Baker's yeast mediated stereoselective biotransformation of 1-acetoxy-3-aryloxypropan-2-ones

Article abstract of DOI:10.1016/S0957-4166(97)00626-5

A series of 1-acetoxy-3-aryloxypropan-2-ones 1a-m were synthesized and subjected to biotransformation by baker's yeast yielding optically active monoacetates 5 or ent-5 and/or diols 4 of moderate to excellent enantiomeric purity. The dependence of the reduction/hydrolysis ratio and stereoselectivity on the size and substitution pattern of the aromatic moiety in the substrate is also discussed.

Full text of DOI:10.1016/S0957-4166(97)00626-5

Pergamon
Tetrahedron: Asymmetry 9 (1998) 271–283
Baker’s yeast mediated stereoselective biotransformation of
1-acetoxy-3-aryloxypropan-2-ones
Gabriella Egri,a Attila Kolbert,a,b József Bálint,a Elemér Fogassy,a Lajos Novák b and
László Poppe c,∗
aDepartment of Organic Chemical Technology, Technical University Budapest, H-1521 Budapest, PO Box 91, Hungary
bInstitute for Organic Chemistry, Technical University Budapest, H-1521 Budapest, PO Box 91, Hungary
cCentral Research Institute for Chemistry, Hungarian Academy of Sciences, H-1525 Budapest, PO Box 17, Hungary
Received 12 November 1997; accepted 8 December 1997
Abstract
A series of 1-acetoxy-3-aryloxypropan-2-ones 1a–m were synthesized and subjected to biotransformation by
baker’s yeast yielding optically active monoacetates 5 or ent-5 and/or diols 4 of moderate to excellent enantiomeric
purity. The dependence of the reduction/hydrolysis ratio and stereoselectivity on the size and substitution pattern
of the aromatic moiety in the substrate is also discussed. © 1998 Elsevier Science Ltd. All rights reserved.
3-Aryloxypropane-1,2-diols 4a–m in enantiomerically pure form are versatile compounds of interest
as intermediates in syntheses of pharmaceuticals such as β-receptor blockers, or as chiral fragments in
optically active crown ethers. Lipase catalyzed acylation has proved to be a useful tool for enantiomer
separation of racemic 3-aryloxypropane-1,2-diol derivatives.1,2 This kinetic resolution using lipase
catalyzed sequential transesterification was found to be highly enantiomer selective for diols having
m- or p-substituted aromatic moieties, whereas the most sterically hindered o-substituted derivatives
showed decreased enantiomer selectivity or were not accepted as substrates. Without racemization of the
remaining enantiomer, however, even highly enantiomer selective processes can provide only 50% of the
starting racemate in optically active form.
Alternatively, an enantiotope selective method, such as reduction of a prochiral ketone, might yield
an optically active product quantitatively. Since acetoxymethyl ketones with phenyl,3 benzyloxymethyl,4
or azidomethyl5 moieties resulted in the corresponding monoacetates of high enantiomeric purity by
reduction with baker’s yeast, it seemed worthwhile to investigate the analogous biotransformation of 3-
aryloxy-1-acetoxypropan-2-ones 1a–m. Here we report our results on the preparation and baker’s yeast
mediated stereoselective biotransformation of these ketones.
The 3-aryloxy-1-acetoxypropan-2-ones 1a–m were prepared by alkylation of the corresponding
phenols (3a–m) with racemic 3-chloropropane-1,2-diol rac-2, followed by acetylation of the primary
∗
Corresponding author. E-mail: poppe.szk@chem.bme.hu
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(97)00626-5

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Table 1
Preparation of 3-aryloxy-1-acetoxypropan-2-ones (1a–m)
hydroxyl moiety of the resulting diols (rac-4a–m) and Swern-oxidation of the monoacetates rac-5a–m
(Table 1).
Having the desired ketones in hand, the effect of the reaction conditions on enantiotope selectivity of
the baker’s yeast reduction of 1-acetoxy-3-phenoxypropan-2-one 1a was investigated (Table 2). Under
various conditions, the reaction yielded the expected optically active monoacetate 5a without noticeable
hydrolysis, in accordance with the results of the analogous baker’s yeast reductions.3–5
In baker’s yeast mediated enantiotope selective reduction of carbonyl compounds there may be two
factors responsible for the incomplete stereoselectivity. Firstly, it may be due to participation of more
than one reductase enzyme with different kinetic parameters and eventually opposite selectivity,6–8 or
secondly, the process may be catalyzed by a single enzyme but with incomplete selectivity.9 In the
majority of cases, it turned out that competing enzymes of opposite selectivity was the factor responsible
for poor selectivity. Since the kinetic behavior of these competing enzymes is different, the selectivity
may be controlled by the reaction conditions. The most frequently used modifications for influencing
the selectivity are e.g.: modification of pH;10,11 application of lyophilized yeast instead of the row cake
form;12,13 use of various additives such as metal salts;14 allylic alcohol or α,β-unsaturated carbonyl
compounds;12,15 ethyl chloroacetate and similar compounds.16 In Table 2 the effect of these factors on
the enantiotope selectivity is shown. The reaction performed by wet caked baker’s yeast at pH 7 (entry 2)
provided the best selectivity. This selectivity remained practically unaltered at pH 8, or by adding some
salts or allylic alcohol (entries 3 and 5–7). On the other hand, decreased selectivity was observed in the

