Lipase-Mediated Synthesis of Both Enantiomers of Levoglucosenone from Acrolein Dimer

Article abstract of DOI:10.1002/1615-4169(200108)343:6/7<618::AID-ADSC618>3.0.CO;2-E

A synthesis of both enantiomers of levoglucosenone from acrolein dimer has been developed by employing lipase-mediated kinetic hydrolysis. Thus, acrolein dimer is transformed into racemic dihydrolevoglucosenone by sequential hydride reduction, oxidative acetalization, and Swern oxidation. Employing Saegusa-Larock conditions, dihydrolevoglucosenone is transformed into racemic levoglucosenone. The lipase-mediated resolution was best carried out under hydrolysis conditions with the endo-acetate generated from racemic levoglucosenone to give rise to highly enantioenriched (+)-alcohol and enantiopure (-)-acetate serving as the precursors of enantiopure levoglucosenone having the corresponding chirality.

Full text of DOI:10.1002/1615-4169(200108)343:6/7<618::AID-ADSC618>3.0.CO;2-E

FULL PAPER
Lipase-Mediated Synthesis of Both Enantiomers of
Levoglucosenone from Acrolein Dimer
Kohei Kadota, Takashi Kurusu, Takahiko Taniguchi, Kunio Ogasawara*
Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980
Fax: (+81)-217 6845, e-mail: konol@mail.cc.tohoku.ac.jp
-8578, Japan
-
Received April 20, 2001; Accepted June 22, 2001
Abstract: A synthesis of both enantiomers of levo- tion was best carried out under hydrolysis condi-
glucosenone from acrolein dimer has been devel- tions with the endo-acetate generated from racemic
oped by employing lipase-mediated kinetic hydroly- levoglucosenone to give rise to highly enantioen-
sis. Thus, acrolein dimer is transformed into riched (+)-alcohol and enantiopure (±)-acetate ser-
racemic dihydrolevoglucosenone by sequential hy- ving as the precursors of enantiopure levoglucose-
dride reduction, oxidative acetalization, and Swern none having the corresponding chirality.
oxidation. Employing Saegusa-Larock conditions,
dihydrolevoglucosenone is transformed into race- Keywords: chiral pool; chiral resolution; dehydro-
mic levoglucosenone. The lipase-mediated resolu- genation; enzymatic resolution; heterocycles
isolevoglucosenone. We report here a fourth method
which involves an efficient synthesis of racemic levo-
Introduction
glucosenone [(±)-1] and its lipase-mediated resolu-
(±)-Levoglucosenone [1,6-anhydro-3,4-dideoxy-b-d-
glycerohex-3-enopyranos-2-ulose); (±)-1] is a pyroly-
sis product of cellulose[1] (Figure 1). Owing to the
high chemical potential exhibited by an enone func-
tionality and masked formyl and 1,2-glycol function-
alities and the inherent stereochemical potential ex-
hibited by the biased framework, this molecule has
received considerable attention as a versatile chiral
building block and actually is being utilized for enan-
tio- and diastereoselective construction of a variety of
optically active compounds.[2,3] However, its utiliza-
tion is still limited as its preparation from cellulose af-
fords only the (±)-enantiomer in very low yield
(<10%). Therefore, the development of an efficient
synthesis of levoglucosenone 1 in both enantiomeric
forms is essential for its more versatile utilization.
Three methods which are capable of producing enan-
tiomeric (+)-levoglucosenone [(+)-1] have been re-
ported: two utilizing natural sugar precursors with a
multi-step sequence[4,5] and one employing the
Sharpless asymmetric dihyroxylation[6] or lipase-
mediated resolution[7] with a circuitous sequence via
tion[7] through the allyl acetate intermediate (±)-9.
