A straightforward synthesis of (3S)-4-methoxybutane-1,3-diol and its use as chiral auxiliary for the preparation of (p5)-1-(diphenylphosphino)-2-formyl- 1′,2′,3′,4′,5′-pentamethylferrocene

Article abstract of DOI:10.1055/s-2006-942415

(3S′)-4-Methoxybutane-1,3-diol [(S)-4], an important auxiliary for the synthesis of planar-chiral metallocenes, has been obtained from (S)-1,2,4-butanetriol via formation of an isomerically pure acetal of p-nitrobenzaldehyde, O-methylation and hydrolysis.

Full text of DOI:10.1055/s-2006-942415

PAPER
2201
A Straightforward Synthesis of (3S)-4-Methoxybutane-1,3-diol and its Use as
Chiral Auxiliary for the Preparation of (pS)-1-(Diphenylphosphino)-2-formyl-
1¢,2¢,3¢,4¢,5¢-pentamethylferrocene
S
ynthesis of (3
e
S
)-4-Meth
l
i
ne-1,3
x
-diol and its
Use as
M
Chiral
A
uxiliary . Geisler, Günter Helmchen*
Organisch-Chemisches Institut, Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
Fax +49(6221)544205; E-mail: g.helmchen@oci.uni-heidelberg.de
Received 21 April 2006
Dedicated to Professor Dieter Hoppe on the occasion of his 65th birthday
CSA, toluene,
O
Abstract: (3S)-4-Methoxybutane-1,3-diol [(S)-4], an important
auxiliary for the synthesis of planar-chiral metallocenes, has been
obtained from (S)-1,2,4-butanetriol via formation of an isomerically
pure acetal of p-nitrobenzaldehyde, O-methylation and hydrolysis.
Diol (S)-4 was used in a synthesis of the new planar-chiral ferrocene
(pS)-1-(diphenylphosphino)-2-formyl-1¢,2¢,3¢,4¢,5¢-pentamethylfer-
rocene [(pS)-9].
100 °C
HO
H
R
isomeric
acetals
CH(OMe)2
R
+
O
OH
HO
(S,S)-1
HO
a R = p-nitro-phenyl
b R = 2-naphthyl
c R = p-biphenylyl
d R = phenyl
92%*
91%
91%
86%
85%*
83%
8%
Key words: acetals, asymmetric synthesis, chiral pool, lithiation,
metallocenes
9%
9%
14%
15%
17%
Planar-chiral ferrocenes and related metallocenes have
found widespread use as ligands in asymmetric catalysis.1
The most important method for introduction of planar
chirality is the directed ortho-lithiation induced by a chiral
ortho-directing group (ODG*, Scheme 1) followed by re-
action with an electrophile.
e R = ferrocenyl
f R = p-OMe-phenyl
* purification by recrystallization from toluene possible
Scheme 2 Preparation of chiral acetals (S,S)-1a–f
ODG*
ODG*
E
lanes 1 (Scheme 2) are preferentially formed by acetaliza-
tion,3 despite a variety of possible isomeric acetals.2d The
selectivity of their formation is particularly high upon
transacetalization from dimethyl acetals of aromatic alde-
hydes.2,4 Kagan and coworkers found that the ferrocenyl
derivative (S,S)-1e is crystalline and can be obtained in
pure form by recrystallization after transacetalization ac-
cording to Scheme 2.2a,2b,5 The acetal was O-methylated in
a standard manner, the product subjected to lithiation–
electrophilic substitution, and the final acetal eventually
hydrolyzed to give (S)-4-methoxybutane-1,3-diol.
1. RLi, solvent
2. EX
Fe
Fe
planar-chiral
dr up to >99:1
O
S
O
H
Me2N
O
H
R
ODG* =
N
R
O
Me
amine
acetal
oxazoline
sulfoxide
OMe
Scheme 1 Preparation of planar-chiral ferrocenes
We wondered whether the procedure of Kagan and co-
workers could be carried out with an aldehyde cheaper
than formylferrocene in order to obtain an acetal from
which 4-methoxybutane-1,3-diol could be prepared via a
short route involving O-methylation and subsequent hy-
drolysis. By screening several acetals (S,S)-1 (Scheme 2),
it was found that the p-nitrophenyl derivative (S,S)-1a
could be obtained in isomerically pure form by recrystal-
lization from toluene. Even better results were obtained
when the solvent was removed from the reaction mixture
by slow distillation (over a period of 4 h), forming acetal
(S,S)-1a quantitatively and with complete selectivity.
