Mechanistic analysis of oxidative C-H cleavages using inter- and intramolecular kinetic isotope effects

Article abstract of DOI:10.1016/j.tet.2009.10.088

A series of monodeuterated benzylic and allylic ethers were subjected to oxidative carbon-hydrogen bond cleavage to determine the impact of structural variation on intramolecular kinetic isotope effects in DDQ-mediated cyclization reactions. These values

Full text of DOI:10.1016/j.tet.2009.10.088

Tetrahedron 65 (2009) 10830–10836
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Mechanistic analysis of oxidative C–H cleavages using inter- and intramolecular
kinetic isotope effects
*
Hyung Hoon Jung, Paul E. Floreancig
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 August 2009
Received in revised form 9 October 2009
Accepted 26 October 2009
Available online 29 October 2009
A series of monodeuterated benzylic and allylic ethers were subjected to oxidative carbon–hydrogen
bond cleavage to determine the impact of structural variation on intramolecular kinetic isotope effects in
DDQ-mediated cyclization reactions. These values are compared to the corresponding intermolecular
kinetic isotope effects that were accessed through subjecting mixtures of non-deuterated and dideu-
terated substrates to the reaction conditions. The results indicate that carbon–hydrogen bond cleavage is
rate determining and that a radical cation is most likely a key intermediate in the reaction mechanism.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
promising method would be facilitated by a greater understanding
of the mechanistic nuances of the individual steps of the process.
Oxygen-containing heterocycles are present in numerous bio-
logically active compounds, making these structures the focus of
intensive reaction development studies.1 These units are often
prepared through variations in the Prins reaction, in which ring
formation occurs via intramolecular additions of carbon nucleo-
philes to oxocarbenium ions.2 These processes often require the use
of strongly acidic conditions to initiate ionization, thereby limiting
functional group compatibility. We have been actively pursuing
a program that utilizes oxidative carbon–carbon bond cleavage
reactions to form oxocarbenium ions in an effort to enhance
functional group tolerance.3 Recently we reported4 that cyclization
reactions can be initiated by forming oxocarbenium ions through
DDQ-mediated oxidative carbon–hydrogen bond activation from
benzylic and allylic ethers (Scheme 1). The development of this
We have initiated studies that are directed toward elucidating the
details of the carbon–hydrogen bond activation step. In this man-
uscript we report our findings from inter- and intramolecular ki-
netic isotope effect studies and present evidence for the formation
of a radical cation intermediate prior to hydrogen atom abstraction
en route to the oxocarbenium ion intermediate.
2. Results and discussion
2.1. Background
Three mechanisms have been postulated for the generation
of stabilized carbocations through DDQ-mediated oxidation
(Scheme 2). The most direct pathway proceeds through a one-step
hydride transfer to DDQ.5 The other two pathways proceed through
OAc
O
CN
DDQ
DDQ
74%
80%
HO
Cl
CN
O
X
O
OAc
O
O
OAc
+
MeO
AcO
MeO
AcO
O
R
hydride
transfer
OAc
Cl
CN
Cl
O
CN
O
X
hydrogen
atom
proton transfer
then
H
R
+
or
O
OAc
O
OAc
transfer
electron transfer
Cl
O
electron
transfer
Scheme 1. Cyclization reactions through oxidative carbon–hydrogen bond activation.
CN
O
CN
O
X
H
R
+
Cl
O
Cl
* Corresponding author. Tel.: þ1 412 624 8727; fax: þ1 412 624 8611.
E-mail address: florean@pitt.edu (P.E. Floreancig).
Scheme 2. Possible mechanisms of oxidative carbocation formation.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.088

H.H. Jung, P.E. Floreancig / Tetrahedron 65 (2009) 10830–10836
10831
an initial electron transfer to form the radical cation of the substrate
and the radical anion of DDQ. The oxocarbenium ion can then be
accessed through hydrogen atom abstraction or proton abstraction
followed by a second electron transfer. Bordwell postulated6 that
proton transfer should be favored over hydrogen atom transfer for
radical cations in solution based on the highly favorable proton
solvation energy, though this analysis does not discuss the role that
a quinone radical anion would play in partitioning the pathways.
Baciocchi provided solvent-dependent spectroscopic evidence7 for
both hydrogen atom transfer and proton transfer in photoinitiated
oxidations of diarylmethanes by tetrachloroquinone.
We initiated a series of intermolecular and intramolecular
kinetic isotope effect studies on several benzylic and allylic ether
substrates (Scheme 3) to study the mechanism of carbocation for-
mation in these reactions. Intramolecular kinetic effects are used to
determine the preference for cleaving a C–H bond when a C–D
bond is present in the same methylene group. Intermolecular
kinetic isotope effects measure the rate difference between sub-
strates that contain a reactive CH2 group relative to substrates that
contain a CD2 group at the corresponding position.
because of their similar oxidation potentials, and the rate of bond
cleavage would not be isotope dependent because this step would
have a lower energetic barrier than return electron transfer.
Intermolecular kinetic isotope effects would be approximately
equal to intramolecular kinetic isotope effects if electron transfer
was not rate determining since equilibration of the radical cations
would occur prior to bond cleavage.
2.2. Substrate design and synthesis
The substrates in this study were selected to cover a wide range
of reactivities in the oxidative cyclization reactions (Scheme 5).4a
We prepared benzylic ethers that undergo oxidative cyclization
quickly (p-methoxybenzyl ether 1), moderately quickly
(p-methylbenzyl ether 2), and slowly (benzyl ether 3), with
reactivity paralleling the ease of substrate oxidation. We also pre-
pared ether 4 in which the cyclization proceeds at a moderate rate
despite the low substrate oxidation potential. Highly reactive allylic
ether 5 and relatively unreactive allylic ether 6 were also prepared.
While our prior work utilized substrates that contain branched
ethers, we employed unbranched ether groups to circumvent the
possibility of a kinetic resolution in the carbon–hydrogen bond
activation step. Compounds 1–5 were prepared (Eq. 1) through
standard Williamson ether syntheses between the non-, mono-,
and dideuterated benzylic or allylic bromides, and the sodium
alkoxide of 3-butyn-1-ol followed by ruthenium catalyzed enol
acetate formation.9 Compound 6 was prepared (Eq. 2) through the
Lewis acid-mediated reaction between the allylic alcohol and the
Intramolecular kinetic isotope effect experiment
O
OAc
DDQ
H or D
activation
H
D
O
O
X
H(D)
X
Intermolecular kinetic isotope effect experiment
OAc
O
OAc
DDQ
H or D
activation
D
D
H
H
OAc
OAc
OAc
+
O
O
O
X
H(D)
Dn
Dn
Dn
X
X
O
O
O
O
O
1:1 mixture
Scheme 3. Intra- and intermolecular kinetic isotope effects.
