Phosphonium salt catalyzed addition of diethylzinc to aldehydes

Article abstract of DOI:10.1055/s-0030-1260230

The addition of diethylzinc to aromatic, heteroaromatic, and aliphatic aldehydes at room temperature is efficiently catalyzed by 1-7 mol% tetrabutylphosphonium chloride. The corresponding addition products are obtained in good to excellent yields of up to 99%. Moreover, polymer bond phosphonium salts can be used to catalyze this reaction with excellent recovery of the polymer bond catalyst up to three cycles. The application of chiral bifunctional phosphonium salts revealed a remarkable counter anion effect. Changing the anion, the activity of the tetrabutylphosphonium salt decreased in the order Cl^- > Br^- > I^- ≈ TsO^- > BF₄^- ≈ PF₆^-. However, the nature of the cation had also significant influence. Tetraalkyl-ammonium chlorides showed similar activity compared to phosphonium chlorides, while alkaline metal chlorides proved to be considerably less active. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0030-1260230

3482
PAPER
Phosphonium Salt Catalyzed Addition of Diethylzinc to Aldehydes
Thomas Werner,* Abdol Majid Riahi, Heiko Schramm
Leibniz-Institut für Katalyse e. V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
Fax +49(381)128151326; E-mail: thomas.werner@catalysis.de
Received 9 June 2011; revised 26 July 2011
This provoked us to evaluate the potential of inexpensive
and commercially available phosphonium salts as Lewis
acidic catalysts for the addition of organozinc reagents to
aldehydes. The frequently used benchmark for the evalu-
Abstract: The addition of diethylzinc to aromatic, heteroaromatic,
and aliphatic aldehydes at room temperature is efficiently catalyzed
by 1–7 mol% tetrabutylphosphonium chloride. The corresponding
addition products are obtained in good to excellent yields of up to
99%. Moreover, polymer bond phosphonium salts can be used to ation of new catalysts is the addition of diethylzinc to
catalyze this reaction with excellent recovery of the polymer bond
catalyst up to three cycles. The application of chiral bifunctional
benzaldehyde (1a). Herein we report the application of
commercially available tetrabutylphosphonium chloride
phosphonium salts revealed a remarkable counter anion effect.
as a catalyst for this conversion. As expected the reaction
Changing the anion, the activity of the tetrabutylphosphonium salt
proceeded very sluggishly in the absence of a cata-
–
decreased in the order Cl– > Br– > I– ≈ TsO– > BF4– ≈ PF6 . However,
lyst.11d,12 Even at room temperature the conversion was
the nature of the cation had also significant influence. Tetraalkyl-
<20% after 24 hours (Table 1, entry 1). However, to our
delight quantitative conversion was observed after 24
hours at room temperature in the presence of 7 mol% of
Bu4PCl (entry 2). If lower amounts of catalyst (1 and 5
mol%) were employed the desired alcohol 2a could still
be isolated in up to 90% yield (entries 3 and 4).
ammonium chlorides showed similar activity compared to phos-
phonium chlorides, while alkaline metal chlorides proved to be
considerably less active.
Key words: catalysis, phosphonium salt, addition, diethylzinc, al-
dehydes
Table 1 Bu4PCl-Catalyzed Addition of Et2Zn to Benzaldehyde (1a)
Among the organic transformations carbon–carbon bond-
forming processes are of considerable importance. In par-
ticular, the nucleophilic addition reaction of organozinc
reagents to carbonyl compounds offers elegant opportuni-
ties for the synthesis of a variety of multifunctional sub-
strates. Although organozinc compounds are long
known,1 their application in organic synthesis has been
developed only over the past three decades2 and led to sig-
nificant success regarding chemical yields and enantio-
meric purities of the addition products.3 Nevertheless, this
research area remains an object of intensive research.4
Chiral ligands such as amino alcohols as well as Lewis
acid chiral transition-metal complexes are typically em-
ployed as catalysts. The term Lewis acid catalysts gener-
ally refers to metal salts like aluminum, titanium, or iron
chloride.5 However, not only metal centers can function as
Lewis acids,6 but compounds containing for example
carbenium,7 imidazolinium,8 imidazolium,9 or phos-
phonium10 cations also exhibit Lewis acidity. Only very
few examples for the addition of alkylzinc reagents to al-
dehydes catalyzed by onium salts are known.11 McNulty
et al. reported the addition of diethylzinc to benzaldehyde
in the presence of a phosphonium salt presumably acting
as a mild Lewis acidic catalyst.11d To the best of our
knowledge this is the only example for the addition of an
organozinc reagent to a carbonyl group catalyzed by a
phosphonium salt. We are generally interested in the use
of (chiral) phosphonium salts as Lewis acidic catalysts.6a
O
OH
Bu4PCl (1–7 mol%)
+
Et2Zn
toluene, 23 °C, 24–30 h
Ph
1a
Ph
Et
2a
Entry
Bu4PCl (mol%) Et2Zn (equiv) Time (h)
Yield (%)
11a
1
2
3
4
5
6
7
8
–
7
5
1
5
5
7
7
2.0
2.0
2.0
2.0
1.0
0.5
1.0
0.5
24
24
24
24
24
24
30
30
95a
90b
90a
53b
80b
93b
67b
a Determined by GC with hexadecane as internal standard.
b Isolated yield.
The conversion of 1a with 1.0 and even 0.5 equivalents of
diethylzinc and 5 mol% of the catalyst gave 2a in 80 and
53% yield, respectively (entries 5 and 6). In both cases the
yields could be improved by increasing the amount of cat-
alyst to 7 mol% and an extended reaction time of 30 hours
(entries 7 and 8). For further evaluation of the scope of
this catalyst a range of aromatic aldehydes were employed
(Table 2). First, we were interested in the selectivity of the
reaction concerning 1,2- versus 1,4-addition as well as the
selectivity with respect to aldehydes and ketones. To ex-
plore the chemoselectivity of the reaction, initially
SYNTHESIS 2011, No. 21, pp 3482–3490
x
x.
x
x
.
2
0
1
1
Advanced online publication: 26.09.2011
DOI: 10.1055/s-0030-1260230; Art ID: N59811SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Phosphonium Salt Catalyzed Addition of Diethylzinc to Aldehydes
3483
Table 2 Bu4PCl-Catalyzed Addition of Et2Zn to Various Aldehydes
1a (continued)
1 mol% Bu4PCl of the catalyst and one equivalent of di-
ethylzinc in the conversion of cinnamaldehyde (1b) and
4-acetylbenzaldehyde (1c) were used. However, the reac-
tion proceeded very slowly under these conditions. When
two equivalents of diethylzinc were utilized the conver-
sion was quantitative after 72 hours. The addition oc-
curred selectively to the carbonyl group of the aldehyde
and the corresponding products 2b and 2c were isolated in
excellent yields (Table 2, entries 1 and 2). In order to gen-
erally achieve full conversion in a reasonable reaction
time, 7 mol% of the catalyst was used. Several 4-substitut-
ed benzaldehyde derivatives were converted under these
conditions and the corresponding alcohols 2d–i were ob-
tained in good to excellent yields (entries 3–8). If 2-chlo-
ro- (1j) or 3-chlorobenzaldehyde (1k) is used instead of
the 4-isomer 1h, the addition product could be isolated in
85 and 91% yield, respectively (entries 9 and 10). The
conversion of 1-naphthyl 1l (entry 11) as well as of the
sterically crowded di- and trisubstitued aromatic alde-
hydes 1m and 1n was also succesfully accomplished (en-
tries 12 and 13). Though yields were slightly lower, it is
noteworthy that even the hydroxy derivative 2n was ob-
tained in 80% yield. Our attention was next turned to the
conversion of aliphatic and heteroaromatic substrates.