Results and Discussion
Commercially available acrolein dimer [2H-3,4-dihy-
dropyran-2-carbaldehyde; (±)-2] was reduced with
sodium borohydride to give the primary alcohol[8]
(±)-3. Internal acetal formation of (±)-3 under oxida-
tive conditions proceeded in a one-pot, two-step se-
quence involving oxidative treatment in methanol
and intramolecular acetalization to give 5 having a di-
oxabicyclo[3.2.1]octane framework as a mixture of
epimers, presumably via the methyl acetal 4. When
the oxidation was carried out without using metha-
nol, a complex mixture of products was generated.
Thus, (±)-3 was first stirred with m-chloroperbenzoic
acid (m-CPBA) in methanol at 0 °C to give a mixture
of oxidation products which, after evaporation of the
solvent, was refluxed with a catalytic amount of p-to-
luenesulfonic acid in benzene to afford the bicyclic
acetal 5 in acceptable overall yield. We first examined
the direct conversion of 5 into racemic levoglucose-
none [(±)-1] using o-iodoxybenzoic acid (IBX) which
was recently employed by Nicolaou[9] to convert a
cyclic alcohol into the corresponding enone in one
step. Indeed, the desired reaction did occur to give a
mixture containing levoglucosenone [(±)-1] as a ma-
Figure 1. (±)-Levoglucosenone [(±)-1].
618
Ó WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2001
1615-4150/01/34306±7-618±623 $ 17.50-.50/0
Adv. Synth. Catal. 2001, 343, No. 6±7

FULL PAPER
Scheme 3. Lipase-mediated transesterification.
Resolution of the alcohol (±)-8 under transesterifi-
cation conditions[7] was first examined using four im-
mobilized lipases in THF containing an excess
amount of vinyl acetate (10 equiv.) at room tempera-
ture. Among the lipases examined, three catalyzed
the transesterification to give enantioenriched ace-
tate (+)-9 and enantioenriched alcohol (±)-8 in good
yields. Fortunately, since both products were pre-
pared in enantiomerically pure forms from natural
carbohydrate precursors,[1c,15,16,17] their absolute
configurations were assigned as shown (Scheme 3).
However, the optical purity of both products was
found to be less than satisfactory for practical use in
every case (Table 1).
On the other hand, resolution of acetate (±)-9 under
hydrolysis conditions in a mixture of a phosphate buf-
fer and acetone using the same four immobilized li-
pases proceeded in an enantiocomplementary way to
the transesterification reaction above to give the en-
antiomeric alcohol (+)-8 and the enantiomeric ace-
tate (±)-9, respectively; this way was much superior
to the transesterification. In particular, lipase PS
brought about excellent resolution giving rise to
highly enantioenriched alcohol[1c,15,16,17] (+)-8 (87%
ee) and enantiopure acetate[15,17] (±)-9 in good yields
(Scheme 4 and Table 2). The enantioenriched alcohol
(+)-8 obtained could be optically purified using lipase
AK which exhibited the best result among the lipases
examined (Table 1, entry 4). Thus, (+)-8 (87% ee), on
stirring with a limited amount of vinyl acetate
(1 equiv.) at room temperature, furnished the enan-
tiopure (+)-acetate (+)-9 in 80% yield with some re-
Scheme 1. Synthesis of racemic levoglucosenone [(±)-1].
jor component, but the by-products could not be re-
moved in a practical manner. Swern oxidation[10] of 5
was thus carried out to give racemic dihydrolevoglu-
cosenone [(±)-6] whose 1H NMR spectral data were
identical with those reported for optically active (±)-6
from a natural origin.[11] IBX oxidation of (±)-6 again
generated the same inseparable mixture together
with levoglucosenone [(±)-1].
