A new photolabile protecting group for release of carboxylic acids by visible-light-induced direct and mediated electron transfer

Article abstract of DOI:10.1021/jo900182x

(Chemical Equation Presented) A new aqueous-compatible photoinduced electron transfer based photolabile protecting group has been developed for the release of carboxylic acids. The reduction potential of this group is more positive than previous systems,

Full text of DOI:10.1021/jo900182x

A New Photolabile Protecting Group for Release of Carboxylic
Acids by Visible-Light-Induced Direct and Mediated Electron
Transfer
J. Brian Borak and Daniel E. Falvey*
Department of Chemistry and Biochemistry, UniVersity of Maryland, College Park, Maryland 20742
falVey@umd.edu
ReceiVed January 27, 2009
A new aqueous-compatible photoinduced electron transfer based photolabile protecting group has been
developed for the release of carboxylic acids. The reduction potential of this group is more positive than
previous systems, thereby allowing the use of sensitizers with modest oxidation potentials. Release of
several carboxylic acids has been demonstrated using tris(bipyridyl)ruthenium(II) as both a direct sensitizer
and a mediator for electron transfer between a good donor and the protecting group.
Introduction
systems have also been investigated.25-27 Ideally, a PRPG would
be stable before excitation, have fast rates of release, high
quantum yields of release (Φrel), solubility in a wide range of
solvents, and produce benign side products. Additionally, it
would be convenient for the release to be initiated by low-energy
light such as visible or infrared irradiation. Unfortunately, a large
number of the aforementioned PRPGs absorb ultraviolet (UV)
light, which can present a problem if other UV-active com-
pounds are included in the system. Through the selection of
Photoremovable protecting groups (PRPGs) have become
broadly applicable for convenient and controlled release of
functional molecules in a variety of environments.1,2 Some of
the more interesting applications include photolithography,3-6
the “caging” and release of biologically significant compounds,7-9
and organic synthesis.10,11 Many PRPGs have been developed
around a rearrangement and/or radical bond fragmentation
process that occurs within a chromophore upon excitation.
Examples of such PRPGs include the o-nitrobenzyl esters and
ethers,12-14 benzoin,15-18 phenacyl ester,19-21 and coumarin22-24
derivatives. Several wavelength-addressable multiple PRPG
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3894 J. Org. Chem. 2009, 74, 3894–3899
10.1021/jo900182x CCC: $40.75 2009 American Chemical Society
Published on Web 04/10/2009

Protecting Group for Release of Carboxylic Acids
sensitization and release of NAP-protected carboxylic acids.37
Mediated sensitization has also been investigated using UV-
absorbing dyes and VIS-absorbing gold nanoparticles in the
presence of a good electron donor.38,41 Since direct sensitization
often leads to the degradation of the chromophore, the mediated
scheme offers a significant improvement in that the chromophore
is regenerated by the end of the deprotection process. Thus, it
is possible to use substoichiometric amounts of potentially
expensive sensitizer to fully deprotect a solution of NAP-
protected compounds. Additionally, mediated PET deprotection
has frequently demonstrated higher quantum yields of release
and faster overall deprotection compared to direct sensitization.
To further improve upon all of the benefits of the mediated
systems previously mentioned, it would be desirable to be able
to use a wider variety of readily available VIS-absorbing
chromophores so that this deprotection strategy may utilize a
broader range of irradiation wavelengths. A great number of
inorganic dyes exist that possess beneficial properties, i.e., strong
molar absorptivities in the visible, aqueous solubility, and high
stability under irradiation, that make them promising candidates
for use in these systems. Tris(bipyridyl)ruthenium(II) (Ru(bpy))
is one such dye that we have chosen as our focus. Ru(bpy) is
widely available and has been heavily studied across many
disciplines due to its strong VIS-absorption, relative stability
under irradiation, and unique optoelectronic properties applicable
to photosensitization, imaging, and solar energy conversion,
among others.42-45 Unfortunately, Ru(bpy), along with many
other dyes, has fairly modest redox potentials, E(Ru2+/+(bpy))
) -1.33 V vs SCE and E(Ru2+/3+(bpy)) ) 1.29 V vs SCE.44
As such, electron transfer to the NAP group (Ered ) -1.1 V vs
SCE) is less favorable under our standard conditions. In order
to tune the redox potentials to make the PET reaction more
favorable, the electronics of either Ru(bpy) or the NAP group
must be altered. Since we wish to preserve Ru(bpy) in its widely
available form, we must therefore alter the NAP group to make
it a better electron acceptor even though this may have an
influence on the efficiency of deprotection as previously
discussed. In this work, we report the development of a modified
version of the NAP group that allows the use of Ru(bpy) and,
presumably, a wider array of inorganic and organic sensitizers
for PET deprotection reactions. The deprotection reactions can
be initiated by either a direct or mediated PET process using
visible light. In the presence of a good electron donor, mediated
PET is effective in initiating deprotection using substoichio-
metric amounts of Ru(bpy).
