Methoxy-substituted α, n-didehydrotoluenes. photochemical generation and polar vs diradical reactivity

Article abstract of DOI:10.1021/ja507735u

The photoreactivity of differently substituted (chloromethoxybenzyl)trimethylsilanes in alcohols and alcohol/water mixtures has been investigated by means of a combined computational and experimental approach. Subsequent elimination of the chloride anion and the trimethylsilyl cation gives the corresponding methoxy-substituted α,n-didehydrotoluenes (α,n-MeO-DHTs). The rate of desilylation is evaluated through the competition with arylation via phenyl cation (ca. 10⁸s^-1). α,2-MeO- and α,4-MeO-DHTs show a purely radical behavior (H abstraction from the solvent, methanol), while α,3-MeO-DHT shows mainly a ionic chemistry, as when the parent α,3-DHT is thermally generated. This is likely due to triplet-singlet surfaces crossing occurring during desilylation.

Full text of DOI:10.1021/ja507735u

Article
pubs.acs.org/JACS
Methoxy-Substituted α,n‑Didehydrotoluenes. Photochemical
Generation and Polar vs Diradical Reactivity
Carlotta Raviola, Davide Ravelli, Stefano Protti, and Maurizio Fagnoni*
Photogreen Lab, Department of Chemistry, University of Pavia, V. Le Taramelli 12, 27100 Pavia, Italy
S
* Supporting Information
ABSTRACT: The photoreactivity of differently substituted
(chloromethoxybenzyl)trimethylsilanes in alcohols and alcohol/water mixtures
has been investigated by means of a combined computational and experimental
approach. Subsequent elimination of the chloride anion and the trimethylsilyl
cation gives the corresponding methoxy-substituted α,n-didehydrotoluenes
(α,n-MeO-DHTs). The rate of desilylation is evaluated through the
competition with arylation via phenyl cation (ca. 108 s−1). α,2-MeO- and α,4-MeO-DHTs show a purely radical behavior (H
abstraction from the solvent, methanol), while α,3-MeO-DHT shows mainly a ionic chemistry, as when the parent α,3-DHT is
thermally generated. This is likely due to triplet−singlet surfaces crossing occurring during desilylation.
rejected by Carpenter, since the mixing of these two electronic
structures is symmetry forbidden in this heterosymmetric
diradical.5 He further considered a closed-shell cyclic allene (F)
fairly close in enthalpy to the open-shell singlet α,3-diradical,
but this was also discarded because of the failed trapping and its
involvement was not supported by theoretical calculations.
Direct nucleophile assistance during cyclization (see formula
G) was likewise incompatible with experiments. Recently,
Carpenter suggested the occurrence of a nonadiabatic surface
crossing from the ground state to the first excited-state singlet
surface (that has a zwitterionic character) during the cyclo-
aromatization process as responsible for the formation of such
“ionic addition” products.6
INTRODUCTION
■
α,3-Didehydrotoluenes (A) have been the subject of intense
attention in recent years, in particular due to their potential
application in medicine as antitumor agents,1 as well as to the
involved mechanistic issues. These diradicals have been
generated by a cycloaromatization process (the Myers−Saito
reaction)2 starting from an enyne−allene (B; Scheme 1, path
Scheme 1. Thermal Route to α,3-Didehydrotoluenes from
Enyne−Allenes via the Myers−Saito Reaction (Path a) and
the Competing Schmittel Cyclization (Path b) and Proposed
Intermediates (E−G) Invoked in the Formation of Products
D
An in-depth examination of these diradicals and their
chemistry thus seemed advisable.4,7 However, it has proven
difficult to change systematically the range of didehydroto-
luenes (A) available from enyne−allenes (B) via the Myers−
Saito reaction, because some of the substituents introduced in
B completely suppressed the rearrangement3 and other
compounds underwent a different rearrangement, the Schmittel
cyclization to give C (Scheme 1, path b).8 At any rate, a major
stumbling block is that this cycloaromatization gives access
exclusively to the α,3- but not to the α,2- and α,4-
didehydrotoluene isomers. This situation obviously called for
an alternative approach.