MeO
MeO
1
2
3
OAc
OAc
OAc
Dn
Dn
Dn
Comparisons of intermolecular and intramolecular kinetic iso-
O
tope effects have been used to provide evidence for the formation
of a reactive intermediate as a rate determining step prior to bond
cleavage.8 In this study, rate determining electron transfer would
not necessarily diminish the kinetic isotope effect in the intra-
molecular experiments because the C–H and C–D bond strengths
would still be different in a putative radical cation intermediate.
Isotope effects would significantly lessen if electron transfer were
rate determining in the intermolecular experiments, however
(Scheme 4). The radical cations from the H2 and D2 substrates are
expected to form in approximately identical concentrations
9
9
OMe
4
5
6
O
O
O
O
O
O
H(D)
H(D)
H(D)
MeO
Me
7
8
9
O
O
O
O
D
D
H
H
MeO
O
approximately
1:1 mixture
OR
H(D)
O
H(D)
OR
+
9
9
H(D)
OMe
10
11
12
1. NaH, then benzylic
or allylic bromide
k
k
D
H
OAc
2. HOAc, Fur3P, NaOAc,
[(p-cymene)RuCl]2,
1-decyne
(1)
(2)
Dn
H
D
HO
R
R
R
O
O
O
OAc
1. TMSOTf
Dn
2. HOAc, Fur3P, NaOAc,
[(p-cymene)RuCl]2,
1-decyne
NH
Dn
R
+
OH
rate determining electron transfer: kH = k
reversible electron transfer: kH > k
R
D
Cl3C
O
O
D
Scheme 4. Relative rate constants for intermolecular KIE studies.
Scheme 5. Cyclization substrates, products, and synthetic routes, n¼0ꢀ2.

10832
H.H. Jung, P.E. Floreancig / Tetrahedron 65 (2009) 10830–10836
trichloroacetimidate of butynol to avoid the possibility of label
scrambling through an SN20 reaction. The products of the oxidative
cyclizations were tetrahydropyrones 7–12.
stronger carbon–
hydrogen bond
weaker carbon–
hydrogen bond
H
O
H
R
R
O
2.3. Isotope effect determination
MeO
stabilized radical cation
H
non-stabilized radical cation
Intramolecular kinetic isotope effect studies were conducted by
exposing monodeuterated substrates to DDQ and 2,6-dichloropyr-
idine, while intermolecular kinetic isotope effect studies were
conducted by exposing 1:1 mixtures of non-deuterated and
dideuterated substrates to the reaction conditions. The reactions
were taken to approximately 10% conversion to avoid in-
terpretation errors that could arise from product oxidation in the
intramolecular series and from selective starting material depletion
in the intermolecular series. Kinetic isotope effects were
determined by comparing the intensities of 1H NMR (500 MHz)
signals from the benzylic or allylic hydrogens in the products to
reference signals.
Values for intra- and intermolecular kinetic isotope effects are
shown in Table 1. The magnitudes of the kinetic isotope effects were
largest with the more reactive substrates 1, 2, 4, and 5. Intra- and
intermolecular effects were reasonably consistent for each
substrate.
BDE(RC) = BDE(S) – E (S) + E (E•)
(3)
pa
pa
Figure 1. Bond strength as a function of radical cation stability.
Eq. 3,10 in which BDE(RC) is the bond dissociation energy of the
cleaving bond in the radical cation, BDE(S) is the bond dissociation
energy of this bond in the neutral substrate, Epa(S) is the oxidation
potential of the substrate, and Epa(Eꢁ) is the oxidation potential of
the radical from the fragment that becomes the carbocation in the
cleavage step. Thus lowering the oxidation potential of the sub-
strate11 by appending electron donating groups increases the bond
dissociation energy of the scissile carbon–hydrogen bond. While
these results strongly suggest the presence of an intermediate
radical ion pair, a concern for the electron transfer mechanism lies
in the considerably disfavorable thermodynamics of electron
transfer between the substrates in this study and DDQ. Kochi,
however, has reported12 that rates for electron transfer and carbon–
hydrogen bond cleavage for quinone/arene mixtures are
substantially faster than predicted values based on Rehm–Weller13
considerations, particularly for endergonic transformations, due to
the formation of an encounter complex that promotes inner sphere
electron transfer.
Table 1
Intra- and intermolecular kinetic isotope effects
Entry
Substrate
Product
KIE (intra)
KIE (inter)
1
2
3
4
5
6
1
2
3
4
5
6
7
8
9
10
11
12
7.3
7.4
1.6
8.0
6.5
1.4
6.8
7.5
2.8
7.9
6.7
2.0
The high rates of reactions for compounds that have low
oxidation potentials appear to contrast the high KIE values for these
substrates. These observations can be reconciled by considering the
rate equation for cation formation that would arise from the pro-
posed mechanism in Scheme 5. In this relationship (Eq. 4) the rate
of cation formation depends on the rate constant for hydrogen
atom transfer k, the concentration of the radical cation [RC], and the
concentration of the DDQ radical anion [RA]. While the values of k
are expected to be smaller for substrates with low oxidation
potentials than for substrates with high oxidation potentials, the
concentrations of the radical cations and the radical anions would
be higher. The higher concentrations for these species overwhelm
the smaller values of k and lead to faster reactions.
3. Discussion
Several aspects of these data merit further comment. All
substrates showed a kinetic isotope effect, indicating that carbon–
hydrogen bond cleavage is involved in the rate determining step.
The similar values between the intra- and intermolecular KIE’s in all
examples confirm that reactive intermediate formation prior to
carbon–hydrogen cleavage is not the rate determining step.
The magnitudes of the values for rapidly reacting substrates 1, 2,
4, and 5 are at or above the theoretically maximum value of 6.5 for
primary KIE’s at room temperature. Secondary KIE’s are also pos-
sible for these reactions since bond cleavage results in a change of
hybridization at the benzylic or allylic position. Secondary KIE
values would be >1 when D is retained after cleavage and <1 when
H is retained, indicating that primary and secondary effects are
synergistic for intramolecular experiments and are antagonistic for
intermolecular experiments. The generally close agreement
between the intra- and intermolecular KIE values indicates that
secondary KIE’s are minimal and do not contribute to the large
observed values. The largest KIE values are consistent with a mod-
est contribution from tunneling in the transition states.
The magnitude of the KIE values correlates to substrate
reactivity, with compounds that react quickly showing large effects
and compounds that react slowly showing small effects. This
indicates that bond cleavage is more difficult for substrates that
react most quickly, in contrast to the result that would be expected
for a one-step hydride transfer process. The result is consistent,
however, with an electron transfer mechanism. Substrates with
lower oxidation potentials, upon single electron oxidation,
will form less reactive radical cations than substrates with high
oxidation potentials (Fig. 1). This phenomenon can be explained by
Rate ¼ k½RCꢂ½RAꢂ
(4)
While these data provide compelling evidence for an electron
transfer pathway, determining whether the bond cleavage results
from hydrogen atom abstraction to form the cation directly or from
deprotonation, with carbocation formation arising from sub-
sequent radical oxidation, remains a difficult issue to resolve.