Under our standard conditions the reaction of Et2Zn and
heptanal (1o) gave the desired product in a moderate yield
of 51% (entry 14). Beside unreacted starting material 1o,
the corresponding alcohol and aldol products were ob-
served. The heteroaromatic substrates 1p and 1q, howev-
er, reacted very sluggishly. To achieve full conversion a
much longer reaction time was needed. Nevertheless, al-
cohol 2p was obtained in 72% yield whereas the conver-
sion of 1q gave 2q in 74% yield (entries 15 and 16).
O
OH
Bu4PCl (7 mol%)
+
Et2Zn
toluene, 23 °C, 24–120 h
R
R
Et
2b–q
1b–q
Entry Aldehyde Time (h) Product
Yield (%)b
OH
5
6
7
8
9
1f
1g
1h
1i
30
30
30
24
30
2f
Et
94
MeO
Br
OH
2g
2h
2i
98
99
92
85
Et
Et
OH
Cl
OH
Et
F
OH
Cl
1j
2j
Et
OH
Et
10
1k
30
2k
2l
91
87
Cl
Table 2 Bu4PCl-Catalyzed Addition of Et2Zn to Various Aldehydes
1a
OH
11
12
1l
30
30
Et
O
OH
Bu4PCl (7 mol%)
+
Et2Zn
toluene, 23 °C, 24–120 h
R
R
Et
2b–q
OH
1b–q
1m
2m 85
Et
Entry Aldehyde Time (h) Product
Yield (%)b
87c
MeO
OMe
OH
OH
OH
1
2
1b
72
2b
t-Bu
Et
Et
Et
13
1n
30
2n
80
OH
t-Bu
89c
OH
1c
72
2c
14
15
1o
1p
30
2o
2p
51
n-Hex
Et
OH
O
120
72c
O
OH
Et
OH
3
4
1d
1e
30
30
2d
2e
97
96
Et
Ph
16
1q
120
2q
74c
Et
OH
N
Et
a Reaction conditions: Bu4PCl (7 mol%), Et2Zn (2 equiv), toluene, 23 °C.
b Isolated yields.
c Bu4PCl used: 1 mol%.
Synthesis 2011, No. 21, 3482–3490 © Thieme Stuttgart · New York

3484
T. Werner et al.
PAPER
Our attention was then turned to the conversion of other
commercially available organozinc reagents (Table 3).
Under our standard conditions the reaction of Ph2Zn with
benzaldehyde (1a) yielded the desired product 2r only in
moderate yield (Table 3, entry 1). The conversion of 1a
with Bu2Zn and i-Pr2Zn gave the corresponding products
2s and 2t only in low isolated yield of 40 and 26%, respec-
tively (entries 2 and 3). Interestingly, besides unreacted
starting material significant amounts of benzyl alcohol
were detected in the crude reaction mixture as a by-prod-
uct in both cases. Moreover, in the addition of i-Pr2Zn the
corresponding ketone was isolated in 12% yield. The ad-
dition of Cy2Zn to benzaldehyde (1a) lead to complex re-
action mixtures (entry 4) and the desired product could
not be detected.
Table 4 Polymer Bond Phosphonium Salt Catalyzed Addition of
Et2Zn to Benzaldehyde (1a)a
O
OH
catalyst (10 mol%)
toluene, 23 °C, 30 h
+
Et2Zn
Ph
1a
Ph
Et
2a
Ph
Br
Cl
PPh3
catalyst:
P
Ph Ph
3
4
Entry Catalyst Cycle Recovery (%) Conv. (%)b Yield (%)c
1
2
3
4
3
4
4
4
1
1
2
3
99
99
99
63
83
99
90
77
62
99
90
67b
Table 3 Bu4PCl-Catalyzed Addition of R2Zn to Benzaldehyde (1a)a
O
OH
Bu4PCl (7 mol%)
+
R2Zn
toluene, 23 °C, 30 h
a Conditions: catalyst (10 mol%), R2Zn (2 equiv), toluene, 30 h,
Ph
1a
Ph
R
23 °C.
2r–u
b Determined by GC with hexadecane as internal standard.
c Isolated yield.
Entry
1
R
Product
Yield (%)b
58
OH
hydes we were interested in developing an asymmetric
version of this reaction. Hence, bifunctional chiral
phosphonium salts 6 and 8 were prepared (Scheme 1).
The b-aminophosphonium salt 6 was readily prepared
from L-prolinol (5) by treatment with triphenylphosphine
and HBr as described by Anderson.13 The reaction of
(R)-BINAP (7) with one equivalent of MeI selectively af-
forded salt 8.14 It was envisioned that these compounds
might show a dual mode of activation. Based on our re-
sults we presumed the activation of the carbonyl group by
the Lewis acidic phosphonium cation and the activation of
the zinc reagent by the second functional group.
Ph
2r
Ph
Ph
OH
OH
OH
2
3
4
Bu
i-Pr
Cy
2s
2t
40
26
Ph
Ph
Ph
Bu
i-Pr
Cy
c
2u
–
a Conditions: Bu4PCl (7 mol%), R2Zn (2 equiv), toluene, 24 h, 23 °C.
b Isolated yield.
c Not detected.
Ph3P, HBr
OH
PPh3 Br
N
N
150–200 °C
H
H
The possibility of employing immobilized phosphonium
salts as recyclable catalysts in the addition of diethylzinc
to aldehydes was explored further. Benzaldehyde (1a)
was employed as a model substrate and polystyrene bond
benzyltriphenylphosphonium bromide (3) and triphenyl-
phosphonium chloride (4) as catalysts (Table 4). In the
presence of 10 mol% of 3 based on the polymer loading
the conversion after 30 hours at 23 °C was only 83%
(Table 4, entry 1). In contrast the chloride salt 4 showed
higher activity. In the indicated reaction time 99% conver-
sion under selective formation of the desired product 2a
was observed (entry 2). The catalyst could be almost com-
pletely recovered from the reaction mixture and was re-
used. In the second cycle comparable results were
obtained (entry 3). Again the catalyst was recovered and
reused in a third cycle. Lower conversion was observed in
this run but the desired product 2a could still be isolated
in 67% yield (entry 4).
5
6
I
PPh2Me
PPh2
MeI, CH2Cl2
23 °C, 16 h
PPh2
PPh2
7
8
Scheme 1 Preparation of chiral phosphonium salts 6 and 8
Subsequently 6, 8, and the commercially available [(2S)-
3-hydroxy-2-methylpropyl](triphenyl)phosphonium bro-
mide (9)15 were employed as chiral catalysts for the con-
version of benzaldehyde (1a) with diethylzinc (Table 5).
