ddd, J = 11.0, 9.0, 6.5 Hz, 2H), 3.84 (ddd, J =
11.0, 9.0, 7.0 Hz, 2H), 3.23 (m, 2H); 13C{1H} NMR (125 MHz,
CDCl3) δ 138.9, 133.8, 133.7, 129.3, 129.2, 128.0, 127.9, 101.7, 95.0,
73.6, 69.1, 651, 52.7, 50.6, 27.0, 26.4. The NMR spectroscopic data of
the major regioisomer are consistent with those reported in the
literature.48,49
2-(1,3-Dioxolan-2-yl)chroman-4-one (18ap). Colorless oil (38
mg, 86%), synthesized using Method A of the general procedure. Rf =
0.22 (30% EtOAc in hexanes); IR (neat) 2892, 1683, 1609, 1579,
1
1474, 1465 cm−1; H NMR (500 MHz, CDCl3) δ 7.87 (dd, J = 8.0,
1.5 Hz, 1H), 7.48 (ddd, J = 9.0, 7.5, 1.5 Hz, 1H), 7.03 (app d, J = 8.0
Hz, 1H), 7.01 (d, J = 7.0 Hz), 5.20 (d, J = 3.5 Hz, 1H), 4.53 (app dt, J
= 12.0, 4.0 Hz, 1H), 4.07−4.01 (m, 2H), 4.01−3.96 (m, 2H), 2.89
(dd, J = 17.0, 12.0 Hz, 1H), 2.77 (dd, J = 17.0, 3.5 Hz, 1H); 13C{1H}
NMR (125 MHz, CDCl3) δ 191.3, 160.7, 136.0, 126.7, 121.5, 121.1,
117.9, 103.0, 65.7, 65.4, 37.1; HRMS (ESI-TOF) m/z for [M + H]+
C12H13O4 calcd 221.0808, found 221.0808. The spectrocopic data are
consistent with those reported in the literature.50
Dimethyl 2-((1,3-Dioxolan-2-yl)(pyridin-2-yl)methyl)malonate
(18ar). Yellow oil (53 mg, 89%), synthesized using Method B of
the general procedure. Rf = 0.31 (60% EtOAc in hexanes); IR (neat)
2955, 2894, 1736, 1633, 1593, 1473 cm−1; 1H NMR (500 MHz,
CDCl3) δ 8.52 (ddd, J = 5.0, 1.5, 1.0 Hz, 1H), 7.62 (app dt, J = 7.5,
1.5 Hz, 1H), 7.31 (app d, J = 7.5 Hz, 1H), 7.14 (ddd, J = 7.5, 5.0, 1.0
Hz, 1H), 5.28, (d, J = 5.0 Hz, 1H), 3.93, (dd, J = 10.5, 5.0 Hz, 1H),
3.89−3.79 (m, 4H), 3.78 (s, 3H), 3.53 (s, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 169.0, 168.4, 157.3, 149.0, 136.1, 124.9, 122.0, 104.9,
65.1, 65.0, 52.6, 52.4, 51.8, 50.6; HRMS (ESI-TOF) m/z for [M +
H]+ C14H18O6N, calcd 296.1129, found 296.1118.
134.7, 129.4, 128.4, 127.9, 121.6, 121.5, 110.8, 108.5, 108.4, 52.8,
52.5, 49.3; HRMS (ESI-TOF) m/z for [M + H]+ C19H19O6, calcd
343.1186, found 343.1159.
Dimethyl 2-(Phenyl(1,3,5-trioxan-2-yl)methyl)malonate (18ca).
The crude yellow oil was obtained using Method D. Note: Because of
the low yield and the scale of the reaction, we were unable to obtain
1
accurate isolated yields for 18ca. We determined the yield using H
1
NMR spectroscopy. The H NMR spectrum of the crude mixture is
provided in the Supporting Information.
