Highly regioselective primary etherification of racemic propane-1,2-diol by the tin(II) bromide-catalyzed reaction with diazo[bis(4-methoxyphenyl)]methane and the resolution of enantiomers with the help of Pseudomonas cepacia lipase

Article abstract of DOI:10.1016/j.tetasy.2009.03.003

The tin(II) bromide-catalyzed reaction of diazo[bis(4-methoxyphenyl)]methane with racemic propane-1,2-diol in 1,2-dimethoxymethane resulted in the highly regioselective etherification of the primary hydroxyl group. After tritylation of the minor 2-ether,

Full text of DOI:10.1016/j.tetasy.2009.03.003

Tetrahedron: Asymmetry 20 (2009) 887–891
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Highly regioselective primary etherification of racemic propane-1,2-diol by
the tin(II) bromide-catalyzed reaction with diazo[bis(4-methoxyphenyl)]
methane and the resolution of enantiomers with the help
of Pseudomonas cepacia lipase
*
Sigthor Petursson
Faculty of Business and Science, University of Akureyri, Borgum v/Nordurslod, 600 Akureyri, Iceland
a r t i c l e i n f o
a b s t r a c t
Article history:
The tin(II) bromide-catalyzed reaction of diazo[bis(4-methoxyphenyl)]methane with racemic propane-
1,2-diol in 1,2-dimethoxymethane resulted in the highly regioselective etherification of the primary
hydroxyl group. After tritylation of the minor 2-ether, 1-[bis(4-methoxyphenyl)]methoxypropane-2-ol
was obtained in pure form. The enantiomeric mono-ethers were resolved by kinetic resolution by trans-
acetylation with the help of Pseudomonas cepacia lipase.
Received 4 February 2009
Accepted 4 March 2009
Available online 1 April 2009
This paper is dedicated to Professor George
Fleet, on the occasion of his 65th birthday
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
trans eq–eq pyranose systems as, for example, the 2,3-diol pair
in glucose.8–11 The selectivity of the etherification of diol pairs
The protection of hydroxyl groups in carbohydrates dates back
to the pioneering work of Emil Fischer in the late 19th century
and his use of cyclic acetals.1 Acetals are probably the most
widely used carbohydrate protecting groups, but are limited to
neutral and basic conditions. If acid stability is required, ethers
give the best protection. Benzyl ethers are by far the most com-
mon ethers used in polyol chemistry, but triphenylmethyl (trityl)
ethers have found a use for the selective primary protection of
monosaccharides and in nucleoside chemistry.2–5 More recently
the use of diphenylmethyl (benzhydryl) ethers for the protection
of carbohydrate hydroxyl groups has been explored.6 One of the
advantages of the use of the benzhydryl group is the mild reaction
conditions for its introduction by the use of diazodiphenylme-
thane in refluxing non-protic solvents and removal by catalytic
hydrogenolysis using a palladium catalyst. This has recently been
demonstrated for a series of sugar lactones.7 These reactions take
place via a reactive carbene intermediate, which makes the reac-
tion non-selective and only suitable where peretherification is de-
sired. Methods for the mono-etherification of a vicinal diol pair
were also developed using tin(II) chloride catalysis in 1,2-dime-
thoxyethane. Varied regioselectivities were observed for different
diaryldiazomethanes in reactions with methyl 4,6-O-isopropylid-
in simple
chloride-catalyzed reaction of diazo[bis(4-methylphenyl)]meth-
ane with -erythronolactone which gave a five-fold excess of the
2-ether, that is 2-O-(4,40-dimethylbenzhydryl)-
-erythronolac-
c-lactones has also been demonstrated by the tin(II)
L
L
tone.12 The considerable regioselectivity that has been observed
is an important aspect of the tin(II) chloride diaryldiazomethane
etherification methodology for vicinal diols. Enantiomerically pure
alcohol derivatives of simple alkanes are valuable synthons. Per-
haps the best known group of compounds in this category are
glycerol derivatives, which includes triacylglycerols and phospho-
lipids, both of which are of industrial and biological interest.13–17
Propane-1,2-diol is a bulk chemical with various applications,
such as an antifreeze, an emulsifier, a solvent for food colours
