New preparation of benzylic zinc reagents via a fragmentation reaction

Article abstract of DOI:10.1016/S0022-328X(00)00840-8

The fragmentation of sterically hindered homobenzylic zinc alcoholates proceeds readily leading to benzylic zinc reagents free from any Wurtz-coupling product. Reaction of these organometallic intermediates with various aldehydes produces new homobenzylic

Full text of DOI:10.1016/S0022-328X(00)00840-8

Journal of Organometallic Chemistry 624 (2001) 88–95
www.elsevier.nl/locate/jorganchem
New preparation of benzylic zinc reagents via a fragmentation
reaction
Claudia Piazza, Nicolas Millot, Paul Knochel *
Department Chemie, Ludwig–Maximilians-Uni6ersita¨t Mu¨nchen, Butenandtstrasse 5-13, 81377 Munich, Germany
Received 11 September 2000; accepted 17 October 2000
Dedicated to Professor Jean Normant for his 65th birthday
Abstract
The fragmentation of sterically hindered homobenzylic zinc alcoholates proceeds readily leading to benzylic zinc reagents free
from any Wurtz-coupling product. Reaction of these organometallic intermediates with various aldehydes produces new
homobenzylic alcohols in moderate to good yields. A 1,4-addition of these newly prepared benzylic organometallics to an
alkylidenemalonate is also reported. © 2001 Elsevier Science B.V. All rights reserved.
Keywords: Zinc; Benzylic organometallics; Fragmentation; Addition to aldehydes
1. Introduction
shown that sterically hindered homoallylic zinc alcoho-
lates undergo a smooth fragmentation reaction provid-
ing highly substituted allylic zinc compounds with the
absence of formation of any homocoupling product
formation [5]. Herein, we wish to report a new prepara-
tion of benzylic zinc reagents, based on a similar frag-
mentation reaction of homobenzylic zinc alcoholates of
type 1. Because of the steric hindrance of the large
substituent (RL=t-Bu) a fragmentation reaction occurs
leading to the benzylic zinc reagent 2 and to the unreac-
tive sterically hindered ketone 3. By generating the
benzylic organometallic 2 in the presence of an elec-
trophile, products of type 4 are obtained (Scheme 1).
Benzylic organometallics are important intermediates
for preparing polyfunctional molecules of pharmaceuti-
cal interest [1]. Although several methods are available
for the preparation of benzylic lithium and magnesium
compounds [1b,2], these reactions are all complicated
by the formation of homocoupling products. Benzylic
zinc reagents prepared by the direct insertion of zinc
dust are obtained in a more straightforward fashion
and the formation of Wurtz-coupling products is mini-
mized in many cases [3]. However, even for the prepa-
ration of benzylic zinc reagents starting from
electron-rich benzylic halides, the formation of Wurtz-
coupling is a serious side-reaction [4]. This is due to the
radical nature of the reaction of a metal like magne-
sium or zinc with a benzylic halide. Recently, we have
2. Results and discussion
The required homobenzylic alcohols 5 were prepared
easily starting from commercially available phenylacetyl
chloride (6). First, reaction of the acid chloride 6 with
t-BuCu·MgX2 [6] provides the ketone 7 in 68% yield.
Treatment of the ketone 7 with sodium hydride (room
temperature (r.t.), 1 h) followed by the addition of an
electrophile (methyl iodide, allyl bromide or 4-methoxy-
benzyl chloride) furnishes after a reaction time between
3 and 24 h the expected alkylated products 8a–c in
61–91% yield (Scheme 2). The ketones 8a–c were
treated with t-BuLi at −78°C for 1 h in ether leading
Scheme 1.
* Corresponding author. Fax: +49-89-21807680.
E-mail address: paul.knochel@cup.uni-muenchen.de (P. Knochel).
0022-328X/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(00)00840-8

C. Piazza et al. / Journal of Organometallic Chemistry 624 (2001) 88–95
89
Scheme 2.
to the desired alcohols 5a–c in 81–93% yield. These
alcohols were treated at −78°C with n-BuLi (1.1
equiv) followed by the addition of a THF solution of
zinc chloride (1.1 equiv) and subsequent addition of an
aldehyde (1.1 equiv). The reaction mixture was allowed
to reach r.t. within 12 h leading to the expected ho-
mobenzylic alcohols 9a–j in 46–80% yield (Scheme 3
and Table 1). Aromatic aldehydes like benzaldehyde
(entries 1, 7 and 10), 1-naphthaldehyde (entries 2 and 8)
and furfural (entries 3 and 9) react rapidly leading to
the alcohol 9 as a mixture of diastereoisomers.
The reaction proceeds also with a,b-unsaturated
aldehydes such as trans-cinnamaldehyde (entry 4) and
perillaldehyde (entry 5). Finally, an aliphatic aldehyde
such as cyclohexanecarboxaldehyde gives also the ex-
pected alcohol 9f in 60% yield (entry 6). The reaction
can be extended to other electrophiles like alkylidene-
malonates. Thus, by using diethyl benzylidenemalonate
10 and the alcohol 5a, the Michael-adduct 11 is ob-
tained as a mixture of diastereoisomers (syn/anti 40:60)
in 60% yield (Scheme 4).
completely avoids the formation of Wurtz-byproducts.
The starting homobenzylic alcohols 5 required for the
fragmentation are readily prepared making our method
complementary to other known procedures.
