Looking for a paradigm for the reactivity of phenonium ions

Article abstract of DOI:10.1002/ejoc.201100305

The addition of a photogenerated phenyl cation to an alkene offers an entry, under mild conditions, to the phenethyl cation/phenonium ion system in organic solvents. Taking advantage of this, a product study has been carried out in parallel with a computational characterization of the intermediates. Thus, 4-methoxy- and 4-dimethyaminophenyl cations have been photogenerated from the corresponding chlorobenzenes in the presence of mono- to tetrasubstituted olefins in polar or protic media. The chemistry that occurs has been correlated with the degree of anchimeric assistance offered by the phenyl group, as predicted by calculations. Two limiting situations arise, the first one when starting from mono- or 1,2-disubstituted alkenes. In these cases, calculations evidence a large stabilization of the intermediate (phenonium character), particularly with electron-donating substituents on the aromatic ring, and the main products in acetonitrile are phenethyl chlorides. Variation of the ion-stabilizing solvent such as trifluoroethanol (TFE) leads to alkyl and hydride migration before chloride addition. In contrast, with less electron-rich aromatics and highly substituted alkenes the stabilization of the intermediate is modest and the typical reaction is deprotonation to yield an allylbenzene or, in TFE, the formation of a phenethyl ether. In between these two extremes, there are intermediate cases, more easily directed by a change in the conditions. These generalizations and the mildness of the method help to assess the synthetic potential of this reaction. Copyright

Full text of DOI:10.1002/ejoc.201100305

FULL PAPER
DOI: 10.1002/ejoc.201100305
Looking for a Paradigm for the Reactivity of Phenonium Ions
Stefano Protti,[a] Daniele Dondi,[a] Mariella Mella,[a] Maurizio Fagnoni,[a] and
Angelo Albini*[a]
Keywords: Photolysis / Solvent effects / Density functional calculations / Carbocations / Electrophilic addition
The addition of a photogenerated phenyl cation to an alkene
offers an entry, under mild conditions, to the phenethyl cat-
ion/phenonium ion system in organic solvents. Taking ad-
character), particularly with electron-donating substituents
on the aromatic ring, and the main products in acetonitrile
are phenethyl chlorides. Variation of the ion-stabilizing sol-
vantage of this, a product study has been carried out in paral- vent such as trifluoroethanol (TFE) leads to alkyl and hydride
lel with a computational characterization of the intermedi-
ates. Thus, 4-methoxy- and 4-dimethyaminophenyl cations
have been photogenerated from the corresponding chloro-
benzenes in the presence of mono- to tetrasubstituted olefins
in polar or protic media. The chemistry that occurs has been
correlated with the degree of anchimeric assistance offered
by the phenyl group, as predicted by calculations. Two limit-
ing situations arise, the first one when starting from mono-
or 1,2-disubstituted alkenes. In these cases, calculations evi-
dence a large stabilization of the intermediate (phenonium
migration before chloride addition. In contrast, with less elec-
tron-rich aromatics and highly substituted alkenes the stabi-
lization of the intermediate is modest and the typical reaction
is deprotonation to yield an allylbenzene or, in TFE, the for-
mation of a phenethyl ether. In between these two extremes,
there are intermediate cases, more easily directed by a
change in the conditions. These generalizations and the
mildness of the method help to assess the synthetic potential
of this reaction.
More recently, the synthetic potential of these carbocations
has been pointed out by Nagumo and Akita and co-
Introduction
The β-stabilization effect of the aryl group in phenethyl workers, with the suggested synthesis of oxygen heterocycles
cations and the attending formation of a σ-bridged interme- (lactones and tetrahydrofurans)[11] upon solvolysis of the
diate, the phenonium ion, was first evidenced by Cram[1] corresponding phenethyl sulfonates. This approach
through pioneering studies on the stereochemical course of (Scheme 1, a) is appealing for synthetic applications,[12]
the solvolysis of optically active phenethyl sulfonates. The whereas other methods, such as the ring-opening of benzo-
role of such an intermediate has since been explored from cyclobutene in superacids, are of spectroscopic interest.[13]
both the experimental[2] and computational points of Some years ago we demonstrated a novel, mild access to
view.[3] Recent work favours a continuum of situations in phenonium ions by the addition of triplet phenyl cation IV,
between the phenethyl cation I and the σ-bridged structure photogenerated from phenyl halides or esters,[14] to olefins
III, and the possible role of a weak π complex II (see (Scheme 1, b).[15–17] The first-formed triplet adduct cation
Scheme 1).[4] Substituents on the ring and on the phenethyl with alkenes has a diradical character (V), just like the
moiety clearly affect the structure and reactivity of the in- starting phenyl cation, but then intersystem crossing occurs
termediate, as do the medium characteristics. Apart from to the more stable singlet phenethyl cation/phenonium ion
the initial experiments, most mechanistic studies have been system (I/III), which, contrary to what happens in the trip-
carried out under conditions quite different to those suit- let manifold, undergoes addition of nucleophiles. The multi-
able for preparative purposes, for example, in the gas plicity-dependent selectivity has been exploited in some
phase[5] or in superacids,[2] a fact that has contributed to three-component photoarylations[15,17a–17c,18a] (Scheme 1,
the slow development of synthetic processes via this inter- c) and in the intramolecular version when the trap bears
mediate. Application of this intermediate in organic synthe- two nucleophilic sites, as is the case with ω-alkenols[19] and
sis for carbon–carbon or carbon–heteroatom bond forma- ω-alkenoic acids.[20] Whatever the mode of generation, the
tion was reported in the 90s by Olah and co-workers.[6,7,10] phenonium may be involved competitively in various pro-
cesses (nucleophile addition, deprotonation and rearrange-
ment). This often leads to an unsatisfactory selectivity, but
[a] Department of Chemistry, University of Pavia,
no systematic examination of such competition and on the
dependence on structure and conditions has been carried
out, also because of the limited choice allowed for the gen-
eration of the key intermediate. The mild conditions of the
V. Le Taramelli 12, 27100 Pavia, Italy
Fax: +39-0382-987323
E-mail: angelo.albini@unipv.it
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100305.