In all three cases the isolated yields of the corresponding
alcohol 2a were slightly lower (68–77%) compared to the
reaction in which tetrabutylphosphonium chloride was
Having established tetrabutylphosphonium chloride as an
efficient catalyst for the addition of diethyl zinc to alde-
Synthesis 2011, No. 21, 3482–3490 © Thieme Stuttgart · New York

PAPER
Phosphonium Salt Catalyzed Addition of Diethylzinc to Aldehydes
3485
employed as catalyst. It is noteworthy that in case of cat- obtained (entries 13 and 14). It is noteworthy that, if sim-
alyst 8 the lowest yield was obtained (Table 5, entry 2). ple lithium, sodium or potassium chloride was employed
Moreover, to our surprise and disappointment no enantio- as catalyst, the desired product 1a was obtained only in
meric excess was observed.
low yield <35% indicating the significant influence of the
nature of the cation (entries 15–17).
Table 5 Addition of Et2Zn to Benzaldehyde (1a) Catalyzed by
Chiral Phosphonium Saltsa
Table 6 Conversion of 1a in the Presence of Different Phosphoni-
um Salt Catalystsa
Entry
Catalyst
Substrate Product
Yield(%)b ee (%)c
Entry
1
Catalyst
[Bu4P]Cl
[Bu4P]Br
[Bu4P]Cl
[Bu4P]Br
[Bu4P]I
Time (h)
24
24
6
Conv. (%)b Yield(%)b
1
2
3
6
8
9
1a
1a
1a
2a
2a
2a
77
<5
<5
<5
>99
95
97
94
71
57
79
74
28
25
91
93
96
76
96
93
33
30
31
68
2
77c
3
72
a Reaction conditions: catalyst (7 mol%), Et2Zn (2 equiv), toluene,
23 °C.
4
6
57
b Isolated yield.
c Determined by Chiral HPLC.
5
24
24
24
24
24
24
24
24
24
24
24
24
24
82
6
[Bu4P]OTs
[Bu4P]BF4
[Bu4P]PF6
[Ph4P]Cl
[Ph3PMe]Cl
[Ph3PBn]Cl
[Bu4N]Cl
[Et4N]Cl
[Et3NBn]Cl
LiCl
77
A possible explanation would be the formation of a phos-
phorane along with EtZnCl after the addition of Et2Zn to
the aldehyde. EtZnCl itself is a Lewis acid and could cat-
alyze further addition reactions. However, the only ob-
served signal in the 31P NMR spectrum was assigned to
the phosphonium salt. The formation of a phosphorane
was not observed in 31P NMR spectrum. These findings
provoked us to further investigate the influence of the
phosphonium cation structure as well as the effect of the
counter anion on the reactivity. In the presence of a range
of structurally different phosphonium salts (7 mol%) 1a
was converted into 2a with diethylzinc at 23 °C for 24
hours. The results are summarized in Table 6. Initial ex-
periments were performed based on salts containing tet-
rabutylphosphonium as the cation. If the chloride or
bromide salt were employed as the catalyst the conversion
is almost quantitative and yields >90% were obtained
(Table 6, entries 1 and 2). To clearly distinguish the reac-
tivity of the chloride and the bromide salt the reaction time
was reduced to 6 hours (entries 3 and 4). In the presence
of tetrabutylphosphonium chloride 72% conversion and
71% yield were observed after 6 hours (entry 3), whereas
the bromide gave significant lower conversion and yield
(entry 4). Utilizing the iodide salt the yield and conversion
after 24 hours were 82 and 79%, respectively (entry 5).
Similar results were obtained with the tosylate (entry 6).
However, the influence of the anion is even more signifi-
7
28
8
34
9
>99
>99
>99
78
10
11
12
13
14
15
16
17
97
94
35
NaCl
33
KCl
31
a Conditions: catalyst (7 mol%), Et2Zn (2 equiv), toluene, 23 °C.
b Determined by GC with hexadecane as internal standard.
Tian and Plumet et al. described the addition of TMSCN
to aldehydes and ketones catalyzed by simple phosphoni-
um salts.16 The authors proposed a double activation
mechanism in which the Lewis acidic phosphonium cat-
ion coordinates to the carbonyl group of the ketone and
thereby increases its electrophilicity. On the other hand IR
spectroscopic experiments imply a Lewis basic activation
of TMSCN by the anion.
–
–
cant when the less basic BF4 or PF6 salts were employed
(entries 7 and 8). In these cases conversions and yields lay
far below 50%. Based on these results the order of activa-
So far our attempts to identify the activation mode by in
situ IR and NMR spectroscopy were not successful. How-
ever, based on our results it can be concluded that beside
the possible Lewis acidic activation by the phosphonium
cation a second (nucleophilic) activation mode by the an-
ion has to be taken into account as well. Halide effects are
generally recognized in transition metal catalysis and
have been observed even in the addition of organozinc re-
agents to aldehydes.17 Knochel et al. reported the activa-
tion of diorganozinc reagents by MgCl2 by the possible
formation of ate complex intermediates in analogy to the
tion in respect to the anion is: Cl– > Br– > I– ≈ TsO– > BF4
–
–
≈ PF6 . On the contrary, the structure of the cation seems
to have no significant influence, since tetrabutyl-, tet-
raphenyl-, methyltriphenyl-, as well as benzyltriphe-
nylphosphonium chloride gave conversions >99% and
similar yields (entries 1, 9–11). However, if the nature of
the cation is changed from phosphonium to ammonium
the yield dropped from >99% (entry 1) to 76% (entry 12).
If ammonium salts with sterically less demanding substit-
uents were employed, higher yields up to 97% could be
Synthesis 2011, No. 21, 3482–3490 © Thieme Stuttgart · New York

3486
T. Werner et al.
PAPER
procedure was repeated twice, and then the combined organic layers
were dried (MgSO4), and the solvent removed by rotary evapora-
tion. The residue was purified by chromatography on silica gel (cy-
clohexane–EtOAc, 10:1) to yield the desired product 2a as a
colorless liquid. The aqueous phase of the extraction procedure was
filtered and the residue was washed with aq HCl (1 M, 3 × 5 mL),
distilled H2O (3 × 5 mL), and then dried till constant weight to re-
gain the polymer for recylization. When catalyst 3 was used, the res-
idue was washed with aq HBr.
Suzuki reaction where a boronic acid is converted into a
boronate through the addition of a base.18
In conclusion, we have described a novel procedure for
the addition of diethylzinc to aldehydes under mild condi-
tions in the presence of catalytic amounts of inexpensive
and commercially available tetrabutylphosphonium chlo-
ride. The desired products were usually obtained in good
to excellent yields. Moreover, polymer bond phosphoni-
um salts could be employed as recyclable catalysts. How-
ever, when chiral bifunctional catalysts based on
phosphonium salts were employed, no asymmetric induc-
tion has been observed. In this context we explored the ef-
fect of the anion and cation on the catalyst activity. For
1-Phenylpropan-1-ol (2a)19
Benzaldehyde (1a; 159 mg, 1.50 mmol) was converted with Et2Zn
in toluene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (22 mg,
0.075 mmol) into 2a, which was isolated after chromatography (sil-
ica gel, cyclohexane–EtOAc, 10:1, Rf = 0.68) as a colorless oil (184
mg, 1.35 mmol, 90%).
tetrabutylphosphonium salts, activity strongly depended
3
1H NMR (300 MHz, CDCl3): d = 0.83 (t, J = 7.3 Hz, 3 H), 1.59–
–
on the nature of the anion (Cl– > Br– > I– ≈ TsO– > BF4
≈
1.79 (m, 2 H), 1.94 (br s, 1 H), 4.50 (t, 3J = 6.9 Hz, 1 H), 7.16–7.29
–
PF6 ). In addition, the nature of the cation had also signif-
icant influence. Tetraalkylammonium chlorides showed
similar activity compared to phosphonium chlorides,
while alkaline metal chlorides proved to be considerably
less active.