4. Experimental
4.1. General considerations
All reactions were carried out under an argon atmo-
sphere. THF was distilled from sodium/benzophenone.
Zinc chloride was freshly dried before use for 2 h at
150°C and less than 0.1 mmHg. Reactions were moni-
tored by gas chromatography (GC) analysis of reaction
aliquots. Analytical thin-layer chromatography (TLC)
was performed using Merck silica gel (60 F-254) plates
(0.25 mm) precoated with a fluorescent indicator.
Column chromatography was carried out on silica gel
60 (70–230 mesh). NMR spectra were recorded on a
300 MHz NMR spectrometer. The ionization method
used was electron impact ionization (EI, 70 eV). Ele-
mental analyses were performed by the Microanalytical
Service Laboratory of Universita¨t Mu¨nchen.
3. Conclusion
We have developed a new preparation of benzylic
zinc reagents via the fragmentation of sterically hin-
dered homobenzylic zinc alcoholates. This method
4.2. Preparation of 3,3-dimethyl-1-phenyl-butan-2-one
(7) [7]
A solution of tert-butylmagnesium chloride (0.11
mol) in THF (1.7 M, 65 ml) was added dropwise over
1 h at 0°C to a stirred suspension of copper(I) bromide
(14.3 g, 0.10 mol) in THF (30 ml) containing pheny-
lacetyl chloride (15.5 g, 0.10 mol). After complete addi-
tion the black reaction mixture was stirred at r.t. for 1
h and poured into ice (200 ml). The mixture was then
filtered over celite and acidified with HCl 1 N. The
yellow solution was extracted with ether (3×), and the
combined organic layer was washed with water (2×)
Scheme 3.

90
C. Piazza et al. / Journal of Organometallic Chemistry 624 (2001) 88–95
Table 1
Homobenzylic alcohols 9a–j prepared by the fragmentation of zinc alcoholates obtained from the corresponding homobenzylic alcohols 5a–c in
the presence of an aldehydea
a Isolated yields of analytically pure products.
IR (film, cm−1): w 2967, 1711, 1477, 1060, 724, 696.
1H-NMR (CDCl3, 300 MHz): l 7.24–7.08 (m, 5H),
3.71 (s, 2H), 1.11 (s, 9H). 13C-NMR (CDCl3, 75 MHz):
l 212.8, 135.1, 129.7, 128.5. m/z (EI) 176.1199 ([M+],
12%, C12H16O requires 176.1197), 91 (48), 85 (62), 57
(100).
Scheme 4.
4.3. Preparation of
2,2-dimethyl-4-phenylhept-6-en-3-one (8a) [8]
and brine, dried over MgSO4 and concentrated under
reduced pressure. The crude material was distilled un-
der vacuum to give the ketone 7 (11.9 g, 68% yield) as
a light yellow oil (bp: 115°C, 1 mmHg).
A solution of tert-butyl benzyl ketone (6.3g, 35.7
mmol) and allyl bromide (3.7 ml, 42.7 mmol) in THF
(10 ml) was added at r.t. to a suspension of sodium

C. Piazza et al. / Journal of Organometallic Chemistry 624 (2001) 88–95
91
hydride (2.68 g, 67 mmol, 60% in oil) in THF (40 ml).
The reaction mixture was stirred for 3 h and a saturated
aqueous solution of NH4Cl was added carefully at 0°C.
The aqueous layer was extracted with ether (3×). The
combined organic layer was washed with water and
brine, then dried over MgSO4 and concentrated under
reduced pressure. The resulting oil was purified by flash
chromatography (eluent: pentane/ether 9:1) to afford
the desired product 8a as a colourless oil (7.55 g, 98%
yield).
under reduced pressure. The resulting oil was purified
by flash chromatography (eluent: pentane/ether
98.5:1.5) to afford the desired product 8c (2.03 g, 61%
yield) as an orange solid (mp: 63°C).
IR (film, cm−1): w 2970, 1694, 1454, 1176, 1036, 700.
1H-NMR (CDCl3, 300 MHz): l 7.39 (d, 2H, J=8.0
Hz), 7.25–7.05 (m, 3H), 6.96 (d, 2H, J=8.4 Hz), 3.91
(m, 1H), 3.67 (s, 3H), 3.59 (m, 2H), 1.35 (s, 9H).
13C-NMR (CDCl3, 75 MHz): l 212.8, 156.2, 137.6,
130.1, 128.3, 126.7, 126.4, 125.0, 111.7, 53.7, 53.3, 43.2,
39.2, 24.3. m/z (EI) 296.1771 ([M+], 9%, C20H24O2
requires 296.1776), 211 (27), 121 (100).
IR (film, cm−1): w 2967, 1702, 1477, 1073, 700.
1H-NMR (CDCl3, 300 MHz): l 7.24–7.10 (m, 5H),
5.61–5.47 (m, 1H), 4.96–4.84 (m, 2H), 4.08–4.04 (m,
1H), 2.68–2.58 (m, 1H), 2.38–2.28 (m, 1H), 0.99 (s,
9H). 13C-NMR (CDCl3, 75 MHz): l 214.9, 139.6,
136.4, 129.0, 128.6, 127.3, 117.1, 53.3, 45.4, 40.2, 26.9.
m/z (EI) 216 (1), 159 (17), 131 (84), 115 (19), 103 (8), 91
(52), 85 (45), 77 (11), 57 (100). Anal. Calc. for C15H20O:
C, 83.28; H, 9.32. Found: C, 83.16; H, 9.43.
