Carbolithiation of simple terminal and strained internal alkenes by the naphthalene and the biphenyl dianion: New modes of reactivity of highly reduced organic species in solution

Article abstract of DOI:10.1002/ejoc.200700447

Dianions derived from arenes of high reduction potential (biphenyl, naphthalene) and Li_(s) can carbometallate propene, isobutene or norbornene among other alkenes, in an intermolecular fashion. This reaction runs at room temperature to afford p

Full text of DOI:10.1002/ejoc.200700447

FULL PAPER
DOI: 10.1002/ejoc.200700447
Carbolithiation of Simple Terminal and Strained Internal Alkenes by the
Naphthalene and the Biphenyl Dianion: New Modes of Reactivity of Highly
Reduced Organic Species in Solution
Cristóbal Melero,[a] Albert Guijarro,*[a] Vitus Baumann,[a][‡] Ángel J. Pérez-Jiménez,[b] and
Miguel Yus*[a]
Keywords: Arene dianion / Dearomatization / Intermolecular carbolithiation / Lithium
Dianions derived from arenes of high reduction potential (bi-
phenyl, naphthalene) and Li(s) can carbometallate propene,
isobutene or norbornene among other alkenes, in an inter-
molecular fashion. This reaction runs at room temperature to
afford partially dearomatized alkylated aryl anions that are
susceptible to further functionalization by electrophilic cap-
ture. This form of reactivity, typical of the arene dianion, de-
viates from the specific alkali metal-like reactivity displayed
by these complexes, affording regio- and in many cases ste-
reo-controlled products. DFT calculations help to figure out
the regiochemical outcome of this reaction, where some of
the most inexpensive organic starting materials are involved.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
form complexes with alkali metals in ethereal solvents. In
the case of lithium, complexes with naphthalene or 4,4Ј-di-
tert-butylbiphenyl are well shifted to the right and have seen
much success as reductive-cleaving reagents, giving rise to
a variety of organolithium compounds used in preparative
organic chemistry.[4,5] We focused recently our attention on
the differences in reactivity between the different species
postulated as coexisting in these solutions, namely the radi-
cal anion (LiC10H8) and dianion (Li2C10H8) in the case of
naphthalene, in relation to their roles in the mechanism of
the arene-catalyzed lithiations.[6] For instance, both LiC10H8
as well as Li2C10H8 display an ET reactivity profile before
alkyl chlorides, generating high yields of organolithium
compounds.[7] Intrinsically different electronic configura-
tions between radical-anions and dianions (with an open
and closed shell, respectively) anticipate, however, the oc-
currence of a markedly different reactivity when substrates
are appropriately chosen. Among the reagents that are cap-
able of discriminating between both kind of reagents, we
found the case of low-strained cyclic ethers.[6] It is also the
case of many arene dianions reacting with alkyl fluorides as
alkylating reagents, since the corresponding radical anions
remain unreactive under identical conditions,[8] except for a
Introduction
The carbolithiation of alkenes is a synthetically useful
strategy that allows the formation of a new carbon–carbon
bond, while at the same time a new organolithium center is
generated. This provides the opportunity of further pro-
cessing of the molecule by electrophilic capture, making the
whole one-pot process especially attractive. In practice,
most carbolithiations described in the literature are of the
intramolecular type, often taking advantage of favorable 5-
exo-trig cyclizations as a main reaction pathway.[1] Intermo-
lecular carbolithiations remain, otherwise, much more un-
common. They are restricted to the use of alkenes activated
by conjugation or by other carbanion-stabilizing substitu-
ents,[2] as well as the carbolithiation of ethylene.[3] However,
so far no nucleophilic addition of an organoalkali com-
pound to propene or isobutene has ever been reported un-
der mild conditions.
With the exception of benzene, which does not form its
radical anion in a synthetically significant concentration in
most solvents, arenes of less negative reduction potential do
[a] Departamento de Química Orgánica e Instituto de Síntesis
Orgánica (ISO), Facultad de Ciencias, Universidad de Alicante, few arenes of very high reduction potential. In this article
Apdo. 99,
we would like to present the reaction of lithium dianions of
03080 Alicante, Spain
three common aromatic hydrocarbons, biphenyl (1), naph-
thalene (2) and, to a lesser extent, phenanthrene (3), with
terminal non-functionalized alkenes, as well as with one ex-
ample of a strained internal alkene. This reaction affords,
after electrophilic quenching, regiochemically function-
alized alkylated dihydroarenes through an intermolecular
carbolithiation as the key step of the synthesis.[9] It is also
Fax: +34-965-90-35-49
E-mail: aguijarro@ua.es, yus@ua.es
[b] Departamento de Química Física, Facultad de Ciencias, Uni-
versidad de Alicante, Apdo. 99,
03080 Alicante, Spain
[‡] Undergraduate student on Erasmus program from Albert-
Ludwigs-Universität, Freiburg/Breisgau, Germany
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
5514
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5514–5526

Carbolithiation of Alkenes
an additional example of a specific reaction of the dianions the second reduction potential is beyond the cathodic limit.
of arene, since the corresponding radical anions remain un- The effect could be interpreted as an attainment of the
reactive under identical reaction conditions (see below).
Hückel aromatic character of I–2, the opposite being true
for II–2 (and phenanthrene dianion C14H10–2, III–2). This
has been observed also as a paratropic NMR shift in the
1H NMR spectrum of III-Li2 (and other dianions derived
from larger, more easily reducible polycyclic aromatic hy-
drocarbons of benzenoid structure)[15] which is not ascribed
solely to electronic shielding.
We have observed previously that, in the presence of an
excess of Li(s), 2 is doubly reduced in THF (or better in
THP) to its dianion, II-Li2, to a certain extent.[6,7] Based
on reduction potential criteria,[14] the remaining arenes are
also expected to be reduced to the corresponding dianion
under the same conditions according to Equation (1).
Results and Discussion
Arene dianions of high reduction potential arenes are ex-
ceedingly reactive and rather elusive species. Previous de-
scriptions of the arene dianions employed in this work were
done in more or less depth elsewhere. Dilithionaphthalene
(II-Li2) was prepared by double deprotonation of 1,4-dihy-
dronaphthalene and crystallized as a dilithium salt coordi-
nated with TMEDA, its structure being determined by X-
rays diffraction.[10] Low-temperature 1H- and 13C-NMR
spectra of dilithiophenanthrene (III-Li2) have been re-
1
ported.[11,15] For dilithiobiphenyl (I-Li2) one H- and 13C-
NMR spectrum at –70 °C was also reported,[12] as well as
the UV and IR spectra of sublimed layers.[13] In addition to
spectroscopic claims, there is electrochemical evidence in
the literature on the generation of the dianions I–2 and III–2,
so the arguments concerning the generation and stability of
(1)
The proposed reaction scheme for the species I-Li2, II-
some of these highly reduced species do not rest exclusively Li2 and III-Li2 with terminal alkenes followed by electro-
on spectroscopic grounds. Biphenyl (1) has the highest re- philic capture is described in Scheme 1.
duction potential (E°1 = –2.68 V, E°2 = –3.18 V) followed
The reactions described in Scheme 1 were carried out
by naphthalene (2) (E°1 = –2.53 V) and phenanthrene (3) using simple equipment in a one-pot fashion. The carboli-
(E°1 = –2.49 V, E°2 = –3.13 V), all vs. Ag/AgCl under iden- thiation step can be followed appropriately by change in
tical experimental conditions by cyclic voltammetry.[14] color: the arene dianion changes from greenish-blue (I-Li2),
Interestingly, the second-reduction-wave does not follow the purple (II-Li2) or dark magenta (III) to brown or brownish
same sequence. The biphenyl dianion (I–2, C12H10–2) is tones within the times indicated in Table 1 and Table 2, in-
formed at a less negative cathodic potential than the corre- dicating the consumption of I-III-Li2. Terminal alkenes
sponding dianion of naphthalene (II–2, C10H8–2), for which such as propene, isobutene, 1-octene and methylenecyclo-
Scheme 1.
Eur. J. Org. Chem. 2007, 5514–5526
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5515

C. Melero, A. Guijarro, V. Baumann, Á. J. Pérez-Jiménez, M. Yus
FULL PAPER
pentane were carbometallated by I-III-Li2, followed by in seems to depend on the nature of the electrophile itself. As
situ electrophilic capture and hydrolysis to afford products electrophiles, non-prochiral electrophiles such as symmetric
12a–h, 13 and 14 (Table 1, entries 1–8 and Table 2). In gene- ketones or oxiranes were preferred to assess the scope of
ral, nonstrained internal (cis- or trans-)alkenes failed to re- the process and to avoid tedious separations. Regarding the
act at a reasonable rate. However, slightly strained ones solvent, relatively short reaction times and the convenience
such as norbornene afforded products in moderate yield of using THF vs. THP (m.p. –45 °C) prompted us to choose
(Table 1, entries 9–10). While the site of the arene attack is THF in most cases to the detriment of THP, despite the
adequately confirmed by the HOMO coefficients of I–2 (e.g. better stability known for THP in these very reactive me-
C4 for biphenyl, see Figure 1), the final electrophilic capture dia.[6] In the case of ketones 9–10, addition occurs at C3
Table 1. Reaction of biphenyl dianion (I-Li2) with alkenes and capture with electrophiles.
1
[a] Unless otherwise stated, all compounds were isolated (Ͼ94% purity by GLC and/or 300/500 MHz H NMR) giving consistent NMR
spectra and correlations (1H-, 13C-, DEPT, COSY, HSQC and HMBC), as well as HRMS and IR spectra. The stereochemistry is based
on NOESY experiments. [b] Yield based on arene 1. [c] 1:1 Mixture of diastereomers corresponding to the two possible configurations
of the 1-methylheptyl moiety. [d] Separated cis- (major, shown in Table) and trans-stereoisomer (minor) in 6:1 ratio. [e] Separated two
exo-trans-stereoisomers in 1.1:1 ratio, one of them shown in Table (the major exo-trans stereoisomer was separated with 64% purity,
contaminated with a 36% of minor exo-trans stereoisomer). The exo-endo stereochemistry was assigned by comparison with published
NMR studies on assignment of substituted norbornane derivatives; see ref.[17]. [f] Separated cis (major, shown in Table) and trans stereoiso-
mer (minor) in 1.7:1 ratio, both with the exo configuration in the norbornane moiety determined as above. This reaction was carried out
in THP.
5516
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5514–5526

Carbolithiation of Alkenes
Table 2. Reaction of naphthalene dianion (II-Li2) and phenanthrene dianion (III-Li2) with propene and capture with electrophiles.
[a] All compounds were isolated (Ͼ95% purity by GLC and/or 300/500 MHz 1H NMR) giving consistent NMR spectra and correlations
(1H, 13C, DEPT, COSY, HSQC and HMBC), as well as HRMS and IR spectra. Stereochemistry was determined in base of NOESY
experiments. [b] Yield based on arene 2, 3. [c] Separated trans- (major, shown in Table) and cis-stereoisomers (minor) in 3.5:1 ratio.[19]
–2
Figure 1. HOMO atomic coefficients, Mulliken charges (in parentheses) and atomic charges from NPA (in parentheses, italics) for C12H10
–2
–2
(I–2, point group C2h), C10H8 (II–2, D2h) and C14H10 (III–2, C2), from B3LYP calculations at the 6-311G(d,p) level in the gas phase.
yielding substituted 3,4-dihydrobiphenyls of trans-configu- tentials from different sources, but still a good approach for
ration, presumably to avoid the generation of two adjacent our purposes).
quaternary centers, which is a sterically compromised situa-
Semiempirical calculations are a first qualitative ap-
tion (Table 1, Entries 1–7, 9). On the contrary, for sterically proach to the theoretical description of the reactivity of
less demanding outcomes such as trapping with isobutylene I–2–III–2 that proved to be helpful in the past[8] and so are
oxide (11), reaction at C1 is preferred, affording substituted in the present case.[9] Density Functional Theory calcula-
1,4-dihydrobiphenyls, although with low cis-/trans-stereose- tions,[20] using the B3LYP exchange-correlation func-
lectivity (Table 1, Entries 8, 10).[16]
tional,[21] have been performed here to support the theoreti-
In Table 2, the products obtained by carbolithiation of cal description of the reactivity of I–2–III–2. The geometries
propene with the naphthalene dianion (II-Li2) or phenan- of the isolated dianions have been optimized both in the
threne dianion (III-Li2), followed by capture with 3-penta- gas phase and in the presence of the THF solvent described
none, are described. Roughly, for arenes with a second re- by a continuum model,[22,23] using the 6-311G(d,p) basis
duction potential less-negative than phenanthrene (E°2
=
set.[24] The corresponding Mulliken charges, the atomic
–3.13 V under the given conditions),[14] the reaction with charges derived from a NPA (Natural Population Analy-
alkenes does not proceed in a synthetically useful way. In- sis)[25] and the atomic gross populations for the HOMO are
deed, yields are low for phenanthrene itself (Table 2, entry reported in Figure 1, and clearly indicate that the alkene
2) and drop sharply for other polycyclic arenes of less-nega- attack takes place at the carbon atom of the arene support-
tive second reduction potential, such as anthracene (E°1 = ing the highest contribution to the HOMO of the dianion,
–2.04 V, E°2 = –2.64 V), pyrene (E°1 = –2.13 V, E°2
=
rather than at the carbon of highest calculated charge. This
–2.86 V), both in DMA/TBAB vs. Ag/AgCl,[14] or chrysene, conclusion is also supported when standard diffuse func-
[E1/2(1) = –2.31 V, E1/2(2) = –2.82 V], in DMF/TMAB vs. Ag/ tions,[26] are included in the basis set, provided that the sol-
AgCl,[14,18] (this last value is only approximate, given the vent is considered, as can be seen from the B3LYP/6-
different experimental conditions and expression of the po- 31+G(d,p) results reported in the electronic supporting in-
Eur. J. Org. Chem. 2007, 5514–5526
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5517