Indeed, the above limitations can be overcome by using an
alternative path, as recently found in our laboratory, which
involves the elimination of two substituting groups in a one-
photon-induced process from an aromatic precursor. Thus,
irradiation of (n-chlorobenzyl)trimethylsilanes (I) in protic
media causes the photoheterolytic cleavage of the Ar−Cl bond
from the triplet state and the formation of a triplet phenyl
cation (3II). The desired α,n-DHT isomers (III, n = 2−4) are
a).3 The parent α,3-didehydrotoluene (R1 = R2 = R3 = H) as
well as a few derivatives having substituents in position 1 (that
become the α-substituents in the product; Scheme 1) or on the
3−5-positions (that become the aromatic substituents) have
been generated.4
The mechanistic debate results from the fact that the main
products from α,3-didehydrotoluene (A) arise from ionic
addition to give D, not from radical reactions (minor path).
Various mechanisms were considered for rationalizing this
unexpected behavior. A resonance structure between an open-
shell diradical (A) and a closed-shell zwitterion (E) was
Received: July 29, 2014
Published: September 8, 2014
© 2014 American Chemical Society
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obtained by detachment of the electrofugal group (Me3Si+,
Scheme 2, path a).9
aromatic ring is expected to induce a red shift in the absorption
of the (chlorobenzyl)trimethylsilanes, allowing the adoption of
a longer irradiation wavelength, thus avoiding 254 nm and its
carcinogenic effects.
Scheme 2. Generation of α,n-DHTs Starting from (n-
We report below an investigation of the photochemistry of
methoxy-substituted (chlorobenzyl)trimethylsilanes, as a first
attempt to evaluate the significance of this approach to DHTs.
In recent years, we have demonstrated that chloroanisoles are
excellent photochemical precursors of aryl cations.10−12
However, the position of the methoxy group with respect to
the halogen greatly affects the energy of the resulting phenyl
cation and it is not obvious whether the triplet or the singlet
will be the lowest state.11 Thus, introducing a donating group is
not per se a guarantee that a DHT will be formed efficiently.
Chlorobenzyl)trimethylsilanes via Phenyl Cations
RESULTS
■
Choice of the Model Compounds. Ten isomeric
methoxy(trimethylsilylmethyl)phenyl cations are possible (see
Chart 1). The choice of the model compounds for the
Chart 1. Isomeric Methoxy(trimethylsilylmethyl)phenyl
Cations
The three isomeric parent α,n-DHTs formed in this way gave
a different distribution of products. In aqueous methanol, α,4-
and α,2-DHT diradicals showed primarily a radical reactivity,
with hydrogen abstraction to yield radicals that then coupled
(to form bibenzyl IV and phenethyl alcohol V). On the other
hand, a “polar” solvent addition (to give benzyl ether VI and
benzyl alcohol VII in aqueous methanol) was the main process
observed with the α,3-DHT isomer, consistent with the results
from thermal generation.2
This finding was appealing, because the introduction of
substituents in aromatic compounds is facile, and this suggests
that a large-scope variation (and, in principle, a tuning) of the
properties of these intermediates is possible in this way. Notice,
however, that this requires that the two groups are eliminated
as indicated in Scheme 2. In fact, in contrast to the Myers−
Saito cyclization where the two radical sites are formed
simultaneously in a single process, the photochemical
generation involves two subsequent processes, and elimination
of the Me3Si+ group has to be fast enough to overcome
competitive pathways at the triplet phenyl cation (3II) level.
Apart from trapping by π-bond nucleophiles (NuE) when
present, accessible paths include hydrogen abstraction from the
solvent (path b) and, most importantly, intersystem crossing
(ISC) to the singlet phenyl cation (1II), a fast process (followed
by solvent addition) when this is more stable than the triplet
(Scheme 2, paths c and d).10,11
Conditions for a convenient generation of DHTs thus are
3
that (i) heterolysis of the Ar−Cl bond via triplet Ar−Cl is
efficient and (ii) no competitive processes from the triplet
phenyl cation occur. As mentioned above, these include
hydrogen abstraction from the solvent, which depends on the
intrinsic reactivity of the cation, and ISC to the singlet, which is
avoided if the ground state of the phenyl cation is a triplet. As
for the first condition, previous work has demonstrated that
photoheterolytic cleavage is a quite general process and occurs
with all chlorobenzene derivatives bearing an (even weakly)
electron-donating substituent, such as the trimethylsilylmethyl
group above.9 The second condition requires a detailed
examination of each case. A further bonus is that the
introduction of an additional electron-donating group on the
experimental investigation was made on the basis of a
computational study, by determining which of the correspond-
ing phenyl cations has a triplet ground state. The complete
active space self-consistent field (CASSCF) method, a
multiconfigurational approach that has previously been
demonstrated to handle and describe properly the electronic
structure of such intermediates, was adopted.9c The resulting
energy values were then refined to take into account the solvent
effect (adopting the C-PCM model) and the dynamic electron
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correlation term (MP2 theory). A detailed description of the
theoretical approach is available in the Supporting Information.
