The reaction of biphenyl radical anion and dianion with alkyl fluorides. From ET to SN2 reaction pathways and synthetic applications

Article abstract of DOI:10.1016/j.tet.2009.09.027

The reaction of dilithium biphenyl (Li₂C₁₂H₁₀) with alkyl fluorides has been studied from the point of view of the distribution of products. Two main reaction pathways, the nucleophilic substitution (S_N2) and the electron transfer (ET), can compete to yield the same alkylation products in what is known as the S_N2-ET dichotomy. S_N2 seems to be the main mechanism operating with primary alkyl fluorides (n-RF). Alkylation proceeds in good yields, and the resulting alkylated dihydrobiphenyl anion (n-RC₁₂H₁₀Li) can be trapped with a second conventional electrophile (E⁺) affording synthetically interesting dearomatized biphenyl derivatives (n-RC₁₂H₁₀E). The reaction gives a higher amount of ET products as we move to secondary (s-RF) and to tertiary alkyl fluorides (t-RF), in which case the mechanism seems to be dominated by ET. In this case, alkylation by radical coupling is still feasible, giving access to the synthesis of t-RC₁₂H₁₀E, although in lower yields. A rational interpretation of this S_N2-ET dichotomy is given on the basis of the full distribution of products observed when 5-hexenyl fluoride and 1,1-dimethyl-5-hexenyl fluoride were are used as radical probes in their reaction with Li₂C₁₂H₁₀ and LiC₁₂H₁₀.

Full text of DOI:10.1016/j.tet.2009.09.027

Tetrahedron 65 (2009) 10769–10783
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
The reaction of biphenyl radical anion and dianion with alkyl fluorides.
From ET to SN2 reaction pathways and synthetic applications
*
*
´
´
Henoc Perez, Cristobal Melero, Albert Guijarro , Miguel Yus
´
´
´
Departamento de Qu´ımica Organica, Facultad de Ciencias and Instituto de Sıntesis Organica (ISO), Universidad de Alicante, Apdo. 99, 03080 Alicante, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 July 2009
Received in revised form 24 August 2009
Accepted 7 September 2009
Available online 11 September 2009
The reaction of dilithium biphenyl (Li2C12H10) with alkyl fluorides has been studied from the point of view of
thedistribution of products. Two mainreactionpathways, the nucleophilicsubstitution(SN2)and theelectron
transfer (ET), can compete to yield the same alkylation products in what is known as the SN2–ET dichotomy.
SN2 seems to be the main mechanism operating with primary alkyl fluorides (n-RF). Alkylation proceeds in
good yields, and the resulting alkylated dihydrobiphenyl anion (n-RC12H10Li) can be trapped with a second
conventional electrophile (Eþ) affording synthetically interesting dearomatized biphenyl derivatives
(n-RC12H10E). ThereactiongivesahigheramountofETproductsaswemovetosecondary(s-RF)andtotertiary
alkyl fluorides (t-RF), in which case the mechanism seems to be dominated by ET. In this case, alkylation by
radicalcoupling isstillfeasible, givingaccesstothesynthesisof t-RC12H10E, althoughinloweryields. Arational
interpretation of this SN2–ET dichotomy is given on the basis of the full distribution of products observed
when5-hexenyl fluorideand 1,1-dimethyl-5-hexenyl fluoridewereareusedasradicalprobes intheir reaction
Keywords:
Biphenyl radical anion
Biphenyl dianion
Alkyl fluorides
Dearomatization
SN reaction
with Li2C12H10 and LiC12H10
.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
to SHE.4 This allows in principle the highest reduction power in co-
ordinating solvents.5 Biphenyl (1, C12H10) has the highest first re-
ductionpotential Eꢀ1 (giving rise to the radical anion), and the second
1.1. The radical anion and dianion of biphenyl
higher Eꢀ (which affords the dianion) among polycyclic arenes:
2
Radical anions and dianions of aromatic hydrocarbons of high
reduction potential, such as naphthalene or biphenyl, should be
considered among the strongest ET (electron transfer) reagents in
solution.1 They can be prepared, inter alia, by direct reaction of the
aromatic hydrocarbon with an alkali metal. These anionic species
have very high energy electrons, which are also highly delocalized
Eꢀ ¼ꢁ2.68 V, Eꢀ ¼ꢁ3.18 V, in Me2NH versus Ag/AgCl.6 It is impor-
1
2
tant noticing that these values rival with those of lithium metal itself,
both in water and in THF, for which similar values are reported.5 In
spite of the imprecision inherent to the comparison of electro-
chemical data obtained from different sources under different ex-
perimental conditions, it is evident that there is only a narrow
window for a feasible double reduction of biphenyl in solution. In-
deed, the information found in the literature regarding the existence
of the biphenyl dianion is ambiguous in that respect. The biphenyl
dianion, 1-Li2 (Li2C12H10) was suggested in early studies as a com-
ponent of the Li(s)–biphenyl solutions of stoichiometry 2:1 in THF,
and was used for reductive-cleavage applications akin to Li(s).7 Since
1-Li2 was not isolated or characterized in this work, the idea that
some of the Liþ in solution could come from side reactions prevailed.
Further studies on Raman spectroscopy reported the view that the
dianion of biphenyl was not a component of biphenyl–alkali metal
solutions, inparticular, in the case of sodium.8 Later, descriptive work
of the biphenyl dianion was reported, dealing with the 1H NMR and
13C NMR of 1-Li2 (Li2C12H10) at ꢁ80 ꢀC in THF-d8.9 In the solid phase
there is better consensus. The UV and IR and Raman spectra of dif-
ferent alkali metal salts of biphenyl in sublimated layers and code-
posits are described by different groups.10 We have observed
previously that, in the presence of an excess of Li(s), naphthalene is
in an extended
p-cloud that spreads all over the molecule. This
determines much of the reactivity displayed by these species,
which is often dominated by ET to acceptors and reminiscent of the
alkaline metal they originated from. Applications of these alkali
metal-like solutions are well developed. Indeed, the use of naph-
thalene, biphenyl or alkylated derivatives (such as 4,40-di-tert-
butylbiphenyl) as an ET mediator in Li(s) reductions has been shown
to be advantageous over the direct, non catalyzed Li(s) reduction,2
and this has been rationalized by means of a quantitative consid-
eration of the electron transfer kinetics involved.3
Lithium is the preferred alkali metal for these chemical re-
ductions since the pair Li(s)/Liþ(H2O) is the most negative among alkali
metals, with a standard potential Eꢀ
¼ꢁ3.04 V, in water relative
(Li/Liþ)
* Corresponding authors.
E-mail addresses: aguijarro@ua.es (A. Guijarro), yus@ua.es (M. Yus).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.027

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H. Pe´rez et al. / Tetrahedron 65 (2009) 10769–10783
doubly reduced in THF or better in THP to its dianion,11 and this has
been substantiated with the determination of the crystal structure of
a first hint suggesting a special behavior of alkyl fluorides was antic-
ipated by Eberson.17 He observed the failure of the alkyl fluorides to
conform in a reasonable way with the Marcus theory of ET, which
adequately fitted the ET reaction between arene radical anions and
the rest of alkyl halides (RI, RBr, and RCl). The thermodynamic/elec-
trochemical data needed (e.g., the unavailable Eꢀ of RX) were esti-
mated from indirect thermodynamic measures, according to the
method given by Hush.18 After being overlooked for two decades,
recent studies of competitive kinetics on lithium naphthalene
(LiC10H8) and dilithium naphthalene (Li2C10H8) confirmed an ET re-
activityprofilewithalkyl chlorides (n-, s-, andt-octyl chlorides), while
revealed an apparent mechanistic shift toward the SN2 when alkyl
fluorides (n-, s-, and t-octyl fluorides) were employed as electron
acceptors.19 The reactivity was shown to decrease in the order pri-
mary>secondary>tertiary for reactions of octyl fluorides in both the
naphthalene radical anion and dianion, just the opposite behavior
that would be intuitively expected if ET was the main process.
the naphthalene dianion, (LiþTMEDA)2C10H8ꢁ2, obtained by direct
12
reduction of naphthalene with Li(s)
.
Based on reduction potential
criteria,1 biphenyl (1) would be also expected to be reduced to the
corresponding dianion (1-Li2) at least to some extent under similar
conditions, according to Scheme 1.13
–2
•–
Li(s)
Li(s)
Li+
2Li+
THF
THF
1-Li2
1
1-Li
Scheme 1.
In this paper we report on the reactivity of biphenyl radical
anion and dianion with different (primary, secondary, and tertiary)
alkyl fluorides in order to establish the mechanistic and synthetic
aspects of these reactions.
2. Results and discussion
We want to report here the differences in chemical reactivity
between the lithium salts of biphenyl radical anion (LiC12H10, 1-Li)
and its dianion (Li2C12H10, 1-Li2), specifically their differences when
reacting with alkyl fluorides as an exampleof poor electron acceptors.
The synthetic applications derived from this study are also evaluated.
1.2. Alkyl fluorides as electron acceptors
The carbon–fluoride bond cannot be electrochemically reduced
below the solvent cut-off limit.14 Solvents or supporting electrolytes
are invariably reduced at lower potentials than that required for an
alkyl fluoride, therefore there are no reports of cathodic reductions of
regular alkyl fluorides by electrochemical means. They can however
be the electron acceptor counterpart in homogeneous reactions with
arene radical anions as ET reagents. In this regard, the alkyl halide
series including alkyl fluorides (RI, RBr, RCl, and RF) has been the
subject of numerous studies in their reactions with arene radical
anions.15 A widely accepted mechanism of reaction for alkyl halides
has been described in identical terms for all alkyl halides, including
alkyl fluorides.16 It involves ET from the arene radical anion and dis-
sociation of the alkyl halide with generation of the alkyl radical. Thus,
the reaction of alkyl halides (R–X) with sodium naphthalene affords
similar crude products mainly consisting in mixtures of reduction (R–
H) and coupling products (R–C10H9, R2C10H8), regardless the nature of
X (F, Cl, Br or I). According to the authors, the lack of effect of halogen
variation onthe distribution ofproducts mitigates the possibilityofan
SN2 reaction pathway.16 This statement remained unchallenged until
2.1. Previous studies
Some aspects of the reactivity of these species (1-Li, 1-Li2), pos-
tulated as coexisting in more or less extension in solutions con-
taining biphenyl and an excess of an alkali metal, have already been
reported, in part as a preliminary communication.20 For instance,
1-Li2 reacts with terminal alkenes, affording dearomatized carboli-
thiationproducts, which can be further functionalized in subsequent
steps.21 Instead, 1-Li is unreactive under the same reaction condi-
tions. Analogous results were obtained for lithium naphthalene
dianion and the corresponding radical anion.21 The reaction is not an
ET process, but rather a nucleophilic attack to the alkene resulting
a carbolithiation. Lithium naphthalene radical anion and dianion
were also studied in concern with their roles with the mechanism of
the arene-catalyzed lithiation.11 Also, the reaction of a large number
of dianions of polycyclic aromatic hydrocarbons (PAHs) with alkyl
fluorides provided a route to alkylated dihydro-PAHs, which was
+
H2O
–2
Li+
2a
2a'
(33%)
F
2Li+
(48%)
THF, 0 °C
H
D
D2O
H
1-Li2
D
I
+
2a-D
2a'-D
(31%)
(47%)
Scheme 2. Alkylation of dilithium biphenyl (Li2C12H10) with n-fluorooctane. Yields were determined by quantitative GLC using pure isolated products for the calibration curve and
dodecane as internal standard. 4-Deuterio-1-octyl-1,4-dihydrobiphenyl (2a-D, 47%, 53:47 dr, >98.5% deuterium incorporation) and 2-deuterio-1-octyl-1,2-dihydrobiphenyl (2a0-D,
31%, 62:38 dr, >99.8% deuterium incorporation) were obtained using D2O for deuterolysis (diastereomeric ratio by 1H NMR and 13C NMR, deuterium incorporation by MS and 1H
NMR, natural isotopic distribution corrected). Product characterization: Ref. 22.