SCHEME 1. Direct Electron Transfer (DET) versus
Mediated Electron Transfer (MET) Deprotection40
new visible-light (VIS)-absorbing chromophores28,29 or by
modifying existing PRPGs to red-shift their absorption pro-
files,30-32 deprotection reactions can be initiated using visible
light. Unfortunately, finding new chromophores with a predict-
able and reproducible bond fragmentation can be exceedingly
difficult, and modification of existing PRPGs often has the
unintended consequence of negatively altering the efficiencies
and rates of the release reaction or other properties such as
solubility.
One approach to address this dilemma is to separate the light
absorption step from the bond-breaking step by using a sensitizer
to activate a protecting group through energy or electron
transfer.33 Our group has protected carboxylic acids and
carbamates using the phenacyl20,34,35 and N-alkyl-4-picolinium
(NAP)36-39 groups that undergo a bond scission reaction upon
simple one electron reduction through photoinduced electron
transfer (PET) from a photoexcited donor. Deprotection can be
accomplished by direct electron transfer (DET) or mediated
electron transfer (MET) (Scheme 1). DET occurs through
donation of an electron from the excited-state chromophore
(Sens*) to the protecting group (DET1, Scheme 1). If a donor
is present in the system, the oxidized chromophore may abstract
an electron to regenerate the original chromophore (DET2,
Scheme 1), assuming the oxidized state is stable for a sufficient
period of time. MET proceeds through the donation of an
electron from a ground-state donor to the excited chromophore
(MET1, Scheme 1) followed by reduction of the protecting
group (MET2, Scheme 1). The redox potentials of all compo-
nents are a critical design consideration to ensure that electron
transfer from the sensitizer to the PRPG and from the donor to
the sensitizer are favorable processes. The judicious selection
of an appropriate donor is also essential to prevent undesirable
thermal or photochemical reactions that are not part of the
desired phototriggered deprotection. We have previously re-
ported the successful use of VIS-absorbing laser dyes for direct
Results and Discussion
(28) Chen, Y.; Steinmetz, M. G. J. Org. Chem. 2006, 71, 6053–6060.
(29) Shembekar, V. R.; Chen, Y.; Carpenter, B. K.; Hess, G. P. Biochemistry
2005, 44, 7107–7114.
(30) Conrad, P. G.; Givens, R. S.; Weber, J. F. W.; Kandler, K. Org. Lett.
2000, 2, 1545–1547.
(31) Aujard, I.; Benbrahim, C.; Gouget, M.; Ruel, O.; Baudin, J.-B.; Neveu,
P.; Jullien, L. Chem.-Eur. J. 2006, 12, 6865–6879.
(32) Stensrud, K. F.; Heger, D.; Sebej, P.; Wirz, J.; Givens, R. S. Photochem.
Photobiol. 2008, 7, 614–624.
It was expected that substitution of the existing NAP group
with a strongly electron-withdrawing substituent would adjust
the reduction potential to more positive values. Toward this goal,
4-methyl-2-pyridinecarbonitrile was methylated to act as a model
for the NAP group with a 2-cyano substitution. Using cyclic
voltammetry, a value of -0.63 V (vs SCE, in MeCN, taken
(33) Falvey, D. E.; Sundararajan, C. Photochem. Photobiol. 2004, 3, 831–
838.
(34) Banerjee, A.; Lee, K.; Falvey, D. E. Tetrahedron 1999, 55, 12699–
12710.