Briefly, the computational study on phenyl cations was carried
out at the CASSCF (8,9)/6-31g(d) level of theory, with the
three π and the three π* orbitals of the aromatic ring, the σ/σ*
pair of the Cα−Si bond, and the orbital at the dicoordinated
carbon included in the active space. The role of the lone pair on
the oxygen atom was initially considered by adopting larger
active spaces, but it was found that its contribution was
negligible, while heavily affecting the computational cost. We
thus decided not to include it in the active space.
Chart 2. Substrates 1−3 (Top) and the Products Considered
in This Work (Bottom), Classified According to the Pathway
Involved in Their Formation
The results are reported in Figure 1, in which the relative
stabilities of the triplet and singlet phenyl cations of Chart 1 are
shown and compared with those of the related monosub-
stituted phenyl cations.
Figure 1. Singlet−triplet (S-T) gaps for the monosubstituted (red,
green) and disubstituted (blue) phenyl cations studied. A positive bar
indicates a triplet ground-state cation.
maximum around 285−290 nm with a clear vibronic structure
attributed to a nonpolar π−π* transition (with a slight blue
shift observed for compound 3; see Figure S1 in the Supporting
Information).10,13 Thus, 310 nm lamps were convenient for the
photolysis experiments (rather than the 254 nm lamp used for
the unsubstituted chlorobenzylsilanes). Compounds 1−3 were
all weakly fluorescent (ΦF < 0.05 in all of the solvents tested).
Irradiation of 1−3 (0.025 M) was carried out in neat alcohols
(MeOH, EtOH) and alcohol/water mixtures (MeOH/H2O, 4/
1 v/v; EtOH/H2O, 2/1 v/v) by using a multilamp reactor
equipped with 10 Hg phosphor-coated lamps (λem centered at
310 nm).
In order to acquire further insight, the reactions were also
carried out in the presence of a π-bond nucleophile
(allyltrimethylsilane, ATMS). As previously reported,10−12,14
ATMS is capable of trapping triplet phenyl cations to give
allylated derivatives 5a−c upon Me3Si+ loss from the
phenonium ion intermediate.10−12,14 The competition between
the addition to ATMS and the desilylation from the phenyl
cation will give insight into the rate of formation of DHTs. The
measured disappearance quantum yield (Φ−1) of compounds 1
and 2 in methanol was around 0.5, significantly higher than that
of the parent 4-choroanisole,11 while Φ−1 for compound 3 was
comparable (0.05) to that of the corresponding 2-chloroanisole
(see Table 1).10
It is apparent that intermediates bearing the dicoordinated
carbon in the meta position with respect to the methoxy group
(indicated by an M as the first character of the abbreviations
used in Figure 1 and in Chart 1) have a singlet ground state,
independent of the position of the −CH2SiMe3 group with
respect to the dicoordinated carbon (second character) and
also independent of the position of the methoxy group with
respect to the trimethylsilylmethyl group (third character).
Likewise, the monosubstituted m-methoxyphenyl cation also
has a singlet ground state.
These derivatives were thus not experimentally studied. The
other cations all had a triplet ground state. Among these, the
two isomers having the dicoordinated carbon para to the
methoxy group (POM and PMO) were selected, also because
we previously demonstrated10−12 that p-chloroanisoles were the
best precursors for triplet phenyl cations, as well as OPM, the
only potential precursor of an α,4-DHT.9 Accordingly, (2-
chloro-5-methoxybenzyl)trimethylsilane (1), (5-chloro-2-
methoxybenzyl)trimethylsilane (2), and (4-chloro-3-
methoxybenzyl)trimethylsilane (3; see Chart 2, top), the
putative precursors of the above phenyl cations, were
synthesized and tested in the present work.