4.6. Preparation of
3-tert-butyl-2,2-dimethyl-4-phenylhept-6-en-3-ol (5a)
A solution of tert-butyllithium (30 ml, 18.3 mmol,
1.64 M in pentane) was added at −78°C to a solution
of the ketone 8a (5 g, 23.1 mmol) in ether (35 ml). The
reaction mixture was stirred at this temperature for 1 h
and quenched with a saturated aqueous solution of
NH4Cl. The aqueous layer was extracted with ether
(3×). The combined organic layer was washed with
brine, then dried over MgSO4 and concentrated under
reduced pressure. The resulting oil was purified by flash
chromatography (eluent: pentane/ether 9:1) to afford a
colourless oil (5.9 g, 93% yield).
4.4. Preparation of 2,2-dimethyl-4-phenylpentan-3-one
(8b) [9]
A solution of tert-butyl benzyl ketone (1 g, 5.7
mmol) and methyl iodide (0.78 ml, 12 mmol) in THF (5
ml) was added at r.t. to a suspension of sodium hydride
(0.48 g, 12 mmol, 60% in oil) in THF (5 ml). The
reaction mixture was stirred for 3 h and a saturated
aqueous solution of NH4Cl was carefully added at 0°C.
The aqueous layer was extracted with ether (3×). The
combined organic layer was washed with water and
brine, then dried over MgSO4 and concentrated under
reduced pressure. The resulting oil was purified by flash
chromatography (eluent: pentane/ether 125:1) to afford
the desired product 8b as a light yellow oil (0.98 g, 91%
yield).
IR (film, cm−1): w 3592, 2963, 1491, 1393, 994, 911,
705. 1H-NMR (CDCl3, 300 MHz): l 7.33–7.08 (m,
5H), 5.49–5.37 (m, 1H), 4.90 (d, 1H, J=17.0 Hz), 4.83
(d, 1H, J=14 Hz), 3.42 (d, 1H, J=7.4 Hz), 3.10–2.87
(m,2H), 1.21 (s, 9H), 1.07 (s, 9H). 13C-NMR (CDCl3,
75 MHz): l 140.0, 138.4, 132.5, 127.8, 126.7, 115.6,
81.9, 52.4, 44.2, 44.0, 35.6, 31.1, 30.0. m/z (EI) 217 (5),
161 (2), 143 (21), 131 (39), 87 (54), 57 (100). Anal. Calc.
for C19H30O: C, 83.15; H, 11.02. Found: C, 83.28; H,
11.21.
IR (film, cm−1): w 2969, 1703, 1477, 1367, 1063, 700.
1H-NMR (CDCl3, 300 MHz): l 7.21–7.17 (m, 5H),
4.18 (q, 1H, J=6.9 Hz), 1.02 (s, 9H). 13C-NMR
(CDCl3, 75 MHz): l 216.1, 141.6, 128.7, 128.0, 126.9,
46.5, 45.3, 26.7, 21.2. m/z (EI) 190 (14), 105 (93), 85
(69), 77 (35), 57 (100). Anal. Calc. for C13H18O: C,
82.06; H, 9.53. Found: C, 81.76; H, 9.63.
4.7. Preparation of
2,2,4,4-tetramethyl-3-(1-phenylethyl)-pentan-3-ol (5b)
A solution of tert-butyllithium (2.7 ml, 3.3 mmol, 1.2
M in pentane) was added at −78°C to a solution of
the ketone 8b (0.3 g, 1.6 mmol) in ether (2.5 ml). The
reaction mixture was stirred at this temperature for 45
min and quenched with a saturated aqueous solution of
NH4Cl. The aqueous layer was extracted with ether
(3×). The combined organic layer was washed with
brine, then dried over MgSO4 and concentrated under
reduced pressure. The resulting oil was purified by flash
chromatography (eluent: pentane/ether 99:1) to afford a
colourless oil (0.34 g, 89% yield).
4.5. Preparation of 1-(4-methoxyphenyl)-
4,4-dimethyl-2-phenylpentan-3-one (8c)
A solution of tert-butyl benzyl ketone (2 g, 11.4
mmol) and 4-methoxybenzyl chloride (1.7 ml, 12.5
mmol) in THF (10 ml) was added at r.t. to a suspension
of sodium hydride (0.5 g, 12.5 mmol, 60% in oil) in
THF (10 ml). The reaction mixture was stirred for 24 h
and a saturated aqueous solution of NH4Cl was added
carefully at 0°C. The aqueous layer was extracted with
ether (3×). The combined organic layer was washed
with brine, then dried over MgSO4 and concentrated
1
IR (film, cm−1): w 3595, 2963, 1393, 988. H-NMR
(CDCl3, 300 MHz): l 7.37–7.33 (m, 2H), 7.20–7.10 (m,
3H), 3.55 (q, 1H, J=7.4 Hz), 1.65 (d, 3H, J=7.4 Hz),
1.20 (s, 9H). 13C-NMR (CDCl3, 75 MHz): l 144.0,

92
C. Piazza et al. / Journal of Organometallic Chemistry 624 (2001) 88–95
131.6, 127.8, 126.5, 81.9, 45.7, 44.3, 43.8, 30.8, 30.4,
27.0, 19.6. m/z (EI) 191 (2), 143 (13), 105 (72), 87 (49),
57 (100). Anal. Calc. for C17H28O: C, 82.20; H, 11.36.