H. Pe´rez et al. / Tetrahedron 65 (2009) 10769–10783
10771
complementary to the classical Birch reductive alkylation of PAHs
since a different set of regioisomers was obtained.22
n-octane (95%), with only trace amounts of 2aþ2a0 by quantitative
GLC (Scheme 3).
2.2.2. Studies with a primary radical probe: 5-hexenyl fluoride. The
use of 5-hexenyl radical probes was seen as an obvious choice to
obtain data more sensible to the mechanism of the reactions. 6-
Fluoro-1-hexene was prepared and used as alkylating reagent, in
search for potential radical reaction pathways. The results are col-
lected in Scheme 4 and Table 1. When 6-fluoro-1-hexene was
reacted with an equivalent of 1-Li2 in THF at 0 ꢀC (formal [1-
Li2]¼0.2 M), the reaction crude afforded the non-rearranged
products 2b and 2b0 in 75% overall yield, while the rearranged
(cyclized) products 2c and 2c0 could not be detected by GLC (Table 1,
entry 3). To confirm this finding beyond doubt, 2c and 2c0 were
synthesized directly from fluoromethylcyclopentane by reaction
with 1-Li2 (72% overall yield).22 The pure compounds were used as
control in GLC analyses. The amounts of 2c and 2c0 remained zero
(undetectable) in experiments of dilution with formal [1-Li2]¼0.1,
0.05 and 0.01 M. On the other hand, the radical anion 1-Li afforded
mainly reduction products (3 and 4) in 92% overall yield, with
a clear prevalence of the rearranged product (methylcyclopentane
4, 91%, Table 1, entry 2). This reaction had to be carried out in THP
since in THF a complete overlap of 4 by the solvent peak occurred.
In spite of the information provided by these data regarding major
products, the overall picture including the yields of the minor
2.2. Reactions with primary alkyl fluorides
2.2.1. Differences in the reactivity of 1-Li and 1-Li2 with a primary
alkyl fluoride. The reaction of a solution of biphenyl with an excess of
Li(s) powder in THF at 0 ꢀC is assumed to afford lithium biphenyl
dianion (1-Li2, deep dark blue) in an unknown concentration, which
is used throughout this work as such. Its reactionwith n-fluorooctane
affords, after hydrolysis with water, a mixture of two regioisomers 2a
and 2a0 in 81% overall yield (Scheme 2). Further support of the par-
ticipation of intermediate I in Scheme 2 was obtained from deuter-
olysis experiments. Deuterolysis employing D2O afforded 2a-D and
2a0-D in 78% overall yield with excellent deuterium incorporation
(see footnotes in Scheme 2). It points toward the presence of a living
dianionic species in the reaction medium that is alkylated by n-flu-
orooctane, in agreement with Scheme 2.22
Still, the main evidence of the participation of the dianion comes
from the analysis of the distribution of products in the absence of
dianionic biphenyl. The analogous reaction carried out using the
radical anion of biphenyl (1-Li, LiC12H10) has a very different out-
come. Using a substoichiometric amount of Li(s) with respect to
biphenyl in THF at 0 ꢀC, a deep dark-blue solution of 1-Li is gener-
ated. Using this reagent, n-fluorooctane is mainly reduced to
•–
i.
F
Li+
2a (<1%)
2a'(<1%)
+
+
THF, 0 °C
ii. H2O
(95%)
1-Li
Scheme 3. Reaction of lithium biphenyl radical anion (LiC12H10) with n-fluorooctane affords octane as the main reaction product, consistent with an ET mechanism. Yields were
determined by quantitative GLC using pure commercial and isolated products for the calibration curve and n-dodecane as internal standard.
i. 1-Li or 1-Li2
2b
+
2c
+
+
F
THF or THP, 0 °C
ii. H2O
3
4
2b'
Scheme 4.
2c'
Table 1
Distribution of products from Scheme 4a,b,c
Solvent
2b
2b0
2c
2c0
3
4
Total
1
2
3
1-Li
THF
THP
THF
1.6ꢂ1
0.6ꢂ1
45ꢂ8
1ꢂ0.9
0.4ꢂ0.9
30ꢂ10
0
0
0
0
0
0
7ꢂ4
dd
d
93
d
1.4ꢂ0.6
91ꢂ2
1-Li2
2ꢂ1.7
dd
a
Reactions performed by addition of the halide (0.2 mmol diluted in THF or THP at 0 ꢀC, 30 min) to a 0.2 M solution of 1-Li or 1-Li2 in THF or THP at 0 ꢀC and hydrolysis at low
temperature (ꢁ80 ꢀC), followed by immediate GLC analysis.
b
Yields (%) followed by standard deviations were the average of 3–7 determinations (relative standard deviation, rsd¼2–33% for major components), determined by
quantitative GLC using pure isolated or commercially available compounds and n-decane as internal standard. Yield of coupling products were contrasted with 400 MHz 1H
NMR yields using N,N-diphenyl formamide as internal standard.
c
Product characterization: Ref. 22.
Hidden behind the solvent peak.
d

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H. Pe´rez et al. / Tetrahedron 65 (2009) 10769–10783
components proved to be very disperse in nature (relative standard
deviations (rsd) of the minor yields spanning 57–225%) and very
sensitive to small, undefined changes. A complete kinetic study of
these reactions as a function of the concentration of 1-Li or 1-Li2
was initially considered, but the overall results did not show well
defined trends and was later dismissed given the lack of accuracy,
especially in the determination of minor, yet key products. In-
terestingly, this erratic behavior had already been reported in the
past by other groups, with no given explanation.16c It seems that the
complexity of these blue solutions and their changing nature as
a function of the concentration may play an important role in this
misleading behavior.
silicon), but it was not so with protons or deuterons from water, as
seen before (Scheme 2). When water or deuterium oxide was used
as the electrophile, together with the expected mixture of 1,4-di-
substituted deuterated products 2a and 2a-D, the corresponding
mixture of 1,2-disubstituted deuterated adducts 2a0 and 2a0-D was
also isolated (Scheme 2). It is well known that the cyclohexadienyl
anion is kinetically more reactive at the central position (e.g., C(4) of
I in Scheme 2).23 This carbon supports a higher coefficient in the
HOMO of the anion. However, for the highly polarized H–O (or D–
O) bond of water (or D2O), the protonation step may be primarily
controlled by electrostatic interactions. The density of charge is
more equally distributed between the C(2), C(4), and C(6) positions
than the values for these atoms in the HOMO of I.20 Therefore a loss
of selectivity is expected in a reaction pathway driven by polar
interactions.
2.2.3. Synthetic applications derived from 1-Li2 and n-alkyl fluo-
rides. The results described in Schemes 2 and 4 leave an open door
for potential synthetic applications. A second electrophile (Eþ) can
be added to the intermediate of alkylation (e.g., I in Scheme 2),
giving rise to doubly functionalized dearomatized biphenyl de-
rivatives according to Scheme 5 and Table 2.
2.3. Reactions with secondary and tertiary alkyl fluorides
We next explored the potential use of this synthetically ap-
pealing methodology of alkylation/dearomatization for the case of
secondary and tertiary alkyl fluorides. As the substrates become less
prone to undergo SN2 (i.e., with secondary and tertiary RF), the ET
pathway should gain share and eventually become dominant. This
would limit in principle the synthetic utility of the process. How-
ever, secondary and tertiary radicals generated from a hypothetic ET
step are reduced to carbanions with increasing difficulty, so they
should also tend to couple with the biphenyl radical anion (1-Li,
always present in the reaction media) in greater extension than
their primary counterparts. This alkylation by coupling of radicals
affords, in principle, the same alkylated intermediates than a direct
nucleophilic substitution, in what is called the SN2–ET dichotomy.
The final outcome is described below as an evolution from SN to ET
reaction pathways as we move from primary to secondary to ter-
tiary alkyl fluorides. The experimental data that follow show that
the yields of the alkylation products are indeed lower than those
reported for primary alkyl fluorides, and a diminished regiochem-
ical control is observed with tertiary alkyl fluorides.
E
i. Li(s), THF, rt
ii. RCH2F, 0 °C
R
iii. E+
iv. H2O
1
2d-k
Scheme 5.
Thus, the reaction of biphenyl (1) with an excess of lithium
powder (ca. 1:12 molar ratio) in THF at room temperature gave
a deeply colored dark-blue solution containing the dianion 1-Li2,
which was alkylated with a primary alkyl fluoride (RCH2F: n-C8H17F,
c-C5H9CH2F, CH2]CH(CH2)4F; 1:1.1 molar ratio, 0 ꢀC, 30 min). The
resulting mixture was then treated with a conventional electrophile
[Eþ: n-C4H9Br, Et2CO, Me2C(O)CH2, i-Pr3SiCl; 1:1.1 molar ratio,
ꢁ78 ꢀC, 15 min], affording after final hydrolysis with water (ꢁ78 ꢀC
to rt) the corresponding 1,4-disubstituted compounds 2d–k, as
a mixture of cis/trans-diastereomers (Scheme 5 and Table 2).
The results reported in entries 7 and 8 back up the previously
reported behavior with radical clocks. The reaction of 1-Li2 with 6-
fluoro-1-hexene (Table 2, entries 7 and 8) affords good and fair
yields of the expected products (86% of 2j and 58% of 2k). The cor-
responding cyclopentylmethyl rearranged products (i.e., products
2h and 2i, which were prepared from fluoromethylcyclopentane:
Table 1, entries 5 and 6) could not be detected in the reaction crudes,
at least within the detection limits of GLC. Again, this points toward
a bimolecular substitution reaction as the key step of the process,
rather than an ET reaction from the dianion intermediate 1-Li2 to 6-
fluoro-1-hexene. After coupling with the primary alkyl fluoride, the
resulting intermediate of type I reacts regio but not stereo-
selectively with the conventional electrophile to give, after hydro-
lysis, a cis/trans-mixture of the 1,4-disubstituted diastereomers 2.
From a preparative point of view it is worthy to note that both di-
astereomers could be separated by column chromatography in all
cases except for the minor components trans-2f, trans-2g (Table 2,
entries 3 and 4), which were contaminated with variable amounts of
the major cis-diastereomer (ca. 30% for trans-3f) or other byprod-
ucts (ca. 20% for trans-3g). The stereochemistry of both cis and trans
diastereomers was assigned in all cases by NMR experiments, spe-
cially by means of NOESY measurements.
2.3.1. Reaction of a sec-octyl fluoride and a tert-octyl fluoride with
1-Li2. The reaction of a solution of biphenyl with an excess of Li(s) in
powder in THF at 0 ꢀC (1-Li2) followed by the addition of 2-fluo-
rooctane or 2-fluoro-2-methylheptane afforded, after quenching
with CH3CN and then water, a mixture of the corresponding al-
kylation products 5a (82%) and 6a (45% as a mixture of p-6a and
m-6a), along with the corresponding n-octane and isooctane, re-
spectively (Scheme 6). The use of CH3CN as a Brønsted acid weaker
than water for the protonation step maximizes the formation of
a major regioisomer of protonation, simplifying considerably the
analysis of the crude mixture and separations.22 The regiochemis-
try of alkylation is different for both substrates. We have observed
that secondary alkyl fluorides alkylate the 1-position of biphenyl,
while tertiary alkyl fluorides are directed to the 4-position and, in
less extent, to the 3-position, in considerably lower yields. Again,
the generation of two adjacent quaternary centers is disfavored.
The reacting carbon of the biphenyl moiety shifts to the less hin-
dered 4-position (and 3-position). This general behavior is main-
tained with other secondary and tertiary alkyl fluorides. Whether
this regiochemical shift is connected or not with a shift in the main
operating mechanism is still to be determined. But at this point it is
tempting to attribute the decreased regioselectivity observed with
tertiary alkyl fluorides to a poor selective mechanism of radical
coupling.
Regarding the regiochemistry displayed at the electrophilic
capture, Eþ is invariably introduced at the C(4) position yielding 1,4-
dihydrobiphenyl derivatives. This is a special feature of the cyclo-
hexadienyl anion (I) in its reaction with an electrophilic carbon (or
2.3.2. Studies with a tertiary radical probe: 1,1-dimethyl-5-hexenyl
fluoride. The use of a radical probe was again considered to study
this reaction. 6-Fluoro-6-methylhept-1-ene (7) was synthesized

H. Pe´rez et al. / Tetrahedron 65 (2009) 10769–10783
10773
Table 2
Preparation of compounds 2d–l according to Scheme 3
Entry
RF, Eþ
Products 2d–k
Structurea
No.
Yieldb
cis/transc
0.9:1
tR valuesd
1
n-C8H17F, n-C4H9Br
2d
98
14.11:14.18
OH
OH
2
n-C8H17F, Et2CO
2e
61
1:0.7
15.69:15.84
3
4
5
n-C8H17F, Me2C(O)CH2
2f
58
82
81
1:0.4
1:0.4
15.15:15.21
16.77:17.00
13.38:13.48
i
Si Pr3
n-C8H17F, i-Pr3SiCl
2g
c-C5H9CH2F, n-C4H9Br
2h
0.9:1
OH
6
7
c-C5H9CH2F, Et2CO
2i
59
86
58
0.5:1
0.9:1
1:0.6
14.70:14.87
13.48:13.62
14.57:14.77
CH2]CH(CH2)4F, n-C4H9Br
2j
OH
8
CH2]CH(CH2)4F, Et2CO
2k
a
Both diastereomers of all compounds 2d–k were isolated >95% pure, except for trans-2f (ca. 70%) and trans-2g (ca. 80%), as determined by GLC and/or 300/400 MHz
1H NMR, and were fully characterized by spectroscopic means (IR, 1H and 13C NMR, LRMS, and HRMS). All the compounds gave consistent NMR correlations (DEPT, COSY,
HSQC, and HMBC), which were used for signal assignment.
b
Determined by quantitative NMR, using N,N-diphenyl formamide as internal standard and/or GLC using pure isolated products and decane as internal standard.
c
Determined by GLC and/or 300 MHz 1H NMR of the reaction crude. The cis/trans assignment of the stereochemistry was done after examination of the cross-signals in
NOESY experiments.
d
Measured with a Hewlett-Packard HP-5890 instrument equipped with a flame ionization detector and an HP-5 capillary column (30 m, 0.32 mm diam.), using nitrogen as
gas carrier, Tinjector¼275 ꢀC; Tdetector¼300 ꢀC; Tcolumn¼60 ꢀC (3 min) and 60–270 ꢀC (15 min), P¼12 psi; tR (min) are given under these conditions.