C. Melero, A. Guijarro, V. Baumann, Á. J. Pérez-Jiménez, M. Yus
FULL PAPER
formation. Without the stabilizing effect of the solvent the MS fragmentations (Scheme 1). The reaction employing
tendency of high-energy electrons to escape from the di- [D10]biphenyl was examined at this point. After reaction
anion leads to large coefficients for several diffuse functions with Li(s) in THF and methylenecyclopentane (2 h), and
in the HOMO, which spreads throughout space, yielding electrophilic capture with 3-pentanone, [D10]12f, with all 10
meaningless values for the Mulliken charges and HOMO D in ring positions was isolated and characterized, proving
gross populations. This deleterious effect has been noted that biphenyl or subsequent intermediates were not source
previously for a number of organic,[27] and inorganic di- of quenchable protons in this reaction (Scheme 3). The only
anions.[28] It should be stated that, for the qualitative pur- remaining source of protons is the alkene. Sufficient (al-
pose of pinpointing the reactive site in a kinetically-driven though indirect) evidence of the alkene participation in the
reaction of the arene dianion, both semiempirical and DFT protonation step Ia–IIIa Ǟ IaH-IIIaH (Scheme 1) was ob-
calculations afford the same information. The atomic gross tained upon detection of alcohols 16–21 as side-products in
populations for the HOMO (DFT, this paper) correlate well variable yields (in parenthesis) in the reaction crudes
with the HOMO coefficients (semiempirical, preliminary (Table 1, entries 1–4, 6,7). The presence of these side-prod-
communication),[9] indicating the place in the molecule ucts was confirmed by independent synthesis of 16–21 (see
where the alkene attack will take place most probably.[29] Exp. Sect.) and quantitative reexamination of the corre-
Calculated charge distributions afford also the same quali- sponding reaction crudes.
tative results, in spite of the population analysis em-
ployed.[30]
With the results of Tables 1 and 2 in hand, we tried to
execute the same kind of reactions by using the radical
anions of 1, 2 and 3 (i.e. I-Li, II-Li or III-Li). The results
were clear and also significant concerning the reactivity of
the species involved. The reaction of the corresponding ar-
ene radical anions I-Li, II-Li or III-Li with alkenes did not
take place at all (0% carbolithiation using a 1:1 Li/arene
ratio for 1–3, THF, room temp.).
Scheme 3.
Regarding the mechanism in Scheme 1, the intermediates
Ia–IIIa are postulated after carbolithiation of the corre-
sponding alkenes by I–2–III–2. These species carry two well
differentiated organolithium centers, one primary alkyllith-
ium and one highly conjugated organolithium center (ben-
zylic type or both benzyic-allylic type depending on the ar-
ene). We have not been able to capture the primary organo-
lithium compound by any means. By the time the carboli-
thiation is complete, the primary alkyllithium is already
quenched by the reaction media. In order to clarify this
point, a reaction employing [D8]THF was carried out. After
3 h of reaction of I-Li2 with propene in [D8]THF and H2O
hydrolysis, analysis of the crude products showed no deute-
rium incorporation at all (non-separated mixture of 4-iso-
propyl-3,4-dihydrobiphenyl and trans- and cis-4-isopropyl-
We also tried to set the limits for the regioselectivity dis-
1,4-dihydrobiphenyl, 15a–c, 90%, in ratios 15a/15b/15c = played by the electrophilic capture. The reaction of IaH
46:33:21). When D2O was used for quenching, an analo- (with R = H, RЈ = Me) with CO2 followed by hydrolysis
gous mixture of monodeuterated products was observed and extractive work up afforded a separable mixture of two
{[D1]15a–c (Scheme 2), monodeuterium incorporation carboxylic acids characterized as 22a and 22b in a 70:30
Ͼ99.5%, natural isotopic abundance for C15H17D ratio. Indeed, delocalized carbanion IaH, which is of the
corrected}. Deuterium incorporation took place exclusively cyclohexadienyl type, is expected to react with electrophiles
1
at the ring, as could be determined both by H NMR and at the C1 or C3 positions, affording substituted 3,4- and 1,4-
Scheme 2.
5518
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5514–5526

Carbolithiation of Alkenes
dihydrobiphenyls, respectively, showing a priori a preference this work comes from its contributions in two fronts: from
for the addition at C1 (PM3 HOMO coefficients: C1 = 0.60; one side, as a reaction in which arene radical anion and
C3 = –0.40. Mulliken charge: C1 = –0.40; C3 = –0.44).[31,32] dianion display clear-cut different reactivity. From the other
This is evidenced by the 70:30 ratio of carboxylic acids, 22a side, as one of the few reactions of arene dianions of high
being the major component of the crude.[33] However, for reduction potential displaying reactivity profiles other than
ketones only 3,4-dihydroderivatives 12a–g could be isolated. alkali-metal-like soluble forms. Interestingly, nucleophilic
As pointed out before, the reason for this behavior seems reactivity is manifested vs. substituted alkenes, such as pro-
to be merely steric. The occurrence of two contiguous qua- pene and isobutene, which only very seldomly undergo nu-
ternary centers should severely hamper the reaction path- cleophilic substitution processes, especially in the absence
ways towards 1,4-dihydrobiphenylic tertiary alcohols, i.e., of transition metal catalysts.
the regioisomers of 12a–g, which could not be detected. In-
deed, this substitution pattern is only observed with electro-
philes of low steric demand like oxirane 11, CO2 or H2O
(15a–c). For the naphthalene framework, the reaction of
IIaH (with R = H, RЈ = Me) with H2O also affords a mix-
ture of two separable hydrocarbon isomers in 76% yield,
characterized as 23a and 23b in 52:48 ratio. A little prefer-
ence for 1-isopropyl-1,4-dihydronaphthalene (23a) over the
isomeric 1,2-dihydro derivative 23b is, again, observed, also
in reasonable agreement with calculations on IIaH
(PM3).[31]
Experimental Section
General: All moisture-sensitive reactions were carried out under ar-
gon atmosphere. THF was dried and distilled from Na/K alloy
right before use. Starting arenes, olefins and electrophiles were
commercially available (Acros, Aldrich, Fluka) and used without
further purification. Deuterated reagents were of the following
grade: [D8]THF (99.5% D), D2O (99.9% D) and C12D10 (99% D).
Lithium powder was prepared from lithium granules (99%, high
sodium content) using an impact grinding mill and was also com-
mercially available (MEDALCHEMY S. L.). All glassware was
dried in an oven at 100 °C and cooled to room temperature under
Ar before use. Column chromatography was performed with
Merck silica gel 60 (0.040–0.063 µm, 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 val-
ues are given under these conditions. NMR spectra were recorded
on a Bruker Avance 300, Bruker Avance 400 or Bruker Avance
DRX500 (300, 400 and 500 MHz for 1H NMR, and 75, 100 and
125 MHz for 13C NMR, respectively) using CDCl3 as solvent and
TMS as internal standard. Multiplicity is reported as follows: s =
singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br. s =
broad singlet, app. = apparent. 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 spec-
trometer. Infrared (FT-IR) spectra were obtained on a Nicolet Im-
pact 400D spectrophotometer using NaCl plates. The purity of vol-
atile compounds and the chromatographic analyses (GC) were de-
termined with a Hewlett–Packard HP-5890 instrument equipped
with a flame ionization detector and a 12 m HP-1 capillary column
(0.2 mm diam, 0.33 µm film thickness, OV-1 stationary phase),
using nitrogen (2 mLmin–1) as carrier gas.
Conclusions
New reactivity patterns have been identified for lithium
dianions of polycyclic arenes of high reduction potential.
Largely unexplored, the reactivity displayed by these highly
reduced species (I–2, II–2 and to less extent III–2) other than
ET is notable and has straightforward synthetic uses. They
react nucleophilically with terminal alkenes and norbornene
through an intermolecular carbolithiation as the key step,
the resulting organolithium intermediate generated being
trapped with conventional electrophiles. This synthesis af-
fords highly elaborated, regiochemically and in many cases
stereochemically well defined products, which are obtained
after processing of among some of the most low-cost or-
ganic starting materials. The reaction involves partial de-
aromatization and produces doubly functionalized 2-
phenyl-1,3-cyclohexadienes as well as functionalized 1,4-di-
hydronaphthalenes and 9,10-dihydrophenanthrenes when
starting from biphenyl, naphthalene and phenanthrene,
General Procedure for the Preparation of Compounds 12a–d: To a
deeply colored solution of biphenyl (3 mmol) and lithium powder
(Li(s), 12 mmol) in dry THF (10 mL) at 25 °C with vigorous stirring
under Ar, propene or isobutene was delivered using a balloon (ap-
prox. 3 L, 1 atm). Proper evacuation of Ar is critical for the reac-
tion with gaseous alkenes in order not to unnecessarily lengthen
the reaction times. After ca. 1 h for propene or 1.5 h for isobutene,
the initial greenish-blue color of I turned brown. The reaction was
then cooled down to –78 °C and 3-pentanone (9) or diisopropyl
ketone (10) (6 mmol) was added. After 15 min the reaction was
hydrolyzed (H2O) and worked up as usual (3ϫ20 mL diethyl ether,
Na2SO4, 15 Torr), purifying 12a–d by flash chromatography (silica
gel, Hx/EtOAc); 0.5 wt.-% of hydroquinone was added for stabilisa-
tion during storage (see ref.[6]).
3-[(1RS,6SR)-6-Isopropyl-3-phenylcyclohexa-2,4-dienyl]pentan-3-ol
respectively. Besides the synthetic scope, the relevance of (12a): R = 0.36 (9:1, hexane/ethyl acetate). IR (film): ν = 3583,
˜
f
Eur. J. Org. Chem. 2007, 5514–5526
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5519