Found: C, 81.94; H, 11.42.
4.10. Preparation of
1-(2-naphthyl)-2-phenylpent-4-en-1-ol (9b)
A solution of n-butyllithium (0.57 ml, 0.84 mmol,
1.47 M in hexane) was added at −78°C to a solution
of the tertiary alcohol 5a (0.3 g, 1.1 mmol) in THF (3
ml). The reaction mixture was stirred at this tempera-
ture for 30 min and a solution of zinc chloride (115 mg,
0.84 mmol) in THF (2 ml) was added, followed by
1-naphthaldehyde (0.118 ml, 0.87 mmol). The reaction
was slowly warmed to r.t. overnight and quenched with
a saturated aqueous solution of NH4Cl. The aqueous
layer was extracted with ether (3×). The combined
organic layer was washed with brine, then dried over
MgSO4 and concentrated under reduced pressure. The
resulting oil was purified by flash chromatography (elu-
ent: pentane/ether 9:1) to afford a light yellow oil (158
mg, 63% yield).
4.8. Preparation of 1-(4-methoxyphenyl)-4,4-
dimethyl-3-(2-methyl-2-propyl)-2-phenylpentan-3-one
(5c)
A solution of tert-butyllithium (8.4 ml, 12.3 mmol,
1.46 M in pentane) was added at −78°C to a suspen-
sion of 8c (1.82 g, 6.15 mmol) in ether (40 ml). The
reaction mixture was slowly warmed to r.t. over 4 h and
quenched with a saturated aqueous solution of NH4Cl.
The aqueous layer was extracted with ether (3×). The
combined organic layer was washed with brine, then
dried over MgSO4 and concentrated under reduced
pressure. The resulting oil was purified by flash chro-
matography (eluent: pentane/ether 98:2) to afford a
colourless oil (1.75 g, 81% yield).
IR (film, cm−1): w 3436, 1678, 1494, 699. H-NMR
1
(CDCl3, 300 MHz): l 7.95–6.97 (m, 12H), 5.44–5.36
(m, 2H), 4.78–4.64 (m, 2H), 3.34–3.31 (m, 1H), 3.19-
3.16 (m, 2H), 2.70–2.25 (m, 1H). 13C-NMR (CDCl3, 75
MHz): l 141.2, 137.3, 135.9, 132.7, 129.3, 128.1, 127.9,
127.5, 127.3, 127.1, 127.0, 126.8, 125.8, 125.5, 124.9,
124.4, 124.3, 124.0, 123.8, 123.4, 123.3, 122.2, 122.1,
115.5, 114.9, 73.9, 72.7, 52.7, 51.6, 35.7, 31.8. m/z (EI)
288 (5), 270 (7), 229 (8), 158 (29), 129 (100). Anal. Calc.
for C21H20O: C, 87.46; H, 6.99. Found: C, 87.35; H,
6.68.
IR (film, cm−1): w 3586, 2922, 1512, 1246, 1179, 1038,
704. 1H-NMR (CDCl3, 300 MHz): l 7.39 (d, 2H, J=8.0
Hz), 7.25–7.05 (m, 3H), 6.96 (d, 2H, J=8.4 Hz), 3.91
(m, 1H), 3.67 (s, 3H), 3.59 (m, 2H), 1.35 (s, 9H).
13C-NMR (CDCl3, 75 MHz): l 157.9, 140.1, 133.8,
132,8, 129.6, 127.8, 126.7, 113.9, 82.3, 55.4, 53.8, 44.4,
44.3, 36.1, 31.4, 30.5. m/z (EI) 331 (3), 301 (5), 211 (15),
143 (21), 121 (100), 87 (46), 57 (50). Anal. Calc. for
C24H34O2: C, 81.31; H, 9.66. Found: C, 81.25; H, 9.64.
4.9. Preparation of 1,2-diphenylpent-4-en-1-ol (9a)
4.11. Preparation of 1-(2-furyl)-2-phenylpent-4-en-1-ol
(9c)
A solution of n-butyllithium (0.53 ml, 0.84 mmol, 1.6
M in hexane) was added at −78°C to a solution of the
tertiary alcohol 5a (0.27 g, 1.1 mmol) in THF (3 ml).
The reaction mixture was stirred at this temperature for
30 min and a solution of zinc chloride (115 mg, 0.84
mmol) in THF (2 ml) was added, followed by benzalde-
hyde (68 ml, 672 mmol). The reaction was slowly warmed
to r.t. overnight and quenched with a saturated aqueous
solution of NH4Cl. The aqueous layer was extracted
with ether (3×). The combined organic layer was
washed with brine, then dried over MgSO4 and concen-
trated under reduced pressure. The resulting oil was
purified by flash chromatography (eluent: pentane/ether
92:8) to afford a colourless oil (118 mg, 74% yield).