Success with this procedure requires that the temperature
in the flask, preferentially ca. 120 °C, is maintained below
the melting point of (S,S)-1a (137–138 °C). Thus, the pro-
In the course of an effort to prepare enantiomerically
enriched 1-(diphenylphosphino)-2-formyl-1¢,2¢,3¢,4¢,5¢-
pentamethylferrocene (9, see Scheme 4), we wanted to
apply the method of Kagan and co-workers,2 who showed
that lithiation of acetals derived from 4-methoxybutane-
1,3-diol proceeds with very high diastereoselectivity. A
drawback of this otherwise very effective method is the
necessity to prepare the requisite acetals from commer-
cially available (R)- or (S)-1,2,4-butanetriol rather than
the O-methyl derivative. It is well established that dioxo-
SYNTHESIS 2006, No. 13, pp 2201–2205
x
x.
x
x
.
2
0
0
6
Advanced online publication: 12.06.2006
DOI: 10.1055/s-2006-942415; Art ID: C01506SS
© Georg Thieme Verlag Stuttgart · New York

2202
F. M. Geisler, G. Helmchen
PAPER
cess relies on reversible transacetalization–in situ crystal- overall yield of 92%. Both 6 and (S,S)-7 are very suscep-
lization. tible to hydrolysis and, therefore, should not be stored.
Methyl ether (S,S)-3 was prepared in 82% yield directly The planar-chiral phosphine (S,S,pS)-8 was obtained with
from crude (S,S)-1a, contaminated with camphorsulfonic very high diastereomeric excess (>98%, 1H and 31P NMR)
acid (CSA), by treatment with 1.2 equivalents of NaH in in 70% yield via metallation of (S,S)-7 (1.1 equiv of pre-
THF followed by reaction with 3 equivalents of methyl io- cooled s-BuLi, Et2O, –78 °C to –30 °C) followed by addi-
dide (Scheme 3). Hydrolysis of (S,S)-3 gave diol (S)-4 as tion of PPh2Cl. Finally, aldehyde (pS)-9 was prepared in
a colorless and very hygroscopic liquid. As mentioned quantitative yield from (S,S,pS)-8 by hydrolysis with p-
above, compound (S)-4 is known,2b,4c but our procedure TsOH in H2O–CH2Cl2.
will likely improve its availability compared to previous
methods.
The absolute configuration of (pS)-9 was assigned on the
basis of an X-ray crystal structure analysis9 and was as an-
Diol (S)-4 was used to prepare aldehyde (pS)-9 ticipated. An ORTEP diagram of (pS)-9 is shown in
(Scheme 4), which can serve as building block for the Figure 1. The conformation of the molecule is obviously
preparation of a variety of new chiral ligands, for example determined by minimization of steric interactions.
imines, that are of interest in homogeneous catalysis.
Further reactions with (S,S)-7 and use of (pS)-9 as build-
The achiral aldehyde 56 has been previously prepared by ing block for the preparation of chiral ligands for asym-
Bildstein et al.6a from Fe(acac)2, lithium pentamethylcy- metric catalysis are under active investigation in our
clopentadienide and sodium formyl-cyclopentadienide7 in laboratory.
46% yield. Use of FeCl28 instead of Fe(acac)2 allowed us
to slightly improve the yield of 5 to 62%.
Melting points were determined in open-glass capillaries and are
not corrected. For all compounds 1H NMR, 13C{1H} NMR, 31P{1H}
The direct acetalization of aldehyde 5 with diol (S)-4 was
attempted in various ways, but yields were generally un-
satisfactory. Again, transacetalization solved the problem.
Thus, dimethyl acetal 6 was prepared by the reaction of al-
dehyde 5 with HC(OMe)3 and a catalytic amount of CSA
in MeOH within a few minutes. The reaction of 6 with the
NMR, 1H,1H-gs-COSY and 1H,13C-gs-HMQC spectra were record-
ed on a 300 MHz spectrometer [300 MHz (1H), 75 MHz (13C), 121
MHz (31P)]. Chemical shifts are reported in d (ppm) using residual
CHCl3 [7.26 (1H), 77.36 (13C)] or DMSO [2.50 (1H), 39.52 (13C)] as
internal standards and H3PO4 as an external standard [0.00 (31P)].
Mass spectra were determined on a Jeol JMX 700 spectrometer. Op-
diol (S)-4 gave the desired acetal (S,S)-7 in an excellent tical rotations were measured at r.t. with a Perkin Elmer 241 pola-
5
5
6
6
OH
OMe
4
4
CH(OMe)2
CSA (cat.), toluene
1
O
O
2
O
O
2
HO
HO
2
4
H
H
1. NaH, THF, 0 °C
2. MeI, 0 °C to r.t.
6 N HCl
3
HO
HO
MeO
NO2
NO2
(S,S)-1a
NO2
(S)-4 (63%)
2
HO
(S,S)-3
(82% over 2 steps)
Scheme 3 Ex chiral pool synthesis of (S)-4
6' '
O
H
5' '
4' '
OMe
OH OH
(S)-4
2' '
CH(OMe)2
CHO
1
O
1
CH(OMe)3, MeOH
CSA (cat.)