C. Melero, A. Guijarro, V. Baumann, Á. J. Pérez-Jiménez, M. Yus
1364, 1021, 1005, 951, 910, 766, 744, 697 cm–1 1H NMR
(300 MHz, CDCl3): δH = 0.21–0.49 (m, 8 H, 4ϫCH2 of cyclopro-
pyl), 0.92 (s, 9 H, 3ϫCH3C), 0.94–1.02 (m, 2 H, 2ϫCH of cy-
FULL PAPER
3486, 3032, 2963, 2879, 1599, 1494, 1461, 1447, 1384, 1367, 1123,
.
948, 917, 771, 750, 697 cm–1. H NMR (300 MHz, CDCl3): δH
=
1
0.88 (t, 3 H, J = 7.6, CH3CH2), 0.92 (d, J = 6.6 Hz, 3 H, CH3CH),
0.93 (d, J = 6.9 Hz, 3 H, CH3CH), 0.95 (t, J = 7.7 Hz, 3 H, clopropyl), 1.15 (br. s, 1 H, OH), 2.48 (app. d, J = 5.9 Hz, 1 H,
CH3CH2), 1.49 (br. s, 1 H, OH), 1.51–1.70 (m, 5 H, 2ϫCH2CH3,
CH3CHCH3), 2.42–2.48 (2 m, 2 ϫ 1 H, C=CHCHCOH and
CH=CHCHiPr), 5.82 (app. d, J = 6.4 Hz, 1 H, C=CHCHCOH),
CH=CHCHtBu), 2.73 (app. d, J = 6.4 Hz, 1 H, C=CHCHCOH),
5.91 (app. dd, J = 6.2, J = 9.9 Hz, 1 H, CH=CHCHtBu), 6.07 (app.
d, J = 5.9 Hz, 1 H, C=CHCHCOH), 6.30 (app. d, J = 10.1 Hz, 1
5.88 (app. dd, J = 10.0, J = 6.2 Hz, 1 H, CH=CHCHiPr), 6.28 H, CH=CHCPh), 7.26 (app. t, J = 7.3 Hz, 1 H, PhpH), 7.34 (app.
(app. d, J = 9.8 Hz, 1 H, CH=CHCPh), 7.24–7.42 (m, 5 H, Ph)
ppm. 13C NMR (75 MHz): δC = 7.61, 7.89 (2ϫCH3CH2), 18.45,
19.43 (CH3 CHCH3 ), 27.11, 27.99 (2 ϫ CH2 CH3 ), 34.72
(CH3CHCH3), 38.38 (CH=CHCHiPr), 43.12 (C=CHCHCOH),
t, J = 7.3 Hz, 2 H, PhmH) 7.40 (app. d, J = 7.3 Hz, 2 H, PhoH)
ppm. 13C NMR (75 MHz): δC = –0.39, –0.15, 1.38, 1.57 (4ϫCH2
of cyclopropyl), 16.30, 17.27 (2ϫCH of cyclopropyl), 26.79 [3 C,
(CH3)3C], 36.14 [(CH3)3C], 42.33 (CH=CHCHtBu), 45.79
78.81 (COH), 122.57 (C=CHCHCOH), 124.33 (CCH=CHCHiPr), (C=CHCHCOH), 74.10 (COH), 123.96 (C=CHCHCOH), 124.68
125.49 (2 C, PhoC), 127.04 (PhpC), 128.40 (2 C, PhmC), 130.70
(CH=CHCHiPr), 136.12 [CH=C(Ph)CH], 140.78 (PhiC) ppm. MS:
m/z (%) = 268 (0.09) [(M+ – 18) + 2], 267 (0.49) [(M+ – 18) + 1],
266 (2.16) [M+ – 18], 198 (34), 155 (100), 154 (32), 87 (34). HRMS:
calcd. for C20H28O: 284.2140; found 284.2092.
(CH=CHCHtBu), 125.43 (2 C, PhoC), 126.84 (PhpC), 128.38 (2 C,
PhmC), 130.12 (CH=CHCHtBu), 135.15 [CH=C(Ph)CH], 141.01
(PhiC) ppm. MS: m/z (%) = 322 (0.005) [M+], 304 (0.08) [M+ – 18],
212 (12), 155 (18), 154 (22), 111 (100), 69 (39), 57 (16). HRMS:
calcd. for C23H30O 322.2297; found 322.2278.
General Procedure for the Preparation of Compounds 12e–f,
[D10]12f, 12g–j: To a deeply colored solution of biphenyl or [D10]-
biphenyl (3 mmol) and lithium powder (Li(s), 12 mmol) in dry THF
(10 mL) at 25 °C with stirring under Ar, the corresponding alkene
(methylenecyclopentane, 3 mmol, 1-octene or norbornene,
3.3 mmol) was added. After ca. 1.5 h the initial greenish-blue color
of I-Li2 or [D10]I-Li2 turned brown. The reaction was then cooled
down to –78 °C and 3-pentanone (8, 6 mmol), dicyclopropyl ketone
(9, 6 mmol) or isobutene oxide (11) was added. After 15 min the
reaction was hydrolyzed (H2O) and worked up as usual (3ϫ20 mL
diethyl ether, Na2SO4, 15 Torr), purifying 12e–j by flash
chromatography (silica gel, Hx/EtOAc), respectively; 0.5 wt.-% of
hydroquinone was added for stabilisation during storage (see
ref.[6]).
Dicyclopropyl[(1RS,6SR)-6-isopropyl-3-phenylcyclohexa-2,4-dienyl]-
methanol (12b): R = 0.36 (9:1, hexane/ethyl acetate). IR (film): ν
˜
f
= 3583, 3490, 3082, 3008, 2956, 2927, 2869, 1599, 1493, 1462, 1447,
1384, 1366, 1021, 1007, 948, 911, 771, 745, 697 cm–1. 1H NMR
(300 MHz, CDCl3): δH = 0.20–0.49 (m, 8 H, 4ϫCH2 of cyclopro-
pyl), 0.92 (app. d, J = 6.9 Hz, 3 H, CH3CHCH3), 0.94 (app. d, J =
6.9 Hz, 3 H, CH3CHCH3), 0.94–1.02 (m, 2 H, 2ϫCH of cyclopro-
pyl), 1.25 (br. s, 1 H, OH), 1.63–1.74 (m, 1 H, CH3CHCH3), 2.57
(app. dd, J = 6.2, 1.6 Hz, 1 H, C=CHCHCOH), 2.63 (app. t, J =
5.6 Hz, 1 H, CH=CHCHiPr), 5.88 (app. dd, J = 9.8, 5.9 Hz, 1 H,
CH=CHCHiPr), 6.06 (app. d, J = 6.1 Hz, 1 H, C=CHCHCOH),
6.27 (app. d, J = 9.8 Hz, 1 H, CH=CHCPh), 7.22–7.43 (m, 5 H,
Ph) ppm. 13C NMR (75 MHz): δC = –0.49, –0.31, 1.33, 1.52
(4ϫCH2 of cyclopropyl), 16.33, 17.17 (2ϫCH of cyclopropyl),
18.76, 19.25 (CH3 CHCH3 ), 34.22 (CH3 CHCH3 ), 38.70
(CH=CHCHiPr), 48.02 (C=CHCHCOH), 74.11 (COH), 123.43
(C=CHCHCOH), 124.23 (CCH=CHCHiPr), 125.47 (2 C, PhoC),
126.85 (PhpC), 128.38 (2 C, PhmC), 130.54 (CH=CHCHiPr), 135.47
[CH=C(Ph)CH], 141.08 (PhiC) ppm. MS: m/z (%) = 308 (0.01)
[M+], 290 (0.12) [M+ – 18], 198 (19), 155 (41), 154 (18), 111 (100),
69 (44). HRMS: calcd. for C22H28O 308.2140; found 308.2135.
3-[(1RS,6SR)-6-(1-Methylheptyl)-3-phenylcyclohexa-2,4-dienyl]pen-
tan-3-ol (12e, 1:1 mixture of diastereomers): Rf = 0.41 (9:1, hexane/
ethyl acetate). IR (film): ν = = 3583, 3490, 3032, 2961, 2927, 2872,
˜
2856, 1599, 1495, 1460, 1448, 1378, 1302, 1261, 1150, 1124, 1004,
1
993, 945, 911, 857, 772, 750, 736, 697 cm–1. H NMR (500 MHz,
CDCl3): δH = 0.84–0.91 (m, 9 H, CH3CH2CO, CH3CHCH2,
CH3CH2CH2), 0.85–0.92 (m, 9 H, CH3CH2CO, CH3CHCH2,
CH3CH2CH2), 0.94 (t, J = 7.3 Hz, 3 H, CH3CH2CO), 0.95 (t, J =
7.3 Hz, 3 H, CH3CH2CO), 1.21–1.32 [m, 10 H, (CH2)5], 1.21–1.32
[m, 10 H, (CH2)5], 1.36 (br. s, 1 H, OH), 1.36 (br. s, 1 H, OH),
1.39–1.45 (m, 1 H, CH3CHCH2), 1.45–1.53 (m, 1 H, CH3CHCH2),
1.56–1.63 (m, 4 H, 2 ϫ CH3 CH2CO), 1.56–1.63 (m, 4 H,
2ϫCH3CH2CO), 2.40 (app. d, J = 5.0 Hz, 1 H, C=CHCHCOH),
2.45 (app. d, J = 5.9 Hz, 1 H, C=CHCHCOH), 2.52 (m, 1 H,
CHCHCH3), 2.59 (m, 1 H, CHCHCH3), 5.78–5.84 [m, 2 H,
CH=C(Ph)CH=CH], 5.78–5.84 [m, 1 H, CH=C(Ph)CH=CH], 5.86
[app. dd, J = 9.6, 5.5 Hz, 1 H, CH=C(Ph)CH=CH], 6.25 [app. d,
J = 9.6 Hz, 1 H, CH=C(Ph)CH=CH], 6.29 [app. d, J = 10.1 Hz, 1
H, CH=C(Ph)CH=CH], 7.25 (app. t, J = 7.8 Hz, 1 H, PhpH), 7.26
(app. t, J = 7.8 Hz, 1 H, PhpH), 7.33 (app. t, J = 6.9 Hz, 2 H, PhmH),
7.33 (app. t, J = 6.9 Hz, 2 H, PhmH), 7.39 (app. d, J = 8.2 Hz, 2 H,
PhoH), 7.39 (app. d, J = 8.2 Hz, 2 H, PhoH) ppm. 13C NMR
(75 MHz, CDCl3): δC = 7.52, 7.55, 7.82, 7.82, 14.06, 14.06, 15.27,
15.89 (8ϫCH3), 22.64, 22.64, 27.08, 27.14, 27.50, 27.64, 27.89,
27.89, 29.52, 29.58, 31.86, 31.91, 32.44, 33.39 (14ϫCH2), 36.74,
37.54 (2ϫCHCHCH3), 39.37, 41.16 (2ϫCHCHCH3), 42.26, 44.33
(2 ϫ CHCOH), 78.70, 78.80 (2 ϫ COH), 122.69, 122.73
[2ϫCH=C(Ph)CH=CH], 123.95, 124.74 [2ϫCH=C(Ph)CH=CH],
3-[(1RS,6SR)-6-tert-Butyl-3-phenylcyclohexa-2,4-dienyl]pentan-3-ol
(12c): R = 0.39 (9:1, hexane/ethyl acetate). IR (film): ν = 3584,
˜
f
3500, 3036, 2964, 2879, 1599, 1494, 1463, 1447, 1392, 1365, 1224,
1151, 1128, 994, 945, 856, 767, 750, 699, 638 cm–1 1H NMR
.
(300 MHz, CDCl3): δH = 0.87 (t, J = 7.5 Hz, 3 H, CH3CH2), 0.91
(s, 9 H, 3ϫCH3C), 0.97 (t, J = 7.5 Hz, 3 H, CH3CH2), 1.47 (br. s,
1 H, OH), 1.54–1.68 (m, 4 H, 2 ϫ CH3CH2), 2.30 (app. d, J =
5.9 Hz, 1 H, CH=CHCHtBu), 2.59 (app. d, J = 6.4 Hz, 1 H,
C=CHCHCOH), 5.80 (app. d, J = 6.4 Hz, 1 H, C=CHCHCOH),
5.93 (app. dd, J = 6.1, 9.9 Hz, 1 H, CH=CHCHtBu), 6.31 (app. d,
J = 9.8 Hz, 1 H, CH=CHCPh), 7.23–7.41 (m, 5 H, Ph) ppm. 13C
NMR: δC = 7.53, 7.92 (2ϫCH3CH2), 26.77 [3 C, (CH3)3C], 26.99,
27.87 (2ϫCH2CH3), 36.17 (CCH3), 40.47 (C=CHCHCOH), 41.96
(CH=CHCHtBu), 78.82 (COH), 123.04 (C=CHCHCOH), 124.59
(CCH=CHCHtBu), 125.45 (2 C, PhoC), 127.02 (PhpC), 128.41 (2 C,
PhmC), 130.67 (CH=CHCHtBu), 135.69 [CH=C(Ph)CH], 140.73
(PhiC) ppm. MS: m/z (%) = 282 (0.16) [(M+ – 18) + 2], 281 (0.94)
[(M+ – 18) + 1], 280 (3.73) [M+ – 18], 212 (28), 156 (44), 155 (100),
154 (59), 153 (12), 87 (61), 57 (24). HRMS: calcd. for C21H28
280.2191; found 280.2197.
Dicyclopropyl[(1RS,6SR)-6-tert-butyl-3-phenylcyclohexa-2,4-dienyl]- 125.42 (2 C), 125.42 (2 C, 4 ϫ PhoC), 126.92, 126.92 (2 ϫ PhpC),
methanol (12d): R = 0.44 (9:1, hexane/ethyl acetate). IR (film): ν
= 3584, 3082, 3008, 2960, 2904, 2866, 1599, 1492, 1465, 1447, 1392,
1 2 8 . 3 0 ( 2 C ), 1 2 8 . 3 0 ( 2 C, 4 ϫ P h m C ) , 1 2 9 . 8 7 , 1 3 1 . 3 7
[2 ϫ CH=C(Ph)CH=CH], 136.10, 136.14 [2 ϫ CH=C(Ph)CH],
˜
f
5520
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5514–5526