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273
Table 2
Effect of the reaction conditions on the selectivity of reduction of the 1-acetoxy-3-phenoxypropan-2-
one 1a
non-buffered reaction (entry 1), by using lyophilized yeast (entry 4) or by adding ethyl chloroacetate
(entry 8).
Hence, baker’s yeast mediated biotransformations of further 1-acetoxy-3-aryloxypropan-2-ones 1a–k
were performed under the conditions which gave the best selectivity with the unsubstituted phenoxy
derivative 1a. The results of these reactions are summarized in Table 3.
Surprisingly, only the unsubstituted phenoxy-derivative 1a was reduced without noticeable amounts of
hydrolysis. The 2-naphthyloxy-derivative 1b was not reduced at all, and all the other ketones 1c–m were
transformed not only into the corresponding monoacetates 5 or ent-5 but partially or even fully into the
corresponding diols 4 indicating the enzyme action of some hydrolases beside oxidoreductases in these
reactions. The differences between the enantiomeric purities or even the configuration of the produced
monoacetates 5 or ent-5 and diols 4 imply that in these reactions more than one type of selectivity may
be decisive. Analysis of the possible pathways and selectivities is shown in Fig. 1.
The original enantiomeric composition of the monoacetate fraction 5 versus ent-5 is determined by the
enantiotope selectivity of the direct reduction (k1,R versus k1,ent-R). The formation of the diol fraction
4 and ent-4 may proceed via two alternative routes. The first possible way is the hydrolysis of the
monoacetate fraction (5 and ent-5) by which the original enantiomeric composition may be altered by
the enantiomer selectivity (k2,H versus k2,ent-H) of the hydrolysis. The second alternative way to diols
4 and ent-4 is the non-stereoselective hydrolysis (k1,H) of the achiral acetoxy ketone 1 followed by an
enantiotope selective reduction (k2,R versus k2,ent-R) of the forming hydroxy ketone 6.
The reactions of the 1-acetoxy-3-aryloxypropan-2-ones 1a–m (Table 3) in buffered (pH 7) media with
fermenting baker’s yeast resulted, with the exception of the 2-isopropyloxyphenoxy compound 1d, (S)-
monoacetates 5a,f–j,l,m and/or of the (R)-diols 4b,d–m indicating the same geometric preference for
both products. In the case of the sterically most demanding 1-naphthyl 1b or phenyl derivatives with
at least one substituent in the o-position 1d,e,h,l,m, the formation of the diol 4d,e,h,l,m of high (>90%

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Table 3
Baker’s yeast mediated biotransformation of 1-acetoxy-3-aryloxypropan-2-ones (1a–k)a
Fig. 1. Baker’s yeast mediated reaction of 1-acetoxy-3-aryloxypropan-2-ones 1a–m

G. Egri et al. / Tetrahedron: Asymmetry 9 (1998) 271–283
275
e.e.) enantiomeric purity is common. The reaction of ketone with the more bulky m-nitrophenyl moiety
1k proceeded also with high selectivity, while the compounds with smaller m-substitutents of the phenyl
moiety 1f,i were transformed with less remarkable stereoselectivities. The lowest selectivities were found
in the reactions of the compounds with p-substituted phenyl rings 1g,j. In three cases, the diol 4b,e,k was
the sole product, while in the other reactions, both the non-hydrolyzed monoacetate ent-5d, 5f–j,l,m
and the diol 4d,f–j,l,m were obtained with variable enantiomeric compositions. These results might
be best interpreted by assuming first a fast enantiotope selective reduction of the acetoxy ketones 1
with variable degree of (S)-enantiomer preference (k1,R>k1,ent-R), followed by an enantiomer selective
hydrolysis (k2,H>k2,ent-H) with preference towards the (R)-diols 4.18 By this assumption, formation of the
(R)-monoacetate ent-5d of low enantiomeric excess can also be interpreted without assuming the unlikely
configuration-preference change of the reduction within the series of acetoxy ketones 1. Accordingly,
this reaction may be the result of the reduction of the acetoxy ketone 1d with moderate (S)-enantiotope
selectivity followed by hydrolysis with high enantiomer selectivity towards the (R)-diol 4d, leaving the
non-hydrolyzed (R)-monoacetate ent-5d in excess in the remaining monoacetate fraction.
In conclusion, baker’s yeast mediated reaction of the 1-acetoxy-3-aryloxypropan-2-ones 1a–m proved
to be a useful method for the preparation of optically active 3-aryloxypropan-1,2-diol derivatives. This
transformation showed high selectivities with the ketones of sterically hindered aryl moieties, while lower
selectivities were found for the less hindered ketones with m- or p-substituted phenyl moieties. Since the
opposite tendency (i.e. higher selectivity for the less hindered compounds) was found by the lipase-
catalyzed enantiomer selective acylation processes of the similar 3-aryloxypropan-1,2-diol derivatives,
the present baker’s yeast mediated method seems to be useful for preparing such diols bearing a sterically
hindered aryl moiety.
1. Experimental
1
1
The H NMR spectra were recorded on a Bruker AW-250 spectrometer operating at 250 MHz. H
NMR spectra for enantiomeric excess determinations were recorded at 500 MHz on a Bruker DRX-
500 spectrometer. All spectra were taken in CDCl3 solution and chemical shift values are expressed
in ppm values from TMS as internal standard on δ scale. IR spectra of thin film samples were
taken on a Specord 2000 spectrometer. Optical rotations were determined on a Perkin–Elmer 241
polarimeter. Thin layer chromatography was carried out using Merck Kieselgel 60 F254 alumina sheets
applying hexane:acetone=10:4 (A) or chloroform:methanol=10:0.5 (B) mixtures for elution. Spots were
visualized by treatment with 5% ethanolic phosphomolybdic acid solution and heating of the dried plates.
Preparative chromatographic separations were performed using vacuum-chromatography19 on Merck
Kieselgel 60 (0.063–0.200 mm). Phenols, racemic 3-chloropropane-1,2-diol and acetic anhydride were
products of FLUKA or Aldrich. All solvents used were freshly distilled. Wet cake or lyophilized form of
baker’s yeast were from a local store.
1.1. Preparation of 3-aryloxypropane-1,2-diols rac-4a–m
To the solution of the phenol derivative 3a–m, 0.1 mol in ethanol (60 ml) a solution of NaOH (5.0 g,
0.125 mol) in water (20 ml) was added and the resulting mixture was heated under reflux for 10 minutes.
Then a solution of racemic 3-chloropropane-1,2-diol rac-2, 13.3 g, 0.12 mol in ethanol (10 ml) was
added within 5 minutes and the mixture was further heated under reflux for between 1 and 2 hours (the
progress of the reaction was monitored by TLC; solvent A). After cooling, the volume of the resulting

