Palladium-promoted arylation of functionalised organolithium compounds via their zinc derivatives

Article abstract of DOI:10.1002/1099-0690(200206)2002:12<1989::AID-EJOC1989>3.0.CO;2-A

The reaction of different functionalised organolithium compounds 2, 5, 8, and 13 [easily prepared by DTBB-catalysed lithiation of isochromane (1), phthalane (4), 2,3-dihydrobenzofuran (7) and 1-chloro-3,3-diethoxypropane (12), respectively] with an equimo

Full text of DOI:10.1002/1099-0690(200206)2002:12<1989::AID-EJOC1989>3.0.CO;2-A

FULL PAPER
Palladium-Promoted Arylation of Functionalised Organolithium Compounds
via Their Zinc Derivatives
[a]
[a]
´
Miguel Yus* and Joaquın Gomis
Dedicated to Professor E. Negishi for his outstanding contributions to main-group metal organometallic chemistry
Keywords: Lithium / Zinc / Palladium / Cross-coupling / Lithiation
The reaction of different functionalised organolithium com-
pounds 2, 5, 8, and 13 [easily prepared by DTBB-catalysed
lithiation of isochromane (1), phthalane (4), 2,3-dihydrobe-
gives the expected cross-coupling products 3, 6, 9 and 14,
respectively. This arylation or alkenylation process, which
also works with the corresponding iodinated derivatives, is
nzofuran (7) and 1-chloro-3,3-diethoxypropane (12), respect- not possible in the absence of both the zinc and palladium
ively] with an equimolecular amount of zinc bromide, fol-
lowed by reaction with an aryl or an alkenyl bromide in the
compounds, under the same reaction conditions.
presence of
a
catalytic amount of [Pd(PPh3)4] or
( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
[Pd(PPh3)2(OAc)2] (5 mol %) under THF reflux overnight
2002)
Introduction
paper we describe a solution to this problem by using a
lithiumϪzinc transmetallation[10] followed by a palladium-
catalysed cross-coupling arylation or alkenylation (Negishi-
type reaction)[11] with the corresponding bromides.[12] This
process is essentially an sp3-sp2-carbon hybridised cross-
coupling reaction, generating a new type of functionalised
organic molecules.
Organolithium compounds are versatile carbanionic in-
termediates in synthetic organic chemistry, especially in car-
bon-carbon bond formation reactions.[1] When organoli-
thium reagents bear a functional group, their utility in syn-
thesis is strongly increased as they are able to transfer the
functionality to the electrophilic reagent, so polyfunction-
alised molecules can be prepared directly in only one reac-
tion step.[2] In general, whereas alkylation of organolithi-
ums works nicely, especially with primary alkyl halides, the
reaction of these intermediates with vinylic or aromatic hal-
ides works only in special cases, mainly through the in situ
generation of the corresponding arynes.[3] In fact, a useful
methodology to prepare aryllithium compounds is halogen
(mainly iodine or bromine)-lithium exchange using an al-
kyllithium reagent for that purpose.[3,4] In the last few years,
we have been preparing functionalised organolithium com-
pounds[2] by an arene-catalysed lithiation[5Ϫ7] starting from
(a) functionalised chlorinated materials, or (b) from hetero-
cyclic compounds[8] by chlorine-lithium exchange or reduct-
ive ring opening, respectively. As expected, these interme-
diates react with different electrophiles, such as H2O, D2O,
RCHO, RRЈCO, CO2 or Me3SiCl, and in some cases alkyl
halides,[9] although they are resistant to arylation or alken-
ylation, with the corresponding bromides or iodides. In this
Results and Discussion
The
4,4Ј-di-tert-butylbiphenyl
(DTBB)-catalysed
lithiation[5] of isochromane (1)[13] in THF at 20 °C led to a
suspension which, after filtration of the excess of lithium,
gave a solution of the corresponding functionalised organ-
olithium compound 2. This intermediate was treated with
zinc bromide (1:1 molar ratio) and then successively with
the corresponding aryl bromide (1:1.1 molar ratio) and a
catalytic amount of a palladium compound {[Pd(PPh3)4]
(Method A) or [Pd(PPh3)2(OAc)2] (Method B); 5 mol %}
and refluxed overnight. Final hydrolysis with hydrochloric
acid afforded the expected products 3a؊3l (Scheme 1 and
Table 1, entries 1Ϫ13). This Negishi cross-coupling reaction
also worked nicely with aryl iodides, as was shown with
iodobenzene (Table 1, entry 1 and footnote [d]), although
the reaction failed with chlorobenzene. In addition, aryl
bromides containing electron-withdrawing (F, CF3, MeCO,
CN, CO2Et) or -donating (MeO, Me2N) groups can be used
for the coupling reaction, as well as naphthyl or heterocyclic
derivatives. Concerning the catalyst, both methods A and
B, gave comparable results (see, for instance, Table 1, entries
1 and 2).
[a]
´
´
Departamento de Quımica Organica, Facultad de Ciencias,
Universidad de Alicante, Apdo. 99,
03080 Alicante, Spain
Fax: (internat) ϩ34-965/903-549
E-mail: yus@ua.es
URL: http://www.ua.es/dept.quimorg/
Eur. J. Org. Chem. 2002, 1989Ϫ1995  WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1434Ϫ193X/02/0612Ϫ1989 $ 20.00ϩ.50/0
1989

M. Yus, J. Gomis
FULL PAPER
Table 1. Preparation of compounds 3, 6 and 9
Entry
Starting
material
Organolithium
intermediate
Aryl bromide
PhBr
Method[a]
Product[b]
Yield
(%)[c]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1
2
A
B
B
A
A
B
A
B
B
A
A
A
B
B
B
B
B
3a
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
6a
6b
6c
9
77 (83)[d]
74
69
1
1
1
1
1
1
1
1
1
1
1
4
4
4
7
2
2
2
2
2
2
2
2
2
2
2
5
5
5
8
4-FC6H4Br
4-CF3C6H4Br
4-MeOC6H4Br
4-Me2NC6H4Br
4-MeCOC6H4Br
4-NCC6H4Br
4-EtO2CC6H4Br
1-bromonaphthalene
4-bromopyridine
2-bromothiophene
3-bromofuran
PhBr
67
63
38[e]
33
78[e]
49[e]
56
29[e]
59
30
43
41
26
4-tBuC6H4Br
4-MeOC6H4Br
PhBr
49
[a]
[b]
1
Method A: [Pd(PPh3)4]; Method B: [Pd(PPh3)2(OAc)2]. All products 3, 6 or 9 were Ն 95% pure (300 MHz H NMR and/or GC).
[c] Isolated yield after column chromatography (silica gel, hexane/ethyl acetate) based on the heterocyclic precursors 1, 4 or 7, respectively.
[d]
[e]
Iodobenzene was used instead of bromobenzene. Water was used in the final hydrolysis.