Carbolithiation of Alkenes
140.81, 140.81 (2ϫPhiC) ppm. MS: m/z (%) = 354 (0.01) [M+], 336
(0.60) [M+ – 18], 268 (21) 156 [30], 155 (100), 154 (52), 111 (100), 87
(35), 57 (10). HRMS: calcd. for C25H36 336.2817; found 336.2824.
(0.01) [(M+ – 18) + 1], 330 (0.12) [M+ – 18], 156 (20), 155 (12), 154
(22), 111 (100), 83 (18), 69 (36), 55 (12). HRMS: calcd. for C25H32O
348.2453; found 348.2454.
3-[(1RS,6SR)-6-(1-Methylcyclopentyl)-3-phenylcyclohexa-2,4-di- cis-2-Methyl-1-[4-(1-methylcyclopentyl)-1-phenylcyclohexa-2,5-di-
1
enyl]pentan-3-ol (12f): Rf = 0.45 (9:1, hexane/ethyl acetate). IR
enyl]propan-2-ol (cis-12h): Rf = 0.48 (8:2, hexane/ethyl acetate). H
NMR (300 MHz): δH = 0.69 (s, 3 H, CH3C), 1.27 [s, 6 H, (CH3)2-
COH], 1.40–1.55 (m, 4 H, 4ϫCHH of cyclopentyl), 1.58–1.69 (m,
4 H, 4ϫCHH of cyclopentyl), 2.14 (s, 2 H, CCH2COH), 2.25 (br.
s, 1 H, OH), 2.57–2.63 [m, 1 H, (CH=CH)2CHCCH3], 5.87 [app.
dd, J = 10.6, J = 3.1 Hz, 2 H, (CH=CH)2CH], 6.14 [dd, J = 10.6,
J = 2.0 Hz, 2 H, (CH=CH)2C(Ph)], 7.12–7.20 (m, 1 H, Ph), 7.25–
(film): ν = 3483, 3033, 2958, 2876, 1599, 1494, 1460, 1447, 1376,
˜
1124, 1004, 947, 911, 855, 748, 734, 698 cm–1. 1H NMR (300 MHz,
CDCl3): δH = 0.85 (s, 3 H, CH3C), 0.87 (app. t, J = 7.5 Hz, 3 H,
CH3CH2), 0.97 (t, J = 7.3 Hz, 3 H, CH3CH2), 1.25 (br. s, 1 H,
OH), 1.36–1.68 [m, 8 H, (CH2)4], 1.55–1.68 (m, 4 H, 2ϫCH2CH3),
2.41 (app. d, J = 5.8 Hz, 1 H, CH=CHCHCCH3), 2.55 (app. d, J
= 6.2 Hz, 1 H, C=CHCHCOH), 5.81 (d, J = 6.4 Hz, 1 H, 7.32 (m, 2 H, Ph), 7.35–7.41 (m, 2 H, Ph) ppm. 13C NMR
C=CHCHCOH), 5.90 (app. dd, J = 10.0, 5.9 Hz, 1 H,
CH=CHCHCCH3), 6.29 (app. d, J = 10.0 Hz, 1 H, CH=CHCPh),
7.25–7.42 (m, 5 H, Ph) ppm. 13C NMR (75 MHz): δC = 7.50, 7.86
(2ϫCH3CH2), 21.30 (CH3C), 23.35, 23.93 (CH2CH2CH2C), 27.05,
(75 MHz): δC = 23.14 (CH3C), 24.18 (2ϫ CH2 of cyclopentyl),
31.29 [2 C, (CH3)2COH], 38.35 (2 ϫCH2 of cyclopentyl), 43.59
[(CH=CH)2C(Ph)], 46.27 (CH3C), 46.62 [(CH=CH)2CH], 53.67
(CCH2COH), 72.31 (COH), 125.79 (CHPh), 126.13 (2 C, CHPh),
27.79 (2 ϫ CH2CH3), 37.07, 37.33 [CH2C(CH3)CH2], 42.22 127.21 [2 C, (CH=CH)2CH], 128.21 (2 C, CHPh), 134.36 [2 C,
(C=CHCHCOH), 42.37 [CH=CHCHC(CH3)], 48.56 [CH2C(CH3)- (CH=CH)2C(Ph)], 148.77 (CPh) ppm. IR (film): ν = 3436, 3020,
˜
CH2], 78.73 (COH), 123.14 [CH=C(Ph)CH=CH], 124.62
2956, 2869, 1597, 1492, 1446, 1373, 1216, 1161, 912, 803, 744, 698
[CH=C(Ph)CH=CH], 125.45 (2 C, PhoC), 127.01 (PhpC), 128.39 cm–1. MS: m/z (%) = 311 (0.01) [M+ + 1], 310 (0.02) [M+], 292
(2 C, PhmC), 131.13 (CH=CHCHC), 135.93 [CH=C(Ph)CH],
140.83 (PhiC) ppm. MS: m/z (%) = 324 (0.002) [M+], 306 (1.75)
(2.4), 236 (14), 221 (14), 210 (14), 209 (54), 178 (10), 168 (14), 167
(86), 165 (16), 155 (35), 154 (100), 153 (18), 152 (17), 83 (95), 55
[M+ – 18], 238 (18), 236 (11), 221 (19), 167 (17), 157 (12), 156 (100), (33). HRMS: calcd. for C22H28: 292.2191; found 292.2161.
155 (81), 154 (74), 153 (14), 152 (11), 87 (64), 83 (37), 57 (10), 55
(17). HRMS: calcd. for C23H30 306.2348; found 306.2343.
trans-2-Methyl-1-[4-(1-methylcyclopentyl)-1-phenylcyclohexa-2,5-di-
enyl]propan-2-ol (trans-12h): Rf = 0.47 (8:2, hexane/ethyl acetate).
3-[(1RS,6SR)-6-(1-Methylcyclopentyl)-3-(2,3,4,5,6-pentadeuterio-
1H NMR (300 MHz): δH = 0.88 (s, 3 H, CH3C), 1.29 [s, 6 H, (CH3)2-
phenyl)-1,2,4,5,6-pentadeuteriocyclohexa-2,4-dienyl]pentan-3-ol COH], 1.51–1.58 (m, 4 H, 4ϫCHH of cyclopentyl), 1.62–1.72 (m,
([D10]12f): 1H NMR (300 MHz, CDCl3): δH = 0.85 (s, 3 H, CH3C), 4 H, 4ϫCHH of cyclopentyl), 2.06 (br. s, 1 H, OH), 2.17 (s, 2 H,
0.86 (app. t, J = 7.4 Hz, 3 H, CH3CH2), 0.97 (t, J = 7.3 Hz, 3 H, CCH2COH), 2.52–2.56 [m, 1 H, (CH=CH)2CH], 5.90 [app. dd, J
CH3CH2), 1.35 (br. s, 1 H, OH), 1.37–1.69 [m, 8 H, (CH2)4], 1.56– = 10.4, J = 2.3 Hz, 2 H, (CH=CH)2CH], 6.10 [app. dd, J = 10.4,
1.69 (m, 4 H, 2ϫCH2CH3) ppm. 13C NMR (75 MHz): δC = 7.50,
7.86 (2ϫCH3CH2), 21.31 (CH3C), 23.38, 23.94 (CH2CH2CH2C),
J = 2.5 Hz, 2 H, (CH=CH)2C(Ph)], 7.13–7.21 (m, 1 H, Ph), 7.27–
7.41 (m, 4 H, Ph) ppm. 13C NMR (75 MHz): δC = 23.57 (CH3C),
27.07, 27.79 (2ϫCH2CH3), 37.03, 37.31 [CH2C(CH3)CH2], 41.59 24.28 (2ϫCH2 of cyclopentyl), 31.62 [2 C, (CH3)2COH], 38.51
(t, J = 18.8 Hz, C=CHCDCOH), 41.62 [t, J = 18.8 Hz, (2ϫCH2 of cyclopentyl), 43.78 [(CH=CH)2C(Ph)], 45.91 (CH3C),
CH=CHCDC(CH3)], 48.46 [CH2C(CH3)CH2], 78.67 (COH), 46.52 [(CH=CH)2CH], 52.89 (CCH2COH), 72.34 (COH), 125.99
122.64 [t, J = 24.3 Hz, CH=C(Ph)CH=CH], 124.21 [t, J = 24.3 Hz, (2 C, CHPh), 126.02 (CHPh), 127.42 [(CH=CH)2CH], 128.42 (2 C,
CH=C(Ph)CH=CH], 125.01 (t, J = 24.3 Hz, 2 C, PhoC), 126.48 (t, CHPh), 134.73 [2 C, (CH=CH)2C(Ph)], 148.32 (CPh) ppm. IR
J = 24.3 Hz, PhpC), 127.88 (t, J = 24.3 Hz, 2 C, PhmC), 130.58 (t, J
= 24.3 Hz, CH=CHCHC), 135.74 [CH=C(Ph)CH], 140.60 (PhiC)
(film): ν = 3445, 3021, 2955, 2869, 1597, 1491, 1445, 1372, 1140,
˜
914, 741, 697 cm–1. MS: m/z (%) = 311 (0.02) [M+ + 1], 310 (0.11%)
ppm. MS: m/z (%) = 317 (0.06) [(M+ – 18) + 1], 316 (0.24) [M+
–
[M+], 292 (1.6), 221 (13), 209 (18), 167 (45), 165 (11), 155 (21), 154
18], 248 (19), 167 (13), 166 (100), 165 (77), 164 (50), 163 (32),162
(11), 87 (53), 83 (32), 55 (13). HRMS: calcd. for C23H20D10
316.2975; found 316.2929.
(71), 153 (10), 83 (100), 55 (28). HRMS: calcd. for C22H28
292.2191; found 292.2228.
:
3-{trans-[6-(exo-2-Norbornyl)-3-phenylcyclohexa-2,4-dienyl]}pentan-
3-ol (trans-exo-12i, minor isomer): Rf = 0.29 (8:2, hexane/ethyl ace-
tate). 1H NMR (300 MHz): δH = 0.85 (app. t, J = 7.5 Hz, 3 H,
CH3CH2), 0.93 (app. t, J = 7.5 Hz, 3 H, CH3CH2), 1.01–1.67 (m,
Dicyclopropyl[(1RS,6SR)-6-(1-methylcyclopentyl)-3-phenylcyclo-
hexa-2,4-dienyl]methanol (12g): Rf = 0.48 (9:1, hexane/ethyl ace-
tate). IR (film): ν = 3582, 3082, 3007, 2954, 2869, 1599, 1491, 1447,
˜
1376, 1020, 1005, 910, 953, 761, 740, 697 cm–1
(300 MHz, CDCl3): δH = 0.20–0.49 (m, 8 H, 4ϫCH2 of cyclopro-
pyl), 0.87 (s, 3 H, CH3C), 0.94–1.04 (m, 2 H, 2ϫCH of cyclopro- H, H1 , H4 of norbornyl), 2.32 (app. d, J = 6.4 Hz, 1 H,
pyl), 1.25 (br. s, 1 H, OH), 1.38–1.69 (m, 8 H, 4ϫCH2 of cyclopen- C=CHCHCOH), 5.85 (app. d, J = 6.4 Hz, 1 H, C=CHCHCOH),
tyl), 2.60 (app. d, J = 5.9 Hz, 1 H, CH=CHCHCCH3), 2.68 (app. 6.14 (app. dd, J = 9.9, J = 5.8 Hz, 1 H, CH=CHCH), 6.22 (app.
d, J = 6.3 Hz, 1 H, C=CHCHCOH), 5.89 (app. dd, J = 9.9, 5.9 Hz, dd, J = 9.8, J = 1.4 Hz, 1 H, CH=CHCPh), 7.26–7.30 (m, 1 H,
1 H, CH=CHCHCCH3), 6.08 (app. d, J = 6.2 Hz, C=CHCHCOH) Ph), 7.31–7.39 (m, 2 H, Ph), 7.40–7.46 (m, 2 H, Ph) ppm. 13C NMR
.
1H NMR 14 H, 4ϫCH2 and H2-endo of norbornyl, 2ϫCH2CH3, OH), 2.14
(app. dd, J = 10.7, J = 6.0 Hz, 1 H, CH=CHCH), 2.19–2.29 (m, 2
6.29 (app. d, J = 9.9 Hz, 1 H, CH=CHCPh), 7.23–7.43 (m, 5 H,
Ph) ppm. 13C NMR (75 MHz): δC = –0.50, –0.17, 1.43, 1.61
(4ϫCH2 of cyclopropyl), 16.31, 17.22 (2ϫCH of cyclopropyl),
(75 MHz): δC = 7.59, 7.98 (2ϫCH3), 27.26, 28.27 (2ϫCH2CH3),
28.81, 30.47, 35.70 (3 ϫ CH2), 36.56 (CH), 36.74 (CH2), 36.89
(CH=CHCH), 38.63 (CH), 42.34 (C=CHCHCOH), 46.28 (CH),
21.45 (CH3C), 23.49, 24.05 (CH2CH2CH2CH2), 37.13, 37.26 78.78 (COH), 121.56 (C=CHCHCOH), 122.94 (CCH=CHCH),
( CH2 CH2 CH2 CH2 ), 42.54 (CH=CHCHCCH 3 ) , 4 7. 53 125.52 (2 C, PhoC), 127.12 (PhpC), 128.41 (2 C, PhmC), 133.72
(C=CHCHCOH), 48.52 (CH3 C), 74.09 (COH), 124.03 (CH=CHCH), 136.18 [CH=C(Ph)CH], 140.39 (PhiC) ppm. IR
(C=CHCHCOH), 124.74 (CCH=CHCHCCH3) 125.45 (2 C, PhoC),
126.83 (PhpC), 128.39 (2 C, PhmC), 130.60 (CH=CHCHCCH3),
135.42 [CH=C(Ph)CH], 141.13 (PhiC) ppm. MS: m/z (%) = 331
(film): ν = 3441, 2947, 2867, 1660, 1644, 1633, 1494, 1454, 748,
˜
733, 696 cm–1. MS (70 eV, EI): m/z (%) = 320 (0.45) (M+ – 18) +
2], 319 (1.84) [(M+ – 18) + 1], 318 (6.90) [M+ – 18], 289 (10), 251
Eur. J. Org. Chem. 2007, 5514–5526
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5521