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H. Pe´rez et al. / Tetrahedron 65 (2009) 10769–10783
F
i.
THF, 0 °C
+
–2
ii. CH3CN
iii. H2O
(14%)
5a (82%)
2Li+
F
i.
THF, 0 °C
+
+
1-Li2
ii. CH3CN
iii. H2O
(48%)
p-6a + m-6a (ca. 1.8:1, 45%)
Scheme 6. Alkylation of dilithium biphenyl (Li2C12H10) with 2-fluorooctane and 2-fluoro-2-methylheptane. Yields of alkanes were determined by quantitative GLC using pure
commercial products for the calibration curve and diphenylmethane as internal standard. Yields of coupling products were obtained by 400 MHz 1H NMR using N,N-diphenyl
formamide as internal standard, and was estimated for m-6a, which consisted in a decaying mixture of non isolable regioisomers.
Table 3
Distribution of products from Scheme 7a,b
Entry
c
c (M)
7
8
9
10
p-6b
m-6b
% Total
1
2
1-Li
1-Li2
0.5
0.1
0
0
1.4ꢂ0.5
2.8ꢂ1.3
40ꢂ4
45ꢂ8
11ꢂ3
9ꢂ3
19ꢂ3
23ꢂ4
11ꢂ2
13ꢂ6
82
93
a
Reactions performed by addition of the halide (0.2 mmol diluted in THF or THP at 0 ꢀC, 30 min) to a solution of 1-Li or 1-Li2 in THF at 0 ꢀC and hydrolysis at low temperature
(ꢁ80 ꢀC), followed by immediate GLC analysis.
b
Yields followed by standard deviations determined by quantitative GLC using pure isolated or commercially available compounds and n-decane as internal standard, and
contrasted when necessary with 400 MHz 1H NMR yields using N,N-diphenyl formamide as internal standard. Yields were the average of 3–5 determinations (relative
standard deviation, rsd¼ꢂ17–47%).
c
Formal concentration of 1-Li or 1-Li2, not actual concentration, which is unknown for 1-Li2.
and was reacted with an equivalent of 1-Li2 in THF at 0 ꢀC (formal
[1-Li2]¼0.1 M). Results are gathered in Table 3, entry 2. The reaction
crude afforded a mixture of products that was first analyzed for
volatiles (GLC), and subsequently was rearomatized using DDQ to
afford a mixture of the non-rearranged coupling products p-6b and
m-6b in limited yield (36% overall). The corresponding rearranged
(cyclized) coupling products could not be detected in the reaction
crude (GLC and 400 MHz 1H NMR), and remained undetectable in
experiments of dilution (formal [1-Li2]¼0.05, 0.02, and 0.01 M). The
observed regioselectivity in the alkylation displayed in products p-
6 and m-6 results remarkable: it is different to that found for
products 2b and 2c in that the attack is directed to the 4- and 3-
position of biphenyl, instead of the 1-position. This is so to preclude
the formation of two contiguous quaternary centers, a significantly
destabilizing situation. We found an analogous behavior in differ-
ent reactions of attachment of a tertiary group to the biphenyl
moiety in the 4-position, while primary or secondary groups
generally reacted at the 1-position.21a Regarding low molecular
weight products (C8), the hydrocarbons 6-methylhept-1-ene (8),
1,1,2-trimethylcyclopentane (9), and 6-methylhepta-1,5-diene (10)
were detected and quantified by GLC (Table 3, Scheme 7) using pure
commercial or synthesized samples for the preparation of calibra-
tion curves. Rearranged product 9 was the major component of the
reaction mixture (45%). Along with 9, the presence of 10 (9%) also
indicates the existence of an ET pathway. Compound 10 is likely
originated from disproportionation of its precursor radical with
other radicals. A decrease in the regioselective control of the for-
mation of p-6b and m-6b may also be attributed to a radical course
of the reaction. When the radical anion 1-Li was used as a reagent,
the rearranged product 9 was obtained as major reaction product
(40%) as expected. A reasonable amount of coupling products p-6b
and m-6b (30% overall) was also found in the reaction crude.
Again, the realization of a complete kinetic study as a function of
the concentration of 1-Li or 1-Li2 was not viable for the
+
+
i. 1-Li or 1-Li2
8
9
10
F
THF, 0 °C
ii. H2O
7
but not
C12H10
C12H10
DDQ, CHCl3, 25 °C
+
p-6b
m-6b
Scheme 7.

H. Pe´rez et al. / Tetrahedron 65 (2009) 10769–10783
10775
bimolecular nucleophilic substitution (kSN), which prevails in the
case of a primary substrate (R¼H). On the other hand, also the
bimolecular electron transfer (kET), which dominates in the case
of a tertiary alkyl fluoride (R¼Me). After ET, the corresponding
radical clock evolves depending on its nature (substitution) in
three competing ways: one unimolecular way (kr) affording
rearranged products, for which exact activation parameters are
E
Li+
R
RR'CHF
E+
R
R'
THF, 0 °C
R'
–2
well documented,24 and two bimolecular ways (kred and kcoupl
)
II
5a-e
2Li+
that afford non-rearranged products. At this point, for the sim-
plest case of reactions with the radical anion 1-Li and making
a few simplifying assumptions (as setting kET and k0r¼0), an
evaluation of the ratio between the non-rearranged products and
rearranged products versus the concentration of 1-Li (in large
R'
R'
R
R''
R
R''
E
1-Li2
Li+
E+
RR'R''CF
THF, 0 °C
excess) would afford
a linear plot: [non-rearranged]/[rear-
ranged]¼(kredþkcoupl)[1-Li]/kr. From it, all rate constants should
be evaluated, and most importantly, the radical mechanism
established. Unfortunately, this was not experimentally feasible
for the aforementioned reasons. Even for the case of 1-Li2, which
was also explored, the concentration of 1-Li (now variable) could
be expressed as a function of the advance of the reaction and the
resulting differential equations integrated. Still, no well defined
trends were found in this and other explored situations. The
reaction network is complicated by the possible participation of
anionic cyclizations (k0r), which may be especially important in
the case of a tertiary carbanion. In spite of that and although no
absolute rates could be measured, the distribution of products is
consistent with the two competing reaction pathways and the
reaction network described in Scheme 9.
p-6a-c, major
p-III, major
(+ m-6a-c, minor)
(+ m-III, minor)
Scheme 8.
aforementioned reasons. Still, in spite of the dispersed nature of data,
the distribution of products found in Table 3 reveals that the data
from entry 1 (results from the radical anion, 1-Li) are statistically
indistinguishable from that in entry 2 (from dianion, 1-Li2). This is
significant, and supports a common reaction pathway initiated by an
ET to the fluoride. Radicals so generated evolve according to their
specific nature. Thus the long-lived tertiary radical is prone to give
coupling products (6) [among others (10)] rather than being reduced
to the corresponding carbanion. Conversely, upon unimolecular
rearrangement, a primary radical arises, which is easily reduced now
by ET to the corresponding carbanion, affording eventually 9.
From a synthetic point of view, the successive reaction of the
dianion of biphenyl (1-Li2) with a primary alkyl fluoride as the first
electrophile and with a second conventional electrophile works
regioselectively affording 1-alkyl-4-substituted-1,4-dihydrobi-
phenyls in good yields (2a–k).25
2.3.3. Synthetic applications derived from 1-Li2 and sec- and tert-
alkyl fluorides. The methodology described in Scheme 8 entails
again both dearomatization plus double functionalization of bi-
phenyl in one pot. In addition to that the initial alkylation site can
be chosen using either a secondary alkyl fluoride (RR0CHF) or
4. Experimental section
4.1. General
All moisture sensitive reactions were carried out under argon
atmosphere. THF and THP were dried and distilled over Na/K alloy
right before use. Commercially available (Acros, Aldrich, Fluka) bi-
phenyl, alkyl fluorides, and electrophiles were used without further
purification. Deuterium oxide was 99.98% D grade. Lithium powder
was prepared from lithium granules (Chemetall, 99%, high sodium
content) using an impact grinding mill and was also commercially
available (Medalchemy). All glassware were dried in an oven at
100 ꢀC and cooled to room temperature under Ar before use. Col-
umn chromatography was performed with Merck silica gel 60
a
tertiary alkyl fluoride (RR0R00CF) (Scheme 8). This affords
1-alkylated or 4-alkylated carbanionic intermediates as major in-
termediates (II and III in Scheme 8), which can be further trapped
with an appropriate electrophilic reagent (Eþ). Thus, 1-Li2 was
alkylated with different secondary and tertiary alkyl fluorides (RF,
Table 4) and was reacted later with an electrophile (Eþ: Et2CO,
CH3CN, H2O) followed by hydrolysis with water, all under the
same conditions described before (Scheme 5 and Table 2), to af-
ford the corresponding compounds 5b–e and 6b,c, along with the
byproducts of reduction RH. The reaction product described in
entry 6 was rearomatized using DDQ.
(0.040–0.063
mm, 240–400 mesh). Thin-layer chromatography
(TLC) was performed on precoated silica gel plates (Merck 60, F254
,
0.25 mm). Detection was done by UV254 light and/or developing
with phosphomolybdic acid spray; Rf values are given under these
conditions. NMR spectra were recorded on a Bruker Avance 300
and Bruker Avance 400 (300 and 400 MHz for 1H NMR, and 75 and
100 MHz for 13C NMR, respectively) using CDCl3 as solvent and TMS
as internal standard. Mass spectra (EI) were obtained at 70 eV on
a Shimadzu QP-5000 and Agilent 5973 spectrometers, fragment
ions in m/z with relative intensities (%) in parenthesis. HRMS
analyses were carried out on a Finnigan MAT95S spectrometer.
Infrared (FTIR) spectra were obtained on a Nicolet Impact 400D
spectrophotometer using NaCl plates. The purity of volatile com-
pounds and the quantitative chromatographic analyses (GC) were
carried out with a Hewlett-Packard HP-5890 instrument equipped
with a flame ionization detector and a 30 m HP-5 capillary column
3. Conclusions
In this paper we report a new and different reactivity of the
lithium biphenyl dianion (1-Li2) in its reaction with a poor
electron acceptor, namely an alkyl fluoride, as compared to that
of lithium biphenyl radical anion (1-Li). The analysis of the dis-
tribution of products in the reaction of dilithium biphenyl (1-Li2)
with several alkyl fluorides in THF at 0 ꢀC points toward a nu-
cleophilic substitution, SN2, as a competing mechanism with the
general ET mechanism, in another example of SN2–ET dichotomy.
The picture that emerges from this study is based on the analysis
of the distribution of products derived from the well known 5-
hexenyl radical probes, which is best described with the help of
Scheme 9. According to our findings, two main reaction pathways
compete for the alkyl fluoride substrate. On one hand, the
(0.32 mm diam., 0.25
gas (12 psi).
mm film thickness), using nitrogen as carrier

10776
H. Pe´rez et al. / Tetrahedron 65 (2009) 10769–10783
Table 4
Preparation of compounds 5b–e and 6b, c according to Scheme 7
Entry
RF
Eþ
Products
Structuresa
Yieldb (%)
Ratioc
Yield RH
HO
HO
H
H
F
1
55%
c-/t-
2.7:1
37%
O
cis-5b
trans-5b
F
2
70%
21%
CH3CN
5c
5d
5e
F
3
4
5
40%
38%
49%
51%
CH3CN
Ph
F
55%
CH3CN
OH
OH
F
c-/t-
1.3:1
O
41%
cis-6b
trans-6b
F
m-/p-
1.8:1
6
42%
53%
i. H2O; ii. DDQ
p-6c
m-6c
a
Both isomers of 5b, and 6b–c were isolated >95% pure, as well as the remaining compounds, as determined by GLC and/or 300/400 MHz 1H NMR, and were characterized
by spectroscopic means (IR, 1H and 13C NMR, LRMS, and HRMS). All the compounds gave consistent NMR correlations (DEPT, COSY, HSQC, and HMBC), which were used for
signal assignment.
b
Determined by quantitative 400 MHz 1H NMR, using N,N-diphenyl formamide as internal standard and/or GLC using pure isolated products and decane as internal
standard.
c
Determined by 300/400 MHz 1H NMR from the reaction crude. The cis/trans assignment of the stereochemistry was done after examination of the cross-signals in NOESY
experiments.
4.2. Preparation of the fluorinated reagents
was previously reported by us.19 2-Fluorooctane,26 2-fluoro-2-
methylheptane,27 2-fluoro-1-phenylpropane,28 5-fluoro-5-methyl-
1-hexene,29 and 1-(1-fluoroethyl)adamantane30 were prepared
according to the corresponding literature procedures and were
characterized by comparing their physical and spectroscopic data
All alkyl fluorides were colorless liquids. Octyl fluoride was
commercially available (Aldrich) and was used as supplied. The
preparation of 6-fluoro-1-hexene and fluoromethylcyclopentane