Baciocchi’s studies7 of diarylmethane oxidation by tetra-
chloroquinone are instructive in this regard. This work showed that
hydrogen atom abstraction should be favored on thermodynamic
grounds, but that the pathway could be perturbed by solvent
polarity. Polar solvents promote direct hydrogen atom transfer
while non-polar solvents promote deprotonation through desta-
bilizing the negative charge on the quinone radical anion. Accord-
ing to Eq. 1 our substrates should be more prone to undergo direct
cation formation than those in the Baciocchi study because alkoxy
groups lower the oxidation potential of alkyl radicals more than
aryl groups.14 Moreover the negative charge of the radical anion of
DDQ will be stabilized by the cyano groups to a greater degree than
the corresponding charge in the radical anion of tetra-
chloroquinone, thereby lessening its capacity for deprotonation.

H.H. Jung, P.E. Floreancig / Tetrahedron 65 (2009) 10830–10836
10833
Thus we postulate that these reactions proceed through hydrogen
atom abstraction to form the oxocarbenium ions directly, as shown
in Scheme 6.
4.2. Method for determining intramolecular kinetic isotope
effects
To a 0.1 M solution of the ether substrate-d1 (1.0 equiv) and
2,6-dichloropyridine (0.2 equiv) in anhydrous 1,2-dichloroethane
was added powdered 4 Å molecular sieves (2 mass equiv). In the
case of the allylic ether substrate, LiClO4 (0.1 equiv) was added. The
mixture was stirred at room temperature for 15 min, and then DDQ
(0.1 equiv) was added in one portion. The resulting reaction mix-
ture was stirred at room temperature for 24 h. The crude solution
was directly purified by flash chromatography, and a mixture of
non- (d0) and monodeuterated (d1) products was separated from
the starting substrate. The product ratio of d1 to d0 was calculated
by acquiring a 1H NMR spectrum (500 MHz, pulse delay time¼10 s)
and comparing the intensities of the signals from the benzylic or
allylic hydrogen to a signal from a hydrogen that was unaffected by
the reaction.
OAc
OAc
O
O
O
O
Cl
Cl
CN
CN
Cl
Cl
CN
CN
H
H
fast
+
+
O
O
X
X
OH
OAc
O
Cl
Cl
CN
CN
slow
+
O
O
O
X
X
Scheme 6. Proposed reaction mechanism.
3.1. Summary and conclusions
4.3. Method for determining intermolecular kinetic isotope
effects
We have shown that cyclization reactions that proceed through
oxidative carbon–hydrogen bond activation exhibit moderate to
large kH/kD kinetic isotope effects. This result is consistent with
bond cleavage occurring in the rate determining step. The magni-
tudes of the effects were consistent when determined by intra-
molecular and intermolecular processes, confirming that the
formation of a reactive intermediate prior to bond cleavage is not
rate determining. KIE values were largest for substrates that have
low oxidation potentials and react quickly. This behavior suggests
the intermediacy of radical cation intermediates in which the bond
dissociation energies for allylic and benzylic carbon–hydrogen
bonds are highest when substrate oxidation potentials are low. The
higher reaction rates for substrates that form stable radical cations
with stronger carbon–hydrogen bonds must be attributed to the
higher concentrations of reactive intermediates. Literature analogy
indicates that these reactions most likely proceed through hydro-
gen atom abstraction from the radical cation to form oxocarbenium
ions directly.
To a 0.1 M solution of the ether substrate-d0 (0.5 equiv) and
ether substrate-d2 (0.5 equiv) and 2,6-dichloropyridine (0.2 equiv)
in anhydrous 1,2-dichloroethane was added powdered 4 Å molec-
ular sieves (2 mass equiv). In the case of the allylic ether substrates,
LiClO4 (0.1 equiv) was added. The mixture was stirred at room
temperature for 15 min, and then DDQ (0.1 equiv) was added in one
portion. The resulting reaction mixture was stirred at room tem-
perature for 24 h. The crude solution was directly purified by flash
chromatography, and a mixture of non- (d0) and monodeuterated
(d1) products was separated from the starting substrate. The
product ratio of d1 to d0 was calculated by acquiring a 1H NMR
spectrum (500 MHz, pulse delay time¼10 s) and comparing the
intensities of the signals from the benzylic or allylic hydrogen to
a signal from a hydrogen that was unaffected by the reaction.
4.4. General method for preparing benzylic substrates
4. Experimental section
4.1. General experimental
To a solution of the benzylic bromide (1.0 equiv) and 3-butyn-1-
ol (1.2 equiv) in DMF was added sodium hydride (60% dispersion in
mineral oil, 1.5 equiv) at 0 ꢃC. The reaction mixture was stirred at
room temperature for approximately 2–3 h and quenched with
water at 0 ꢃC. The organic fraction was extracted with EtOAc, dried
over MgSO4, filtered, and concentrated under reduced pressure.
The crude material was filtered through a short pad of silica gel
with EtOAc/hexanes (1:4) as the eluent to afford the homo-
proparylic benzylic ether as a colorless oil (>90% yield).
To a mixture of [Ru(p-cymene)Cl2]2 (0.01 equiv), tri(2-furyl)-
phosphine (0.02 equiv), Na2CO3 (0.5 equiv), and 1-decyne
(0.3 equiv) in toluene was added acetic acid (5.0 equiv). The brown
mixture was stirred at 80 ꢃC until the reaction color changed to
green (ca. 2–4 h) and then was cooled to room temperature. A
solution of homopropargylic benzylic ether (1.0 equiv) in toluene
was added. The resulting mixture was stirred at 80 ꢃC overnight.
The reaction mixture was cooled to room temperature and con-
centrated under reduced pressure. The residue was purified via
flash column chromatography to afford the benzylic ether substrate
as a colorless oil (>70% yield).
Proton (1H NMR) and carbon (13C NMR) nuclear magnetic res-
onance spectra were recorded at 300 MHz and 75 MHz, re-
spectively, or at 500 MHz and 125 MHz if specified. The chemical
shifts are given in parts per million (ppm) on the delta (
solvent peak was used as
d) scale. The
a
reference value, for 1H NMR:
CDCl3¼7.26 ppm, for 13C NMR: CDCl3¼77.23. Data are reported as
follows: s¼singlet; d¼doublet; t¼triplet; q¼quartet; dd¼doublet of
doublets; dt¼doublet of triplets; br¼broad. High resolution and
low resolution mass spectra were recorded on a VG 7070 spec-
trometer. Infrared (IR) spectra were collected on a Mattson Cygnus
100 spectrometer. Samples for IR were prepared as a thin film on
a NaCl plate by dissolving the compound in CH2Cl2 and then
evaporating the CH2Cl2. Methylene chloride was distilled under N2
from CaH2. 1,2-Dichloroethane was dried over 4 Å molecular sieves.