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mixture was reduced to about one third by a rotary evaporator followed by addition of water (60 ml)
and extraction with diethyl ether (2×75 ml). The combined organic layers were dried over Na2SO4 and
the solvent was removed. The resulting diols 4a–m were usually purified by recrystallization from a 1:1
mixture of hexane and diethyl ether. For yields, see Table 1.
1.1.1. rac-3-Phenoxypropane-1,2-diol rac-4a
1H NMR: 3.65–3.85 (m, 2H, CH2–OH), 4.0 (m, 1H, CH), 4.10–4.22 (m, 2H, ArO–CH2), 6.84–7.25
(m, 5H, ArH). IR: 3450 (br), 2910, 1600, 1590, 1500, 1460, 1170, 1120, 1060, 1050, 880, 750, 690 cm−1
Calcd for C9H12O3: C 64.27, H 7.19. Found: C 64.46, H 7.17.
.
1.1.2. rac-3-(1-Naphthyloxy)propane-1,2-diol rac-4b
1H NMR: 3.86 (m, 2H, CH2), 4.02–4.14 (m, 3H, CH and ArO–CH2), 6.75–8.24 (m, 7H, ArH). IR:
3290 (br), 2940, 1730, 1580, 1510, 1470, 1390, 1270, 1240, 1130, 1110, 1040, 990, 890, 790, 770 cm−1.
Calcd for C13H14O3: C 71.54, H 6.47. Found: C 71.68, H 6.46.
1.1.3. rac-3-(2-Naphthyloxy)propane-1,2-diol rac-4c
1H NMR: 3.77 (m, 2H, CH2–OH), 3.92 (m, 1H, CH), 4.07–4.26 (m, 2H, ArO–CH2), 7.09–7.73 (m,
7H, ArH). IR: 3400 (br), 2940, 1630, 1600, 1510, 1460, 1260, 1220, 1180, 1060, 1000, 840, 740 cm−1
Calcd for C13H14O3: C 71.54, H 6.47. Found: C 71.25, H 6.50.
.
1.1.4. rac-3-(2-Isopropylphenoxy)propane-1,2-diol rac-4d
1H NMR: 1.24 (d, 6H, 2CH3), 3.16, (m, 1H, CH–Ar), 3.74 (m, 2H, CH2–OH), 4.03 (m, 1H, CH),
4.07–4.18 (m, 2H, ArO–CH2), 6.81–7.25 (m, 4H, ArH). IR: 3300 (br), 2960, 2870, 1600, 1500, 1460,
1380, 1240, 1080, 1050, 930, 760 cm−1. Calcd for C12H18O3: C 68.55, H 8.63. Found: C 68.28, H 8.66.
1.1.5. rac-3-(2-Chlorophenoxy)propane-1,2-diol rac-4e
1H NMR: 3.78 (m, 2H, CH2–OH), 4.07 (m, 1H, CH), 4.10 (m, 2H, ArO–CH2), 6.88–7.31 (m, 4H,
ArH). IR: 3300 (br), 2940, 1590, 1490, 1450, 1300, 1250, 1130, 1070, 1030, 740 cm−1. Calcd for
C9H11O3Cl: C 53.35, H 5.47. Found: C 53.40, H 5.46.
1.1.6. rac-3-(3-Chlorophenoxy)propane-1,2-diol rac-4f
1H NMR: 3.75 (m, 2H, CH2–OH), 3.96 (m, 1H, CH), 4.07 (m, 2H, ArO–CH2), 6.69–7.24 (m, 4H,
ArH). IR: 3300 (br), 2930, 1600, 1470, 1430, 1280, 1230, 1120, 1060, 890, 860, 770, 680 cm−1. Calcd
for C9H11O3Cl: C 53.35, H 5.47. Found: C 53.37, H 5.45.
1.1.7. rac-3-(4-Chlorophenoxy)propane-1,2-diol rac-4g
1H NMR: 3.78 (m, 2H, CH2–OH), 4.01 (m, 1H, CH), 4.10 (m, 2H, ArO–CH2), 6.79–7.26 (m, 4H,
ArH). IR: 3300 (br), 2920, 1600, 1490, 1450, 1280, 1240, 1110, 1050, 880, 820 cm−1. Calcd for
C9H11O3Cl: C 53.35, H 5.47. Found: C 53.33, H 5.49.
1.1.8. rac-3-(2-Methylphenoxy)propane-1,2-diol rac-4h
1H NMR: 2.23 (s, 3H, CH3), 3.76 (m, 2H, CH2–OH), 4.01 (m, 1H, CH), 4.12 (m, 2H, ArO–CH2),
6.78–7.18 (m, 4H, ArH). IR: 3260 (br), 2930, 1610, 1500, 1460, 1310, 1250, 1120, 1050, 990, 750
cm−1. Calcd for C10H14O3: C 65.92, H 7.74. Found: C 65.69, H 7.72.