The photoproducts can be grouped in two different classes as
shown in Chart 2 (bottom):
Experimental Study. Substrates 1−3 were prepared from
the corresponding benzyl chlorides through the coupling of the
corresponding Grignard reagents with trimethylsilyl chloride
(TMSCl; see the Supporting Information for further details).
The UV absorption spectra of 1−3 showed an absorption
• silyl-containing products, viz. those resulting from the
reductive dehalogenation (products 4) and from
arylation (in the presence of ATMS, products 5).
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a
Table 1. Irradiation of 1−3 in Neat Solvent and in the Presence of Allyltrimethylsilane (ATMS)
yield (%)
DHT product
c
halide
solvent
conversn (%)
cation product
diradical
polar
DHT/cation
polar/radical
b
1, Φ−1 = 0.41
MeOH
100
90
4a, 18
6a, 15; 7a, 2; 8a, 4
6a, 7; 7a, 3; 8a, 2
6b, 12; 7a, 4; 8a, 1
6b, 12; 7a, 7; 8a, 3
8a, 1
1.17
0.57
0.71
1.10
0.03
0
0
0
0
0
0
MeOH/H2O 4/1
EtOH
4a, 21
100
100
100
100
100
100
100
100
100
100
100
80
4a, 24
EtOH/H2O 2/1
MeOH, 0.2 M ATMS
MeOH, 1 M ATMS
MeOH
4a, 20
4a, 13; 5a, 16
4a, 9; 5a, 24
4b, 6
b
2, Φ−1 = 0.55
6c, 8; 7b, 3; 8b, 5
7b, 4; 8b, 5
9c, 18
5.67
1.59
4.71
2.76
1.27
1.38
0.18
0
1.13
2.00
0.14
0.31
1.80
0.20
0
MeOH/H2O 4/1
EtOH
4b, 17
9c, 18
9d, 4
4b, 7
6d, 18; 7b, 4; 8b, 7
6d, 24; 7b, 6; 8b, 6
6c, 4; 7b, 1; 8b, <1
6d, 7; 7b, 4; 8b, 4
6d, 1; 7b, 3; 8b, <1
8a, <1
EtOH/H2O 2/1
MeOH, 0.2 M ATMS
EtOH, 0.2 M ATMS
EtOH, 1 M ATMS
MeOH
4b, 17
9d, 5; 10b, 6
9c, 9
d
4b, 4; 5b, 7
4b, 6; 5b, 7
4b, 5; 5b, 17
4a, 67
9d, 3
b
3, Φ−1 = 0.05
MeOH/H2O 4/1
EtOH
26
4a, 91
0
100
54
4a, 53
7a, 2
0.04
0.41
0
0
0
EtOH/H2O 2/1
MeOH, 0.2 M ATMS
4a, 66
6b, 20; 7a, 7
72
4a, 67
a
Conditions: 0.025 M solution of 1−3 (in the presence of ATMS where indicated) in the chosen solvent irradiated at 310 nm. tirr = 2−8 h (see
b
Supporting Information for further details). Yields were based on consumed 1−3 and determined by GC analysis. Quantum yields of disappearance
c
d
(Φ−1) of 1−3 (10−2 M in MeOH) were measured at 254 nm. Ratio between DHT vs phenyl cation derived products. A partial secondary
desilylation of 5 to the corresponding 4-(2-propenyl)-1-methoxy-2-methylbenzene was observed (see the Supporting Information for details).
Mechanism. A rationalization to the product distribution
obtained was sought for by computational methods. Thus, the
nature of the excited states involved in the photochemistry of
compounds 1−3, as well as the structure of the intermediates
formed along the competing paths, was examined. The study of
the ground state (S0) and the lowest lying singlet and triplet
excited states (S1 and T1, respectively) clearly demonstrated
that heterolytic C−Cl cleavage was feasible exclusively from the
T1 state. Since these results essentially duplicate conclusions
from our previous work on simpler derivatives,9c details are
reported in the Supporting Information only (see section 2.2).
The phenyl cation intermediates formed by dechlorination of
1−3 from the triplet state were then examined. The aromatic
rings in triplets (311+−313+) are planar with a geometry close
to that of a regular hexagon.
