Photochemical functionalization of allyl benzoates by C-H insertion

Article abstract of DOI:10.1016/j.tet.2013.05.093

The photoreactivity of allyl benzoates, containing an electron-rich double bond, has been explored by irradiation at 305 nm in different solvents. Solvent addition products arising from an insertion of the alpha H-C bonds of THF, dioxane, and i-PrOH to the allylic double bond was realized. The observed reactivity depended on reaction conditions and substitution pattern of the substrate. A DFT study on this unusual reaction was performed allowing the formulation of two mechanistic pathways.

Full text of DOI:10.1016/j.tet.2013.05.093

Tetrahedron 69 (2013) 6065e6069
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Photochemical functionalization of allyl benzoates by CeH insertion
,
,
b
,
c
,
a,b
Ivana Pibiri a b, Antonio Palumbo Piccionello a
, Andrea Pace
,
*
Giampaolo Barone a b, Silvestre Buscemi a
,
,c
a
ꢀ
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Universita degli Studi di Palermo, Viale delle Scienze,
I-90128 Palermo, Italy
b Istituto EuroMediterraneo di Scienza e Tecnologia (IEMEST) e Via E. Amari 123, I-90139 Palermo, Italy
c Istituto di Biofisica, Consiglio Nazionale delle Ricerche, Via U. La Malfa, 153, 90146 Palermo, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
The photoreactivity of allyl benzoates, containing an electron-rich double bond, has been explored by
irradiation at 305 nm in different solvents. Solvent addition products arising from an insertion of the
alpha HeC bonds of THF, dioxane, and i-PrOH to the allylic double bond was realized. The observed
reactivity depended on reaction conditions and substitution pattern of the substrate. A DFT study on this
unusual reaction was performed allowing the formulation of two mechanistic pathways.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 8 March 2013
Received in revised form 2 May 2013
Accepted 20 May 2013
Available online 24 May 2013
Keywords:
Organic photochemistry
CeH insertion
CeC bond formation
DFT
1. Introduction
of perfluoroalkylethylenes in an acetone/i-PrOH mixture, which
occurs with good preparative yields.6
The formation of CeC bonds is one of the most important re-
actions in organic synthesis. Organic chemists have devoted much
effort in order to find and develop new and efficient strategies to
link organic fragments by thermal processes. In this context, the
photochemical approach, despite its great potential, is still an
under-explored synthetic methodology. Photoalkylation reactions
have been reported so far as radical additions to electron-deficient
olefins1 and the proposed reaction pathway usually involves the
photo-generation of radicals by photocatalysts such as aromatic
ketones or decatungstate salts.1,2 In this context, since photo-
addition to olefins can be performed under environmentally
friendly conditions, photochemical reactions can be considered
a ‘green tool’ for the synthetic chemist.2 Many examples are re-
ported in the literature, mainly belonging to the HeC addition
(hydroalkylation reactions) of alkanes, alcohols, amines, and am-
ides to electron-deficient olefins.1e3 Although ethers have been
used less frequently than alcohols as alkylating agents, their photo-
functionalization, activated by tetrabutylammonium decatungstate
(TBADT),4 or TiO25 has also been reported. An interesting example
of this general approach is the easy regioselective photoalkylation
This procedure has also been recently employed in the total
synthesis of a non-peptidal ligand with high-affinity for the human
immunodeficiency virus (HIV) protease inhibitor UIC-940177 and in
the synthesis of (ꢀ)-tetrahydrolipstatin,8 a potent pancreatic lipase
inhibitor. On the other hand, photoaddition reactivity of non-
conjugated alkenes and alkenes bearing an electron-donating
substituent has been explored in the context of HeX addition
(X¼O, N, S, etc.)2 with rare reported examples of hydroalkylation
reactions.9
Within the framework of our ongoing studies on the photo-
reactivity of organic compounds10 we decided to explore the
photo-mediated hydroalkylation reactions of electron-rich olefins,
such as allyl benzoates.