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1.1.9. rac-3-(3-Methylphenoxy)propane-1,2-diol rac-4i
1H NMR: 2.27 (s, 3H, CH3), 3.76 (m, 2H, CH2–OH), 4.00 (m, 1H, CH), 4.08 (m, 2H, ArO–CH2),
6.67–7.18 (m, 4H, ArH). IR: 3290 (br), 2930, 1610, 1590, 1490, 1450, 1290, 1260, 1160, 1060, 910,
860, 770, 690 cm−1. Calcd for C10H14O3: C 65.92, H 7.74. Found: C 65.74, H 7.73.
1.1.10. rac-3-(4-Methylphenoxy)propane-1,2-diol rac-4j
1H NMR: 2.25 (s, 3H, CH3), 3.72–4.00 (m, 2H, CH2–OH), 3.96 (m, 1H, CH), 4.13 (m, 2H, ArO–CH2),
7.24–7.87 (m, 4H, ArH). IR: 3390 (br), 1580, 1520, 1440, 1360, 1320, 1250, 1140, 1080, 1010, 870, 820
cm−1. Calcd for C10H14O3: C 65.92, H 7.74. Found: C 65.99, H 7.74.
1.1.11. rac-3-(3-Nitrophenoxy)propane-1,2-diol rac-4k
1H NMR: 3.72–4.00 (m, 2H, CH2), 4.13 (m, 3H, CH2 and CH), 7.24–7.87 (m, 4H, ArH). IR: 3390
(br), 1580, 1520, 1440, 1360, 1320, 1250, 1140, 1080, 1010, 870, 820, 740 cm−1. Calcd for C9H11NO5:
C 50.71, H 5.20, N 6.57. Found: C 50.56, H 5.22, N 6.59.
1.1.12. rac-3-(2,6-Dimethylphenoxy)propane-1,2-diol rac-4l
1H NMR: 2.21 (s, 6H, CH3), 3.78 (m, 4H, CH2–OH and CH2–OAr), 4.07 (m, 1H, CH), 6.80–7.00 (m,
3H, ArH). IR: 3384 (br), 2925, 1592, 1477, 1264, 1201, 1026, 768 cm−1. Calcd for C11H16O3: C 67.32,
H 8.22. Found: C 67.38, H 8.19.
1.1.13. rac-3-(2,4,6-Trichlorophenoxy)propane-1,2-diol rac-4m
1H NMR: 3.50–4.55 (m, 5H, CH2–OH, CH2–OAr and CH), 7.25 (s, 2H, ArH). IR: 3312 (br), 2943,
1572, 1553, 1447, 1256, 1053, 858 cm−1. Calcd for C9H9Cl3O3: C 39.81, H 3.34. Found: C 39.67, H
3.39.
1.2. Preparation of 1-acetoxy-3-aryloxypropan-2-ols rac-5a–m
To a solution of 3-aryloxypropane-1,2-diol rac-4a–m, 50 mmol, pyridine (60 mmol) and (4-N,N-
dimethylamino)pyridine (100 mg) in methylene chloride (100 ml) acetic anhydride (50 mmol) was added
dropwise and the resulting solution was stirred for between 10 and 60 minutes. Then the mixture was
washed with 5% hydrochloric acid (2×20 ml), saturated NaHCO3 solution (20 ml) and brine (15 ml).
After drying over Na2SO4 the solvent was removed by rotary evaporation. The residue was purified by
preparative vacuum-chromatography by eluting with hexane:acetone 10:1-→10:3. Yields of the products
rac-5a–m are given in Table 1.
1.2.1. rac-1-Acetoxy-3-phenoxypropan-2-ol rac-5a
1H NMR: 2.04 (s, 3H, CH3COO), 4.05 (m, 2H, ArO–CH2), 4.09 (m, 1H, CH), 4.08–4.17 (m, 2H,
AcO–CH2), 6.76–7.22 (m, 5H, ArH). IR: 3450 (br), 2940, 1740, 1600, 1500, 1370, 1240, 1050, 760
cm−1. Calcd for C11H14O4: C 62.85, H 6.71. Found: C 62.66, H 6.70.
1.2.2. rac-1-Acetoxy-3-(1-naphthyloxy)propan-2-ol rac-5b
1H NMR: 2.14 (s, 3H, CH3COO), 4.19 (m, 2H, ArO–CH2), 4.28–4.46 (m, 3H, AcO–CH2 and CH),
6.77–8.25 (m, 7H, ArH). IR: 3450 (br), 1710, 1580, 1460, 1400, 1370, 1270, 1240, 1110, 1050, 950, 790,
270 cm−1. Calcd for C15H16O4: C 69.22, H 6.20. Found: C 69.43, H 6.19.