1
1. Cp*Li, THF
2.
Fe
Fe
FeCl2
Fe
CSA (cat.), 100 °C
NaO
H
MeO
1'
1'
1'
6
(S,S)-7
(92% over 2 steps)
1. s-BuLi, Et2O, –78 °C to –30 °C
2. PPh2Cl, –30 °C to r.t.
5 (62%)
6' '
O
H
5' '
2
2
2' '
CHO
4' '
O
p-TsOH (cat.)
CH2Cl2–H2O
Fe 1
1'
(pS)-9 (99%)
Fe 1
PPh2
PPh2
MeO
1'
(S,S,pS)-8 (70%)
Scheme 4 Application of the diol (S)-4 as a chiral auxiliary
Synthesis 2006, No. 13, 2201–2205 © Thieme Stuttgart · New York

PAPER
Synthesis of (3S)-4-Methoxybutane-1,3-diol and its Use as Chiral Auxiliary
2203
(2S,4S)-4-(Methoxymethyl)-2-(4-nitrophenyl)-1,3-dioxane
[(S,S)-3]
A solution of crude (S,S)-1a (100.0 mmol), prepared as described
above, in anhyd THF (100 mL) was cooled in an ice bath. NaH (2.88
g, 120.0 mmol) was added over a period of 10 min and the resulting
suspension was well stirred for further 10 min, then MeI (42.57 g,
300.0 mmol) was added dropwise. The ice bath was removed and
the mixture was stirred for 12 h. Volatile materials were removed in
vacuo and the residue was subjected to column chromatography
(silica gel, petroleum ether–EtOAc, 1:1) to yield 20.65 g (82% over
two steps) of (S,S)-3 as a microcrystalline solid.
Mp 97–98 °C; Rf 0.45 (petroleum ether–EtOAc, 1:1); [a]D20 15.5 (c
0.73, EtOH).
1H NMR (300 MHz, CDCl3): d = 1.55 (d, J = 13.4 Hz, 1 H, 5-Ha),
1.88 (ddd, J = 12.5, 7.4, 5.1 Hz, 1 H, 5-Hb), 3.41 (s, 3 H, OCH3),
3.46 (dd, J = 10.3, 3.8 Hz, 1 H, CH2OCH3), 3.57 (dd, J = 10.4, 6.5
Hz, 1 H, CH2OCH3), 4.01 (dt, J = 11.8, 2.6 Hz, 1 H, 6-Ha), 4.12 (mc,
1 H, 4-H), 4.32 (dd, J = 11.5, 5.0 Hz, 1 H, 6-Hb), 5.60 (s, 1 H, 2-H),
7.68 (d, J = 8.9 Hz, 2 H, ArH), 8.21 (d, J = 8.9 Hz, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 27.9 (C-5), 59.8 (OCH3), 67.2
(C-6), 75.7 (CH2OMe), 76.8 (C-4), 99.9 (C-2), 123.7 (ArC), 127.7
(ArC), 145.2 (ArCquart.), 148.4 (ArCquart.).
Figure 1 X-ray crystal structure of (pS)-9
HRMS: m/z calcd for C12H15NO5 [M+]: 253.0950; found: 253.0934.
rimeter. Microanalyses were performed at the Institut für
Organische Chemie der Universität Heidelberg. For TLC Macherey
& Nagel Polygram Sil G/UV254 plates were used with spot detection
by UV light. Macherey & Nagel Kieselgel S (0.032–0.063 mm) was
used for flash chromatography. The petroleum ether used for chro-
matography had a boiling range of 30–75 °C. Pentamethylcyclo-
pentadiene was prepared according to the method of Jutzi.10 (S)-
1,2,4-butanetriol was purchased from Lancaster. If not stated other-
wise, reactions were carried out under dry argon with magnetic stir-
ring.
Anal. Calcd for C12H15NO5: C, 56.91; H, 5.97; N, 5.53. Found: C,
56.85; H, 6.01; N, 5.43.
(3S)-4-Methoxybutane-1,3-diol [(S)-4]
Acetal (S,S)-3 (20.60 g, 81.3 mmol) and 6 N HCl (81 mL) were
mixed in a distillation apparatus and ca. 70 mL of H2O were dis-
tilled off. The residue was extracted with CH2Cl2 (2 × 40 mL) to re-
move p-nitro-benzaldehyde and acetal (S,S)-3 (conversion >85% as
determined by 1H NMR). After careful bulb-to-bulb distillation
(135 °C/10 mbar) of the residual water phase 6.15 g (51.2 mmol,
63%) of diol (S)-4 were obtained as a colorless liquid. The com-
pound is hygroscopic and was stored over 4 Å MS.
