2-Arylpropionyl chlorides in kinetic resolution of racemic 3-methyl-2,3-dihydro-4H-[1,4]benzoxazines

Article abstract of DOI:10.1007/s11172-011-0149-0

Kinetic resolution of racemic 3-methyl-2,3-dihydro-4H-[1,4]benzoxazines in the reaction with chiral 2-arylpropionyl chloride predominantly yielded R*,R*-diastereomers. Ibuprofen acyl chloride as acylating agent was found to be more selective and sensitive

Full text of DOI:10.1007/s11172-011-0149-0

Russian Chemical Bulletin, International Edition, Vol. 60, No. 5, pp. 948—954, May, 2011
948
2ꢀArylpropionyl chlorides in kinetic resolution
of racemic 3ꢀmethylꢀ2,3ꢀdihydroꢀ4Hꢀ[1,4]benzoxazines
E. N. Chulakov, D. A. Gruzdev, G. L. Levit, L. Sh. Sadretdinova, V. P. Krasnov, and V. N. Charushin
I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22/20 ul. S. Kovalevskoi, 620041 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 1189. Eꢀmail: ca@ios.uran.ru
Kinetic resolution of racemic 3ꢀmethylꢀ2,3ꢀdihydroꢀ4Hꢀ[1,4]benzoxazines in the reaction
with chiral 2ꢀarylpropionyl chloride predominantly yielded R*,R*ꢀdiastereomers. Ibuprofen
acyl chloride as acylating agent was found to be more selective and sensitive to the changes in
the reaction temperature as compared to naproxen acyl chloride and 2ꢀphenylpropionyl chloride.
Key words: kinetic resolution, 2ꢀarylpropionic acids, acyl chlorides, acylation, 3ꢀmethylꢀ
2,3ꢀdihydroꢀ4Hꢀ[1,4]benzoxazine, naproxen, ibuprofen, carboxamides, amines, enantiomers,
diastereoselectivity.
Kinetic resolution (KR)1 based on the difference in the
process, whose selectivity was evaluated based on the
diastereomeric excess (de (%)) of the amides formed,
and developed efficient method for the preparation of opꢀ
tically pure (S)ꢀenantiomer of amine 1 30 — the key inꢀ
termediate in the synthesis of antibacterial agent Levoꢀ
floxacin.
transformation rates of individual stereoisomers of a raceꢀ
mate in the reactions with an asymmetric agent or a cataꢀ
lyst is successfully used for the preparation of opticalꢀ
ly pure biologically active compounds and intermediꢀ
ate products of their synthesis.2—4 Kinetic resolution is
often used to obtain chiral amines in enantiomerically
pure forms by acylation in the presence of either acylatꢀ
ing enzymes5—8, or synthetic acyl transfer catalysts.9—13
In the last years, a lot of attention is attracted by methꢀ
ods of KR using enantiomerically pure chiral acylating
agents.14—19
One of the approaches to KR of racemic amines conꢀ
sists in the use of chiral acyl chlorides as acylating agents.
Such an approach, which allows one to obtain individual
enantiomers of chiral heterocyclic amines in high enough
yields, is being successfully developed in our research group
during last years.20—25
It is known26—29 that 2ꢀarylpropionic acid derivatives
can be used for the KR of racemic amines and alcohols.
(S)ꢀNaproxen ((2S)ꢀ2ꢀ(6ꢀmethoxynaphthꢀ2ꢀyl)proꢀ
pionic acid) acyl chloride was for the first time used for
the KR of racemic heterocyclic amines,20,21 including
7,8ꢀdifluoroꢀ3ꢀmethylꢀ2,3ꢀdihydroꢀ4Hꢀ[1,4]benzoxazine
(1) and 3ꢀmethylꢀ2,3ꢀdihydroꢀ4Hꢀ[1,4]benzoxazine (2).
We found the optimum conditions to carry out the
At the same time, the regularities between the strucꢀ
ture of reagents used in KR and stereochemical result of
the process are not still found. Therefore, information on
the KR results with the use of maximum structurally difꢀ
ferent resolution agents is very important. One of the posꢀ
sible approaches to the search for efficient resolution agents
consists in the running the reaction between racemic amine
and racemic acylating agent. The reaction results in
the formation of two pairs of diastereomeric amides,
(S,S)—(R,R) and (R,S)—(S,R), whose ratio (dr) is equal
to the selectivity factor s = kfast/kslow,
1,26,31 where kfast and
kslow are the rate constants of the reactions for the fast and
slow reacting enantiomer, respectively. It should be emꢀ
phasized that in this case the ratio of concentrations of
diastereomeric products depends on neither the proporꢀ
tion of the starting reactants, nor the reaction time. In
addition, chiral compounds, which are of interest as poꢀ
tential agents for KR, most often are available in the form
of racemates (excluding some groups of substances, for
example, amino acid derivatives).
The purpose of the present work is to evaluate diastereoꢀ
selectivity of acylation of racemic heterocyclic amines 1
and 2 with 2ꢀarylpropionyl chlorides, viz., naproxen
(2ꢀ(6ꢀmethoxynaphthꢀ2ꢀyl)propionic acid) acyl chloride (3),
ibuprofen (2ꢀ(4ꢀisobutylphenyl)propionic acid) acyl chloꢀ
ride (4), and 2ꢀphenylpropionyl chlorides (5), under conꢀ
ditions of kinetic resolution.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 926—931, May, 2011.
1066ꢀ5285/11/6005ꢀ948 © 2011 Springer Science+Business Media, Inc.