C. Melero, A. Guijarro, V. Baumann, Á. J. Pérez-Jiménez, M. Yus
FULL PAPER
(14), 250 (68), 223 (19), 181 (14), 167 (24), 156 (25), 155 (100), 154
(80), 153 (12), 95 (67), 87 (46), 67 (15). HRMS: calcd. for C24H30:
318.2348; found 318.2370.
304 (1.6), 248 (10), 167 (22), 154 (17), 95 (100), 67 (14). HRMS:
calcd. for C23H28: 304.2191; found 304.2173.
Preparation of Compounds trans-13, cis-13 and 14: To a deeply col-
ored solution of naphthalene or phenanthrene (3 mmol) and lith-
ium powder [Li(s), 12 mmol] in dry THF (10 mL) at 25 °C with
vigorous stirring under Ar, propene was delivered using a ballon
(approx. 3 L, 1 atm), ensuring a complete evacuation of the Ar.
After ca. 2 h the reaction was then cooled down to –78 °C and 3-
pentanone (8) (6 mmol) was added. After 15 min the reaction was
hydrolyzed (H2O) and worked up as usual (3ϫ20 mL diethyl ether,
Na2SO4, 15 Torr), purifying trans-13, cis-13 or 14, respectively, by
flash chromatography (silica gel, Hx/EtOAc); 0.5 wt.-% of hydro-
quinone was added for stabilisation during storage (see ref.[6]).
3-{trans-[6-(exo-2-Norbornyl)-3-phenylcyclohexa-2,4-dienyl]}pentan-
1
3-ol (trans-exo-12i, major isomer): H NMR (300 MHz): δH = 0.87
(t, J = 7.4 Hz, 3 H, CH3CH2), 0.94 (t, J = 7.4 Hz, 3 H, CH3CH2),
1.02–1.18 (m, 3 H, H7-anti, H6-endo and H5-endo of norbornyl), 1.32–
1.68 (m, 10 H, H7-syn, H2-endo, H3-exo, H3-endo, H5-exo and H6-exo of
norbornyl, 2ϫCH2CH3), 2.10–2.30 (m, 4 H, CH=CHCH, H1 and
H4 of norbornyl, OH), 2.54 (app. d, J = 6.3 Hz, C=CHCHCOH),
5.85 (app. d, J = 6.4 Hz, 1 H, C=CHCHCOH), 6.01 (app. dd, J =
9 . 9 , J = 6. 0 Hz, 1 H, CH=CHCH), 6. 24 (app. d, 1 H,
CH=CHCPh), 7.26–7.30 (m, 1 H, Ph), 7.30–7.38 (m, 2 H, Ph),
7.40–7.46 (m, 2 H, Ph) ppm. 13C NMR (75 MHz): δC = 7.63, 7.94
(2ϫCH3), 27.18, 28.21 (2ϫCH2CH3), 28.65, 30.41, 35.60, 35.85
(4 ϫ CH2), 36.43 (CH), 36.71 (CH=CHCH), 38.40 (CH), 44.54
(C=CHCHCOH), 46.52 (CH), 121.66 (C=CHCHCOH), 123.75
(CCH=CHCH), 125.48 (2 C, PhoC), 127.08 (PhpC), 128.39 (2 C,
PhmC), 132.04 (CH=CHCH), 136.15 [CH =C(Ph)CH], 140.38
(PhiC) ppm. MS (70 eV, EI): m/z (%) = 337 (0.03) [M+ + 1], 336
(0.10) [M+], 318 (11), 289 (16), 251 (17), 250 (85), 223 (24), 181
(17), 167 (26), 165 (11), 156 (24), 155 (100), 154 (87), 153 (14), 152
(11), 95 (58), 87 (41), 67 (16). HRMS: calcd. for C24H30: 318.2348;
found 318.2303
3-[(1RS,4RS)-4-Isopropyl-1,4-dihydronaphth-1-yl]pentan-3-ol (trans-
13): R = 0.39 (9:1, hexane/ethyl acetate). IR (film): ν = 3582, 3537,
˜
f
3489, 3060, 3035, 2962, 2936, 2880, 1485, 1462, 1384, 1367, 1154,
1
1121, 1089, 938, 823, 750 cm–1. H NMR (300 MHz, CDCl3): δH
= 0.55 (d, J = 6.9 H, 3 H, CH3CHCH3), 0.78 (app. t, J = 7.5 Hz,
3 H, CH3CH2), 1.00 (app. t, J = 7.4 Hz, 3 H, CH3CH2), 1.19 (d, J
= 6.9 Hz, 3 H, CH3CHCH3), 1.39 (br. s, 1 H, OH), 1.41–1.53 (m,
2 H, CH2CH3), 1.52–1.64 (m, 2 H, CH2CH3), 2.52–2.64 (m, 1 H,
CH3CHCH3), 3.28–3.32 (m, 1 H, CH=CHCHiPr), 3.59–3.63 (m, 1
H, CH=CHCHCOH), 6.02–6.11 (m, 2 H, CH=CHCHCOH), 7.14–
7.29 (m, 3 H, CHCH=CHCCHCO), 7.39 (app. d, J = 7.7 Hz, 1
H, CH=CHCCHiPr) ppm. 13C NMR (75 MHz): δC = 7.48, 7.70
(2 ϫ CH3 CH2), 16.08, 21.07 (CH3 CHCH3), 27.91, 28.07
(2ϫCH2CH3), 30.18 (CH3CHCH3), 43.22 (CH=CHCHiPr), 46.99
(CH=CHCHCOH), 79.24 (COH), 125.12, 125.99, 126.19
(3ϫCHar), 127.77, 128.27 (CH=CHCHiPr), 129.32 (CHar), 136.04,
139.85 (2ϫCar) ppm. MS: m/z (%) = 241 (0.11) [(M+ – 18) + 1],
240 (0.53) [M+ – 18], 172 (25), 130 (11), 129 (100), 128 (51), 87
(35). HRMS: calcd. for C18H24 240.1878; found 240.1881.
cis-2-Methyl-1-[4-(exo-2-norbornyl)-1-phenylcyclohexa-2,5-dienyl]-
propan-2-ol (trans-12h): Rf = 0.31 (8:2, hexane/ethyl acetate). 1H
NMR (400 MHz): δH = 1.06–1.13 (m, 3 H, H7-anti, H6-endo, H5-endo
of norbornyl), 1.26 (2s, 6 H, 2ϫCH3), 1.26–1.39 (m, 4 H, H7-syn
,
,
H2-endo, H3-exo, H3-endo of norbornyl), 1.44–1.50 (m, 2 H, H5-exo
H6-exo of norbornyl), 2.15 (app. s, 2 H, CCH2COH), 2.19–2.25 (m,
2 H, H1, H4 of norbornyl), 2.21 (br. s, 1 H, OH), 2.45–2.51 [m, 1
H, (CH=CH)2CH], 5.80–5.85 [m, 1 H, (CH=CH)CH], 5.90–6.01
[m, 3 H, (CH=CH)CH, (CH=CH)2CH], 7.15–7.21 (m, 1 H, Php),
7.27–7.33 (m, 2 H, Pho), 7.34–7.40 (m, 2 H, Phm) ppm. 13C NMR
(100 MHz): δC = 28.52, 30.56 (2ϫCH2), 31.36, 31.37 (2ϫCH3),
35.75, 35.94 (2ϫCH2), 36.67, 38.58 (2ϫCH), 39.81 [(CH=CH)2-
CH], 43.86 [(CH=CH)2C(Ph)], 47.98 (CH), 52.95 (CH2COH),
72.30 (COH), 125.90 (CHPh), 126.16 (2 C, CHPh), 126.94, 127.86
[(CH=CH)2CH], 128.32 (2 C, CHPh), 133.29, 133.65 [(CH=CH)2-
3-[(1RS,4SR)-4-Isopropyl-1,4-dihydronaphth-1-yl]pentan-3-ol (cis-
13): R = 0.45 (9:1, hexane/ethyl acetate). IR (film): ν = 3582, 3507,
˜
f
3058, 3031, 2964, 2880, 2868, 1486, 1461, 1382, 1365, 1247, 1157,
1125, 971, 952, 936, 846, 825, 752 cm–1 1H NMR (300 MHz,
.
CDCl3): δH = 0.88 (app. t, J = 7.6 Hz, 3 H, CH3CH2), 1.00 (app.
t, J = 7.6 Hz, 3 H, CH3 CH2 ), 1.02 (d, J = 6.9 Hz, 3 H,
CH3CHCH3), 1.10 (d, J = 6.6 Hz, 3 H, CH3CHCH3), 1.22 (br. s,
1 H, OH), 1.39–1.47 (m, 1 H, CHHCH3), 1.51–1.65 (m, 2 H,
CH2CH3), 1.66–1.76 (m, 1 H, CHHCH3), 1.93–2.03 (m, 1 H,
CH3CHCH3), 2.98–3.03 (m, 1 H, CH=CHCHiPr), 3.60–3.65 (m, 1
H, CH=CHCHCOH), 5.93 (app. dd, J = 10.4, 5.1 Hz, 1 H,
CH=CHCHCOH), 6.21 (app. dd, J = 10.4, 5.0 Hz, 1 H,
CH=CHCHiPr), 7.14–7.31 (m, 3 H, CHar), 7.32 (app. d, J =
6.3 Hz, 1 H, CHar) ppm. 13C NMR (75 MHz): δC = 7.85, 7.89
(CH3CH2), 21.10, 22.67 (CH3CHCH3), 29.12, 29.15 (CH2CH3),
35.58 (CH3CH), 46.98 (CH=CHCHCOH), 47.54 (CH=CHCHiPr),
76.75 (COH), 125.18, 125.52 (CHar), 126.52 (CH=CHCHCOH),
129.98, 130.47 (CHarom), 131.34 (CH=CHCHiPr), 135.48, 140.13
(Car) ppm. MS: m/z (%) = 241 (0.06) [(M+ – 18) + 1], 240 (0.30)
[M+ – 18], 172 (24), 130 (11), 129 (100), 128 (49), 87 (56). HRMS:
calcd. for C18H24 240.1878: found 242.1904.
CH], 148.58 (CPh) ppm. IR (film): ν = 3436, 3020, 2949, 2867, 1596,
˜
1491, 1454, 1372, 1139, 744, 697 cm–1. MS (70 eV, EI): m/z (%) =
324 (0.003) [M+ + 2], 323 (0.06) [M+ + 1], 322 (0.24) [M+], 248
(16), 209 (10), 168 (11), 167 (27), 154 (21), 95 (100), 67 (16).
HRMS: calcd. for C23H28 304.2191; found 304.2182.
trans-2-Methyl-1-[4-(exo-2-norbornyl)-1-phenylcyclohexa-2,5-dienyl]-
propan-2-ol (trans-12h): Rf = 0.47 (8:2, hexane/ethyl acetate). 1H
NMR (300 MHz): δH = 1.10–1.18 (m, 3 H, H7-anti, H6-endo, H5-endo
of norbornyl), 1.29 (2s, 6 H, 2ϫCH3), 1.22–1.57 (m, 6 H, H7-syn
,
H2-endo, H3-exo, H3-endo, H5-exo, H6-exo of norbornyl), 2.18 (app. s, 2
H, CCH2COH), 2.20 (br. s, 1 H, OH), 2.24–2.29 (m, 1 H, H4 of
norbornyl), 2.29–2.35 (m, 1 H, H1 of norbornyl), 2.36–2.44 [m, 1
H, (CH=CH)2CH], 5.82–5.89 [m, 1 H, (CH=CH)CH], 5.93–6.04
[m, 3 H, (CH=CH)CH, (CH=CH)2C(Ph)], 7.13–7.20 (m, 1 H, Pho),
7.24–7.40 (m, 4 H, Ph) ppm. 13C NMR (75 MHz): δC = 28.53, 3-[(9RS,10RS)-10-Isopropyl-9,10-dihydrophenanthren-9-yl]pentan-3-
30.52 (2ϫCH2), 31.63, 31.69 (2ϫCH3), 35.59, 36.37 (2ϫCH2),
36.74, 38.60 (2ϫCH), 39.67 [(CH=CH)2CH], 43.84 [(CH=CH)2-
C(Ph)], 47.52 (CH), 52.51 (CCH2COH), 72.35 (COH), 125.99
ol (14): R = 0.27 (9:1, hexane/ethyl acetate). IR (film): ν = 3585,
˜
f
3482, 3066, 3031, 2965, 2880, 1726, 1482, 1461, 1438, 1383, 1256,
1156, 1132, 975, 938, 910, 741 cm–1. 1H NMR (300 MHz, CDCl3):
(CHPh), 126.03 (2 C, CHPh), 126.75, 127.52 [(CH=CH)2CH], δH = 0.70 (d, J = 6.4 Hz, 3 H, CH3CHCH3), 0.76 (app. t, J =
128.35 (2 C, CHPh), 133.37, 133.62 [(CH=CH)2CH], 148.25 (CPh
)
7.3 Hz, 3 H, CH3CH2), 0.87 (app. t, J = 7.3 Hz, 3 H, CH3CH2),
0.91 (d, J = 6.9 Hz, 3 H, CH3CHCH3), 1.22–1.32 (m, 2 H,
C H 2 C H3 ) , 1 . 2 7 ( b r. s, 1 H , O H ) , 1 . 3 8 – 1 . 4 9 ( m , 2 H ,
CH3CHHCOH, CH3CHCH3), 1.52–1.60 (m, 1 H, CH3CHHCOH),
ppm. IR (film): ν = 3435, 3022, 2950, 2868, 1667, 1597, 1491, 1454,
˜
1372, 1299, 1214, 1033, 916, 743, 697 cm–1. MS (70 eV, EI): m/z
(%) = 324 (0.005) [M+ + 2], 323 (0.04) [M+ + 1], 322 (0.15) [M+],
5522
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5514–5526