In order to carry out the requisite dehydrogenation
under more familiar conditions,[12] ketone (±)-6 was
transformed into the tert-butyldimethylsilyl (TBS)
enol ether (±)-7 under standard conditions. Employ-
ing the Larock modification[13] of the Saegusa reac-
tion,[12] (±)-7 was exposed to oxygen in DMSO in the
presence of a catalytic amount of palladium(II) ace-
tate. The reaction proceeded in the desired way to
give rise to racemic levoglucosenone [(±)-1] in satis-
factory yield. The overall yield of racemic levogluco-
senone [(±)-1] from acrolein dimer (±)-2 was 36% in
six steps (Scheme 1).
Having established a new synthesis of racemic le-
voglucosenone [(±)-1], we next examined its resolu-
tion by employing lipase-mediated conditions. To car-
ry out the resolution under transesterification or ester
hydrolysis conditions, (±)-1 was transformed diaster-
eoselectively into the endo-alcohol (±)-8 and the
endo-acetate (±)-9 by sequential 1,2-reduction[14] and
acetylation (Scheme 2).
Table 1. Kinetic transesterification of allyl alcohol (±)-8.[a]
Entry Lipase[b]
Time (h) (±)-8 (%:% ee)[c] (+)-9 (%:% ee)[c]
1
2
3
4
Novozyme 12
Lipase LIP 12
-:-[d]
53:38
60:70
46:70
-:-[d]
42:61
45:84
44:70
Lipase AK
Lipase PS
12
12
[a] Reaction was carried out in THF at room temperature
with ten equivalents of vinyl acetate.
[b] Novozyme (Candida antarctica, Roche); Lipase LIP (Pseu-
domonas sp., Toyobo); Lipase PS (Pseudomonas cepacia,
Amano); Lipase AK (Pseudomonas sp., Amano).
[c]
Enantiomeric excess was determined by HPLC equipped
with a chiral column (CHIRALCEL OJ) after conversion
into the benzoate.
[d] Reaction did not proceed.
Scheme 2. Preparation of resolution substrates.
Adv. Synth. Catal. 2001, 343, 618±623
619

asc.wiley-vch.de
methanolysis conditions in the presence of potassium
carbonate, which furnished the corresponding levo-
glucosenone (1) on oxidation with manganese(IV)
oxide[6] (Scheme 5).
Conclusion
We have developed a new route to racemic levogluco-
senone. Employing a lipase-mediated kinetic hydro-
lysis reaction, the racemic acetate generated from
racemic levoglucosenone was resolved and recon-
verted into both enantiomers of enantiopure levoglu-
cosenone. The present synthesis involving an effi-
cient acquisition of racemic levoglucosenone and its
resolution is highly promising for the stereocon-
trolled construction of a variety of both natural and
unnatural optically active compounds.
Scheme 4. Lipase-mediated resolution and optical purifica-
tion.
Table 2. Kinetic hydrolysis of allyl acetate (±)-9.[a]
Entry Lipase[b]
Time (h) (+)-8 (%:% ee)[c] (±)-9 (%:% ee)[c]
Experimental Section
1
2
3
4
Novozyme 216
Lipase LIP 16
30:76
40:48
60:70
44:87
53:26
43:26
34:90
42:>99
General Remarks
Lipase AK
Lipase PS
288
27
The solvents used were distilled prior to use. IR spectra were
recorded on a JASCO-IR-700 spectrometer. 1H NMR and
13C NMR were obtained in CDCl3 using a Varian Gemini
(300 and 75 MHz). Optical rotations were measured using a
JASCO DIP-370 digital polarimeter. Optical purity was deter-
mined on a Gilson Model-307 instrument equipped with a
chiral column. Mass spectra were obtained using a JMS-
AX-500 and a JMX-MX-303 instrument.
[a] Reaction was carried out in phosphate buffer-acetone
mixture (9:1 v/v) at room temperature.
[b] Novozyme (Candida antarctica, Roche); Lipase LIP (Pseu-
domonas sp., Toyobo); Lipase PS (Pseudomonas cepacia,
Amano); Lipase AK (Pseudomonas sp., Amano).
[c]
Enantiomeric excess was determined by HPLC equipped
with a chiral column (CHIRALCEL OJ) after conversion
into the benzoate.
