Organolithium addition to styrene and styrene derivatives: Scope and limitations

Article abstract of DOI:10.1039/a910195k

Styrene and a range of aryl-substituted styrene derivatives are shown to undergo efficient carbolithiation-trapping reactions in diethyl ether at -78 to -25 °C. The reactivities of different types of organolithium reagents were found to be: tertiary, secondary > primary; ? alkenyl, methyl, phenyl. Electron donating groups (e.g. methoxy and dialkylamino) at the ortho- or para- positions of the benzene ring deactivate the double bond towards organolithium addition, but their reactions with butyllithium can be facilitated by using TMEDA as co-solvent. 2-Benzyloxystyrene and 2-allyloxystyrene undergo efficient carbolithiation at -78 °C, but at room temperature alkyl transfer occurs, generating the corresponding alkylated phenol. 2-Vinylnaphthalene also undergoes carbolithiation-carboxylation in reasonable yield.

Full text of DOI:10.1039/a910195k

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Organolithium addition to styrene and styrene derivatives:
scope and limitations
Xudong Wei, Paul Johnson and Richard J. K. Taylor*
1
Department of Chemistry, University of York, Heslington, York, UK YO10 5DD.
E-mail: rjkt1@york.ac.uk
Received (in Cambridge, UK) 20th December 1999, Accepted 4th February 2000
Published on the Web 13th March 2000
Styrene and a range of aryl-substituted styrene derivatives are shown to undergo efficient carbolithiation–trapping
reactions in diethyl ether at Ϫ78 to Ϫ25 ЊC. The reactivities of different types of organolithium reagents were
found to be: tertiary, secondary > primary; ӷ alkenyl, methyl, phenyl. Electron donating groups (e.g. methoxy and
dialkylamino) at the ortho- or para- positions of the benzene ring deactivate the double bond towards organolithium
addition, but their reactions with butyllithium can be facilitated by using TMEDA as co-solvent. 2-Benzyloxystyrene
and 2-allyloxystyrene undergo efficient carbolithiation at Ϫ78 ЊC, but at room temperature alkyl transfer occurs,
generating the corresponding alkylated phenol. 2-Vinylnaphthalene also undergoes carbolithiation–carboxylation
in reasonable yield.
Introduction
Alkene carbolithiation is, in principle, a synthetically efficient
and versatile procedure (Scheme 1).1 The intermediate organo-
Scheme 1
lithium is produced with complete atom economy and can be
trapped with a range of electrophiles, thus assembling three
components in a one-pot process.2 In practice, however, such a
process is not always viable. The reaction is usually accom-
panied by anionic oligomerisation and this process often dom-
inates. Therefore it is usually necessary to adjust the reaction
conditions according to the reactivity of the organolithium
reagent, the nature of the alkene, steric effects, etc. in order to
minimise this side reaction.
Scheme 2
substituents which could inhibit the oligomerisation process.
However, the reactions of styrene with butyllithium and iso-
butyllithium were also efficient (>80%), although the lower
reactivity of these reagents required that a higher reaction tem-
perature (Ϫ25 ЊC) be employed (Table 1, entries 5 and 10);
compounds 7a,b resulting from the addition of a second mole-
The anionic polymerisation of styrene using organolithium
reagents is a well-known process3 and, presumably for this
reason, there are few reports1,4,5 in the literature of its organo-
metallic addition reactions, although some of its alkenyl-
substituted derivatives have been more thoroughly studied.1,6–8
We recently discovered that organolithium addition reactions to
styrene are synthetically viable under appropriate conditions.9
We went on to develop an enantioselective variant of this pro-
cess10 and extended the basic methodology to tetralin syn-
thesis.11 Herein, we report our full results on the scope and
limitations of the styrene–organolithium addition process.
cule of styrene to the intermediate organolithium were present
as minor by-products in these reactions.
In the addition of butyllithium to styrene, a comparison of
the solvents was carried out (Table 1, entries 5, 7 and 8). No
reaction was observed using hexane as solvent from Ϫ78 ЊC
to room temperature. In contrast, with THF as solvent, rapid
polymerisation was observed on addition of the alkyllithium
reagent, even at Ϫ78 ЊC. The absence of reaction in hexane was
unsurprising but the dramatic difference between diethyl ether
and THF is noteworthy. These observations presumably indi-
cate that the organolithium reagent must be reactive enough to
add to styrene but that the resulting lithiated intermediate has
to be sufficiently stabilised to minimise oligomerisation. In the
cases mentioned the use of diethyl ether as solvent appears to
meet these requirements. This delicate balance is emphasised
in the reaction of methyllithium with styrene (Table 1, entry
11). No reaction was observed in diethyl ether from Ϫ78 ЊC to
Results and discussion
(i) Organolithium additions to styrene
As illustrated in Table 1 and Scheme 2, styrene underwent effi-
cient addition reactions with a range of commercial and home-
made organolithium reagents in diethyl ether giving adducts
in good isolated yields. Thus, treatment of styrene with tert-
butyllithium or sec-butyllithium in diethyl ether as solvent
at Ϫ78 ЊC followed by protonation using methanol gave the
expected adducts in almost quantitative yields (Table 1, entries
1 and 3). It seemed possible that the facility of these additions
was due to the steric bulk of the secondary and tertiary
DOI: 10.1039/a910195k
J. Chem. Soc., Perkin Trans. 1, 2000, 1109–1116
This journal is © The Royal Society of Chemistry 2000
1109

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Table 1 Organolithium addition reactions with styrenea
Entry
R
E
Solvent
T/ЊC
Ϫ78
Ϫ78
Ϫ78
Ϫ78
Ϫ25
Ϫ25
Ϫ78
Ϫ78→room temp.
Ϫ25
Ϫ25
Ϫ78→room temp.
Ϫ78→room temp.
Ϫ78→room temp.
Ϫ25
Product
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
But
H
CO2H
H
CO2H
H
CO2H
H
H
Me3Si
H
H
H
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
THF
Hexane
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
1a
1b
2a
2b
3a
3b
93b
92
94
86
85c
84
—
—
51
82f
—
—
—
82
60
But
Bus
Bus
Bu
Bu
Bu
Bu
d
—
e
—
Bu
3c
Bui
4a
g
Me
Ph
—
h
—
—
h
Cyclohex-1-enyl
C10H21
PhCH2CH2
H
H
H
5a
6a
Ϫ25
a All products were isolated and fully characterised by spectroscopy; new compounds were also characterised by HRMS or elemental analysis.
b Styrene did not react with tert-butylmagnesium chloride, even at room temperature; But2CuLi gave 1a in 85% yield. c Diadduct 7a was also obtained
(7%). d Polymer obtained. e No reaction. f Diadduct 7b was also obtained (12%). g No reaction in diethyl ether or THF (polymerisation occurred
when TMEDA was added to ether reaction). h Polymerisation occurred in ether, THF and ether–TMEDA.
room temperature but in this case changing to THF had no
effect. The addition of N,N,NЈ,NЈ-tetramethylethylenediamine
(TMEDA) to the methyllithium in the diethyl ether reaction,
however, caused polymerisation. Although phenyllithium and
cyclohexenyllithium are more reactive than methyllithium, their
addition reaction to styrene did not occur in diethyl ether
between Ϫ78 and Ϫ10 ЊC, and warming the reaction mixture
produced only polystyrene when TMEDA was added.
All of the above transformations were accomplished using
commercial organolithium reagents. Entries 14 and 15 in Table
1 indicate that this is not a requirement. Decyllithium (entry
14) and 2-phenylethyllithium (entry 15), prepared by trans-
metallation of the corresponding iodides,12 gave good to fair
yields of the required adducts.
In several cases the intermediate organolithium reagent was
trapped with other electrophiles. Thus carboxylation gave the
expected acids 1b–3b in high isolated yields (Table 1, entries 2, 4
and 6, respectively), and trimethylsilylation (R = Bu) gave 3c in
51% yield (Table 1, entry 9).
Scheme 3
(ii) Organolithium addition to aryl-substituted styrene derivatives
Thus, in the presence of two equivalents of TMEDA, the
We next examined the reaction of aryl-substituted styrenes in
order to assess the substituent effects. Scheme 3 and Table 2
illustrate a number of examples in which aryl-substituted
styrenes have been shown to react with organolithium reagents.
The reactions of the three methoxystyrene isomers (ortho-,
meta- and para-) were tested first. We anticipated that an ortho-
or para-methoxy group would deactivate the alkene more
than the meta-methoxy group, and this was indeed the case.