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1.2.3. rac-1-Acetoxy-3-(2-naphthyloxy)propan-2-ol rac-5c
1H NMR: 2.12 (s, 3H, CH3COO), 4.14 (m, 2H, ArO–CH2), 4.31 (m, 3H, CH and AcO–CH2),
7.13–7.78 (m, 7H, ArH). IR: 3450 (br), 2940, 1740, 1630, 1600, 1510, 1460, 1390, 1260, 1220, 1180,
1050, 840 cm−1. Calcd for C15H16O4: C 69.22, H 6.20. Found: C 69.35, H 6.22.
1.2.4. rac-1-Acetoxy-3-(2-isopropylphenoxy)propan-2-ol rac-5d
1H NMR: 1.10 (d, 6H, 2CH3), 2.10 (s, 3H, CH3COO), 3.17 (m, 1H, CH–Ar), 3.84 (m, 2H, ArO–CH2),
4.16 (m, 3H, CH and AcO–CH2), 6.67–7.11 (m, 4H, ArH). IR: 3460 (br), 2960, 2870, 1740, 1490, 1250,
1370, 1240, 1090, 1050, 750 cm−1. Calcd for C14H20O4: C 66.65, H 7.99. Found: C 66.45, H 8.02.
1.2.5. rac-1-Acetoxy-3-(2-chlorophenoxy)propan-2-ol rac-5e
1H NMR: 1.94 (s, 3H, CH3COO), 3.91 (m, 2H, ArO–CH2), 4.16 (m, 3H, CH and AcO–CH2),
6.74–7.21 (m, 4H, ArH). IR: 3440 (br), 2950, 1740, 1590, 1490, 1450, 1370, 1250, 1130, 1060 cm−1
Calcd for C11H13O4Cl: C 54.00, H 5.36. Found: C 54.16, H 5.34.
.
1.2.6. rac-1-Acetoxy-3-(3-chlorophenoxy)propan-2-ol rac-5f
1H NMR: 1.97 (s, 3H, CH3COO), 3.81 (m, 2H, ArO–CH2), 4.11 (m, 3H, CH and AcO–CH2),
6.62–7.09 (m, 4H, ArH). IR: 3440 (br), 2950, 1740, 1600, 1480, 1370, 1230, 1070, 1050, 860 cm−1
Calcd for C11H13O4Cl: C 54.00, H 5.36. Found: C 53.89, H 5.38.
.
1.2.7. rac-1-Acetoxy-3-(4-chlorophenoxy)propan-2-ol rac-5g
1H NMR: 2.06 (s, 3H, CH3COO), 3.98 (m, 2H, ArO–CH2), 4.07 (m, 1H, CH), 4.25 (m, 2H,
AcO–CH2), 6.77–7.23 (m, 4H, ArH). IR: 3450 (br), 2950, 1740, 1600, 1490, 1370, 1240, 1170, 1090,
1050, 850 cm−1. Calcd for C11H13O4Cl: C 54.00, H 5.36. Found: C 54.12, H 5.35.
1.2.8. rac-1-Acetoxy-3-(2-methylphenoxy)propan-2-ol rac-5h
1H NMR: 2.02 (s, 3H, CH3COO), 2.22 (s, 3H, CH3), 3.95 (m, 2H, ArO–CH2), 4.08 (m, 1H, CH), 4.25
(m, 2H, AcO–CH2), 6.75–7.12 (m, 4H, ArH). IR: 3450 (br), 2950, 1740, 1600, 1500, 1460, 1380, 1240,
1190, 1120, 1050, 750 cm−1. Calcd for C12H16O4: C 64.27, H 7.19. Found: C 64.40, H 7.20.
1.2.9. rac-1-Acetoxy-3-(3-methylphenoxy)propan-2-ol rac-5i
1H NMR: 1.96 (s, 3H, CH3COO), 2.16 (s, 3H, CH3), 3.79 (m, 2H, ArO–CH2), 3.90–4.10 (m, 3H,
CH and AcO–CH2), 6.56–7.00 (m, 4H, ArH). IR: 3450 (br), 2926, 1740, 1600, 1590, 1490, 1460, 1370,
1260, 1160, 1050, 780 cm−1. Calcd for C12H16O4: C 64.27, H 7.19. Found: C 64.18, H 7.18.
1.2.10. rac-1-Acetoxy-3-(4-methylphenoxy)propan-2-ol rac-5j
1H NMR: 1.89 (s, 3H, CH3COO), 2.10 (s, 3H, CH3), 3.80 (m, 2H, ArO–CH2), 4.04–4.11 (m, 3H,
CH and AcO–CH2), 6.62–6.91 (m, 4H, ArH). IR: 3450 (br), 2930, 1740, 1610, 1510, 1460, 1370, 1240,
1180, 1050, 820 cm−1. Calcd for C12H16O4: C 64.27, H 7.19. Found: C 64.21, H 7.18.
1.2.11. rac-1-Acetoxy-3-(3-nitrophenoxy)propan-2-ol rac-5k
1H NMR: 2.12 (s, 3H, CH3COO), 3.72–4.00 (m, 2H, ArO–CH2), 4.14 (m, 1H, CH), 4.31 (m, 2H,
AcO–CH2), 7.25–7.83 (m, 4H, ArH). IR: 3330 (br), 2950, 1740, 1620, 1530, 1350, 1240, 1050, 1030,
820, 740 cm−1. Calcd for C11H13O6N: C 51.77, H 5.13, N 5.49. Found: C 51.56, H 5.12, N 5.51.

