M. S. Workentin and D. C. Magri
halides.[18] By exploiting the competition between the frag-
mentation and heterogeneous reduction of electrogenerated
intermediates,[10,13] we have begun to create a library of radi-
cal-anion clocks.
Dissociative ET theory was applied to the activation-driv-
ing force relationships to obtain unknown thermochemical
information. Most interestingly, the evaluated BDEs of di-
phenyl-substituted endoperoxides are extremely low. The
reasoning for this observation is attributed to the eclipsing
interaction of the electron lone pairs on the oxygen atoms
and the presence of phenyl rings in the bridgehead positions.
Instrumentation: Melting points were recorded on an Electrothermal
9100 capillary melting point apparatus and were corrected. UV/Vis spec-
tra were recorded on a Varian Cary 100 Bio UV/Vis spectrometer. IR
spectra were recorded on a Bruker Vector 33 FT-IR spectrometer on
NaCl plates or in a solution cell. The IR frequencies were reported in
cmꢀ1 and followed by a letter (w, m, or s) designating the relative
strength of the IR stretches as weak, medium, or strong. NMR spectra
were recorded on a Varian Mercury spectrometer and reported in ppm.
1H and 13C NMR spectra were recorded at 400.1 and 100.6 MHz, respec-
tively, with CDCl3 as the solvent. Spectra are reported in ppm versus tet-
ramethylsilane (d=0.00 ppm) for 1H NMR and CDCl3 (d=77.00 ppm)
for 13C NMR spectra. Mass spectrometry was performed on a MAT 8200
Finnigan high-resolution mass spectrometer by electron impact (EI) and
by chemical ionization (CI) with isobutane.
ꢀ
Several studies have demonstrated that ET to O O bonds is
Synthesis: 1,4-Diphenyl-1,4-butanedione was synthesized by Friedel–
Crafts acylation by reacting succinyl chloride with benzene. 1,4-Diphen-
yl-1,4-butanediol was synthesized by reduction of 1,4-diphenyl-1,4-bu-
non-adiabatic,[6,13,27,38] possibly due to violation of the Born–
Oppenheimer approximation at the transition state during
[39]
ꢀ
ET to the O O bond. This electronic barrier is manifest-
AHCTREtUNG anedione with excess sodium borohydride. The endoperoxides were syn-
thesized according to literature procedures with slight modifications.[14,15]
ed as a kinetic contribution as observed by the low magni-
tude of kohet. This kinetic barrier is the reason why endoper-
oxides with rather weak covalent bonds of 20 kcalmolꢀ1 are
thermally stable with melting points in excess of 1408C.
This study also highlights an unprecedented radical-anion
chain mechanism initiated by the concerted DET reduction
of a bicyclic endoperoxide. Upon reduction of 2, the distonic
radical anion 2a undergoes a b-scission fragmentation in
competition with direct reduction from the electrode. The
fragmentation results in the formation of ethylene and the
ketyl radical anion 2e, which can homogeneously reduce 2
and propagate the radical-anion chain mechanism. Although
a competing self-protonation mechanism involving 1,4-di-
phenyl-1,4-butanedione as well as the presence of other
weak non-nucleophilic acids can protonate the distonic radi-
cal anion 2a, thus decreasing the efficiency of the radical-
anion chain reaction, the significance of this unusual mecha-
nism should not be understated. Recently we reported, in
collaboration, the first example of a competition between a
concerted and stepwise DET mechanism for antimalarial
G3-factor endoperoxides,[40] which potentially opens up an
alternative mode of action. Our present results reveal anoth-
er novel mode of reactivity initiated by ET that could have
implications not only on understanding the reduction mech-
anism of naturally occurring endoperoxides, but could also
be useful in the design and synthesis of antimalarial prodrug
models.[41]
Compound 1: 1,4-Diphenyl-2,3-dioxabicyclo[2.2.2]oct-5-ene (1) was puri-
fied by flash chromatography using hexanes and dichloromethane (3:2)
and recrystallized from a mixture of diethyl ether/dichloromethane as
white needles (48%). M.p. 145–1468C; 1H NMR (CDCl3, 400 MHz): d=
1.96–2.09 (m, 2H), 2.59–2.72 (m, 2H), 6.88 (s, 2H), 7.35–7.46 (m, 6H),
7.51–7.58 ppm (m, 4H); 13C NMR (CDCl3, 100 MHz): d=29.68, 78.37,
125.94, 128.24, 128.37, 136.32, 139.20 ppm; IR (CCl4): n˜ =3090 (w), 3063
(s), 3033 (m), 2972 (m), 2935 (s), 2860 (w), 1496 (w), 1449 (s), 1370 (s),
ꢀ1
1317(w), 1184 (w), 1063 (m), 933 (m), 908 (m), 696 (s), 679 cm
(m);
MS EI: m/z (%): 264 (1) [M+], 233 (20), 232 (100), 154 (8), 141 (11), 115
(15), 105 (34), 91 (17), 77 (33); MS CI: m/z (%): 265 (8) [M++1], 249
(10), 248 (38), 233 (20), 232 (100), 218 (12), 206 (18), 105 (27), 77 (8);
exact mass: 264.1156 (calcd 264.1150).