1-(Dimethoxymethyl)-4-nitrobenzene (2)
A mixture of p-nitro-benzaldehyde (25.00 g, 165.6 mmol), MeOH
(100 mL), trimethoxymethane (268 mL) and p-TsOH·H2O (1.57 g,
8.28 mmol) was heated in an oil bath at 120 °C while distilling off
the solvents over a period of ca. 1 h. The residue was distilled (bp
113 °C/1 mbar) to give 31.98 g of 2 (98%) as a light yellow oil.11
[a]D20 –21.5 (c 1.30, EtOH) {Lit.4c [a]D20 –28.8 (c 0.50, CHCl3)}.
1H NMR (300 MHz, DMSO-d6): d = 1.34–1.46 (m, 1 H, 2-Ha),
1.49–1.61 (m, 1 H, 2-Hb), 3.20 (d, J = 5.9, 2 H, 4-H), 3.24 (s, 3 H,
OCH3), 3.48 (dd, J = 12.1, 5.9 Hz, 2 H, 1-H), 3.68 (m, 1 H, 3-H),
4.32 (t, J = 5.1 Hz, 1 H, 1-OH), 4.51 (d, J = 5.2 Hz, 1 H, 3-OH).
13C NMR (75 MHz, DMSO-d6): d = 37.0 (C-2), 57.8 (C-1), 58.3
(OCH3), 66.2 (C-3), 77.3 (C-4).
[(2S,4S)-2-(4-Nitrophenyl)-1,3-dioxan-4-yl]methanol [(S,S)-1a]
In a distillation apparatus, a solution of vacuum-dried (1 h, 0.05
mbar) (S)-1,2,4-butanetriol (10.60 g, 100.0 mmol), camphorsulfon-
ic acid (0.21 g, 2.0 mmol) and acetal 2 (19.70 g, 100.0 mmol) in an-
hyd toluene (50 mL) was heated in an oil bath kept at 120 °C.
Toluene was distilled off over a period of 4 h. The residue consisted
of (S,S)-1a, which was sufficiently pure for further transformations
(isomeric purity >99.5%). An analytically pure sample of (S,S)-1a
was obtained by column chromatography (silica gel, petroleum
ether–EtOAc, 1:1).
Anal. Calcd for C5H12O3: C, 49.98; H, 10.07. Found: C, 49.77; H,
10.06.
1-Formyl-1¢,2¢,3¢,4¢,5¢-pentamethylferrocene (5)
A: A suspension of FeCl2 (10.4 g, 82.0 mmol) in THF (800 mL) was
vigorously stirred in the dark for 1 h.
B: A mixture of sodium cyclopentadienide (41.0 mL of a 2.0 M so-
lution in THF, 82.0 mmol) and methyl formate (7.6 mL, 121.8
mmol) in THF (100 mL) was stirred at r.t. for 4 h.
Mp 137–138 °C (white needles); Rf 0.21 (petroleum ether–EtOAc,
1:1); [a]D20 19.1 (c 0.75, EtOH).
1H NMR (300 MHz, CDCl3): d = 1.50 (d, J = 12.5 Hz, 1 H, 5-Ha),
1.94 (ddd, J = 12.4, 7.3 Hz, 5.1 Hz, 1 H, 5-Hb), 2.21 (br s, 1 H, OH),
3.62–3.79 (m, 2 H, CH2OH), 3.93–4.12 (m, 2 H, 4-H and 6-Ha),
4.33 (dd, J = 11.5, 4.9 Hz, 1 H, 6-Hb), 5.62 (s, 1 H, 2-H), 7.67 (d,
J = 8.5 Hz, 2 H, ArH), 8.21 (d, J = 8.7 Hz, 2 H, ArH).
13C NMR (75 MHz, CDCl3): d = 27.0 (C-5), 65.9 (CH2OH), 67.0
(C-6), 78.1 (C-4), 99.9 (C-2), 123.8 (ArC), 127.6 (ArC), 145.1
(ArCquart.), 148.5 (ArCquart.).
C: For the preparation of lithium pentamethylcyclopentadienide, n-
BuLi (56.4 mL of a 1.6 M solution in n-hexane, 90.2 mmol) was
added dropwise to a cooled (–78 °C) solution of pentamethylcyclo-
pentadiene (14.1 mL, 90.2 mmol) in THF (200 mL) and the result-
ant mixture was stirred at r.t. for 2 h.
The suspension C was transferred via cannula to the suspension A
and the mixture was stirred at r.t. for 1 h while its color turned to
green. Then, suspension B was added via cannula and the resultant
mixture was stirred at r.t. for 16 h. The solvents were then removed
in vacuo, the residue dissolved in petroleum ether–Et2O (1:1) and
the solution filtered through a short pad of alumina (neutral, 13%
HRMS: m/z calcd for C11H13NO5 [M+]: 240.0872; found: 240.0849.