Scheme 1. Preparation of compounds 3, 6 and 9: (i) Li, DTBB (5
mol %), THF, 0 or 20 °C, then filter off the excess of lithium; (ii)
ZnBr2, THF, 20 °C; (iii) ArBr (1:1.1 molar ratio), [Pd(PPh3)4]
(Method A) or [Pd(PPh3)2(OAc)2] (Method B) (5 mol %), THF, 70
°C; (iv) HCl/H2O
The reaction with isochromane (1) shown in Scheme 1 is
applicable to other functionalised organolithium com-
pounds prepared by ring opening of different heterocycles.
Thus, starting from phthalane (4)[14] or 2,3-dihydrobenzofu-
ran (7),[15] and by using the same procedure, intermediates
5 and 8 were prepared, which, after lithiumϪzinc trans-
metallation and palladium-catalysed cross-coupling reac-
tion, gave products 6a؊6c and 9, respectively (Scheme 1
and Table 1, entries 14Ϫ16 and 17, respectively).
The cross-coupling reaction with sp3- or sp-hybridised
bromides failed. For instance, when the same protocol
(methods A or B) was applied to the intermediate 2 and
cyclohexyl bromide or 1-bromo-2-phenylacetylene, only the
‘‘reduced’’ product, 2-(2-methylphenyl)ethanol (Ͼ 90%), re-
sulting from a metal-hydrogen exchange, was isolated with- methylpropene, giving the expected products 10 (from
out any detectable coupling product. However, the reaction isochromane 1) or 11 (from phthalane 4) using either
worked nicely with olefinic bromides, such as 1-bromo-2- method A or B.
1990
Eur. J. Org. Chem. 2002, 1989Ϫ1995

Palladium-Promoted Arylation of Functionalised Organolithium Compounds
FULL PAPER
Finally, we studied the application of the Negishi-type
In order to shed some light on the mechanism of the
cross-coupling reaction shown in Scheme 1 to different whole process shown in Schemes 1 and 2, we carried out
functionalised organolithium compounds, generated by three blank experiments: (1) in the absence of both the zinc
chlorine-lithium exchange under arene-catalysis condi- bromide and the palladium catalyst, the reaction of inter-
tions.[16] For instance, the reaction of the chloroacetal 12 mediate 2 with bromobenzene gave only the ‘‘reduced’’
with lithium and a catalytic amount of DTBB (5 mol %) in product, 2-(2-methylphenyl)ethanol (Ͼ 90%), and bromob-
THF at Ϫ78 °C led, after filtration of the excess of lithium, enzene (ഠ 90%); (2) in the absence of zinc bromide, and
to a solution of the corresponding organolithium interme- using method A for the same process, only 2-(2-methyl-
diate 13.[17,18] This reagent was submitted to a lithiumϪzinc phenyl)ethanol (Ͼ 90%), and biphenyl (91%) were isolated;
transmetallation and final palladium-catalysed cross-coup- (3) in the absence of the palladium catalyst the only reac-
ling reaction with different aryl bromides under the reaction tion products obtained almost quantitatively were 2-(2-
conditions shown in Scheme 1, to give the expected prod- methylphenyl)ethanol and bromobenzene. With this in-
ucts 14, after hydrolysis under acidic conditions (Scheme 2 formation in hand, we assume that after the lithiumϪzinc
and Table 2). The reaction, which was studied employing transmetallation, and considering the stoichiometry used
the method B, seems to be sensitive to steric hindrance, (1:1), intermediates of the type I؊III (for starting materials
since 2-chlorobromobenzene gave a much lower yield than 1, 4, and 7, respectively) or IV (for the precursor 12) should
the 4-substituted analogue (Table 2, entries 2 and 3). The be involved in the process.[19] These in situ generated func-
mentioned acidic workup with concomitant hydrolysis of tionalised organozinc compounds[2d] take part in the cata-
the acetal moiety is more convenient than the isolation of lytic cycle generally accepted for the Negishi cross-coup-
the corresponding acetal intermediates 15 due to difficulties ling reaction.[11]
found during their purification by column chromatography,
in which partial deprotection occurred.
Scheme 2. Preparation of compounds 14: (i) Li, DTBB (5 mol %),
Conclusions
THF, Ϫ78 °C, then filter off the excess of lithium; (ii) ZnBr2, THF,
Ϫ78 to 20 °C; (iii) ArBr (1:1.1 molar ratio), [Pd(PPh3)2(OAc)2]
(Method B) (5 mol %), THF, 70 °C; (iv) NH4Cl/H2O, then HCl/
H2O
In conclusion, the palladium-catalysed Negishi cross-
coupling reaction can be applied successfully to in situ gen-
erated functionalised organozinc reagents (easily prepared
from the corresponding functionalised organolithium com-
pounds by a lithiumϪzinc transmetallation process); this
reaction is not possible without the help of both the zinc
and palladium components. Finally, the process works well
for arylic and vinylic bromides, as well as with iodides.
Table 2. Preparation of compounds 14
Entry Aryl bromide
Method[a] Product[b] Yield (%)[c]
1
2
3
4
PhBr
B
B
B
B
14a
14b
14c
14d
51
2-ClC6H4Br
4-ClC6H4Br
4-MeCOC6H4Br
10 (19)[d]
48
50
Experimental Section
[a]
[b]
See footnote [a] in Table 1. All products 14 were Ն 93% pure
[c]
General: FT-IR spectra were obtained on a Nicolet Impact 400D
spectrophotometer. NMR spectra were recorded on a Bruker AC-
300 spectrometer with CDCl3 as solvent and TMS as internal
standard; chemical shifts are given in ppm and coupling constants
(J) are given in Hz. 13C NMR assignments were made on the basis
of DEPT experiments. Mass spectra (EI) were obtained at 70 eV
on a Shimadzu QP-5000 spectrometer, fragment ions in m/z with
relative intensities (%) in parentheses. High resolution mass spectra
were obtained by the corresponding service at the University of
Alicante using a Finnigan MAT 95 S apparatus. The purity of vol-
atile products and the chromatographic analyses (GLC) were deter-
mined with a HewlettϪPackard HPϪ4890 instrument equipped
with a flame ionisation detector and a 30-m capillary column
(0.25 mm diameter, 0.25 µm film thickness), nitrogen (2 mL/min)
as carrier gas, Tinjector ϭ 275 °C, Tcolumn ϭ 80 °C (3 min) and
80Ϫ270 °C (15 °C/min); retention times (tR) are given under these
conditions. Thin layer chromatography (TLC) was carried out on
Merck plastic sheets coated with silica gel 60 F254. All starting mat-
erials were commercially available (Acros, Aldrich, Fluka) of the
(300 MHz 1H NMR and/or GC).
Isolated yield after column
chromatography (silica gel, hexane/ethyl acetate) based on the
[d]
starting chloroacetal 12. Yield after refluxing for 1 day.