• silicon-free products, arising either via benzyl radicals
(products 6−8) or via polar addition (9 and 10) from an
α,n-MeO-DHT diradical intermediate.
The product distributions obtained in the irradiation
experiments under conditions where the substrate was fully
consumed (less than 4 h in neat alcohol, 2 h in alcohol−water
for 1 and 2, much longer for 3; see the Supporting Information
for details) are gathered in Table 1. Thus, irradiation of 1 in
both methanol and ethanol yielded a mixture of (3-
methoxybenzyl)trimethylsilane (4a) and of the corresponding
phenethyl alcohols 6a,b along with a minor amount (<10%
overall yield) of 3-methylanisole (7a) and of 1,2-diarylethane
8a. The addition of water to the mixture had a limited effect.
Neither benzyl ethers 9a,b nor benzyl alcohol 10a was
observed. On the other hand, in the presence of ATMS (0.2
M) the formation of 6−8 was almost completely suppressed,
and allylarene 5a became the main product (with a yield
increasing with the ATMS concentration), along with some 4a.
Compound 2 was found to react efficiently regardless of the
solvent used. In contrast to compound 1, polar products such
as benzyl ethers 9c,d and benzyl alcohol 10b were formed in
variable amounts and were the main products in MeOH-
containing media (Table 1). Diradical products were mainly
formed in ethanol with a limited effect of the presence of water.
Trapping with ATMS gave the corresponding allylanisole 5b,
but small amounts of DHT-derived products were obtained
even when using 1 M ATMS.
More varied is the situation of the singlet phenyl cations,
which were also studied for the sake of comparison. Thus, in
1
111+ and 13+ a marked puckering of the ring and an out-of-
plane displacement of the dicoordinated carbon are evident,
1
while in 12+ the dicoordinated carbon remains in the plane
and a (limited) distortion involves the adjacent carbon atoms
(Figure 2).15
3
As for the electronic structure, 11+−313+ can be described
to a good approximation by a single configuration (the
coefficient of the lowest eigenvector is >0.94 in every case).
Accordingly, the localization of the two unpaired electrons is
easily determined, as shown in Figure 3: viz., one of the
SOMOs is located at the dicoordinated carbon, while the
3
second is part of the π cloud, making 11+−313+ straightfor-
Isomer 3 reacted much less efficiently, and the presence of
water further slowed down the conversion. Dechlorination of 3
to 4a was the only observed pathway, in the presence of ATMS
as well. Of the silicon-free products, only 6b was obtained in a
significant yield (20%) in EtOH/H2O, along with a minor
amount of 3-methylanisole (7a).
ward examples of the typical radical/radical-cation character of
triplet phenyl cations. A detailed description of the electronic
structure of the corresponding singlet phenyl cations has been
included in the Supporting Information (see section 2.3 for
details).
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Table 2. Gibbs Free Energy (ΔGCASMP2; See Eq S1 in the
Supporting Information) Changes for Phenyl Cations 11+−
13+ According to the Isodesmic Equation Below, Calculated
at the CASMP2/6-31G(d) Level of Theory in Bulk Methanol
ΔGCASMP2 (kcal mol‑1)
species
1Ar+
3Ar+
11+
12+
13+
−10.46
−5.68
−10.68
−18.93
−21.39
−15.19
the length of the Cα−Si bond at the equilibrium geometry in
112+ (2.09 Å) is in any case larger (by about 0.1 Å) than in
isomeric 1,311+, 12+, and 1,313+ (1.98 Å). As shown in Figure
3
4, desilylation of 112+ confronts the lowest energy barrier
(around 16 kcal mol−1), while for the other cations the barrier
is higher, around 20−26 kcal mol−1. Importantly, in the case of
12+ a crossing between the singlet and triplet surfaces takes
place during Cα−Si bond stretching. This results in a further
Figure 2. Optimized geometries at the CASSCF/6-31G(d) level and
relevant parameters calculated for phenyl cations 11+−13+.
3
1
desilylation path for the conversion of 12+ to 15 via this
surface crossing, confronting a barrier of around 24 kcal mol−1
(Figure 4b).
A CASSCF analysis was then carried out on the diradicals
arising through desilylation of the phenyl cations. All of these
structures are planar and have the two SOMOs located in
orthogonal orbitals (one at the dicoordinated carbon and the
second delocalized over the π cloud; see section 2.4 in the
Supporting Information for details), similarly to what was
found for the unsubstituted derivatives.