7,8-Dioxabicyclo[3.2.1]octan-2-ol (5)
To a stirred solution of alcohol (±)-3 (100 mg, 0.88 mmol) in
MeOH (2 mL) was added m-CPBA (259 mg, 1.05 mmol) at
0 °C and the stirring was continued for 30 min at the same
temperature. The solvent was evaporated under reduced
pressure to give a residue containing 4. This was dissolved
in benzene (10 mL) containing p-TsOH (8.3 mg, 0.04 mmol)
and the mixture heated at reflux for 5 h. The solvent was
evaporated under reduced pressure and the residue chro-
matographed (SiO2 7 g, elution with Et2O-hexane, 20:1 v/v)
to give 5 as a colorless oil; yield: 67 mg (58%); IR (film): m =
3450, 2950, 1095, 1014, 884 cm±1; 1H NMR: d = 5.32 (br. s, 1H,
H-1), 4.50 (m, 1H, H-5), 3.93 (d, J6,5 = 7 Hz, 0.5H, H-6), 3.87 ±
3.79 (m, 1.5H, H-6), 3.63 ± 3.58 (m, 1H, H-2), 2.10 ± 1.90 (m,
2H,), 1.67 ± 1.40 (m, 2H); HRMS: calcd. for C6H10O3:
130.0629; found: m/z = 130.0595; anal. calcd. for C6H10O3: C
55.35, H 7.74; found: C 55.06, H 7.56.
covery of the (±)-alcohol (±)-8 (14% with <30% ee).
The configuration and structure of the products were
deduced unambiguously by comparison of the spec-
troscopic data with those reported[1c,15,16,17]
(Scheme 4).
Conversion of the enantiopure products into enan-
tiopure levoglucosenone (1) having the correspond-
ing chirality could be carried out satisfactorily under
standard conditions. Thus, both enantiomers of ace-
tate 9 were first transformed into alcohol 8, under
(±)-7,8-Dioxabicyclo[3.2.1]octan-2-one [(±)-6]
To a stirred solution of oxalyl chloride (4 mL, 46 mmol) in
CH2Cl2 (40 mL) was added DMSO (6.5 mL, 92 mmol) at ±70 °C
and, after 30 min, 5 (2.0 g, 15.4 mmol) in CH2Cl2 (10 mL) was
added at the same temperature. After stirring for 1 h at the
same temperature, Et3N (19 mL, 138 mmol) was added and
the mixture was gradually warmed to room temperature. The
Scheme 5. Synthesis of enantiopure levoglucosenone.
620
Adv. Synth. Catal. 2001, 343, 618±623

FULL PAPER
reaction was quenched by addition of saturated aqueous NH4Cl
and extracted with CH2Cl2. The extract was washed with brine,
dried (MgSO4), evaporated under reduced pressure, and the
residue chromatographed (SiO2 150 g, elution with Et2O-hex-
ane, 3:1 v/v) to give (±)-6 as a pale yellow oil; yield: 1.70 g
ring was continued for 20 min at the same temperature.