Eur. J. Org. Chem. 2002, 1989Ϫ1995
1991

M. Yus, J. Gomis
FULL PAPER
best grade and were used without further purification. Lithium
powder was prepared from commercially available lithium granules
(OH), 3066, 3019, 1618, 1418 (CϭCH), 1121 (CF3), 1067 cmϪ1
1
(CϪO). H NMR (300 MHz, CDCl3): δ ϭ 1.90 (br. s, 1 H, OH),
(99%, high sodium content, Aldrich) as already reported by us.[20] 2.84 (t, J ϭ 7.0 Hz, 2 H, ArCH2CH2), 3.75 (t, J ϭ 7.0 Hz, 2 H,
THF was dried over benzophenone ketyl under a nitrogen atmo-
sphere and distilled before use. Zinc bromide was dried by heating
at 120 °C under reduced pressure (0.1 Torr) for 2 hours before use.
CH2OH), 4.11 (s, 2 H, ArCH2Ar), 7.10Ϫ7.27 (m, 6 H, ArH), 7.51
(d, J ϭ 8.0 Hz, 2 H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ
35.8, 38.6 (2 ϫ CH2Ar), 62.8 (CH2OH), 124.2 (q, JC,F ϭ 271.8 Hz,
CF3), 125.2 (q, JC,F ϭ 3.7 Hz, ArCCF3), 126.8, 127.0, 128.8, 130.1,
130.6, 136.8, 137.9, 144.9 (11 C, ArC) ppm. GC-LRMS: m/z (%) ϭ
280 (6) [Mϩ], 263 (16), 262 (97), 261 (49), 249 (14), 247 (28), 235
(15), 234 (12), 233 (11), 229 (13), 214 (12), 194 (17), 193 (100), 183
(12), 180 (18), 179 (33), 178 (66), 166 (14), 165 (62), 159 (13), 117
(24), 116 (18), 115 (27), 91 (64), 89 (16), 77 (20), 63 (11), 51 (15).
HRMS for C16H15F3O: calcd. 280.1075; found 280.1093 [Mϩ].
DTBB-Catalysed Lithiation of Isochromane (1), Phthalane (4) and
2,3-Dihydrobenzofuran (7), and the Palladium-Catalysed Cross-
Coupling Reaction with Aryl and Vinyl Bromides. Isolation of Com-
pounds 3, 6 and 9؊11. General Procedure: Isochromane (1), phthal-
ane (4) or 2,3-dihydrobenzofuran (7) (2 mmol) was added dropwise
at room temperature (for 1 and 7) or 0 °C (for 4) under an argon
atmosphere to a stirred green suspension of lithium powder (70 mg,
10 mmol) and DTBB (53 mg, 0.2 mmol) in THF (10 mL). The col-
our disappeared after the addition, and after 45 min (for 1 and 4)
or 2 h (for 7) stirring the green colour appeared again. The excess
2-[2-(4-Methoxybenzyl)phenyl]ethanol (3d): Rf ϭ 0.25 (hexane/ethyl
acetate, 2:1), tR ϭ 17.91 min. IR (film): ν˜ ϭ 3670Ϫ3125 (OH),
3059, 3013, 1508, 1458 (CϭCH), 1029 cmϪ1 (CϪO). 1H NMR
of lithium was then filtered off under an inert atmosphere and the (300 MHz, CDCl3): δ ϭ 2.20 (br. s, 1 H, OH), 2.85 (t, J ϭ 7.0 Hz,
filtrate was added to a solution of dry zinc bromide (450 mg,
2 mmol) in THF (5 mL). After 30 min stirring, a solution of the
2 H, ArCH2CH2), 3.68 (t, J ϭ 7.0 Hz, 2 H, CH2OH), 3.73 (s, 3 H,
CH3O), 3.98 (s, 2 H, ArCH2Ar), 6.80, 7.02 (2d, J ϭ 8.6 Hz, 2 H
corresponding aryl bromide (2.2 mmol) and the palladium catalyst and 2 H, ArH), 7.11Ϫ7.21 (m, 4 H, ArH) ppm. 13C NMR
(0.1 mmol for both Methods A and B) in THF (10 mL) was added
to the resulting solution and refluxed overnight. After cooling to
room temperature, the mixture was successively treated with 3 
hydrochloric acid (4 mL) (see Table 1, footnote e) and water
(75 MHz, CDCl3): δ ϭ 35.8, 37.8 (2 ϫ CH2Ar), 55.0 (CH3O), 62.7
(CH2OH), 114, 126.3, 126.4, 129.4, 129.9, 130.3, 132.6, 136.6,
139.2, 157.7 (12 C, ArC) ppm. GC-LRMS: m/z (%) ϭ 243 (18)
[Mϩ ϩ 1], 242 (100) [Mϩ], 224 (17), 223 (41), 209 (32), 198 (13),
(10 mL), and extracted with ether (3 ϫ 10 mL). The organic layer 197 (88), 195 (10), 194 (23), 193 (55), 181 (12), 179 (32), 178 (43),
was washed with brine (10 mL), dried (Na2SO4) and the solvents
evaporated (15 Torr) to give a residue, which was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate) to give pure
166 (16), 165 (40), 153 (15), 152 (21), 133 (12), 121 (32), 116 (30),
115 (35), 106 (12), 105 (80), 104 (23), 91 (27), 89 (14), 78 (14), 77
(25), 65 (11), 63 (11), 51 (14), 45 (11). HRMS for C16H18O2: calcd.
compounds 3, 6, and 9؊11. Yields are included in Table 1. Phys- 242.1307; found 242.1310 [Mϩ].
ical, analytical and spectroscopic data follow.