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S. Protti, D. Dondi, M. Mella, M. Fagnoni, A. Albini
FULL PAPER
phenyl cation path offers a convenient way to explore this Table 1. Products from the photoreaction of 4-chloro-N,N-dimeth-
ylaniline (1a) and 4-chloroanisole (1b) with monosubstituted alk-
point. Accordingly, an experimental and computational
study was performed and is reported below.
enes.[a]
1a
1a
1b
1b
MeCN 2a, 5 3a, 35 3Јa, 18
TFE[b] 2a, 3 3a, 45
MeCN 2b, 5 3b, 54
TFE[c] 2b, 5 3b, 36
4b, 10
5b, 40
1a
1a
MeCN 2a, 10 6a, 40
[d]
TFE
1b[e] AcOEt 2b, 6 6b, 25 7b, 16
8b, 19
8b, 22
1b
TFE[c] 2b, 13
9b, 55
[a] Ar = pNMe2C6H4 or pOMeC6H4. Experimental conditions:
ArCl (0.05 m) and the alkene (0.5 m) were irradiated in a degassed
solution of the chosen solvent until the complete consumption of
the aromatic. Isolated yields based on consumed 1, except in the
case of compounds 2a,b, were determined by GC analysis. Data
presented as product, yield [%]. [b] 90% conversion of 1a. [c] Caes-
ium carbonate (0.025 m) was added. [d] Sluggish reaction forming
a complex mixture. [e] The same distribution products were ob-
tained in MeCN, but the conversion of 1b was lower (Ͻ50%).
Scheme 1.
Results and Discussion
As indicated in part b of Scheme 1, the adduct cations
were generated from the trapping by alkenes of aryl cations
arising from the photoheterolysis of electron-donating-sub-
stituted phenyl chlorides, namely 4-chloro-N,N-dimeth-
As for the other primary alkenes tested, with 3,3-di-
ylaniline (1a)[21] and 4-chloroanisole (1b).[18] Alkenes with methyl-1-butene, 1a gave the phenethyl chloride 6a in 40%
increasing degrees of substitution (1-hexene, 3,3-dimethyl- yield in MeCN, whereas irradiation in TFE gave a complex
1-butene, cyclohexene, 2-methyl-2-butene and 2,3-dimethyl- mixture, a result not improved by adding Cs2CO3. Anisole
2-butene) were used as traps in two solvents, acetonitrile 1b gave analogous chlorides 6b and 7b along with styrene
and 2,2,2-trifluoroethanol (TFE). Irradiation was per- 8b in MeCN. In this solvent the photoreaction occurred
formed until complete consumption of the aryl chloride, with limited conversion, but in ethyl acetate the reaction
except where indicated, and the adducts formed were sepa- proceeded to completion with the formation of the same
rated by chromatography, identified and quantified. In ad- compounds. In TFE, ether 9b was by far the most abundant
dition to adducts, reduced products, N,N-dimethylaniline product (55% yield) along with 8b.
(2a) and anisole (2b), respectively, were consistently formed
as minor products and their amounts were determined by 1-aryl-2-chlorocyclohexane 10a was the only adduct formed
GC analysis. in both solvents from 1a and correspondingly 10b was
In the presence of cyclohexene, the corresponding trans-
Because the reactions considered involved the release of formed from 1b in MeCN, whereas in TFE, 10b was ac-
acidity,[17d] it was checked in every case that this did not companied by rearranged benzyl ethers 11b and 12b, as pre-
induce acid-catalysed secondary processes and in some viously established (Table 2).[18,22] Irradiation with 2-
cases a base (Cs2CO3) was added to buffer the solution. methyl-2-butene gave the allyl derivatives 13 as the major
The results are presented in Tables 1–3. Thus, irradiation products from both halides in acetonitrile, along with a
of 4-chloro-N,N-dimethylaniline (1a) in the presence of 1- small amount of methoxystyrene 15b in the case of 1b. Irra-
hexene afforded the regioisomeric phenethyl chlorides 3a diation in TFE gave phenethyl ethers 14a,b as the main
and 3Јa in acetonitrile, but only the 3a in TFE (Table 1). 4- products. Finally, chlorides 1a,b gave the corresponding al-
Chloroanisole (1b) gave the analogous adduct (isomer 3b lylbenzenes 16a,b in the presence of 2,3-dimethylbutene in
only) in acetonitrile, but in TFE 3b was accompanied by acetonitrile and TFE, although comparable yields of alkyl-
phenethyl ether 4b as well as by benzyl ether 5b, indeed, the benzene 17b and ethers 18b and 19b were likewise formed
most abundant product.
from 1b in TFE (Table 3).
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Looking for a Paradigm for the Reactivity of Phenonium Ions
Table 2. Products from the photoreaction of 1a and 1b with cyclo- phenonium ion) was slightly stronger (by ca. 1 kcalmol–1)
hexene and 2-methyl-2-butene.[a]
for the 4-methoxy-substituted derivatives than for the 4-di-
methylamino derivatives. As for the geometry, the six-mem-
bered ring had the expected cyclohexadienyl structure al-
ready evidenced in previous studies of phenonium
ions.[13,26] As for the spirocyclopropane ring, the introduc-
tion of substituents caused a lengthening of the C1–Cα(β)
bonds, with a stepwise increase of about 0.03 Å for each
methyl group added in the NMe2 series and of 0.04 Å in
the OMe series (see Table 4, some examples of the geome-
tries are shown in Figure 2). Thus, the most stable configu-
ration varied from a “fully formed” phenonium ion, as in
the case of 20 (FG = NMe2, C1–Cα 1.577 Å), to what ap-
pears to be a complex rather than a covalently bonded
structure (see 24b, FG = OMe, C1–Cα 1.674 Å) or to a
strongly asymmetric structure (see 23b). A parallel effect is
the diminishing of the fraction of positive charge calculated
on the cyclopropane with increasing substitution (see the
total charge on the cyclopropane moiety, which varies from
0.26 to 0.18 and from 0.31 to 0.18 in the two series in
Table 5; correspondingly, more charge remains at C4).