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1.2.12. rac-1-Acetoxy-3-(2,6-dimethylphenoxy)propan-2-ol rac-5l
1H NMR: 2.12 (s, 3H, CH3COO), 2.30 (s, 6H, CH3), 3.80 (m, 2H, ArO–CH2), 3.95 (m, 1H, CH), 4.30
(m, 2H, AcO–CH2), 6.90–7.10 (m, 3H, ArH). IR: 3456 (br), 2926, 1740, 1592, 1375, 1243, 1201, 1092,
1046, 771 cm−1. Calcd for C13H18O4: C 65.53, H 7.61. Found: C 64.97, H 7.72.
1.2.13. rac-1-Acetoxy-3-(2,4,6-trichlorophenoxy)propan-2-ol rac-5m
1H NMR: 2.05 (s, 3H, CH3COO), 4.10 (m, 3H, ArO–CH2 and CH), 4.30 (m, 2H, AcO–CH2), 7.30
(s, 2H, ArH). IR: 3448 (br), 3076, 2953, 1741, 1553, 1448, 1248, 1047, 1005, 857, 809 cm−1. Calcd for
C11H11Cl3O4: C 42.14, H 3.54, Cl 33.92. Found: C 42.25, H 3.50.
1.3. Preparation of 1-acetoxy-3-aryloxy-propan-2-ones 1a–m by Swern-oxidation
To a solution of oxalyl chloride (1.35 ml, 15.0 mmol) in methylene chloride (25 ml) dimethyl
sulfoxide (2.3 ml, 32.0 mol) in methylene chloride (5.0 ml) was added dropwise at −60°C. After stirring
the resulting mixture for 10 minutes, racemic 1-acetoxy-3-aryloxypropan-2-ol rac-5a–m, 10 mmol in
methylene chloride (10 ml) was added at −60°C followed by stirring for 20 minutes at −60°C. Then
triethylamine (7.0 ml, 50 mmol) was added and the temperature was increased to room temperature
within 30 min. The resulting mixture was washed with water (30 ml) and the aqueous layer was extracted
with methylene chloride (20 ml). The combined organic solutions were washed with 5% hydrochloric
acid (20 ml), saturated NaHCO3 solution (15 ml) and brine (15 ml). After drying over Na2SO4 and
the solvent was removed in vacuo. The resulting product was usually pure enough for the next step.
In several cases the product was purified by preparative vacuum-chromatography using hexane:acetone
10:0.5-→10:1 for the elution. For yields of the resulting ketones 1a–m, see Table 1.
1.3.1. 1-Acetoxy-3-phenoxypropan-2-one 1a
1H NMR: 2.15 (s, 3H, CH3COO), 4.63 (s, 2H, CH2), 4.98 (s, 2H, CH2), 6.87–7.35 (m, 5H, ArH). IR:
1740, 1600, 1500, 1430, 1380, 1240, 1160, 1070, 760, 690 cm−1. Calcd for C11H12O4: C 63.45, H 5.81.
Found: C 63.58, H 5.79.
1.3.2. 1-Acetoxy-3-(1-naphthyloxy)propan-2-one 1b
1H NMR: 2.11 (s, 3H, CH3COO), 4.62 (s, 2H, ArO–CH2), 4.96 (s, 2H, AcO–CH2), 6.48–8.17 (m, 7H,
ArH). IR: 1740, 1630, 1580, 1510, 1420, 1400, 1370, 1310, 1240, 1110, 1040, 1020, 980, 860, 790, 770
cm−1. Calcd for C15H14O4: C 69.76, H 5.46. Found: C 69.48, H 5.44.
1.3.3. 1-Acetoxy-3-(2-naphthyloxy)propan-2-one 1c
1H NMR: 2.21 (s, 3H, CH3COO), 4.75 (s, 2H, ArO–CH2), 5.02 (s, 2H, AcO–CH2), 7.04–7.81 (m, 7H,
ArH). IR: 1750, 1730, 1630, 1600, 1510, 1430, 1410, 1370, 1300, 1260, 1250, 1220, 1180, 1110, 1080,
1030, 1000, 840, 810, 740 cm−1. Calcd for C15H14O4: C 69.76, H 5.46. Found: C 69.57, H 5.45.
1.3.4. 1-Acetoxy-3-(2-isopropylphenoxy)propan-2-one 1d
1H NMR: 1.15 (d, 6H, 2CH3), 2.03 (d, 6H, 2CH3), 3.25 (m, 1H, CH–Ar), 4.51 (s, 2H, ArO–CH2),
4.92 (s, 2H, AcO–CH2), 6.58–7.19 (m, 4H, ArH). IR: 2960, 1740, 1600, 1590, 1490, 1450, 1370, 1240,
1170, 1090, 1070, 750 cm−1. Calcd for C14H18O4: C 67.18, H 7.25. Found: C 67.42, H 7.25.