A solution of n-butyllithium (2.5 ml, 4.3 mmol, 1.7 M
in pentane) was added at −78°C to a solution of the
tertiary alcohol 5a (1.3 g, 4.7 mmol) in THF (5 ml). The
reaction mixture was stirred at this temperature for 30
min and a solution of zinc chloride (600 mg, 4.4 mmol)
in THF (5 ml) was added, followed by furfural (0.3 ml,
3.6 mmol). The reaction was slowly warmed to r.t.
overnight and quenched with a saturated aqueous solu-
tion of NH4Cl. The aqueous layer was extracted with
ether (3×). The combined organic layer was washed
with brine, then dried over MgSO4 and concentrated
under reduced pressure. The resulting oil was purified
by flash chromatography (eluent: pentane/ether 9:1) to
afford a colourless oil (600 mg, 73% yield).
1
IR (film, cm−1): w 3436, 1680, 1494, 698. H-NMR
1
(CDCl3, 300 MHz): l 7.33–7.05 (m, 10H), 5.72–5.41
(m, 1H), 4.99–4.77 (m, 3H), 3.13–2.95 (m, 1H), 2.75–
2.58 (m, 1H), 2.35–2.18 (m, 1H). 13C-NMR (CDCl3, 75
MHz): l 143.0, 142.9, 141.3, 140.8, 137.3, 136.6, 130.6,
129.4, 129.3, 128.9, 128.7, 128.5, 128.4, 128.2, 127.7,
127.4, 127.3, 126.9, 126.2, 116.7, 116.5, 78.5, 78.3, 54.4,
53.7, 36.8, 34.8. m/z (EI) 220.1247 ([M–H2O], 3%,
C17H16 requires 220.1252), 178 (5), 132 (62), 107 (100),
91 (55).
IR (film, cm−1): w 3398, 1668, 1475, 703. H-NMR
(CDCl3, 300 MHz): l 7.30–7.01 (m, 6H), 6.22 (d,
J=3.1 Hz, 1H), 6.11 (d, J=3.4 Hz, 1H), 5.70–5.30 (m,
1H), 4.85–4.72 (m, 3H), 3.15–3.08 (m, 1H), 2.60–2.40
(m, 1H), 2.97–2.24 (m, 1H). 13C-NMR (CDCl3, 75
MHz): l 155.5, 142.3, 141.9, 141.1, 140.6, 137.0, 136.3,
129.2, 129, 128.9, 128.5, 127.5, 127.0, 126.2, 116.8,
116.7, 110.5, 107.9, 107.3, 72.3, 71.6, 66.2, 51.6, 51.4,
36.8, 35.5, 15.6. m/z (EI) 228 (6), 210 (6), 170 (4),

C. Piazza et al. / Journal of Organometallic Chemistry 624 (2001) 88–95
93
141 (8), 132 (100), 115 (32), 104 (12). Anal. Calc. for
C15H16O2: C, 78.92; H, 7.06. Found: C, 78.82; H, 6.99.
142.3, 141.3, 138.5, 138.0, 137.6, 136.9, 136.8, 129.2,
128.5, 127.3, 126.2, 116.4, 109.1, 80.5, 50.2, 41.4, 37.3,
31.1, 27.9, 25.4, 24.8, 23.9, 21.3, 21.1. m/z (EI) 282 (1),
241 (37), 223 (12), 157 (16), 131 (45), 117 (19), 91 (100).
Anal. Calc. for C20H26O: C, 85.09; H, 9.28. Found: C,
84.84; H, 9.82.
4.12. Preparation of (1E)-1,4-diphenylhepta-1,6-dien-3-
ol (9d)
A solution of n-butyllithium (0.53 ml, 0.84 mmol, 1.6
M in hexane) was added at −78°C to a solution of the
tertiary alcohol 5a (0.30 g, 1.1 mmol) in THF (3 ml).
The reaction mixture was stirred at this temperature for
30 min and a solution of zinc chloride (115 mg, 0.84
mmol) in THF (2 ml) was added, followed by 3-phenyl-
2-propenal (85 ml, 672 mmol). The reaction was slowly
warmed to r.t. overnight and quenched with a saturated
aqueous solution of NH4Cl. The aqueous layer was
extracted with ether (3×). The combined organic layer
was washed with brine, then dried over MgSO4 and
concentrated under reduced pressure. The resulting oil
was purified by flash chromatography (eluent: pentane/
ether 88:12) to afford a colourless oil (80 mg, 46%
yield).
4.14. Preparation of
1-cyclohexyl-2-phenylpent-4-en-1-ol (9f)
A solution of n-butyllithium (3.2 ml, 5.1 mmol, 1.6
M in hexane) was added at −78°C to a solution of the
tertiary alcohol 5a (1.5 g, 5.4 mmol) in THF (5 ml). The
reaction mixture was stirred at this temperature for 30
min and a solution of zinc chloride (700 mg, 5.1 mmol)
in THF (5 ml) was added, followed by cyclohexanecar-
boxaldehyde (0.49 ml, 4.1 mmol). The reaction was
slowly warmed to r.t. overnight and quenched with a
saturated aqueous solution of NH4Cl. The aqueous
layer was extracted with ether (3×). The combined
organic layer was washed with brine, then dried over
MgSO4 and concentrated under reduced pressure. The
resulting oil was purified by flash chromatography (elu-
ent: pentane/ether 95:5) to afford a light yellow oil (600
mg, 60% yield).