H. Pe´rez et al. / Tetrahedron 65 (2009) 10769–10783
10777
k
ET
R
R
R
R
k
1-Li or 1-Li2
r
F
R
R
k
k'
k'
red
red
coupl
k
coupl
k
SN
1-Li2
1-Li or 1-Li2
1-Li or 1-Li2
1-Li
1-Li
(R = H or Me)
1-Li
Li
R
R
k'
R
R
r
R
R
1-Li
Li
R
R
•–
–2
2Li+
Li+
1-Li2
1-Li
Scheme 9. Proposed overall reaction network, including both SN as well as ET reaction pathways. The corresponding hydrocarbon products of Tables 1 and 3 would be generated in
a final hydrolysis step (not drawn).
with those already reported. Some characteristic data of these
known compounds as well as the preparation of the two new fluo-
rinated reagents follows.
(m, 3H, 3ꢃCH ring),1.59–1.77,1.97–2.03 (2m,12H, 6ꢃCH2 ring), 4.13
1 1
(dq, JHF¼47.4 Hz, JHH¼6.4 Hz, 1H, CHF); 13C-NMR (100 MHz,
2
CDCl3): dC¼14.22 (d, JCF¼24.4 Hz, CH3), 28.06 (3ꢃCH ring), 36.33
(d, 2JCF¼18.3 Hz, CCF), 36.97, 37.11, 37.31, 37.35, 37.48, 38.53 (6ꢃCH2
ring), 97.63 (d, 1JCF¼169.2 Hz, CF); MS (70 eV, EI): m/z (%)¼169 (12%,
MþꢁCH), 168 (100), 154 (30), 139 (11), 133 (10), 125 (14), 119 (27),
112 (26), 11 (37), 109 (21), 108 (31), 107 (63), 106 (16), 105 (11), 99
(11), 98 (38), 97 (96), 96 (33), 95 (25), 94 (17), 93 (83), 92 (28), 91
(37), 85 (13), 81 (40), 80 (18), 79 (62), 78 (10), 77 (26), 68 (12), 67
(40), 65 (12), 59 (13), 55 (18), 53 (18).
4.2.1. 2-Fluorooctane26. Yield 50%; 1H NMR (300 MHz, CDCl3):
dH¼0.89 (t, J¼6.7 Hz, 3H, CH2CH3), 1.20–1.77 (m, 10H, 5ꢃCH2), 1.30
3
3
(dd, JHF¼23.8 Hz, JHH¼6.1 Hz, 3H, CH3CHF), 4.49–4.80 (dm,
2JHF¼48.8 Hz, 1H, CHF); 13C NMR (75 MHz, CDCl3): dC¼14.05
3
(CH2CH3), 21.00 (d, JCF¼23.2 Hz, CH3CHF), 22.55 (CH2CH3), 25.05
3
2
(d, JCF¼4.9 Hz), 29.10, 31.75 (CH2CH2CHF), 36.95 (d, JCF¼20.8 Hz,
1
CHF), 91.05 (d, JCF¼164.8 Hz, CHF); MS (70 eV, EI): m/z (%)¼112
(<1%, MþꢁHF), 84 (14), 83 (25), 70 (50), 69 (19), 57 (26), 56 (56), 55
4.2.6. 2-Fluoro-1,1-dimethylcyclohexane. To a suspension of mag-
nesium (1.6 g, 67 mmol) in Et2O (20 mL) was added dropwise
a solution of 5-bromo-1-pentene (5.0 g, 53.5 mmol) in Et2O (10 mL)
and the mixture was stirred for 1 h. The resulting mixture was
cooled at 0 ꢀC, anhydrous acetone (3.7 mL, 30 mmol) was added
and the resulting mixture was stirred for 1 h. After hydrolysis with
water (40 mL), it was extracted with Et2O (3ꢃ20 mL), the organic
layer dried over MgSO4 and the solvent evaporated at 15 Torr. The
resulting oil was dissolved in hexane (20 mL) and the resulting
solution was added to a 70% solution of HF in pyridine (10 mL) in
a polyethylene flask. After 3 h stirring at ꢁ40 ꢀC it was hydrolyzed
with a saturated solution of NaHCO3 (3ꢃ30 mL), extracted with
hexane, and distilled in vacuo (15 Torr) to give the title compound
(trapped at ꢁ78 ꢀC) with 60% yield; 1H NMR (300 MHz, CDCl3):
dH¼0.89, 0.99 (2s, 6H, 2ꢃCH3), 1.16–1.48, 1.67–1.77, 1.89–2.03 (3m,
8H, 4ꢃCH2 ring), 4.53–4.80 (dm, 1JHF¼49.0 Hz, 1H, CHF); 13C-NMR
(72), 46 (27), 43 (88), 42 (54), 41 (100).
4.2.2. 2-Fluoro-2-methylheptane27. Yield 60%; 1H NMR (300 MHz,
CDCl3): dH¼0.90 (t, J¼7 Hz, 3H, CH2CH3), 1.20–1.48 [m with a dd at
1.35, 3JHF¼18.3 Hz, 12H, CH3(CH2)3 and 2ꢃCH3CF], 1.48–1.70 (m, 2H,
CH2CF); 13C NMR (75 MHz, CDCl3): dC¼14.00 (CH2CH3), 22.60
(CH3CH2), 23.65 (d, 3JCF¼5.5 Hz, CFCH2CH2), 26.60 (d, 2JCF¼24.8 Hz,
2
CH3CFCH3), 32.15 (CH3CH2CH2), 41.45 (d, JCF¼22.9 Hz, CFCH2),
1
95.85 (d, JCF¼164.1 Hz, CF); MS (70 eV, EI): m/z (%)¼113 (<1%,
MþꢁF), 112 (1%, MþꢁHF), 97 (15), 70 (15), 69 (13), 61 (100), 60 (45),
58 (10), 57 (29), 56 (54), 55 (63), 43 (35), 42 (12), 41 (64); HRMS:
calcd for C8H17 113.1330; found 113.1305.
4.2.3. 2-Fluoro-1-phenylpropane28. Yield 60%; 1H NMR (300 MHz,
3
3
CDCl3): dH¼1.35 (dd, JHF¼23.7 Hz, JH–H¼6.2 Hz, 3H, CH3), 2.76–
3.07 (m, 2H, CH2), 4.72–5.01 (dm, 1JH–F¼54.0 Hz, 1JH–H¼6.2 Hz 1H,
CHF), 7.18–7.34 (m, 5H, Ph); 13C-NMR (75 MHz, CDCl3): dC¼20.53
3
(75 MHz, CDCl3): dC¼19.68 (d, JCF¼9.8 Hz, CH2CH2CHF), 26.66,
2
31.72 (2C, 2ꢃCH3), 32.45 (d, JC–F¼18.5 Hz, CH2CHF), 38.19 (d,
2
2
2
(d, JC–F¼21.8 Hz, CH3), 43.26 (d, JC–F¼20.7 Hz, CH2), 90.04 (d,
1JC–F¼92.9 Hz, CHF), 126.51, 128.38 (2C), 129.35 (2C), 137.19 (d,
3JC–F¼4.4 Hz) (Ph); MS (70 eV, EI): m/z (%)¼138 (24%, Mþ), 92 (9),
91 (100), 65 (9).
4JCF¼2.2 Hz, CH2CH2CH2CHF), 44.89 (d, JCF¼16.4 Hz, CCHF), 90.60
(d, 1JCF¼168.0 Hz, CHF); MS (70 eV, EI) m/z (%)¼130 (0.5%, Mþ), 115
(29), 95 (100), 87 (20), 73 (19), 69 (20), 67 (16), 59 (11), 56 (20),
55 (28).
4.2.4. 5-Fluoro-5-methyl-1-hexene29. Yield 70%; 1H NMR (300 MHz,
4.2.7. 6-Fluoro-6-methyl-1-heptene. The procedure was the same
as described in Section 4.2.6 but the crude alcohols (after the
Grignard reaction) were dissolved in triglyme (10 mL) and
the resulting solution was added to (diethylamino)sulfur trifluoride
(DAST; 1.8 mL, 15.28 mmol) at ꢁ30 ꢀC and the mixture was stirred
for 3 h at the same temperature. After hydrolysis with a saturated
solution of NaHCO3 (3ꢃ30 mL), it was extracted with hexane and
distilled in vacuo (15 Torr) to give the title compound (trapped at
ꢁ78 ꢀC) with 40%yield; 1HNMR(400 MHz, CDCl3): dH¼1.34 (d, 3JH–F¼2
1.6 Hz, 6H, 2ꢃCH3),1.45–1.64,1.57–1.64 (2m, 2H, CH2CH2CF), 2.07 (app
3
CDCl3): dH¼0.90 (d, JHF¼21.4 Hz, 6H, 2ꢃCH3), 1.64–1.78 (m, 2H,
CH2CF), 2.16 (app q, J¼6.9 Hz, 2H, CH2C]C), 4.93–5.09 (m, 2H,
CH2]CH), 5.76–5.91 (m,1H, CH2]CH); 13C-NMR (100 MHz, CDCl3):
2
3
dC¼26.62 (d, JCF¼25.91 Hz, 2C, 2ꢃCH3), 28.22 (d, JCF¼6.10 Hz,
2
1
CH2C]C), 40.47 (d, JCF¼22.9 Hz, CH2CF), 95.87 (d, JCF¼164.6 Hz,
CF), 114.48 (CH2]CH), 138.35 (CH2]CH).
4.2.5. 1-(1-Fluoroethyl)adamantane30. Yield 40%; 1H NMR (300 MHz,
CDCl3): dH¼1.21 (dd, 3JHF¼25.3 Hz, 3JHH¼6.4 Hz, 3H, CH3), 1.44–1.53