Although tert-butyllithium added to all three isomers at low
temperature (Ϫ78 ЊC) gave the corresponding protonated or
carboxylated products 19a, 19b, 21a, 23a and 23b in good (75–
91%) yields (Table 2, entries 1, 2, 6, 8 and 9), reactions of the
o- and p-methoxystyrene isomers were slower than that of the
meta-isomer as monitored by TLC. The reaction of the para-
isomer was so slow that a higher temperature (Ϫ44 ЊC) was
required to ensure that the reaction was complete within 1 hour
(Table 2, entries 8 and 9). This effect was reflected more obvi-
ously in the reaction of these compounds with butyllithium. As
with styrene, m-methoxystyrene reacted with butyllithium
smoothly at Ϫ25 ЊC giving product 22a in 61% yield after
protonation with methanol (Table 2, entry 7). However, o- and
p-methoxystyrenes were found not to be reactive enough at this
temperature: no reaction was observed within 1 hour, but
at higher temperature both reactions gave polymer (Table 2,
entries 3 and 10). For synthetic purposes, this problem was
overcome by the addition of TMEDA to the reaction mixture.
reaction of butyllithium with o-methoxystyrene proceeded
smoothly at Ϫ78 ЊC producing the substituted benzylic organo-
lithium intermediates within one hour. The intermediates were
subsequently quenched using methanol or trimethylsilyl chlo-
ride giving products 20a and 20c in fair yields (Table 2, entries 4
and 5). Under the same conditions, however, no adduct could
be detected from the reaction of butyllithium with p-methoxy-
styrene. Although a red solution was obtained after 1 hour,
quenching with methanol at Ϫ78 ЊC gave recovered starting
material only. However, slowly warming this red solution to
room temperature and then quenching with methanol produced
the desired product 24a but in only 7% yield along with an
unidentified polymer (Table 2, entry 11). It seems unlikely that
at Ϫ78 ЊC directed ortho-metallation13 is faster than organo-
lithium addition. We therefore carried out the reaction at a
higher temperature (Ϫ40 ЊC), and in this case, the organo-
lithium addition reaction proceeded rapidly giving the product
24a in 58% yield after protonation with methanol (Table 2,
entry 12).
Some other aryl-substituted styrenes were also evaluated
(Table 2, entries 13–21). The o-allylamino-substituted styrene
derivatives 11 and 12 also underwent addition with tert-
butyllithium at a slower rate than styrene, presumably due to
similar electron donating effects to those observed in the anisyl
systems (entries 8–12). The formation of adducts 25a and 26a
in high yield after protonation (90 and 91%), however, clearly
1110
J. Chem. Soc., Perkin Trans. 1, 2000, 1109–1116

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Table 2 Organolithium addition reactions with aryl-substituted styrenes
Entry
R1
R2
E
Solvent
T/ЊC
Ϫ78
Ϫ78
Ϫ78→rt
Ϫ78
Ϫ78
Ϫ78
Ϫ25
Ϫ44
Product
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
o-MeO 8
o-MeO 8
o-MeO 8
o-MeO 8
o-MeO 8
m-MeO 9
m-MeO 9
p-MeO 10
p-MeO 10
p-MeO 10
p-MeO 10
p-MeO 10
But
But
Bu
H
CO2H
H
H
Me3Si
H
H
H
CO2H
H
H
H
H
H
H
H
H
H
Et2O
Et2O
Et2O
Et2O–TMEDA
Et2O–TMEDA
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O–TMEDA
Et2O–TMEDA
Et2O
Et2O
Et2O
Et2O
Et2O
19a
19b
83
84
—
68
63
91
61
75
75
—
7
58
90
91
70
74
—
81c
70c
45
75
b
—
Bu
20a
20c
21a
22a
23a
23b
Bu
But
Bu
But
But
Bu
Ϫ44
b
Ϫ78→rt
Ϫ78→rt
Ϫ40
Ϫ78
Ϫ78
Ϫ35
Ϫ78
Ϫ78→rt
Ϫ78
—
Bu
24a
24a
25a
26a
27a
28a
Bu
o-N(Me)CH2CH᎐CH2 11
o-N(CH2Ph)CH2CH᎐CH2 12
But
But
Bu
᎐
᎐
o-Ph 13
p-Ph 14
o-OH 15
o-O(CH2)4OH 16
p-CO2H 17
18
Bus
But
But
But
But
Bu
b,c
—
Et2O
Et2O
Et2O
Et2O
30a
31b
32b
33b
CO2H
CO2H
CO2H
Ϫ78
Ϫ78
Ϫ25
18
a All products were isolated and fully characterised by spectroscopy; new compounds were also characterised by HRMS or elemental analysis.
b Polymer was obtained. c 2.4 Equivalents of organolithium reagent were used.
shows that the addition occurred selectively at the conjugated
double bond. o- and p-Phenylstyrenes 13 and 14 were studied
next: as expected they were found to undergo addition at a
faster rate with sec-butyllithium and butyllithium, at Ϫ78 and
Ϫ35 ЊC respectively (Table 2, entries 15 and 16), indicating
that the phenyl group can facilitate the addition reaction by
stabilising the intermediate benzylic carbanion.
Although 2-vinylphenol 15 did not undergo addition on
treatment with 2 equivalents of tert-butyllithium (Table 2, entry
17), the reaction of alcohol 16 to produce 30a illustrates that
hydroxy groups can be present in the substrate, providing that
an additional equivalent of organolithium reagent is employed
(Table 2, entry 18). We therefore used the same conditions in the
reaction of 4-vinylbenzoic acid (17) with tert-butyllithium. This
Scheme 4
transformation proceeded efficiently giving, after carboxyl-
ation, diacid 31b as a crystalline solid in 70% yield. It
is apparent that at Ϫ78 ЊC in ether, alkene carbolithiation
observed in almost quantitative yield. When the reaction was
occurs at a faster rate than organolithium addition to the
allowed to warm up to room temperature before work-up,
lithium carboxylate.
however, a new product 36 was obtained in 72% yield.
All of the above examples employed aryl-substituted
styrenes. We also demonstrated that the reaction is applicable
The intermediate organolithium reagent is presumably C-
benzylated via an intermolecular process14 or by way of a
to other aromatic systems. Thus, vinylnaphthalene 18 was
dissociation–recombination pathway (a vinylogous Wittig
rearrangement).15
carbolithiated–carboxylated to give acids 32 and 33 in 45 and
75% unoptimised yields.
Related substrates were examined under similar reaction
conditions. The O-methyl analogue (8) did not undergo methyl
transfer on warming, and with ortho-amino compounds 11
and 12 complex mixtures were obtained and transfer of the
N-methyl, N-benzyl or N-allyl groups was not observed. We
therefore investigated O-allyloxy compounds on the assump-
tion that an “activated” O-alkyl system was required. 2-Allyl-
oxystyrene 37 underwent carbolithiation–allyl transfer with a
range of organolithium reagents in good yields (Scheme 5). The
efficient addition of butyllithium and decyllithium using diethyl
ether as solvent was expected from the reactions using styrene.
With styrene in diethyl ether, however, no reactions were
observed with the relatively unreactive methyllithium, phenyl-
lithium and cyclohexenyllithium, and in ether–TMEDA or
THF, styrene polymerisation occurred. The fact that the
methyl, phenyl and cyclohexenyl adducts 40–42 were
formed using ether–TMEDA in this study is therefore note-
worthy. We presume that the intermediate organolithium
adducts leading to 40–42 undergo alkylation at a faster rate
than polymerisation.
(iii) Organolithium addition–alkyl transfer reactions
All of the above reactions were carried out and quenched at low
temperature. The reaction of 2-benzyloxystyrene 34 with tert-
butyllithium was originally investigated using this protocol
(Scheme 4) and the expected product 35 after protonation was
J. Chem. Soc., Perkin Trans. 1, 2000, 1109–1116
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Experimental
NMR spectra were recorded on a JEOL EX-270 spectrometer.
Tetramethylsilane (TMS) or residual CHCl3 was used as the
internal standard and J values are in Hz. Carbon spectra were
verified using DEPT experiments. Melting points were recorded
on an Electrothermal IA 9100 digital melting point apparatus
and are uncorrected. Infrared (IR) spectra were recorded on an
ATI Mattson Genesis FT-IR spectrometer. Low resolution
electron impact (EI) mass spectra were recorded on a Kratos
MS25 spectrometer. Chemical ionisation (CI) and high reso-
lution mass spectra were recorded on a Micromass Autospec
spectrometer. Elemental analyses were carried out at the
University of East Anglia. TLC was carried out using pre-
prepared plates (Merck silica gel 60 F-254, 5715). PE is petrol-
eum ether (bp 40–60 ЊC), EtOAc is ethyl acetate, ether is diethyl
ether and THF is tetrahydrofuran. Dry ether and THF were
distilled from sodium–benzophenone ketyl immediately before
use, and TMEDA was dried over anhydrous sodium hydroxide.
Except where specified, all reagents were purchased from com-
mercial sources and were used without further purification.
Butyllithium is a 1.6 M solution in hexanes, sec-butyllithium is
a 1.3 M solution in cyclohexane, tert-butyllithium is a 1.7 M
solution in pentane, phenyllithium is a 1.8 M solution in
cyclohexane–ether, methyllithium is a 1.4 M solution in ether.
Starting materials
Starting materials 11, 12, 2-benzyloxystyrene (34) and 2-allyl-
oxystyrene (37) were prepared by Wittig reaction of the
corresponding benzaldehydes according to literature pro-
cedures.16,17 Starting materials 4-(2Ј-vinylphenoxy)butan-1-ol
(16), (Z)-4-(2Ј-vinylphenoxy)but-2-en-1-ol (43) and (E)-4-(2Ј-
vinylphenoxy)but-2-en-1-ol (48) were prepared by standard
Mitsunobu reactions18 of 2-hydroxystyrene with butane-
1,4-diol, (Z)-but-2-ene-1,4-diol and (E)-but-2-ene-1,4-diol,
respectively.