Anal. Calcd for C11H13NO5: C, 55.23; H, 5.48; N, 5.85. Found: C,
55.28; H, 5.62; N, 5.76.
Synthesis 2006, No. 13, 2201–2205 © Thieme Stuttgart · New York

2204
F. M. Geisler, G. Helmchen
PAPER
(pS)-1-(Diphenylphosphino)-2-[(2S,4S)-4-(methoxymethyl)-
H2O). Column chromatography (silica gel, petroleum ether–Et2O,
2:1) afforded 16.3 g (62%) of 5 as a deep-red solid.
Mp 59–62 °C (Lit.6b 62.5–63 °C); Rf 0.48 (petroleum ether–Et2O,
2:1).
1H NMR (300 MHz, CDCl3): d = 1.82 (s, 15 H, CH3), 4.15 (t,
J = 1.7 Hz, 2 H, 3-H, 4-H), 4.25 (t, J = 1.7 Hz, 2 H, 2-H, 5-H), 9.69
(s, 1 H, CHO).
13C NMR (75 MHz, CDCl3): d = 11.3 (CH3), 72.2 (C-3, C-4), 77.8
(C-2, C-5), 80.5 (C-1), 82.6 (C-1¢, C-2¢, C-3¢, C-4¢, C-5¢), 194.1
(CHO).
1,3-dioxan-2-yl]-1¢,2¢,3¢,4¢,5¢-pentamethylferrocene [(S,S,pS)-8]
A cold (–78 °C) solution of acetal (S,S)-7 (3.50 g, 9.06 mmol) in an-
hyd Et2O (45 mL) was treated dropwise with a precooled (ca.
–70 °C) 1.3 M solution of s-BuLi (9.97 mmol) in cyclohexane (7.67
mL). The reaction mixture was then allowed to warm up to –30 °C
within 1 h. A light-red precipitate appeared. At this temperature
P-chlorodiphenylphosphine (2.20 g, 9.97 mmol) was added drop-
wise, and the reaction mixture was allowed to warm up to r.t. over
a period of 12 h. Solvents were removed in vacuo and the residue
was subjected to column chromatography (silica gel, petroleum
ether–EtOAc–Et3N, 16:4:1) to yield 3.61 g (70%) of (S,S,pS)-8 as a
microcrystalline yellow solid.
HRMS: m/z calcd for C16H20OFe [M+]: 284.0864; found: 284.0870.
Anal. Calcd for C16H20OFe: C, 67.63; H, 7.09. Found: C, 67.70; H,
7.17.
Mp >120 °C (dec.); Rf 0.39 (petroleum ether–EtOAc–Et3N, 16:4:1,
yellow spot); [a]D20 –245 (c 0.88, CHCl3).
1H NMR (300 MHz, CDCl3): d = 1.34–1.43 (m, 1 H, 5¢¢-Ha), 1.55–
1.70 (m, 1 H, 5¢¢-Hb), 1.76 (s, 15 H, CH3), 2.70–2.83 (m, 2 H,
CH2OCH3), 3.08 (s, 3 H, OCH3), 3.49 (mc, 1 H, 4-H), 3.66 (mc, 1 H,
4¢¢-H), 3.75–3.84 (m, 1 H, 6¢¢-Ha), 3.83 (t, J = 2.4 Hz, 1 H, 3-H),
4.13–4.17 (m, 1 H, 5-H), 4.18 (dd, J = 11.3 Hz, 3.8 Hz, 1 H, 6¢¢-Hb),
5.37 (d, J = 1.8 Hz, 1 H, 2¢¢-H), 7.08–7.18 (m, 5 H, Ph), 7.30–7.37
(m, 3 H, Ph), 7.61–7.69 (m, 2 H, Ph).
13C NMR (75 MHz, CDCl3): d = 11.3 (CH3), 28.5 (C-5¢¢), 59.4
(OCH3), 66.9 (C-6¢¢), 73.5 (C-5), 74.2 (C-4), 74.8 (C-3), 75.0
(CH2OCH3), 75.5 (C-4¢¢), 77.6 (C-2), 81.4 (C-1¢, C-2¢, C-3¢, C-4¢,
C-5¢), 89.1 (1JC,P = 19.4 Hz, C-1), 99.8 (C-2¢¢), 127.4, 127.6, 127.7,
128.1, 128.3, 129.4, 132.9, 133.1, 136.3, 136.6 (Ph).
1-(Dimethoxymethyl)-1¢,2¢,3¢,4¢,5¢-pentamethylferrocene (6)
A mixture of aldehyde 5 (2.84 g, 10.0 mmol), MeOH (6 mL), tri-
methyl orthoformate (16 mL) and camphorsulfonic acid (0.05 g, 0.2
mmol) was stirred for 5 min, then volatiles were removed in vacuo.