1a
1a
1b
1b
MeCN
TFE
2a, 30
2a, 11
2b, 3
10a, 55
10a, 59
10b, 30
10b, 9
MeCN
TFE[b]
2a, 10
11b, 20
12b, 21
1a
1a
1b
1b
MeCN
TFE
2a, 15
2a, 15
2b, 5
13a, 54
13a, 5
13b, 55
13a, 54
14a, 43
14b, 50
MeCN
15b, 12
15b, 18
TFE[b]
2b, 5
[a] See Table 1 for experimental details. Data presented as product,
yield [%]. [b] Caesium carbonate (0.025 m) added.
Table 3. Products from the photoreaction of 1a and 1b with 2,3-
dimethyl-2-butene.[a]
(1)
Table 4. Calculated geometries for selected substituted phenonium
intermediates.
1a
1a
1b
1b
MeCN 2a, 15
TFE 2a, 5
16a, 64
16a, 60
MeCN 2b, 2
16b, 49
TFE[b] 2b, 2
16b, 21 17b, 14 18b, 17 19b, 7
[a] Ar = pNMe2C6H4 or pOMeC6H4. See Table 1 for experimental
details. Data presented as product, yield [%]. [b] Caesium carbonate
(0.025 m) added.
In parallel to the experimental study, DFT calculations
were carried out on the key intermediates, singlet adduct
cations I/III, formally resulting from the reaction with in-
creasingly methyl-substituted alkenes, from ethylene to 2,3-
dimethyl-2-butene.[23] The structures were optimized in
vacuo and checked to have no imaginary frequencies. Sol-
vent effects were evaluated by single-point calculations of
the optimized geometries by using the CPCM method (see
the Supporting Information).
In all cases, the minima corresponded to structures in
which the Cα–Cβ bond (see Table 4) lies in the plane per-
pendicular to that of the six-membered ring. Substituents
at Cα and Cβ made such cations less stable, with an almost
monotonic increase in energy of 3.5–4 kcalmol–1 per methyl
group, with the energy of the tetramethyl system twice as
much as that with the tert-butyl group, as shown in Figure 1
in which the energy involved in the isodesmic reaction
[Equation (1)] is reported.[25] The effect (resulting from the
C1–Cα
[Å]
C1–Cβ
[Å]
Cation
FG
RЈ
RЈЈ
RЈЈЈ RЈЈЈЈ
20
21
NMe2
NMe2
NMe2
NMe2
NMe2
NMe2
H
H
H
H
H
H
H
H
H
Me
Me
Me
H
H
H
1.577
1.577
1.611
1.630
1.608
1.607
1.661
1.642
Me 1.574
tBu 1.570
Me 1.608
21Ј
22-trans-22
cis-22
23
24
H
H
Me
H
1.606
Me Me 1.596
Me Me 1.641
NMe2 Me Me
20
21
21Ј
trans-22
cis-22
23
MeO
MeO
MeO
MeO
MeO
MeO
H
H
H
H
H
H
H
H
H
Me
Me
Me
H
H
H
1.594
1.594
1.648
1.697
1.632
1.633
1.759
1.674
Me 1.583
tBu 1.571
Me 1.632
H
H
Me
H
1.628
Me Me 1.591
Me Me 1.674
24
MeO Me Me
Furthermore, the cyclopropane-localized charge in-
algebraic sum of two contributions by the methyl groups, creased somewhat (by 1 to 10%) on passing from an aprotic
the stabilization of the alkene and the destabilization of the to a protic solvent, although the effect was smaller for tri-
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Table 5. Computed Mulliken charges of the cation adducts and
paths followed in the photoarylation (lettering, see Scheme 2 and
Table 4).
Cation-FG
Solvent
Fractional charge[a]
cyclo-
Reaction path[b]
Cα
Cβ
main
minor
propane
21-NMe2
21-NMe2
MeCN 0.115 0.118
0.248
a
a
RO-
0.122 0.12
H[a,b]
0.259
21Ј-NMe2
22-NMe2
22-NMe2
23-NMe2
23-NMe2
24-NMe2
24-NMe2
21-OMe
MeCN 0.096 0.113
MeCN 0.104 0.104
0.223
0.215
0.227
0.197
0.210
0.185
0.184
0.298
0.312
0.265
0.238
0.250
0.266
0.217
0.231
0.181
0.187
a
a
a
c
b
c
c
a
e, a
a
e
a
e
c
b
c
ROH
MeCN 0.117 0.078
ROH 0.119 0.089
MeCN 0.095 0.095
ROH 0.096 0.096
MeCN 0.145 0.16
ROH 0.155 0.164
MeCN 0.13 0.155
ROH 0.141 0.157
MeCN 0.131 0.131
ROH 0.141 0.141
MeCN 0.135 0.092
ROH 0.137 0.106
MeCN 0.101 0.101
ROH 0.104 0.104
0.111 0.111
c
Figure 1. Calculated ΔG for the isodesmic reaction in Equation (1)
for methoxy- (grey bars) and dimethylamino-substituted (black
bars) cations. For the numbering, see Table 4.
21-OMe
b
e, d
d
21Ј-OMe
21Ј-OMe
cis-22-OMe
cis-22-OMe
23-OMe
23-OMe
24-OMe
a
d
c
24-OMe
c
e, b
[a] Calculated fractional charges in either acetonitrile or methanol.
[b] Experimentally observed path in either acetonitrile or trifluoro-
ethanol.