2. Results and discussion
Preliminary irradiations of allyl benzoate 1a at different wave-
lengths (254, 305, or 365 nm) and in different solvents such as
acetone, acetonitrile, DCM, cyclohexane, and THF, revealed the
formation of photoproducts only in the latter media. Screening of
the reaction conditions performed by GCeMS analyses of THF so-
lutions of allyl benzoate after irradiations at different wavelengths,
revealed a fast conversion of 1a at 254 nm, but analyses also
showed the presence of several by-products as a consequence of
photodegradation due to the use of high energy radiation. On the
* Corresponding author. Tel.: þ39 09123897544; fax: þ39 091596825; e-mail
address: antonio.palumbopiccionello@unipa.it (A. Palumbo Piccionello).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.05.093

6066
I. Pibiri et al. / Tetrahedron 69 (2013) 6065e6069
Table 1 (continued)
other hand, only trace amounts of photoproducts were revealed
after prolonged irradiation at 365 nm. Irradiation at 305 nm
allowed good conversion of 1a and the formation of a main pho-
toproduct with a good compromise between substrate conversion
and reaction cleanliness. Thus, preparative scale irradiation of
compound 1a at
matographic separation, compound 2a in 45% isolated yield, as well
as 25% of recovered starting material (Scheme 1).
Starting compound
Solvent
THF
Photoproductsb (yield %)
O
O
Ph
O
Ph
Ph
O
l
¼305 nm for 8 h in THF furnished, after chro-
1d (20%)c
O
O
2d (38%)f
O
O
Ph
O
THF
O
1e (18%)c
O
O
O
2e (40%)f
Ph
O
hν
THF/ 8h
Ph
O
1a
O
2a
THF
THF
NRe
Ph
O
Scheme 1.
1f (90%)c
HO
Moreover, irradiation performed in freshly distilled THF as well
as in commercial THF containing BHT as solvent stabilizer produced
similar results. The formation of compound 2a that can be easily
HO
O
1g
2g (8%)
cRecovered substrate.
interpreted in terms of an insertion of the
a HeC bond of the cyclic
dDetermined by means of GCeMS.
ether into the double bond of the allylic moiety, revealed the fea-
sibility of the desired photo-mediated hydroalkylation reactions of
electron-rich olefins.
We next preliminarily explored the generality of the reaction
performing photoreactions with other solvents and with different
allyl derivatives 1 (Table 1). The formation of compound 3a was ob-
served (35%) during the irradiation of compound 1a in isopropanol.
Interestingly, when compound 1a was irradiated in dioxane under
the same reaction conditions, the solvent addition product 4a was
formed in 39% together with recovered starting material.
fSum of diastereoisomers.
a
Reaction conditions:
Isolated yields.
No reaction.
l
¼305 nm, reaction time 8 h.
b
e
Considering the role of the aromatic moiety, the HeC insertion
reaction was not affected by the presence of an electron-donating
substituent on the benzoate part of the substrate: irradiation of
compound 1b in THF and i-PrOH afforded, respectively, 2b and 3b
in 39% and 36% yields, values comparable to that obtained for
compound 1a. The presence of an electron-withdrawing group,
such as in the case of compound 1c, did not allow the isolation of
addition photoproducts mainly due to the formation of de-
composition mixtures.
Concerning the substitution pattern of the allylic moiety, methyl
substitution did not affect the formation of the corresponding ad-
dition products (see irradiations of compounds 1d and 1e in Table
1), while dimethyl substituted substrate 1f was not able to pro-
duce the corresponding insertion product, likely because of steric
interactions. Finally, also starting from allylic alcohol 1g the pho-
toaddition product 2g was obtained, albeit in very low isolated
yield, likely due to its volatility.
As a general comment, the reaction yields are fair to good,
considering recovered starting material, but unfortunately are re-
duced during work-up and purification, due to the volatility of final
products, as evidenced in the case of compound 2a, by observing
reaction yield determined by means of GCeMS (see Table 1).
The presence of oxygen in the reaction media did not affect the
reactivity since similar results were obtained from irradiations of
1a in either nitrogen- or oxygen-purged THF solutions. Moreover,
the involvement of photoinitiated chain-reaction processes could
be excluded since shorter irradiations (30 and 120 min) followed by
standing in the dark for 12 h did not result in significant substrate
conversion.