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1.3.5. 1-Acetoxy-3-(2-chlorophenoxy)propan-2-one 1e
1H NMR: 2.01 (s, 3H, CH3COO), 4.57 (s, 2H, ArO–CH2), 5.0 (s, 2H, AcO–CH2), 6.72–7.31 (m,
4H, ArH). IR: 1740, 1590, 1480, 1420, 1400, 1370, 1300, 1240, 1160, 1070, 750 cm−1. Calcd for
C11H11O4Cl: C 54.45, H 4.57. Found: C 54.57, H 4.55.
1.3.6. 1-Acetoxy-3-(3-chlorophenoxy)propan-2-one 1f
1H NMR: 2.05 (s, 3H, CH3COO), 4.60 (s, 2H, ArO–CH2), 4.88 (s, 2H, AcO–CH2), 6.62–7.22 (m,
4H, ArH). IR: 2930, 1740, 1590, 1480, 1430, 1380, 1290, 1230, 1170, 1070, 1020, 860, 770, 680 cm−1.
Calcd for C11H11O4Cl: C 54.45, H 4.57. Found: C 54.61, H 4.58.
1.3.7. 1-Acetoxy-3-(4-chlorophenoxy)propan-2-one 1g
1H NMR: 2.05 (s, 3H, CH3COO), 4.56 (s, 2H, ArO–CH2), 4.87 (s, 2H, AcO–CH2), 6.73–7.21 (m,
4H, ArH). IR: 1740, 1600, 1490, 1430, 1370, 1280, 1240, 1160, 1070, 1020, 830 cm−1. Calcd for
C11H11O4Cl: C 54.45, H 4.57. Found: C 54.39, H 4.57.
1.3.8. 1-Acetoxy-3-(2-methylphenoxy)propan-2-one 1h
1H NMR: 2.10 (s, 3H, CH3COO), 2.23 (s, 3H, CH3), 4.60 (s, 2H, ArO–CH2), 4.95 (s, 2H, AcO–CH2),
6.64–7.09 (m, 4H, ArH). IR: 1750, 1600, 1590, 1490, 1430, 1400, 1370, 1240, 1160, 1120, 1060, 850,
810, 750 cm−1. Calcd for C12H14O4: C 64.85, H 6.35. Found: C 64.59, H 6.34.
1.3.9. 1-Acetoxy-3-(3-methylphenoxy)propan-2-one 1i
1H NMR: 2.02 (s, 3H, CH3COO), 2.17 (s, 3H, CH3), 4.51 (s, 2H, ArO–CH2), 4.87 (s, 2H, AcO–CH2),
6.54–7.07 (m, 4H, ArH). IR: 2920, 1740, 1600, 1590, 1490, 1430, 1370, 1290, 1230, 1150, 1070, 1030,
880, 780, 690 cm−1. Calcd for C12H14O4: C 64.85, H 6.35. Found: C 64.90, H 6.35.
1.3.10. 1-Acetoxy-3-(4-methylphenoxy)propan-2-one 1j
1H NMR: 2.11 (s, 3H, CH3COO), 2.21 (s, 3H, CH3), 4.57 (s, 2H, ArO–CH2), 4.95 (s, 2H, AcO–CH2),
6.61–7.03 (m, 4H, ArH). IR: 2930, 1740, 1610, 1510, 1430, 1410, 1380, 1290, 1240, 1160, 1070, 1020,
820 cm−1. Calcd for C12H14O4: C 64.85, H 6.35. Found: C 64.71, H 6.33.
1.3.11. 1-Acetoxy-3-(3-nitrophenoxy)propan-2-one 1k
1H NMR: 2.11 (s, 3H, CH3COO), 4.78 (s, 2H, ArO–CH2), 4.91 (s, 2H, AcO–CH2), 7.19–7.87 (m,
4H, ArH). IR: 1750, 1730, 1530, 1480, 1410, 1350, 1240, 1100, 1030, 870, 810, 740 cm−1. Calcd for
C11H11O6N: C 52.18, H 4.38, N 5.53. Found: C 52.03, H 4.39, N 5.52.
1.3.12. 1-Acetoxy-3-(2,6-dimethylphenoxy)propan-2-one 1l
1H NMR: 2.05 (s, 3H, CH3COO), 2.14 (s, 6H, CH3), 4.36 (s, 2H, ArO–CH2), 4.99 (s, 2H, AcO–CH2),
6.92 (m, 3H, ArH). IR: 2937, 1750, 1734, 1475, 1396, 1231, 1168, 1075, 1058, 788 cm−1. Calcd for
C13H16O4: C 66.09, H 6.83. Found: C 66.01, H 6.79.
1.3.13. 1-Acetoxy-3-(2,4,6-trichlorophenoxy)propan-2-one 1m
1H NMR: 2.18 (s, 3H, CH3COO), 4.60 (s, 2H, ArO–CH2), 5.20 (s, 2H, AcO–CH2), 7.34 (s, 2H,
ArH). IR: 3066, 2934, 1739, 1728, 1554, 1456, 1422, 1281, 1259, 1070, 1015, 858, 769 cm−1. Calcd for
C11H9Cl3O4: C 42.41, H 2.91. Found: C 42.36, H 2.95.