and in deodorant sticks.18 Its enantiomerically pure forms have
interest as chiral synthons. Propane-1,2-diol is also of pharmaceu-
tical and other industrial interest, for example, in the synthesis of
optically active liquid crystals.19–25 Selective protection of the pri-
mary hydroxyl group of racemic propane-1,2-diol would give a
vicinal ether–alcohol systems similar to those resolved by transe-
sterification by the use of lipases in organic solvents.26,27 An ear-
lier investigation of the mono-diarylmethylation methodology is
the benzhydrylation of propane-1,2-diol, which gave a disappoint-
ing 53:47 preference for the primary hydroxyl group.11 It has re-
cently been shown that tin(II) bromide is also a catalyst for the
monoalkylation of vicinal diols with diaryldiazomethanes.28 Here-
in we report the use of tin(II) bromide to catalyze the reaction of
diazo[bis(4-methoxyphenyl)]methane with racemic propane-1,2-
diol to obtain the 1-ether which is then resolved with the help
of the Pseudomonas cepacia lipase.
enes-a-D-mannopyranoside containing an ax–eq vicinal diol.
Interestingly, in the case of the equivalent benzylidene mannopy-
ranoside, the equatorial 3-OH was always favoured. Instability
of the catalyst is sometimes observed, especially in the case of
* Tel.: +354 460 8000; fax: +354 460 8999.
E-mail address: sigthor@unak.is.
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.03.003

888
S. Petursson / Tetrahedron: Asymmetry 20 (2009) 887–891
nylmethyloxypropane formed during the reaction could not be
2. Results and discussion
separated from by-products and was not investigated further.
2.1. Regioselective etherification of propane-1,2-diol
2.2. Kinetic resolution of enantiomers by lipase-catalyzed
transacetylation
The results from the tin(II) chloride-catalyzed reaction of dia-
zodiphenylmethane with racemic propane-1,2-diol predominantly
gave mono-etherification with a slight preferential selectivity for
either hydroxyl group. Based on steric consideration only, one
would predict a preferential reaction of the primary position, how-
ever, based on results for the tin(II) chloride-catalyzed reaction of
diazo(phenyl)methane and diazomethane with glycerol obtained
by Chittenden one might have predict the opposite selectivity.29
Chittenden reacted the two diazo compounds with glycerol in a
mixture of methanol and dichloromethane in the presence of tin(II)
chloride and in both cases isolated only the 2-ether and unreacted
starting material. Earlier work on the reaction of diaryldiazo com-
pounds catalyzed by tin(II) chloride showed that the most reactive
compound (diazo[bis(4-methoxyphenyl)]methane) gave the high-
est selectivity for the less sterically hindered hydroxyl group of a
vicinal diol pair. Preliminary work with the tin(II) bromide catalyst
has also shown that the selectivity for the primary hydroxyl group
increases with increased reactivity of the diazo compound. The
reaction of diazo[bis(4-methoxyphenyl)]methane with propane-
1,2-diol (I) in the presence of tin(II) bromide gave mono-etherifica-
tion in 68% yield. The 1:2-selectivity can be easily monitored by the
integration of the proton-NMR signal for the diarylmethyl proton
(Ar2CH–) which appears around 5.55 ppm, with the signal for the
2-ether always 0.1–0.2 units further downfield. A high selectivity
for the primary position was observed with the 1/2 ratio = 8.3. In
addition to the use of the chemical shift for the ‘benzhydryl’ proton
(Ar2CH-) to distinguish between the 1- and 2-ether, the proton sig-
nal for the free hydroxyl group also shows whether the alcohol is
primary or secondary. Thus, the signal for the secondary –OH of
the major 1-ether (II) appears as a doublet with JOH,H2 2.53 Hz,
whereas the signal for the primary –OH of the minor 2-ether (III)
appears as a triplet with JOH,H1 5.56 Hz. A confirmation of these
assignments was obtained by the removal of the minor 2-ether
on tritylation and subsequent enantiomeric enzymatic acetylation
which gave the 2-acetate as shown by the shift of the multiplet 2-
CH signal from 3.94 ppm for the free alcohol to 5.12 ppm for the
acetate. The reaction is shown in Scheme 1.