2-[2-(4-Dimethylaminobenzyl)phenyl]ethanol (3e): Rf ϭ 0.19 (hex-
2-(2-Benzylphenyl)ethanol (3a):[21] Rf ϭ 0.38 (hexane/ethyl acetate, ane/ethyl acetate, 2:1), tR ϭ 19.71 min. IR (film): ν˜ ϭ 3702Ϫ3118
2:1), tR ϭ 15.79 min. IR (film): ν˜ ϭ 3670Ϫ3118 (OH), 3060, 3024,
(OH), 3061, 3015, 1615, 1519 (CϭCH), 1045 cmϪ1 (CϪO). 1H
NMR (300 MHz, CDCl3): δ ϭ 1.65 (br. s, 1 H, OH), 2.84Ϫ2.88
1494, 1452 (CϭCH), 1044 cmϪ1 (CϪO). 1H NMR (300 MHz,
CDCl3): δ ϭ 1.75 (br. s, 1 H, OH), 2.85 (t, J ϭ 6.9 Hz, 2 H, (m, 8 H, ArCH2CH2 and (CH3)2N), 3.70 (t, J ϭ 7.0 Hz, 2 H,
ArCH2CH2), 3.68 (t, J ϭ 6.9 Hz, 2 H, CH2OH), 4.05 (s, 2 H, Ar-
CH2Ar), 7.10Ϫ7.21 (m, 7 H, ArH), 7.26 (t, J ϭ 7.3 Hz, 2 H, ArH)
CH2OH), 3.94 (s, 2 H, ArCH2Ar), 6.66, 6.97 (2d, J ϭ 8.6 Hz, 2 H
and 2 H, ArH), 7.15Ϫ7.22 (m, 4 H, ArH) ppm. 13C NMR
ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 35.9, 39.9 (2 ϫ CH2Ar), (75 MHz, CDCl3): δ ϭ 35.9, 37.9 (2 ϫ CH2Ar), 40.8 (2 C, 2 ϫ
62.9 (CH2OH), 126.0, 126.6, 128.4, 128.6, 130.0, 130.7, 136.7,
138.9, 140.7 (12 C, ArC) ppm. GC-LRMS: m/z (%) ϭ 212 (21) 130.6, 136.6, 139.8, 149.0 (12 C, ArC) ppm. GC-LRMS: m/z (%) ϭ
[Mϩ], 195 (15), 194 (100), 193 (92), 181 (22), 180 (18), 179 (99), 255 (52) [Mϩ], 210 (11), 178 (12), 165 (11), 134 (27), 122 (14), 121
CH3), 63.0 (CH2OH), 113.0, 126.3, 126.5, 128.8, 129.2, 129.9,
178 (57), 167 (47), 166 (61), 165 (94), 153 (10), 152 (17), 117 (18), (100), 120 (21), 118 (16), 105 (11), 104 (12), 91 (12). HRMS for
116 (49), 115 (36), 104 (13), 103 (13), 91 (65), 89 (24), 82 (17), 77 C17H21NO: calcd. 255.1623; found 255.1622 [Mϩ].
(26), 76 (13), 65 (20), 63 (14), 51 (21). HRMS for C15H16O: calcd.
4Ј-[2-(2-Hydroxyethyl)benzyl]acetophenone (3f): Rf ϭ 0.13 (hexane/
ethyl acetate, 2:1), tR ϭ 19.92 min. IR (film): ν˜ ϭ 3638Ϫ3131 (OH),
3059, 3020, 1604, 1450 (CϭCH), 1677 (CϭO), 1046 cmϪ1 (CϪO).
1H NMR (300 MHz, CDCl3): δ ϭ 1.50 (br. s, 1 H, OH), 2.57 (s, 3
212.1201; found 212.1207 [Mϩ].
2-[2-(4-Fluorobenzyl)phenyl]ethanol (3b): Rf ϭ 0.32 (hexane/ethyl
acetate, 2:1), tR ϭ 15.67 min. IR (film): ν˜ ϭ 3683Ϫ3118 (OH),
3063, 3019, 1508 (CϭCH), 1223 (CF), 1044 cmϪ1 (CϪO). 1H H, CH3), 2.84 (t, J ϭ 6.7 Hz, 2 H, ArCH2CH2), 3.74 (t, J ϭ 6.7 Hz,
NMR (300 MHz, CDCl3): δ ϭ 1.46 (br. s, 1 H, OH), 2.85 (t, J ϭ 2 H, CH2OH), 4.11 (s, 2 H, ArCH2Ar), 7.11Ϫ7.26 (m, 6 H, ArH),
7.0 Hz, 2 H, ArCH2CH2), 3.73 (t, J ϭ 7.0 Hz, 2 H, CH2OH), 4.02
7.87 (d, J ϭ 7.8 Hz, 2 H, ArH) ppm. 13C NMR (75 MHz, CDCl3):
(s, 2 H, ArCH2Ar), 6.92Ϫ7.25 (m, 8 H, ArH) ppm. 13C NMR δ ϭ 26.5 (CH3), 35.9, 38.9 (2 ϫ CH2Ar), 63.0 (CH2OH), 126.9,
(75 MHz, CDCl3): δ ϭ 35.8, 38.0 (2 ϫ CH2Ar), 62.9 (CH2OH), 127.0, 128.6, 128.8, 130.1, 130.7, 135.2, 136.8, 138.0, 146.5 (12 C,
115.1 (d, JC,F ϭ 20.8 Hz), 126.7, 126.8, 129.9, 130.0 (d, JC,F
ϭ
ArC), 197.8 (CO) ppm. GC-LRMS: m/z (%) ϭ 254 (6) [Mϩ], 193
6.1 Hz), 130.5, 136.2 (d, JC,F ϭ 3.7 Hz), 136.6, 138.8, 161.3 (d,
(14), 179 (10), 178 (17), 121 (25), 44 (11), 43 (100), 40 (14). HRMS
JC,F ϭ 244.1 Hz) (12 C, ArC) ppm. GC-LRMS: m/z (%) ϭ 230 for C17H18O2: calcd. 254.1307; found 254.1311 [Mϩ].
(20) [Mϩ], 213 (15), 212 (100), 199 (14), 198 (14), 197 (78), 196
(45), 185 (35), 184 (37), 183 (60), 179 (72), 178 (20), 177 (12), 165
(18), 133 (16), 117 (14), 116 (25), 115 (18), 109 (36), 105 (13), 104
4-[2-(2-Hydroxyethyl)benzyl]benzonitrile (3g): Rf ϭ 0.20 (hexane/
ethyl acetate, 2:1), tR ϭ 19.22 min. IR (film): ν˜ ϭ 3702Ϫ3118 (OH),
3062, 3019, 1607, 1503 (CϭCH), 2227 (CN), 1045 cmϪ1 (CϪO).
(10), 91 (30), 89 (11), 82 (17), 77 (19), 63 (12), 51 (16). HRMS for
1H NMR (300 MHz, CDCl3): δ ϭ 2.25 (br. s, 1 H, OH), 2.80 (t,
J ϭ 7.0 Hz, 2 H, ArCH2CH2), 3.71 (t, J ϭ 7.0 Hz, 2 H, CH2OH),
4.11 (s, 2 H, ArCH2Ar), 7.08Ϫ7.53 (m, 8 H, ArH) ppm. 13C NMR
(75 MHz, CDCl3): δ ϭ 35.7, 38.8 (2 ϫ CH2Ar), 62.7 (CH2OH),
C15H15FO: calcd. 230.1107; found 230.1105 [Mϩ].