Analytical TLC was performed on E. Merck pre-coated (25 mm)
silica gel 60F-254 plates. Visualization was done under UV light
(254 nm). Flash chromatography was done using ICN SiliTech 32–
63 60 Å silica gel. Sodium borodeuteride and lithium aluminum
deuteride were purchase from Sigma–Aldrich. Reagent grade ethyl
acetate, diethyl ether, pentane, and hexanes (commercial mixture)
were purchased from EM Science and used as purchased for chro-
matography. All reactions were performed in oven or flame-dried
glassware under a positive pressure of N2 with magnetic stirring
unless otherwise noted.
4.4.1. 4-(4-Methoxybenzyloxy)but-1-en-2-yl acetate (1). 1H NMR
(500 MHz, CDCl3):
d
7.26 (d, J¼8.5 Hz, 2H), 6.87 (d, J¼8.5 Hz, 2H),
4.80 (s, 2H), 4.45 (s, 2H), 3.80 (s, 3H), 3.57 (t, J¼6.5 Hz, 2H), 2.53 (t,
J¼6.5 Hz, 2H), 2.10 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 169.1, 159.2,
153.5, 130.3, 129.3, 113.8, 102.8, 72.6, 66.7, 55.3, 33.9, 21.0; IR (neat):
3003, 2936, 2862,1754,1667,1612,1513,1369,1249,1215,1181,1098,

10834
H.H. Jung, P.E. Floreancig / Tetrahedron 65 (2009) 10830–10836
1032, 822 cmꢀ1; HRMS (EI) m/z calcd for C14H18O4 (M)þ 250.1205,
(75 MHz, CDCl3):
d 169.1, 153.4, 138.0, 128.4, 127.7, 127.6, 102.9, 66.9,
found 250.1192.
33.9, 21.0; IR (neat): 3028, 2863, 2168, 2063, 1755, 1667, 1370, 1217,
1185, 1111, 1021, 882, 721 cmꢀ1
; HRMS (ESI) m/z calcd for
4.4.2. 4-(4-Methoxybenzyloxy)but-1-en-2-yl acetate (1-d1). 1H NMR
(500 MHz, CDCl3):
C13H14D2O3Na (MþNa)þ 245.1123, found 245.1348.
d
7.26 (dm, J¼8.5 Hz, 2H), 6.88 (dm, J¼8.5 Hz, 2H),
4.80 (s, 2H), 4.43 (s, 1H), 3.80 (s, 3H), 3.56 (t, J¼6.5 Hz, 2H), 2.52 (t,
4.4.10. 4-(3,5-Dimethoxybenzyloxy)but-1-en-2-yl acetate (4). 1H NMR
J¼6.5 Hz, 2H), 2.10 (s, 3H); 13C NMR (75 MHz, CDCl3):
d
169.0, 159.2,
(300 MHz, CDCl3):
d
6.50 (d, J¼2.4 Hz, 2H), 6.38 (t, J¼2.4 Hz, 1H), 4.81
153.5,130.3,129.3,113.8,102.7, 72.2 (t,1:1:1, 2J(13C, 2H)¼22 Hz), 66.7,
55.3, 33.9, 21.0; IR (neat): 3002, 2932, 2862, 2120, 1755, 1667, 1612,
1513, 1370, 1247, 1183, 1101, 1032, 881, 822 cmꢀ1; HRMS (ESI) m/z
calcd for C14H17DO4Na (MþNa)þ 274.1166, found 274.1167.
(sm, 2H), 4.47 (s, 2H), 3.79 (s, 6H), 3.58 (t, J¼6.3 Hz, 2H), 2.55
(t, J¼6.3 Hz, 2H), 2.11 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 169.1, 160.9,
153.4, 140.6, 105.3, 102.9, 99.6, 72.9, 67.0, 55.3, 33.9, 21.0; IR (neat):
2939, 2841, 1754, 1598, 1463, 1367, 1206, 1156, 1106, 835 cmꢀ1; HRMS
(ESI) m/z calcd for C15H20O5Na (MþNa)þ 303.1208, found 303.1182.
4.4.3. 4-(4-Methoxybenzyloxy)but-1-en-2-yl acetate (1-d2). 1H NMR
(500 MHz, CDCl3):
4.80 (s, 2H), 3.80 (s, 3H), 3.56 (t, J¼6.5 Hz, 2H), 2.52 (t, J¼6.5 Hz, 2H),
2.10 (s, 3H); 13C NMR (75 MHz, CDCl3):
169.1, 159.2, 153.5, 130.1,
d
7.26 (dm, J¼8.5 Hz, 2H), 6.88 (dm, J¼8.5 Hz, 2H),
4.4.11. 4-(3,5-Dimethoxybenzyloxy)but-1-en-2-yl acetate (4-d1). 1H
NMR (300 MHz, CDCl3):
d
6.50 (d, J¼2.4 Hz, 2H), 6.38 (t, J¼2.4 Hz,
d
1H), 4.81 (sm, 2H), 4.44 (s, 1H), 3.79 (s, 6H), 3.58 (t, J¼6.3 Hz, 2H),
129.3, 113.8, 102.8, 66.6, 55.3, 33.9, 21.0; IR (neat): 3003, 2957, 2862,
2165, 2061, 1754, 1667, 1612, 1513, 1370, 1255, 1183, 1104, 1030, 879,
2.55 (t, J¼6.3 Hz, 2H), 2.11 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 169.1,
160.9, 153.4, 140.6, 105.3, 102.9, 99.7, 72.6 (t, 1:1:1, 2J(13C,
2H)¼22 Hz), 66.9, 55.3, 33.9, 21.0; IR (neat): 3001, 2940, 2868, 2840,
2121, 1754, 1667, 1598, 1462, 1350, 1206, 1155, 1109, 1063, 1021, 883,
833 cmꢀ1; HRMS (EI) m/z calcd for C15H19DO5Na (M)þ 281.1373,
found 281.1363.
801 cmꢀ1
275.1228, found 275.1271.