Moreover, irradiation performed in the presence of benzophe-
none as a photocatalyst did not affect the reaction. Finally, irradi-
ations performed in the presence of 10 equiv E-piperylene as
a triplet quencher did not produce the photoaddition products. On
the basis of these results we propose the involvement of a triplet
state of the alkene, following a mechanistic pathway different from
the common carbon-centered radical conjugate addition mecha-
nism previously reported for electron-poor olefins.1,2 Since the
coupling of experimental data with a theoretical approach has
Table 1
Products distribution for the irradiation reactionsa
Starting compound
Solvent
Photoproductsb (yield %)
O
O
Ph
O
THF
Ph
O
O
1a (25%)c
2a (45 %, 73%d)
O
O
O
Ph
i-PrOH
Ph
Ph
O
OH
1a (22%)c
3a (35%)
O
O
Ph
O
O
Dioxane
O
O
1a (19%)c
4a (39%)
O
O
O
O
THF
O
MeO
MeO
1b (35%)c
2b (39%)
O
O
O
O
i-PrOH
OH
MeO
MeO
O2N
1b (26%)c
3b (36%)
O
O
THF
NRe
1c (11%)c

I. Pibiri et al. / Tetrahedron 69 (2013) 6065e6069
6067
proven successful to unravel competitive photochemical and
hν
1
[1a]*
thermal reaction pathways,11 we have performed a computational
study at the DFT level for the representative system 1aeTHF, both
in vacuo and in the mimicked THF solvent. The values of the vertical
transition energies of both singlet and triplet states for 1a and THF,
show that only allyl benzoate could be excited under the experi-
mental conditions, with triplet states possibly accessible through
an inter-system crossing (isc) (Table 2). The energies calculated
along the reaction coordinate, and the geometries of the transition
states and intermediates are reported in Table 3, and allowed us to
rationalize several aspects of this unusual reactivity.
1a
isc
3
H
PhCO2
H
H
3
[1a]
THF
H
THF
3
3
H
H
H
PhCO2
PhCO2
H
Table 2
H
H
Vertical excitation energies (kJ/mol (nm)) of singlet (S) and triplet (T) states, cal-
culated in THF solution at the TD-DFT level, for 1a and THF
H
H
O
O
H
1a
THF
3[TS 1a-5]
3[TS 1a-6]
S1
S2
T1
T2
393.4 (304.1)
433.9 (275.7)
337.9 (354.0)
391.7 (305.4)
565.2 (211.7)
623.2 (192.0)
561.3 (213.1)
618.9 (193.3)
3
3
H
H
H
H
PhCO2
PhCO2
H
H
H
H
Table 3
Standard free energy values (
species along the reaction pathway, and activation barriers (
sition states, relative to the given starting compounds, calculated in vacuo and in
THF at 298.15 K
O
D
Gꢁ, kJ/mol) relative to 1aeTHFa for singlet and triplet
Gz, kJ/mol) for tran-
H
O
H
D
3
3
[6]
[5]
Scheme 2. Proposed mechanism for the formation of triplet adducts.
Species
D
Gꢁ in vacuo
D
Gꢁ in THF
1aþTHF
3[1a]þTHF
3[2a]
0.0
0.0
237.5
247.7
ꢀ64.6
211.5
220.9
235.1
242.5
ꢀ64.6
214.5
222.1
the 3[5] pair. This, could explain why photoinitiated chain-reaction
processes were not observed. This, mechanism could be interpreted
in terms of a self-catalyzed reaction that represents a new insight
into the photohydroalkylation of olefins.
2a
3[5]
3[6]
Despite the fact that formation of radical pair 3[5] is more fa-
vored, the competitive formation of radical pair 3[6] could not be
excluded considering the possible involvement of triplet states of
higher energy (see T2 in Table 1), by means of direct formation
through a forbidden transition or after isc.
Transition states
D
Gꢁ in vacuo
D
Gꢁ in THF
D
Gz in vacuo
DG
z in THF
3[TS 1a-5]z
299.7
311.7
299.9
311.8
62.2
74.2
64.8
76.7
3[TS 1a-6]z
a
The standard free energy values calculated for 1aþTHF at the B3LYP/6-
31þþG(d,p) level are ꢀ769.794273 au in vacuo and ꢀ769.802900 au in THF.