(35) Lee, K.; Falvey, D. E. J. Am. Chem. Soc. 2000, 122, 9361–9366.
(36) Sundararajan, C.; Falvey, D. E. Org. Lett. 2005, 7, 2631–2634.
(37) Sundararajan, C.; Falvey, D. E. J. Am. Chem. Soc. 2005, 127, 8000–
8001.
(38) Sundararajan, C.; Falvey, D. E. Photochem. Photobiol. 2006, 5, 116–
121.
(40) See Supporting Information for an alternate representation of Scheme
1.
(41) Borak, J. B.; Lopez-Sola, S.; Falvey, D. E. Org. Lett. 2008, 10, 457–
460.
(42) Balzani, V.; Barigelletti, F.; De Cola, L. Top. Curr. Chem. 1990, 158,
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(39) Sundararajan, C.; Falvey, D. E. J. Org. Chem. 2004, 69, 5547–5554.
J. Org. Chem. Vol. 74, No. 10, 2009 3895

Borak and Falvey
SCHEME 2. Synthesis of mPCN-Protected Esters
gradual formation of one broad absorption band around 350
nm followed by subsequent reduction of that band concurrent
with the growth of a second longer wavelength band around
510 nm (see Supporting Information). The second band persists,
and there are no apparent changes in the NMR spectrum over
the course of these color changes. Irradiation of this band does
not result in any significant amount of deprotection products.
The formation of these bands appears to be a consequence of
deprotonation at the benzylic position of the mPCN group. In
comparison to the unsubstituted NAP group, the mPCN group
possesses greater electron-withdrawing ability, thus increasing
the acidity of the benzylic protons. Trace amounts of base may
be sufficient for deprotonation. The increased acidity of these
protons is evidenced by NMR studies of 3bBF4 in CD3CN/
D2O in which deuterium incorporation occurs at the benzylic
position slowly over the course of 24 h and more rapidly in the
presence of a catalytic amount of triethylamine. Studies of
3bBF4 prepared in acetonitrile/methanol (1/1) with varying
concentrations of triethylamine also support this suggestion, as
all samples exhibited the 350 nm absorption band to varying
degrees proportional to the concentration of base. After several
minutes, the 350 nm band was diminished and the 510 nm band
had begun to develop. Samples of 3bBF4 prepared in the
presence of varying concentrations of sulfuric acid remained
stable and colorless for several days. Upon acidification of the
basic solutions with excess sulfuric acid, the 510 nm band is
diminished and a persistent weakly absorbing broadband at ca.
380 nm develops (see Supporting Information). Thus, it is clear
that the deprotonation of a benzylic proton contributes to the
formation of these colored species. However, the behavior is
more complex than a simple acid/base reaction, and the identities
of each absorption are not known with certainty. It is likely
that the deprotonated mPCN group is participating in a slow,
irreversible side reaction to a certain degree that results in the
persistent 380 nm absorption. Since the color changes are not
observed for at least several hours in acetonitrile/methanol (1/
1), photolysis solutions were prepared in this solvent for
preliminary experimentation.
TABLE 1. Synthesized mPCN Esters and Their Respective
Reduction Potentials
compound
R
X
Ered (V)a
3aBF4
3bBF4
3cOTf
phenyl
4-bromobenzyl
4-tert-butylbenzyl
BF4
BF4
OTf
-0.50
-0.51
-0.52
a Versus SCE, in acetonitrile, taken from the half-maximum current of
an irreversible wave.
from the half-maximum current of an irreversible wave) was
obtained for the reduction potential of this model compound, a
substantial shift to less negative potentials compared to the
previously used NAP group. The driving force for the direct
electron transfer reaction between Ru2+(bpy) and the modified
NAP group (DET1, Scheme 1) can be estimated from eq 1
where Eox is the oxidation potential of the Ru2+/3+(bpy) couple,
Ered is the reduction potential of the modified NAP group, and
Eoo is the energy of the triplet metal-ligand charge transfer
excited state of Ru(bpy) (3*MLTC) equal to 48.9 kcal/mol.44
The driving force for mediated electron transfer from Ru+(bpy)
to the modified NAP group (MET2, Figure 1) can be estimated
from eq 2 where Eox now represents the ground-state oxidation
potential for the Ru2+/+(bpy) couple.