Lipases, for example, from P. cepacia and Candida antarctica,
have proven very effective for the kinetic resolution of propane-
1,2-diol derivatives.26,27 The enzyme used for the resolution of
the racemic 1-[bis(4-methoxyphenyl)]methoxypropane-2-ol by
transacetylation from vinyl acetate was the P. cepacia lipase immo-
bilized on ceramic particles. The reaction was carried out on a
0.5 mmol scale using di-isopropyl ether as a solvent and 10 mg
of the immobilized enzyme. The reaction was monitored by HPLC
with UV detection at 254 nm. Samples were extracted at regular
intervals and were quenched in a tenfold volume of acetonitrile be-
fore injecting 0.010 mL into the HPLC instrument. The results are
shown in Table 1.
The formation of the acetylated product is shown in Figure 1a as
an integration area of the product peak as a percentage of the total
integrated area for both starting material and product. It is clear
from this plot that the reacting enantiomer is virtually exhausted
after about 12 h under the reaction conditions used the first-order
rate plot (ln(%REM) vs time, REM = reacting enantiomer) shows this
more accurately. The reaction was, however, left to proceed for
19 h. The magnitude of the first-order rate constant (0.317 hꢀ1) is
related to the amount of enzyme present. The rate is first order with
respect to the reacting enantiomer; for a fixed amount of enzyme
used, the reaction appears first order overall. It is pseudo first order.
Based on earlier results with lipase-catalyzed transesterifica-
tion, it is the (R)-enantiomer which reacts according to the Kazl-
auskas rule.26,27,30 It is therefore proposed that the reaction
which takes place is the one shown in Scheme 2. This was con-
firmed by the removal of the 4,40-dimethoxybenzhydryl ether by
catalytic hydrogenation in the case of the alcohol (IV) and catalytic
hydrogenation followed by Zemplen deacetylation in the case of
the acetate (V), giving in both cases the free diol. The 1H and 13C
NMR in D2O were in both cases identical to authentic racemic pro-
pane-1,2-diol. The specific rotation of free diol [(S)-propane-1,2-
Table 1
The racemic mono-ether products turned out to be chromato-
graphically indistinguishable on silica gel and it was impossible
to separate them. To obtain the pure 1-ether, it was decided to re-
act the mixture (II and III) with triphenylmethyl chloride in the
hope that an insignificant amount of the 1-ether (II) would react,
but the 2-ether (III) would react to completion, making the chro-
matographic purification of the 1-ether possible. This reaction gave
the pure unreacted 4,40-dimethoxybenzhydryl 1-ether in 76%, yield
after chromatography, based on the total amount of the 1- and
2-ether. The minor 2-(4,40-dimethoxybenzhydryloxy)-1-triphe-
HPLC monitoring of the lipase-catalyzed transacetylation from vinyl acetate to 1-
[bis(4-methoxyphenyl)]methoxypropane-2-ol
Day Time
Reaction time (h) % A, reacting enantiomer (REM) ln (% AREM
0
)
1
2
13:30
14:45
15:30
18:00
22:30
0.75
2
4.5
9
39.2
26.8
11.3
2.9
3.67
3.29
2.42
1.06
07:30
19
1.1
0.0517
N2
SnBr2
CH3
CH3
R
CH3
+
+
C
1,2-Dimethoxy-
ethane
OH
R
OH
I
R
R
O
OH
O
OH
C
R
C
H
R
H
III
II
R = p-CH3OC6H4
8.3
:
1
Scheme 1. Mono-etherification of a propane-1,2-diol by the tin(II) bromide-catalyzed reaction with diazo[bis(4-methoxyphenyl)]methane.