The reaction was quenched by addition of acetone and the
mixture was evaporated under reduced pressure. The resi-
due was diluted with water and extracted with Et2O. The ex-
tract was washed with brine, dried (MgSO4), evaporated un-
der reduced pressure, and the residue chromatographed
(SiO2 60 g, elution with Et2O-hexane, 5:1 v/v) to give (±)-8
as a colorless oil; yield: 1.39 g (89%); IR (film): m = 3457,
(86%); IR (film): m = 2966, 2898, 1716, 1105, 971, 890, 831 cm±1
;
1H NMR: d = 5.11 (s, 1H, H-1), 4.72
-4.70 (m, 1H, H-5), 4.05 (dd,
J6,6' = 7.4 and J6,5 = 0.8 Hz, 1H, H-6), 3.99 ± 3.94 (m, 1H, H-6'),
2.72 ± 2.52 (m, 1H, H-3), 2.43 ± 2.25 (m, 2H, H-3' and H-4'),
2.05 ± 1.98 (m, 1H, H-4'); HRMS: calcd. for C6H8O3: 128.0473;
found: m/z = 128.0483. 1H NMR data were identical with those
reported.[11]
1
3017, 2960, 2894, 1123, 1046, 983, 885, 820 cm±1; H NMR: d
= 6.12 (dd, J4,5 = 9.9 and J4,3 = 4.4 Hz, 1H, H-4), 5.72 (dt, J3,4
= 9.9, J3,2 = 2.5, and J3,1 = 2.5 Hz 1H, H-3), 5.52 (dd, J1,2 = 2.5
and J1,3 = 2.5 Hz, 1H, H-1), 4.66 (dd, J5,4 = 4.4 and J5,6 = 4.4 Hz,
1H, H-5), 4.34(d, J2,OH = 11.8 Hz, 1H, H-2), 3.84 (d, J6,6'
6.6 Hz, 1H, H-6), 3.78 3.74 (m, 1H, H-6'), 2.08 (d, JOH,2
=
=
-
12.1 Hz, 1H, OH); 13C NMR: d = 130.8, 129.2, 101.3, 71.1,
70.6, 68.7. HRMS: calcd. for C6H8O3: 128.0473; found: m/z =
128.0459; anal. calcd. for C6H8O3: C 56.50, H 6.29; found: C
56.50, H 6.41. The 1H NMR spectra were identical with those
reported,[1c,16] but not identical with those of the epimeric
alcohol.[6]
(±)-2-(tert-Butyldimethylsiloxy)-7,8-dioxabicy-
clo[3.2.1]oct-2-ene [(±)-7]
To a stirred solution of LDA [prepared in situ by treating i-
Pr2NH (77 lL, 0.6 mmol) in THF (2 mL) at ±78 °C with BuLi
(1.56 M in hexane, 0.3 mL, 0.47 mmol) in the same flask]
was added (±)-6 (50 mg, 0.39 mmol) in THF (1 mL) at 0 °C.
After 20 min at the same temperature, the mixture was
cooled to
-78 °C and to this mixture was added TBS-Cl
(90 mg, 0.6 mmol) and HMPA (0.08 mL, 0.47 mmol) in
THF (1 mL) and the mixture was warmed gradually to
0 °C. The reaction was quenched by addition of 5% aqu-
eous NaHCO3 and extracted with a mixture of Et2O-AcOEt
(6:1, v/v). The extract was dried (MgSO4), evaporated un-
der reduced pressure, and the residue chromatographed
(SiO2 5 g, elution with AcOEt-hexane, 1:20 v/v) to give (±)-
7 as a pale yellow oil; yield: 88 mg (93%); IR (film): m = 2957,
(±)-2-Acetoxy-7,8-dioxabicyclo[3.2.1]oct-3-ene
[(±)-9]
To a stirred solution of (±)-8 (1.30 g, 10.2 mmol) in CH2Cl2
(30 mL) were added pyridine (1.64 mL, 20 mmol), 4-N,N-di-
methylaminopyridine (DMAP; 12 mg, 0.1 mmol), and acetic
anhydride (1.43 mL, 15 mmol) at room temperature and the
stirring was continued for 5 h at the same temperature. The
mixture was diluted with Et2O and washed successively with
10% HCl and brine, dried (MgSO4), evaporated under re-
duced pressure, and the residue chromatographed (SiO2
70 g, elution with AcOEt-hexane, 1:20 v/v) to give (±)-9 as a
colorless oil; yield: 1.42 g (82%); IR (film): m = 2968, 2892,
;
2894, 2859, 1664, 1220, 1101, 868, 841 cm±1 1H NMR: d =
5.17 (d, J3,4 = 1.4 Hz, 1H, H-3), 4.65 ± 4.62 (m, 2H, H-1 and
H-5), 3.95 ± 3.90 (m, 1H, H-6'), 3.64 (dd, J6,6' = 6.9 and J6,5
1.6 Hz, 1H, H-6), 2.76 2.69 (m, 1H, H-4), 1.83 (dd, J4',4
=
=
-
17.0 and J4',3 = 5.8 Hz, 1H), 0.925 (s, 9H), 0.164 (s, 3H),
0.158 (s, 3H); HRMS: calcd. for C12H22O3Si: 242.1337; found:
m/z = 242.1313.