Figure 2. Geometries of the cations 21 and 24.
and tetramethyl derivatives. The addition of phenyl cations
to alkenes (see Scheme 1, b) is a convenient approach to
phenonium ions that are thus generated at room tempera-
ture in solution in the presence of weak nucleophiles such
as the chloride anion or TFE. This is an important advan-
tage because the limited choice of precursors and/or the
harsh conditions required in the other methods of genera-
tion have previously hampered the rationalization of the
chemistry that occurs and the comparison with computa-
tional data.[13,24,26]
The experimentally observed processes are presented in
Scheme 2 and lead to a) phenethyl halides, b) phenethyl
ethers, c) allylbenzenes, d) styrenes and e) benzyl halides or
ethers as a result of a hydrogen or carbon shift. Corre-
lations with the calculated properties of the ions were estab-
lished, as discussed below (see Scheme 2 and Table 5).
a) Formation of phenethyl chlorides: The reaction is
characteristic of mono- and 1,2-disubstituted olefins. The
intermediate cation can have both large (with FG = OMe)
and small (with Me2N) differences in length between the
Scheme 2.
C1–Cα and C1–Cβ bonds. Characteristically, these species almost simultaneously. The small charge difference between
showed a large amount of charge on the cyclopropane ring Cα and Cβ is reflected in the formation of both regioiso-
(Ͼ 0.21), but a small difference between the charges at Cα mers in the reaction of chloroaniline with 1-hexene in
and Cβ (Ͻ 0.025). Reasonably, a tight ion pair, Ar+ Cl–, MeCN, although in the more charge-stabilizing TFE the
was formed and addition across the alkene termini occurred arylation was regioselective.
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Looking for a Paradigm for the Reactivity of Phenonium Ions
b) Formation of phenethyl ethers (solvent addition): This the diagonal). The preferred path is a, arising from in-cage
differed from the previous group by there being a larger nucleophilic addition, as indeed expected from a strong
difference between the charges at Cα and Cβ (Ͼ 0.03). This charge on the cyclopropane moiety. At the left border of
increased the “hard” character of the cation and facilitated this region, when the cation is more asymmetric because an
attack by alcohols versus in-cage recombination with the OMe is substituted for a NMe2 group or a more charge-
chloride anion.
stabilizing solvent such as TFE is adopted, a cationic re-
c) Deprotonation of the allylic position: This process oc- arrangement (path e) participates. Below the diagonal, less-
curred with cations with a small amount of charge at the stabilized ions are present, that is, those that contain either
cyclopropane ring (Ͻ 0.22). This is characteristic of tri- and a less-donating substituent (OMe) or a more substituted cy-
tetrasubstituted olefins, in which steric reasons reduced do- clopropane. Here, the six-membered ring contributes to a
nation to the phenyl cations and weakened the bonding. lesser extent so that the charge remains higher at Cα,β.
With these intermediates, weak nucleophiles such as the sol- Therefore the solvent acts as a base rather than as nucleo-
vents used acted as bases.
phile (path c). At the upper limit of this region, and with
d) Benzylic deprotonation: Some of the above intermedi- less substituted cations, solvolysis (path b, but not chloride
ates also yielded a styrene as a byproduct. The requisites addition) is observed.
for such a minor path are not clear, but apparently this has
something to do with steric reasons, because it is limited to
the tert-butyl and trimethyl derivatives.
e) Rearrangement (observed in TFE): This reaction oc-
curred with weakly bonded (Cα–Cβ Ͼ 1.63 Å) asymmetric
cations (bond lengths differing by Ͼ 0.006 Å) bearing a
large amount of charge at the cyclopropane moiety
(Ͼ 0.23). As such, it was mainly observed with the 4-meth-
oxy-substituted derivatives, not with the strongly donating
4-amino-substituted derivatives. Note that in this case,
Wagner–Meerwein chemistry, well known under strongly
acidic conditions,[27,28] occurred here in neutral media.
Interestingly, in the case of the adduct with 3-methyl-1-but-
ene (25), both hydride migration from the benzylic position
(26) and an alkyl shift from the tertiary position (27) took
place (and in MeCN the only case of rearrangement cou-
pled with chloride addition was observed, see Scheme 3).
This is clearly due to the high asymmetry of the intermedi-
ate involved.
Figure 3. Correlation between the calculated charge at the cyclo-
propane moiety and the C1–Cβ bond length for phenonium ions.
For numbering, see Table 4. At each point the main process occur-
ring (paths a–e in Scheme 2) and the solvent in which the reaction
was carried out are indicated.
Summing up, reagents that undergo process a exclusively
are grouped close to the y axis and those undergoing pro-
cess c are exclusively close to the x axis. Here, the process
occurring is determined by the reagent structure, with little
alternative. Points close to the diagonal on the other hand
are more subject to cationic rearrangement (path e) and
more sensitive to conditions, for example, the main path
for intermediate 23a is c in MeCN and b in TFE. These
characteristics make the last group of cations better suited
to attack by external nucleophiles, which is the most useful
reaction from a synthetic point of view, and more easily
directed.
Scheme 3.
In view of this satisfying correlation, a paradigm for the
reactions via phenonium ions could be proposed. Although
a detailed picture presumably requires consideration of
more parameters, a rough classification is already apparent
by using only two, as indicated in Figure 3, in which the
total charge on the cyclopropane moiety is plotted versus
the length of the bond to the most substituted carbon (C1–
Cβ). In other terms, the strength of the stabilizing donation
Conclusions
The chemistry of phenonium ions has been revisited on
from the phenyl ring (clearly always stronger with the NMe2 the basis of a systematic comparison of the reaction path-
group) is compared with the asymmetry of the cyclopro- ways via this intermediate, generated in organic solvents un-
pane moiety. Moving towards the upper left corner involves der neutral conditions. This has allowed a rationalization
an increase in “phenonium” character (symmetric cyclopro- of structure and medium effects. Nucleophilic addition, de-
pane, strong, short C1–Cα, C1–Cβ bonds, large amount of protonation and rearrangement compete in a way that is
charge on the cyclopropane ring). A strong electron-donat- correlated with the calculated charge distribution and bond
ing substituent (NMe2) and an unhindered olefin favour lengths in the ions. The diagram in Figure 3 offers a practi-
such structural characteristics (represented by points above cal way to predict the preferred path(s) and support the
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chromatography (eluent: neat cyclohexane) afforded 3a[22] (162 mg,
45% yield, based on the consumption of 1a, oil).
recently growing interest for syntheses via phenonium ions.