(m, 5 H).
13C NMR (75 MHz, CDCl3): d = 10.27 (CH3), 31.02 (CH2), 76.13
(CH), 126.12 (2 CH), 127.61 (CH), 128.52 (2 CH), 144.79 (C).
MS (EI, 70 eV): m/z (%) = 136 ([M]+, 12), 107 (100), 79 (70), 77
(39), 51 (26).
HRMS (EI, 70 eV): m/z [M]+ calcd for C9H12O: 136.0883; found:
136.0887.
All reactions were carried out under argon atmosphere using
Schlenk techniques. Toluene was dried over Na and freshly distilled
before use. All starting materials as well as the polymer bond phos-
phonium salt 9 were commercially available and used without fur-
ther purification except benzaldehyde (1a), which was purified by
distillation and then stored under argon atmosphere. TLC was per-
formed on Macherey-Nagel silica gel plates 60 (UV 254). Prepara-
tive column chromatography was carried out using Macherey-
Nagel M60 silica gel (0.04–0.063 mm) with cyclohexane and
EtOAc as eluents for flash column chromatography. NMR spectra
were recorded on a Bruker AV 400 or a Bruker AV 300 spectrom-
eter. Multiplicities of carbon signals were determined by DEPT ex-
periments. Mass spectra were recorded on an MAT 95XP mass
spectrometer from Thermo. IR spectra were recorded on a Bruker
Alpha P spectrophotometer. Elemental analyses were performed on
a TruSpec CHNS micro analyzer from Leco. Chiral HPLC was per-
formed on an Agilent 1100 HPLC System with a Chiralcel OD-H
column.
Anal. Calcd for C9H12O: C, 79.37; H, 8.88. Found: C, 79.31; H,
8.70.
Chiral HPLC: Chiralcel OD-H, heptane–EtOH, 97:3, flow = 1.0
mL min–1, tR (enantiomer A) = 8.53 min, tR (enantiomer B) = 9.82
min (Table 5).
(E)-1-Phenylpent-1-en-3-ol (2b)20
Aldehyde 1b (198 mg, 1.50 mmol) was converted with Et2Zn in tol-
uene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (4.4 mg, 0.015
mmol) into 2b, which was isolated after chromatography (silica gel,
cyclohexane–EtOAc, 20:1, Rf = 0.46) as a colorless oil (212 mg,
1.31 mmol, 87%).
3
1H NMR (400 MHz, CDCl3): d = 1.02 (t, J = 7.5 Hz, 3 H), 1.66–
1.77 (m, 2 H,), 2.00 (br s, 1 H), 4.26 (ddt, 3J = 1 Hz, 3J = 6.5 Hz,
3J = 6.6 Hz, 1 H), 6.26 (dd, 3J = 15.7 Hz, 3J = 6.5 Hz, 1 H), 6.63 (d,
3J = 15.7 Hz, 1 H), 7.27–7.40 (m, 5 H).
13C NMR (75 MHz, CDCl3): d = 9.90 (CH3), 30.32 (CH2), 74.54
(CH), 126.57 (2 CH), 127.74 (CH), 128.35 (2 CH), 130.54 (CH),
132.34 (CH), 136.86 (C).
MS (EI, 70 eV): m/z (%) = 166 ([M]+, 10), 148 (28), 147 (16), 137
(100), 109 (22), 94 (17), 77 (22).
Bu4PCl Catalyzed Addition of Et2Zn to Aldehydes 1; General
Procedure
To a solution of aldehyde 1 (1.50 mmol, 1.0 equiv) in anhyd toluene
(c = 2.5 mmol mL–1) was added Bu4PCl (1–7 mol%). The mixture
was cooled to 0 °C, followed by dropwise addition of Et2Zn in tolu-
ene (2.7 mL, 3.0 mmol, c = 1.1 mmol mL–1, 2.0 equiv). The reaction
mixture was allowed to warm to 23 °C and stirred for 24–120 h. The
mixture was quenched with aq HCl (5 mL, c = 1 mmol mL–1) and
extracted with CH2Cl2 (3 × 10 mL). The combined organic layers
were dried (Na2SO4), filtered, and all volatiles were removed in vac-
uo. The residue was purified by chromatography on silica gel (SiO2)
with cyclohexane and EtOAc as eluents.
1-[4-(1-Hydroxypropyl)phenyl]ethanone (2c)21
Aldehyde 1c (148 mg, 1.00 mmol) was converted with Et2Zn in tol-
uene (1.8 mL, 2.0 mmol) in the presence of Bu4PCl (2.9 mg, 0.010
mmol) into 2c, which was isolated after chromatography (silica gel,
cyclohexane–EtOAc, 20:1, Rf = 0.35) as a colorless oil (159 mg,
0.892 mmol, 89%).
1H NMR (400 MHz, CDCl3): d = 0.84 (t, 3J = 7.5 Hz, 3 H), 1.18 (br
s, 1 H), 1.66–1.73 (m, 2 H), 2.50 (s, 3 H), 4.59 (t, 3J = 6.5 Hz, 1 H),
7.32–7.35 (m, 2 H, CH), 7.81–7.84 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 10.02 (CH3), 26.72 (CH3), 32.06
(CH2), 75.38 (CH), 126.16 (2 CH), 128.59 (2 CH), 136.26 (C),
150.22 (C), 198.19 (C=O).
Addition of Et2Zn to Benzaldehyde (1a) Catalyzed by Polymer
Bound Phosphonium Salts 3 and 4; General Procedure
To a solution of benzaldehyde (1a; 300 mg, 2.83 mmol, 1.0 equiv)
in anhyd toluene (c = 0.38 mmol mL–1) was added catalyst 3 or 4
(10 mol%). The mixture was cooled to 0 °C, followed by dropwise
addition of Et2Zn in toluene (5.1 mL, c = 1.1 mmol mL–1, 5.61
mmol, 2.0 equiv). The mixture was allowed to warm to 23 °C and
was then shaken for 30 h. Subsequently aq HCl (1 M, c = 3.1 mmol
mL–1) and CH2Cl2 (c = 3 mmol mL–1) were added, the mixture was
shaken for 1 min and the CH2Cl2 was carefully removed again. This
1-(Biphenyl-4-yl)propan-1-ol (2d)22
Aldehyde 1d (273 mg, 1.50 mmol) was converted with Et2Zn in tol-
uene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (30 mg, 0.10
Synthesis 2011, No. 21, 3482–3490 © Thieme Stuttgart · New York

PAPER
Phosphonium Salt Catalyzed Addition of Diethylzinc to Aldehydes
3487
mmol) into 2d, which was isolated after chromatography (silica gel,
cyclohexane–EtOAc, 10:1, Rf = 0.69) as colorless crystals (308 mg,
1.45 mmol, 97%); mp 58–59 °C.