2-[2-(4-Trifluoromethylbenzyl)phenyl]ethanol (3c): Rf ϭ 0.27 (hex-
ane/ethyl acetate, 2:1), tR ϭ 15.52 min. IR (film): ν˜ ϭ 3715Ϫ3112
1992
Eur. J. Org. Chem. 2002, 1989Ϫ1995

Palladium-Promoted Arylation of Functionalised Organolithium Compounds
FULL PAPER
118.8 (CN), 109.6, 126.7, 127.1, 129.2, 130.1, 130.5, 132.0, 136.8,
(69), 184 (37), 173 (52), 172 (13), 171 (18), 167 (48), 166 (12), 165
(19), 154 (24), 153 (44), 152 (34), 141 (26), 134 (11), 129 (13), 128
137.2, 146.4 (12 C, ArC) ppm. GC-LRMS: m/z (%) ϭ 237 (5) [Mϩ],
220 (12), 219 (72), 218 (100), 206 (14), 205 (16), 204 (65), 203 (23), (29), 127 (11), 116 (32), 115 (50), 105 (34), 104 (16), 103 (12), 97
192 (13), 191 (22), 190 (32), 179 (22), 178 (19), 165 (10), 117 (13),
(45), 91 (22), 85 (30), 77 (24), 65 (14), 63 (18), 53 (16), 51 (20), 45
116 (17), 91 (36), 89 (18), 77 (16), 63 (11), 51 (14). HRMS for (48). HRMS for C13H14OS: calcd. 218.0765; found 218.0766 [Mϩ].
C16H15NO: calcd. 237.1154; found 237.1146 [Mϩ].
2-[2-(3-Furylmethyl)phenyl]ethanol (3l): Rf ϭ 0.31 (hexane/ethyl
acetate, 2:1), tR ϭ 14.23 min. IR (film): ν˜ ϭ 3657Ϫ3144 (OH),
3061, 3019, 1491, 1452 (CϭCH), 1043 cmϪ1 (CϪO). 1H NMR
(300 MHz, CDCl3): δ ϭ 1.60 (br. s, 1 H, OH), 2.90 (t, J ϭ 7.0 Hz,
2 H, ArCH2CH2), 3.76Ϫ3.84 (m, 4 H, CH2OH and ArCH2Ar),
6.21, 7.08, 7.15Ϫ7.24, 7.34 (4m, 1 H, 1 H, 4 H and 1 H, ArH)
ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 28.5, 35.8 (2 ϫ CH2Ar),
63.1 (CH2OH), 111.1, 124.2, 126.6, 126.7, 129.9, 130.0, 136.3,
138.5, 139.6, 143.0 (ArC) ppm. GC-LRMS: m/z (%) ϭ 202 (25)
[Mϩ], 183 (12), 171 (12), 169 (12), 157 (23), 155 (37), 153 (30), 152
(31), 143 (18), 142 (18), 141 (65), 134 (11), 129 (34), 128 (100), 127
(16), 116 (23), 115 (64), 106 (94), 105 (25), 104 (15), 103 (11), 98
(10), 97 (34), 91 (34), 89 (13), 81 (22), 78 (13), 77 (30), 76 (13), 69
(96), 65 (21), 63 (27), 55 (69), 53 (24), 52 (11), 51 (41), 50 (16), 44
(14), 43 (12), 41 (14). HRMS for C13H14O2: calcd. 202.0994; found
202.0997 [Mϩ].
Ethyl 4-[2-(2-Hydroxyethyl)benzyl]benzoate (3h): Rf ϭ 0.18 (hexane/
ethyl acetate, 2:1), tR ϭ 21.05 min. IR (film): ν˜ ϭ 3676Ϫ3118 (OH),
3060, 3023, 1610, 1415 (CϭCH), 1718 (CO2), 1046, 1021 cmϪ1
1
(CϪO). H NMR (300 MHz, CDCl3): δ ϭ 1.37 (t, J ϭ 7.0 Hz, 3
H, CH3), 1.70 (br. s, 1 H, OH), 2.83 (t, J ϭ 6.7 Hz, 2 H,
ArCH2CH2), 3.71 (t, J ϭ 6.7 Hz, 2 H, CH2OH), 4.10 (s, 2 H, Ar-
CH2Ar), 4.34 (q, J ϭ 7.0 Hz, 2 H, OCH2CH3), 7.10Ϫ7.25 (m, 6
H, ArH), 7.94 (d, J ϭ 7.9 Hz, 2 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ ϭ 14.3 (CH3), 35.9, 38.9 (2 ϫ CH2Ar), 60.8, 62.9 (2 ϫ
CH2O), 126.8, 126.9, 128.4, 128.6, 129.7, 130.1, 130.7, 136.8, 138.1,
146.1 (12 C, ArC), 166.5 (CO2) ppm. GC-LRMS: m/z (%) ϭ 284
(26) [Mϩ], 254 (18), 239 (24), 238 (18), 237 (42), 225 (10), 207 (10),
194 (17), 193 (100), 181 (28), 180 (14), 179 (44), 178 (76), 166 (26),
165 (49), 152 (12), 135 (13), 117 (16), 116 (13), 115 (31), 105 (28),
104 (12), 103 (12), 91 (40), 89 (26), 77 (21), 76 (15), 65 (10), 51
(11), 44 (20), 40 (17). HRMS for C18H20O3: calcd. 284.1412; found
284.1417 [Mϩ].
2-Benzylphenylmethanol (6a):[22] Rf ϭ 0.48 (hexane/ethyl acetate,
2:1), tR ϭ 15.05 min. IR (film): ν˜ ϭ 3676Ϫ3106 (OH), 3062, 3025,
1494, 1452 (CϭCH), 1038 cmϪ1 (CϪO). 1H NMR (300 MHz,
CDCl3): δ ϭ 2.26 (br. s, 1 H, OH), 4.01 (s, 2 H, ArCH2Ar), 4.54 (s,
2 H, CH2OH), 7.07Ϫ7.36 (m, 9 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ ϭ 38.3 (ArCH2Ar), 62.8 (CH2OH), 126.0, 126.6, 127.8,
128.1, 128.4, 128.6, 130.4, 138.4, 138.7, 140.4 (12 C, ArC) ppm.
GC-LRMS: m/z (%) ϭ 181 (14) [Mϩ Ϫ OH], 180 (89), 179 (100),
178 (37), 165 (42), 91 (27), 89 (31), 77 (16), 76 (13), 65 (17), 51 (15),
40 (12). HRMS for C14H12: calcd. 180.0939; found 180.0931 [Mϩ
Ϫ H2O].
2-[2-(1-Naphthylmethyl)phenyl]ethanol (3i): Rf ϭ 0.36 (hexane/ethyl
acetate, 2:1), tR ϭ 21.51 min. IR (film): ν˜ ϭ 3689Ϫ3125 (OH),
3059, 3016, 1597, 1509 (CϭCH), 1044 cmϪ1 (CϪO). 1H NMR
(300 MHz, CDCl3): δ ϭ 1.79 (br. s, 1 H, OH), 2.84 (t, J ϭ 6.9 Hz,
2 H, ArCH2CH2), 3.76 (t, J ϭ 6.9 Hz, 2 H, CH2OH), 4.42 (s, 2 H,
ArCH2Ar), 6.91Ϫ7.95 (m, 11 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ ϭ 35.6, 35.9 (2 ϫ CH2Ar), 62.8 (CH2OH), 123.7, 125.5,
125.6, 126.0, 126.4, 126.5, 126.7, 126.9, 128.6, 129.8, 130.3, 13.0,
133.6, 136.3, 136.8, 138.4 (ArC) ppm. GC-LRMS: m/z (%) ϭ 263
(18) [Mϩ ϩ 1], 262 (89) [Mϩ], 244 (24), 243 (38), 231 (11), 230 (18),
229 (88), 228 (48), 227 (11), 226 (14), 217 (33), 216 (38), 215 (84),
202 (23), 153 (10), 141 (23), 129 (28), 128 (27), 122 (10), 121 (11),
117 (17), 116 (100), 115 (70), 114 (20), 113 (12), 107 (42), 105 (28),
104 (18), 103 (10), 101 (18), 94 (12), 91 (23), 77 (17), 51 (10).