3. Conclusions
From the computational analysis of the PES of the reagents
3[1a]þTHF, two potentially competitive pathways were evidenced.
A favorable pathway, with activation barrier of 64.8 kJ/mol, sug-
gests the possible conversion of 3[1a]þTHF to intermediate di-
radical adduct 3[5] (Scheme 2, Fig. 1a) through a hydrogen trans-
fer from the C(2) of THF into the less substituted carbon of the
double bond. A less favorable pathway, with activation barrier of
76.7 kJ/mol, leads to intermediate di-radical adduct 3[6] (Scheme 2,
Fig. 1a) through a hydrogen transfer into the highly substituted
carbon of the double bond.
The photoreactivity of allyl benzoates has been explored by ir-
radiation at 305 nm in different solvents, revealing the feasibility of
an unusual photo-mediated hydroalkylation reaction of electron-
rich olefins with THF, dioxane, and i-PrOH. The observed re-
activity depended on reaction conditions and substitution pattern
of the substrate. The solvent addition product could be interpreted
in terms of an insertion of the
a HeC bonds of the solvent into the
allylic double bond and was interestingly realized in the absence of
additional photocatalysts. Experimental as well computational
studies allowed formulation of two concurrent pathways for the
photohydroalkylation reaction: a self-catalyzed radical mechanism
without chain-reaction propagation and a new mechanism that
essentially presents inverted steps with respect to the common
carbon-centered radical conjugate additions mechanism, usually
invoked for electron-poor olefins.
The formation of 2a can be explained through two alternative or
concurrent pathways, both involving the formation of 20-THF rad-
ical. The formation of radical pair 3[6], through the thermody-
namically less favored pathway, would naturally evolve toward
product 2a by radical coupling and consequential spin multiplicity
change (Scheme 3).
On the other hand, the favored formation of radical pair 3[5]
would need subsequent steps to evolve toward final product 2a.
Indeed, the addition of formed 20-THF radical into 1a, in a similar
fashion to common carbon-centered radical conjugate additions
mechanism, would involve the formation of radical 2[7] through
4. Experimental section
4.1. Instrumentation and chemicals
the easily accessible transition state 2[TS 1a-5]z (
(Scheme 4, Table 4, Fig. 1b). Finally, formation of compound 2a
D
Gz¼45.6 kJ/mol)
IR spectra were registered with a Shimadzu FTIR-8300 in-
strument. 1H and 13C NMR spectra were recorded on a BRUKER 300
Avance spectrometer, operating at 300 and 75 MHz, respectively,
could be ascribed to back hydrogen transfer from the alkyl radical of

6068
I. Pibiri et al. / Tetrahedron 69 (2013) 6065e6069
Fig. 1. (a) Standard free energy profiles along the reaction coordinate of 1a in solution, at 298.15 K. (b) Standard free energy profiles along the reaction coordinate of 1aeTHFꢂ in
solution, at 298.15 K.
3
H
H
4.2. General procedure for preparative photochemical
reactions
PhCO2
PhCO2
H
H
O
Photochemical reactions were carried out in anhydrous solvent
by using a Rayonet RPR-100 photoreactor fitted with 16 Hg lamps
irradiating at 305 nm (in 45 mL Pyrex vessels) and a merry-go-
round apparatus. In the case of analytical scale photoreactions,
qualitative determinations were accomplished by GCeMS analysis.
A sample of the substrate (0.4 g) in the appropriate solvent
(350 mL), apportioned into nine Pyrex tubes, was irradiated for 8 h.
After removal of the solvent, chromatography of the residue
returned starting material and gave the following products (yields
and recovering of starting materials are reported in Table 1).
2a
O
H
3
[6]
Scheme 3. Radical coupling for the formation of compound 2a.