13C NMR (75 MHz, CDCl3): d = 10.11 (CH3), 32.03 (CH2), 75.42
(CH), 121.30 (C), 127.84 (CH), 131.57 (CH), 143.63 (C).
MS (EI, 70 eV): m/z (%) = 216 ([MH]+, 11), 214 (10), 187 (94), 185
(100), 159 (15), 157 (20), 78 (29), 77 (58), 51 (10).
HRMS (EI, 70 eV): m/z [M]+ calcd for C9H11BrO: 215.9967; found:
215.9966.
3
1H NMR (300 MHz, CDCl3): d = 0.97 (t, J = 7.4 Hz, 3 H), 1.77–
1.88 (m, 2 H), 1.92 (br s, 1 H, OH), 4.66 (dt, 3J = 3.0 Hz, 3J = 6.4
Hz, 1 H), 7.32–7.38 (m, 1 H), 7.40–7.47 (m, 4 H), 7.57–7.62 (m, 4
H).
13C NMR (75 MHz, CDCl3): d = 10.36 (CH3), 32.10 (CH2), 75.90
(CH), 126.56 (2 CH), 127.21 (2 CH), 127.29 (2 CH), 127.38 (CH),
128.89 (2 CH), 140.58 (C), 141.02 (C), 143.74 (C).
MS (EI, 70 eV): m/z (%) = 212 ([M]+, 15), 194 (22), 184 (14), 183
(100), 178 (10), 155 (44), 154 (10), 153 (16), 152 (20), 77 (12).
Anal. Calcd for C9H11BrO: C, 50.26; H, 5.15. Found: C, 50.32; H,
5.07.
1-(4-Chlorophenyl)propan-1-ol (2h)22
Aldehyde 1h (210 mg, 1.49 mmol) was converted with Et2Zn in tol-
uene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (30 mg, 0.10
mmol) into 2h, which was isolated after chromatography (silica gel,
cyclohexane–EtOAc, 20:1, Rf = 0.66) as a colorless oil (253 mg,
1.48 mmol, 99%).
HRMS (EI, 70 eV): m/z [M]+ calcd for C15H16O: 212.1195; found:
212.1189.
Anal. Calcd for C15H16O: C, 84.87; H, 7.60. Found: C, 85.27; H,
7.17.
3
1H NMR (300 MHz, CDCl3): d = 0.83 (t, J = 7.4 Hz, 3 H), 1.61–
1.74 (m, 2 H), 1.86 (br s, 1 H), 4.50 (dt, 3J = 3.3 Hz, 3J = 6.4 Hz, 1
H), 7.18–7.21 (m, 2 H), 7.22–7.26 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 10.12 (CH3), 32.08 (CH2), 75.42
(CH), 127.48 (2 CH), 128.65 (2 CH), 133.21 (C), 143.13 (C).
MS (EI, 70 eV): m/z (%) = 170 ([M]+, 10), 143 (34), 142 (10), 141
(100), 139 (12), 117 (15), 115 (17), 113 (16), 77 (56), 51 (10), 32
(43).
HRMS (EI, 70 eV): m/z [M]+ calcd for C9H11ClO: 170.0492; found:
170.0494.
1-(4-Methylphenyl)propan-1-ol (2e)22
Aldehyde 1e (180 mg, 1.50 mmol) was converted with Et2Zn in tol-
uene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (30 mg, 0.10
mmol) into 2e, which was isolated after chromatography (silica gel,
cyclohexane–EtOAc, 20:1, Rf = 0.83) as a colorless oil (215 mg,
1.43 mmol, 96%).
1H NMR (300 MHz, CDCl3): d = 0.96 (t, J = 7.4 Hz, 3 H), 1.74–
3
3
1.92 (m, 2 H), 1.98 (d, J = 3.0 Hz, 1 H), 2.41 (s, 3 H), 4.60 (dt,
3J = 2.6 Hz, 3J = 6.8 Hz, 1 H), 7.20–7.23 (m, 2 H), 7.27–7.31 (m, 2
H).
1-(4-Fluorophenyl)propan-1-ol (2i)22
13C NMR (75 MHz, CDCl3): d = 10.33 (CH3), 21.23 (CH3), 31.91
(CH2), 76.00 (CH), 126.01 (2 CH), 129.34 (2 CH), 137.25 (C),
141.76 (C).
MS (EI, 70 eV): m/z (%) = 150 ([M]+, 9), 121 (100), 93 (47), 91
(43), 77 (25), 65 (10).
HRMS (EI, 70 eV): m/z [M]+ calcd for C10H14O: 150.1039; found:
150.1041.
Aldehyde 1i (186 mg, 1.50 mmol) was converted with Et2Zn in tol-
uene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (30 mg, 0.10
mmol) into 2i, which was isolated after chromatography (silica gel,
cyclohexane–EtOAc, 20:1, Rf = 0.47) as a colorless oil (213 mg,
1.38 mmol, 92%).
1H NMR (300 MHz, CDCl3): d = 0.81 (t, J = 7.4 Hz, 3 H), 1.57–
3
1.76 (m, 2 H), 2.00 (br s, 1 H), 4.48 (t, 3J = 6.6 Hz, 1 H), 6.91–6.98
(m, 2 H), 7.18–7.24 (m, 2 H).
1-(4-Methoxyphenyl)propan-1-ol (2f)22
13C NMR (75 MHz, CDCl3): d = 10.17 (CH3), 32.09 (CH2), 75.45
(CH), 115.28 (d, 2JC,F = 21.3 Hz, 2 CH), 127.70 (d, 3JC,F = 7.9 Hz, 2
CH), 140.39 (d, 4JC,F = 3.0 Hz, C), 162.2 (d, 1JC,F = 245.2 Hz, C).
19F NMR (282 MHz, CDCl3): d = –115.0.
MS (EI, 70 eV): m/z (%) = 154 ([M]+, 6), 125 (100), 97 (46), 95
(14), 77 (14).
Aldehyde 1f (204 mg, 1.50 mmol) was converted with Et2Zn in tol-
uene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (44 mg, 0.15
mmol) into 2f, which was isolated after chromatography (silica gel,
cyclohexane–EtOAc, 20:1, Rf = 0.66) as a colorless oil (234 mg,
1.41 mmol, 94%).
1H NMR (400 MHz, CDCl3): d = 0.95 (t, J = 7.6 Hz, 3 H), 1.71–
3
HRMS (EI, 70 eV): m/z [M]+ calcd for C9H11FO: 154.0788; found:
154.0787.
1.92 (m, 2 H), 1.99 (br s, 1 H), 3.85 (s, 3 H), 4.58 (dt, 3J = 2.3 Hz,
3J = 7.3 Hz, 1 H), 6.91–6.94 (m, 2 H), 7.29–7.33 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 10.42 (CH3), 31.96 (CH2), 55.39
(CH3), 75.75 (CH), 114.08 (2 CH), 127.66 (2 CH), 137.15 (C),
159.45 (C).
MS (EI, 70 eV): m/z (%) = 166 ([M]+, 10), 148 (28), 147 (16), 137
(100), 109 (22), 94 (17), 77 (22).