Carbolithiation of Alkenes
2.58 (app. d, J = 8.7 Hz, 1 H, CCHiPr), 3.11 (app. s, 1 H,
CCHCOH), 7.12–7.35 (m, 6 H, CHar), 7.70 (app. d, J = 7.8 Hz, 1
H, CHar), 7.74 (app. d, J = 7.3 Hz, 1 H, CHar) ppm. 13C NMR
calcd. for C15H17D 199.1471: found 199.1463. [D1]15b (second
major isomer): 1H NMR (400 MHz, CDCl3): δH = 0.97 (d, J =
6.8 Hz, 6 H, CH3CHCH3), 1.75–1.86 (m, 1 H, CH3CHCH3), 2.69–
(75 MHz): δC = 7.54, 8.10 (CH3CH2), 21.00, 21.51 (CH3CHCH3), 2.77 (m, 1 H, CHiPr), 5.67–5.81 [m (app. AAЈBBЈ), 4 H,
28.04, 28.38 (CH2CH3), 31.37 (CH3CHCH3), 46.99 (CCHiPr), PhCD(CH=CH)2CHiPr], 7.19–7.41 (m, 5 H, Ph) ppm. MS: m/z
47.27 (CCHCOH), 77.1 (COH), 123.60, 123.60, 127.03, 127.21,
127.30, 127.44, 130.01, 131.58 (CHar), 134.53, 135.17, 135.74, [M+], 198 (0.00%) [M+ – 1], 157 (13), 156 (100), 155 (17), 154 (17).
138.99 (Car) ppm. MS: m/z (%): 291 (0.13) [(M+ – 18) + 1], 290
HRMS: calcd. for C15H17D 199.1471: found 199.1471. [D1]15c
(0.55) [M+ – 18], 222 (22), 180 (14), 179 (100), 178 (41), 87 (11). (minor isomer): 1H NMR (400 MHz, CDCl3): δH = 0.94 (d, J =
(%) = 201 (0.22) [M+ + 2], 200 (2.62%) [M+ + 1], 199 (15.43%)
HRMS: calcd. for C22H26 290.2035: found 290.2038.
6.8 Hz, 6 H, CH3CHCH3), 1.75–1.86 (m, 1 H, CH3CHCH3), 2.69–
2.77 (m, 1 H, CHiPr), 5.67–5.83 [m, 4 H, PhCH(CH=CH)2CHiPr],
7.19–7.41 (m, 5 H, Ph) ppm. MS: m/z (%) = 201 (0.19) [M+ + 2],
200 (2.42%) [M+ + 1], 199 (14.56%) [M+], 198 (0.00%) [M+ – 1],
157 (13), 156 (100), 155 (15), 154 (18). HRMS: calcd. for C15H17D
199.1471: found 199.1465.
Preparation of Compounds 15a–c and [D1]15a–c: To a deeply col-
ored solution of biphenyl (3 mmol) and lithium powder [Li(s)
,
12 mmol] in dry THF (10 mL), at 25 °C with vigorous stirring un-
der Ar, propene was delivered using a ballon (approx. 3 L, 1 atm),
ensuring complete evacuation of the Ar atmosphere. After ca. 3 h
the reaction was then cooled down to –78 °C and D2O (20 mmol
in 2 mL of THF) or H2O (20 mmol in 2 mL of THF), respectively,
was added drop by drop via syringe. Afterwards, the reaction was
hydrolyzed (H2O) and worked up as usual (3ϫ20 mL diethyl ether,
Na2SO4, 15 Torr), purifying 15a–c and [D1]15a–c by flash
chromatography (silica gel doped with 1 wt.-% of hydroquinone,
Hx/EtOAc); 0.5 wt.-% of hydroquinone was added for stabilisation
during storage (see ref.[6]). The reactions carried out in [D8]THF
(2 mL) were run and worked up under analogous reaction condi-
tions, scaling down all the reagents appropriately.
Preparation of Minor Products 16–19: Allyl bromide (1 mmol) or
3-bromo-2-methylpropene (1 mmol) was added to a suspension of
Mg (5 mmol) in dry THF (5 mL) and was stirred vigorously at
room temperature. After 1 h, 3-pentanone (1 mmol) or dicyclopro-
pyl ketone (1 mmol) was added, allowing the mixture to react dur-
ing 15 min. The reaction was then hydrolyzed (H2O), extracted
(3ϫ20 mL diethyl ether, Na2SO4, 15 Torr) and the resulting prod-
ucts 16 (ca. 60%), 17 (ca. 60%), 18 (ca. 55%), 19 (ca. 65%) (unopti-
mized yields) were purified by column chromatography (silica gel,
Hx/EtOAc).
3-Ethyl-5-hexen-3-ol (16)[34] and 3-ethyl-5-methyl-5-hexen-3-ol (18)[34]
were prepared according to the above-mentioned procedure. The
spectroscopic data are identical to those described in the literature.
4-Isopropyl-3,4-dihydrobiphenyl (15a) and trans- and cis-4-Isopropyl-
1,4-dihydrobiphenyl (15b and 15c, respectively). Mixture of Isomers:
1
15a (major isomer): H NMR (300 MHz, CDCl3): δH = 0.94 (d, J
= 6. 9 Hz, 3 H, CH3 CHCH3 ), 0.95 (d, J = 6.9 Hz, 3 H,
CH3CHCH3), 1.68–1.82 (m, 1 H, CH3CHCH3), 2.18–2.25 (2 m,
2ϫ1 H, CHHCHiPr), 2.25–2.40 (m, 1 H, CHHCHiPr), 5.92 (app.
dd, J = 9.8, 2.6 Hz, 1 H, CH=CHCHiPr), 6.05–6.10 (m, 1 H,
C=CHCH2), 6.32 (app. dt, J = 9.8, 1.8 Hz, 1 H, CH=CHCHiPr),
7.19–7.41 (m, 5 H, Ph) ppm. MS: m/z (%) = 200 (0.29) [M+ + 2],
199 (3.69%) [M+ + 1], 198 (22.58%) [M+], 156 (14), 155 (100), 154
(32), 153 (16), 77 (10). HRMS: calcd. for C15H18 198.1409: found
198.1382. 15b (second major isomer): 1H NMR (300 MHz,
CDCl3): δH = 0.98 (d, J = 6.8 Hz, 6 H, CH3CHCH3), 1.70–1.88
(m, 1 H, CH3CHCH3), 2.69–2.78 (m, 1 H, CHiPr), 3.94–4.02 (m,
1 H, PhCH), 5.67–5.81 [m (app. AAЈBBЈ), 4 H, PhCH(CH=CH)2-
CHiPr], 7.19–7.41 (m, 5 H, Ph) ppm. MS: m/z (%): 200 (0.31,
[M++2), 199 (2.44%, [M++1), 198 (14.91%, [M+), 156 (13), 155
(100), 154 (22), 153 (14), 77 (11). HRMS: calcd. for C15H18
198.1409: found 198.1393. 15c (minor isomer): 1H NMR
(300 MHz, CDCl3): δH = 0.95 (d, J = 6.8 Hz, 6 H, CH3CHCH3),
1.70–1.88 (m, 1 H, CH3CHCH3), 2.70–2.80 (m, 1 H, CHiPr), 3.86–
3.93 (m, 1 H, PhCH), 5.67–5.83 [m, 4 H, PhCH(CH=CH)2CHiPr],
7.19–7.41 (m, 5 H, Ph) ppm. MS: m/z (%) = 200 (0.21) [M+ + 2],
199 (2.24%) [M+ + 1], 198 (13.20%) [M+], 156 (14), 155 (100), 154
(20), 153 (14), 77 (11). HRMS: calcd. for C15H18 198.1409: found
198.1385.
1,1-Dicyclopropylbut-3-en-1-ol (17): IR (film): ν = 3422, 2925, 1728,
˜
1644, 1463, 1261, 1074, 797 cm–1. 1H NMR (300 MHz, CDCl3): δH
= 0.26–0.43 (m, 8 H, 4ϫCH2 of cyclopropyl), 0.80–0.92 (m, 2 H,
2ϫCH of cyclopropyl), 1.03 (br. s, 1 H, OH), 2.35 (d, J = 7.3 Hz,
2 H, CH2CH=CH2), 5.08–5.15 (2 m, 2ϫ1 H, CH2=CH), 5.97–6.09
(m, 1 H, CH2CH=CH2) ppm. 13C NMR (75 MHz): δC = –0.48
(2 C), 0.64 (2 C, 4ϫCH2 of cyclopropyl), 18.73 (2 C, 2ϫCH of
cyclopropyl), 47.16 (CH2CH=CH2), 118.13 (CH2=CH), 134.49
(CH=CH2) ppm. MS: m/z (%) = 134 (M+ – 18) [0.03], 111 (100),
69(99), 55 (11). HRMS: calcd. for C7H11O: 111.0810; found
111.0814.
1,1-Dicyclopropyl-3-methylbut-3-en-1-ol (19): IR (film): ν = 3548,
˜
3084, 3007, 2918, 1643, 1438, 1374, 1230, 1171, 1122, 1022, 991,
1
893, 828 cm–1. H NMR (300 MHz, CDCl3): δH = 0.26–0.48 (m, 8
H, 4ϫCH2 of cyclopropyl), 0.80–0.87 (m, 2 H, 2ϫCH of cyclopro-
pyl), 1.24 (br. s, 1 H, OH), 1.91 (app. s, 3 H, CH3C=CH2), 2.31
[app. s, 2 H, CH2C(CH3)=CH2], 4.77, 4.91 [2 app. s, 2 ϫ 1 H,
CH2=C(CH3)] ppm. 13C NMR (75 MHz): δC = –0.26 (2 C), 1.01
(2 C, 4ϫCH2 of cyclopropyl), 19.18 (2 C, 2ϫCH of cyclopropyl),
25.01 [CH2C(CH3)=CH2], 49.94 [CH2C(CH3)=CH2], 69.90 (COH),
114.53 (CH2=C), 143.10 (C=CH2) ppm. MS: m/z (%) = 111 (1.05)
[M+ – C4H7], 110 (13), 109 (13), 69 (100). HRMS: calcd. for
C11H18O: 166.1358; found 166.1377.
(3RS,4SR)-3-Deuterio-4-isopropyl-3,4-dihydrobiphenyl ([D1]15a)
and trans- and cis-1-Deuterio-4-isopropyl-1,4-dihydrobiphenyl
([D1]15b and [D1]15c, respectively). Mixture of Isomers: [D1]15a
(major isomer): 1H NMR (400 MHz, CDCl3): δH = 0.93 (d, J =
6.9 Hz, 3 H, CH3CHCH3), 0.95 (d, J = 6.9 Hz, 3 H, CH3CHCH3),
Preparation of Minor Products 20 and 21: To a solution of 1-methyl-
cyclopentene (2 mmol) in dry cyclohexane (10 mL), TMEDA
(2 mmol) and tert-butyllithium (1.5 mmol, 1.7  in pentane) was
added, the mixture being stirred for 1 h at room temperature. The
1.70–1.80 (m, 1 H, CH3CHCH3), 2.17–2.21 [2 m, 2 ϫ 1 H, reaction was then cooled down to 0 °C and 3-pentanone
CHDCHiPr], 5.90 (app. d, J = 9.9 Hz, 1 H, CH=CHCHiPr), 6.05 (1.5 mmol), or dicyclopropyl ketone (1.5 mmol) was added, respec-
(app. br. s, 1 H, C=CHCHD), 6.32 (app. d, J = 10.1 Hz, 1 H, tively. After 15 min the reaction was hydrolyzed (H2O) and worked
CH=CHCHiPr), 7.19–7.41 (m, 5 H, Ph) ppm. MS: m/z (%) = 201 up as usual (3ϫ20 mL diethyl ether, Na2SO4, 15 Torr), purifying
(0.34) [M+ + 2], 200 (4.09%) [M+ + 1], 199 (23.92%) [M+], 198
compounds 20 (60%) and 21 (50%) (unoptimized yields) by flash
chromatography (silica gel, Hx/EtOAc).
(0.00%) [M+ – 1], 157 (14), 156 (100), 155 (29), 154 (18). HRMS:
Eur. J. Org. Chem. 2007, 5514–5526
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5523