Scheme 5
Organolithium addition to styrenes—general procedure
To a stirred solution of styrene (0.5 mmol) in dry diethyl ether
(25 cm3) at Ϫ78 ЊC under nitrogen was added the organolithium
solution (0.55 mmol). The reaction mixture was then stirred at
Ϫ78 ЊC for 0.5 to 2 h until the styrene was no longer evident by
TLC (PE). Methanol (1 cm3) was then added and the reaction
stirred for a further 10 min. The solution was diluted with ether
(50 cm3), washed with water (2 × 25 cm3) and dried with
anhydrous sodium sulfate. Evaporation of solvent and column
chromatography on silica gel (PE) gave the product.
For carboxylation of the intermediate organolithium
reagent, gaseous carbon dioxide was bubbled through the reac-
tion mixture for 3 min at low temperature, then the reaction was
warmed to rt. Normal work-up with 5% aqueous HCl solution
and brine followed by column chromatograhy on silica gel
(PE–ether 5:1) gave the pure product. For trimethylsilylation,
trimethylsilyl chloride (1.5 equivalents) was added at low tem-
perature and then the reaction was warmed to rt and stirred
at rt for 2 h. Work-up with water and column chromatography
on silica gel (PE) gave the product.
This process also takes place with substituted allyloxy deriv-
atives (Scheme 5). Thus, with several alkyllithium reagents in
ether, (Z)-butenol 43 was converted into the rearranged
adducts 44–47. We assume that allyloxy transfer occurred with
retention of alkene configuration as only one alkene was
obtained in each case, but unfortunately the alkene coupling
1
constants could not be obtained from the H NMR spectra.
The isomeric (E)-butenol 48 was therefore subjected to a simi-
lar reaction with butyllithium. Again, only one compound 49
1
was isolated but it had completely different H and 13C NMR
spectra (see Experimental section), suggesting that in both
reactions the stereochemistry of the transferred group remains
intact.
In summary, we have established that organolithium addition
reactions with styrene, and a range of aryl-substituted styrene
analogues, are synthetically viable when diethyl ether is
employed as the solvent. tert-Butyllithium and sec-butyllithium
react with most of the aryl-substituted styrene derivatives at
Ϫ78 ЊC, but primary organolithium reagents usually need
higher temperatures (ca. Ϫ25 ЊC) to react. Electron donating
groups, such as methoxy, at the ortho- or para-position of the
benzene ring can slow down the reaction, and in this case
TMEDA can be used to activate butyllithium for efficient trans-
formation. 2-Benzyloxystyrene and 2-allyloxystyrene undergo
carbolithiation at low temperature but an O- to C-transfer
occurs if the reaction is warmed to room temperature. Phenyl-
lithium, cyclohexyllithium and methyllithium, which do
not add efficiently to styrene, can be used for this addition–
alkyl transfer sequence in the presence of TMEDA. The
reactions described above provide a useful method for the
preparation of a range of alkylated benzene derivatives.
1-Phenyl-3,3-dimethylbutane (1a). Following the general
procedure, this was obtained in 93% yield as a clear oil with
spectroscopic data consistent with those published.19
2-Phenyl-4,4-dimethylpentanoic acid (1b). Following the gen-
eral procedure, this was obtained in 92% yield as a white solid,
Rf 0.40 (PE–ether, 1:2), mp 80–81 ЊC (Found: C, 76.0; H, 8.9.
C13H18O2 requires C, 75.7; H, 8.8%); νmax(Nujol)/cmϪ1 3300–
2500 (CO2H), 1709, 725, 696; δH (270 MHz, CDCl3) 0.89 (9 H,
s, t-Bu), 1.61 (1 H, dd, J 4.3 and 14.2, t-BuCHAHB), 2.25 (1 H,
dd, J 8.6 and 14.2, t-BuCHAHB), 3.62 (1 H, dd, J 4.3 and 8.6,
1112
J. Chem. Soc., Perkin Trans. 1, 2000, 1109–1116

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CH), 7.20–7.35 (5 H, m, Ph); δC (67.5 MHz, CDCl3) 29.4, 31.0,
46.8, 48.1, 127.2, 127.9, 128.6, 140.2, 181.1; m/z (EI) 206.1314
(C13H18O2 requires 206.1307, Ϫ3.3 ppm error), 206 (Mϩ, 20%),
161 (8), 145 (16), 136 (30), 105 (25), 92 (20), 79 (14), 57 (100).
(3 H, m, Me2CHCH2CH2), 1.80–2.00 (2 H, m, PhCH2CH2),
2.40–2.56 (3 H, m, PhCH2 and PhCH), 7.08–7.35 (10 H, m,
2 × Ph); δC (67.5 MHz, CDCl3) 22.4, 22.7, 28.1, 33.8, 34.8, 36.8,
45.9, 125.6, 125.9, 127.7, 128.2, 128.3, 128.4, 142.7, 145.8; m/z
(EI) 266.2030 (C20H26 requires 266.2035, 1.8 ppm error), 266
(Mϩ, 15%), 162 (15), 117 (26), 105 (29), 91 (100), 77 (10).
1-Phenyl-3-methylpentane (2a). Following the general
procedure, this was obtained in 94% yield as a clear oil with
spectroscopic data consistent with those published.20
2-(3Ј,3Ј-Dimethylbutyl)anisole (19a). Following the general
procedure, this was obtained in 83% yield as a clear oil, Rf 0.60
(PE); νmax(film)/cmϪ1 2954, 2905, 1601, 1587, 1494, 1465, 1107,
1045, 750; δH (270 MHz, CDCl3) 0.96 (9 H, s, t-Bu), 1.40–1.48
(2 H, m, t-BuCH2), 2.52–2.60 (2 H, m, ArCH2), 3.79 (3 H, s,
MeO), 6.78–6.90 (2 H, m, ArH), 7.10–7.20 (2 H, m, ArH);
δC (67.5 MHz, CDCl3) 25.4, 29.3, 30.6, 44.4, 55.2, 110.2, 120.4,
126.7, 129.5, 132.0, 157.4; m/z (EI) 192.1506 (C13H20O requires
192.1514, 4.0 ppm error), 192 (Mϩ, 35%), 135 (25), 121 (100),
105 (7), 91 (50), 77 (10), 57 (22).
2-Phenyl-4-methylhexanoic acid (2b). Mixture of two
diastereoisomers. Following the general procedure, this was
obtained in 86% yield as a clear oil, Rf 0.40 (PE–ether, 1:2);
νmax(film)/cmϪ1 3300–2500 (CO2H), 3029, 2961, 1706, 1283, 698;
δH (270 MHz, CDCl3) 0.75–0.92 (6 H, m, 2 × CH3), 1.10–1.40
(3 H, m, CH2 and CH), 1.45–1.55 (0.5 H, m, CHAHB,
diastereoisomer 1), 1.75–1.92 (1 H, m, CHAHB), 2.05–2.18
(0.5 H, m, CHAHB, diastereoisomer 2), 3.60–3.71 (1 H, m, CH),
7.20–7.35 (5 H, m, Ph); δC (67.5 MHz, CDCl3) 10.9 and 11.0,
18.7 and 19.0, 29.2 and 29.4, 31.7 and 32.1, 39.5 and 40.2, 49.3
and 49.4, 127.4 (C-4), 128.0 and 128.2, 128.6 (C-3), 138.4
and 138.9 (C), 180.5 and 181.0 (CO2H); m/z (EI) 206.1316
(C13H18O2 requires 206.1307, Ϫ4.4 ppm error), 206 (Mϩ, 2%),
161 (3), 136 (100), 118 (17), 105 (23), 91 (62).
2-(2Ј-Methoxyphenyl)-4,4-dimethylpentanoic acid (19b). Fol-
lowing the general procedure, this was obtained in 84% yield as
a white solid, Rf 0.33 (PE–ether, 1:2), mp 67–68 ЊC; νmax(Nujol)/
cmϪ1 3300–2500 (CO2H), 1700, 1491, 1027, 752; δH (270 MHz,
CDCl3) 0.88 (9 H, s, t-Bu), 1.53 (1 H, dd, J 4.8 and 14.1,
t-BuCHAHB), 2.20 (1 H, dd, J 7.8 and 14.1, t-BuCHAHB), 3.84
(3 H, s, MeO), 4.20 (1 H, dd, J 4.8 and 7.8, CH), 6.82–6.95 (2 H,
m, ArH), 7.18–7.33 (2H, m, ArH); δC (67.5 MHz, CDCl3) 29.4,
31.1, 39.9, 46.2, 55.6, 110.9, 120.8, 128.1, 128.3, 129.1, 156.3,
180.9; m/z (EI) 236.1415 (C14H20O3 requires 236.1412, Ϫ1.3 ppm
error), 236 (Mϩ, 30%), 192 (12), 175 (19), 165 (12), 148 (16),
135 (50), 121 (100), 107 (16), 91 (36).