The study further evidences the versatility of photochemical
reactions that often arrive at a highly reactive intermediate
1
3a: H NMR (300 MHz, CD3COCD3): δ = 0.90–1.00 [t, J(H,H) =
under mild conditions that can be varied at choice with 7 Hz, 3 H], 1.25–1.65 (m, 6 H), 2.90–3.00 (m, 2 H), 2.95 (s, 6 H),
4.10–4.15 (m, 1 H), 6.70–7.15 (AAЈBBЈ, 4 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 14.6 (CH3), 23.2 (CH2), 30.5 (CH2), 38.2
(CH2), 41.0 (CH3), 45.2 (CH2), 66.1 (CH), 113.7 (CH), 127.0, 131.2
minimal effect on the photochemical activation step and
thus offers a way to direct the ensuing reactions of such
an intermediate. In particular, these results rationalize the
course of the second addition (phenonium + alkene) step
in the three-component syntheses based on the scheme in
Equation (2).
(CH), 150.9 ppm. IR (neat): ν = 2930, 1614, 1521, 1347, 1163,
˜
807 cm–1. C14H22ClN (239.78): calcd. C 70.13, H 9.25, N 5.84;
found C 68.8, H 9.3, N 5.7.
Irradiation of 4-Chloroanisole (1b) in the Presence of 1-Hexene: The
photolysis of 1b in both acetonitrile and TFE in the presence of 1-
hexene has been described previously by our research group.[16]
Ph–X + hν Ǟ phenyl cation + alkene Ǟ phenonium + nucleophile
Ǟ three-component adduct
(2)
Irradiation of 1a in the Presence of 3,3-Dimethyl-1-butene in Aceto-
nitrile: A solution of 1a (233 mg, 1.5 mmol, 0.05 m) and 3,3-di-
methyl-1-butene (1.95 mL, 15 mmol, 0.5 m) in TFE (30 mL) was
irradiated for 4 h. Purification by column chromatography (eluent:
neat cyclohexane) afforded 144 mg of N,N-dimethyl-4-(2-chloro-
3,3-dimethylbutyl)aniline (6a; 40% yield, oil). 1H NMR (300 MHz,
CDCl3): δ = 0.95 (s, 9 H), 2.70–2.75 [dd, J(H,H) = 12 and 3.5 Hz,
1 H], 2.95 (s, 6 H), 3.85–3.90 [t, J(H,H) = 12 Hz, 1 H], 4.05–4.10
[dd, J(H,H) = 10 and 3.5 Hz, 1 H], 6.80–7.20 (AAЈBBЈ, 4 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 28.2 (CH3), 34.6, 40.5 (CH3),
45.9 (CH2), 58.1 (CH), 111.8 (CH), 127.6, 129.7 (CH), 149.2 ppm.
Considering that the initial phenyl cation addition step
had been previously rationalized, the present conclusions
help the development of the synthetic applications of this
sequence.
Experimental Section
General: 1H and 13C NMR spectra were recorded with a 300 MHz
spectrometer. The structural assignments were made on the basis of
the 1H and 13C NMR spectra as well as by DEPT-135 experiments.
Chemical shifts are reported in ppm downfield from TMS. 4-Chlo-
roanisole (1b), anisole (2b) and all the olefins used were commercial
samples and were freshly distilled before use. 4-Chloro-N,N-di-
methylaniline (1a) and N,N-dimethylaniline (2a) were prepared
from the corresponding anilines.[29] The presence of photoproducts
2a and 2b was determined by comparison with authentic samples
and the amount determined from calibration curves.
IR (neat): ν = 2949, 1609, 1519, 1347, 1164, 817 cm–1. C H ClN
˜
14 22
(239.78): calcd. C 70.13, H 9.25, N 5.84; found C 70.1, H 9.3, N
5.7.
In TFE: Compound 1a (233 mg, 1.5 mmol, 0.05 m) and 3,3-di-
methyl-1-butene (1.95 mL, 15 mmol, 0.5 m) in TFE (30 mL) were
irradiated for 4 h. The photolysed solution was evaporated, but pu-
rification by column chromatography afforded a complex mixture
of photoproducts that were not fully characterized.
General Procedure for the Photolysis of Chlorides 1a and 1b: A solu-
tion (30 mL) containing the chosen chloride (0.05 m) and olefin
(0.5 m) in degassed acetonitrile or 2,2,2-trifluoroethanol (TFE) was
irradiated in a multilamp reactor fitted with six 15 W phosphor-
coated lamps until complete consumption of the aromatic substrate
(except where indicated). In the case of the irradiation of 1b in
TFE, caesium carbonate (0.025 m) was added to the solution before
irradiation to avoid acid-catalysed secondary processes. The pho-
tolysed solution was then evaporated and the resulting residue puri-
fied by column chromatography (eluent: cyclohexane/ethyl acetate).
Irradiation of 1a in acetonitrile in the presence of 1-hexene, cyclo-
hexene and 2,3-dimethyl-2-butene have previously been reported by
our research group.[22] In the latter case, a 1 m concentration of the
chosen olefin was used and anhydrous potassium carbonate
(K2CO3) was added in some cases to the irradiating solution. To
have a set of comparable data we repeated the experiments under
the above conditions.