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H. Pe´rez et al. / Tetrahedron 65 (2009) 10769–10783
q, J¼6.9 Hz, 2H, CH2]CHCH2), 4.93–5.06 (m, 2H, CH2]CH), 5.74–
5.86 (m, 1H, CH2]CH); 13C-NMR (100 MHz, CDCl3): dC¼23.16
(CFCH2CH2), 26.60 (d, 2JC–F¼25.1 Hz, 2C, 2ꢃCH3), 33.89
(100), 154 (14), 57 (30); HRMS: calcd for C24H36 342.2817;
found 324.2838.
2
1
(CH2]CHCH2), 40.80 (d, JC–F¼22.9 Hz, CH2CF), 71.25 (d, JC–F
¼
99.3 Hz, CF), 114.70 (CH2]CH), 138.51 (CH2]CH); MS (70 eV): 130
(0.14%, Mþ), 95 (75), 82 (12), 81 (18), 73 (27), 69 (53), 68 (13), 67
(18), 61 (100), 59 (14), 56 (70), 55 (47), 54 (68), 53 (14).
4.3. General procedure for the preparation of compounds
2d–k
4.3.3. cis-3-(4-Octyl-4-phenylcyclohexa-2,5-dienyl)pentan-3-ol (cis-
2e). tR¼15.69 min; IR (film):
n
(cmꢁ1)¼3478, 3023, 2961, 2927,
2854, 1492, 1462, 1446, 1378, 1123, 1032, 938, 831, 819, 799, 763,
698; 1H NMR (300 MHz, CDCl3): dH¼0.88 (t, J¼7.0 Hz, 3H,
CH3CH2CH2), 0.89 (t, J¼7.5 Hz, 6H, 2ꢃCH2CH3), 1.18–1.33 (m, 12H,
6ꢃCH2), 1.46–1.63 (m, 5H, 2ꢃCH2CO, OH), 1.72–1.82 (m, 2H,
CCH2CH2), 2.92–2.98 (m, 1H, CHCO), 5.81–5.91 [m, 4H,
C(CH]CH)2], 7.14–7.20, 7.27–7.33, 7.34–7.40 (3m, 5H, Ph); 13C NMR
(75 MHz, CDCl3): dC¼7.61 (2C), 14.11 (3ꢃCH3), 22.66, 24.76, 28.81,
29.34, 29.57, 30.20, 31.88, 41.18 (8ꢃCH2), 42.36 (CHCO), 44.43 (CPh),
124.27 [2C, (CH]CH)2], 125.80, 126.47 (2C), 128.28 (2C) (Ph), 134.97
[2C, (CH]CH)2], 147.89 (Ph); MS (70 eV, EI): m/z (%)¼336 (<1%,
Mþꢁ18), 268 (20), 156 (13), 155 (82), 154 (43), 153 (10), 87 (100);
HRMS: calcd for C25H36 336.2817; found 336.2817.
To a stirred (rt, 30 min) greenish-blue suspension of a mixture of
biphenyl (1 mmol) and lithium powder (12 mmol) in dry THF (10 mL)
was added the corresponding alkyl fluoride (1.1 mmol) at 0 ꢀC. After
30 min at the same temperature the mixture was cooled down to
ꢁ78 ꢀC. The second commercially available electrophile (1.1 mmol)
was then added. After 15 min stirring, the resulting mixture was
hydrolyzed with water (5 mL), allowing the temperature to rise to
room temperature. The mixture was extracted with diethyl ether
(3ꢃ20 mL), the organic layer dried over Na2SO4, and evaporated
(15 Torr) to give a residue that was purified by column chromato-
graphy (silica gel, hexane/ethyl acetate). Yields of colorless liquid
compounds 2 are given in Table 2; physical, analytical, and spectro-
scopic data for compounds 2d–k follow, except for compounds cis-
and trans-2i, which were fully described in the preliminary
communication.20
OH
4.3.1. cis-(4-Butyl-1-octylcyclohexa-2,5-dienyl)benzene (cis-2d). tR¼
14.11 min; IR (film):
n
(cmꢁ1)¼30, 2926, 2854, 1492, 1465, 1377, 1115,
743, 697; 1H NMR (300 MHz, CDCl3): dH¼0.87 (t, J¼6.9 Hz, 3H,
CH3CH2), 0.90 (t, J¼7.1 Hz, 3H, CH3CH2), 1.20–1.39 (m, 16H, 8ꢃCH2),
1.41–1.48 (m, 2H, CHCH2), 1.74–1.81 (m, 2H, CCH2), 2.65–2.72 [m, 1H,
(CH]CH)2CH], 5.59 [app dd, J¼10.3,1.9 Hz, 2H, (CH]CH)2C(Ph)], 5.76
[app dd, J¼10.3, 3.2 Hz, 2H, (CH]CH)2CHCH2CH2], 7.13–7.19, 7.27–
7.32, 7.34–7.39 (3m, 5H, Ph); 13C NMR (75 MHz, CDCl3): dC¼14.03,
14.10 (2ꢃCH3), 22.66, 22.92, 24.86, 28.86, 29.37, 29.62, 30.30, 31.90
(8ꢃCH2), 35.39 (CHCH2), 35.89 (CHCH2), 40.21(CCH2), 44.63 (CPh),
125.70, 126.73 (2C), 128.15 (2C) (Ph), 128.34 [2C, (CH]CH)2CH],
132.31[2C, (CH]CH)2C], 148.22 (Ph); MS (70 eV, EI)¼m/z (%): 326
(0.06%, Mþþ2), 325 (0.41, Mþþ1), 324 (1.60, Mþ), 212 (16), 211 (93),
210 (12), 167 (14), 156 (13), 155 (100), 154 (16), 57 (36); HRMS: calcd
for C24H36 342.2817; found 324.2834.
4.3.4. trans-3-(4-Octyl-4-phenylcyclohexa-2,5-dienyl)pentan-3-ol
(trans-2e). tR¼15.84 min; IR (film):
n
(cmꢁ1)¼3453, 3024, 2928,
2855, 1727, 1599, 1491, 1463, 1378, 1290, 1124, 1032, 938, 796, 762,
698; 1H NMR (300 MHz, CDCl3): dH¼0.87 (t, J¼7.0 Hz, 3H,
CH3CH2CH2), 0.93 (t, J¼7.5 Hz, 6H, 2ꢃCH2CH3), 1.18–1.35 (m, 12H,
6ꢃCH2), 1.56–1.69 (2m, 5H, 2ꢃCH2CO, OH), 1.78–1.88 (m, 2H,
CCH2CH2), 2.94–3.00 (m,1H, CHCOH), 5.80 [app dd, J¼10.7,1.9 Hz, 2H,
(CH]CH)2C] 5.86 [dd, J¼10.7 Hz, J¼2.3 Hz, 2H, (CH]CH)2CH], 7.12–
7.20, 7.24–7.37 (2m, 5H, Ph); 13C NMR (75 MHz, CDCl3): dC¼7.55 (2C),
14.08 (3ꢃCH3), 22.65, 25.36, 29.02, 29.25, 29.54, 30.23, 31.89, 40.29
(8ꢃCH2), 42.26 (CHCO), 44.39 (CPh), 123.95 [2C, (CH]CH)2], 125.89,
126.59 (2C), 128.29 (2C) (Ph), 135.10 [2C, (CH]CH)2],147.48 (Ph); MS
(70 eV, EI): m/z (%)¼336 (3.90%, Mþꢁ18), 307 (10), 268 (11), 223 (31),
181 (17), 167 (38), 156 (12), 155 (72), 154 (39), 153 (11), 87 (100), 69
(12), 57 (14); HRMS: calcd for C25H36 336.2817; found 336.2796.
OH
4.3.2. trans-(4-Butyl-1-octylcyclohexa-2,5-dienyl)benzene (trans-
2d). tR¼14.18 min; IR (film):
n
(cmꢁ1)¼3084, 3057, 3014, 2956,
2926, 2855, 1598, 1491, 1465, 1446, 1378, 1116, 1032, 925, 740,
697; 1H NMR (400 MHz, CDCl3): dH¼0.87 (t, J¼6.9 Hz, 3H,
CH3CH2), 0.91 (t, J¼7.1 Hz, 3H, CH3CH2), 1.19–1.41 (m, 16H,
8ꢃCH2), 1.42–1.5 [m, 2H, (CH]CH)2CHCH2CH2], 1.76–1.81 (m, 2H,
CCH2CH2), 2.66–2.75 [m, 2H, (CH]CH)2CHCH2CH2], 5.59 [app dd,
J¼10.3 Hz, J¼2.0 Hz, 2H, (CH]CH)2C(Ph)], 5.75 [dd, J¼10.4 Hz,
J¼3.0 Hz, 2H, (CH]CH)2CHCH2CH2], 7.13–7.19 (m, 1H, Ph), 7.26–
7.32 (m, 2H, Ph), 7.33–7.39 (m, 2H, Ph); 13C NMR (100 MHz,
CDCl3): dC¼14.11 (2C, 2ꢃCH3), 22.67, 23.01, 25.46, 28.82, 29.33,
29.62, 30.28, 31.91 (8ꢃCH2), 35.18 (CHCH2), 35.89 (CHCH2), 39.85
(CCH2), 44.52 (CPh), 125.76, 126.62 (2C), 128.20 (2C) (Ph), 128.33
[2C, (CH]CH)2CH], 132.38 [2C, (CH]CH)2C], 148.22 (Ph); MS
(70 eV, EI): m/z (%)¼326 (0.06%, Mþþ2), 325 (0.37, Mþþ1),
1324 (1.44, Mþ), 212 (17), 211 (99), 167 (11), 156 (13), 155
4.3.5. cis-2-Methyl-1-(4-octyl-4-phenylcyclohexa-2,5-dienyl)propan-
2-ol (cis-2f). tR¼15.15 min; IR (film):
n
(cmꢁ1)¼3383, 3057, 3018,
2959, 2927, 2854, 1491, 1466, 1446, 1377, 1223, 1130, 909, 764, 741,
697; 1H NMR (300 MHz, CDCl3): dH¼0.88 (t, J¼6.6 Hz, 3H, CH3CH2),
1.19–1.37 (m, 13H, 6ꢃCH2, OH), 1.28 [s, 6H, (CH3)2CO], 1.62 [d,
J¼6.0 Hz, 2H, (CH2CO)], 1.72–1.84 (m, 2H, CCH2), 2.86–2.97 (m, 1H,
CHCH2CO), 5.59 [app dd, J¼10.3, 1.7 Hz, 2H, (CH]CH)2C], 5.89 [app
dd, J¼10.3, 3.4 Hz, 2H, (CH]CH)2CH], 7.10–7.21, 7.25–7.40 (2m, 5H,
Ph); 13C NMR (75 MHz, CDCl3): dC¼14.11 (CH3CH2), 22.65, 24.92,
29.35, 29.60 (4ꢃCH2), 30.04 [2C, (CH3)2CO], 30.26, 31.88 (2ꢃCH2),
32.01 (CHCH2), 40.28 (CCH2), 44.12 (CPh), 50.00 (CH2CO), 71.51

H. Pe´rez et al. / Tetrahedron 65 (2009) 10769–10783
10779
(CO), 125.77, 126.61 (2C), 128.22 [2C, (CH]CH)2CH], 129.18 (2C, Ph),
131.92 [2C, (CH]CH)2C], 147.94 (Ph); MS (70 eV, EI): m/z (%)¼322
(1.92%, Mþꢁ18), 210 (17), 209 (100), 168 (13), 167 (51); HRMS: calcd
for C24H34 322.2661; found 322.2657.
2857, 1491, 1445, 764, 740, 696; 1H NMR (400 MHz, CDCl3):
dH¼0.91 (t, J¼7.0 Hz, 3H, CH3), 1.02–1.13 (m, 2H, 2ꢃCHH cyclo-
pentyl), 1.28–1.39 (m, 4H, CH2CH2CH3), 1.40–1.50 (2m, 4H, CHCH2,
2ꢃCHH cyclopentyl), 1.51–1.62 (m, 2H, 2ꢃCHH cyclopentyl), 1.74–
1.86 [2m, 3H, 2ꢃCHH cyclopentyl, CH2CH(CH2)2], 1.91 (d, J¼4.9 Hz,
2H, CCH2), 2.65–2.75 [m, 1H, (CH]CH)2CHCH2], 5.67 [app dd,
J¼10.4, 2.0 Hz, 2H, (CH]CH)2C], 5.74 [app dd, J¼10.4, 2.7 Hz, 2H,
(CH]CH)2CH], 7.10–7.18, 7.24–7.32, 7.33–7.40 (3m, 5H, Ph); 13C
NMR (100 MHz, CDCl3): dC¼14.10 (CH3), 23.01 (CH2CH3), 25.03 [2C,
CH(CH2CH2)2], 28.82 (CH2), 34.84 [2C, CH(CH2CH2)2], 35.12
[(CH]CH)2CH], 35.87 (CH2), 37.13 [CH2CH(CH2)2], 44.90
[(CH]CH)2C], 47.02 (CCH2), 125.73 (Ph), 126.59 [2C, (CH]CH)2CH],
128.04 (2C), 128.17 (2C) (Ph), 133.11 [2C, (CH]CH)2C], 148.54 (Ph);
MS (70 eV, EI): m/z (%)¼296 (0.04%, Mþþ2), 295 (0.29, Mþþ1), 294
(1.21, Mþ), 212 (15), 211 (86), 210 (10), 167 (12), 156 (13), 155 (100),
154 (18), 153 (10), 57 (25), 55 (11); HRMS: calcd for C22H30
294.2348; found 294.2321.
OH
4.3.6. cis-Triisopropyl(4-octyl-4-phenylcyclohexa-2,5-dienyl)silane
(cis-2g). tR¼16.77 min; IR (film):
n
(cmꢁ1)¼3021, 2927, 2865, 1464,
1101, 1016, 902, 883, 761, 735, 698; 1H NMR (400 MHz, CDCl3):
dH¼0.87 (t, J¼6.7 Hz, 3H, CH3CH2), 1.00 [d, J¼6.8 Hz, 18H,
3ꢃSiCH(CH3)2], 1.05–1.14 [m, 3H, SiCH(CH3)2], 1.19–1.31 (m, 12H,
6ꢃCH2), 1.62–1.71 (m, 2H, CCH2), 2.65–2.69 (m, 1H, CHSiiPr), 5.64
[app dd, J¼10.4, 2.0 Hz, 2H, (CH]CH)2C], 5.90 [app dd, J¼10.4,
3.3 Hz, 2H, (CH]CH)2CH], 7.10–7.16, 7.23–7.30, 7.31–7.36 (3m, 5H,
Ph); 13C NMR (100 MHz, CDCl3): dC¼11.07 [3C, SiCH(CH3)2], 14.13
(CH3CH2), 18.93 [6C, SiCH(CH3)2], 22.67, 25.15 (2ꢃCH2), 26.96
[SiCH(CH3)2], 29.38, 29.59, 30.24, 31.91 (4ꢃCH2), 43.62 (CPh), 43.99
(CCH2), 125.33, 126.08 (2C), 126.41 [2C, (CH]CH)2CH], 127.95 (2C,
Ph), 128.99 [2C, (CH]CH)2C], 149.38 (Ph); MS (70 eV, EI): m/z
(%)¼267 (1.66%, MþꢁSiiPr3), 158 (15), 157 (100), 154 (14), 115 (46),
87 (17), 73 (19), 59 (23).
4.3.9. cis-(4-Butyl-1-(hex-5-enyl)cyclohexa-2,5-dienyl)benzene (cis-
2j). tR¼13.48 min; IR (film):
n
(cmꢁ1)¼3082, 3066, 3022, 2957,
2929, 2858, 1640, 1591, 1503, 1471, 1443, 995, 919, 761, 695; 1H
NMR (300 MHz, CDCl3): dH¼0.88 (m, 3H, CH2CH3), 1.18–1.48 (2m,
10H, CH2CH2CH2CH3, CCH2CH2CH2), 1.76–1.82 (m, 2H, CCH2), 2.00–
2.10 (m, 2H, CH2CH]CH2), 2.64–2.72 (m, 1H, CHCH2), 4.89–5.03 (m,
2H, CH]CH2), 5.58 [app dd, J¼10.4, 1.9 Hz, 2H, (CH¼CH)2C], 5.77
[app dd, J¼10.3, 3.3 Hz, 2H, (CH]CH)2CH], 5.70–5.88 (m, 1H,
CH]CH2), 7.14–7.20, 7.27–7.39 (2m, 5H, Ph); 13C NMR (75 MHz,
CDCl3): dC¼14.05 (CH3), 22.91 (CH3CH2), 24.42 (CCH2CH2), 28.84
(CH2CH2CH3), 29.56 (CH2CH2CH]CH2), 33.78 (CH2CH]CH2), 35.34
(CHCH2), 35.86 (CH2CH2CH2CH3), 39.93 (CCH2CH2), 44.56 (CPh),
114.14 (CH]CH2), 125.74, 126.69 (2C), 128.17 (2C) (Ph), 128.43 [2C,
(CH]CH)2CH], 132.16 [2C, (CH]CH)2C], 139.13 (CH]CH2), 148.09
(Ph); MS (70 eV, EI): m/z (%)¼296 (0.03%, Mþþ2), 295 (0.21, Mþþ1),
294 (0.91, Mþ), 212 (15), 211 (89), 167 (25), 156 (13), 155 (100), 154
(14), 153 (10), 57 (27); HRMS: calcd for C22H30 294.2348; found
294.2330.
i
Si Pr3
4.3.7. cis-(4-Butyl-1-(cyclopentylmethyl)cyclohexa-2,5-dien-
yl)benzene (cis-2h). tR¼13.38 min; IR (film):
n
(cmꢁ1)¼3084, 3057,
3014, 2954, 2928, 2858, 1597, 1491, 1446, 1377, 1033, 952, 914, 743,
697; 1H NMR (400 MHz, CDCl3): dH¼0.88 (t, J¼7.0 Hz, 3H, CH3),
1.02–1.16 (m, 2H, 2ꢃCHH cyclopentyl), 1.25–1.39 (m, 4H,
CH2CH2CH3), 1.40–1.50 (2m, 4H, CHCH2, 2ꢃCHH cyclopentyl), 1.51–
1.63 (m, 2H, 2ꢃCHH cyclopentyl), 1.72–1.85 [2m, 3H, 2ꢃCHH
cyclopentyl, CH2CH(CH2)2], 1.92 (d, J¼5.9 Hz, 2H, CCH2), 2.68–2.76
[m, 1H, (CH]CH)2CHCH2], 5.66 [app dd, J¼10.4, 1.9 Hz, 2H,
(CH]CH)2C], 5.75 [app dd, J¼10.4, 3.2 Hz, 2H, (CH]CH)2CH], 7.12–
7.18, 7.26–7.32, 7.34–7.40 (3m, 5H, Ph); 13C NMR (100 MHz, CDCl3):
dC¼14.03 (CH3), 22.91 (CH2CH3), 25.12 [2C, CH(CH2CH2)2], 28.89
(CH2), 34.80 [2C, CH(CH2CH2)2], 35.34 [(CH]CH)2CH], 35.90 (CH2),
37.23 [CH2CH(CH2)2], 44.91 [(CH]CH)2C], 47.31 (CCH2), 125.65
(Ph), 126.67 [2C, (CH]CH)2CH], 128.05 (2C), 128.12 (2C) (Ph),
133.00 [2C, (CH]CH)2C], 148.60 (Ph); MS (70 eV, EI): m/z (%)¼296
(0.05%, Mþþ2), 295 (9.91, Mþþ1), 294 (0.97, Mþ), 212 (14), 211 (84),
210 (14), 167 (11), 156 (13), 155 (100), 154 (17), 153 (10), 57 (25), 55
(11); HRMS: calcd for C22H30 294.2348; found 294.2370.
4.3.10. trans-(4-Butyl-1-(hex-5-enyl)cyclohexa-2,5-dienyl)benzene
(trans-2j). tR¼13.62 min; IR (film):
n
(cmꢁ1)¼3071, 3011, 2918,
2864, 1640, 1591, 1498, 1454, 1034, 913, 695; 1H NMR (400 MHz,
CDCl3): dH¼0.92 (t, J¼7.0 Hz, 3H, CH3), 1.19–1.49 (2m, 10H,
CH2CH2CH2CH3, CCH2CH2CH2), 1.75–1.81 (m, 2H, CCH2), 2.01–2.09
(m, 2H, CH2CH]CH2), 2.68–2.74 (m, 1H, CHCH2), 4.92 (app d,
J¼10.1 Hz, 1H, CH]CHH), 4.98 (app d, J¼17.0 Hz, 1H, CH]CHH),
5.59 [app dd, J¼10.2, 2.0 Hz, 2H, (CH]CH)2C(Ph)], 5.76 [app dd,
J¼10.2, 2.9 Hz, 2H, (CH]CH)2CH], 5.74–5.86 (m, 1H, CH]CH2), 7.14–
7.18 (m, 1H, Ph), 7.27–7.37 (m, 4H, Ph); 13C NMR (100 MHz, CDCl3):
dC¼14.09 (CH3), 22.97 (CH3CH2), 25.01 (CCH2CH2), 28.77
(CH2CH2CH3), 29.54 (CH2CH2CH]CH2), 33.82 (CH2CH]CH2), 35.15
[(CH]CH)2CHCH2 ], 35.84 (CH2CH2CH2CH3), 39.60 (CCH2), 44.49
4.3.8. trans-(4-Butyl-1-(cyclopentylmethyl)cyclohexa-2,5-dienyl)benz-
ene (trans-2h). tR¼13.48 min; IR (film):
n
(cmꢁ1)¼3016, 2952, 2927,