;
HRMS (ESI) m/z calcd for C14H16D2O4Na (MþNa)þ
4.4.4. 4-(4-Methylbenzyloxy)but-1-en-2-yl acetate (2). 1H NMR
(500 MHz, CDCl3):
(s, 2H), 4.48 (s, 2H), 3.58 (t, J¼6.5 Hz, 2H), 2.54 (t, J¼6.5 Hz, 2H), 2.34
(s, 3H), 2.10 (s, 3H); 13C NMR (75 MHz, CDCl3):
169.1, 153.5, 137.3,
d
7.22 (d, J¼8.0 Hz, 2H), 7.15 (d, J¼8.0 Hz, 2H), 4.80
4.4.12. 4-(3,5-Dimethoxybenzyloxy)but-1-en-2-yl acetate (4-d2). 1H
d
NMR (300 MHz, CDCl3):
d
6.50 (d, J¼2.4 Hz, 2H), 6.38 (t, J¼2.4 Hz,
135.1, 129.0, 127.8, 102.7, 72.8, 66.9, 33.9, 21.1, 21.0; IR (neat): 3021,
1H), 4.82 (sm, 2H), 3.79 (s, 6H), 3.58 (t, J¼6.3 Hz, 2H), 2.54 (t,
2923, 2862, 1755, 1667, 1368, 1214,1183,1100, 1020, 881, 804 cmꢀ1
;
J¼6.3 Hz, 2H), 2.11 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 169.1, 160.8,
HRMS (EI) m/z calcd for C14H18O3 (M)þ 234.1256, found 234.1261.
153.4, 140.5, 105.3, 102.9, 99.6, 66.8, 55.3, 33.9, 21.0; IR (neat): 3001,
2941, 2864, 2840, 2170, 2068, 1753, 1598, 1428, 1369, 1156, 1112,
1063, 882, 831 cmꢀ1; HRMS (EI) m/z calcd for C15H18D2O5Na (M)þ
282.1436, found 282.1432.
4.4.5. 4-(4-Methylbenzyloxy)but-1-en-2-yl acetate (2-d1). 1H NMR
(500 MHz, CDCl3):
7.22 (d, J¼8.0 Hz, 2H), 7.15 (d, J¼8.0 Hz, 2H),
4.80 (sm, 2H), 4.46 (s, 1H), 3.57 (t, J¼6.5 Hz, 2H), 2.53 (t, J¼6.5 Hz,
d
2H), 2.34 (s, 3H), 2.10 (s, 3H); 13C NMR (75 MHz, CDCl3):
d
169.0,
4.4.13. (E)-4-(2-Methyltridec-2-enyloxy)but-1-en-2-yl acetate (5). 1H
153.5, 137.3, 135.1, 129.0, 127.8, 102.7, 72.5 (t, 1:1:1, 2J(13C,
2H)¼22 Hz), 66.9, 34.0, 21.1, 21.0; IR (neat): 3022, 2923, 2865, 2121,
1756, 1667, 1370, 1185,1104, 1020, 881, 794 cmꢀ1; HRMS (EI) m/z
calcd for C14H17DO3 (M)þ 235.1319, found 235.1323.
NMR (500 MHz, CDCl3):
d
5.38 (t, J¼7.0 Hz, 1H), 4.78 (s, 1H), 4.77 (s,
1H), 3.83 (s, 2H), 3.46 (t, J¼7.0 Hz, 2H), 2.48 (t, J¼7.0 Hz, 2H), 2.11 (s,
3H), 2.00 (q, J¼7.0 Hz, 2H), 1.61 (s, 3H), 1.35–1.29 (m, 2H), 1.29–1.20
(br s, 14H), 0.86 (t, J¼7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 168.9,
153.6, 131.8, 128.6, 102.5, 77.0, 66.3, 33.9, 31.8, 29.6, 29.5, 29.4, 29.30,
29.27, 27.6, 22.6, 20.9, 14.0, 13.7; IR (neat): 2924, 2854, 1760, 1667,
1464, 1369, 1213, 1185, 1093, 1019, 871 cm–1; HRMS (EI) m/z calcd for
C20H36O3 (M)þ 324.2664, found 324.2673.
4.4.6. 4-(4-Methylbenzyloxy)but-1-en-2-yl acetate (2-d2). 1H NMR
(500 MHz, CDCl3):
4.81 (s, 2H), 3.57 (t, J¼6.5 Hz, 2H), 2.53 (t, J¼6.5 Hz, 2H), 2.34 (s, 3H),
2.10 (s, 3H); 13C NMR (75 MHz, CDCl3):
169.0, 153.5, 137.3, 135.0,
129.0, 127.8, 102.7, 66.8, 34.0, 21.1, 21.0; IR (neat): 3022, 2923, 2863,
d
7.23 (d, J¼8.0 Hz, 2H), 7.15 (d, J¼8.0 Hz, 2H),
d
4.4.14. (E)-4-(2-Methyltridec-2-enyloxy)but-1-en-2-yl acetate (5-
2167, 2064, 1755, 1667, 1370, 1216, 1186, 1107, 1020, 880, 780 cmꢀ1
;
d1). 1H NMR (500 MHz, CDCl3):
d
5.39 (t, J¼7.0 Hz, 1H), 4.80 (s, 1H),
HRMS (EI) m/z calcd for C14H16D2O3 (M)þ 236.1381, found 236.1377.
4.79 (s, 1H), 3.82 (s, 1H), 3.47 (t, J¼7.0 Hz, 2H), 2.50 (t, J¼7.0 Hz, 2H),
2.13 (s, 3H), 2.02 (q, J¼7.0 Hz, 2H), 1.63 (s, 3H), 1.35–1.29 (m, 2H),
1.29–1.20 (br s, 14H), 0.88 (t, J¼7.0 Hz, 3H); 13C NMR (75 MHz,
4.4.7. 4-(Benzyloxy)but-1-en-2-yl acetate (3). 1H NMR (500 MHz,
CDCl3):
d
7.33 (sm, 4H), 7.28 (m, 1H), 4.81 (s, 2H), 4.52 (s, 2H), 3.60
CDCl3): d
169.1, 153.7, 131.8, 128.7, 102.6, 76.7 (t, 1:1:1, 2J(13C,
(t, J¼6.5 Hz, 2H), 2.55 (t, J¼6.5 Hz, 2H), 2.10 (s, 3H); 13C NMR
2H)¼21 Hz), 66.3, 34.0, 31.9, 29.6, 29.54, 29.50, 29.4, 29.3, 27.7, 22.7,
(75 MHz, CDCl3):
d
169.1, 153.4, 138.2, 128.4, 127.7, 127.6, 102.9, 73.0,
21.0, 14.1, 13.8; IR (neat): 2924, 2855, 2130, 1759, 1668, 1464, 1369,
67.0, 33.9, 21.0; IR (neat): 3031, 2862, 1755, 1667, 1369, 1214, 1184,
1103, 1020, 739 cmꢀ1; HRMS (ESI) m/z calcd for C13H16O3Na
(MþNa)þ 243.0997, found 243.1127.
1215, 1186, 1102, 1020, 873 cmꢀ1
; HRMS (EI) m/z calcd for
C20H35DO3 (M)þ 325.2727, found 325.2719.