The residue, which contained 6, CSA and traces of trimethyl ortho-
formate, was directly used for the preparation of (S,S)-7 (see be-
low). An analytically pure sample of 6 was obtained by quick
column chromatography (silica gel, petroleum ether–EtOAc–Et3N,
10:10:1) as an orange oil. The compound is very susceptible to hy-
drolysis.
Rf 0.98 (petroleum ether–EtOAc–Et3N, 10:10:1, yellow spot).
1H NMR (300 MHz, CDCl3): d = 1.87 (s, 15 H, CH3), 3.21 (s, 6 H,
OCH3), 3.67 (t, J = 2.2 Hz, 2 H, 3-H, 4-H), 3.77 (t, J = 2.1 Hz, 2 H,
2-H, 5-H), 5.31 [s, 1 H, CH(OCH3)2].
31P NMR (121 MHz, CDCl3): d = –25.8.
HRMS: m/z calcd for C33H39O3PFe [M+]: 570.1986; found:
13C NMR (75 MHz, CDCl3): d = 11.3 (CH3), 51.7 (OCH3), 69.8
(C-3, C-4), 72.2 (C-2, C-5), 80.7 (C-1¢, C-2¢, C-3¢, C-4¢, C-5¢), 84.3
(C-1), 101.4 [CH(OCH3)2].
HRMS: m/z calcd for C18H26O2Fe [M+]: 330.1282; found:
330.1281.
570.2012.
Anal. Calcd for C33H39O3PFe: C, 69.48; H, 6.89; P, 5.43. Found: C,
69.46; H, 6.89; P, 5.36.
(pS)-1-(Diphenylphosphino)-2-formyl-1¢,2¢,3¢,4¢,5¢-penta-
methylferrocene [(pS)-9]
A mixture of degassed CH2Cl2 (12 mL), degassed H2O (12 mL), ac-
etal (S,S,pS)-8 (3.50 g, 6.14 mmol) and p-TsOH·H2O (0.06 g, 0.32
mmol) was stirred for 12 h at r.t. The organic phase was separated
and the aqueous phase extracted twice with CH2Cl2. The organic
phases were combined, dried over Na2SO4 and the solvents were re-
moved in vacuo to yield 2.85 g (99%) of aldehyde (pS)-9 as orange
plates.
Mp 149–150 °C; Rf 0.38 (petroleum ether–EtOAc, 4:1); [a]D20 429
(c 0.19, EtOH).
1H NMR (300 MHz, CDCl3): d = 1.75 (s, 15 H, CH3), 3.80 (mc, 1 H,
4-H), 4.29 (t, J = 2.5 Hz, 1 H, 3-H or 5-H), 4.50 (mc, 1 H, 3-H or
5-H), 7.08–7.15 (m, 2 H, Ph), 7.16–7.23 (m, 3 H, Ph), 7.33–7.43 (m,
3 H, Ph), 7.58–7.68 (m, 2 H, Ph), 9.78 (d, J = 2.6 Hz, 1 H, CHO).
13C NMR (75 MHz, CDCl3): d = 11.2 (CH3), 74.4 (C-3 or C-5), 79.2
(C-3 or C-5), 79.4 (C-4), 80.4 (1JC,P = 16.6 Hz, C-1), 83.1 (C-1¢,
C-2¢, C-3¢, C-4¢, C-5¢), 83.4 (2JC,P = 11.1 Hz, C-2), 128.4, 128.5,
128.5, 128.6, 128.6, 129.9, 132.3, 132.6, 136.1, 136.4 (Ph), 136.9
(1JC,P = 11.8 Hz, Ph-Cquart.), 140.5 (1JC,P = 12.5 Hz, Ph-Cquart.), 193.1
(CHO).
31P NMR (121 MHz, CDCl3): d = –28.5.
HRMS: m/z calcd for C28H29OPFe [M+]: 468.1306; found:
1-[(2S,4S)-4-(Methoxymethyl)-1,3-dioxan-2-yl]-1¢,2¢,3¢,4¢,5¢-
pentamethylferrocene [(S,S)-7]
A mixture of crude compound 6 (see above, 10.0 mmol), CSA (0.2
mmol) and freshly distilled diol (S)-4 (1.22 g, 10.2 mmol) was heat-
ed at 100 °C for 4 h. Conversion was monitored by TLC. Volatiles
were removed in vacuo and the residue was purified by column
chromatography (silica gel, petroleum ether–EtOAc–Et3N, 16:4:1)
to yield 3.56 g (92% over 2 steps) of (S,S)-7 as an orange-brown oil.