1730, 1372, 1237, 1125, 1041, 984, 901, 885, 803 cm±1
1H NMR: d = 6.20 (ddd, J4,3 = 10.4, J4,5 = 4.1 and J4,2 = 1.4 Hz,
1H, H-4), 5.66 5.62 (m, 2H, H-2 and H-3), 5.53 (s, 1H, H-1),
4.70 (t, J5,4 = 4.1, J5,6' = 4.1 Hz, 1H, H-5), 3.99 (d, J6,6'
;
-
=
(±)-Levoglucosenone [(±)-1]
6.9 Hz, 1H, H-6), 3.81 (m, 1H, H-6'), 2.15 (s, 3H, OAc); HRMS:
calcd. for C8H10O4: 170.0578; found: m/z = 170.0576; anal.
calcd. for C8H10O4: C 56.47, H 5.92; found: C 56.57, H 5.92.
A solution of (±)-7 (118 mg, 0.49 mmol) and Pd(OAc)2
(10 mg, 0.05 mmol) in DMSO (2 mL) was stirred under an
oxygen atmosphere at 80 °C for 48 h. The mixture was di-
luted with CH2Cl2 and water and the organic layer was sepa-
rated. The organic layer was washed, dried (MgSO4), evapo-
rated under reduced pressure, and the residue
chromatographed (SiO2 10 g elution with Et2O-hexane, 4:1
v/v) to give (±)-1 as a colorless oil; yield: 47 mg (77%); IR
1
The H NMR spectra were identical with those reported for
the optically active product.[15,17]
Kinetic Transesterification of Racemic Alcohol
(±)-8: Typical Example
(film): m = 2976, 2899, 1699, 1107, 972, 892, 832 cm±1
;
1H NMR: d = 7.29 (dd, J4,3 = 9.9 and J4,5 = 4.7 Hz, 1H, H-4),
6.14 (dd, J3,4 = 9.9 and J3,1 = 1.6 Hz, 1H, H-3), 5.38 (d, J1,3
1.6 Hz, 1H, H-1), 5.02 (t, J5,4 = 4.7 and J5,6' = 4.7 Hz, 1H, H-5),
3.91(dd, J6',6 = 6.9 and J6',5 = 4.7 Hz, 1H, H-6'), 3.78 (d, J6,6'
A suspension of (±)-8 (30 mg, 0.23 mmol), vinyl acetate
(215 lL, 2.3 mmol), and immobilized lipase (Lipase AK;
39 mg) in THF (1 mL) was stirred at room temperature for
12 h. The mixture was filtered through a Celite pad and the
filtrate was evaporated under reduced pressure and the resi-
due chromatographed (SiO2 2 g, elution with Et2O-hexane,
1:4 v/v) to give the (+)-acetate (+)-9 (yield: 18 mg, 46%) and
the (±)-alcohol (±)-8 (yield: 13 mg, 44%), each as a colorless
oil. The enantiomeric excess of the products was deter-
mined by HPLC equipped with a chiral column (CHIRAL-
CEL OJ, elution with i-PrOH-hexane, 1:9 v/v) after transfor-
mation of each product into the benzoate: (+)-9 (70% ee) and
(±)-8 (70% ee).