HRMS (EI, 70 eV): m/z [M]+ calcd for C10H14O2: 166.0988; found:
166.0994.
Anal. Calcd for C9H11FO: C, 70.11; H, 7.19. Found: C, 70.15; H,
7.59.
1-(2-Chlorophenyl)propan-1-ol (2j)22
Aldehyde 1j (210 mg, 1.49 mmol) was converted with Et2Zn in tol-
uene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (30 mg, 0.10
mmol) into 2j, which was isolated after chromatography (silica gel,
cyclohexane–EtOAc, 20:1, Rf = 0.55) as a colorless oil (216 mg,
1.27 mmol, 85%).
1-(4-Bromophenyl)propan-1-ol (2g)23
3
1H NMR (300 MHz, CDCl3): d = 0.91 (t, J = 7.4 Hz, 3 H), 1.60–
Aldehyde 1g (277 mg, 1.50 mmol) was converted with Et2Zn in tol-
uene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (30 mg, 0.11
mmol) into 2g, which was isolated after chromatography (silica gel,
cyclohexane–EtOAc, 20:1, Rf = 0.77) as a colorless oil (314 mg,
1.46 mmol, 98%).
1.80 (m, 2 H), 2.02 (br s, 1 H), 4.96–5.00 (m, 1 H), 7.08–7.14 (m, 1
H), 7.18–7.26 (m, 2 H), 7.44–7.47 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 10.18 (CH3), 30.59 (CH2), 72.07
(CH), 127.14 (CH), 127.27 (CH), 128.46 (CH), 129.48 (CH),
132.09 (C), 142.10 (C).
MS (EI, 70 eV): m/z (%) = 170 ([M]+, 7), 143 (34), 142 (9), 141
(100), 113 (15), 77 (52), 51 (9).
3
1H NMR (300 MHz, CDCl3): d = 0.82 (t, J = 7.4 Hz, 3 H), 1.60–
1.73 (m, 2 H), 1.91 (br s, 1 H), 4.48 (t, 3J = 6.6 Hz, 1 H), 7.11–7.15
(m, 2 H), 7.37–7.41 (m, 2 H).
Synthesis 2011, No. 21, 3482–3490 © Thieme Stuttgart · New York

3488
T. Werner et al.
PAPER
HRMS (EI, 70 eV): m/z [M]+ calcd for C9H11ClO: 170.0492; found:
2,4-Di-tert-butyl-6-(1-hydroxypropyl)phenol (2n)25
170.0489.
Aldehyde 1n (351 mg, 1.50 mmol) was converted with Et2Zn in tol-
uene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (44 mg, 0.15
mmol) into 2n, which was isolated after chromatography (silica gel,
cyclohexane–EtOAc, 25:1, Rf = 0.86) as a colorless oil (316 mg,
1.20 mmol, 80%).
1H NMR (300 MHz, CDCl3): d = 1.00 (t, 3J = 7.3 Hz, 3 H), 1.30 (s,
9 H), 1.44 (s, 9 H), 1.83–2.01 (m, 2 H), 2.44 (d, 3J = 2.3 Hz, 1 H),
4.74–4.73 (m, 1 H), 6.81 (d, 4J = 2.4 Hz, 1 H), 7.25 (d, 4J = 2.4 Hz,
1 H), 8.19 (s, 1 H).
Anal. Calcd for C9H11ClO: C, 63.35; H, 6.50. Found: C, 63.15; H,
6.80.
1-(3-Chlorophenyl)propan-1-ol (2k)22
Aldehyde 1k (210 mg, 1.50 mmol) was converted with Et2Zn in tol-
uene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (30 mg, 0.10
mmol) into 2k, which was isolated after chromatography (silica gel,
cyclohexane–EtOAc, 20:1, Rf = 0.48) as a yellow oil (233 mg, 1.37
mmol, 91%).
13C NMR (75 MHz, CDCl3): d = 10.50 (CH3), 29.87 (CH2), 29.89
(3 CH3), 31.77 (3 CH3), 34.32 (CH), 35.21 (C), 79.24 (CH), 122.25
(CH), 123.47 (CH), 126.53 (C), 137.02 (C), 141.20 (C), 152.71 (C).
1H NMR (300 MHz, CDCl3): d = 0.96 (t, J = 7.4 Hz, 3 H), 1.72–
3
1.88 (m, 2 H), 2.05 (br s, 1 H), 4.62 (t, 3J = 6.5 Hz, 1 H), 7.23–7.28
(m, 1 H), 7.29–7.35 (m, 2 H), 7.38–7.40 (m, 1 H).
MS (EI, 70 eV): m/z (%) = 246 ([M – H2O]+, 21), 232 (18), 231
(100).
HRMS (EI, 70 eV): m/z [M – H2O]+ calcd for C17H26O: 246.1978;
found: 246.1978.
13C NMR (75 MHz, CDCl3): d = 10.11 (CH3), 32.04 (CH2), 75.44
(CH), 124.25 (CH), 126.28 (CH), 127.69 (CH), 129.79 (CH),
134.41 (C), 146.78 (C).
MS (EI, 70 eV): m/z (%) = 170 ([M]+, 12), 143 (33), 142 (8), 141
(100), 115 (15), 113 (14), 77 (66), 51 (8).
HRMS (EI, 70 eV): m/z [M]+ calcd for C9H11ClO: 170.0493; found:
170.0491.
Anal. Calcd for C17H28O2: C, 77.22; H, 10.67. Found: C, 77.38; H,
10.70.
Nonan-3-ol (2o)24
Aldehyde 1o (171 mg, 1.50 mmol) was converted with Et2Zn in tol-
uene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (30 mg, 0.11
mmol) into 2o, which was isolated after chromatography (silica gel,
cyclohexane–EtOAc, 25:1, Rf = 0.86) as a colorless oil (110 mg,
0.763 mmol, 51%).
1H NMR (300 MHz, CDCl3): d = 0.92 (t, 3J = 7.3 Hz, 3 H), 0.98 (t,
3J = 7.5 Hz, 3 H), 1.28–1.37 (m, 8 H), 1.37–1.59 (m, 4 H), 3.53–
3.59 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 9.99 (CH3), 14.19 (CH3), 22.75
(CH2), 25.75 (CH2), 29.52 (CH2), 30.26 (CH2), 32.98 (CH2), 37.09
(CH2), 73.43 (CH).
MS (EI, 70 eV): m/z (%) = 144 ([M]+, 10), 115 (30), 97 (72), 69
(18), 59 (100), 58 (11), 57 (16), 55 (73), 43 (22), 41 (30), 31 (14),
29 (16).
Anal. Calcd for C9H11ClO: C, 63.35; H, 6.50. Found: C, 63.20; H,
6.37.
1-(Naphthalen-1-yl)propan-1-ol (2l)22
Aldehyde 1l (234 mg, 1.50 mmol) was converted with Et2Zn in tol-
uene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (30 mg, 0.10
mmol) into 2l, which was isolated after chromatography (silica gel,
cyclohexane–EtOAc, 25:1, Rf = 0.71) as a pale yellow oil (242 mg,
1.30 mmol, 87%).