20
Rf 0.33 (petroleum ether–EtOAc–Et3N, 16:4:1, yellow spot); [a]D
–51.2 (c 0.85, CHCl3).
1H NMR (300 MHz, CDCl3): d = 1.44–1.55 (m, 1 H, 5¢¢-Ha), 1.69–
1.83 (m, 1 H, 5¢¢-Hb), 1.88 (s, 15 H, CH3), 3.41 (s, 3 H, OCH3), 3.41
(dd, J = 10.1, 4.9 Hz, 1 H, CH2OCH3), 3.55 (dd, J = 10.1, 5.9 Hz,
1 H, CH2OCH3), 3.65 (br s, 2 H, 3-H, 4-H), 3.79, 3.83 (2 br s, 2 H,
2-H, 5-H), 3.91 (dt, J = 12.2, 2.6 Hz, 1 H, 6¢¢-Ha), 3.95–4.05 (m,
1 H, 4¢¢-H), 4.21 (dd, J = 11.3, 5.1 Hz, 1 H, 6¢¢-Hb), 5.28 (s, 1 H,
2¢¢-H).
13C NMR (75 MHz, CDCl3): d = 11.4 (CH3), 28.4 (C-5¢¢), 59.7
(OCH3), 66.9 (C-6¢¢), 69.0 (C-3, C-4), 72.6 (C-2, C-5), 76.0
(CH2OCH3), 76.2 (C-4¢¢), 80.8 (C-1¢, C-2¢, C-3¢, C-4¢, C-5¢), 85.3
(C-1), 100.3 (C-2¢¢).
HRMS: m/z calcd for C21H30O3Fe [M+]: 386.1544; found:
386.1553.
468.1324.
Anal. Calcd for C28H29OPFe: C, 71.81; H, 6.24; P, 6.61. Found: C,
71.81; H, 6.18; P, 6.66.
Anal. Calcd for C21H30O3Fe: C, 65.29; H, 7.83. Found: C, 65.53; H,
7.93.
Synthesis 2006, No. 13, 2201–2205 © Thieme Stuttgart · New York

PAPER
Synthesis of (3S)-4-Methoxybutane-1,3-diol and its Use as Chiral Auxiliary
2205
(4) (a) Pawlak, J.; Nakanishi, K.; Iwashita, T.; Borowski, E. J.
Org. Chem. 1987, 52, 2896. (b) Corcoran, R. C.
Acknowledgment
This work was supported by the Fonds der Chemischen Industrie.
We thank R. Haufe and M. Beilmann for experimental assistance
and F. Rominger for the X-ray crystal structure analysis.
Tetrahedron Lett. 1990, 31, 2101. (c) Thiam, M.; Slassi, A.;
Chastrette, F.; Amouroux, R. Synth. Commun. 1992, 22, 83.
(d) Thiam, M.; Chastrette, F. Bull. Soc. Chim. Fr. 1992, 129,
161. (e) Uemura, M.; Daimon, A.; Hayashi, Y. J. Chem.
Soc., Chem. Commun. 1995, 1943.
References
(5) Another crystalline compound is the O-tosyl derivative of
(S,S)-1d: (a) Hungerbühler, E.; Seebach, D.; Wasmuth, D.
Angew. Chem., Int. Ed. Engl. 1979, 18, 958; Angew. Chem.
1979, 91, 1025. (b) Hungerbühler, E.; Seebach, D.;
Wasmuth, D. Helv. Chim. Acta 1981, 64, 1467.
(6) (a) Bildstein, B.; Hradsky, A.; Kopacka, H.; Malleier, R.;
Ongania, K.-H. J. Organomet. Chem. 1997, 540, 127.
(b) Herberich, G. E.; Gaffke, A.; Eckenrath, H. J.
Organometallics 1998, 17, 5931.
(7) Hart, W. P.; Macomber, D. W.; Rausch, M. D. J. Am. Chem.
Soc. 1980, 102, 1196.
(8) (a) Norinder, J.; Cotton, H. K.; Bäckvall, J.-E. J. Org. Chem.
2002, 67, 9096. (b) Geisler, F. M.; Helmchen, G. J. Org.
Chem. 2006, 71, 2486.
(9) Crystal Data for (pS)-9: C28H29FeOP, MW = 468.33,
monoclinic, space group P21/c, a = 9 3345 (1) Å, b = 14
1901 (2) Å, c = 27 7268 (3) Å, b = 98 691 (1)°, V = 3630.45
(8) Å3, Z = 6, Dcalcd = 1.285 g/cm3, crystal size 0.28 × 0.26 ×
0.26 mm3. Intensity data were collected at 200(2) K with
Mo-Ka radiation (l = 0.71073 Å). A total of 16501
independent reflections were measured in range
0.74 < Q < 26.00° and 14474 reflections were considered as
observed applying the condition I > 2s(I). The crystal used
for X-ray diffraction was grown in a solution of CH2Cl2 and
pentane. All calculations were performed using the
SHELXL-97 program. Structure solved by direct methods
and refined against F2 with a Full-matrix least-squares
algorithm. Hydrogen atoms were treated using appropriate
riding models. Flack absolute structure parameter 0.002 (9),
goodness of fit 1.02 for observed reflections, final residual
values R1 (F) = 0.040, wR2 (F2) = 0.096 for observed
reflections, residual electron density –0.47 to 1.13 e Å–3.