∆G ) 23.06(Eox - Ered) - Eoo
∆G ) 23.06(Eox - Ered)
(1)
(2)
A value of -4.6 kcal/mol is obtained for DET1 and -16.1
kcal/mol for MET2, suggesting that both the direct and mediated
pathways should be favorable. Thus, several simple 2-cyano-
NAP (mPCN) esters were prepared for further experimentation
(Scheme 2).
At first, deprotection photolysis experiments were carried out
on systems containing only Ru(bpy) and one of the esters (i.e.,
direct electron transfer). Representative data for these experi-
ments are found in Table 2. Surprisingly, photolysis yields peak
at 0.5 equiv of Ru(bpy) (compared to ester concentration).
Decreasing the concentration of Ru(bpy) from this point
subsequently reduces the yield for a given irradiation time
period. Increasing the concentration to 1 equiv actually has the
effect of reducing the yield of free acid.
2-Substitution of 4-(hydroxymethyl)pyridine is accomplished
using a modified procedure by El Hadri and Leclerc46 to
generate 4-((tert-butyldimethylsilyloxy)methyl)picolinonitrile,
which is subsequently deprotected using aqueous acid. Coupling
of 4-(hydroxymethyl)picolinonitrile (PCN) to a carboxylic acid
is accomplished by simply using the respective acid chloride.
Due to the increased electron deficiency of the pyridine ring
by the cyano group, N-methylation must be completed using a
strong methylating reagent: methyl triflate (MeOTf) and trim-
ethyloxonium tetrafluoroborate (TMOBF4) were both employed
to create the respective methylated PCN (mPCN) ester salts.
Three simple mPCN esters have been synthesized by this
method (Table 1). Cyclic voltammetry of each ester revealed
an irreversible reduction wave that is approximately 100 mV
more positive than the model compound, which subsequently
decreases ∆GDET1 to approximately -7 kcal/mol and ∆GMET2
to approximately -19 kcal/mol (Table 1).
Control solutions that lacked Ru(bpy) or light resulted in an
insignificant yield of the free acid product (e5%). One of the
advantages of the triflate salts of the PCN esters is their aqueous
compatibility (with mild warming and stirring); however, these
solutions develop the same long wavelength absorption band
within minutes. In an effort to develop a more robust system
that does not form the long wavelength band, it was determined
that the mPCN esters are soluble and stable in 0.5 M acetate
buffer at pH 4.0. The development of the long wavelength
absorption band is delayed by several hours to 1 day and does
not seem to occur during photolysis experiments. Direct
photolysis of the esters with Ru(bpy) in acetate buffer results
in clean release of the free acid (Table 2, entries 4-8) in yields
similar to those in the acetonitrile/methanol (1/1) solvent system.
An unusual observation noted when these compounds are
dissolved in very polar solvents, such as acetonitrile, is the
(46) El Hadri, A.; Leclerc, G. J. Heterocycl. Chem. 1993, 30, 631–635.
3896 J. Org. Chem. Vol. 74, No. 10, 2009

Protecting Group for Release of Carboxylic Acids
TABLE 2. Selected Data for DET Deprotection Experiments
entry
ester
[ester] (mM)
[Ru(bpy)] (mM)
conditions
% yielda
% conversiona
1
2
3
4
5
6
8
3bBF4
3bBF4
3bBF4
3bOTf
3bOTf
3bOTf
3bOTf
4.8
4.8
4.8
4.8
4.8
4.8
0.6
0.24
2.4
4.8
0.24
2.4
4.8
1 h, MeCN/MeOH (1/1)
1 h, MeCN/MeOH (1/1)
1 h, MeCN/MeOH (1/1)
1 h, acetate bufferb
9.9
23.9
15.1
12.8
15.8
14.1
29.7
21.7
28.5
13.8
23.5
20.7
22.1
42.1
1 h, acetate bufferb
1 h, acetate bufferb
0.3
30 min, acetate bufferb
a Determined by HPLC, relative to [ester] in a dark control sample, corrected for any dark deprotection, estimated error <5%. b 0.5 M acetate buffer,
pH 4.0.