1
IR (film, cm−1): w 3027, 1640, 1494, 700. H-NMR
(CDCl3, 300 MHz): l 7.36–7.20 (m, 10H), 6.51 and
6.57 (2d, J=21.0 Hz, 1H), 6.15 and 6.08 (2dd, J=21.0,
6.6 Hz, 1H), 5.78–5.55 (m, 1H), 5.06–4.85 (m, 2H),
4.52–4.40 (m, 1H), 3.02–2.83 (m, 1H), 2.73–2.38 (m,
2H). 13C-NMR (CDCl3, 75 MHz): l 141.0, 140.8,
137.2, 137.1, 136.8, 134.9, 132.4, 131.4, 130.8, 130.5,
129.4, 129.0, 128.8, 128.7, 128.2, 128.0, 127.4, 127.2,
127.0, 126.9, 126.2, 125.9, 116.8, 116.7, 76.5, 76.3, 52.8,
52.4, 36.6, 35.6. m/z (EI) 246.1402 ([M−H2O], 0.7%,
C19H18 requires 246.1409), 205 (2), 133 (100), 115 (23),
91 (32), 77 (14).
IR (film, cm−1): w 3400, 2913, 1640, 701. H-NMR
1
(CDCl3, 300 MHz): l 7.23–7.06 (m, 5H), 5.52 (m, 1H),
4.94–4.80 (m, 2H), 3.42–3.38 (m, 1H), 2.3–2.40 (m,
2H), 1.64–0.97 (m, 11H). 13C-NMR (CDCl3, 75 MHz):
l 143.1, 141.6, 137.7, 137.3, 129.5, 128.8, 127.0, 126.7,
116.5, 116.2, 80.4, 78.6, 66.2, 49.1, 48.2, 40.9, 40.4, 37.7,
35.5, 30.8, 30.6, 27.9, 27.0, 26.9, 26.7, 26.6, 26.4, 15.7.
m/z (EI) 226 (4), 185 (4), 132 (100), 117 (37), 91 (74).
Anal. Calc. for C17H24O: C, 83.55; H, 9.89. Found: C,
83.53; H, 9.99.
4.13. Preparation of 1-(4-isopropenylcyclohex-1-
en-1-yl)-2-phenylpent-4-en-1-ol (9e)
A solution of n-butyllithium (3.5 ml, 4.9 mmol, 1.4
M in hexane) was added at −78°C to a solution of the
tertiary alcohol 5a (1.3 g, 4.6 mmol) in THF (5 ml). The
reaction mixture was stirred at this temperature for 30
min and a solution of zinc chloride (690 mg, 5 mmol) in
4.15. Preparation of 1,2-diphenylpropan-1-ol (9g) [10]
A solution of n-butyllithium (0.6 ml, 0.91 mmol, 1.6
M in hexane) was added at −78°C to a solution of the
tertiary alcohol 5b (0.25 g, 1 mmol) in THF (2 ml). The
reaction mixture was stirred at this temperature for 30
min and a solution of zinc chloride (115 mg, 0.84
mmol) in THF (1 ml) was added, followed by benzalde-
hyde (68 mL, 670 mmol). The reaction was slowly
warmed to r.t. overnight and quenched with a saturated
aqueous solution of NH4Cl. The aqueous layer was
extracted with ether (3×). The combined organic layer
was washed with brine, then dried over MgSO4 and
concentrated under reduced pressure. The resulting oil
was purified by flash chromatography (eluent: pentane/
ether 88:12) to afford a colourless oil (104 mg, 73%
yield).
THF (5 ml) was added, followed by
L-perillaldehyde
(0.26 ml, 1.7 mmol). The reaction was slowly warmed
to r.t. overnight and quenched with a saturated
aqueous solution of NH4Cl. The aqueous layer was
extracted with ether (3×). The combined organic layer
was washed with brine, then dried over MgSO4 and
concentrated under reduced pressure. The resulting oil
was purified by flash chromatography (eluent: pentane/
ether 95:5) to afford an oil (340 mg, 70% yield).
IR (film, cm−1): w 3435, 2921, 1642, 1453, 700.
1H-NMR (CDCl3, 300 MHz): l 7.26–7.06 (m, 5H),
5.70–5.46 (m, 2H), 4.87–4.56 (m, 4H), 4.06–4.02 (m,
1H), 2.80–1.97 (m, 7H), 1.68 (s, 3H), 1.60 (s, 3H), 1.44
(s, 1H). 13C-NMR (CDCl3, 75 MHz): l 150.2, 149.9,
IR (film, cm−1): w 3436, 2259, 1681, 1494, 700.
1H-NMR (CDCl3, 300 MHz): l 7.30–7.05 (m, 10H),

94
C. Piazza et al. / Journal of Organometallic Chemistry 624 (2001) 88–95
4.73 (d, J=6.0 Hz, 1H), 2.97 (m, 1H), 1.22 (d, J=7.0
Hz, 3H), 0.99 (d, J=7.0 Hz, 3H). 13C-NMR (CDCl3,
75 MHz): l 143.7, 143.6, 143.1, 142.7, 128.8, 128.4,
128.2, 128.1, 128.0, 127.4, 127.2, 127.1, 126.6, 126.5,
79.9, 78.9, 48.3, 47.4, 18.5, 15.1. m/z (EI) 107 (100), 106
(81), 105 (38), 91 (45), 79 (54). Anal. Calc. for C15H16O:
C, 84.87, H, 7.60. Found C, 84.67, H, 7.65.