S. Petursson / Tetrahedron: Asymmetry 20 (2009) 887–891
889
Figure 1. (a) Percentage product formed during transesterification (% product of total integration for starting material + product). (b) First order rate plot ꢀ ln(% reacting
enantiomer) versus time.
CH3
CH3
CH3
Lipase
Pseudomonas
cepacia
O
O
C
H
CH2
O
+
+
O
O
OH
OH
O
C
RCHR
RCHR
RCHR
O
C
CH3
CH3
(i-Pr)2O
II
R = p-CH3OC6H4
V
IV
(R)-1-[bis(4-Methoxy-
phenyl)]methoxy-
2-actoxypropane
(S)-1-[bis(4-Methoxy-
phenyl)]methoxy-
propan-2-ol
Scheme 2. Kinetic resolution of the racemic 1-[bis(4-methoxyphenyl)]methoxypropane-2-ol by transacetylation from vinyl acetate using Pseudomonas cepacia lipase as
catalyst.
diol] from IV was ½a D20
ꢁ
¼ þ29 (c 1.1, CHCl3). Lit. ½a D20
¼ þ16:6
ꢁ
4. Experimental
4.1. General
(neat).33 The optical rotation of the free diol from V [(R)-pro-
pane-1,2-diol] was ½a D20
ꢁ
¼ ꢀ28 (c 0.34, CHCl3). Lit. ½a D20
¼ ꢀ16:5
ꢁ
(neat).34 The –OH signal in the proton NMR which appears as a
doublet at 2.35 ppm with a coupling constant to the single proton
on the 2-carbon (JOH,H2 2.53 Hz) strongly indicates that the tin(II)
bromide-catalyzed etherification gave the 1-ether (rac-1-[bis(4-
methoxyphenyl)]methoxypropane-2-ol) as a major product. This
was further supported by the triphenylmethylation and confirmed
with the formation of the 2-acetate in the lipase-catalyzed acetyla-
tion when the 2-CH multiplet signal is shifted downfield from 3.94
to 5.12 ppm. Further confirmation of this was obtained when the
Mosher ester of the unreacted alcohol was prepared and this signal
was shifted still further downfield to 5.36 ppm. The results from
the determination of the specific rotations of the fully deprotected
propanediols show a complete or at least a very high degree of
enantiomeric discrimination by the enzyme. Preliminary analysis
of one of the enantiomers, (S)-1-[bis(4-methoxy-phenyl)]methoxy-
propan-2-ol, by the preparation of a Mosher ester [(R)-3,3,3-tri-
Thin layer chromatography (TLC) was carried out on aluminium
sheets coated with silica gel 60-F254 and detected using a spray of
0.2% w/v cerium(IV) sulfate and 5% ammonium molybdate in 2 M
sulfuric acid with heating. 1H and 13C NMR spectra were run on a
Bruker AV400 instrument with Me4Si as the external standard.
Diaryldiazomethanes were prepared using published methods.8
General reagents and the catalyst were obtained from chemical
suppliers and usually used without further purification. 1,2-Dime-
thoxyethane was distiled from and stored over sodium. Ethyl ace-
tate and hexane were of HPLC grade and used as received. The
enzyme used was Fluka P. cepacia lipase immobilized on ceramic
particles supplied by Sigma/Aldrich. High resolution mass spectra
(HRMS) were recorded on a VG Autospec mass spectrometer using
chemical ionization. The HPLC instrument was Shimadzu Promi-
nence with a reversed phase 150 ꢂ 4.6 mm SS Wakosil C18RS
3 mm column. The elution was isocratic with acetonitrile/water
4:1 and detection was done with a UV detector at 254 nm.
fluoro-2-methoxy-2-phenylpropanoyl ester] has confirmed
a
complete acetylation of the (R)-enantiomer. The work on the acet-
ylated enantiomer is not complete and further results will be pub-
lished later.