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1.4. Optimization of the reaction conditions for reduction of 1-acetoxy-3-phenoxypropan-2-one 1a
To 200 ml of media (as indicated in Table 2) 1-acetoxy-3-phenoxypropan-2-one 1a, 500 mg, sucrose
(5.0 g), baker’s yeast (wet cake 12 g; or lyophilized 2.5 g) and additive (as indicated in Table 2) were
added and the resulting mixture was stirred at room temperature for a period indicated in Table 2. Then the
reaction mixture was extracted with ethyl acetate (2×150 ml), the combined organic layers were washed
with brine (20 ml) and dried over Na2SO4. After removing the solvent the residue was subjected to
preparative vacuum-chromatography (hexane:acetone 10:1-→10:5) to yield 75–85% of pure monoacetate
5a. The enantiomeric composition of the product 5a (Table 2) was determined by esterification with (R)-
MTPA-Cl [0.05 mmol scale; triethylamine, cat. DMAP, in CCl4, 50°C, 3 h] and 1H NMR analysis of the
5a-MTPA-ester [characteristic signals: 2.001 (s, COCH3) for (S)-5a-MTPA ester; 2.065 (s, COCH3) for
(R)-5a-MTPA ester].
1.5. Preparation of optically active 1-acetoxy-3-aryloxypropan-2-ols 5 or ent-5 and/or 3-
aryloxypropane-1,2-diols (4 or ent-4) by baker’s yeast reaction
General procedure: To 200 ml of sodium phosphate buffer (0.15 M, pH 7) 1-acetoxy-3-aryloxypropan-
2-one 1a–k, 0.5 g, sucrose (5.0 g) and baker’s yeast (12.0 g wet) were added and the resulting mixture was
stirred at room temperature for a period indicated in Table 3. Work up and chromatographic separation
was carried out similarly as described in the preceding section and yielded monoacetate 5 or ent-5 and/or
diol 4 or ent-4 fractions. The IR and 1H NMR spectra of the resulting 1-acetoxy-3-aryloxypropan-2-ols 5
or ent-5 and/or 3-aryloxypropan-1,2-diols 4 or ent-4 were similar to those of the corresponding racemic
compounds. For yield, enantiomeric composition and configuration of the products, see Table 3.
1
Enantiomeric composition of several diols 4d–j were determined from H NMR spectra of the
corresponding di-MTPA derivatives [esterification with (R)-MTPA-Cl: triethylamine, cat. DMAP, in
CCl4, 50°C, 3 h; characteristic signals: di-MTPA ester of (R)-4d: 5.638 (mc, CH–O); di-MTPA ester
of (S)-4d: 5.699 (mc, CH–O); di-MTPA ester of (R)-4e: 5.669 (mc, CH–O); di-MTPA ester of (S)-4e:
5.713 (mc, CH–O); di-MTPA ester of (R)-4f: 5.620 (mc, CH–O); di-MTPA ester of (S)-4f: 5.665 (mc,
CH–O); di-MTPA ester of (R)-4g: 5.627 (mc, CH–O); di-MTPA ester of (S)-4g: 5.645 (mc, CH–O); di-
MTPA ester of (R)-4h: 5.641 (mc, CH–O); di-MTPA ester of (S)-4h: 5.705 (mc, CH–O); di-MTPA ester
of (R)-4i: 5.630 (mc, CH–O); di-MTPA ester of (S)-4i: 5.675 (mc, CH–O); di-MTPA ester of (R)-4j:
5.627 (mc, CH–O); di-MTPA ester of (S)-4j: 5.655 (mc, CH–O)].
For determination of configuration, several (R)-diols 4 were prepared from (R)-3-chloropropane-1,2-
diol [(R)-2, 95% e.e.] by coupling with the corresponding phenol 3 [(R)-2: 1.2 mmol, 3: 1.5 mmol;
according to the procedure used for the preparation of the racemic diols].
For direct comparison of the specific rotations, the monoacetate fractions 5 were saponified [1.2 M
NaOMe/MeOH, r.t., 10 min, 80–95% yields] to diols 4 (Table 4).
Acknowledgements
The Hungarian OTKA Foundation (Project Nos: 1759 and 14894) is gratefully acknowledged for
financial support. J.B. thanks the Zoltán Magyary Foundation for a postdoctoral fellowship.

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Table 4
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