Hexylbenzene (3a). Following the general procedure, but with
the reaction mixture being stirred at Ϫ25 ЊC for 1 h, this was
obtained in 85% yield as a clear oil with spectroscopic data
consistent with those published.21
2-Phenylheptanoic acid (3b). Following the general pro-
cedure, but with the reaction mixture being stirred at Ϫ25 ЊC
for 1 h, this was obtained in 84% yield as a clear oil with
spectroscopic data consistent with those published.22
2-Hexylanisole (20a). Following the general procedure, but
with 2 equivalents of TMEDA added before the organolithium
reagent, this was obtained in 68% yield as a clear oil with
spectroscopic data consistent with those published.27
1-Phenyl-1-trimethylsilylhexane (3c). Following the general
procedure, but with the reaction mixture being stirred at
Ϫ25 ЊC for 1 h, this was obtained in 51% yield as a clear oil with
spectroscopic data consistent with those published.23
2-(1Ј-Trimethylsilylhexyl)anisole (20c). Following the general
procedure, but with 2 equivalents of TMEDA added before the
organolithium reagent, this was obtained in 63% yield as a clear
oil, Rf 0.69 (PE); νmax(film)/cmϪ1 2957, 2929, 1595, 1584, 1489,
1464, 1238, 1033, 836, 750; δH (270 MHz, CDCl3) Ϫ0.10 (9 H, s,
TMS), 0.83 (3 H, t, J 6.5, Me), 1.10–1.30 (6 H, m, 3 × CH2),
1.60–1.80 (2 H, m, CH2), 2.59 (1 H, dd, J 4.6 and 11.1, CH),
3.77 (3 H, s, MeO), 6.79–6.90 (2 H, m, ArH), 7.00–7.10 (2 H, m,
ArH); δC (67.5 MHz, CDCl3) Ϫ2.8, 14.1, 22.5, 27.6, 28.8, 29.0,
31.9, 55.0, 109.9, 120.3, 124.6, 127.1, 132.7, 157.0; m/z (EI)
264.1904 (C16H28OSi requires 264.1909, 2.0 ppm error), 264
(Mϩ, 22%), 249 (65), 179 (100), 163 (14), 147 (8), 121 (15), 91
(15), 73 (60).
1-Phenyl-5-methylpentane (4a). Following the general pro-
cedure, but with the reaction mixture being stirred at Ϫ25 ЊC
for 1 h, this was obtained in 82% yield as a clear oil with
spectroscopic data consistent with those published.24
Dodecylbenzene (5a). Following the general procedure, but
with the reaction mixture being stirred at Ϫ25 ЊC for 1 h, this
was obtained in 82% yield as a clear oil with spectroscopic data
consistent with those published.25
1,4-Diphenylbutane (6a). Following the general procedure,
but with the reaction mixture being stirred at Ϫ25 ЊC for 1 h,
this was obtained in 60% yield as a clear oil with spectroscopic
data consistent with those published.26
3-(3Ј,3Ј-Dimethylbutyl)anisole (21a). Following the general
procedure, this was obtained in 91% yield as a clear oil, Rf 0.60
(PE); νmax(film)/cmϪ1 2953, 1601, 1585, 1492, 1466, 1260, 1152,
1043, 782, 694; δH (270 MHz, CDCl3) 0.96 (9 H, s, t-Bu), 1.45–
1.55 (2 H, m, t-BuCH2), 2.50–2.68 (2 H, m, ArCH2), 3.80 (3 H,
s, MeO), 6.69–6.80 (3 H, m, ArH), 7.15–7.21 (1 H, m, ArH);
δC (67.5 MHz, CDCl3) 29.3, 30.5, 31.3, 46.3, 55.1, 110.8,
114.1, 120.7, 129.2, 145.3, 159.6; m/z (EI) 192.1515 (C13H20O
requires 192.1514, Ϫ0.3 ppm error), 192 (Mϩ, 70%), 177 (10),
135 (40), 121 (100), 91 (30), 77 (32), 57 (95).
1,3-Diphenyloctane (7a). Obtained as a by-product with 3a,
this was isolated in 7% yield as a clear oil, Rf 0.28 (PE);
νmax(film)/cmϪ1 3061, 3025, 2926, 1602, 1493, 1452, 748, 698;
δH (270 MHz, CDCl3) 0.80 (3 H, t, J 7.0, CH3), 1.00–1.30 (6 H,
m, 3 × CH2), 1.50–1.70 (2 H, m, CH2), 1.80–2.00 (2 H, m, CH2),
2.40–2.58 (3 H, m, PhCH2 and CH), 7.05–7.35 (10 H, m,
2 × Ph); δC (67.5 MHz, CDCl3) 14.1, 22.5, 27.2, 31.9, 33.9, 37.1,
38.6, 45.6, 125.6, 125.9, 127.7, 128.2, 128.3, 128.4, 142.7, 145.8;
m/z (EI) 266.2036 (C20H26 requires 266.2035, Ϫ0.7 ppm error),
266 (Mϩ, 17%), 162 (11), 117 (20), 104 (15), 91 (100), 77 (6).
3-Hexylanisole (22a). Following the general procedure, this
was obtained in 61% yield as a clear oil, Rf 0.61 (PE); νmax(film)/
cmϪ1 2955, 2928, 1602, 1584, 1488, 1465, 1455, 1260, 1152,
1048, 775, 694; δH (270 MHz, CDCl3) 0.89 (3 H, t, J 7.0, Me),
1.20–1.40 (6 H, m, 3 × CH2), 1.55–1.65 (2 H, m, CH2), 2.59
(2 H, t, J 7.0, ArCH2), 3.80 (3 H, s, MeO), 6.70–6.80 (3 H, m,
ArH), 7.15–7.23 (1 H, m, ArH); δC (67.5 MHz, CDCl3) 14.1,
22.6, 29.0, 31.4, 31.7, 36.0, 55.1, 110.8, 114.1, 120.8, 129.1,
144.6, 159.5; m/z (EI) 192.1509 (C13H20O requires 192.1514,
1,3-Diphenyl-6-methylheptane (7b). Obtained as a by-product
with 4a, this was isolated in 12% yield as a clear oil, Rf 0.28
(PE); νmax(film)/cmϪ1 3061, 3025, 2926, 1602, 1493, 1452, 747,
689; δH (270 MHz, CDCl3) 0.79 (3 H, d, J 6.5, CH3), 0.81 (3 H,
d, J 6.5, CH3), 0.95–1.18 (2 H, m, Me2CHCH2CH2), 1.40–1.70
J. Chem. Soc., Perkin Trans. 1, 2000, 1109–1116
1113

View Article Online
2.7 ppm error), 192 (Mϩ, 25%), 135 (14), 122 (100), 91 (16), 78
(10).
127.9, 129.2 (×2), 130.0, 140.4, 141.8, 142.0; m/z (EI) 238.1727
(C18H22 requires 238.1722, Ϫ2.2 ppm error), 238 (Mϩ, 15%),
181 (10), 167 (100), 152 (15).
4-(3Ј,3Ј-Dimethylbutyl)anisole (23a). Following the general
procedure, but with the reaction mixture stirred at Ϫ44 ЊC
for 1 h, this was obtained in 75% yield as a clear oil, Rf 0.61
(PE); νmax(film)/cmϪ1 2951, 1614, 1585, 1513, 1465, 1364, 1247,
1177, 1038, 820; δH (270 MHz, CDCl3) 0.95 (9 H, s, t-Bu), 1.42–
1.50 (2 H, m, t-BuCH2), 2.47–2.54 (2 H, m, ArCH2), 3.76 (3 H,
s, MeO), 6.81 (2 H, d, J 8.7, H-2), 7.09 (2 H, d, J 8.7, H-3);
δC (67.5 MHz, CDCl3) 29.3, 30.3, 30.5, 46.7, 55.2, 113.7, 129.1,
135.6, 157.5; m/z (EI) 192.1514 (C13H20O requires 192.1514,
0 ppm error), 192 (Mϩ, 16%), 135 (6), 121 (100), 78 (7), 57 (7).
1-Phenyl-4-(3Ј-methylpentyl)benzene (28a). Following the
general procedure, this was obtained in 74% yield as a clear oil,
Rf 0.42 (PE); νmax(film)/cmϪ1 2962, 1602, 1487, 1462, 909, 696;
δH (270 MHz, CDCl3) 1.00–1.18 (6 H, m, 2 × Me), 1.25–1.47
(1 H, m), 1.45–1.70 (3 H, m), 1.71–1.90 (1 H, m), 2.65–2.90
(2 H, m, ArCH2), 7.35–7.74 (9 H, m, ArH); δC (67.5 MHz,
CDCl3) 11.3, 19.1, 29.4, 33.1, 34.1, 38.5, 126.9, 127.0, 128.6
(×2), 128.7, 138.5, 141.1, 142.3; m/z (EI) 238 (Mϩ, 65%), 167
(100), 152 (7), 57 (6).