HRMS for C14H18O: calcd. 262.1358; found 262.1342 [Mϩ].
2-[4-(tert-Butyl)benzyl]phenylmethanol (6b): Rf ϭ 0.49 (hexane/ethyl
acetate, 2:1), tR ϭ 17.55 min. IR (film): ν˜ ϭ 3638Ϫ3118 (OH),
3061, 3023, 1514, 1454 (CϭCH), 1393, 1363 (tBu), 1039 cmϪ1
1
(CϪO). H NMR (300 MHz, CDCl3): δ ϭ 1.28 [s, 9 H, C(CH3)3],
1.62 (br. s, 1 H, OH), 4.03 (s, 2 H, ArCH2Ar), 4.61 (s, 2 H,
CH2OH), 7.03Ϫ7.40 (m, 8 H, ArH) ppm. 13C NMR (75 MHz,
CDCl3): δ ϭ 31.3 (3 C, 3 ϫ CH3), 34.3 (C), 37.9 (ArCH2Ar), 63.1
(CH2OH), 125.4, 126.7, 127.9, 128.2, 128.3, 130.5, 137.4, 138.6,
138.8, 148.9 (12 C, ArC) ppm. GC-LRMS: m/z (%) ϭ 236 (3) [Mϩ
Ϫ H2O], 180 (21), 179 (100), 178 (26), 91 (16), 89 (11), 57 (13), 41
(13). HRMS for C18H22O: calcd. 254.1671; found 254.1681 [Mϩ].
2-[2-(4-Pyridylmethyl)phenyl]ethanol (3j): Rf ϭ 0.23 (ethyl acetate),
tR ϭ 16.67 min. IR (film): ν˜ ϭ 3657Ϫ3120 (OH), 3065, 3023, 1491
(CϭCH), 1049 cmϪ1 (CϪO). 1H NMR (300 MHz, CDCl3): δ ϭ
2.82 (t, J ϭ 7.0 Hz, 2 H, ArCH2CH2), 3.32 (br. s, 1 H, OH), 3.75
(t, J ϭ 7.0 Hz, 2 H, CH2OH), 4.05 (s, 2 H, ArCH2Ar), 7.02Ϫ7.28
(m, 6 H, ArH), 8.37 (d, J ϭ 4.9 Hz, 2 H, ArH) ppm. 13C NMR
(75 MHz, CDCl3): δ ϭ 35.9, 38.2 (2 ϫ CH2Ar), 62.6 (CH2OH),
121.4, 124.0, 126.7, 127.2, 130.2, 130.6, 136.6, 137.2, 149.3 (11 C,
ArC) ppm. GC-LRMS: m/z (%) ϭ 213 (39) [Mϩ], 195 (12), 194
(39), 183 (11), 182 (27), 181 (18), 180 (100), 168 (13), 167 (21), 152
(14), 121 (13), 117 (13), 115 (12), 91 (34), 80 (14), 77 (12), 65 (10),
51 (15). HRMS for C14H15NO: calcd. 213.1154; found 213.1159
[Mϩ].
2-(4-Methoxybenzyl)phenylmethanol (6c):[23] Rf ϭ 0.34 (hexane/
ethyl acetate, 2:1), tR ϭ 17.09 min. IR (film): ν˜ ϭ 3638Ϫ3118 (OH),
3063, 3024, 1511, 1455 (CϭCH), 1035 cmϪ1 (CϪO). 1H NMR
(300 MHz, CDCl3): δ ϭ 1.65 (br. s, 1 H, OH), 3.77 (s, 3 H, CH3O),
4.02 (s, 2 H, ArCH2Ar), 4.64 (s, 2 H, CH2OH), 6.82, 7.05 (2d, J ϭ
8.6 Hz, 2 H and 2 H, ArH), 7.16, 7.26, 7.40 (3m, 1 H, 2 H and 1
H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 37.6 (ArCH2Ar),
55.2 (CH3O), 63.2 (CH2OH), 113.9, 126.7, 128.0, 128.4, 129.6,
130.4, 132.5, 138.7, 139.0, 158.0 (12 C, ArC) ppm. GC-LRMS:
m/z (%) ϭ 228 (15) [Mϩ], 211 (16), 210 (100), 209 (95), 195 (15),
194 (31), 180 (16), 179 (94), 178 (37), 167 (14), 166 (10), 165 (29),
152 (19), 121 (12), 120 (26), 118 (31), 105 (12), 91 (38), 89 (13), 82
(12), 77 (18), 65 (14), 51 (14). HRMS for C15H16O2: calcd.
228.1150; found 228.1160 [Mϩ].
2-[2-(2-Thienylmethyl)phenyl]ethanol (3k): Rf ϭ 0.32 (hexane/ethyl
acetate, 2:1), tR ϭ 15.74 min. IR (film): ν˜ ϭ 3626Ϫ3131 (OH),
3055, 3017, 1491, 1458 (CϭCH), 1041 cmϪ1 (CϪO). 1H NMR
(300 MHz, CDCl3): δ ϭ 1.72 (br. s, 1 H, OH), 2.88 (t, J ϭ 7.0 Hz,
2 H, ArCH2CH2), 3.71 (t, J ϭ 6.7 Hz, 2 H, CH2OH), 4.18 (s, 2 H,
ArCH2Ar), 6.69, 6.88, 7.12, 7.20 (4m, 1 H, 1 H, 1 H and 4 H,
ArH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 33.3, 35.8 (2 ϫ 2-Phenethylphenol (9):[24] Rf ϭ 0.61 (hexane/ethyl acetate, 2:1), tR ϭ
CH2Ar), 63.1 (CH2OH), 123.8, 124.9, 126.8, 127.0, 130.1, 130.2,
14.89 min. IR (KBr): ν˜ ϭ 3528 (OH), 3059, 3022, 1590, 1500 (Cϭ
136.5, 138.6, 144.1 (10 C, ArC) ppm. GC-LRMS: m/z (%) ϭ 218 CH), 1267 cmϪ1 (CϪO). 1H NMR (300 MHz, CDCl3): δ ϭ 2.91
(69) [Mϩ], 201 (13), 200 (63), 199 (100), 187 (13), 186 (12), 185 (s, 4 H, CH2CH2), 4.83 (s, 1 H, OH), 6.71 (d, J ϭ 8.6 Hz, 1 H,
Eur. J. Org. Chem. 2002, 1989Ϫ1995
1993

M. Yus, J. Gomis
FULL PAPER
ArH), 6.85, 7.07 (2t, J ϭ 7.3 Hz, 1 H and 2 H, ArH), 7.18Ϫ7.30 3-Phenylpropanal (14a):[25] Rf ϭ 0.61 (hexane/ethyl acetate, 2:1),
(m, 5 H, ArH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 32.3, 36.1 tR ϭ 8.71 min. IR (film): ν˜ ϭ 3062, 3028, 1496, 1451 (CϭCH),
(2 ϫ CH2), 115.3, 120.8, 125.9, 127.3, 127.9, 128.3, 128.4, 130.3, 1724 (CHO). 1H NMR (300 MHz, CDCl3): δ ϭ 2.73, 2.93 (2t, J ϭ
142.0, 153.5 (12 C, ArC) ppm. GC-LRMS: m/z (%) ϭ 198 (31) 7.3 Hz, 2 H and 2 H, CH2CH2), 7.19Ϫ7.27 (m, 5 H, ArH), 9.76 (s,
[Mϩ], 107 (100), 91 (34), 77 (27), 65 (14), 51 (10). HRMS for 1 H, CHO) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 27.5, 46.5 (2
C14H14O: calcd. 198.1045; found 198.1041 [Mϩ].