As for the parent α,n-DHTs, the ground state is a singlet for
the α,3-derivative (with a small S-T gap) and a triplet for the
other two isomers. The present computational analysis
confirmed the same trend, with a triplet ground state for
derivatives 14 and 16, while 15 (an α,3-MeO-DHT) has a
singlet ground state. The isodesmic equation reported in Table
3 was then used to evaluate the stabilization imparted by the
methoxy group with respect to the corresponding parent
DHTs. As shown in Table 3, the effect is minimal, and the
singlets are slightly more stabilized than the corresponding
triplets.
Figure 3. Singly occupied molecular orbitals (SOMOs) for triplet
phenyl cations 311+−313+ as determined from CASSCF/6-31G(d)
calculations.
DISCUSSION
■
The initial part of the reaction conforms to what has been
observed in other phenyl halides, with efficient ISC to triplet
states 31−33 (Scheme 3, path a)12,16 and heterolysis of the Ar−
Cl bond (Scheme 3, path b; see section 2.2 in the Supporting
Information for further details). All of the photoproducts
obtained were chlorine-free; thus, the efficiency of path b (ηb)
coincided with the quantum yield of reaction.17 The quantum
yield of heterolytic dechlorination remains sufficiently high to
make these reasonable precursors of MeO-DHTs, at least for
the case of 1 and 2. Note that the presence of the methoxy
group in the ortho position with respect to the nucleofugal
group −Cl effectively suppressed the photoreactivity of the
simpler model (4-chlorobenzyl)trimethylsilane (for which the
measured disappearance quantum yield was Φ−1 = 0.71).9a,18
The first intermediate formed was in every case a triplet phenyl
cation (311+−313+), which was consistently lower in energy
The stabilization imparted by the methoxy group to phenyl
cations 11+−13+ was quantified by using the isodesmic
equation reported in Table 2 with the corresponding
Me3SiCH2-substituted phenyl cations as a reference. The
results show that the stabilization by the methoxy group
depends on the position on the ring and is much larger for
triplets than for the corresponding singlets, particularly with
12+.
The likelihood of the detachment of the Me3Si+ group from
cations 11+−13+ to form diradicals 14−16 was then evaluated
by a relaxed PES (potential energy surface) scan: viz., by
stretching the Cα−Si bond from the equilibrium geometry up
to ∼3 Å by 0.1 Å intervals (see section 2.8 in the Supporting
Information for details). It is worth noting (see Figure 2) that
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Table 3. Gibbs Free Energy (ΔGCASMP2; See Eq. S1 in the
Supporting Information) Changes for MeO-DHTs 14−16
According to the Isodesmic Reaction Illustrated Below,
Calculated at the CASMP2/6-31G(d) Level of Theory in
Bulk Methanol
Scheme 3. Generation of MeO-DHTs 14−16 from Silanes
1−3
Figure 4. Energy profiles for the relaxed scans of the Cα-Si bond in (a)
11+, (b) 12+, and (c) 13+ at the CPCM-CASSCF/6-31G(d) level of
theory in bulk methanol.
than the corresponding singlet.10,11,19,20 Accordingly, the typical
chemistry of triplet cations, viz. hydrogen abstraction from the
alcoholic solvent (Scheme 3, path e) to form methoxybenzylsi-
lanes 4a,b and trapping in the presence of a sufficient amount
of a π-bond nucleophile to give allylbenzenes 5a,b (path f), was
observed, with no solvolysis that would point to a role for
singlet cations 111+−113+ (Scheme 3, paths c and d). Cleavage
of Me3Si+ from the triplet cations 311+−313+ took place to give
α,n-MeO-DHTs (314−316; path g).
ca. 5 × 107 s−1 and kf is 1 × 108 M−1 s−1.11 The data in Table 1
thus show that the rate of desilylation from the cation kg may
reach the same value and increases from kg/(ke + kf[ATMS])
ca. 1 for 11+ up to 6 for 12+ (in the last case kh rather than kg is
likely involved).
As for the 2-methoxyphenyl cation 13, some MeO-DHT-
derived products are formed, at least in EtOH−H2O.