6.18–6.14 (dt, J=3.1 and 0.8 Hz, 1H), 5.96 (dd, J=
3.1 and 2.6, 1H), 4.15 (d, J=4.8, 1H), 3.18 (q, J=4.8
Hz, 1H), 1.9 (bs, 1H), 1.29 (d, J=13.1 Hz, 3H).
13C-NMR (CDCl3, 75 MHz): l 155.8, 155.4, 147.7,
143.6, 143.2, 142.4, 141.9, 129.1, 128.7, 128.3, 128.8,
127.4, 126.9, 110.6, 110.5, 107.9, 107.0, 77.9, 77.4, 77.0,
73.3, 73.2, 46.0, 45.3, 18.5, 16.4. m/z (EI) 202 (3), 185
(2), 105 (21), 97 (100), 91 (25), 77 (19). Anal. Calc. for
C13H14O2: C, 77.72; H, 6.97. Found: C, 77.67; H, 7.10.
4.16. Preparation of 1-(2-naphthyl)-2-phenylpropan-1-ol
(9h)
4.18. Preparation of
A solution of n-butyllithium (0.53 ml, 0.84 mmol, 1.6
M in hexane) was added at −78°C to a solution of the
tertiary alcohol 5b (0.30 g, 1.1 mmol) in THF (3 ml).
The reaction mixture was stirred at this temperature for
30 min and a solution of zinc chloride (124 mg, 0.91
mmol) in THF (2 ml) was added, followed by 1-naph-
thaldehyde (90 ml, 670 mmol). The reaction was slowly
warmed to r.t. overnight and quenched with a saturated
aqueous solution of NH4Cl. The aqueous layer was
extracted with ether (3×). The combined organic layer
was washed with brine, then dried over MgSO4 and
concentrated under reduced pressure. The resulting oil
was purified by flash chromatography (eluent: pentane/
ether 92:8) to afford a light yellow oil (140 mg, 80%
yield).
3-(4-methoxyphenyl)-1,2-diphenylpropan-1-ol (9j)
A solution of n-butyllithium (0.54 ml, 0.87 mmol, 1.6
M in hexane) was added at −78°C to a solution of the
tertiary alcohol 5c (0.40 g, 1.1 mmol) in THF (3 ml).
The reaction mixture was stirred at this temperature for
15 min and a solution of zinc chloride (120 mg, 0.87
mmol) in THF (2 ml) was added, followed by benzalde-
hyde (71 ml, 695 mmol). The reaction was slowly
warmed to r.t. overnight and quenched with a saturated
aqueous solution of NH4Cl. The aqueous layer was
extracted with ether (3×). The combined organic layer
was washed with brine, then dried over MgSO4 and
concentrated under reduced pressure. The resulting oil
was purified by flash chromatography (eluent: pentane/
ether 8:2) to afford a light yellow oil (160 mg, 73%
yield).
IR (film, cm−1): w 3428, 2919, 1678, 1489, 700.
1H-NMR (CDCl3, 300 MHz): l 8.03–7.12 (m, 12H),
5.55 (d, J=5.7 Hz, 1H), 5.45 (d, J=8.7 Hz, 1H), 3.30
(m, 2H), 1.85 (s, 2H), 1.16 (d, J=7.1 Hz, 3H), 1.12 (d,
J=7.1 Hz, 3H). 13C-NMR (CDCl3, 75 MHz): l 143.7,
137.4, 132.7, 129.2, 128.0, 127.5, 126.7, 125.5, 124.9,
124.3, 124. 2, 123.0, 122.0, 75.6, 73.9, 44.1, 43.8, 12.6,
11.5. m/z (EI) 262 (4), 233 (7), 158 (45), 128 (100), 105
(23). Anal. Calc. for C19H18O: C, 86.99; H, 6.91.
Found: C, 86.78; H, 7.17.
IR (film, cm−1): w 3446, 3029, 1611, 1512, 1494,
1
1453, 701. H-NMR (CDCl3, 300 MHz): l 7.29–6.99
(m, 10H), 6.86 (d, J=8.7 Hz, 1H), 6.79 (d, J=8.7 Hz),
6.65 (d, J=8.7 Hz), 4.91–4.82 (m, 1H), 3.67 (s, 3H),
3.28–2.72 (m, 3H). 13C-NMR (CDCl3, 75 MHz): l
158.1, 143.2 141.4, 140.7, 132.8, 130.8, 130.4, 130.2,
129.5, 129.4, 128.9, 128.7, 128.4, 128.1, 127.7, 127.2,
127.0, 126.8, 113.9, 78.3, 77.6, 56.8, 55.9, 55.5, 38.2,
36.0. m/z (EI) 318 (1), 212 (50), 121 (100), 107 (46), 91
(10), 77 (26). Anal. Calc. for C22H14O2: C, 77.72; H,
6.97. Found: C, 77.67; H, 7.10.
4.17. Preparation of 1-(2-furyl)-2-phenylpropan-1-ol
(9i) [11]
A solution of n-butyllithium (0.7 ml, 1.1 mmol, 1.6
M in hexane) was added at −78°C to a solution of the
tertiary alcohol 5b (0.30 g, 1.1 mmol) in THF (3 ml).