2
PhCO2
2[TS 1a-7]
+
PhCO2
O
O
1a
4.2.1. 3-(Tetrahydrofuran-2-yl)propyl benzoate (2a). 260 mg, 45%
yield; oil; 1H NMR (CDCl3) 8.05 (dt, J¼7.0, 1.5 Hz, 2H, CH arom.), 7.56
(tt, J¼7.0, 1.5 Hz,1H, CH arom.), 7.45 (dt, J¼7.0, 1.5 Hz, 2H, CH arom.),
4.36 (t, J¼6.3 Hz, 2H, OCH2), 3.87 (m, 2H, OCH2), 3.73 (ddd, J¼15.6,
7.5, 6.3 Hz, 1H, OCH), 2.10e1.80 (m, 5H), 1.80e1.60 (m, 2H), 1.50 (m,
1H); 13C NMR (CDCl3) 166.2 (C]O), 132.5 (CH arom.), 130.1 (C
arom.), 129.2 (2CH arom.), 128.0 (2CH arom.), 78.5 (OCH), 67.4
(OCH2), 64.6 (OCH2), 31.8 (CH2), 31.1 (CH2), 25.5 (CH2), 25.4 (CH2);
IR (liquid film) 2955, 2866, 1718, 1452, 1315, 1275, 1113, 1070, 1026,
712 cmꢀ1; MS m/z 206 ([MꢀCO]þ, 5),191 (10),129 (12),112 (15),105
(30), 84 (30), 77 (25), 71 (100),43 (25). Anal. Calcd for C14H18O3: C,
71.77; H, 7.74; O, 20.49. Found: C, 71.65; H, 7.60; O, 20.40.
2
PhCO2
PhCO2
hydrogen
transfer
O
O
2a
2
[7]
Scheme 4. Proposed mechanism for the formation of compound 2a.
Table 4
Standard free energy values (
and product along the reaction pathway, calculated in vacuo and in THF at 298.15 K
D
Gꢁ, kJ/mol), relative to 1aeTHFꢂa for transition states,b
4.2.2. 3-(1,4-Dioxan-2-yl)propyl benzoate (4a). 241 mg, 39% yield;
oil; 1H NMR (CDCl3) 8.00 (br d, J¼8.7, 2H, CH arom.), 7.50 (tt, J¼8.7,
2.7 Hz, 1H, CH arom.), 7.38 (br t, J¼8.7 Hz, 2H, CH arom.), 4.29 (m,
2H, OCH2), 3.74e3.47 (m, 5H, OCH2), 3.24 (br t, J¼12.7 Hz, 1H, OCH),
2.03e1.65 (m, 2H), 1.58e1.60 (m, 2H); 13C NMR (CDCl3) 166.4 (C]
O), 132.8 (CH arom.), 130.3 (C arom.), 129.5 (2CH arom.), 128.3 (2CH
arom.), 74.8 (OCH), 71.1 (OCH2), 66.7 (OCH2), 66.4 (OCH2), 64.7
(OCH2), 28.1 (CH2), 24.5 (CH2); IR (liquid film) 2956, 2852, 1714,
1602, 1451, 1314, 1275, 1099,, 1070, 713 cmꢀ1; MS m/z 219 ([Mꢀ1]þ,
5), 128 (50), 105 (100), 85 (60), 77 (50), 71 (25), 59 (30), 43 (25).
Anal. Calcd for C14H18O4: C, 67.18; H, 7.25; O, 25.57. Found: C, 67.35;
H, 7.30; O, 25.30.
Species
D
Gꢁ in vacuo
D
Gꢁ in THF
1aþTHFꢂ
3[TS 1a-7]z
3[7]
0.0
46.2
0.0
45.6
ꢀ44.4
ꢀ44.6
a
The standard free energy values calculated for 1aþTHFꢂ at the B3LYP/6-
31þþG(d,p) level are ꢀ769.149619 au in vacuo and ꢀ769.158237 au in THF; the
thermal correction to the Gibbs free energy is 0.225066 au.
b
Here the activation free energy,
the transition state.
D
Gz, coincides with the standard free energy of
with TMS as an internal standard. GCeMS determinations were
carried out on a Shimadzu QP-2010. Flash chromatography was
performed by using silica gel (Merck, 0.040e0.063 mm) and mix-
tures of ethyl acetate and petroleum ether (fraction boiling in the
range of 40e60 ꢁC) in various ratios. All solvents and compounds
1aeg were obtained from commercial sources. Compounds 2g12
and 3a13 had physical characteristics identical to those of the
compounds prepared by alternative procedures as reported in the
literature.