=
=
6.9 Hz, 1H, H-6); HRMS: calcd. for C6H6O3: 126.0313; found:
m/z = 126.0280. Spectra and TLC were identical with those
of an authentic sample.[6]
(±)-7,8-Dioxabicyclo[3.2.1]oct-3-en-2-ol [(±)-8]
To a stirred solution of (±)-1 (1.53 g, 12.1 mmol) in MeOH
(20 mL) was added CeCl3´7 H2O (4.51 g, 12.1 mmol) fol-
lowed by NaBH4 (229 mg, 6.1 mmol) at ±50 °C and the stir-
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asc.wiley-vch.de
Kinetic Hydrolysis of Racemic Acetate (±)-9:
Typical Example
(+)-(1R,2S,5S)-7,8-Dioxabicyclo[3.2.1]oct-3-en-2-
ol [(+)-8] from Enantiopure (+)-Acetate +-(9)
A suspension of (±)-9 (1.0 g, 6.0 mmol) and immobilized li-
pase (Lipase PS 680 mg) in 0.1 M phosphate buffer (pH 7.6;
16 mL) and acetone (1.7 mL) was stirred at room tempera-
ture for 27 h. The mixture was diluted with Et2O and filtered
through a Celite pad, and the organic layer was separated.
The organic layer was washed with brine, dried (MgSO4),
evaporated under reduced pressure, and the residue chro-
matographed (SiO2 70 g, elution with Et2O-hexane, 1:4 v/v)
to give (±)-9 (yield: 425 mg, 42%), [a]2D6: ±34.5 (c 1.1, CHCl3)
{lit.: [a]D26: ±26 (c 1.2, CHCl3)[15]; [a]D27: ±40.7 (c 1.3, CHCl3)[17]},
and (+)-8 (yield: 340 mg, 44%), [a]2D6: +22.1 (c 1.0, CHCl3),
each as a colorless oil. The enantiomeric excess of the
products was determined as above by HPLC equipped with
a chiral column which revealed (±)-9 as >99% ee and (+)-8
as 87% ee. The spectroscopic data (1H NMR and MS) and
TLC of the products were identical with those of (±)-8 and
(±)-9.
To a stirred solution of K2CO3 (187 mg, 1.35 mmol) in MeOH
(3 mL) was added (+)-acetate (+)-9 (230 mg, 1.35 mmol) at
room temperature and the stirring was continued for
30 min at the same temperature. The mixture was evapo-
rated under reduced pressure, the residue was diluted with
water and extracted with Et2O. The extract was washed with
brine, dried (MgSO4), evaporated under reduced pressure,
and the residue chromatographed (SiO2 6 g, elution with
Et2O-hexane, 3:1 v/v) to give the (+)-alcohol (+)-8; yield:
149 mg (86%); mp 67-
68 °C, [a]2D0: +28.1 (c 1.0, CHCl3). The
spectroscopic data (1H NMR and MS) were identical with
those of (±)-8.
(±)-Levoglucosenone [(±)-1]
To a stirred solution of (±)-8 (34 mg, 0.27 mmol) in CH2Cl2 (2
mL) was added MnO2 (342 mg, 3.94 mmol) at room tem-
perature and the stirring was continued for 5 h at the same
temperature. After filtration through a Celite pad, the filtrate
was evaporated under reduced pressure and the residue
chromatographed (SiO2 1.5 g, elution with Et2O-hexane, 5:1
v/v) to give (±)-1 as a pale yellow oil; yield: 29 mg (87%);
Optical Purification of Enantioenriched (+)-
Alcohol (+)-8
[a]2D8: ±525 (c 1.2, CHCl3) {lit.: [a]D: ±460 (c 1.0, CHCl3)[1a]
;
A suspension of (+)-8 (87% ee: 290 mg, 2.27 mmol), vinyl
acetate (251 lL, 2.27 mmol), and Lipase AK (290 mg) in
THF (5 mL) was stirred at room temperature for 7 h. The
mixture was filtered through a Celite pad, the filtrate was
evaporated under reduced pressure, and the residue chro-
matographed (SiO2 15 g, elution with Et2O-hexane, 1:4 v/v)
to give enantiopure (+)-acetate (+)-9 (yield: 310 mg, 80%),
[a]2D9: +35.7 (c 0.8, CHCl3), and poorly enantioenriched (±)-
alcohol (±)-8 (yield: 41 mg, 14%), [a]2D9: ±9.2 (c 0.8, CHCl3).