Irradiation of 1b in the Presence of 3,3-Dimethyl-1-butene in Ethyl
Acetate: Compound 1b (200 μL, 1.5 mmol, 0.05 m) and 3,3-di-
methyl-1-butene (1.95 mL) in ethyl acetate (30 mL) were irradiated
for 24 h. The photolysed reaction was evaporated and the resulting
residue purified by column chromatography to afford 139 mg of
a mixture of 2-chloro-1-(4-methoxyphenyl)-3,3-dimethylbutane (6b;
85 mg, 25% yield), 1-chloro-1-(4-methoxyphenyl)-3,3-dimethyl-
butane (7b; 54 mg, 16% yield) and 54 mg of (E)-1-(4-meth-
oxyphenyl)-3,3-dimethyl-1-butene (8b; 19% yield, oil).
1
6b: H NMR (300 MHz, CDCl3, from the mixture): δ = 1.15 (s, 9
H), 3.20–3.25 [dd, J(H,H) = 14 and 2 Hz, 2 H], 3.80 (s, 3 H) 3.80–
3.90 (m, 1 H), 6.85–7.15 (AAЈBBЈ, 4 H) ppm. 13C NMR (75 MHz,
CDCl3, from the mixture): δ = 26.7 (CH3), 36.1, 45.6 (CH2), 55.1
(CH3), 58.2 (CH), 113.6 (CH), 130.0 (CH), 131.4, 158.1 ppm. 7b:
1H NMR (300 MHz, CDCl3, from the mixture): δ = 0.95 (s, 9 H),
2.70–2.80 (m, 2 H), 3.80 (s, 3 H), 4.05–4.15 [dd, J(H,H) = 13 and
3.5 Hz, 1 H], 6.80–7.15 (AAЈBBЈ, 4 H) ppm. 13C NMR (75 MHz,
CDCl3, from the mixture): δ = 28.2 (CH3), 34.4, 38.7 (CH2), 55.0
(CH3), 75.9 (CH), 113.1 (CH), 130.0 (CH), 130.0 (CH), 131.8,
Irradiation of 4-Chloro-N,N-dimethylaniline (1a) in the Presence of
1-Hexene in Acetonitrile: A solution containing 1a (233 mg,
1.5 mmol, 0.05 m) and 1-hexene (1.90 mL, 15 mmol, 0.5 m) in ace-
tonitrile (30 mL) was irradiated for 5 h. Column chromatography
(eluent: cyclohexane/ethyl acetate, 99:1) gave 191 mg of a mixture
of N,N-dimethyl-4-(2-chlorohexyl)aniline (3a; 126 mg 35% yield)
and N,N-dimethyl-4-[1-(chloromethyl)pentyl]aniline (3Јa; 65 mg,
18% yield). The spectroscopic data of the photoproducts are in
agreement with the literature.[22]
158.2 ppm. IR of the mixture (neat): ν = 2957, 1509, 1246,
˜
1
1038 cm–1. 8b: H NMR (300 MHz, CDCl3):[30] δ = 1.00 (s, 9 H),
3.80 (s, 3 H), 5.55–5.60 [d, J(H,H) = 13 Hz, 1 H], 6.35–6.40 [d,
J(H,H) = 13 Hz, 1 H], 6.80–7.15 (AAЈBBЈ, 4 H) ppm. 13C NMR
(75 MHz, CDCl3):[30] δ = 31.1 (CH3), 33.9, 55.1 (CH3), 112.8 (CH),
126.6 (CH), 130.0 (CH), 131.5, 142.4 (CH), 157.9 ppm. IR (neat):
ν = 2957, 1509, 1246, 1038 cm–1. C H O (190.28): calcd. C 82.06,
˜
13 18
H 9.53; found C 81.8, H 9.6.
In 2,2,2-Trifluoroethanol (TFE): A solution containing 1a (233 mg,
1.5 mmol, 0.05 m) and 1-hexene (1.90 mL, 15 mmol, 0.5 m) in TFE
(30 mL) was irradiated for 8 h (90% of 1a consumed). Column
In TFE: A solution of 1b (200 μL, 1.5 mmol, 0.05 m), 3,3-dimethyl-
1-butene (1.95 mL, 15 mmol, 0.5 m) and Cs2CO3 (222 mg,
3234
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3229–3237

Looking for a Paradigm for the Reactivity of Phenonium Ions
0.75 mmol, 0.025 m) in TFE (30 mL) was irradiated for 12 h and
then evaporated. Purification by column chromatography (eluent:
neat cyclohexane) afforded 63 mg of 8b (22% yield) and 239 mg of
1-chloro-1-(4-methoxyphenyl)-2,3-dimethyl-3-(2,2,2-trifluoroeth-
oxy)butane (9b; 55% yield, oil).
131.2, 149.1 ppm. IR (neat): ν = 2929, 1616, 1552, 1281, 1161, 970,
˜
819 cm–1. C15H22F3NO (289.34): calcd. C 62.27, H 7.66, N 4.84;
found C 62.4, H 7.7, N 4.9.
Irradiation of 1b in the Presence of 2-Methyl-2-butene in Acetoni-
trile: A solution of 1b (200 μL, 1.5 mmol, 0.05 m) and 2-methyl-2-
butene (1.60 mL, 15 mmol, 0.5 m) in acetonitrile (30 mL) was irra-
diated for 14 h. The photolysed solution was evaporated and the
resulting residue purified by column chromatography (eluent: neat
cyclohexane) to afford 177 mg of a mixture of 4-(1,2-dimethyl-2-
propenyl)anisole (13b; 145 mg, 55% yield, oil) and 4-(1,2-dimethyl-
1-propenyl)anisole (15b; 32 mg, 12% yield, oil).