The reaction mixture was stirred at this temperature for
30 min and a solution of zinc chloride (180 mg, 1.3
mmol) in THF (3 ml) was added, followed by furfural
(75 ml, 0.9 mmol). The reaction was slowly warmed to
r.t. overnight and quenched with a saturated aqueous
solution of NH4Cl. The aqueous layer was extracted
with ether (3×). The combined organic layer was
washed with brine, then dried over MgSO4 and concen-
trated under reduced pressure. The resulting oil was
purified by flash chromatography (eluent: pentane/ether
9:1) to afford a red oil (120 mg, 66% yield).
4.19. Preparation of 2-(1,2-diphenyl)-4-pentenyl]-
malonic acid diethyl ester (11)
A solution of n-butyllithium (0.54 ml, 0.84 mmol,
1.56 M in hexane) was added at −78°C to a solution
of the tertiary alcohol 5a (0.30 g, 1.1 mmol) in THF (3
ml). The reaction mixture was stirred at this tempera-
ture for 30 min and a solution of zinc chloride (115 mg,
0.84 mmol) in THF (2 ml) was added, followed by
diethyl benzylidenemalonate 10 (169 mg, 0.672 mmol).
The reaction was slowly warmed to r.t. overnight and
quenched with a saturated aqueous solution of NH4Cl.
The aqueous layer was extracted with ether (3×). The
combined organic layer was washed with brine, then
dried over MgSO4 and concentrated under reduced
pressure. The resulting oil was purified by flash chro-
IR (film, cm−1): w 3400, 2963, 1675, 1478, 711.
1H-NMR (CDCl3, 300 MHz): l 7.32–7.06 (m, 6H),

C. Piazza et al. / Journal of Organometallic Chemistry 624 (2001) 88–95
95
matography (eluent: pentane/ether 85:15) to afford a
periments and BASF AG, Degussa-Hu¨ls, Chemetall
GmbH for the gift of chemicals.
colourless oil (150 mg, 60% yield).
1
IR (film, cm−1): w 2964, 1690, 1462, 736, 698. H-
NMR (CDCl3, 300 MHz): l 7.32–6-98 (m, 10H), 5.70–
5.51 and 5.42–5.25 (dm, 1H), 5.03–4.85 (m, 1H),
4.77–4.62 (m, 1H), 4.34–4-20 (m, 2H), 3.86–3.60 (m,
5H), 3.19–3.01 (m, 1H), 2.48–2.05 (m, 2H), 1.28, 1.03,
0.85, 0.72 (4t, J=7.2 Hz, 6H). 13C-NMR (CDCl3, 75
MHz): l 168.9, 168.2, 168.0, 167.0, 142.5, 141.9, 139.9,
139.2, 137.1, 136.8, 130.6, 130.2, 130.0, 129.8, 129.5,
128.9, 128.6, 128.3, 128.0, 127.6, 127.4, 117.1, 116.4,
62.1, 61.7, 61.5, 61.4, 56.5, 56.2, 51.6, 49.6, 49.2, 47.3,
38.0, 37.2, 15.6, 14.6, 14.4, 14.0, 13.9. m/z (EI) 339 (3),
250 (25), 220 (29), 176 (20), 131 (100), 115 (12), 91 (26),
77 (9). Anal. Calc. for C24H28O4: C, 75.76, H, 7.42.
Found C, 75.80, H, 7.39.
References
[1] (a) D. Lednicer, L.A. Mitscher, Organic Chemistry of Drug
Synthesis, Wiley, New York, 1977. (b) F.R. Hartley (Ed.), The
Chemistry of the Metal–Carbon Bond, vol. 4, S. Patai Series
edn., Wiley, New York, 1987.
[2] (a) C.L. Raston, G.J. Salem, Chem. Soc. Chem. Commun. 1984,
1702. (b) S. Harvey, P.C. Junk, C.L. Raston, G. Salem, J. Org.
Chem. 53 (1988) 3134. (c) B. Bogdanovich, Acc. Chem. Res. 21
(1988) 261.
[3] S.C. Berk, M.C.P. Yeh, N. Jeong, P. Knochel, Organometallics
9 (1990) 3053.
[4] P. Knochel, R.B. Singer, Chem. Rev. 93 (1993) 2117.
[5] P. Jones, P. Knochel, Org. Chem. 64 (1999) 186.
[6] B.H. Lipshutz, S. Sengupta, Org. React. 41 (1992) 135.
[7] K. Chen, F. Koser, J. Org. Chem. 56 (1991) 5764.
[8] M.A. de las Heras, J.J. Vaquero, J.L. Garcia-Navio, J. Alvarez-
Builla, Tetrahedron 52 (1996) 14297.
[9] S. Zushi, Y. Kodama, K. Nishihata, K. Umomura, M. Nishio, J.
Uzawa, M. Hirota, Bull. Chem. Soc. Jpn. 53 (1980) 3631.
[10] A.F. Diaz, Y.Y. Cheng, M. Ochoa, J. Am. Chem. Soc. 99 (1977)
6319.
Acknowledgements
We thank the Deutsche Forschungsgemeinschaft
(Leibniz program) for generous support. N.M. thanks
the Alexander von Humboldt-Stiftung Foundation for
a fellowship. We thank M. Schutt for preliminary ex-
[11] G.A. Molander, A.M. Estevez-Braun, Bull. Soc. Chim. Fr. 134
(1997) 275.
.