4.4.15. (E)-4-(2-Methyltridec-2-enyloxy)but-1-en-2-yl acetate (5-
4.4.8. 4-(Benzyloxy)but-1-en-2-yl
acetate
(3-d1). 1H
NMR
d2). 1H NMR (500 MHz, CDCl3):
d
5.39 (t, J¼7.0 Hz, 1H), 4.80 (s, 1H),
(500 MHz, CDCl3):
d
7.34 (sm, 4H), 7.28 (m, 1H), 4.81 (sm, 2H), 4.50
4.79 (s, 1H), 3.47 (t, J¼7.0 Hz, 2H), 2.50 (t, J¼7.0 Hz, 2H), 2.13 (s, 3H),
2.02 (q, J¼7.0 Hz, 2H), 1.63 (s, 3H), 1.35–1.29 (m, 2H), 1.29–1.20 (br s,
(s, 1H), 3.59 (t, J¼6.5 Hz, 2H), 2.55 (t, J¼6.5 Hz, 2H), 2.10 (s, 3H); 13C
NMR (75 MHz, CDCl3):
d
169.0, 153.5, 138.2, 128.4, 127.7, 127.6,
14H), 0.88 (t, J¼7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 169.0,
102.8, 72.6 (t, 1:1:1, 2J(13C, 2H)¼22 Hz), 67.0, 34.0, 21.0; IR (neat):
3062, 3029, 2865, 2120,1755, 1667, 1369,1215,1184,1107, 1021, 880,
727 cmꢀ1; HRMS (EI) m/z calcd for C13H15D1O3 (M)þ 221.1162,
found 221.1169.
153.7, 131.8, 128.8, 102.6, 66.2, 34.0, 31.9, 29.6, 29.54, 29.50, 29.4,
29.3, 27.7, 22.7, 21.0, 14.1, 13.7; IR (neat): 2925, 2854, 2166, 2061,
1760, 1667, 1464, 1370, 1215, 1186, 1106, 1020, 876 cmꢀ1; HRMS (EI)
m/z calcd for C20H34D2O3 (M)þ 326.2790, found 326.2785.
4.4.9. 4-(Benzyloxy)but-1-en-2-yl
acetate
(3-d2). 1H
NMR
4.4.16. 4-(2-Methylenetridecyloxy)but-1-en-2-yl acetate (6). 1H
(500 MHz, CDCl3):
d
7.34 (sm, 4H), 7.28 (m, 1H), 4.81 (sm, 2H), 3.59
NMR (500 MHz, CDCl3):
(sm, 1H), 3.90 (s, 2H), 3.52 (t, J¼6.5 Hz, 2H), 2.52 (t, J¼6.5 Hz, 2H),
d 4.98 (s, 1H), 4.88 (s, 1H), 4.80 (s, 1H), 4.79
(t, J¼6.5 Hz, 2H), 2.55 (t, J¼6.5 Hz, 2H), 2.10 (s, 3H); 13C NMR

H.H. Jung, P.E. Floreancig / Tetrahedron 65 (2009) 10830–10836
10835
2.13 (s, 3H), 2.03 (t, J¼7.5 Hz, 2H), 1.43 (p, J¼7.5 Hz, 2H), 1.33–1.22
(ddd, J¼11.5, 7.5, 2.0 Hz, 1H), 3.97 (dd, J¼11.0, 2.5 Hz, 1H), 3.70 (td,
J¼11.5, 3.0 Hz, 1H), 2.60 (ddd, J¼14.5, 12.0, 7.5 Hz, 1H), 2.53 (dm,
J¼14.5 Hz, 1H), 2.38 (ddm, J¼14.5, 2.5 Hz, 1H), 2.34 (dm, J¼14.5 Hz,
1H), 2.03 (td, J¼7.0, 4.0 Hz, 1H), 2.02 (td, J¼7.0, 3.0 Hz, 1H), 1.68 (s,
3H),1.38–1.30 (m, 2H),1.30–1.22 (m,14H), 0.88 (t, J¼7.0 Hz, 3H); 13C
(br s, 16H), 0.88 (t, J¼7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 169.1,
153.5, 146.3, 111.1, 102.8, 73.9, 66.9, 34.0, 33.1 31.9, 29.7, 29.6, 29.5,
29.4, 29.3, 27.6, 22.7, 21.0, 14.1; IR (neat): 2925, 2854, 2060, 1760,
1667, 1464, 1369, 1213, 1185, 1103, 1019, 900 cmꢀ1; HRMS (EI) m/z
calcd for C20H34D2O3 (M)þ 324.2664, found 324.2665.
NMR (75 MHz, CDCl3):
d 207.2, 133.5, 128.3, 82.9, 66.1, 47.1, 42.2,
31.9, 29.6, 29.5, 29.3, 27.6, 22.7, 14.1, 12.1; IR (neat): 2924, 2854,
1721, 1465, 1371, 1246, 1155, 1078 cmꢀ1; HRMS (EI) m/z calcd for
C18H32O2 (M)þ 280.2402, found 280.2411.
4.4.17. 4-(2-Methylenetridecyloxy)but-1-en-2-yl acetate (6-d1). 1H
NMR (500 MHz, CDCl3): d 4.98 (s, 1H), 4.88 (s, 1H), 4.81 (s, 1H), 4.79
(sm,1H), 3.88 (s,1H), 3.52 (t, J¼6.5 Hz, 2H), 2.51 (t, J¼6.5 Hz, 2H), 2.14
(s, 3H), 2.03 (t, J¼7.5 Hz, 2H), 1.43 (p, J¼7.5 Hz, 2H), 1.33–1.22 (br s,
4.4.24. 2-(Tridec-1-en-2-yl)dihydro-2H-pyran-4(3H)-one (12). 1H
16H), 0.88 (t, J¼7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 169.1,153.5,
NMR (500 MHz, CDCl3):
d 5.07 (s, 1H), 4.95 (s, 1H), 4.30 (dm,
146.2, 111.2, 102.8, 73.5 (t, 1:1:1, 2J(13C, 2H)¼21 Hz), 66.8, 33.9, 33.1
J¼11.5 Hz, 1H), 4.05 (dd, J¼9.5, 4.0 Hz, 1H), 3.71 (td, J¼11.5, 3.0 Hz,
1H), 2.61 (ddd, J¼14.5,11.5, 7.0 Hz,1H), 2.52–2.46 (m, 2H), 2.37 (dm,
J¼14.5 Hz, 1H), 2.15–2.07 (m, 1H), 2.07–2.00 (m, 1H), 1.50–1.41 (m,
2H), 1.34–1.18 (m, 16H), 0.88 (t, J¼7.0 Hz, 3H); 13C NMR (75 MHz,
31.9, 29.7, 29.6, 29.5, 29.4, 29.3, 27.6, 22.7, 21.0, 14.1; IR (neat): 2925,
2854, 2135,1759, 1667, 1464, 1370,1215, 1186, 1107, 1020, 898 cmꢀ1
;
HRMS (EI) m/z calcd for C20H35DO3 (M)þ 325.2727, found 325.2738.