CCDC 296455 contains the supplementary crystallographic
data for this structure. The data can be obtained free of
charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or
from the CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK;
fax: +44 1223 336033; email: deposit@ccdc.cam.ac.uk).
(10) Kohl, F. X.; Jutzi, P. J. Organomet. Chem. 1983, 243, 119.
(11) Fischer, E.; Giebe, G. Ber. Dtsch. Chem. Ges. 1897, 30,
3058.
(1) (a) Hayashi, T. In Ferrocenes; Togni, A.; Hayashi, T., Eds.;
VCH: Weinheim, 1995, 105–142. (b) Wagner, G.;
Herrmann, R. In Ferrocenes; Togni, A.; Hayashi, T., Eds.;
VCH: Weinheim, 1995, 173–218. (c) Togni, A. Angew.
Chem., Int. Ed. Engl. 1996, 35, 1475; Angew. Chem. 1996,
108, 1581. (d) Kagan, H. B.; Diter, P.; Gref, A.; Guillaneux,
D.; Masson-Szymczak, A.; Rebiere, F.; Riant, O.; Samuel,
O.; Taudien, S. Pure Appl. Chem. 1996, 68, 29. (e) Togni,
A. Chimia 1996, 50, 86. (f) Togni, A.; Dorta, R.; Köllner,
C.; Pioda, G. Pure Appl. Chem. 1998, 70, 1477.
(g) Richards, C. J.; Locke, A. J. Tetrahedron: Asymmetry
1998, 9, 2377. (h) Togni, A.; Bieler, N.; Burckhardt, U.;
Köllner, C.; Pioda, G.; Schneider, R.; Schnyder, A. Pure
Appl. Chem. 1999, 71, 1531. (i) Sturm, T.; Xiao, L.;
Weissensteiner, W. Chimia 2001, 55, 688. (j) Perseghini,
M.; Togni, A. In Science of Synthesis, Vol. 1; Lautens, M.,
Ed.; Thieme: Stuttgart, 2001, 889–929. (k) Dai, L.-X.; Tu,
T.; You, S.-L.; Deng, W.-P.; Hou, X.-L. Acc. Chem. Res.
2003, 36, 659. (l) Colacot, T. J. Chem. Rev. 2003, 103,
3101. (m) Atkinson, R. C. J.; Gibson, V. C.; Long, N. J.
Chem. Soc. Rev. 2004, 33, 313.
(2) (a) Riant, O.; Samuel, O.; Kagan, H. B. J. Am. Chem. Soc.
1993, 115, 5835. (b) Riant, O.; Samuel, O.; Flessner, T.;
Taudien, S.; Kagan, H. B. J. Org. Chem. 1997, 62, 6733.
(c) Iftime, G.; Daran, J.-C.; Manoury, E.; Balavoine, G. G.
A. J. Organomet. Chem. 1998, 565, 115. (d) Kendall, J. D.;
Woodgate, P. D. Aust. J. Chem. 1998, 51, 1083. (e) Son, S.
U.; Park, K. H.; Lee, S. J.; Chung, Y. K.; Sweigart, D. A.
Chem. Commun. 2001, 1290. (f) Mamane, V.; Fort, Y. J.
Org. Chem. 2005, 70, 8220.
(3) (a) Foster, A. B.; Haines, A. H.; Stacey, M. Tetrahedron
1961, 16, 177. (b) Baggett, N.; Buck, K. W.; Foster, A. B.;
Randall, M. H.; Webber, J. M. J. Chem. Soc. Abstr. 1965,
3394. (c) Mori, K.; Uematsu, T.; Watanabe, H.; Yanagi, K.;
Minobe, M. Tetrahedron Lett. 1984, 25, 3875.
(d) Breuilles, P.; Oddon, G.; Uguen, D. Tetrahedron Lett.
1997, 38, 6607. (e) Toshima, H.; Maru, K.; Saito, M.;
Ichihara, A. Tetrahedron 1999, 55, 5793. (f)Gustafsson,T.;
Schou, M.; Almqvist, F.; Kihlberg, J. J. Org. Chem. 2004,
69, 8694.
Synthesis 2006, No. 13, 2201–2205 © Thieme Stuttgart · New York