9b: 1H NMR (300 MHz, CDCl3): δ = 0.80–0.85 [d, J(H,H) = 7 Hz,
3 H], 1.25 (s, 6 H), 1.80–1.85 (m, 1 H), 2.05–2.15 (m, 1 H), 3.00–
3.05 [dd, J(H,H) = 13 and 2 Hz, 1 H], 3.75–3.85 [q, J(H,F) =
12 Hz, 2 H], 3.80 (s, 3 H), 6.85–7.10 (AAЈBBЈ, 4 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 13.7 (CH3), 21.5 (CH3), 22.7 (CH3), 31.1,
36.6 (CH2), 43.9 (CH), 55.1 (CH3), 59.8 [q, J(C,C) = 75 Hz, CH2],
79.1, 113.4 (CH), 126.0 [q, J(C,F) = 275 Hz, CF3], 129.2 (CH),
1
13b: H NMR[31] (300 MHz, CDCl3, from the mixture): δ = 1.30–
133.6, 157.7 ppm. IR (neat): ν = 2968, 1614, 1521, 1136, 948,
˜
1.35 [d, J(H,H) = 7 Hz, 3 H], 1.60 (s, 6 H), 3.35–3.40 [q, J(H,H) =
7 Hz, 1 H], 3.80 (s, 3 H), 4.85–4.95 [dd, J(H,H) = 13 and 2 Hz, 2
H], 6.85–7.15 (AAЈBBЈ, 4 H) ppm. 13C NMR (75 MHz, CDCl3,
from the mixture): δ = 20.0 (CH3), 45.6 (CH3), 55.1 (CH3), 109.5
(CH2), 113.5 (CH), 128.1 (CH), 137.1, 149.4, 157.8 ppm. IR of the
817 cm–1. C15H21F3O2 (290.32): calcd. C 62.06, H 7.29; found C
62.3, H 7.3.
Irradiation of 1a in the Presence of Cyclohexene in Acetonitrile: A
solution containing 1a (233 mg, 1.5 mmol, 0.05 m) and cyclohexene
(1.50 mL, 15 mmol, 0.5 m) in acetonitrile was irradiated for 6 h.
The photolysed solution was then evaporated and the resulting resi-
due purified by column chromatography (eluent: cyclohexane/ethyl
acetate, 95:5) to afford 197 mg of trans-1-chloro-2-[4-(dimeth-
ylamino)phenyl]cyclohexane (10a; 55%, oil). The spectroscopic
data are in agreement with the literature.[22] C14H20ClN (237.77):
calcd. C 70.72, H 8.48, N 5.89; found C 70.4, H 8.6, N 5.7.
mixture (neat): ν = 2966, 1511, 1246, 1177, 1035, 833 cm–1.
˜
15b: 1H NMR[32] (300 MHz, CDCl3, from the mixture): δ = 1.60 (s,
3 H), 1.80 (s, 3 H), 1.95 (s, 3 H), 3.80 (s, 3 H), 6.85–7.10 (AAЈBBЈ, 4
H) ppm. 13C NMR[33] (75 MHz, CDCl3, from the mixture): δ =
20.5 (CH3), 21.1 (CH3), 22.0 (CH3), 55.1 (CH3), 113.1 (CH), 113.2,
128.3, 129.3 (CH), 137.7, 157.4 ppm.
In TFE: A solution of 1b (200 μL, 1.5 mmol, 0.05 m) and 2-methyl-
2-butene (1.60 mL, 15 mmol, 0.5 m) in TFE (30 mL) was irradiated
for 14 h and then evaporated. Purification by column chromatog-
raphy afforded 253 mg of a mixture of 15b (48 mg, 18% yield)
and 2-(4-methoxyphenyl)-3-methyl-3-(2,2,2-trifluoroethoxy)butane
(14b; 205 mg, 50% yield). A small amount of 14b was obtained
by further purification of the mixture by column chromatography
(eluent: neat cyclohexane).
In TFE: A solution of 1a (233 mg, 1.5 mmol, 0.05 m) and cyclohex-
ene (1.50 mL, 15 mmol, 0.5 m) in TFE (30 mL) was irradiated for
6 h. Purification by column chromatography (eluent: neat cyclohex-
ane) led to 210 mg of 10a (59% yield).
Irradiation of 1b in the Presence of Cyclohexene: The photolysis of
1b in both acetonitrile and TFE has been described previously by
our group.[18]
1
14b: H NMR (300 MHz, CDCl3): δ = 1.10 (s, 3 H), 1.15 (s, 3 H),
Irradiation of 1a in the Presence of 2-Methyl-2-butene in Acetoni-
trile: A solution of 1a (233 mg, 1.5 mmol, 0.05 m) and 2-methyl-2-
butene (1.60 mL, 15 mmol, 0.5 m) in TFE (30 mL) was irradiated
for 4 h. The photolysed solution was evaporated and the resulting
residue purified by column chromatography (eluent: neat cyclohex-
ane) to afford 180 mg of a mixture of 2a (27 mg, 15% yield) and 4-
(1,2-dimethyl-2-propenyl)-N,N-dimethylaniline (13a; 153 mg, 54%
yield).
1.30–1.35 [d, J(H,H) = 7 Hz, 3 H], 2.80–2.85 [q, J(H,H) = 7 Hz, 1
H], 3.70–3.80 [q, J(H,F) = 8.5 Hz, 2 H], 3.85 (s, 3 H), 6.80–7.20
(AAЈBBЈ, 4 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 15.4 (CH3),
22.2 (CH3), 23.4 (CH3), 48.2 (CH), 55.1 (CH3), 59.6–60.9 [q, J(C,C)
= 34 Hz, CH2], 78.7, 113.0 (CH), 122.5–129.3 [q, J(C,F) = 276 Hz,
CF ], 129.9 (CH), 135.4, 158.0 ppm. IR (neat): ν = 2973, 1611,
˜
3
1513, 1281, 1160, 1036, 970, 832 cm–1. C14H19F3O2 (276.29): calcd.