4.2. rac-1-[Bis(4-methoxyphenyl)]methoxypropane-2-ol (major)
and rac-2-[bis(4-methoxyphenyl)]methoxypropane-1-ol (minor)
3. Conclusions
Racemic propane-1,2-diol (304 mg, 4,00 mmol) and diazo[-
bis(4-methoxyphenyl)]methane (2,05 g, 8,00 mmol) were dis-
solved in 1,2-dimethoxyethane (DME) (25 mL) and cooled on ice.
Tin(II) bromide (20 mg, 0.072 mmol) was dissolved in DME
(5 mL) and added to the reaction mixture. The purple colour of
the diazo compound had disappeared after about 20 min. TLC (hex-
In conclusion it can be stated that tin(II) bromide is an effective
catalyst for the monoalkylation of vicinal diol pairs. The little used
and highly reactive diazo[bis(4-methoxyphenyl)]methane has pro-
ven to be a useful reagent, which gives excellent regioselectivity
for the primary hydroxyl group in the sterically simple and non-
crowded propane-1,2-diol system. The stereospecificity of the P.
cepacia lipase for the (R)-enantiomer of propane-1,2-diol with the
bulky 4,40-dimethoxybenzhydryl ether on the primary oxygen
has been shown to be excellent.
ane/EtOAc 1:1) showed a complete reaction of the diol (Rf
0.7) and
the product as a deep red spot with the cerium molybdate spray (Rf
0.43). The product was purified on a column of silica gel (Hex/
EtOAc 4:1–3:2) to give a non-crystalline oily mixture. This is a

890
S. Petursson / Tetrahedron: Asymmetry 20 (2009) 887–891
8.3:1 inseparable mixture of the title compounds (823 mg, 68%);
1H NMR (400 MHz, CDCl3). dH 1.057 (3H d, JH3,H2 6.32 Hz, CH3 for
1-ether), 1.057 (3H d, JH3,H2 6.06 Hz, CH3 for 2-ether), 1,84 (1H t,
JOH,H1 5.56 Hz (OH for 2-ether), 2.351 (1H d, JOH,H2 2.53 Hz (OH
for 1-ether) 3.178 (1H, dd, JAB 9.60 Hz, JH1,H2 7.83 Hz, H-1A), 3.349
(1H, dd, JBA 9.35 Hz, JH1,H2 3.03 Hz, H-1B for 1-ether), 3.44, 3.52,
3.60 (3 ꢂ 1H multiplets, geminal H1’s and H-2 for 2-ether), 3.71
(7H s, 2 ꢂ OCH3 for 1 and 2 ethers), 3.94 (1H m, H-2 for 1-ether),
5.24 (1H s, Ar2CH for 1-ether, relative integration 10,0), 5.39 (1H
s, Ar2CH for 2-ether, relative integration 1.2), 6.79 (4H m, 2 ꢂ aro-
matic meta H), 7.17 (4H m, 2 ꢂ aromatic ortho H); 13C NMR
(100 MHz, CDCl3) dC 16.17, 18.7 (C-3 2-ether, C-3 1-ether), 55.29
(OCH3 1- and 2-ether), 66.56, 66.77 (C-2 2-ether, C-2 1-ether),
73.23, 74.61 (C-1 2-ether, C-1 1-ether), 80.67, 83.42 (Ar2CH 2-
ether, Ar2CH 1-ether), 100, 113 (aromatic C-2 and 6 2-ether, aro-
matic C-2 and 6 1-ether), 128 (aromatic C-3 and 5), 134 (aromatic
C-1), 159 (aromatic C-4). Anal. Calcd for C18H22O4: C, 71.50; H,
7.33; O, 21.17. Found: C, 71.10; H, 7.61. HRMS, C18H22NaO4 re-
quires: 325.1410. Found 325.1408 (M+Na+).