2-(4Ј-Methoxyphenyl)-4,4-dimethylpentanoic acid (23b). Fol-
lowing the general procedure, but with the reaction mixture
stirred at Ϫ44 ЊC for 1 h, this was obtained in 84% yield as a
white solid, Rf 0.35 (PE–ether, 1:2), mp 93–94 ЊC (Found: C,
71.4; H, 8.6. C14H20O3 requires C, 71.2; H, 8.5%); νmax(Nujol)/
cmϪ1 3250–2500 (CO2H), 1707, 1608, 1583, 1510, 1299, 1244,
1177, 1031, 831; δH (270 MHz, CDCl3) 0.88 (9 H, s, t-Bu), 1.59
(1 H, dd, J 4.6 and 14.0, t-BuCHAHB), 2.21 (1 H, dd, J 8.7 and
14.0, t-BuCHAHB), 3.59 (1 H, dd, J 4.6 and 8.7, CH), 3.77 (3 H,
s, MeO), 6.82 (2 H, d, J 8.7, H-2), 7.24 (2 H, d, J 8.7, H-3);
δC (67.5 MHz, CDCl3) 29.4, 31.0, 46.8, 47.2, 55.2, 114.0, 129.0,
132.3, 158.8, 181.4; m/z (EI) 236.1413 (C14H20O3 requires
236.1412, Ϫ0.1 ppm error), 236 (Mϩ, 30%), 192 (12), 175 (19),
165 (12), 148 (16), 135 (50), 121 (100), 107 (16), 91 (36).
1-(4Ј-Hydroxybutyloxy)-2-(3Љ,3Љ-dimethylbutyl)benzene
(30a). Following the general procedure, but using 2.4 equiv-
alents of organolithium, this was obtained in 81% yield as a
clear oil, Rf 0.14 (PE–ether, 1:1); νmax(film)/cmϪ1 3340, 2951,
1600, 1588, 1494, 1243, 1050, 750; δH (270 MHz, CDCl3) 0.96
(9 H, s, t-Bu), 1.40–1.48 (2 H, m, t-BuCH2), 1.70–1.93 (4 H, m,
OCH2CH2CH2CH2OH), 2.50–2.60 (2 H, m, ArCH2), 3.70 (2 H,
t, J 6.0, CH2OH), 3.97 (2 H, t, J 6.0, CH2OAr), 6.78–6.88 (2 H,
m, ArH), 7.09–7.16 (2 H, m, ArH); δC (67.5 MHz, CDCl3) 25.6,
25.9, 29.2, 29.5, 30.5, 44.6, 62.4, 67.4, 111.1, 120.4, 126.6, 129.6,
131.9, 156.6; m/z (EI) 250.1940 (C16H26O2 requires 250.1933,
Ϫ2.9 ppm error), 250 (Mϩ, 10%), 178 (56), 121 (40), 107 (100),
57 (49).
2-(4Ј-Hydroxycarbonylphenyl)-4,4-dimethylpentanoic
acid
4-Hexylanisole (24a). This compound was prepared by
adding butyllithium to a solution of p-methoxystyrene and 2
equivalents of TMEDA in ether at Ϫ40 ЊC followed by stirring
at this temperature for 10 min. After normal work-up as
described in the general procedure, this was obtained in 58%
yield as a clear oil with spectroscopic data consistent with those
published.28
(31b). Following the general procedure, but using 2.4 equiv-
alents of organolithium, this was obtained in 70% yield as a
white solid, mp 180.5–181.5 ЊC; νmax(Nujol)/cmϪ1 3250–2500
(CO2H), 1705, 1606, 1278, 919, 725; δH (270 MHz, acetone-d6)
1.02 (9 H, s, t-Bu), 1.68 (1 H, dd, J 4.1 and 14.0, t-BuCHAHB),
2.41 (1 H, dd, J 8.5 and 14.0, t-BuCHAHB), 3.89 (1 H, dd, J 4.1
and 8.5, CH), 7.60 (2 H, d, J 8.4, ArH), 8.10 (2 H, d, J 8.4,
ArH); δC (67.5 MHz, acetone-d6) 29.7, 31.6, 47.9, 48.6, 128.9,
130.1, 130.7, 147.7, 167.4, 175.3; m/z (EI) 250.1199 (C14H18O4
requires 250.1205, 2.4 ppm error), 250 (Mϩ, 2%), 236 (30), 191
(30), 165 (38), 135 (30), 121 (29), 57 (100).
N-Methyl-N-allyl-2-(3Ј,3Ј-dimethylbutyl)aniline (25a). Fol-
lowing the general procedure, this was obtained in 90% yield as
a clear oil, Rf 0.50 (PE–ether, 5:1); νmax(film)/cmϪ1 2953, 1642,
1597, 1491, 1363, 919, 760; δH (270 MHz, CDCl3) 0.97 (9 H,
s, t-Bu), 1.35–1.44 (2 H, m, t-BuCH2), 2.60–2.68 (2 H, m,
ArCH2), 2.63 (3 H, s, MeN), 3.44 (2 H, m, CH2N), 5.14 (1 H, d,
2-(2Ј-Naphthyl)-4,4-dimethylpentanoic acid (32). Following
the general procedure, this was obtained in 45% yield as a clear
oil, Rf 0.20 (PE–ether, 1:1); νmax(film)/cmϪ1 3250–2500 (CO2H),
2958, 1707, 1600, 1508, 1365, 1290, 1222; δH (270 MHz, CDCl3)
0.91 (9 H, s, t-Bu), 1.71 (1 H, dd, J 4.4 and 14.1, t-BuCHAHB),
2.34 (1 H, dd, J 8.5 and 14.1, t-BuCHAHB), 3.82 (1 H, dd, J 4.4
and 8.5, CH), 7.40–7.47 (3 H, m, Ar), 7.73–7.80 (4 H, m, ArH);
δC (67.5 MHz, CDCl3) 29.5, 31.1, 46.8, 48.2, 125.9, 126.0, 126.2,
126.7, 127.6, 127.8, 128.4, 132.6, 133.4, 137.7, 180.5; m/z (EI)
256.1462 (C17H20O2 requires 256.1463, 0.6 ppm error), 256 (Mϩ,
34%), 186 (15), 141 (100).
J 10.2, CH᎐CH H ), 5.25 (1 H, d, J 17.2, CH᎐CH H ), 5.80–
᎐
᎐
A
B
A
B
5.95 (1 H, m, CH᎐CH ), 6.95–7.20 (4 H, m, ArH); δ (67.5
᎐
2
C
MHz, CDCl3) 25.9, 29.4, 30.7, 41.5, 45.4, 60.7, 116.8, 120.7,
123.5, 126.1, 129.7, 135.9, 138.8, 152.1; m/z (EI) 231.1992
(C16H25N requires 231.1987, Ϫ2.1 ppm error), 231 (Mϩ, 85%),
190 (70), 174 (55), 134 (100), 57 (55).
N-Allyl-N-benzyl-2-(3Ј,3Ј-dimethylbutyl)aniline (26a). Fol-
lowing the general procedure, this was obtained in 91% yield as
a clear oil, Rf 0.47 (PE–ether, 5:1); νmax(film)/cmϪ1 2953, 1643,
1597, 1491, 1364, 918, 761, 698; δH (270 MHz, CDCl3) 0.98
(9 H, s, t-Bu), 1.40–1.48 (2 H, m, t-BuCH2), 2.64–2.75 (2 H,
2-(2Ј-Naphthyl)heptanoic acid (33). Following the general
procedure, but with the reaction mixture stirred at Ϫ25 ЊC for
1 h, this was obtained in 75% yield as a white solid, Rf 0.20 (PE–
ether, 1:1), mp 73–75 ЊC; νmax(Nujol)/cmϪ1 3250–2500 (CO2H),
1698, 1602, 1508, 1228, 810, 747; δH (270 MHz, acetone-d6)
0.77–0.90 (3 H, t, J 6.5, CH3), 1.17–1.32 (6 H, m, 3 × CH2),
1.80–1.93 (1 H, m, CHCHAHB), 2.08–2.21 (1 H, m, CHCHA-
HB), 3.70 (1 H, t, J 7.5, CH), 7.40–7.50 (3 H, m, ArH), 7.73–
7.83 (4 H, m, ArH); δC (67.5 MHz, acetone-d6) 14.0, 22.4, 27.1,
29.7, 31.5, 32.9, 51.7, 125.9 (×2), 126.1, 127.0, 127.6, 127.8,
128.3, 132.7, 133.4, 135.9, 180.3; m/z (EI) 256.1461 (C17H20O2
requires 256.1463, 0.8 ppm error), 256 (Mϩ, 30%), 186 (18), 141
(100), 128 (18), 115 (10).
m, ArCH ), 3.49 (2 H, d, J 6.0, CH ᎐CHCH N), 4.09 (2 H, s,
᎐
2
2
2
PhCH ), 5.03–5.16 (2 H, m, CH᎐CH ), 5.75–5.89 (1 H, m,
᎐
2
2
CH᎐CH ), 6.95–7.33 (9 H, m, ArH); δ (67.5 MHz, CDCl3)
᎐
2
C
25.7, 29.2, 30.7, 45.4, 56.8, 57.8, 117.3, 122.9, 124.0, 125.8,
126.8, 128.0, 128.7, 129.8, 135.1, 138.9, 139.7, 149.7; m/z (EI)
307.2304 (C22H29N requires 307.2300, Ϫ1.2 ppm error), 307
(Mϩ, 15%), 266 (22), 216 (50), 160 (25), 91 (100), 57 (37).