TABLE 3. Selected Data for MET Deprotection Experiments
entry
ester
donora
[ester] (mM)
[Ru(bpy)] (mM)
[donor] (mM)
conditions
% yieldb
% conversionb
1
2
3
4
5
6
7
8
3bBF4
3bBF4
3bBF4
3bBF4
3bBF4
3bOTf
3bOTf
3bOTf
DMA
DMA
DMA
DABCO
DABCO
ASC
4.8
4.8
4.8
0.6
0.6
0.6
0.6
0.6
2.4
2.4
2.4
0.3
0.3
0.3
0.3
0.3
9.6
24
24
1.2
60
3
1 h, MeCN/MeOH
1 h, MeCN/MeOH
3 h, MeCN/MeOH
10 min, MeCN/MeOH
10 min, MeCN/MeOH
10 min, acetate buffer
10 min, acetate buffer
10 min, acetate buffer
38.4
53.8
96.2
6.7
35.1
28.7
35.6
89
48.1
70.4
96.9
15.2
52.2
40.2
62.1
94.2
ASC
ASC
6
60
a DMA ) N,N-dimethylaniline, DABCO) 1,4-diazabicyclo[2.2.2]octane, ASC ) ascorbic acid. b Determined by HPLC, relative to [ester] in a dark
control sample, corrected for any dark deprotection, estimated error <5%.
In order to deprotect the esters using mediated photolysis, a
donor must be chosen that is visible-light-transparent and has
an Eox low enough to donate an electron to the photoexcited
Ru(bpy), MET1 (Scheme 1). The driving force for this reaction
can be estimated using eq 1 by substituting the oxidation
potential of the donor for Eox and the redox potential for the
Ru(bpy)2+/+ couple for Ered. Two amine donors were initially
chosen for experimentation because of their low oxidation
potentials: N,N-dimethylaniline (DMA) and 1,4-diazabicyclo-
[2.2.2]octane (DABCO) with oxidation potentials of 0.8147 and
0.57 V,48 respectively (vs SCE, in MeCN). Both DMA and
DABCO have been observed to quench the luminescence of
the Ru(bpy)2+ 3*MLCT. Mediated deprotection photolysis
experiments were performed in a manner similar to the direct
FIGURE 1. Effect of increasing concentration of Ru(bpy) or ascorbic
photolysis experiments but included an excess amount of donor.
A large increase in the free acid yield can be seen in these
experiments compared to the direct photolysis experiments for
a given irradiation period (Table 3, entries 1-5). Nearly full
deprotection is observed using 5 equiv of DMA after 3 h of
irradiation (Table 3, entry 3). Using DABCO as the donor
demonstrated similar results but generally with higher yields
of free acid for a shorter irradiation period. Unfortunately, a
significant amount of deprotection occurs in the dark control
sample for the DABCO and DMA systems, generating yields
of free acid as high as 50% in some cases. Furthermore, the
dark free acid yield seems to be proportional to the concentration
of donor. The dark electron transfer reaction between either
donor and ester is predicted to be disfavored by about 30 kcal/
mol; however, it is possible that base-catalyzed hydrolysis or
methanolysis by the amine donors is a competitive side reaction
under these conditions. Additionally, in both systems, the slow
formation of a long wavelength band over the course of the
irradiation period is observed that competes with Ru(bpy) for
light absorption. It is likely that this band originates from
acid on the yield of free acid from ester 3bOTf (4.8 mM across all
data points).
deprotonation at the benzylic position of the mPCN group as
discussed above by DMA or DABCO since its appearance is
accelerated in the presence of these donors.
Ascorbic acid was chosen for use as an aqueous soluble donor
in a mediated deprotection scheme due to its low oxidation
potential (0.29 V vs SCE, taken from the half-maximum current
of an irreversible wave). The yields observed for these experi-
ments (Table 3, entries 6-8) are comparable to those using
DMA as the donor. Faster release with the use of less Ru(bpy)
can be achieved in this system by increasing the concentration
of ascorbic acid. In fact, 89% yield of the free acid is observed
after 10 min using 100 equiv of ascorbic acid and 0.5 equiv of
Ru(bpy) (Table 3, entry 8). Figure 1 demonstrates the general
trend observed upon increasing concentration of Ru(bpy) and/
or ascorbic acid.