3
1H NMR (300 MHz, CDCl3): d = 1.04 (t, J = 7.4 Hz, 3 H), 1.86–
2.03 (m, 2 H), 2.05 (br s, 1 H), 5.37–5.42 (m, 1 H), 7.46–7.56 (m, 3
H), 7.63–7.65 (m, 1 H), 7.77–7.80 (m, 1 H), 7.86–7.91 (m, 1 H),
8.09–8.15 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 10.65 (CH3), 31.20 (CH2), 72.70
(CH), 123.02 (CH), 123.36 (CH), 125.52 (CH), 125.60 (CH),
126.03 (CH), 128.99, (CH) 129.00 (CH), 130.62 (C), 133.93 (C),
140.36 (C).
MS (EI, 70 eV): m/z (%) = 186 ([M]+, 29), 168 (12), 158 (12), 157
(100), 153 (24), 152 (12), 130 (11), 129 (99), 128 (55), 127 (32).
1-(Furan-2-yl)propan-1-ol (2p)22
Aldehyde 1p (144 mg, 1.50 mmol) was converted with Et2Zn in tol-
uene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (30 mg, 0.10
mmol) over 5 d into 2p, which was isolated after chromatography
(silica gel, cyclohexane–EtOAc, 20:1, Rf = 0.68) as a pale yellow
oil (136 mg, 1.08 mmol, 72%).
HRMS (EI, 70 eV): m/z [M]+ calcd for C13H14O: 186.1039, found:
186.1033.
3
1H NMR (300 MHz, CDCl3): d = 0.95 (t, J = 7.5 Hz, 3 H), 1.83–
1.90 (m, 2 H), 2.0 (br s, 1 H), 4.59 (t, 3J = 6.6 Hz, 1 H), 6.22–6.23
1-(2,4-Dimethoxyphenyl)propan-1-ol (2m)24
(m, 1 H), 6.32–6.33 (m, 1 H), 7.36–7.37 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 10.06 (CH3), 28.72 (CH2), 69.32
(CH), 106.05 (CH), 110.24 (CH), 142.05 (CH), 156.84 (C).
MS (EI, 70 eV): m/z (%) = 126 ([M]+, 15), 97 (100), 69 (12), 41
(18), 39 (12).
HRMS (ESI): m/z [M – H]– calcd for C7H9O2: 125.0608; found:
125.0607.
Aldehyde 1m (249 mg, 1.50 mmol) was converted with Et2Zn in
toluene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (44 mg, 0.15
mmol) into 2m, which was isolated after chromatography (silica
gel, cyclohexane–EtOAc, 10:1, Rf = 0.38) as a colorless oil (249
mg, 1.27 mmol, 85%).
3
1H NMR (300 MHz, CDCl3): d = 0.86 (t, J = 7.4 Hz, 3 H), 1.70–
1.76 (m, 2 H), 2.40 (br s, 1 H), 3.73 (s, 3 H), 3.74 (s, 3 H), 4.65 (q,
3J = 6.0 Hz, 1 H), 6.38–6.39 (m, 1 H), 6.40–6.41(m, 1 H), 7.10–7.13
(m, 1 H).
1-(Pyridin-2-yl)propan-1-ol (2q)26
13C NMR (75 MHz, CDCl3): d = 10.68 (CH3), 30.25 (CH2), 55.39
(CH3), 55.48 (CH3), 72.16 (CH), 98.78 (CH), 104.10 (CH), 125.06
(C), 127.78 (CH), 157.88 (C), 160.10 (C).
MS (EI, 70 eV): m/z (%) = 196 ([M]+, 5), 178 (11), 168 (10), 167
(100), 151 (14), 137 (18).
HRMS (EI, 70 eV): m/z [M]+ calcd for C11H16O3: 196.1094; found:
196.1095.
Aldehyde 1q (160 mg, 1.50 mmol) was converted with Et2Zn in tol-
uene (2.7 mL, 3.0 mmol) in the presence of Bu4PCl (30 mg, 0.10
mmol) over 5 d into 2q, which was isolated after chromatography
(silica gel, cyclohexane–EtOAc, 20:1, Rf = 0.68) as a pale yellow
oil (106 mg, 0.773 mmol, 52%).
3
1H NMR (300 MHz, CDCl3): d = 0.85 (t, J = 7.5 Hz, 3 H), 1.55–
1.69 (m, 1 H), 1.72–1.86 (m, 1 H), 4.21 (br s, 1 H), 4.58–4.62 (m, 1
H), 7.07–7.12 (m, 1 H), 7.15–7.17 (m, 1 H), 7.55–7.61 (m, 1 H),
8.43–8.44 (m, 1 H).
Anal. Calcd for C11H16O3: C, 67.32; H, 8.22. Found: C, 67.45; H,
8.62.
Synthesis 2011, No. 21, 3482–3490 © Thieme Stuttgart · New York

PAPER
Phosphonium Salt Catalyzed Addition of Diethylzinc to Aldehydes
3489
3
13C NMR (75 MHz, CDCl3): d = 9.52 (CH3), 31.44 (CH2), 73.88
(CH), 120.50 (CH), 122.32 (CH), 136.90 (CH), 148.25 (CH),
162.12 (C).
1H NMR (300 MHz, CDCl3): d = 1.22 (d, J = 6.9 Hz, 6 H), 3.56
(hept, 3J = 6.8 Hz, 1 H), 7.42–7.57 (m, 3 H), 7.93–7.99 (m, 2 H).
MS (EI, 70 eV): m/z (%) = 148 ([M]+, 9), 105 (100), 77 (38), 51
MS (EI, 70 eV): m/z (%) = 137 ([M]+, 12), 120 (14), 109 (77), 108
(12).
(100), 106 (12), 80 (21), 79 (20), 78 (36), 53 (12), 52 (14), 51 (11).
(S)-(2-Pyrrolidinylmethyl)triphenylphosphonium Bromide
(6)13
HRMS (ESI): m/z [M + H]+ calcd for C8H12NO: 138.0913; found:
138.0914.
L-Prolinol (5; 1.40 g, 13.8 mmol) and Ph3P (3.63 g, 13.8 mmol)
were dissolved in toluene (6 mL). The mixture was cooled to 5 °C
and aq 48% HBr (9.0 mL, 166 mmol) was added portionwise (cau-
tiously at first). The reaction mixture was heated to 150 °C, which
caused the toluene and most of the H2O to evaporate to give a melt.
The melt was heated to 200–210 °C and stirred for 1 h and then 3 h
at 150 °C. The reaction mixture was allowed to cool to r.t.,
quenched with H2O (50 mL), and extracted with EtOAc (3 × 25
mL). The acidic aqueous fraction was basified to pH 8 with aq
Na2CO3/NaHCO3, extracted with CH2Cl2 (6 × 40 mL), dried
(Na2SO4), and concentrated in vacuo to give 6 (2.95 g, 6.91 mmol,
50%) as a yellow hygroscopic solid.
Diphenylmethanol (2r)27
Benzaldehyde (1a; 75 mg, 0.74 mmol) in toluene (1.5 mL) was con-
verted with Ph2Zn (325 mg, 1.48 mmol) in the presence of Bu4PCl
(15 mg, 0.06 mmol) over 24 h into 2r, which was isolated after chro-
matography (silica gel, cyclohexane–EtOAc, 20:1 → 10:1;
Rf = 0.58, cyclohexane–EtOAc, 1:1) as colorless crystals (80 mg,
0.43 mmol, 58%); mp 65 °C.