4-Phenyldihydrofuran-2(3H)-one (23). A solution of dimethyl 2-
((1,3-dioxolan-2-yl)(phenyl)methyl)malonate 18aa (100 mg, 0.34
mmol) in water (2.3 mL) and trifluoroacetic acid (2.3 mL) was stirred
at room temperature under air atmosphere in a 25 mL, single-necked,
round-bottomed flask containing a magnetic stir bar. After 2 h, Et3SiH
(540 μL, 10 equiv) was added to the stirring solution, and resulting
mixture was refluxed for 5 h. On completion of the reaction as
indicated by TLC analysis, the reaction flask was allowed to cool to
room temperature. Then the reaction mixture was transferred to a 30
mL separatory funnel, and the organic phase was extracted with
EtOAc (3 × 7 mL). Combined organic layers were washed with
distilled water (2 × 10 mL) and dried by adding Na2SO4. After 10
min, the Na2SO4 was filtered out, and the resulting solution was
concentrated by rotary evaporation. The crude mixture was purified
by flash column chromatography (15 mL of SiO2, 5 to 10% EtOAc in
hexanes) to obtain 4-phenyldihydrofuran-2(3H)-one (23) (74 mg,
Dimethyl 2-((1,3-Dioxolan-2-yl)(pyridin-3-yl)methyl)malonate
(18as). Yellow oil (42 mg, 71%), synthesized using Method B of
the general procedure. Rf = 0.30 (100% EtOAc); IR (neat) 2956,
2895, 2362, 2341, 1735, 1700, 1653, 1577 cm−1; 1H NMR (500 MHz,
CDCl3) δ 8.56 (app d, J = 2.0 Hz, 1H), 8.50 (dd, J = 4.5, 1.5 Hz, 1H),
7.66 (app dt, J = 8.0, 2.0 Hz, 1H), 5.14 (d, J = 3.0 Hz, 1H), 4.08 (d, J
= 11.0 Hz, 1H), 3.86 (dd, J = 11.0, 3.5 Hz, 1H), 3.82−3.76 (m, 3H),
3.76 (s, 3H), 3.74 (dd, J = 3.5, 1.5 Hz, 1H), 3.46 (s, 3H); 13C{1H}
NMR (125 MHz, CDCl3) δ 168.1, 167.6, 150.9, 148.8, 136.9, 132.1,
123.0, 103.8, 65.3, 65.2, 52.8, 52.5, 52.4, 46.6; HRMS (ESI-TOF) m/
z for [M + H]+ C14H18O6N, calcd 296.1129, found 296.1122.
Dimethyl 2-((1,3-Dioxolan-2-yl)(pyridin-4-yl)methyl)malonate
(18at). Pale-yellow oil (48 mg, 82%), synthesized using Method B
of the general procedure. Rf = 0.16 (80% EtOAc in hexanes); IR
1
99%) as a yellow oil. The H NMR spectrum of the product was
identical to that of the literature.51
Lights-On/Lights-Off Experiment (Figure S2). Alkene 16a (0.30
mmol, 1.0 equiv), (n-Bu4N)2S2O8 (0.075 mmol, 0.25 equiv), fac-
Ir(ppy)3 (1.5 μmol, 0.50 mol %), and mesitylene (0.30 mmol, 1.0
equiv) were mixed in a Teflon-coated 2 dram vial. Degassed 1,3-
dioxolane (4.5 mL) was added, and the vial was flushed with argon (1
min) and sealed. The vial was irradiated with household LEDs (15W
× 4) and cooled with a fan. During the lights-off period, the vial was
wrapped with aluminum foil and stirred in the dark. Aliquots (100
μL) were removed periodically (1, 2, 3, 5, and 6 h) using syringes,
transferred to NMR tubes, diluted with CDCl3 (ca. 0.6 mL), and
1
(neat) 2956, 2895, 1738, 1601, 1560, 1436 cm−1; H NMR (500
MHz, CDCl3) δ 8.53 (app d, J = 6.0 Hz, 1H), 7.24 (dd, J = 4.5, 1.5
Hz, 2H), 5.12 (d, J = 3.0 Hz, 1H), 4.09 (d, J = 11.0 Hz, 1H), 3.84
(app d, J = 3.5 Hz, 1H), 3.82−3.79 (m, 3H), 3.78 (s, 3H), 3.48 (s,
3H); 13C{1H} NMR (125 MHz, CDCl3) δ 167.96, 167.5, 149.6,
145.7, 124.6, 103.7, 65.3, 65.2, 52.8, 52.6, 52.2, 48.3; HRMS (ESI-
TOF) m/z for [M + H]+ C14H18O6N, calcd 296.1129, found
296.1115.