ϫ CH2), 125.9, 128.0, 128.2, 140.1 (6 C, ArC), 201.1 (CHO) ppm.
GC-LRMS: m/z (%) ϭ 134 (79) [Mϩ], 133 (14), 105 (37), 103 (16),
92 (87), 91 (100), 79 (32), 78 (66), 77 (43), 65 (30), 63 (11), 55
(10), 51 (41), 50 (17). HRMS for C9H10O: calcd. 134.0732; found
134.0729 [Mϩ].
2-[2-(3-Methyl-2-butenyl)phenyl]ethanol (10): Rf ϭ 0.42 (hexane/
ethyl acetate, 2:1), tR ϭ 13.21 min. IR (film): ν˜ ϭ 3632Ϫ3125 (OH),
3060, 3017, 1490, 1450 (CϭCH), 1044 cmϪ1 (CϪO). 1H NMR
(300 MHz, CDCl3): δ ϭ 1.72 (s, 6 H, 2 ϫ CH3), 1.93 (br. s, 1 H,
OH), 2.89 (t, J ϭ 7.0 Hz, 2 H, ArCH2CH2), 3.35 (d, J ϭ 6.7 Hz,
2 H, ArCH2CH), 3.80 (t, J ϭ 7.0 Hz, 2 H, CH2OH), 5.22 (t, J ϭ
7.0 Hz, 1 H, CHϭC), 7.15 (m, 4 H, ArH) ppm. 13C NMR
(75 MHz, CDCl3): δ ϭ 17.8, 25.6 (2 ϫ CH3), 31.6, 35.9 (2 ϫ
CH2Ar), 63.0 (CH2OH), 123.0, 132.2 (CϭC), 126.0, 126.6, 129.3,
129.8, 136.1, 140.1 (ArC) ppm. GC-LRMS: m/z (%) ϭ 190 (24)
[Mϩ], 159 (13), 158 (13), 157 (100), 145 (61), 143 (19), 142 (28),
141 (15), 132 (19), 130 (19), 129 (88), 128 (40), 126 (12), 117 (64),
116 (21), 115 (52), 105 (52), 104 (13), 103 (12), 91 (49), 77 (25), 65
(17), 63 (11), 55 (12), 53 (12), 51 (16), 43 (51), 41 (65). HRMS for
C13H18O: calcd. 190.1358; found 190.1367 [Mϩ].
3-(2-Chlorophenyl)propanal (14b):[26] Rf ϭ 0.58 (hexane/ethyl acet-
ate, 2:1), tR ϭ 10.56 min. IR (film): ν˜ ϭ 3064, 3022, 1474, 1444
(CϭCH), 1724 (CHO). 1H NMR (300 MHz, CDCl3): δ ϭ 2.79,
3.06 (2t, J ϭ 7.3 Hz, 2 H and 2 H, CH2CH2), 7.12Ϫ7.36 (m, 4 H,
ArH), 9.82 (s, 1 H, CHO) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ
26.1, 43.4 (2 ϫ CH2), 126.9, 127.8, 129.6, 130.4, 133.8, 137.9 (ArC),
201.1 (CHO) ppm. GC-LRMS: m/z (%) ϭ 168 (26) [Mϩ], 139 (10),
133 (100), 127 (25), 126 (19), 125 (74), 115 (14), 112 (30), 105 (33),
104 (14), 103 (44), 102 (11), 91 (69), 89 (21), 78 (13), 77 (70), 75
(22), 63 (19), 56 (22), 55 (24), 51 (44), 50 (21). HRMS for C9H9ClO:
calcd. 168.0342; found 168.0340 [Mϩ].
3-(4-Chlorophenyl)propanal (14c):[27] Rf ϭ 0.52 (hexane/ethyl acet-
ate, 2:1), tR ϭ 10.98 min. IR (film): ν˜ ϭ 3031, 1490 (CϭCH), 1723
(CHO). 1H NMR (300 MHz, CDCl3): δ ϭ 2.76, 2.92 (2t, J ϭ
7.3 Hz, 2 H and 2 H, CH2CH2), 7.13, 7.26 (2d, J ϭ 8.5 Hz, 2 H
and 2 H, ArH), 9.81 (s, 1 H, CHO) ppm. 13C NMR (75 MHz,
CDCl3): δ ϭ 27.4, 45.1 (2 ϫ CH2), 128.6, 129.6, 132.0, 138.8 (6 C,
2-[2-(3-Methyl-2-butenyl)phenyl]phenylmethanol (11): Rf ϭ 0.55
(hexane/ethyl acetate, 2:1), tR ϭ 12.47 min. IR (film): ν˜
ϭ
3645Ϫ3106 (OH), 3064, 3025, 1449 (CϭCH), 1039 cmϪ1 (CϪO).
1H NMR (300 MHz, CDCl3): δ ϭ 1.72 (s, 6 H, 2 ϫ CH3), 2.22 (br.
s, 1 H, OH), 3.36 (d, J ϭ 7.3 Hz, 2 H, ArCH2CH), 4.62 (s, 2 H,
CH2OH), 5.23 (t, J ϭ 7.3 Hz, 1 H, CHϭC), 7.15Ϫ7.34 (m, 4 H,
ArH) ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 17.8, 25.6 (2 ϫ CH3),
31.2 (ArCH2CH), 63.0 (CH2OH), 123.0, 132.6 (CϭC), 126.1,
127.8, 128.0, 129.2, 138.4, 139.5 (ArC) ppm. GC-LRMS: m/z (%) ϭ
176 (0.3) [Mϩ], 158 (29), 144 (12), 143 (100), 129 (14), 128 (44),
127 (10), 120 (31), 119 (40), 116 (14), 115 (24), 91 (35), 77 (24), 65
(19), 63 (10), 53 (11), 51 (21), 43 (23), 41 (44), 40 (11). HRMS for
C12H16O: calcd. 176.1201; found 176.1201 [Mϩ].