The optical purity of (+)-9 was determined as >99% ee by
HPLC equipped with a chiral column (CHIRALCEL OJ, elu-
tion with i-PrOH-hexane, 1:9 v/v) after transformation into
the benzoate by sequential alkaline methanolysis and ben-
zoylation. The spectroscopic data (1H NMR and MS) and
TLC of the products were identical with those of (±)-8 and
(±)-9.
[a]2D7: ±518 (c 1, CHCl3)[1c]; [a]D: ±458 (c 3.97, CHCl3)[1d]}.
The spectroscopic data and TLC were identical with those
of an authentic material.[6]
(+)-Levoglucosenone [(+)-1]
Alcohol (+)-8 (20 mg, 0.16 mmol) was oxidized with MnO2
(203 mg, 2.3 mmol) as above to give (+)-1 as a pale yellow
oil; yield: 18 mg (88%); [a]2D8: +533 (c 1.5, CHCl3) {lit.[4]: [a]D:
+518 (c 1.2, CHCl3)}. The spectroscopic data and TLC were
identical with those of an authentic material.[6]
Acknowledgements
This research was supported by the Ministry of Science, Cul-
ture, and Sports, Japan.
(±)-(1R,2S,5S)-7,8-Dioxabicyclo[3.2.1]oct-3-en-2-
ol [(±)-8] from Enantiopure (±)-Acetate (±)-9
To a stirred solution of K2CO3 (276 mg, 2 mmol) in MeOH
(5 mL) was added (±)-9 (334 mg, 1.96 mmol) at room tem- References and Notes
perature and the stirring was continued for 30 min at the
same temperature. The mixture was evaporated under re-
duced pressure, the residue was diluted with water and ex-
tracted with Et2O. The extract was washed with brine, dried
(MgSO4), evaporated under reduced pressure, and the resi-
due chromatographed (SiO2 10 g, elution with Et2O-hexane
3:1, v/v) to give (±)-8 as colorless needles; yield: 229 mg
[1] (a) Y. Halpern, R. Riffer, A. Broido, J. Org. Chem. 1973,
38, 204; (b) A. Broido, M. Evett, C. C. Hodges, Carbo-
hydr. Res. 1975, 44, 267; (c) P. KoÈll, T. Schultek, R.-W.
Rennecke, Chem. Ber. 1976, 109, 337; (d) F. Shafiza-
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[2] For reviews, see: (a) Z. J. Witczak, Studies in Natural
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(91%); mp 66
66.5 °C, [a]D20: ±35.3 (c 1.0, CHCl3)[1c]; mp 70 °C, [a]2D0: ±6.5
- -
68 °C, [a]2D0: ±28.8 (c 1.0, CHCl3){lit.: mp 65
(c 1.7, CHCl3)[15]; mp 67 69 °C, [a]D: ±34 (c 1, CHCl3)[16]}.
-
The spectroscopic data (1H NMR and MS) and TLC were
identical with those of (±)-8.
622
Adv. Synth. Catal. 2001, 343, 618±623

FULL PAPER
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[15] L. Vegh, E. Hardegger, Helv. Chim. Acta 1973, 56,
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[16] J. S. Brimacombe, F. Hunedy, L. C. N. Tucker, Carbo-
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[5] Z. J. Witczak, R. Mielguj, Synlett 1996, 108.
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Adv. Synth. Catal. 2001, 343, 618±623
623