C 60.86, H 6.93; found C 60.6, H 6.9.
13a: 1H NMR (300 MHz, CDCl3, from the mixture): δ = 1.40–1.45
[d, J(H,H) = 7 Hz, 3 H], 1.70 (s, 3 H), 3.00 (s, 6 H), 3.35–3.45 [q,
J(H,H) = 7 Hz, 1 H], 4.85–4.95 [d, J(H,H) = 14 Hz, 2 H], 6.75–
7.30 (AAЈBBЈ, 4 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 18.7
(CH3), 20.2 (CH3), 40.7 (CH3), 45.5 (CH), 109.1 (CH2), 112.6,
112.7 (CH), 127.9 (CH), 130.0, 149.9 ppm. IR of the mixture
Irradiation of 1a in the Presence of 2,3-Dimethyl-2-butene in Aceto-
nitrile: A solution containing 233 mg of 1a (233 mg, 1.5 mmol,
0.05 m) and 2,3-dimethyl-2-butene (1.80 mL, 15 mmol, 0.5 m) in
acetonitrile (30 mL) was irradiated for 4 h and then evaporated.
Purification by column chromatography (eluent: neat cyclohexane)
afforded 195 mg of N,N-dimethyl-4-(1,1,2-trimethyl-2-propenyl)-
aniline (16a; 64% yield, oil). The spectroscopic data are in agree-
ment with the literature.[22] C14H21N (203.32): calcd. C 82.70, H
10.41, N 6.89; found C 82.5, H 10.3, N 6.7.
(neat): ν = 2929, 1616, 1552, 1281, 1161, 970, 819 cm–1.
˜
In TFE: A solution of 1a (233 mg, 1.5 mmol, 0.05 m) and 2-methyl-
2-butene (1.60 mL, 15 mmol, 0.5 m) in TFE (30 mL) was irradiated
for 6 h and then evaporated. Purification by column chromatog-
raphy (eluent: neat cyclohexane) afforded 187 mg of 3-[4-(dimeth-
In TFE: A solution containing 233 mg of 1a (1.5 mmol, 0.05 m)
and 2,3-dimethyl-2-butene (1.80 mL, 15 mmol, 0.5 m) in TFE
(30 mL) was irradiated for 6 h. The photolysed solution was evapo-
rated and the resulting residue purified by column chromatography
(eluent: neat cyclohexane) to afford 183 mg of 16a (60% yield, oil).
ylamino)phenyl]-2-methyl-3-(2,2,2-trifluoroethoxy)butane
(14a;
43% yield, oil). GC analysis also showed the presence in the pho-
tolysed solution of a small amount of 13a (14 mg, 5% yield based
on GC calibration curve).
Irradiation of 1b in the Presence of 2,3-Dimethyl-2-butene: The pho-
tolysis of 1b in the presence of 2,3-dimethyl-2-butene in both aceto-
nitrile and TFE has been described previously by our research
group.[18]
1
14a: H NMR (300 MHz, CDCl3): δ = 1.15 (s, 6 H), 1.45–1.50 [d,
J(H,H) = 7 Hz, 3 H], 2.75–2.85 [q, J(H,H) = 7 Hz, 1 H], 2.95 (s, 6
H), 3.70–3.85 [q, J(H,F) = 8 Hz, 2 H], 6.75–7.20 (AAЈBBЈ, 4
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 15.3 (CH3), 21.9 (CH3),
23.6 (CH3), 40.6 (CH3), 47.7 (CH), 60.0 [q, J(C,C) = 34 Hz, CH2], DFT Calculations: Optimizations were carried out at the UB3LYP/
79.0, 112.0 (CH), 125.0 [q, J(C,F) = 262 Hz, CF3], 129.6 (CH),
6-31G(d) level of theory by using the Gaussian 03 package.[34] Fre-
Eur. J. Org. Chem. 2011, 3229–3237
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3235

S. Protti, D. Dondi, M. Mella, M. Fagnoni, A. Albini
FULL PAPER
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quency calculations were evaluated at the same level of theory and
in this way the structures reported were certified as minima. The
energies and charges of the solvated cation were evaluated by the
CPCM method[35] using the (in vacuo) optimized geometries with
acetonitrile as solvent and methanol as a model for trifluoro-
ethanol. The solvent cavity was calculated by applying the united
atom topological model to the radii optimized at the HF/6-31G(d)
level of theory. The calculated energies and atomic coordinates are
reported in the Supporting Information.
[12] As an alternative, the dediazoniation of phenethyldiazonium
salts has also been used to generate the phenonium ion, see:
W. A. Bonner, D. D. Tanner, J. Am. Chem. Soc. 1958, 80, 1447–
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[15] See, for example: B. Guizzardi, M. Mella, M. Fagnoni, A. Al-
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Supporting Information (see footnote on the first page of this arti-
cle): Computational data for phenonium intermediates 20–24 and
1H and 13C NMR spectra of compounds 3–19.
Acknowledgments
[16] I. Manet, S. Monti, G. Grabner, S. Protti, D. Dondi, V. Dichia-
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[17] a) V. Dichiarante, M. Fagnoni, Synlett 2008, 787–800; b) A. B.
Penˇenˇory, J. E. Argüello, in: Handbook of Synthetic Photochem-
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Germany, 2010, pp. 319–352; c) M. Fagnoni, Lett. Org. Chem.
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Dr. Alessandra Fallarini is thanked for preliminary investigations
in this area. This work was funded by the CINECA Supercomputer
Center, with computer time granted by the ISCRA ARCAT project
(HP10CZO9W2). Support to S. P. by the Ministero dell’Università
e della Ricerca (MIUR), Rome (FIRB-Futuro in Ricerca 2008 pro-
ject RBFR08J78Q) is gratefully acknowledged.
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[7] Note also that the mechanistic studies of several organic reac-
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Received: March 3, 2011
Published Online: April 21, 2011
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