The stability of this system is far greater compared to the
DMA or DABCO systems as the dark control solution exhibited
very low deprotection over time (less than 3% over 18 h) and
did not seem to be affected by the concentration of ascorbic
acid.
(47) Kitamura, N.; Kim, H. B.; Okano, S.; Tazuke, S. J. Phys. Chem. 1989,
93, 5750–5756.
(48) Ruiz, G.; Rodriguez-Nieto, F.; Wolcan, E.; Feliz, M. R. J. Photochem.
Photobiol., A 1997, 107, 47–54.
The proposed mechanism for mediated deprotection, shown
in Scheme 1, is supported by luminescence quenching and laser
J. Org. Chem. Vol. 74, No. 10, 2009 3897

Borak and Falvey
TABLE 4. Observed Rate Constants and Quantum Yields of
Release for Mediated Deprotection
Ru(bpy) in that region, but it has been observed using the UV-
absorbing sensitizer 9-methylcarbazole (see Supporting Informa-
tion).
kq (MET1)
(M-1 s-1
1.05 × 108
2.40 × 106
3.84 × 107
kobs (MET2)
-1
ester
donor
DMA
DABCO
ascorbic acid
)
(M-1
s
)
Φrel
Quantum yields of release, Φrel, of the free carboxylate for
each system were determined (Table 4) using monochromatic
irradiation at 450 nm ((10 nm). Despite the modest irradiation
times required for full deprotection, it appears that processes
that compete with the productive MET1 and MET2 steps are
fairly fast and efficient, as evidenced by the very low Φrel values
for all systems. In comparison to the previously used NAP
system, substitution of the pyridinium ring with the cyano group
in the current system likely alters the energetics of the
deprotection bond fragmentation; however, it is unclear to what
extent this may contribute to overall efficiencies.
3bBF4
3bBF4
3bOTf
3.17 × 109
0.02
0.002
0.01
a
1.77 × 109
a Unable to determine due to interference from long wavelength
absorption band.
Conclusions
We have demonstrated successful deprotection of a new
photoinduced electron transfer based PRPG using the widely
available Ru(bpy) dye in both direct and mediated photolysis.
As a result of the more positive reduction potential of the mPCN
group, it should be possible to use a wider variety of sensitizers
to initiate deprotection reactions. Additionally, this system is
particularly compelling because of (1) the use of visible light,
(2) the use of substoichiometric amounts of Ru(bpy), and (3)
compatibility in aqueous media. Fluorescence quenching and
transient spectroscopy experiments support the proposed direct
and mediated electron transfer mechanisms. The selection of
donors that have suitable oxidation potentials and do not
participate in undesirable side reactions is critical for a well-
behaved and predictable system. The medium in which these
systems are prepared is another important consideration as
slightly acidic solutions tend to allow more dependable behavior
in which the formation of the long wavelength absorbing species
is suppressed. Although the deprotection photolysis experiments
generally require a modest irradiation period for full deprotec-
tion, quantum yields of release are low possibly due to fast back
electron transfer or a decreased bond fragmentation efficiency
as a result of the cyano substituent. Future work will focus on
identifying derivatives of the mPCN group that will be more
broadly applicable.
FIGURE 2. Time-dependent absorption signals at 510 nm from pulsed
laser photolysis (532 nm, 100-200 mJ, 6 ns) of 0.4 mM Ru(bpy) + 1
M ascorbic acid + varying [3bOTf] in N2-purged acetate buffer (0.5
M, pH 4.0).
flash photolysis (LFP) experiments. Luminescence of the
Ru(bpy) 3*MLCT was reduced upon addition of any of the three
donors and upon addition of the esters. Quenching rate constants
were determined for MET1 and are presented in Table 4. The
quenching rate constant (kq) for DET1 in the direct photolysis
experiments was also determined to be 5.18 × 108 M-1 s-1
.