10780
H. Pe´rez et al. / Tetrahedron 65 (2009) 10769–10783
(CPh), 114.19 (CH]CH2), 125.79, 126.58 (2C), 128.21 (2C) (Ph), 128.43
[2C, (CH]CH)2CH], 132.25 [2C, (CH]CH)2C], 139.08 (CH]CH2),
148.12 (Ph); MS (70 eV, EI): m/z (%)¼296 (0.02%, Mþþ2), 295 (0.21,
Mþþ1), 294 (0.90, Mþ), 212 (15), 211 (88), 167 (25), 156 (13), 155
(100), 154 (13), 153 (10), 91 (10), 57 (25); HRMS: calcd for C22H30
294.2348; found 294.2355.
(75), 154 (42), 153 (19), 152 (20), 115 (11), 91 (14), 87 (96), 69
(20), 57 (10), 55 (16).
OH
4.4. General procedure for the preparation of compounds
5a–d and 6a–c
Compounds 5a–d and 6a–c were synthesized as colorless liq-
uids using the same procedure as for the above described com-
pounds 2d–k. Yields are given in Table 4; physical, analytical, and
spectroscopic data follow.
4.3.11. cis-3-(4-(Hex-5-enyl)-4-phenylcyclohexa-2,5-dienyl)pentan-
3-ol (cis-2k). tR¼14.57 min; IR (film):
n
(cmꢁ1)¼3492, 3028, 2968,
2935, 2847, 1646, 1591, 1487, 1449, 1121, 914, 804, 761, 755; 1H
NMR (400 MHz, CDCl3): dH¼0.88 (t, J¼7.5 Hz, 6H, 2ꢃCH3), 1.19–
1.32 (m with a br s at 123, 3H, CCH2CH2, OH), 1.34–1.45 (m, 2H,
CH2CH2CH]CH2), 1.46–1.62 (m, 4H, 2ꢃCH2CH3), 1.75–1.82 (m, 2H,
CCH2), 1.98–2.06 (m, 2H, CH2CH]CH2), 2.93–2.97 (m, 1H, CHCO),
4.92 (app d, J¼10.2 Hz, 1H, CH]CHH), 4.98 (app d, J¼17.0 Hz, 1H,
CH]CHH), 5.74–5.85 (m, 1H, CH]CH2), 5.83 [app dd, J¼10.4,
1.7 Hz, 2H, (CH]CH)2CH], 5.85 [app dd, J¼10.8, 2.7 Hz, 2H,
(CH]CH)2C], 7.14–7.19, 7.27–7.39 (2m, 5H, Ph); 13C NMR
(100 MHz, CDCl3): dC¼7.60 (2C, 2ꢃCH3), 24.28 (CCH2CH2), 28.83
(2C, 2ꢃCH2CH3), 29.46 (CH2CH2CH]CH2), 33.70 (CH2CH]CH2),
40.97 (CCH2), 42.35 (CHCO), 44.41 (CO), 114.18 (CH2]CH), 124.39
[2C, (CH]CH)2CH], 125.84, 126.45 (2C), 128.29 (2C) (Ph), 134.84
[2C, (CH]CH)2C], 139.04 (CH]CH2), 147.80 (Ph); MS (70 eV, EI):
m/z (%)¼308 (0.16%, Mþþ2), 307 (1.18, Mþþ1), 306 (4.77, Mþ), 277
(10), 238 (11), 224 (12), 223 (64), 181 (36), 179 (15), 178 (13), 168
(15), 167 (85), 166 (10), 165 (20), 156 (12), 155 (81), 154 (46), 153
(20), 152 (19), 91 (10), 87 (100), 69 (20), 55 (14); HRMS: calcd for
C23H30 306.2348; found 306.2345.
4.4.1. [1-(1-Methylheptyl)cyclohexa-2,5-dien-1-yl]benzene
(5a). Rf¼0.64 (hexane); 1H NMR (300 MHz, CDCl3): dH¼0.81 (d,
J¼6.7 Hz, 3H, CHCH3), 0.86 (t, J¼7.0 Hz, 3H, CH2CH3), 1.10–1.45 (m,
10H, 5ꢃCH2), 1.92–2.05 (m, 1H, CHCH3), 2.52–2.73 [m, 2H,
(CH]CH)2CH2], 5.71 [app dt, J¼10.7, 1.7 Hz, 2H, (CH]CH)2C], 5.86
[app t, J¼10.9 Hz, 2H, (CH]CH)2CH2], 7.14–7.19, 7.27–7.35 (2m, 5H,
Ph); 13C NMR (75 MHz, CDCl3): dC¼14.10 (CH3CH), 14.70 (CH3CH2),
22.65 (CH2CH3), 26.47 [(CH]CH)2CH2], 28.32, 29.51, 31.76, 31.89
(4ꢃCH2), 40.97 (CHCH3), 48.10 (CPh), 123.98, 124.55
[(CH]CH)2CH2], 125.45, 126.73 (2C), 128.19 (2C) (Ph), 131.10, 131.27
[2C, (CH]CH)2C], 147.97 (Ph); MS (70 eV, IE): m/z (%)¼269 (0.05%,
Mþþ1), 268 (0.17, Mþ), 156 (13), 155 (100), 154 (15), 153 (12);
HRMS: calcd for C20H28 268.2191; found 268.2163.
OH
4.4.2. [4-(1,1-Dimethylhexyl)-1,5-cyclohexadien-1-yl]-benzene (p-6a).
Rf¼0.58 (hexane); IR (film):
n
(cmꢁ1): 3031, 2971, 2925, 2851, 2804,
1936,1622,1602,1502, 1475,1375,1355, 1168, 988, 794, 767, 714; 1H
NMR (300 MHz, CDCl3): dH¼0.64, 0.73 [2s, 2ꢃ3H, C(CH3)2], 0.83 (t,
J¼7.1 Hz, CH2CH3), 0.94–1.27 (m, 8H, 4ꢃCH2), 2.67–2.89 [m, 2H,
C]CHCH2], 3.30–3.38 [m, 1H, CHC(CH3)2], 5.92–5.98 [m,
3H, CH]CH(Ph)C]CH], 7.16–7.22, 7.25–7.32 (2m, 5H, Ph); 13C NMR
(75 MHz, CDCl3): dC¼14.1 (CH2CH3), 22.67, 23.48 (2ꢃCH2),
25.06, 26.28 (2ꢃCCH3), 28.44 (C]CHCH2), 32.72 (CH3CH2),
40.56 [(CH3)2CCH2], 41.20 [(CH3)2CCH2], 46.16 [(CH3)2CCHCH]CH],
125.90 (Ph),126.09 (CH]CPh),126.09 (2C, Ph),127.34 (CH]CHCPh),
128.10 (2C, Ph), 129.10 (CH]CHCPh), 140.59 (CH2CH]CPh), 145.89
(CPh); MS (70 eV, IE): m/z (%)¼270 (0.04, Mþþ2), 269 (0.36, Mþþ1),
268 (1.54, Mþ),157 (20),156 (100),155 (100),154 (100),153 (31),152
(18), 128 (12), 115 (11), 77 (19), 71 (33), 57 (32); HRMS: calcd for
C20H28 268.2191; found 268.2211.
4.3.12. trans-3-(4-(Hex-5-enyl)-4-phenylcyclohexa-2,5-dien-
yl)pentan-3-ol (trans-2k). tR¼14.77 min; IR (film):
n )
(cmꢁ1
¼3437, 3071, 3028, 2968, 2924, 2853, 1777, 1738, 1689, 1640,
1492, 1460, 1443, 1170, 1127, 935, 908, 793, 733, 695; 1H NMR
(400 MHz, CDCl3): dH¼0.94 (t, J¼7.5 Hz, 6H, 2ꢃCH3), 1.18–1.35
(m with a br s at 1.32, 3H, CCH2CH2, OH), 1.36–1.45 (m, 2H,
CH2CH2CH]CH2), 1.50–1.67 (m, 4H, 2ꢃCH2CH3), 1.80–1.86 (m,
2H, CCH2), 2.00–2.08 (m, 2H, CH2CH]CH2), 2.95–2.99 (m, 1H,
CHCO), 4.92 (app d, J¼10.2 Hz, 1H, CH]CHH), 4.97 (app d,
J¼17.0 Hz, 1H, CH]CHH), 5.73–5.85 (m, 1H, CH]CH2), 5.80
[app dd, J¼10.6, 2.0 Hz, 2H, (CH]CH)2CH], 5.86 [app dd, J¼10.6,
2.5 Hz, 2H, (CH]CH)2C], 7.15–7.20, 7.27–7.38 (2m, 5H, Ph); 13C
NMR (100 MHz, CDCl3): dC¼7.54 (2C, 2ꢃCH3), 24.93 (CCH2CH2),
(2C, 2ꢃCH2CH3), 29.49 (CH2CH2CH]CH2), 33.77 (CH2CH]CH2),
40.07 (CCH2), 42.22 (CHCO), 44.37 (CO), 114.30 (CH2]CH),
124.05 [2C, (CH]CH)2CH], 125.93, 126.46 (2C), 128.30 (2C) (Ph),
134.95 ((CH]CH)2C), 138.98 (CH]CH2), 147.39 (Ph); MS (70 eV,
EI): m/z (%)¼308 (0.13%, Mþþ2), 307 (1.71, Mþþ1), 306 (7.29,
Mþ), 277 (14), 224 (14), 223 (72), 207 (12), 181 (45), 179 (22),
178 (18), 168 (17), 167 (100), 166 (12), 165 (28), 156 (10), 155
4.4.3. 4-(1,1-Dimethylhex-5-en-1-yl)biphenyl (p-6b). Rf¼0.40 (hexa
ne): IR (film):
n
(cmꢁ1)¼3092, 3058, 3031, 2978, 2931, 2851,