4.2.3. 3-(Tetrahydrofuran-2-yl)propyl 4-methoxybenzoate
(2b). 215 mg, 39% yield; oil; 1H NMR (CDCl3) 8.00 (dt, J¼9.0,
2.7 Hz, 2H, CH arom.), 6.92 (dt, J¼9.0, 2.7 Hz, 2H, CH arom.), 4.34 (t,
J¼6.5 Hz, 2H, OCH2), 3.89 (m, 2H, OCH2), 3.75 (m, 1H, OCH),
2.10e1.40 (m, 8H); 13C NMR (CDCl3) 166.2 (C]O), 163.1 (C arom.),
131.4 (2 CH arom.), 122.7 (C arom.), 113.4 (2CH arom.), 78.7 (OCH),
67.5 (OCH2), 64.5 (OCH2), 55.2 (OCH3), 31.9 (CH2), 31.2 (CH2), 25.6

I. Pibiri et al. / Tetrahedron 69 (2013) 6065e6069
6069
(CH2), 25.5 (CH2). IR (liquid film) 2956, 2867, 1712, 1607, 1512, 1462,
1316, 1257, 1168, 1102, 1031, 849, 772, 697, 613 cmꢀ1; MS m/z 236
([MꢀCO]þ, 5), 221 (5), 152 (20), 135 (70), 112 (25), 84 (100), 77 (20),
71 (70), 43 (30). Anal. Calcd for C15H20O4: C, 68.16; H, 7.63; O, 24.21.
Found: C, 67.95; H, 7.60; O, 24.30.
vibration frequency analysis to the DFT energy calculated both in
vacuo and in THF solution. All calculations were performed by the
Gaussian 09 program package.19
Acknowledgements
4.2.4. 4-Hydroxy-4-methylpentyl 4-methoxybenzoate (3b). 189 mg,
36% yield; oil; 1H NMR (CDCl3) 8.00 (dt, J¼9.0, 2.1 Hz, 2H, CH arom.),
6.92 (dt, J¼9.0, 2.1 Hz, 1H, CH arom.), 4.32 (t, J¼6.3 Hz, 2H, OCH2),
Financial support by the University of Palermo is gratefully
acknowledged.
3.86 (s, 3H, OCH3), 1.56 (t, J¼6.3 Hz, 2H, CH2), 1.26 (s, 6H, CH3); 13
C
Supplementary data
NMR (CDCl3) 166.3 (C]O), 163.2 (C arom.), 131.5 (2CH arom.), 122.7
(C arom.),113.5 (2CH arom.), 70.6 (C), 65.0 (OCH2), 55.3 (OCH3), 39.9
(CH2eC), 29.2 (2CH3), 23.8 (CH2). IR (liquid film) 3400, 2967, 2935,
2843, 1711, 1607, 1512, 1317, 1259, 1169, 1104, 1030, 848, 772, 697,
614 cmꢀ1; MS m/z 224 ([MꢀCO]þ, 5), 177 (5), 152 (60), 135 (100),
107 (15), 92 (20), 85 (25), 77 (20), 59 (30), 43 (40). Anal. Calcd for
C14H20O4: C, 66.65; H, 7.99; O, 25.37. Found: C, 66.60; H, 7.90; O,
25.44.
NMR spectra of compounds 2e4 and coordinates of all com-
puted species. Supplementary data associated with this article can
be found in the online version, at http://dx.doi.org/10.1016/
j.tet.2013.05.093. These data include MOL files and InChiKeys of the
most important compounds described in this article.