Transient absorption spectra of samples containing Ru(bpy) and
a large excess of any of the donors exhibited a broad signal
centered at 510 nm characteristic of Ru+(bpy), thereby providing
further evidence for the MET1 process.44,49,50 Upon addition
of esters 3bBF4 or 3bOTf, the signal at 510 nm is reduced in
intensity and its rate of decay increases. This indicates that the
esters can quench Ru(bpy)+, suggesting the MET2 process is
occurring (Figure 2). Decay rate constants (kobs) were determined
at various ester concentrations by second-order analysis of the
time dependent absorption signals and are presented in Table
4. Rate constants for MET2 for both the DMA and ascorbic
acid systems are near the diffusion limit. A rate constant could
not be determined for the DABCO system because of the rapid
thermal formation of the long wavelength absorption band
during the LFP experiment. Surprisingly, kq for DET1 is larger
than all of the MET1 rate constants despite the longer irradiation
time required for the DET experiments to produce an equal
amount of free acid. This suggests that the mechanistic pathway
in the MET experiments may actually follow the DET mech-
anism for a certain percentage of deprotection events and the
predominating pathway is ultimately determined by the relative
concentrations of donor and ester. The reduced mPCN group
could not be directly observed by LFP experiments in either
the DET or the MET systems using Ru(bpy). The expected
signal (410 nm) is likely bleached by the strong absorption of
Experimental Section
Cyclic Voltammetry. All electrochemical experiments were
performed on a voltammetry analyzer with [Bu4N]-[PF6] as the
supporting electrolyte. A carbon working electrode, a platinum
auxiliary electrode, and an Ag/AgCl reference electrode were used
to take measurements. The voltammograms were taken at a scan
rate of 100 mV/s in dry acetonitrile after purging with nitrogen for
15 min. Measurements were taken in reference to the ferrocene/
ferrocenium couple found at ca. 536 mV vs SCE.
Luminescence Quenching. Luminescence quenching experi-
ments were performed using a luminescence spectrometer. Samples
were prepared in a 1 cm quartz cuvette, sealed with a rubber septum,
and purged with N2 for 10 min. Sensitizer concentrations were
prepared such that the optical density of the sensitizer at the
excitation wavelength was between 0.1 and 0.3. Quencher concen-
trations were prepared such that a linear relationship was obtained
with respect to I°/I.
Deprotection Photolysis. A solution containing 0.6-4.8 mM
ester and 0.024-4.8 mM Ru(bpy) was prepared in 5 mL of
methanol/acetonitrile (1/1) when using the tetrafluoroborate salts
and in 5 mL of 0.5 M acetate buffer at pH 4.0 when using the
triflate salts. In mediated photolysis experiments, 0.6-2.4 mM
(49) Rivarola, C. R.; Bertolotti, S. G.; Previtali, C. M. Photochem. Photobiol.
2006, 82, 213–218.
(50) Mulazzani, Q. G.; Emmi, S.; Fuochi, P. G.; Hoffman, M. Z.; Venturi,
M. J. Am. Chem. Soc. 1978, 100, 981–983.
3898 J. Org. Chem. Vol. 74, No. 10, 2009

Protecting Group for Release of Carboxylic Acids
DMA, DABCO, or ascorbic acid was included in the solution. An
aliquot of the solution was set aside as a dark control, and a 2 mL
aliquot was added to a thermostatted water-jacketed test tube that
was sealed with a rubber septum and purged with N2 for 10 min.
The solution was irradiated for various periods of time with
continuous stirring and maintained at 20 °C ((1°). The irradiation
source consisted of a 300 W tungsten/halogen lamp the output of
which was passed through a 330 nm cutoff filter and a Kopp 7093
IR-absorbing filter to ensure visible-light irradiation only. Dark
control and irradiated sample mixtures were analyzed using an
HPLC system equipped with an analytical C18 reversed-phase
column. Gradient elution using an acetonitrile/acetate buffer (100
mM, pH 4.0) mixture that adjusts from 25% acetonitrile to 70%
acetonitrile over 20 min at a flow rate of 0.5 mL/min was sufficient
to resolve the starting material and free acid peaks, monitored at
254 nm. Yields of free acid in the irradiated samples were calculated
relative to the amount of unreacted ester plus any amount of free
acid detected in the dark control sample.
EtOAc/hexanes) after 1 h showed no visible sign of the starting
material. The solvent was evaporated, and water (250 mL) was
added to the residue. The crude product was extracted with EtOAc
(1 × 250 mL), and the solvent was removed to yield a yellow solid.