H. Pe´rez et al. / Tetrahedron 65 (2009) 10769–10783
10781
1629, 1589, 1482, 1368, 1255, 1088, 1014, 908, 827, 754, 727, 701;
1H NMR (400 MHz, CDCl3): dH¼1.14–1.26 (m, 2H, CH2CH2CH2),
1.33 [s, 6H, C(CH3)2], 1.60–1.68 (m, 2H, CH2C), 1.98 (app q,
J¼7.2 Hz, 2H, CH2CH]CH2), 4.91 (app d, 1H, J¼10.2 Hz,
CH]CHH), 4.95 (app d, 1H, J¼17.1 Hz, CH]CHH), 5.74 (ddt,
J¼17.1, 10.2, 6.7 Hz, 1H, CH]CH2), 7.32 (app t, J¼7.4 Hz, 1H, Ar),
7.36–7.47 (m, 4H, Ar), 7.53 (app d, J¼8.6 Hz, 2H, Ar), 7.60 (app d,
J¼8.2 Hz, 2H, Ar); 13C NMR (100 MHz, CDCl3): dC¼24.09
(CH2CH2CH]CH2), 28.96 [2C, C(CH3)2], 34.35 (CH2CH]CH2),
37.48 [(CH3)2C], 44.02 (CCH2), 114.33 (CH]CH2), 126.23 (2C, Ar),
126.69 (2C, Ar), 126.96 (Ar), 126.96 (2C, Ar), 128.67 (2C, Ar),
138.12 (Ar), 138.96 (CH]CH2), 140.99 (Ar), 148.73 (Ar); MS
(70 eV, IE): m/z (%)¼266 (0.22%, Mþþ2), 265 (2.27, Mþþ1), 264
(10.06, Mþ), 196 (16), 195 (100), 167 (18); HRMS: calcd for C20H24
264.1878; found 264.1854.
[(CH]CH)2C], 147.50 (Ph); MS: m/z (%)¼354 (0.00%, Mþ), 336
(0.17, Mþꢁ18), 167 (10), 155 (71), 154 (73), 153 (17), 152 (11), 88
(14), 87 (100), 69 (13), 57 (24); HRMS: calcd for C25H36 336.2817;
found 336.2769.
HO
H
4.4.6. 3-[trans-4-(1-Methylheptyl)-4-phenylcyclohexa-2,5-dien-1-
yl]pentan-3-ol (trans-5b). IR (film):
n
(cmꢁ1)¼3456 (br), 3030,
2965, 2924, 2858, 1639, 1598, 1491, 1468, 1444,1367, 1148,1119, 941,
799, 734, 692; 1H NMR (400 MHz, CDCl3): dH¼0.81 (d, J¼6.8 Hz, 3H,
CHCH3), 0.85 (t, J¼7.0 Hz, 3H, CH2CH2CH3), 0.91 [t, J¼7.5 Hz, 6H,
OC(CH2CH3)2], 1.18–1.42 (m, 10H, 5ꢃCH2), 1.30 (br s, 1H, OH), 1.56–
1.68 [m, 4H, OC(CH2CH3)2], 1.97–2.07 (m, 1H, CHCH3), 2.85–2.89 (m,
1H, CHCOH), 5.85–5.95 [m, 4H, (CH]CH)2], 7.13–7.18, 7.28–7.33
(2m, 5H, Ph); 13C NMR (100 MHz, CDCl3): dC¼7.49, 7.49
(2ꢃCH2CH2CH3), 14.09 (CH2CH2CH3), 15.22 (CHCH3), 22.65, 28.21
(2ꢃCH2), 29.15, 29.15 (2ꢃCCH2CH3), 29.46 (CH2), 31.79 (CHCH2),
32.39 (CH2), 40.77 (CHCH3), 42.48 (CHCO), 48.47 (CPh), 76.25 (CO),
124.92 (Ph), 125.39, 125.63 [2C, (CH]CH)2CH], 126.63 (2C), 128.34
(2C) (Ph), 133.08, 133.21 [(CH]CH)2C], 147.36 (Ph); MS (70 eV, IE):
m/z (%)¼336 (0.11%, Mþꢁ18), 155 (21), 154 (22), 87 (100), 57 (12).
4.4.4. 3-(1,1-Dimethylhex-5-en-1-yl)biphenyl (m-6b). Rf¼0.42 (hex-
ane): IR (film):
n
(cmꢁ1)¼3048, 2970, 2908, 2851, 1729, 1640, 1469,
HO
H
1427, 1256, 1053, 1012, 913, 757; 1H NMR (300 MHz, CDCl3):
dH¼1.17 (s, 6H, 2ꢃCH3), 1.35–1.44 (m, 4H, CH2CH2C), 1.88 (app q,
J¼7.1 Hz, 2H, CH2CH]CH2), 4.89 (app d, J¼10.3 Hz, 2H, CH]CHH),
4.93 (app d, J¼17.0 Hz, 2H, CH]CHH), 5.73 (ddt, J¼17.0, 10.2 Hz,
6.7 Hz, 1H, CH]CH2), 6.99 (app dd, J¼7.5, 1.6 Hz, 1H, Ar), 7.16 (app
dt, J¼7.5, 1.2 Hz, 1H, Ar), 7.26–7.35 (m, 6H, Ar), 7.42 (app d,
J¼8.1 Hz, 1H, Ar); 13C NMR (75 MHz, CDCl3): dC¼24.40
(CH2CH2CH]CH2), 31.06 (2C, 2ꢃCH3), 34.20 (CH2CH]CH2), 39.67
[(CH3)2C], 43.21 (CCH2), 114.17 (CH]CH2), 124.82, 126.52, 127.04
(3C, Ar), 127.13 (2C, Ar), 127.56 (Ar), 129.66 (2C, Ar), 132.50 (Ar),
139.06 (CH]CH2), 142.02, 145.16 (2C, Ar), 145.71 (Ar); MS (70 eV,
IE): m/z (%)¼264 (1.90%, Mþ), 207 (10), 196 (19), 195 (100), 193 (13),
180 (13), 179 (20), 178 (17), 167 (22), 165 (29), 152 (10); HRMS:
calcd for C20H24 264.1878; found 264.1883.
4.4.7. (1-(2,2-Dimethylcyclohexyl)cyclohexa-2,5-dienyl)benzene
(5c). IR (film):
n
(cmꢁ1): 3032, 2925, 2851, 1742, 1602, 1495, 1455,
1362, 1028, 954, 908, 727, 694; 1H NMR (300 MHz, CDCl3): dH¼0.84,
0.90 (2s, 6H, 2ꢃCH3), 1.18–1.45 (m, 8H, 4ꢃCH2), 1.97–2.10 [m, 1H,
CHC(CH3)2], 2.58–2.64 [m, 2H, (CH]CH)2CH2], 5.67–5.78 [m, 2H,
(CH]CH)2C], 5.81–5.93 [m, 2H, (CH]CH)2CH2], 7.12–7.19, 7.28–7.34
(2m, 5H, Ph); 13C NMR (75 MHz, CDCl3): dC¼22.72 (CH2), 24.52 (CH3),
26.45 [(CH]CH)2CH2], 27.72 (CH2), 31.08 [CH2CH2C(CH3)2], 33.61
(CH3), 39.41 (CH2), 41.77 (CCH), 46.81 [C(CH3)2], 46.94 (CPh), 124.08,
124.54 [2C, (CH]CH)2CH2], 125.43, 126.68 (2C), 128.30 (2C) (Ph),
131.25, 131.60 [(CH]CH)2C], 147.57 (Ph); MS (70 eV, IE): m/z (%): 268
(0.03%, Mþþ2), 267 (0.10, Mþþ1), 266 (0.45, Mþ),156 (14), 155 (100),
154 (43),153 (10); HRMS: calcd for C20H26 266.2034; found 266.2022.
4.4.5. 3-[cis-4-(1-Methylheptyl)-4-phenylcyclohexa-2,5-dien-1-yl]-
pentan-3-ol (cis-5b).
IR (film):
n
(cmꢁ1)¼3479 (br), 3082, 3057,
3027, 2962, 2929, 2855, 1597, 1491, 1460, 1446, 1377, 1322, 1267,
1237, 1153, 1125, 1034, 939, 910, 830, 795, 734, 700, 647; 1H NMR
(300 MHz, CDCl3): dH¼0.78 (d, J¼6.7 Hz, 3H, CHCH3), 0.85 [t,
J¼7.5 Hz, 9H, CH2CH2CH3, OC(CH2CH3)2], 1.09–1.30 (m, 10H,
5ꢃCH2), 1.35 (br s, 1H, OH), 1.41–1.57 (m, 4H, 2ꢃOCCH2CH3), 1.89–
2.04 (m, 1H, CHCH3), 2.93–2.96 (m, 1H, CHCO), 5.85–5.94 [m, 4H,
(CH]CH)2], 7.10–7.16, 7.24–7.32 (2m, 5H, Ph); 13C NMR
(100 MHz): dC¼7.61, 7.61 (2CꢃCH2CH3), 14.09 (CH2CH2CH3), 14.53
(CHCH3), 22.64 (CH2CH3), 28.29 (CH2), 28.80, 28.80 (2ꢃCH2CH3),
29.44 (CH2), 31.59 (CHCH2), 31.87 (CH2), 41.58 (CHCH2), 42.82
(CHCO), 48.43 (CPh), 76.84 (CO), 124.94 (Ph), 125.48, 125.48 [2C,
(CH]CH)2CH], 126.70 (2C), 128.27 (2C) (Ph), 133.54, 133.54
4.4.8. 1-[1-(1-Phenylcyclohexa-2,5-dien-1-yl)ethyl]adamantane
(5d). IR (film):
n
(cmꢁ1)¼3025, 2926, 2859, 1716, 1609, 1495, 1454,
1382, 1355, 1028, 1355, 1029, 908, 834, 761, 699; 1H NMR (300 MHz,
CDCl3): dH¼0.87 (m, 3H, CH3), 1.20–1.70 (m, 15H, 6ꢃCH2, 3ꢃCH
adamantyl), 1.99–2.12 (m, 1H, CHCH3), 2.62–2.71 [m, 2H,
CH2(CH]CH)2], 5.64–5.85 [m, 4H, CH2(CH]CH)2], 7.12–7.35 (m,
5H, Ph); 13C NMR (75 MHz, CDCl3): dC¼14.02 (CH3), 22.74, 22.89
(2ꢃCH2), 24.52 (CH adamantyl), 27.67, 28.74 (2 ꢃCH2), 31.08 (C
adamantyl), 33.63 (CH adamantyl), 35.49 [CH2(CH]CH)2], 35.75
(CH adamantyl), 39.49, 40.37 (2ꢃCH2 adamantyl), 41.62 (CHCH3),