C. Melero, A. Guijarro, V. Baumann, Á. J. Pérez-Jiménez, M. Yus
FULL PAPER
3-(2-Methylenecyclopentyl)pentan-3-ol (20): IR (film): ν = 3419, C H = C H C ( P h ) = C H ] , 6 . 3 4 [ ap p. d , J = 1 0 . 0 H z , 1 H ,
˜
2925, 1651, 1455, 1120 cm–1. 1H NMR (300 MHz, CDCl3): δH
0.88 (app. t, 3 H, J = 7.5 Hz, CH3CH2), 0.91 (app. t, J = 7.5 Hz,
=
CH=CHC(Ph)=CH], 7.22–7.44 (m, 5 H, Ph), 10.20 (very br. s, 1
H, CO2H) ppm. MS: m/z (%) = 244 (0.47) [M+ + 2], 243 (4.22%)
3 H, CH3CH2), 1.31 (br. s, 1 H, OH), 1.40–1.70 (2 m, 4 H, [M+ + 1], 242 (23.3%) [M+], 181 (12), 156 (13), 155 (100), 154 (17),
2ϫCH2CH3), 1.41–1.54 (m, 1 H, CHHCH2C=CH2), 1.51–1.68 (m, 153 (17), 152 (14).
1 H, CH2CHHCHCOH), 1.69–1.82 (m, 1 H, CHHCH2C=CH2),
1.78–1.91 (m, 1 H, CH2CHHCHCOH), 2.12–2.34 (m, 2 H,
Preparation of Dihydronaphthalenes 23a and 23b: To a deeply col-
ored solution of naphtalene (3 mmol) and lithium powder [Li(s)
,
CH2C=CH2), 2.65 (app. td, J = 8.3, 1.7 Hz, 1 H, CH2=CCHCOH),
4.92, 5.05 (app. 2s, 2ϫ1 H, CH2=C) ppm. 13C NMR (75 MHz):
δC = 7.69, 7.85 (2 ϫ CH3CH2), 25.17 (CH2CH2C=CH2), 27.73
(CH2CH3), 28.10 (CH2CH2CHCOH), 28.74 (CH2CH3), 36.69
(CH2C=CH2), 49.49 (CH2=CCHCOH), 108.32 (CH2=C), 153.99
(C=CH2) ppm. MS: m/z (%) = 150 (0.20) [M+ – 18], 87 (100), 82
(31), 80 (11), 69 (15), 67 (31), 57 (68). HRMS: calcd. for C11H18:
150.1409; found 150.1463.
12 mmol] in dry THF (10 mL) at 25 °C under Ar, propene was
delivered using a ballon (approx. 3 L, 1 atm) ensuring complete
evacuation of the Ar. After ca. 2 h, the initial purple color of II–2
turned brown. The reaction was then cooled down to –78 °C and
the reaction was hydrolyzed (H2O) and worked up as usual
(3ϫ20 mL diethyl ether, Na2SO4, 15 Torr), purifying 23a and 23b
by flash chromatography (silica gel was doped with 1 wt.-% of hy-
droquinone, Hx/EtOAc); 0.5 wt.-% of hydroquinone was added for
stabilisation during storage (see ref.[6]).
Dicyclopropyl(2-methylenecyclopentyl)methanol (21): IR (film): ν =
˜
3542, 3085, 3007, 2956, 2869, 1647, 1469, 1433, 1376, 1303, 1180,
1112, 1022, 992, 912, 890, 834 cm–1. 1H NMR (300 MHz, CDCl3):
δH = 0.25–0.50 (m, 8 H, 4ϫCH2 of cyclopropyl), 0.80–0.88 (m, 2
H, 2ϫCH of cyclopropyl), 1.26 (br. s, 1 H, OH), 1.08–1.12, 1.78–
1.89 (2 m, 2 ϫ 1 H, CH2CH2C=CH2), 1.83–2.00 (m, 2 H,
CH2CH2CHCOH), 2.29–2.42 (m, 2 H, CH2C=CH2), 2.67–2.73 (m,
1 H, CH2=CCHCOH), 5.01, 5.05 (2 app. s, 2ϫ1 H, CH2=C) ppm.
13C NMR (75 MHz): δC = –1.38, –0.83, 1.12, 1.73 (4ϫCH2 of cy-
clopropyl), 16.38, 16.89 (2 ϫ CH of cyclopropyl), 25.03
(CH2CH2C=CH2), 28.36 (CH2CHC=CH2), 35.67 (CH2C=CH2),
54.78 (CH2CHC=CH2), 71.84 (COH), 108.11 (CH2=C), 154.22
(C=CH2) ppm. MS: m/z (%) = 174 (0.08) [M+ – 18], 111 (100), 69
(68).
1-Isopropyl-1,4-dihydronaphthalene (23a): Rf = 0.58 (hexane). IR
(film): ν = 3029, 2958, 2927, 2869, 2869, 2820, 1492, 1456, 1424,
˜
1
1382, 1365, 745 cm–1. H NMR (300 MHz, CDCl3): δH = 0.68 (d,
J = 6.9 Hz, 3 H, CH3CHCH3 ), 0.98 (d, J = 6.9 Hz, 3 H,
CH3CHCH3), 2.00–2.12 (m, 1 H, CH3CHCH3), 3.21–3.44 (m, 3
H, CH2CH=CHCHiPr), 5.88–5.94 (m, 1 H, CH2CH=CHCHiPr),
6.04–6.08 (m, 1 H, CH2CH=CHCHiPr), 7.08–7.18 (m, 4 H, CHar)
ppm. 13C NMR (75 MHz): δC = 17.42, 20.47 (CH3CHCH3), 30.45
(CH2), 36.07 (CH3CHCH3), 45.80 (CHiPr), 125.51, 125.71, 126.27,
126.69,127.93, (CH=CHCH2, 4ϫCHar), 135.26, 138.48 (2ϫCar)
ppm. MS: m/z (%) = 174 (0.03) [M+ + 2], 173 (0.56) [M+ + 1], 172
(3.80) [M+], 130 (11), 129 (100), 128 (60), 127 (14). HRMS: calcd.
for C13H16 172.1252: found 172.1258.
1-Isopropyl-1,2-dihydronaphthalene (23b): Rf = 0.55 (hexane). IR
Preparation of Carboxylic Acids 22a–b: To a solution containing
dilithium biphenyl (I) prepared as described before for compounds
12, propene was delivered using a balloon (approx. 3 L, 1 atm)
previous evacuation of Ar. After ca. 1 h, the initial greenish-blue
color of I–2 turned brown. The reaction was then cooled down to
–78 °C and CO2(g) was passed through. After 15 min, the reaction
was hydrolyzed with water. The aqueous layer was acidified (12 
HCl) and extracted with diethyl ether (3 ϫ 20 mL). The diethyl
ether extract was then dried (Na2SO4) and concentrated under re-
duce pressure, purifying 22a–b by flash chromatography (silica gel,
Hx/EtOAc); 0.5 wt.-% of hydroquinone was added for stabilisation
during storage (see ref.[6]).
(film): ν = 3032, 2956, 2869, 2831, 1484, 1462, 1450, 1431, 1384,
˜
1
1366, 792, 757, 728, 686 cm–1. H NMR (300 MHz, CDCl3): δH
=
0.82 (d, J = 6.9 Hz, 3 H, CH3CHCH3), 0.90 (d, J = 6.9 Hz, 3 H,
CH3CHCH3), 1.90–1.99 (m, 1 H, CH3CHCH3), 2.35–2.50 (m, 3 H,
CH=CHCH2CHiPr), 5.87–5.95 (m, 1 H, CH=CHCH2), 6.39 (app.
d, J = 9.2 Hz, 1 H, CH=CHCH2), 7.00 (app. d, J = 6.9 Hz, 1 H,
CHar), 7.05–7.16 (m, 3 H, CHar) ppm. 13C NMR (75 MHz): δC
=
20.03, 21.26 (CH3CHCH3), 25.40 (CH2), 30.61 (CH3CHCH3),
43.53 (CHiPr), 125.92, 126.32, (3 ϫ CHar), 127.42, 127.57
(CH=CHCH2), 128.58 (CHar), 133.91, 138.28 (2ϫCar) ppm. MS:
m/z (%) = 174 (0.20) [M+ + 2], 173 (3.01) [M+ + 1], 172 (21.51)
[M+], 130 (13), 129 (100), 128 (64), 127 (16). HRMS: calcd. for
C13H16 172.1252: found 172.1258.
4-trans-Isopropyl-1-phenylcyclohexa-2,5-dienecarboxylic Acid (22a):
R = 0.47 (7:3, hexane/ethyl acetate). IR (film): ν = 3034, 2958,
˜
f
2871, 2621, 1704, 1490, 1386, 1275, 1235, 916, 830, 733, 697 cm–1.
1H NMR (300 MHz, CDCl3): δH = 0.92 (d, J = 6.9 Hz, 6 H,
CH3CHCH3), 1.80–1.91 (m, 1 H, CH3CHCH3), 2.65–2.72 (m, 1 H,
CHiPr), 5.89 [app. dd, J = 10.3, 3.3 Hz, 2 H, (CH=CH)2CHiPr],
6.12 [app. dd, J = 10.4, 1.9 Hz, 2 H, (CH=CH)2C(Ph)CO2H], 7.20–
7.40 (m, 5 H, Ph), 13.10 (very br. s, 1 H, CO2H) ppm. 13C NMR
(75 MHz): δC = 19.14 (2 C, CH3CHCH3), 31.11 (CH3CHCH3),
41.25 (CHiPr), 52.88 [(CH=CH)2C(Ph)CO2H], 126.31 (2 C),
127.05, 127.79 (2 C), 128.61 (2 C), 128.73 (2 C, (CH=CH)2CHiPr,
PhCH], 143.04 (PhiC), 179.44 (CO2H) ppm. MS: m/z (%) = 243
(0.08) [M+ + 1], 242 (0.33%) [M+], 197 (31), 181 (13), 156 (13),
155 (100), 154 (17), 153 (16), 152 (14), 77 (10). HRMS: calcd. for
C16H18O2: 242.1307; found 242.1290.
Supporting Information (see also the footnote on the first page of
this article): Table S1 showing HOMO atomic contributions and
population analysis data of arene dianions I؊2–III؊2 from B3LYP
calculations.
Acknowledgments
CM, AG, VB and MY thank the Spanish Ministerio de Educación
y Ciencia (MEC) (no. CTQ2004-01261, Consolider Ingenio 2010
CSD2007-00006) and the Generalitat Valenciana (GV) (no.
GRUPOS03/135, GV05/52 and GV07/36) for financial support.
A. J. P. J. is thankful for financial support from MEC (no.
CTQ2004-06519/BQU) and from GV through the “Ramón y Ca-
jal” program. C. M. thanks the University of Alicante for a predoc-
toral fellowship. We also thank Medalchemy S. L. and Chemetall
GmbH for gifs of chemicals.
(1RS,6SR)-6-Isopropyl-3-phenylcyclohexa-2,4-dienecarboxylic Acid
(22b) (impure sample contaminated with acid 22a): 1H NMR
(300 MHz, CDCl3): δH = 0.94 (d, J = 6.7 Hz, 3 H, CH3CHCH3),
0.98 (d, J = 6.7 Hz, 3 H, CH3CHCH3), 1.74–1.92 (m, 1 H,
CH3CHCH3), 2.73–2.84 (m, 1 H, CHiPr), 3.43 [app. dd, J = 8.5,
5 . 3 H z , 1 H , ( C H C O 2 H ) ] , 5 . 8 5 – 5 . 9 7 [ 2 m , 2 ϫ 1 H ,
[1] a) F. W. Bailey, J. M. Mealy, B. K. Wiberg, Org. Lett. 2002, 4,
791–794; b) A. Krief, B. Kenda, B. Remacle, Tetrahedron 1996,
5524
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5514–5526