1-Phenyl-2-hexylbenzene (27a). Following the general pro-
cedure, but with the reaction mixture stirred at Ϫ30 ЊC for 1 h,
this was obtained in 70% yield as a clear oil, Rf 0.30 (PE);
νmax(film)/cmϪ1 3060, 2926, 1599, 1479, 1465, 1377, 1071, 1009,
749, 701; δH (270 MHz, CDCl3) 0.82 (3 H, t, J 6.5, CH3), 1.10–
1.25 (6 H, m, 3 × CH2), 1.39–1.49 (2 H, m, CH2CH2Ar), 2.52–
2.60 (2 H, m, CH2Ar), 7.15–7.43 (9 H, m, ArH); δC (67.5 MHz,
CDCl3) 14.0, 22.5, 29.1, 31.3, 31.5, 33.0, 125.5, 126.7, 127.3,
1-Benzyloxy-2-(3Ј,3Ј-dimethylbutyl)benzene (35). Following
the general procedure, this was obtained in 95% yield as a clear
oil, Rf 0.46 (PE); νmax(film)/cmϪ1 3032, 2953, 1600, 1588, 1493,
1114
J. Chem. Soc., Perkin Trans. 1, 2000, 1109–1116

View Article Online
1452, 1242, 1024, 749; δH (270 MHz, CDCl3) 0.93 (9 H, s, t-Bu),
1.42–1.50 (2 H, m, t-BuCH2), 2.59–2.68 (2 H, m, ArCH2), 5.04
(2 H, s, CH2O), 6.83–6.90 (2 H, m, ArH), 7.09–7.16 (2 H, m,
ArH), 7.25–7.45 (5 H, m, ArH); δC (67.5 MHz, CDCl3) 25.8,
19.3, 30.6, 44.6, 69.8, 111.6, 120.7, 126.7, 127.1, 127.7, 128.4,
129.8, 132.3, 137.5, 156.5; m/z (EI) 268.1826 (C19H24O requires
268.1827, 0.4 ppm error), 268 (Mϩ, 8%), 197 (1), 120 (1), 107
(3), 91 (100).
4-(2Ј-Hydroxyphenyl)hex-1-ene (40). Following the general
procedure, but with 2 equivalents of TMEDA added before the
organolithium reagent, 40 was obtained in 80% yield as a clear
oil, Rf 0.26 (PE–ether, 5:1); νmax(film)/cmϪ1 3430, 3073, 2963,
1639, 1607, 1590, 1501, 1453, 1234, 912, 831, 752; δH (270 MHz,
CDCl3) 0.80 (3 H, t, J 7.0, Me), 1.50–1.80 (2 H, m, CH3CH2-
CHAr), 2.38 (2 H, t, J 6.0, CH CH᎐CH ), 2.97 (1 H, quintet ,
᎐
2
2
appt
J 6.0, ArCH), 4.91 (1 H, d, J 9.5, CH᎐CH H ), 4.97 (1 H, d,
᎐
A
B
J 18.0, CH᎐CH H ), 5.15 (1 H, br s, OH), 5.60–5.80 (1 H, m,
᎐
A
B
Organolithium addition followed by alkyl transfer—general
procedure
CH᎐CH ), 6.70 (1 H, dd, J 8.0, 1.2, ArH), 6.89 (1 H, dt, J 1.0
᎐
2
and 8.0, ArH), 7.00–7.17 (2 H, m, ArH); δC (67.5 MHz, CDCl3)
11.8, 27.5, 39.5 (×2), 115.4, 115.8, 120.8, 126.6, 127.9, 131.0,
137.3, 153.3; m/z (EI) 176.1203 (C12H16O requires 176.1201,
Ϫ1.2 ppm error), 176 (Mϩ, 5%), 147 (3), 135 (65), 107 (100),
91 (20).
To a stirred solution of 2-benzyloxystyrene 34 (105 mg, 0.5
mmol) in dry ether (25 cm3) at Ϫ78 ЊC under nitrogen was
added the tert-butyllithium (1.7 M solution in pentane, 0.33
cm3, 0.55 mmol). The reaction mixture was stirred at Ϫ78 ЊC
for 10 min, warmed to rt over 20 min and then stirred at rt
until the initial adduct was no longer evident by TLC.
Methanol (1 cm3) was added and the reaction mixture stirred
for a further 10 min. The solution was diluted with ether (50
cm3), washed with aqueous NH4Cl (saturated solution, 10
cm3) and water (2 × 25 cm3) and dried with anhydrous
sodium sulfate. Evaporation of the solvent and column
chromatography on silica gel (ether–PE, 1:10) gave the
product as a colourless oil.
4-(2Ј-Hydroxyphenyl)-5-phenylpent-1-ene (41). Following the
general procedure, but with 2 equivalents of TMEDA added
before the organolithium reagent, 41 was obtained in 70% yield
as a clear oil, Rf 0.10 (PE–ether, 5:1); νmax(film)/cmϪ1 3350,
3063, 2977, 1640, 1604, 1496, 1454, 1234, 1097, 912, 832, 752,
700; δH (270 MHz, CDCl ) 2.40 (2 H, t, J 6.0, CH CH᎐CH ),
᎐
3
2
2
2.80–3.00 (2 H, m, PhCH2CHAr), 3.34 (1 H, quintetappt, J 6.0,
ArCH), 4.73 (1 H, br s, OH), 4.92 (1 H, d, J 9.5, CH᎐CH H ),
᎐
A
B
4.97 (1 H, d, J 18.0, CH᎐CH H ), 5.60–5.75 (1 H, m, CH᎐
᎐
᎐
A
B
CH2), 6.60 (1 H, d, J 8.0, ArH), 6.86 (1 H, t, J 8.0, ArH), 6.95–
7.25 (7 H, m, ArH); δC (67.5 MHz, CDCl3) 38.4, 40.2, 41.3,
115.6, 116.2, 120.9, 125.8, 126.9, 128.1 (×2), 129.2, 130.5,
136.9, 140.6, 153.2; m/z (EI) 238.1358 (C17H18O requires
238.1358, 0 ppm error), 238 (Mϩ, 7%), 197 (60), 147 (100), 91
(60).
1-Phenyl-2-(2Ј-hydroxyphenyl)-4,4-dimethylpentane (36). Fol-
lowing the general procedure, this was obtained in 72% yield as
a clear oil, Rf 0.21 (PE–ether, 5:1); νmax(film)/cmϪ1 3500, 3028,
2953, 1603, 1591, 1495, 1454, 1263, 1242, 1196, 832, 751, 699;
δH (270 MHz, CDCl3) 0.76 (9 H, s, t-Bu), 1.61 (1 H, dd, J 14.0
and 3.3, t-BuCHAHB), 1.85 (1 H, dd, J 14.0 and 9.0, t-BuCHA-
HB), 2.82 (2 H, d, J 7.5, PhCH2), 3.29–3.40 (1 H, m, CH), 4.49
(1 H, br s, OH), 6.57 (2 H, dd, J 7.8, 1.2, ArH), 6.80–6.86 (1 H,
m, ArH), 6.93–7.02 (3 H, m, ArH), 7.05–7.20 (3 H, m, ArH);
δC (67.5 MHz, CDCl3) 29.9, 31.2, 37.2, 45.1, 48.3, 115.7, 120.9,
125.7, 126.5, 128.0, 128.7, 129.1, 133.1, 141.0, 153.0; m/z (EI)
268.1829 (C19H24O requires 268.1827, Ϫ0.7 ppm error), 268
(Mϩ, 5%), 197 (12), 177 (55), 121 (26), 107 (55), 91 (37), 57
(100).
4-(2Ј-Hydroxyphenyl)-5-cyclohexenylpent-1-ene (42). Follow-
ing the general procedure, but with 2 equivalents of TMEDA
added before the organolithium reagent, 42 was obtained in
74% yield as a clear oil, Rf 0.22 (PE–ether, 5:1); νmax(film)/cmϪ1
3340, 3071, 2929, 1639, 1606, 1592, 1455, 1233, 1099, 910, 835,
751; δH (270 MHz, CDCl3) 1.40–1.65 (4 H, m, 2 × CH2), 1.75–
2.00 (4 H, m, 2 × CH2), 2.05–2.50 (4 H, m, 2 × CH2), 3.20 (1 H,
quintetappt, J 6.0, ArCH), 4.85–5.05 (3 H, m, CH ᎐CH and
᎐
2
C᎐CH), 5.36 (1 H, br s, OH), 5.60–5.77 (1 H, m, CH᎐CH ),
᎐
᎐
2
4-(2Ј-Hydroxyphenyl)non-1-ene (38). Following the general
procedure, this was obtained in 73% yield as a clear oil, Rf 0.25
(PE–ether, 5:1); νmax(film)/cmϪ1 3430, 3073, 2927, 1639, 1606,
1590, 1501, 1453, 1228, 911, 828, 751; δH (270 MHz, CDCl3)
0.83 (3 H, t, J 6.7, Me), 1.10–1.40 (6 H, m, 3 × CH2), 1.50–1.75
6.71 (1 H, dd, J 8.0 and 1.2, ArH), 6.87 (1 H, t, J 8.0, ArH),
6.99–7.12 (2 H, m, ArH); δC (67.5 MHz, CDCl3) 22.4, 22.9,
25.2, 28.5, 36.4, 38.9, 43.8, 115.5, 115.9, 120.8, 123.2, 126.6,
127.9, 131.2, 136.3, 137.3, 153.2; m/z (EI) 242.1671 (C17H22O
requires 242.1671, Ϫ0.2 ppm error), 242 (Mϩ, 5%), 201 (30),
147 (100), 107 (37).