alcohol is (S)-1-[bis(4-methoxyphenyl)]methoxypropan-2-ol, Rf
0.1. The two compounds were separated on a column of silica gel
using Hex/EtOAc 4:1–3:2 as eluent. Fractions 6–10 gave the ace-
tate as an oil, 180 mg, 37% yield or 74% based on the reacting enan-
tiomer. Fractions 18–19 gave the unreacted alcohol, 140 mg, 33%
or 66% based on the non-reacting enantiomer. NMR for (R)-1-
[bis(4-methoxyphenyl)]methoxy-2-acetoxypropane
1H
NMR
(400 MHz, CDCl3). dH 1.25 (3H d, JH3,H2 6.57 Hz, CH3), 2.03 (3H s,
acetate CH3), 3.44 (2H ABM octet, JAB 10.36, JA,H2 4.55, JBA 10.10,
JB,H2 6.06 Hz, gem H1’s), 3.78 (6H s, 2 ꢂ OCH3), 5.12 (1H m, H2),
5.29 (1H s, Ar2CH), 6.84 (4H d, Jm,o 8.84 Hz, 2 ꢂ aromatic meta H),
7.22 (4H d, Jo,m 8.84 Hz, 2 ꢂ aromatic ortho H); 13C NMR
(100 MHz, CDCl3) dC 16.90, (C-3), 21.34, (C-3), 55.27 (OCH3),
69.63, (C-2), 71.01 (C-1), 82.91 (Ar2CH), 113.7 (aromatic C-2 and
6), 128.2 (aromatic C-3 and 5), 134.5 (aromatic C-1), 158.9 (aro-
matic C-4), 170.6 (C@O). NMR for (S)-1-[bis(4-methoxy-
phenyl)]methoxypropan-2-ol 1H NMR (400 MHz, CDCl3). dH 1.06
(3H d, JH3,H2 6.57 Hz, CH3), 2.44 (1H s, –OH), 3.35 (2H ABX octet,
JAB 9.35, JA,H2 8.08, JBA 9.35, JB,H2 3.28 Hz, gem H1’s), 3.80 (6H s,
2 ꢂ OCH3), 4.03 (1H m, H2), 5.33 (1H s, Ar2CH), 6.87 (4H d, Jm,o
8.59 Hz, 2 ꢂ aromatic meta H), 7.25 (4H d, Jo,m 9.35 Hz, 2 ꢂ aro-
matic ortho H); 13C NMR (100 MHz, CDCl3) dC 18.70, (C-3), 55.28
(OCH3), 66.71, (C-2), 74.57 (C-1), 83.28 (Ar2CH), 113.8 (aromatic
C-2 and 6), 128.2 (aromatic C-3 and 5), 134.4 (aromatic C-1),
159.0 (aromatic C-4).