References and notes
4.2.5. 4-(Tetrahydrofuran-2-yl)butan-2-yl benzoate (2d). 214 mg,
38% yield; oil; 1H NMR (CDCl3) 8.05 (dt, J¼7.0, 1.5 Hz, 2H, CH arom.),
7.50 (tt, J¼7.0, 1.5 Hz, 1H, CH arom.), 7.40 (br t, J¼7.0 Hz, 2H, CH
arom.), 5.16 (m, 1H, OCH), 3.81 (m, 2H, OCH2), 3.67 (m, 1H, OCH),
2.00e1.35 (m, 8H), 1.30 (d, J¼7.2 Hz, 3H, CH3); 13C NMR (CDCl3)
166.0 (C]O), 132.6 (CH arom.), 130.6 (C arom.), 129.3 (2CH arom.),
128.1 (2CH arom.), 78.9 and 78.6 (OCH), 71.5 and 71.2 (OCH), 67.5
(OCH2), 32.8 and 32.6 (CH2), 31.5 and 31.2 (CH2), 29.5 (CH2), 25.5
(CH2), 19.9 (CH3). IR (liquid film) 2933, 2865, 1714, 1602, 1450, 1313,
1277, 1099, 1070, 1026, 713 cmꢀ1. MS m/z 220 ([MꢀCO]þ, 5), 105
(40), 84 (55), 77 (25), 71 (100), 43 (25). Anal. Calcd for C15H20O3: C,
72.55; H, 8.12; O, 19.33. Found: C, 72.40; H, 7.98; O, 19.48.
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4.2.6. 3-(Tetrahydrofuran-2-yl)-2-methylpropyl
benzoate
(2e). 225 mg, 40% yield; oil; 1H NMR (CDCl3) 8.05 (dt, J¼7.0, 1.5 Hz,
2H, CH arom.), 7.50 (tt, J¼7.0, 1.5 Hz, 1H, CH arom.), 7.40 (br t,
J¼7.0 Hz, 2H, CH arom.), 4.12 (m, 2H, OCH2), 3.85 (m, 2H, OCH2),
3.65 (m, 1H, OCH), 2.16e1.16 (m, 7H), 1.31 (d, J¼7.2 Hz, 3H, CH3); 13
C
NMR (CDCl3) 166.4 (C]O), 132.7 (CH arom.), 130.3 (C arom.), 129.4
(2CH arom.), 128.2 (2CH arom.), 69.9 (OCH), 69.2 (OCH2), 67.5 and
67.4 (OCH2), 39.4 and 39.3 (CH2), 31.9 and 31.7 (CH2), 30.6 and 30.4
(CH2), 25.5 and 25.4 (CH2), 17.6 and 16.8 (CH3). IR (liquid film) 2874,
1718, 1602, 1451, 1314, 1272, 1176, 1099, 1070, 1027, 712 cmꢀ1. MS m/
z 220 ([MꢀCO]þ, 5), 105 (35), 84 (35), 77 (30), 71 (100), 43 (25).
Anal. Calcd for C15H20O3: C, 72.55; H, 8.12; O, 19.33. Found: C, 72.42;
H, 8.00; O, 19.55.
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The geometry of the molecular species considered, shown in
Schemes 3 and 4, was fully optimized in the singlet or in the triplet
spin state, by using the hybrid unrestricted DFT B3LYP functional14
and the 6-31þþG(d,p)15 basis set. Vertical excitation energies of
THF and 1a, in THF solution, was calculated using the time-
dependent DFT (TD-DFT) method,16 at the same level of theory.
Transition-state structures were found by the synchronous transit
guided quasi-Newton method.17 Vibration frequency calculations,
within the harmonic approximation, were performed on each op-
timized structure, to confirm that its energy was a true minimum or
a first order saddle point (for transition states) on the potential
energy surface. Solvent effects were evaluated by performing single
point calculations on the optimized structures, with the implicit
THF solvent reproduced by the conductor-like polarized continuum
model (CPCM).18 The standard Gibbs free energy, at 298.15 K, of
each energy minimum structure, both in vacuo and in THF solution,
was calculated by adding the thermal correction obtained by
18. Barone, V.; Cossi, M. J. Phys. Chem. A 1998, 102, 1995.
19. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Na-
katsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng,
G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery,
J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K.
N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; A., Rendell;
Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene,
M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.;
Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.;
Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dan-
€
nenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.;
Cioslowski, J.; Fox, D. J.. Gaussian 09, Revision A.1; Gaussian, Inc.: Wallingford
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