(2 H, m, CH CH CHAr), 2.37 (2 H, t, J 6.0, CH CH᎐CH ),
᎐
2
2
2
2
3.00 (1 H, quintetappt, J 6.0, ArCH), 4.78 (1 H, br s, OH), 4.92
(1 H, d, J 9.5, CH᎐CH H ), 4.98 (1 H, d, J 18.0, CH᎐CH H ),
(Z)-5-(2Ј-Hydroxyphenyl)dec-2-en-1-ol (44). Following the
general procedure, but using 2.4 equivalents of organolithium,
this was obtained in 51% yield as a clear oil, Rf 0.12 (PE–ether,
1:1); νmax(film)/cmϪ1 3366, 2926, 1654, 1593, 1489, 1454, 1238,
1018, 752; δH (270 MHz, CDCl3) 0.84 (3 H, t, J 6.5, Me), 1.10–
1.50 (6 H, m, 3 × CH2), 1.60–1.75 (2 H, m, CH2CH2CHAr),
᎐
᎐
A
B
A
B
5.62–5.79 (1 H, m, CH᎐CH ), 6.73 (1 H, dd, J 8.0, 1.2, ArH),
᎐
2
6.90 (1 H, t, J 8.0, ArH), 7.00–7.16 (2 H, m, ArH); δC (67.5
MHz, CDCl3) 14.1, 22.5, 27.1, 31.9, 34.7, 38.1, 40.1, 115.4,
115.8, 120.9, 126.7, 127.9, 131.2, 137.3, 153.3; m/z (EI) 217.1587
(Mϩ Ϫ 1) (C15H21O requires 217.1592, 2.4 ppm error), 218 (Mϩ,
1%), 177 (20), 147 (7), 107 (100).
1.82 (1 H, br s, OH), 2.39 (2 H, t, J 7.0, CH CH᎐CH ), 3.04
᎐
2
2
(1 H, quintetappt, J 7.0, ArCH), 4.00 (2 H, d, J 5.3, CH2OH),
4-(2Ј-Hydroxyphenyl)pentadec-1-ene (39). Following the gen-
eral procedure, this was obtained in 70% yield as a clear oil, Rf
0.27 (PE–ether, 5:1); νmax(film)/cmϪ1 3440, 3073, 2924, 1639,
1607, 1590, 1501, 1453, 1229, 911, 830, 751; δH (270 MHz,
CDCl3) 0.87 (3 H, t, J 7.0, Me), 1.10–1.35 (18 H, m, 9 × CH2),
1.52–1.70 (2 H, m, CH2CH2CHAr), 2.36 (2 H, t, J 6.0,
5.50–5.60 (2 H, m, CH᎐CH), 6.03 (1 H, br s, OH), 6.73 (1 H,
᎐
dd, J 7.8, 1.0, ArH), 6.89 (1 H, t, J 7.8, ArH), 7.00–7.15 (2 H, m,
ArH); δC (67.5 MHz, CDCl3) 14.1, 22.6, 27.4, 31.9, 33.6, 34.5,
39.0, 58.2, 115.6, 120.6, 126.8, 128.0, 128.8, 131.1, 132.1, 153.8;
m/z (EI) 248.1778 (C16H24O2 requires 248.1776, Ϫ0.7 ppm
error), 248 (Mϩ, 2%), 230 (8), 177 (45), 159 (10), 120 (15), 107
(100).
CH CH᎐CH ), 3.00 (1 H, quintetappt, J 6.0, ArCH), 4.82 (1 H,
᎐
2
2
br s, OH), 4.92 (1 H, d, J 9.5, CH᎐CH H ), 4.98 (1 H, d, J 18.0,
᎐
A
B
CH᎐CH H ), 5.60–5.78 (1 H, m, CH᎐CH ), 6.72 (1 H, dd,
(Z)-5-(2Ј-Hydroxyphenyl)-7-methylnon-2-en-1-ol (45). Mix-
ture of two diastereoisomers. Following the general procedure,
but using 2.4 equivalents of organolithium, this was obtained in
60% yield as a clear oil, Rf 0.12 (PE–ether, 1:1); νmax(film)/cmϪ1
3360, 2959, 1655, 1592, 1503, 1454, 1236, 1000, 752; δH (270
MHz, CDCl3) 0.78–0.85 (6 H, m, 2 × CH3), 1.02–1.47 (3 H, m,
MeCH2CHMe), 1.49–1.85 (2 H, m, i-BuCH2CHAr), 2.00 (1 H,
᎐
᎐
A
B
2
J 8.0, 1.2, ArH), 6.89 (1 H, t, J 8.0, ArH), 7.00–7.16 (2 H, m,
ArH); δC (67.5 MHz, CDCl3) 14.4, 23.0, 27.7, 29.6, 29.8, 29.9,
30.0, 30.2, 32.2, 35.8, 38.4, 40.4, 115.7, 116.1, 121.2, 126.9,
128.2, 131.5, 137.6, 153.6; m/z (EI) 302.2614 (C21H34O requires
302.2610, Ϫ1.4 ppm error), 302 (Mϩ, 1%), 261 (25), 147 (5), 107
(100).
J. Chem. Soc., Perkin Trans. 1, 2000, 1109–1116
1115

View Article Online
br s, OH), 2.25–2.45 (2 H, m, CH CH᎐CH ), 3.15–3.25 (1 H, m,
ArCH), 3.99 (2 H, d, J 5.8, CH2OH), 5.50–5.60 (2 H, m,
᎐
References and notes
2
2
1 For
a recent review of alkene carbometallation (including
CH᎐CH), 6.45 (1 H, br s, OH), 6.72 (1 H, d, J 7.8, ArH), 6.88
᎐
carbolithiation) see P. Knochel, in Comprehensive Organic Synthesis,
Pergamon Press, Oxford, 1991, Vol. 4, Ch. 4.4; see also B. J.
Wakefield, The Chemistry of Organolithium Compounds, Pergamon
Press, Oxford, 1974, Section 7.1.
(1 H, t, J 7.8, ArH), 6.99–7.15 (2 H, m, ArH); δC (67.5 MHz,
CDCl3) 10.9 and 11.3, 18.8 and 19.6, 28.7 and 30.3, 31.9 (×2),
36.3 (×2), 33.5 and 34.3, 41.4 and 41.7, 58.1 (×2), 115.6
(×2), 120.4 (×2), 126.8 (×2), 128.1 (×2), 128.6 and 128.7,
130.8 and 131.4, 132.1 and 132.2, 153.8 and 154.0; m/z (EI)
248.1781 (C16H24O2 requires 248.1776, Ϫ1.7 ppm error), 248
(Mϩ, 1%), 230 (5), 177 (35), 159 (8), 147 (7), 121 (10), 107 (100).
2 B. M. Trost, Science, 1991, 254, 1471.
3 M. Merton, Anionic Polymerisation: Principles and Practice,
Academic Press, New York, 1983; R. Waack and M. A. Doran,
J. Org. Chem., 1967, 32, 3395 and references cited therein.
4 T. Fujita, S. Watanabe, K. Suga and H. Nakayama, Synthesis, 1979,
310; A. E. Bey and D. R. Weyenberg, J. Org. Chem., 1965, 30, 2436;
H. Pines and N. E. Sartoris, J. Org. Chem., 1969, 34, 2113 and
references cited therein.
(Z)-5-(2Ј-Hydroxyphenyl)-8-methylnon-2-en-1-ol (46). Fol-
lowing the general procedure, but using 2.4 equivalents of
organolithium, this was obtained in 68% yield as a clear oil, Rf
0.12 (PE–ether 1:1); νmax(film)/cmϪ1 3350, 2953, 1653, 1605,
1591, 1502, 1454, 1236, 1002, 752; δH (270 MHz, CDCl3) 0.83
(6 H, d, J 6.5, 2 × Me), 0.97–1.25 (2 H, m, Me2CHCH2), 1.40–
1.56 (1 H, m, Me2CH), 1.63–1.75 (2 H, m, CH2CH2CHAr), 2.15
5 The process can be facilitated by transmetallation using transition
metal salts or complexes, see ref. 1 and L. S. Hegedus, in Compre-
hensive Organic Synthesis, Pergamon Press, Oxford, 1991, Vol. 4,
Ch. 3.2; J. Terao, K. Saito, S. Nii, N. Kambe and N. Sonoda, J. Am.
Chem. Soc., 1998, 120, 11822.
6 K. Ziegler, F. Crössman, H. Kleiner and O. Schäfer, Liebigs Ann.
Chem., 1929, 471, 1; Y. Okamoto, M. Kato and H. Yuki, Bull. Chem.
Soc. Jpn., 1969, 42, 760; G. Fraenkel, D. Estes and M. J. Geckle,
J. Organomet. Chem., 1980, 185, 147; H. G. Richey, Jr, A. S. Heyn
and W. F. Erickman, J. Org. Chem., 1983, 48, 3821; H. Lehmkuhl,
Pure Appl. Chem., 1990, 62, 731; T. Kato, S. Marumoto, T. Sato and
I. Kuwajima, Synlett, 1990, 671; W. F. Bailey and A. D. Khanolkar,
Tetrahedron, 1991, 47, 7727; J. A. Seijas, M. P. Vázquez-Tato,
L. Castedo, R. J. Estévez and M. Ruíz, J. Org. Chem., 1992, 57, 5283;
S. Klein, I. Marek, J.-F. Poisson and J.-F. Normant, J. Am. Chem.
Soc., 1995, 117, 8853 and references cited therein; S. Superchi, N.