Compound 2: 1,4-Diphenyl-2,3-dioxabicyclo[2.2.2]octane (2) was recrys-
tallized from diethyl ether/methylene chloride to yield white needles
(63%). M.p. 193–1958C; 1H NMR (CDCl3, 400 MHz): d=2.19–2.35 (m,
4H), 2.42–2.58 (m, 4H), 7.25–7.39 (m, 6H), 7.40–7.46 ppm (m, 4H);
13C NMR (CDCl3, 100 MHz): d=31.69, 78.24, 124.90, 127.68, 128.16,
141.97ppm; IR (CCl 4): n˜ =3090 (w), 3064 (m), 3032 (m), 2969 (s), 2936
(s), 1496 (m), 1449 (s), 1437(w), 1339 (m), 1119 (m), 1047(w), 964 (w),
908 (m), 696 (s), 675 cmꢀ1 (m); MS: m/z (%): 266 (25) [M+], 249 (32),
238 (9), 234 (11), 233 (19), 232 (33), 146 (9), 144 (9), 130 (40), 117(14),
105 (100), 91 (16), 77 (57); exact mass: 266.1301 (calcd 266.1302).
Electrochemistry: Cyclic voltammetry was performed either on a Perkin–
Elmer PAR283, or 263A potentiostat interfaced to a personal computer
equipped with PAR270 electrochemistry software. Experiments were per-
formed with a three-electrode arrangement placed in a water-jacket cell
stored in an oven at 1108C. It was placed in a copper Faraday cage,
purged with a continuous flow of high-purity argon and connected to a
cooling bath maintained at 258C throughout the entire experiment. The
electrolyte was added to the cell followed by DMF (25 mL) and a half-
inch magnetic stir bar. The solution was bubbled with argon to expel
oxygen from the solution. The working electrode was a 3 mm diameter
glassy carbon rod (Tokai, GC-20) sealed in glass tubing. Prior to use it
was polished on a polishing cloth with diamond paste, rinsed and sonicat-
ed in 2-propanol for 10 min and finally dried with a stream of cool air.
The working electrode was activated by cycling 25 times between 0 and
ꢀ2.8 V versus SCE at a scan rate of 0.2 Vsꢀ1. The counter electrode was
a 1 cm2 Pt plate. The reference electrode was a silver wire immersed in a
glass tube with a sintered end containing 0.10m TEAP in DMF. After
each experiment, it was calibrated against the ferrocene/ferricinium
couple at 0.475 V versus KCl saturated calomel electrode (SCE) in DMF.
Experimental Section
Materials: N,N-Dimethylformamide (DMF) was distilled over CaH2
under a nitrogen atmosphere at reduced pressure. Tetraethylammonium
perchlorate (TEAP) from Fluka was recrystallized three times from etha-
nol and stored under vacuum. Flash chromatography was performed with
silica gel 60 (230–400 mesh ASTM) from EM science. Fractions were de-
veloped in the chosen eluant with Kieselgel 60F254 thin-layer chromatog-
raphy (TLC) plates and viewed by ultraviolet or visible light or iodine
staining. Methanol and ethanol were freshly distilled from magnesium.
Toluene was freshly dissolved from sodium and benzophenone. Photo-
oxygenation reactions were performed in solutions of spectroscopic grade
dichloromethane (Caledon) and benzene (EM Science). Other solvents
and reagents not specified were used without purification and obtained
from Aldrich.
Heterogeneous product studies: Constant potential electrolyses were per-
formed with a Perkin–Elmer PAR263A potentiostat. The working elec-
trode was a 12 mm tipped glassy carbon rotating-disk electrode (EDI101)
with a CTV101 speed control unit from Radiometer Analytical. The
counter electrode was a platinum wire immersed in a glass frit containing
2 mm layer of neutral alumina. The reference electrode was a silver wire
contained in a sintered glass frit and stored in an electrolyte solution
1708
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 1698 – 1709