Carbolithiation of Alkenes
52, 7435–7463; c) W. F. Bailey, M. R. Luderer, M. J. Mealy, Tet-
rahedron Lett. 2003, 44, 5303–5305; d) N. J. Ashweek, I.
Coldham, D. J. Snowden, G. P. Vennall, Chem. Eur. J. 2002, 8,
195–207; e) W. F. Bailey, A. D. Khanolkar, K. Gavaskar, T. V.
Ovaska, K. Rossi, Y. Thiel, K. B. Wiberg, J. Am. Chem. Soc.
1991, 113, 5720–5727; f) A. Krief, B. Remacle, J. Mercier, Syn-
lett 2000, 1443–1446; g) R. Pedrosa, C. Andrés, J. M. Iglesias,
A. Pérez-Encabo, J. Am. Chem. Soc. 2001, 123, 1817–1821; h)
J. Barluenga, F. J. Fañanas, R. Sanz, C. Marcos, Chem. Eur. J.
2005, 11, 5397–5407; i) M. Yus, R. Ortiz, Eur. J. Org. Chem.
2004, 3833–3841; j) M. J. Woltering, R. Fröhlich, D. Hoppe,
Angew. Chem. Int. Ed. Engl. 1997, 36, 1764–1766; k) D. Hoppe,
T. Hense, Angew. Chem. Int. Ed. Engl. 1997, 36, 2282–2316,
and references therein.
a) H. Felkin, G. Swierczewski, A. Tambuté, Tetrahedron Lett.
1969, 10, 707–710; b) J. K. Crandall, A. C. Clark, J. Org. Chem.
1972, 37, 4236–4242; c) S. Raucher, G. A. Koolpe, J. Org.
Chem. 1978, 43, 4252–4253; d) S. Klein, I. Marek, J.-F. Poisson,
J.-F. Normant, J. Am. Chem. Soc. 1995, 117, 8853–8854; e) E.
Lorthiois, I. Marek, C. Meyer, J. F. Normant, Tetrahedron Lett.
1996, 37, 6689–6692; f) S. Norsikian, I. Marek, S. Klein, J. F.
Poisson, J. F. Normant, Chem. Eur. J. 1999, 5, 2055–2068; g)
X. Wei, R. J. K. Taylor, Angew. Chem. Int. Ed. 2000, 39, 409–
412; h) S. Majumdar, A. De Meijere, I. Marek, Synlett 2002,
423–426; i) X. Wei, R. J. K. Taylor, Tetrahedron Lett. 2003, 44,
7143–7146; j) D. R. Williams, J. T. Reeves, P. P. Nag, W. H. Pit-
cock Jr, M.-H. Baik, J. Am. Chem. Soc. 2006, 128, 12339–
12348.
a) P. D. Barlett, S. J. Tauber, W. P. Weber, J. Am. Chem. Soc.
1969, 91, 6362–6366; b) J. C. Carnahan, W. D. Closson Jr, J.
Org. Chem. 1972, 37, 4469–4471; c) A. Maercker, R. Stoetzel,
J. Organomet. Chem. 1983, 254, 1–12; d) A. Krief, P. Barbeaux,
Tetrahedron Lett. 1991, 32, 417–420; e) C. G. Screttas, B. R.
Steele, J. Organomet. Chem. 1993, 453, 163–170; f) S. Rummel,
S. M. Yunusov, H. Langguth, V. B. Shur, Russ. Chem. Bull.
1999, 48, 2083–2085.
M. Yus in The Chemistry of Organolithium Compounds (Ed.: Z.
Rappoport, I. Marek), part 2, vol. 1, Wiley, Chichester, 2004,
pp. 657–747.
J. J. Eisch, J. Org. Chem. 1963, 28, 707–710.
M. Yus, R. P. Herrera, A. Guijarro, Chem. Eur. J. 2002, 8,
2574–2584.
[17]
a) R. J. Abraham, A. P. Barlow, A. E. Rowan, Magn. Reson.
Chem. 1989, 27, 1074–1084; b) R. J. Abraham, J. Fischer,
Magn. Reson. Chem. 1985, 10, 856–861.
[18]
[19]
T. Saji, S. Aoyagui, J. Electroanal. Chem. 1983, 144, 143–152.
The cis/trans assignment of the stereochemistry was done after
examination of the cross-signals in NOESY experiments be-
tween: i. one of the methylene protons and the opposite me-
thyne proton of the 1,4-dihydronaphthyl moiety in trans-13,
absent in the cis isomer, ii. the two 1,4-methyne protons of the
1,4-dihydronaphthyl moiety, noticeable in cis-13, but absent in
the trans isomer.
[20]
[21]
a) P. Hohenberg, W. Kohn, Phys. Rev. 1964, 136, B864–871; b)
W. Kohn, L. J. Sham, Phys. Rev. 1965, 140, A1133–1138.
a) M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr., T.
Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar,
J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N.
Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K.
Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y.
Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P.
Hratchian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts,
R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pom-
elli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P.
Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich,
A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D.
Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui,
A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu,
A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J.
Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara,
M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W.
Wong, C. Gonzalez, J. A. Pople, GAUSSIAN03, Revision B.01,
Gaussian, Inc., Pittsburgh PA, 2003; b) A. D. Becke, J. Chem.
Phys. 1993, 98, 5648–5652; c) P. J. Stephens, F. J. Devlin, C. F.
Chablowski, M. J. Frisch, J. Phys. Chem. 1994, 98, 11623–
11627.
a) E. Cancès, B. Mennucci, J. Tomasi, J. Chem. Phys. 1997, 107,
3032–3041; b) M. Cossi, V. Barone, B. Mennucci, J. Tomasi, J.
Chem. Phys. Lett. 1998, 286, 253–260; c) B. Mennucci, J. Tom-
asi, J. Chem. Phys. 1997, 106, 5151–5158; d) M. Cossi, G. Scal-
mani, N. Rega, V. Barone, J. Chem. Phys. 2002, 117, 43–54.
This is the simplest approach to take into account the solvent
effect, but has proved to be very reliable for charged species
(see ref.[22d]), including also dianions: a) P. Zazakowny, M.
Makowski, M. T. Pawlikowski, Chem. Phys. Lett. 2006, 418,
555–560 and charged complexes: b) A. J. A. Aquino, D. Tu-
nega, G. Haberhauer, M. Gerzabek, H. Lischka, Phys. Chem.
Chem. Phys. 2000, 2, 2845–2850.
[2]
[3]
[4]
[22]
[23]
[5]
[6]
[7]
M. Yus, R. P. Herrera, A. Guijarro, Tetrahedron Lett. 2001, 42,
3455–3458.
R. P. Herrera, A. Guijarro, M. Yus, Tetrahedron Lett. 2003, 44,
1313–1316.
[8]
[9]
Preliminary communication: C. Melero, A. Guijarro, M. Yus,
[24]
[25]
[26]
[27]
Tetrahedron Lett. 2006, 47, 6267–6271.
J. J. Brooks, W. Rhine, G. D. Stucky, J. Am. Chem. Soc. 1972,
94, 7346–7351.
K. Muellen, Helv. Chim. Acta 1978, 61, 1296–1304.
W. Huber, A. May, K. Muellen, Chem. Ber. 1981, 114, 1318–
1336.
R. Krishnan, J. S. Binkley, R. Seeger, J. A. Pople, J. Chem.
Phys. 1980, 72, 650–654.
A. E. Reed, L. A. Curtiss, F. Weinhold, Chem. Rev. 1988, 88,
899–926.
T. Clark, J. Chandrasekhar, G. W. Spitznagel, P. v. R. Schleyer,
J. Comput. Chem. 1983, 4, 294–301.
[10]
[11]
[12]
[13]
a) M. Guerra, Chem. Phys. Lett. 1992, 197, 205–212; b) A.
Alberti, C. Barberis, M. Campredon, G. Gronchi, M. Guerra,
J. Phys. Chem. 1995, 99, 15779–15784; c) T. Sommerfeld, J.
Am. Chem. Soc. 2002, 124, 1119–1124.
A. I. Boldyrev, M. Gutowski, J. Simons, Acc. Chem. Res. 1996,
29, 497–502.
R. G. Parr, W. Yang, Density-Functional Theory of Atoms and
Molecules, international series of monographs on chemistry,
no. 16 (Eds.: R. Breslow, J. B. Goodenough, J. Halpern J. S.
Rowlinson), Oxford Science Publications, Oxford University
Press, New York, 1994, p. 99–101.
A noticeable difference between these two kinds of calculations,
interesting from a theoretical point of view, is the geometry of
the stationary point. While PM3 afforded flat structures (D2h
for I–2 and II–2, C2v for III–2), B3LYP/6-31+G(d,p) gave sta-
tionary points of lower symmetry (C2h for I–2, D2h for II–2, and
a) A. N. Sidorov, Opt. Spektrosc. 1979, 47, 678–683. Chem.
Abstr. 1979, 92, 110107; b) J. P. Devlin, J. S. McKennis, C.
Thornton, J. C. Moore, J. Phys. Chem. 1982, 86, 2613–2616.
K. Meerholz, J. Heinze, J. Am. Chem. Soc. 1989, 111, 2325–
2326.
a) M. Rabinovitz, Top. Curr. Chem. 1988, 146, 99–169; b) A.
Minsky, A. Y. Meyer, M. Rabinovitz, Tetrahedron Lett. 1982,
23, 5351–5354; c) A. Minsky, A. Y. Meyer, M. Rabinovitz, Tet-
rahedron 1985, 41, 785–791.
The cis/trans assignment of the stereochemistry in these cases
was done after examination of the cross-signals in NOESY ex-
periments between i. the ortho-phenyl protons and the methyl-
cyclopentyl moiety in 12h, present in the cis isomer and absent
in the trans isomer, ii. the ortho-phenyl protons and the only
methyne proton of the cyclohexadienyl moiety in 12j, small but
present in the trans isomer and absent in the cis isomer.
[14]
[15]
[28]
[29]
[16]
[30]
Eur. J. Org. Chem. 2007, 5514–5526
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5525

C. Melero, A. Guijarro, V. Baumann, Á. J. Pérez-Jiménez, M. Yus
FULL PAPER
C2 for III–2), corroborated in both cases by harmonic vi-
brational analysis.
with electrophiles is also well known: b) A. J. Birch, A. L.
Hinde, L. Radom, J. Am. Chem. Soc. 1980, 102, 6430–6437.
[33] The trans-assignment of the stereochemistry was done after ex-
amination of the cross-signals in a NOESY experiments be-
tween the ortho-phenyl protons and the isopropyl protons of
trans-22a.
[31] These calculated data are consistent with classical semiempir-
ical calculations on the cyclohexadienyl anion and benzocy-
clohexadienyl anion: M. J. S. Dewar, R. C. Dougherty, The
PMO Theory of Organic Chemistry, chapter 7.7, Plenum Press,
New York, 1975..
[32] For analogous semiempirical and ab initio calculations on the
cyclohexadienyl anion: a) J. Burdon, I. W. Parsons, E. J. Avra-
mides, J. Chem. Soc. Perkin Trans. 1 1979, 1268–1272. The ex-
perimental regiochemistry displayed by this anion in reaction
[34] D. Guijarro, B. Mancheño, M. Yus, Tetrahedron 1992, 48,
4593–5600.
Received: May 17, 2007
Published Online: September 21, 2007
5526
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 5514–5526