Sotomayor, G. Miao, B. Joseph, M. G. Campbell and V. Snieckus,
Tetrahedron Lett., 1996, 37, 6061; S. Norsikian, I. Marek and J.-F.
Normant, Tetrahedron Lett., 1997, 38, 7523; R. P. Robinson, B. J.
Cronin and B. P. Jones, Tetrahedron Lett., 1997, 38, 8479; M. J.
Woltering, R. Fröhlich and D. Hoppe, Angew. Chem., Int. Ed. Engl.,
1997, 36, 1764; N. Bremand, I. Marek and J.-F. Normant,
Tetrahedron Lett., 1999, 40, 3379; S. Nossikian, I. Marek, S. Klein,
J. F. Poisson and J. F. Normant, Chem. Eur. J., 1999, 5, 2055; R. W.
Hoffman, R. Koberstein and K. Harms, J. Chem. Soc., Perkin Trans.
2, 1999, 183 and references therein.
(1 H, br s, OH), 2.39 (2 H, tappt, J 7.0, CH CH᎐CH ), 3.02 (1 H,
᎐
2
2
quintetappt, J 7.0, ArCH), 4.00 (2 H, d, J 5.5, CH2OH), 5.50–
5.60 (2 H, m, CH᎐CH), 6.53 (1 H, br s, OH), 6.72 (1 H, dd,
᎐
J 7.8, 1.0, ArH), 6.88 (1 H, dt, J 1.0 and 7.8, ArH), 7.00–7.15
(2 H, m, ArH); δC (67.5 MHz, CDCl3) 22.4, 22.7, 28.1, 32.3,
33.5, 36.9, 39.3, 58.1, 115.6, 120.5, 126.8, 127.9, 128.7, 131.1,
132.2, 153.9; m/z (EI) 248.1772 (C16H24O2 requires 248.1776,
1.8 ppm error), 248 (Mϩ, 1%), 230 (3), 205 (1), 177 (17), 159 (7),
121 (7), 107 (100).
(Z)-5-(2Ј-Hydroxyphenyl)-7,7-dimethyloct-2-en-1-ol
(47).
Following the general procedure, but with 2.4 equivalents of
organolithium, this was obtained in 67% yield as a clear oil, Rf
0.11 (PE–ether, 1:1); νmax(film)/cmϪ1 3340, 2952, 1655, 1604,
1592, 1455, 1238, 1005, 752, 734; δH (270 MHz, CDCl3) 0.80
(9 H, s, t-Bu), 1.55 (1 H, dd, J 3.2 and 14.0, t-BuCHAHB), 1.65
(1 H, br s, OH), 1.86 (1 H, dd, J 9.2 and 14.0, t-BuCHAHB),
2.25–2.45 (2 H, m, CH CH᎐CH ), 3.10–3.20 (1 H, m, ArCH),
7 J. A. Landgrebe and J. D. Shoemaker, J. Am. Chem. Soc., 1967, 89,
4465.
᎐
2
2
3.97 (2 H, d, J 5.4, CH2OH), 5.50–5.58 (2 H, m, CH=CH), 6.63
(1 H, br s, OH), 6.69 (1 H, dd, J 7.8 and 1.0, ArH), 6.86 (1 H, dt,
J 1.0 and 7.8, ArH), 7.01 (1 H, dt, J 1.6 and 7.8, ArH), 7.15
(1 H, dd, J 1.6 and 7.8, ArH); δC (67.5 MHz, CDCl3) 29.9, 31.2,
35.4, 36.0, 48.8, 58.1, 115.6, 120.3, 126.6, 128.5, 128.6, 132.3,
132.9, 153.4; m/z (CI) 266.2120 (C16H28NO2 requires 266.2120,
Ϫ0.1 ppm error), 266 (MNH4ϩ, 100%), 248 (Mϩ, 10), 231 (25),
194 (40), 177 (42).
8 R. Waack and M. A. Doran, J. Organomet. Chem., 1971, 29, 329;
see also G. Fraenkel, M. J. Geckle, A. Kaylo and D. W. Estes,
J. Organomet. Chem., 1980, 197, 249 and references cited therein.
9 Preliminary communications: X. Wei and R. J. K. Taylor, Chem.
Commun., 1996, 187; X. Wei and R. J. K. Taylor, Tetrahedron Lett.,
1997, 37, 4209.
10 X. Wei and R. J. K. Taylor, Tetrahedron: Asymmetry, 1997, 8, 665.
11 X. Wei and R. J. K. Taylor, Tetrahedron Lett., 1997, 38, 6467.
12 W. F. Bailey and E. R. Punzalan, J. Org. Chem., 1990, 55, 5404;
E. Negishi, D. R. Swanson and C. J. Rousset, J. Org. Chem., 1990,
55, 5406.
13 N. S. Narasimhan and R. S. Mali, Synthesis, 1983, 957; V. Snieckus,
Chem. Rev., 1996, 90, 879.
14 P. Beak, Acc. Chem. Res., 1992, 25, 215.
15 J. A. Marshall, Comprehensive Organic Synthesis, Pergamon Press,
Oxford, 1991, Vol. 3, Ch. 3.11.
16 A. J. Bird, PhD Thesis, University of York, 1996.
(E)-5-(2Ј-Hydroxyphenyl)dec-2-en-1-ol (49). Following the
general procedure, but with 2.4 equivalents of organolithium,
this was obtained in 59% yield as a clear oil, Rf 0.15 (PE–ether,
1:1); νmax(film)/cmϪ1 3350, 2927, 1668, 1605, 1591, 1503, 1454,
1236, 970, 752; δH (270 MHz, CDCl3) 0.83 (3H, t, J 6.5, Me),
1.06–1.35 (6 H, m, 3 × CH2), 1.50–1.70 (2 H, m, CH2CH2-
CHAr), 1.89 (1 H, br s, OH), 2.20–2.43 (2 H, m, CH CH᎐CH ),
᎐
2
2
17 T. Okamoto, K. Kobayashi, S. Oka and S. Tanimoto, J. Org. Chem.,
1988, 53, 4897.
18 O. Mitsunobu, Synthesis, 1981, 1.
3.05 (1 H, quintetappt, J 6.5, ArCH), 3.97 (2 H, d, J 4.1, CH2-
OH), 5.45–5.62 (2 H, m, CH᎐CH), 5.89 (1 H, br s, OH), 6.71
᎐
19 A. T. Worm and J. H. Brewster, J. Org. Chem., 1970, 35, 1715.
20 U. M. Dzhemilev, R. M. Salta, R. G. Gaimaldinov, R. R.
Muslukhov, S. I. Lomakina and G. A. Tolstikov, Bull. Acad. Sci.
USSR, Div. Chem. Sci. (Engl. Transl.), 1992, 770 and 980.
21 N. Meyer and D. Seebach, Chem. Ber., 1980, 113, 1304.
22 K. Petterson and G. Willdeck, Ark. Kemi, 1956, 9, 333.
23 M. C. Musolf and J. L. Speiser, J. Org. Chem., 1964, 29, 2519.
24 E. P. Kündig and A. F. Cunningham, Jr., Tetrahedron, 1988, 44,
6855.
25 I. Ikeda, T. Takeda and S. Komori, J. Org. Chem., 1970, 35, 2353.
26 G. Cardinale, J. A. M. Laan, D. van der Steen and J. P. Ward,
Tetrahedron, 1985, 41, 6051.
27 P. D. Leeson, D. Ellis, J. C. Emmett, V. P. Shah, G. A. Showell and
A. H. Underwood, J. Med. Chem., 1988, 31, 37.
(1 H, dd, J 7.8, 1.0, ArH), 6.87 (1 H, dt, J 1.2 and 7.8, ArH),
6.99–7.12 (2 H, m, ArH); δC (67.5 MHz, CDCl3) 14.1, 22.6,
27.1, 32.0, 35.0, 38.0, 38.7, 63.6, 115.5, 120.7, 126.6, 127.8,
129.7, 131.4, 132.2, 153.7; m/z (CI) 266.2117 (C16H28NO2
requires 266.2120, 1.0 ppm error), 266 (MNH4ϩ, 8%), 248 (Mϩ,
5), 231 (15), 194 (5), 177 (55), 159 (15), 107 (100).
Acknowledgements
We are grateful to the Royal Society for the award of a Royal
Fellowship (X. W.) and to Glaxo-Wellcome and Dr G. M. P.
Giblin for an Undergraduate Summer Vacation Grant (P. J.).
We would also like to thank Professor R. W. Hoffmann (Univ-
ersity of Marburg) and Dr I. Coldham (University of Exeter)
for helpful comments on the chemistry shown in Scheme 5.
28 D. W. Old, J. P. Wolfe and S. L. Buchwald, J. Am. Chem. Soc., 1998,
120, 9722.
Paper a910195k
1116
J. Chem. Soc., Perkin Trans. 1, 2000, 1109–1116