CDCl3):
d 206.9, 148.3, 110.8, 80.0, 66.2, 47.2, 42.2, 32.1, 31.9, 29.65,
4.4.18. 4-(2-Methylenetridecyloxy)but-1-en-2-yl acetate (6-d2). 1H
NMR (500 MHz, CDCl3): d 4.98 (s, 1H), 4.88 (s, 1H), 4.80 (s, 1H), 4.79
29.62, 29.59, 29.5, 29.4, 29.3, 27.8, 22.7, 14.1; IR (neat): 2925, 2853,
1722, 1465, 1248, 1154, 1088 cmꢀ1; HRMS (EI) m/z calcd for
C18H32O2 (M)þ 280.2402, found 280.2403.
(sm, 1H), 3.52 (t, J¼6.5 Hz, 2H), 2.51 (t, J¼6.5 Hz, 2H), 2.13 (s, 3H),
2.03 (t, J¼7.5 Hz, 2H), 1.43 (p, J¼7.5 Hz, 2H), 1.33–1.22 (br s, 16H),
0.88 (t, J¼7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 169.1, 153.6,
4.4.25. General procedure for the preparation of monodeuterated
benzylic bromides. To a solution of the appropriate benzaldehyde
(1.0 equiv) in THF at 0 ꢃC was added NaBD4 (1.0 equiv) in one
portion, followed by addition of water (several drops). The re-
action mixture was stirred at room temperature for 1–3 h and
quenched with water at 0 ꢃC. The resulting mixture was stirred at
room temperature overnight and extracted with ether or EtOAc.
The organic layer was washed with brine, dried over MgSO4, fil-
tered, and concentrated under reduced pressure. The crude mix-
ture was dissolved in diethyl ether, followed by addition of
phosphorous tribromide (0.5 equiv) at 0 ꢃC. The reaction mixture
was stirred at room temperature for 2–3 h and carefully quenched
with aqueous saturated NaHCO3 solution. The organic layer was
separated and the aqueous layer was extracted with ether. The
combined organic layers were washed with water and brine, dried
over MgSO4, filtered, and concentrated under reduced pressure.
The crude product was used directly in the next step without
further purification.
146.2, 111.3, 102.8, 66.8, 34.0, 33.1 31.9, 29.7, 29.6, 29.5, 29.4, 29.3,
27.6, 22.7, 21.0, 14.1; IR (neat): 2925, 2854, 2170, 2065, 1758, 1668,
1464, 1370, 1216, 1186, 1109, 1020, 875 cmꢀ1; HRMS (EI) m/z calcd
for C20H34D2O3 (M)þ 326.2790, found 326.2785.
4.4.19. 2-(4-Methoxyphenyl)dihydro-2H-pyran-4(3H)-one (7). 1H
NMR (500 MHz, CDCl3):
d
7.30 (d, J¼8.5 Hz, 2H), 6.91 (d, J¼8.5 Hz,
2H), 4.60 (dd, J¼10.5, 3.5 Hz, 1H), 4.40 (ddd, J¼11.5, 7.5, 1.5 Hz, 1H),
3.83 (td, J¼11.5, 2.5 Hz, 1H), 3.81 (s, 3H), 2.75–2.68 (m, 2H), 2.65–
2.59 (m, 1H), 2.42 (dm, J¼14.5 Hz, 1H); 13C NMR (75 MHz, CDCl3):
d
206.5,159.5,132.7,127.1,114.0, 79.5, 66.6, 55.3, 49.8, 42.2; IR (neat):
2964, 2935, 2839, 1718, 1613, 1514, 1369, 1249, 1032, 831 cmꢀ1
;
HRMS (EI) m/z calcd for C12H14O3 (M)þ 206.0943, found 206.0940.
4.4.20. 2-p-Tolyldihydro-2H-pyran-4(3H)-one (8). 1H NMR (500 MHz,
CDCl3):
d
7.26 (d, J¼8.0 Hz, 2H), 7.19 (d, J¼8.0 Hz, 2H), 4.61 (dd, J¼9.0,
5.5 Hz, 1H), 4.42 (ddd, J¼11.5, 7.5, 1.5 Hz, 1H), 3.83 (td, J¼11.5, 3.0 Hz,
1H), 2.72 (ddd, J¼14.5, 9.5, 7.5 Hz, 1H), 2.64 (m, 2H), 2.43 (dm,
J¼14.5 Hz, 1H), 2.35 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 206.4, 137.9,
4.4.26. General procedure for the preparation of dideuterated ben-
zylic bromides. To a solution of the appropriate benzoic acid
(1.0 equiv) in diethyl ether was added LiAlD4 (1.0 equiv) in several
portions at 0 ꢃC. The reaction mixture was stirred at 0 ꢃC for 1–2 h
and then at room temperature overnight. The reaction was
quenched with D2O at 0 ꢃC. Water (H2O) and EtOAc or ether were
added and the organic layer was separated. The organic layer was
washed with brine, dried over MgSO4, filtered, and concentrated
under reduced pressure. The crude material was dissolved in
diethyl ether at 0 ꢃC and phosphorous tribromide (0.5 equiv) was
added. The reaction mixture was stirred at room temperature for
ca. 2–3 h and was quenched with aqueous saturated NaHCO3. The
organic layer was separated and the aqueous layer was extracted
with ether. The combined organic layers were washed with water
and brine, dried over MgSO4, filtered, and concentrated under
reduced pressure. The crude product was used directly in the next
step without further purification.
137.7, 129.3, 125.7, 79.8, 66.7, 49.9, 42.2, 21.1; IR (neat): 2965, 2922,
2855,1720,1516,1370,1315,1247,1167,1073, 805 cmꢀ1; HRMS(EI)m/z
calcd for C12H14O2 (M)þ 190.0994, found 190.0986.
4.4.21. 2-Phenyldihydro-2H-pyran-4(3H)-one (9). 1H NMR (500 MHz,
CDCl3):
d
7.38 (br s, 4H), 7.35–7.31 (m,1H), 4.65 (dd, J¼9.0, 5.5 Hz,1H),
4.44 (ddd, J¼11.0, 7.5, 1.5 Hz, 1H), 3.85 (td, J¼11.0, 2.5 Hz, 1H), 2.72
(ddd, J¼14.5, 12.5, 7.5 Hz, 1H), 2.65 (m, 2H), 2.43 (dm, J¼14.5 Hz, 1H);
13C NMR (75 MHz, CDCl3):
d 206.4, 140.6, 128.7, 128.2, 125.7, 79.8,
66.8, 50.0, 42.2; IR (neat): 3032, 2968, 2924, 2857, 1720, 1415, 1370,
1247, 1152, 1075, 756 cmꢀ1; HRMS (EI) m/z calcd for C11H12O2 (M)þ
176.0837, found 176.0841.