1H NMR (300 MHz, CDCl3): d = 2.41 (s, 1 H), 5.78 (s, 1 H), 7.20–
7.38 (m, 10 H).
13C{1H} NMR (75 MHz, CDCl3): d = 76.16 (CH), 126.50 (4 CH),
127.50 (2 CH), 128.74 (4 CH), 143.87 (2 C).
IR (KBr): 2856 (m, br), 2177 (w), 1586 (w), 1484 (w), 1436 (s),
1109 (s), 919 (s), 719 (vs), 687 (vs), 639 (s), 494 cm–1 (vs).
MS (EI, 70 eV): m/z (%) = 184 ([M]+, 26), 167 (11), 168 (5), 152
1H NMR (300 MHz, CDCl3): d = 1.63–1.78 (m, 1 H), 1.78–1.99 (m,
(7), 105 (100), 77 (56), 51 (20).
3 H), 2.79–2.92 (m, 1 H), 2.95–3.07 (m, 1 H), 3.71–3.97 (m, 2 H),
1-Phenylpentanol (2s)28
3
2
2
4.06 (ddd, J = 5.4 Hz, J = 12.4 Hz, JH,P = 15.6 Hz, 1 H), 4.30
(ddd, 3J = 8.2 Hz, 2J = 12.4 Hz, 2JH,P = 15.7 Hz, 1 H), 7.59–9.00 (m,
15 H).
Benzaldehyde (1a; 160 mg, 1.51 mmol) in toluene (0.4 mL) was
converted with Bu2Zn (3.0 ml, 1 M in heptane, 3.0 mmol) in the
presence of Bu4PCl (30 mg, 0.11 mmol) over 24 h into 2s, which
was isolated after chromatography (silica gel, cyclohexane–EtOAc
20:1 → 10:1; Rf = 0.07, cyclohexane–EtOAc, 20:1) as a colorless
oil (100 mg, 0.609 mmol, 40%).
1H NMR (300 MHz, CDCl3): d = 0.85–0.91 (m, 3 H), 1.19–1.46 (m,
4 H), 1.63–1.90 (m, 3 H), 4.66 (dd, 3J = 5.9 Hz, 3J = 7.5 Hz, 1 H),
7.23–7.31 (m, 1 H), 7.31–7.37 (m, 4 H).
13C{1H}-NMR (75 MHz, CDCl3): d = 13.95 (CH3), 22.54 (CH2),
27.91 (CH2), 38.72 (CH3), 74.56 (CH), 125.85 (2 CH), 127.35 (CH),
128.31 (2 CH), 144.89 (C).
MS (EI, 70 eV): m/z (%) = 164.1 ([M]+, 6), 107 (100), 79 (44), 77
(23), 51 (5).
13C NMR (75 MHz, CDCl3): d = 23.95 (CH2), 26.39 (d, 1JC,P = 53.2
3
Hz, CH2), 31.77 (d, JC,P = 7.0 Hz, CH2), 44.87 (CH2), 54.17 (d,
1
2JC,P = 1.7 Hz, CH), 117.33 (d, JC,P = 86.7 Hz, 3 C), 130.45 (d,
2JC,P = 12.8 Hz, 6 CH), 133.71 (d, 3JC,P = 10.5 Hz, 6 CH), 135.17 (d,
4JC,P = 2.9 Hz, 3 CH).
31P NMR (121 MHz, CDCl3): d = 21.85 (1 P, P+).
HRMS (ESI): m/z [M]+ calcd for C23H25NP: 346.1719; found:
346.1715.
Methylbinapium Iodide (8)14
MeI (227 mg, 1.60 mmol) was added to (S)-BINAP (7; 1.00 g, 1.65
mmol) in CH2Cl2 (20 mL). The reaction mixture was stirred for 16
h at 23 °C. Et2O (20 mL) was added and the precipitate was collect-
ed by filtration, washed with Et2O (40 mL), and dried in vacuo to
give 8 (1.11 g, 1.45 mmol, 91%) as a white amorphous solid; mp
>200 °C (dec.).
2-Methyl-1-phenylpropanol (2t)29
Benzaldehyde (1a; 106 mg, 1.15 mmol) in toluene (1 mL) was con-
verted with i-Pr2Zn (2 mL, 1 M in toluene, 2.0 mmol) in the pres-
ence of Bu4PCl (21 mg, 0.07 mmol) over 24 h into 2t, which was
isolated after chromatography (silica gel, cyclohexane–EtOAc,
20:1 → 10:1 → EtOAc; Rf = 0.27, cyclohexane–EtOAc, 10:1) as a
colorless oil (45 mg, 0.30 mmol, 26%). Phenyl isopropyl ketone (20
mg, 0.13 mmol, 12%, Rf = 0.50 in cyclohexane–EtOAc, 10:1) was
isolated as a by-product (see below).
1H NMR (300 MHz, CDCl3): d = 0.79 (d, 3J = 6.9 Hz, 3 H), 1.00 (d,
3J = 6.7 Hz, 3 H), 1.88–2.03 (m, 2 H), 4.35 (dd, 3J = 2.0 Hz, 3J = 6.8
Hz, 1 H), 7.22–7.36 (m, 5 H).
2
1H NMR (300 MHz, CDCl3): d = 1.99 (d, JP,H = 13.4 Hz, 3 H),
6.57–6.61 (m, 1 H), 6.72–6.93 (m, 6 H), 7.00–7.07 (m, 2 H), 7.14–
7.30 (m, 4 H), 7.38–7.44 (m, 2 H), 7.44–7.56 (m, 8 H), 7.56–7.69
(m, 3 H), 7.74–7.79 (m, 1 H), 7.79–7.83 (m, 1 H), 7.89–7.91 (m, 1
H), 7.92–7.95 (m, 1 H), 7.95–7.97 (m, 1 H), 8.16–8.22 (m, 1 H).
31P NMR (121 MHz, CDCl3): d = 22.65 (1 P, P+), –14.55 (1 P, P).
HRMS (ESI): m/z [M]+ calcd for C45H35OP2: 653.2158; found:
653.2158.
13C{1H} NMR (75 MHz, CDCl3): d = 18.20 (CH3), 18.95 (CH3),
35.21 (CH), 80.00 (CH), 126.52 (2 CH), 127.37 (CH), 128.14 (2
CH), 143.59 (C).
Acknowledgment
Financial support from the Deutsche Forschungsgemeinschaft DFG
(WE 3605/3-1) and the Leibniz-Institute for Catalysis at the Univer-
sity Rostock as well as the support and advice from Prof. M. Beller
are gratefully acknowledged.
MS (EI, 70 eV): m/z (%) = 150 ([M]+, 7), 107 (100), 79 (54), 77
(32), 51 (8).
Phenyl Isopropyl Ketone30
Phenyl isopropyl ketone (20 mg, 0.13 mmol, 12%; Rf = 0.50, cyclo-
hexane–EtOAc, 10:1) was obtained as a by-product in the synthesis
of 2t.
Synthesis 2011, No. 21, 3482–3490 © Thieme Stuttgart · New York

3490
T. Werner et al.
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Synthesis 2011, No. 21, 3482–3490 © Thieme Stuttgart · New York