The compound was dissolved in EtOAc/hexanes (1/1) and passed
through silica to yield a white crystalline solid (6.0 g, 74%).
General Procedure for Synthesis of PCN Esters, 2. The esters
were prepared by modification of previously reported procedures.39
Compound 1 (20 mmol) was dissolved in a minimal amount of
benzene/acetonitrile. Triethylamine (36 mmol) was added, and the
mixture was stirred for several minutes. The respective acid chloride
(32 mmol) was added slowly, and the mixture was allowed to stir
at room temperature for several hours until TLC (50/50 EtOAc/
hexanes) showed the absence of starting material. The solvent was
evaporated, and benzene was added (250 mL). The mixture
was washed with water (1 × 250 mL), and the organic layer was
separated, concentrated, and dried. Purification of each ester was
accomplished with flash column chromatography.
Laser Flash Photolysis. An Nd:YAG laser capable of 532, 355,
and 266 nm pulses between 4-6 ns duration was used as the
excitation source. A 350 W Xe arc lamp was used as the probe
beam passed through a monochromator to a PMT detector. A 350
MHz digital oscilloscope was used to observe the signals. Samples
were prepared such that the optical density at the excitation
wavelength, 532 nm, was between 0.1 and 0.5. The samples were
placed in a 1 cm quartz cuvette, sealed with a rubber septum, and
purged with N2 for 10 min. Samples were stirred continuously
during photolysis. Full transient spectra were obtained using a flow-
cell setup to continuously refresh the photolysis solution over the
course of the experiment.
General Procedure for Synthesis of Methylated Esters, 3.
Tetrafluoroborate Salts. A portion of the ester 2 (8.3 mmol) was
dissolved in a minimal amount of acetonitrile or acetone. Trim-
ethyloxonium tetrafluoroborate was added (16.6 mmol), and the
mixture was stirred for several hours until analysis by TLC (50/50
EtOAc/hexanes) showed the absence of starting material. The
precipitate was filtered off and washed with cold methanol. If no
precipitate formed, the solvent was removed and the residue was
recrystallized from hot pentane/acetone (9/1).
Triflate Salts. A portion of the ester 2 (11 mmol) was dissolved
in a minimal amount of dry dichloromethane. Methyl trifluo-
romethane sulfonate (14.3-16.5 mmol) was added slowly, and the
mixture was stirred for several hours under nitrogen atmo-
sphere until analysis by TLC (50/50 EtOAc/hexanes) showed the
absence of starting material. The solvent was evaporated in vacuo,
and the residue was recrystallized from hot ethanol.
Quantum Yield Determination. Solutions were irradiated with
the light output from a 1000 W Hg-Xe lamp passed through a
spectral energy monochromator with a 10 nm bandpass, set at the
λmax of Ru(bpy). Solutions were prepared as optically thick samples
(optical density greater than 3) using a substoichiometric amount
of sensitizer and a large excess of donor, where applicable. Samples
were placed in a 1 cm quartz cuvette and purged with nitrogen for
10 min. A variety of irradiation periods were selected such that
deprotection yields fell below 30%. Deprotection yields were
determined by HPLC analysis as described for the deprotection
photolysis experiments. Light intensities were measured by a
radiometer calibrated by ferrioxalate actinometry.
Acknowledgment. The authors thank the National Science
Foundation chemistry division for their financial support.
Supporting Information Available: Full synthetic proce-
1
dures; compound characterization; copies of H and 13C NMR
of 2a-c, 3aBF4, 3bBF4, 3aOTf, 3bOTf, and 3cOTf; lumines-
cence data; laser flash photolysis data; cyclic voltammograms;
and UV spectra. This material is available free of charge via
the Internet at http://pubs.acs.org.
Synthesis of 4-(Hydroxymethyl)picolinonitrile, 1. 4-((tert-
Butyldimethylsilyloxy)methyl)picolinonitrile (15.0 g, 60.5 mmol)
was prepared from literature procedures46 and was dissolved in
methanol (100 mL). H2SO4 (2 N, 30 mL) was added slowly, and
the mixture was stirred at room temperature for 1 h. TLC (1/1
JO900182X
J. Org. Chem. Vol. 74, No. 10, 2009 3899