10782
H. Pe´rez et al. / Tetrahedron 65 (2009) 10769–10783
47.54 (CPh), 125.37, 126.75 (2C), 128.19 (2C) (Ph), 129.03, 129.58
[CH2(CH]CH)2], 130.43, 131.23 [C(CH]CH)2], 147.49 (Ph).
(300 MHz, CDCl3): dH¼1.35 (s, 6H, 2ꢃCH3), 1.70–1.78 [m, 2H,
CH2C(CH3)2], 1.81–1.91 (m, 2H, CH2CH]CH2), 4.89 (app d,
J¼10.2 Hz, 1H, CH]CHH), 4.95 (app dd, J¼17.2, 1.6 Hz, 1H,
CH]CHH), 5.77 (ddt, J¼17.3, 10.3, 6.4 Hz, 1H, CH]CH2), 7.28–7.36,
7.37–7.47, 7.51–7.63 (3m, 9H, Ar); 13C NMR (75 MHz, CDCl3):
dC¼28.91 (2C, 2ꢃCH3), 29.22 (CH2CH]CH2), 37.46 [(CH3)2C], 43.59
[(CH3)2CCH2], 113.86 (CH]CH2), 126.24, 126.75, 126.96, 128.68,
138.24 (Ar), 139.29 (CH]CH2), 140.96, 148.35 (Ar); MS (70 eV, IE):
m/z (%)¼253 (0.04%, Mþþ3), 252 (0.64%, Mþþ2), 251 (6.15%,
Mþþ1), 250 (30.70%, Mþ), 196 (35), 195 (100), 194 (8), 181 (9), 179
(13), 178 (22), 167 (41), 165 (19), 155 (14), 152 (14); HRMS: calcd for
C19H22 250.1721; found 250.1736.
4.4.9. 3-[cis-6-(1,1-Dimethylhexyl)-3-phenylcyclohexa-2,4-dien-1-
yl]pentan-3-ol (cis-6b). IR (film):
n
(cmꢁ1)¼3476 (br), 3030, 2952,
2926, 2864, 1734, 1604, 1490, 1464, 1386, 1360, 1262, 945; 1H NMR
(300 MHz, CDCl3): dH¼0.83, 0.87 (2s, 6H, 2ꢃCCH3), 0.86–0.92 (2m,
6H, OCCH2CH3, CH2CH2CH3), 0.97 (t, J¼7.5 Hz, 3H, OCCH2CH3), 1.18–
1.38 (m, 9H, 4ꢃCH2, OH), 1.50–1.70 [m, 4H, OC(CH2CH3)2], 2.40 [d,
J¼6.1 Hz, 1H, CHC(CH3)2], 2.58 [d, J¼6.3 Hz, 1H, CHCO], 5.80 [d,
J¼7.4 Hz, 1H, (C]CHCHCOH)], 5.99 (dd, J¼9.9, 5.9 Hz, 1H,
PhCCH]CHCH), 6.30 (d, J¼9.9 Hz, 1H, PhCCH]CH), 7.18–7.43 (m,
5H, Ph); 13C NMR (75 MHz, CDCl3): dC¼7.55, 7.95 (2ꢃCH2CH3), 14.15
(CH2CH2CH3), 22.74, 23.60 (2ꢃCH2), 24.04, 24.15 (2ꢃCCH3), 27.08,
27.92 (2ꢃCH2), 32.97 (CH2), 38.79 [C(CH3)2], 39.03 (CH2), 40.24
(CHCO), 40.24 [CHC(CH3)2], 78.90 (CO), 123.27 (PhC]CHCHCOH),
124.87 (PhCCH]CH), 125.47 (2C), 127.02, 128.40 (2C) (Ph), 130.85
(PhCCH]CHCH), 135.85 (PhC), 140.83 (Ph); MS (70 eV, IE): m/z
(%)¼336 (0.42%, Mþ–18), 167 (11), 156 (71), 155 (74), 154 (85), 153
(14), 87 (100), 71 (32), 69 (13), 57 (51); HRMS: calcd for C25H36
336.2817; found 336.2823.
4.4.12. 3-(1,1-Dimethylpent-4-en-1-yl)biphenyl
(m-6c). Rf¼0.33
(hexane): IR (film):
n
(cmꢁ1)¼3058, 2958, 2918, 2845, 1642, 1475,
1262, 1008, 908, 761, 701; 1H NMR (300 MHz, CDCl3): dH¼1.20 (s,
6H, 2ꢃCH3), 1.46–1.55 [m, 2H, CH2C(CH3)2], 1.76–1.86 (m, 2H,
CH2CH]CH2), 4.81–4.94 (2m, 2H, CH]CH2), 5.68 (ddt, J¼17.0, 10.4,
6.1 Hz, 1H, CH]CH2), 7.0 (app dd, J¼7.5, 1.5 Hz, 1H, Ar), 7.17 (app dt,
J¼7.4, 1.1 Hz, 1H, Ar), 7.22–7.36, 7.39–7.46, 7.50–7.63 (3m, 7H, Ar);
13C NMR (75 MHz, CDCl3): dC¼29.42 (CH2CH]CH2), 30.99 (2C,
2ꢃCH3), 39.63 [(CH3)2C], 42.48 [(CH3)2CCH2], 113.71 (CH]CH2),
124.94, 126.56, 127.08 (Ar), 127.15 (2C, Ar), 127.55, 129.68 (2C),
132.56 (Ar), 139.14 (CH]CH2), 142.09, 145.03, 145.29 (Ar); MS
(70 eV, IE): m/z (%)¼252 (0.06%, Mþþ2), 251 (0.72, Mþþ1), 250
(3.10, Mþ), 196 (19), 195 (100), 194 (10), 193 (11), 180 (12), 179 (26),
178 (22), 167 (25), 166 (10), 165 (32), 152 (10); HRMS: calcd for
C19H22 250.1721; found 250.1721.
OH
4.4.10. 3-[trans-6-(1,1-Dimethylhexyl)-3-phenylcyclohexa-2,4-dien-
1-yl]pentan-3-ol (trans-6b). IR (film):
n
(cmꢁ1)¼3445 (br), 3035,
2952, 2932, 2859, 1656, 1588, 1459, 1376, 1148; 1H MRN (400 MHz,
CDCl3): dH¼0.64, 0.72 (2s, 6H, 2ꢃCCH3), 0.84 (t, J¼7.3 Hz, 3H,
CH2CH2CH3), 0.89 (t, J¼7.5 Hz, 3H, OCCH2CH3), 0.90 (t, J¼7.3 Hz, 3H,
OCCH2CH3), 0.94–1.27 (m, 8H, 4ꢃCH2), 1.32 (br s, 1H, OH), 1.45–1.65
[m, 4H, OC(CH2CH3)2], 2.95–3.01 (m, 1H, CHCOH), 3.32 [app t,
J¼5.3 Hz, 1H, CHC(CH3)2], 5.93–6.06 [m, 3H, CH]CH(Ph)C]CH],
7.17–7.22, 7.26–7.34 (2m, 5H, Ph); 13C NMR (100 MHz, CDCl3):
dC¼7.45, 7.45 (2ꢃOCCH2CH3), 14.08 (CH2CH2CH3), 22.66, 23.45
(2ꢃCH2), 25.24, 26.44 (2ꢃCCH3), 29.23, 29.29 (2ꢃCH2CH3), 32.68
(CH2), 40.66 [(CH3)2C], 41.16 (CH2), 44.14 (CHCO), 46.42
[CHC(CH3)2], 76.01(CO), 126.17, 126.31 (2C) (Ph), 126.89
(PhC]CHCH), 128.09 (2C) (Ph), 128.46 (PhCCH]CHCH), 130.06
(PhCCH]CH), 141.40 (PhC), 145.91 (Ph); MS (70 eV, IE): m/z
(%)¼336 (0.01%, Mþꢁ18), 156 (46), 155 (30), 154 (51), 153 (12), 87
(100), 71 (16), 69 (10), 57 (28).
Acknowledgements
This work was generously supported by the Spanish Ministerio
´
de Educacion y Ciencia (MEC; CTQ2007-65218 and Consolider
Ingenio 2010-CSD2007-00006) and the Generalitat Valenciana
(PROMETEO/2009/039). C.M. and H.P. thank the University of Ali-
cante for fellowships. We also thank Medalchemy S.L. and Chem-
etall for gifts of chemicals.
References and notes
OH
1. Meerholz, K.; Heinze, J. J. Am. Chem. Soc. 1989, 111, 2325–2326.
2. This has resulted in numerous synthetic applications: Yus, M. In The Chemistry
of Organolithium Compounds; Rappoport, Z., Marek, I., Eds.; Wiley: Chichester,
UK, 2004; Vol. 1, Part 2, pp 657–747.
3. Rees, N. V.; Baron, R.; Kershaw, N. M.; Donohoe, T. J.; Compton, R. G. J. Am. Chem.
Soc. 2008, 130, 12256–12257.
4. CRC Handbook of Chemistry and Physics, 85th ed.; Lide, Dr., Ed.; CRC: Boca Raton,
FL, 2004; pp 8–33.
5. For reduction potentials of Li (a) A reported half-peak potential for the pair Li(s)
/
4.4.11. 4-(1,1-Dimethylpent-4-en-1-yl)biphenyl
(p-6c). Rf¼0.35
Liþ
in THF is found, E1/2(Li/Li ¼ꢁ3.07 V, in THF/LiBPh4 versus Ag/AgCl:
þ
(THF)
)
(hexane); IR (film):
n
(cmꢁ1)¼3069, 3027, 2965, 2918, 2845, 1640,
Mortensen, J.; Heinze, J. Tetrahedron Lett. 1985, 26, 415–418; (b) The formal Li(s)
/
1609, 1484, 1370, 1313, 1110, 1006, 918, 851, 767, 736; 1H NMR
Liþ
potential in THF was measured recently, Ef0¼ꢁ3.48 V versus Fc/
(THF)

H. Pe´rez et al. / Tetrahedron 65 (2009) 10769–10783
10783
FcþPF6ꢁ: Paddon, C. A.; Ward Jones, S. E.; Bhatti, F. L.; Donohoe, T. J.; Compton,
Bank, S.; Juckett, D. A. J. Am. Chem. Soc. 1975, 97, 567–573; (d) Bank, S.; Juckett,
D. A. J. Am. Chem. Soc. 1976, 98, 7742–7746.
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1974, 96, 523–529.
R. G. J. Phys. Org. Chem. 2007, 20, 677–684.
6. Eꢀ1 for biphenyl is some 0.15 V higher than that of naphthalene (C10H8, Eꢀ ¼ꢁ2.
1
53 V, Eꢀ ¼beyond the experimental limit), which on the other hand holds the
2
highestdyet to be measureddsecond reduction potential Eꢀ2: See reference 1.
7. Eisch, J. J. J. Org. Chem. 1963, 28, 707–710.
17. Eberson, L. Acta Chem. Scand., B 1982, 36, 533–543.
8. Takahashi, C.; Maeda, S. Chem. Phys. Lett. 1974, 24, 584–588.
18. Hush, N. S. Z. Elektrochem. 1957, 61, 734–738.
9. Huber, W.; May, A.; Muellen, K. Chem. Ber. 1981, 114, 1318–1336.
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19. Herrera, R. P.; Guijarro, A.; Yus, M. Tetrahedron Lett. 2003, 44, 1309–1312.
20. Melero, C.; Perez, H.; Guijarro, A.; Yus, M. Tetrahedron Lett. 2007, 48, 4105–4109.
21. (a) Melero, C.; Guijarro, A.; Baumann, V.; Perez-Jimenez, A. J.; Yus, M. Eur. J. Org.
Chem. 2007, 5514–5526; (b) Melero, C.; Guijarro, A.; Yus, M. Tetrahedron Lett.
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22. Melero, C.; Herrera, R. P.; Guijarro, A.; Yus, M. Chem.dEur. J. 2007, 13, 10096–10107.
23. Dewar, M. J. S.; Dougherty, R. C. The PMO Theory of Organic Chemistry; Plenum:
New York, NY, 1975; Chapter 7.7.
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3514; (c) Chatgilialoglu, C.; Dickhaut, J.; Giese, B. J. Org. Chem.1991, 56, 6399–6403.
25. The reaction has an identical outcome in the case of secondary alkyl fluorides,
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4-alkyl-3-substituted-1,4-dihydrobiphenyls (6a–c) for tertiary alkyl fluorides,
which are obtained in lower yields. As a whole, it should be emphasized that
using this methodology biphenyl is partially dearomatized and doubly deriv-
atized in a one pot reaction.
26. Flosser, D. A.; Olofson, R. A. Tetrahedron Lett. 2002, 43, 4275–4279.
27. Olah, G. A.; Nojima, M.; Kerekes, I. Synthesis 1973, 786–787.
28. (a) Isogai, K.; Nishizawa, N.; Saito, T.; Sakai, J.-i. Bull. Chem. Soc. Jpn. 1983, 56,
1555–1556; (b) Dax, K. Science of Synthesis; George Thieme Verlag: Stuttgart,
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13. The actual extent to which this reduction takes place (i.e., the concentration of
the dianion in Scheme 1) has not been established quantitatively. The dynamics
of these heterogeneous equilibria depend on a number of variables including, in
addition to the reduction potentials of biphenyl (Eꢀ1, Eꢀ2) and lithium (Eꢀ(Li/Liþ)) in
THF,5 the stabilization due to ion-pairing equilibria of the dissolved species, the
solvent, the concentration and the temperature, all of which can be further
complicated by the appearance of new phases. Disproportionation equilibria are
profoundly affected by the medium (e.g., by small changes in the solvent; Levin,
G.; Holloway, B. E.; Szwarc, M. J. Am. Chem. Soc. 1976, 98, 5706–5709), and the
complex kinetics inherent to heterogeneous ET processes on metal surfaces
along with the intrinsic high reactivity of the species involved makes difficult the
determination of the actual composition of the reaction media. For all this, in
addition to spectroscopic claims, we included available electrochemical data on
the generation of biphenyl dianion, so the arguments concerning the generation
and stability of some of these highly reduced species do not rest exclusively on
spectroscopic grounds.
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