4.3. Triphenylmethylation of rac-1-[bis(4-Methoxyphenyl)]meth-
oxypropane-2-ol (major) and rac-2-[bis(4-methoxyphenyl)]-
methoxypropane-1-ol (minor) mixture and the isolation of rac-
1-[bis(4-methoxyphenyl)]methoxypropane-2-ol
The title mixture (703 mg, 2.32 mmol) was dissolved in dichlo-
romethane (10 mL) after which triethylamine (71 mg, 0.098 mL,
0.70 mmol) and dimethylaminopyridine (2.3 mg, 0.019 mmol)
were added followed by triphenylmethyl chloride (144 mg,
0.52 mmol). The reaction was left at RT overnight when TLC
(Hex/EtOAc, 4:1) showed a new ether product at Rf 0.63 with yel-
low by-products and the main unreacted rac-1-[bis(4-methoxy-
phenyl)]methoxypropane-2-ol (Rf 0.63, 0.21). The reaction was
quenched by washing with 20 mL of 5% ammonium chloride solu-
tion. The layers were separated and the aqueous layer was ex-
tracted with more dichloromethane (20 mL). The mixture was
purified on a column of silica gel eluting with Hex/EtOAc 9:1–
3:2. The faster ether component could not be separated from
by-products but the compound of interest, rac-1-[bis(4-methoxy-
phenyl)]methoxypropane-2-ol, was isolated as a pure oil, 536 mg,
76%. 1H NMR (400 MHz, CDCl3). dH 1.057 (3H d, JH3,H2 6.32 Hz,
CH3), 2.351 (1H d, JOH,H2 2.53 Hz (OH), 3.178 (1H, dd, JAB
9.60 Hz, JH1,H2 7.83 Hz, H-1A), 3.349 (1H, dd, JBA 9.35 Hz, JH1,H2
3.03 Hz, H-1B), 3.71 (6H s, 2 ꢂ OCH3), 3.94 (1H m, H-2), 5.24
(1H s, Ar2CH), 6.79 (4H m, 2 ꢂ aromatic meta H), 7.17 (4H m,
2 ꢂ aromatic ortho H); 13C NMR (100 MHz, CDCl3) dC, 18.7 (C-3),
55.29 (OCH3), 66.77 (C-2), 74.61 (C-1), 83.42 (Ar2CH), 113 (aro-
matic C-2 and 6), 128 (aromatic C-3 and 5), 134 (aromatic C-1),
159 (aromatic C-4).
4.5. Deprotection of S-1-[bis(4-methoxyphenyl)]methoxy-
propan-2-ol
The title compound (186 mg, 0.62 mmol) was dissolved in
methanol (8 mL) after which 10% palladium on charcoal (20 mg)
and a magnetic stirring bar were added. The flask was fitted via
a three-way tap containing a hydrogen balloon on the closed
arm. The system was evacuated before opening the reaction flask
to the hydrogen. The reaction mixture was then magnetically stir-
red. After about 2 h, TLC (EtOAc) showed a complete reaction of
the starting material (Rf 0.78) and the free alcohol product (Rf
0.26). The bis(4-methoxyphenyl)methane byproduct was also vis-
ible at Rf 0.82 but was not investigated further. The product was
purified on a column of silica gel eluting with ether/methanol
9:1. After evaporation of the solvent from the product containing
fraction the yield of (S)-propane-1,2-diol was 6.0 mg, 13%. 1H
NMR (400 MHz, D2O). dH 1.05 (3H d, JH3,H2 6.57 Hz, CH3), 3.35
(1H dd, JAB 11.62, JH1A,H2 6.57 Hz, A part of H1 ABX octet), 3.45
(1H dd, JBA 11.37, JH1B,H2 4.30 Hz, B part of H1 ABX octet), 3.79
(1H ten peak m, JH2,H3 and JH2,H1A 6.57, JH2,H1B 4.04 Hz, H2; 13C
NMR (100 MHz, CDCl3) dC 17.93, (C-3), 66.56, (C-2), 67.89 (C-1).
½
a 2D0
a 2D0
ꢁ
¼ þ29 (c 1.1, CHCl3). Lit.31
¼ þ16:6 (neat)
½
a 2D0
ꢁ
¼ þ22 (CHCl3). Lit.33
½
ꢁ
4.4. Enantiospecific acetylation of rac-1-[bis(4-methoxyphenyl)]-
4.6. Deprotection of (R)-1-[bis(4-methoxyphenyl)]methoxy-2-
methoxypropane-2-ol
acetoxypropane
The racemic title compound (428 mg, 1.42 mmol) was dissolved
in di-isopropyl ether (10 mL). Vinyl acetate (147 mg, 0.155 mL,
1.70 mmol) was added, followed by the immobilized enzyme
(40 mg). The mixture was stirred gently at rt using a magnetic stir-
rer. The reaction was monitored by periodically stopping the stir-
The title compound (200 mg, 0.58 mmol) was dissolved in dry
methanol (6 mL) after which 10% palladium on charcoal (20 mg)
and a magnetic stirring bar were added. The hydrogen was intro-
duced as described above and the reaction stirred magnetically.