ArC), 201.0 (CHO) ppm. GC-LRMS: m/z (%) ϭ 170 (12) [Mϩ
ϩ
2], 168 (40) [Mϩ], 133 (54), 127 (36), 126 (25), 125 (100), 115 (15),
114 (12), 112 (36), 105 (15), 103 (37), 91 (53), 89 (22), 77 (51), 75
(24), 63 (22), 56 (10), 55 (27), 51 (42), 50 (27). HRMS for C9H9ClO:
calcd. 168.0342; found 168.0343 [Mϩ].
3-(4-Acetylphenyl)propanal (14d):[28] Rf ϭ 0.29 (hexane/ethyl acet-
ate, 2:1), tR ϭ 13.24 min. IR (film): ν˜ ϭ 3037, 1606 (CϭCH), 1722
(CHO), 1679 (CO). 1H NMR (300 MHz, CDCl3): δ ϭ 2.59 (s, 3
H, CH3CO), 2.82, 3.02 (2t, J ϭ 7.3 Hz, 2 H and 2 H, CH2CH2),
7.29, 7.89 (2d, J ϭ 7.9 Hz, 2 H and 2 H, ArH), 9.83 (1 H, s, CHO)
ppm. 13C NMR (75 MHz, CDCl3): δ ϭ 26.6 (CH3CO), 27.9, 44.7
(2 ϫ CH2), 128.5, 128.7, 135.4, 146.0 (6 C, ArC), 197.7 (CO), 200.7
(CHO) ppm. GC-LRMS: m/z (%) ϭ 176 (40) [Mϩ], 162 (11), 161
(100), 133 (17), 118 (11), 105 (31), 103 (17), 91 (11), 79 (19), 78
(10), 77 (33), 65 (10), 63 (14), 51 (20), 43 (84). HRMS for C11H12O2:
calcd. 176.0837; found 176.0826 [Mϩ].
DTBB-Catalysed Lithiation of 1-Chloro-3,3-diethoxypropane (12)
and Palladium-Catalysed Cross-Coupling Reaction with Aryl Brom-
ides. Isolation of Compounds 14. General Procedure: 1-Chloro-3,3-
diethoxypropane (2 mmol) was added dropwise at Ϫ78 °C and un-
der an argon atmosphere to a stirred green suspension of lithium
powder (70 mg, 10 mmol) and DTBB (53 mg, 0.2 mmol) in THF
(10 mL). The colour disappeared after the addition, and after 1 h
stirring the green colour appeared again. The excess of lithium was
then filtered off under an inert atmosphere and the filtrate was
added to a solution of dry zinc bromide (450 mg, 2 mmol) in THF
(5 mL) at Ϫ78 °C. After 30 min stirring, the solution was allowed
to rise to room temperature, and a solution of the corresponding
aryl bromide (2.2 mmol) and the palladium catalyst (0.1 mmol) in
THF (10 mL) was added; the resulting solution was refluxed over-
night. After cooling to room temperature, the mixture was treated
successively with saturated NH4Cl and water (10 mL) and extracted
with ether (3 ϫ 10 mL). The organic layer was washed with brine
(10 mL), dried (Na2SO4) and the solvents evaporated (15 Torr) to
give a residue, which was dissolved in THF (20 mL). HCl (3 ,
8 mL) was then added and the mixture was stirred overnight at
room temperature. After the addition of water (10 mL), the mixture
was again extracted with ether (3 ϫ 10 mL) and the organic layer
was washed with brine (10 mL), dried (Na2SO4) and the solvents
evaporated (15 Torr) to give a residue, which was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate) to give pure
compounds 14. Yields are included in Table 2. Physical, analytical
and spectroscopic data follow.
Acknowledgments
This work was financially supported by the DGICYT (no. PB97-
0133) and DGI (no. BQU2001-0538) from the current Spanish
´
Ministerio de Educacion, Cultura y Deportes (MECD) and Minis-
´
terio de Ciencia y Tecnologıa (MCYT), respectively. J. G. thanks
the MECD for a fellowship.
[1]
B. Wakefield, Organolithium Methods, Academic Press, Lon-
don, 1988.
[2]
[2a]
[2b]
Reviews on functionalised organolithium compounds:
C.
C.
´
Najera, M. Yus, Trends Org. Chem. 1991, 2, 155Ϫ181.
´
Najera, M. Yus, Recent. Res. Devel. Org. Chem. 1997, 1,
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´
[2d]
See also: A. Boudier, L. O. Bromm, M. Lotz, P. Knochel,
Angew. Chem. 2000, 112, 4584Ϫ4606; Angew. Chem. Int. Ed.
2000, 39, 4414Ϫ4435.
1994
Eur. J. Org. Chem. 2002, 1989Ϫ1995

Palladium-Promoted Arylation of Functionalised Organolithium Compounds
FULL PAPER
[3] [3a]
[3b]
[16]
See ref.[1], p. 108.
U. Schöllkopf, in Metallorganische
M. Yus, D. J. Ramon, J. Chem. Soc., Chem. Commun. 1991,
´
Verbindungen Li, Na, K, Rb, Cs, Cu, Ag, Au (Houben-Weyl)
(Eds: E. Müller, O. Bayer, H. Meerwein, K. Ziegler), G. Thieme
Verlag, Stuttgart, 1970, vol. 13/I, p. 216.
I. Omae, Applications of Organometallic Compounds, J. Wiley &
Sons, Chichester, 1998, p. 37.
Reviews:
398Ϫ400.
[17] [17a]
´
J. Barluenga, C. Rubiera, J. R. Fernandez, M. Yus, J.
Chem. Soc., Chem. Commun. 1987, 425Ϫ426. [17b] J. Barluenga,
J. R. Fernandez, C. Rubiera, M. Yus, J. Chem. Soc., Perkin
[4]
[5]
´
Trans. 1 1988, 3113Ϫ3117.
[5a]
[5b]
[5c]
[18]
[19]
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M. Yus, Chem. Soc. Rev. 1996, 25, 155Ϫ161.
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D. J. Ramon, M. Yus, Eur. J. Org. Chem. 2000, 225Ϫ237.
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M. Yus, Synlett 2001, 1197Ϫ1205.
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For mechanistic studies, see: M. Yus, R. P. Herrera, A. Gui-
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For a polymer-supported arene-catalysed version of this reac-
For Michael-type additions of functionalised organolithium
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M. Yus, P. Martınez, D. Guijarro, Tetrahedron 2001, 57,
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P. Knochel, Synlett
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