Dimethyl 2-((4-Chloropyridin-2-yl)(1,3-dioxolan-2-yl)methyl)-
malonate (18au). Yellow oil (51 mg, 77%), synthesized using
Method B of the general procedure. Rf = 0.45 (40% EtOAc in
1
analyzed by H NMR spectroscopy.
Scale-Up Experiments (Scheme 3b, 18aa, 18as, 18af). Alkene
16a (1.1011 g, 5.00 mmol), (n-Bu4N)2S2O8 (0.8463 g, 1.25 mmol,
0.25 equiv), and fac-Ir(ppy)3 (1.6 mg, 0.0025 mmol, 0.050 mol %)
were mixed in a 150 mL pressure tube. Degassed 1,3-dioxolane (68
mL) was added using a syringe, and the pressure tube was flushed
with argon for 1 min and sealed. The reaction mixture was stirred
1
hexanes); IR (neat) 2895, 2595, 1738, 1576, 1557, 1468 cm−1; H
NMR (500 MHz, CDCl3) δ 8.40 (app d, J = 5.5 Hz, 1H), 7.35 (app d,
J = 2.0 Hz, 1H), 7.16 (dd, J = 5.5, 2.0 Hz, 1H), 5.24 (d, J = 5.0 Hz,
1H), 3.90−3.80 (m, 5H), 3.78 (s, 3H), 3.56 (s, 3H); 13C{1H} NMR
(125 MHz, CDCl3) δ 168.8, 168.2, 159.0, 149.7, 144.1, 125.3, 122.6,
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Note
under household LED irradiation (15W × 4) for 24 h and was placed
ca. 5 cm from each LED and ca. 15 cm from the fan. The reaction
vessel was shielded with an aluminum-foil wall to maximize
absorption. Upon completion of the reaction as indicated by TLC
analysis, the solvent was removed in vacuo. Mesitylene (600 mg) was
added as an external standard. The yield was determined by NMR
spectroscopic analysis; specifically, the peaks at δ 6.79 (aromatic C−H
of mesitylene) and δ 5.14 (C2−H from dioxolanyl of product) were
compared to calculate the yield.
Screening of [Ir] for α-Bromomalonate Radical Initiator (Table
S2). Alkene 16a (0.20 mmol, 1.0 equiv), bromomalonate (0.050
mmol, 0.25 equiv), and fac-Ir(ppy)3 (0.0010 mmol, 0.50 mol %) were
mixed in a 2 dram vial. Degassed 1,3-dioxolane (3.0 mL) was added
using a syringe, and the vial was flushed with argon for 1 min and
sealed. The vial was stirred under household LED irradiation (15W ×
4) for 24 h. The solvent was removed in vacuo. The vials are placed ca.
5 cm from each LED and ca. 15 cm from the fan. The reaction vial
was shielded with an aluminum-foil wall to maximize absorption.
Mesitylene was added as external standard (for accuracy, and the mass
of mesitylene was recorded instead of volume). The NMR yield was
determined by comparing the peaks at δ 6.79 (aromatic C−H of
mesitylene) and δ 5.14 (C2−H from dioxolanyl of product).
Although Ir-4 (entry 4) afforded partial conversion, only the reaction
with Ir-5 (entry 5) that had full conversion was worked up and
analyzed.
Pittsburgh) is acknowledged for his assistance with LED light
wavelength measurement.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c03044.
■
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Experimental procedures, computational details and
characterization data for new compounds (PDF)
Accession Codes
CCDC 2027551−2027552 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
■
Kazunori Koide − Department of Chemistry, University of
Pittsburgh, Pittsburgh, Pennsylvania 15260, United States;
orcid.org/0000-0001-8894-8485; Email: koide@pitt.edu
Authors
Wei Chuen Chan − Department of Chemistry, University of
Pittsburgh, Pittsburgh, Pennsylvania 15260, United States;
orcid.org/0000-0003-0199-8960
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Jincy K. Vinod − Department of Chemistry, University of
Pittsburgh, Pittsburgh, Pennsylvania 15260, United States;
orcid.org/0000-0003-4269-2159
Complete contact information is available at:
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This research was supported in part by the University of
Pittsburgh Center for Research Computing through the
resources provided and the U.S. National Science Foundation
(CHE-1955758). Professor Eugene Wagner (University of
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