4.4.22. 2-(3,5-Dimethoxyphenyl)dihydro-2H-pyran-4(3H)-one
(10). 1H NMR (500 MHz, CDCl3):
d
6.52 (d, J¼2.5 Hz, 2H), 6.41 (t,
J¼2.5 Hz, 1H), 4.58 (dd, J¼10.0, 4.0 Hz, 1H), 4.43 (ddd, J¼12.0, 7.5,
2.0 Hz, 1H), 3.82 (m, 1H), 3.80 (s, 6H), 2.71 (ddd, J¼14.5, 12.5,
7.5 Hz, 1H), 2.63 (m, 2H), 2.42 (dm, J¼14.5 Hz, 1H); 13C NMR
(75 MHz, CDCl3):
d
206.1, 161.0, 143.0, 103.5, 100.0, 79.7, 66.7, 55.3,
Acknowledgements
49.9, 42.1; IR (neat): 2963, 2843, 1717, 1598, 1462, 1430, 1367, 1204,
1155 cmꢀ1; HRMS (EI) m/z calcd for C13H16O4 (M)þ 236.1048,
found 236.1058.
We thank the National Science Foundation (CHE-0139851) and
the National Institutes of Health (GM062924) for generous support
of this work. We thank Professor Joseph Dinnocenzo (University
of Rochester) for bringing the issue of electron transfer kinetics to
our attention.
4.4.23. (E)-2-(Tridec-2-en-2-yl)dihydro-2H-pyran-4(3H)-one
(11). 1H NMR (500 MHz, CDCl3):
d
5.46 (td, J¼7.0, 1.5 Hz, 1H), 4.29

10836
H.H. Jung, P.E. Floreancig / Tetrahedron 65 (2009) 10830–10836
Floreancig, P. E. J. Am. Chem. Soc. 2004, 126, 12596; (d) Seiders, J. R., II; Wang, L.;
Supplementary data
Floreancig, P. E. J. Am. Chem. Soc. 2003, 125, 2406.
4. (a) Tu, W.; Floreancig, P. E. Angew. Chem., Int. Ed. 2009, 48, 4567; (b) Tu, W.; Liu,
L.; Floreancig, P. E. Angew. Chem., Int. Ed. 2008, 47, 4184.
5. Trost, B. M. J. Am. Chem. Soc. 1967, 89, 1847.
6. Zhang, X.-M.; Bordwell, F. G. J. Am. Chem. Soc. 1994, 116, 904.
7. Baciocchi, E.; Del Giacco, T.; Elisei, F.; Lanzalunga, O. J. Am. Chem. Soc. 1998,
120, 11800.
Supplementary data associated with this article can be found in
online version, at doi:10.1016/j.tet.2009.10.088.
References and notes
8. (a) Anderson, D. R.; Faibish, N. C.; Beak, P. J. Am. Chem. Soc. 1999, 121, 7553; (b)
Baciocchi, E.; Gerini, M. F.; Harvey, P. Z.; Lanzalunga, O.; Prosperi, A. J. Chem. Soc.,
Perkin Trans. 2 2001, 1512; (c) Shearer, J.; Zhang, C. X.; Hatcher, L. Q.; Karlin, K. D.
J. Am. Chem. Soc. 2003, 125, 12670.
9. (a) Goosen, L. J.; Paetzold, J.; Koley, D. Chem. Commun. 2003, 706; (b) Neveux,
M.; Bruneau, C.; Dixneuf, P. H. J. Chem. Soc., Perkin Trans. 1 1991, 1197.
10. Popielarz, R.; Arnold, D. R. J. Am. Chem. Soc. 1990, 112, 3068.
11. For the determination of arene oxidation potentials, see: (a) Zweig, A.; Hodg-
son, W. G.; Jura, W. H. J. Am. Chem. Soc. 1964, 86, 1684; (b) Merkel, P. B.; Luo, P.;
Dinnocenzo, J. P.; Farid, S. J. Org. Chem. 2009, 74, 5163; For alkene oxidation
potentials see: Schepp, N. P.; Johnston, L. J. J. Am. Chem. Soc. 1996, 118, 2872.
12. Hubig, S. M.; Kochi, J. K. J. Am. Chem. Soc. 1999, 121, 1688.
13. Rehm, D.; Weller, A. Isr. J. Chem. 1970, 8, 259.
1. Recent reviews: (a) Larrosa, I.; Romea, P.; Urpı´, F. Tetrahedron 2008, 64, 2683; (b)
Clarke, P. A.; Santos, S. Eur. J. Org. Chem. 2006, 2045; (c) Nakata, T. Chem. Rev.
2005, 105, 4314; (d) Zeni, G.; Larock, R. C. Chem. Rev. 2004, 104, 2285; (e) Elliott,
M. C. J. Chem. Soc., Perkin Trans. 1 2002, 2301.
2. For a representative list of recent examples in complex molecule synthesis, see:
(a) Wender, P. A.;DeChristopher, B.A.;Schrier, A. J.J. Am. Chem. Soc. 2008,130, 6658;
(b) Seden, P. T.; Charmant, J. P. H.; Willis, C. L. Org. Lett. 2008, 10, 1637; (c) Custar, D.
W.; Zabawa, T. P.; Scheidt, K. A. J. Am. Chem. Soc. 2008, 130, 804; (d) Smith, A. B., III;
Basu, K.; Bosanac, T. J. Am. Chem. Soc. 2007,129,14872; (e)Van Orden, L. J.;Patterson,
B. D.; Rychnovsky, S. D. J. Org. Chem. 2007, 72, 5784; (f) Yadav, J. S.; Reddy, M. S.; Rao,
P. P.; Prasad, A. R. Synlett 2007, 2049; (g) Sanchez, C. C.; Keck, G. E. Org. Lett. 2005, 7,
3053;(h)Aubele,D.L.;Wan, S.;Floreancig, P. E.Angew.Chem.,Int.Ed.2005, 44, 3485;
(i) Overman, L. E.; Pennington, L. D. J. Org. Chem. 2003, 68, 7143.
14. (a) Wayner, D. D. M.; McPhee, D. J.; Griller, D. J. Am. Chem. Soc. 1988, 110,
132; (b) Fu, Y.; Liu, L.; Yu, H.-Z.; Wang, Y.-M.; Guo, Q.-X. J. Am. Chem. Soc.
2006, 127, 7227.
3. (a) Jung, H. H.; Seiders, J. R., II; Floreancig, P. E. Angew. Chem., Int. Ed. 2007, 46,
8464; (b) Floreancig, P. E. Synlett 2007, 191; (c) Wang, L.; Seiders, J. R., II;