The reaction was monitored by TLC and went to completion after
24 h. Sodium methoxide (3 mg, 0.06 mmol) in dry methanol
(1 mL) was added and the reaction left for 2 h after which TLC
showed the reaction to be complete. The base was neutralized with
a strong cation exchange resin and purified as described above, to
give the (R)-propane-1,2-diol, 8.5 mg, 19%. This compound had
ring and extracting 20
lL of the clear reaction solution and
injecting into 180 L of acetonitrile. Ten microlitres of this diluted
l
solution were then injected into the HPLC instrument (see discus-
sion). The reaction was stopped after 19 h by removing the enzyme
by filtration and rinsing the reaction vessel and filtered by dichlo-
romethane. Two components were visible on TLC (Hex/EtOAc 4:1).
The faster acetylated enantiomer is (R)-1-[bis(4-methoxy-
phenyl)]methoxy-2-acetoxypropane, Rf 0.3, and the unreacted
identical 1H and 13C NMR to the (S)-enantiomer. ½a 2D0
ꢁ
¼ ꢀ28
(c 0.34, CHCl3). Lit.32
½
a 2D4:4
ꢁ
¼ ꢀ28:6 (CHCl3). Lit.34
½ ꢁ
a 2D0
¼ ꢀ16:5
(neat).

S. Petursson / Tetrahedron: Asymmetry 20 (2009) 887–891
10. Petursson, S. Carbohydr. Res. 2003, 338/9, 963–968.
891
4.7. NMR spectra of rac-propane-1,2-diol
11. Petursson, S. Ethers as Protecting Groups Product Class 8, in Science of
Synthesis, Houben–Weyl Methods of Molecular Transformations. In Ethers;
Forsyth, C. J. Ed.; Stuttgart, 2008; Vol. 37.
12. Petursson, S.; Jenkinson, S. F.; Booth, K. V.; Weymouth-Wilson, A. C.; Watkin, D.
J.; Fleet, G. W. J.; Best, D. Acta Crystallogr., Sect. E 2007, 63, o4121.
13. Halldorsson, A.; Thordarson, B.; Magnusson, C. D.; Haraldsson, G. G.
Tetrahedron: Asymmetry 2004, 15, 2893–2899.
An authentic sample of rac-propane-1,2-diol further purified by
distillation under reduced pressure was submitted for 1H and 13C
NMR. This sample had identical spectra to the two enantiomers re-
ported above.
14. Haraldsson, G. G.; Hjaltason, B. Fish Oils as Sources of Important
Polyunsaturated Fatty Acids. In Structured and Modified Lipids; Gunstone, F.
D., Ed.; Marcel Dekker: NY and Base, 2001.
Acknowledgments
15. Urata, K.; Takaishi, N. J. Am. Oil Chem. Soc. 1996, 73, 819–830.
16. Bittman, R. Chem. Phys. Lipids 2004, 129, 111–131.
The University of Akureyri is thanked for financial support. Pro-
fessor George Fleet and Dr. Sarah F. Jenkinson at the Organic Chem-
istry Laboratory, University of Oxford, are thanked for elemental
and mass spectral analysis. Dr. Sigríður Jónsdóttir, Professor
Guðmundur G. Haraldsson and Rakel Sꢀmundsdóttir at the Sci-
ence Institute, University of Iceland, are thanked for helpful discus-
sions and NMR and optical rotation analysis.
17. Guivisdalsky, P. N.; Bittman, R. J. Org. Chem. 1989, 54, 4637–4642.
18. Wikipedia, http://en.wikipedia.org/wiki/1%2C2-propanediol.
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