Furthermore, no trapping by ATMS occurs. The simplest
explanation is that the rate of reduction (ke) largely increases in
The quantum yield of trapping of the phenyl cation by
ATMS (Φtr) is thus given by eq 1.
Φ = η kf[ATMS]/{kg + ke + kf[ATMS]}
tr
(1)
b
Previous experiments on the 4-methoxyphenyl cation
showed that the pseudounimolecular rate of reduction ke is
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this case and severely limits any competitive path from the
cation.
singlet, although the product distribution depends on the
medium.24
It is hoped that a judicious choice of the substituent pattern
will make it possible to optimize the fragmentation of phenyl
chlorides to yield DHTs and tune the chemistry of such
intermediates, a target that increases the interest for possible
biological applications. Work in this direction is underway.
Importantly for potential applications, this work demonstrated
that the presence of an electron-donating substituent in
compounds 1−3 allows for the use of UV-B irradiation in
place of the more toxic UV-C (254 nm) used in our previous
experiments with unsubstituted (n-chlorobenzyl)-
trimethylsilanes.9
Of the two electron-donating groups (MeO− and
Me3SiCH2−) present,21 it is the former that directs the
reactivity of the system. In addition to the aforementioned
effect on dechlorination, it determines the spin state of the
resulting cation (see Chart 1 and Figure 1). The electron-
donating group stabilizes the phenyl cation but has no
appreciable effect on the energy of the resulting α,n-MeO-
DHT. This makes the desilylation step from the triplets less
favorable (energy barrier up to 26 kcal mol−1) than when no
methoxy group is present (<20 kcal mol−1 when imposing a
similar elongation to the Cα−Si bond; see Figure 4).9c The
products from 1 and 3 result exclusively from the “radical” path,
viz. the MeO-DHT abstracts a hydrogen from the solvent
(more efficiently, as one may expect, from EtOH than from
MeOH), but this is not the case for the MeO-DHT derived
from 2. With this compound, products resulting from “ionic”
addition to the corresponding MeO-DHT were significant
(polar/radical ratio from 0.14 to 2, Table 1) and, as one may
expect, were formed more efficiently in MeOH than in EtOH
(see Table 1).22
ASSOCIATED CONTENT
* Supporting Information
■
S
Text, figures, and tables giving experimental procedures, sample
spectra, and optimized geometries, energies, and CASSCF
output data for all of the structures involved in this work. This
material is available free of charge via the Internet at http://
pubs.acs.org.
3
3
Whereas desilylation from 11+ and 13+ proceeds with spin
AUTHOR INFORMATION
Corresponding Author
*M.F.: fax, +39 0382 987323; tel, +39 0382 987198; e-mail,
fagnoni@unipv.it.
■
3
3
conservation to yield 14 and 16, respectively, in the case of
312+ a surface crossing (see Figure 4b) was detected in the
Me3Si+ cleavage, suggesting that the corresponding singlet α,3-
MeO-DHT (115) is obtained directly from the cation (312+,
path h). It is worth noting that the crossing occurs at an early
stage along the reaction coordinate describing Cα−Si bond
breaking. Thus, the spin−orbit coupling matrix element for the
T-S crossing point should be close to the value for the
equilibrium geometry. Indeed, some reports in the literature
dealing with simple derivatives demonstrated that, despite the
fact that coupling constants are rather small in absolute terms,
they are certainly large enough to efficiently mediate the
transition of the triplet cation to the singlet, fully supporting the
feasibility of path h.23 Furthermore, the product distribution in
Table 1 supports that the latter path is favored (kh ≥ kg
resulting in a high yield of MeO-DHT-derived products). It
seems that this is a general characteristic of α,3-DHT, whether
thermally or photochemically generated.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Fondazione Cariplo (grant
2011-1839). S.P. acknowledges the MIUR, Rome (FIRB-
Futuro in Ricerca 2008 project RBFR08J78Q), for financial
support. We thank Prof. A. Albini (University of Pavia) and P.
Hoggard (Santa Clara University) for fruitful discussions. We
are grateful to B. Mannucci and C. Nicola (Centro Grandi
Strumenti-Pavia) for their valuable assistance. This work was
funded by the CINECA Supercomputer Center, with computer
time granted by ISCRA projects (codes HP10CZEHG6,
HP10C6PCC2, and HP10C3CPWN).
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■
CONCLUSION
■
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