2ꢀArylpropionyl chlorides in kinetic resolution
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
949
+20 and –20 °C (Scheme 2). The initial concentration of
the starting racemic amine was 0.1 mol L–1
.
The forming mixture of diastereomeric amides was anꢀ
alyzed by HPLC and 1H and 19F NMR spectroscopy. For
the assignment of stereoconfiguration of compounds obꢀ
tained, (S,S)ꢀdiastereomers of amides 11—14 were alterꢀ
natively synthesized starting from (S)ꢀamines and (S)ꢀacyl
chlorides 4 and 5, the former are identical to the mixture
of (S,S)ꢀ and (R,R)ꢀdiastereomers in their retention time
(HPLC) and signals in the NMR spectra.
As in the case of acylation of amines 1 and 2 with (S)ꢀ
naproxen acyl chloride,20,21 the use of acyl chlorides 4 and
5 led to the enrichment of amides 11—14 with (S,S)ꢀ and
(R,R)ꢀdiastereomers (see Scheme 2). In the reaction of
racemic amines 1 and 2 and racemic acyl chlorides 3—5,
the formed mixtures of amides 9—14 contained a small
amount of minor (R,S)ꢀ and (S,R)ꢀdiastereomers. Thereꢀ
fore, starting from (S)ꢀamines 1 and 2 and (RS)ꢀacyl chloꢀ
rides 4 and 5, the mixtures of (S,S)ꢀ and (S,R)ꢀamides
11—14 with the enhanced content of (S,R)ꢀdiastereomer
were synthesized in order to unambiguously determine
retention time by HPLC and positions of signals in the
NMR spectra.
Results and Discussion
Acyl chlorides 3—5 were obtained upon the action of
oxalyl chloride on the corresponding 2ꢀarylpropionic acids
6—8 in benzene in 95—97% yields and chemical purity
>98% (from the 1H spectral data) (Scheme 1). The freshly
prepared acyl chlorides were used in the acylation without
additional purification.
Scheme 1
The signals of the methine protons and protons of the
methyl groups at the asymmetric carbon atoms were conꢀ
sidered as diagnostic signals in the 1H NMR spectra, which
allowed us to conclude on the diastereomeric composition
of the amide mixtures. For the amides studied in the
1
present work it was found that in the H NMR spectra
recorded at room temperature, the signals for the CH3 and
CH groups of the acyl and amine fragments are noticeably
broadened, apparently, due to both the retarded rotation
around the amide bond and the conformation lability of
the heterocyclic fragment. When 1H NMR spectra of
amides 11—14 were recorded in DMSOꢀd6 at 100 °C, the
narrowing of the signals was observed and the spectra beꢀ
Ar = 6ꢀmethoxynaphthꢀ2ꢀyl (3, 6), 4ꢀMe2CHCH2C6H4 (4, 7),
Ph (5, 8)
Acylation of racemic amines 1 and 2 with racemic acyl
chlorides 3—5 was carried out with the reactant ratio 2 : 1
in toluene, dichloromethane, and acetonitrile for 6 h at
Scheme 2
X = F (1, 9, 11, 13), H (2, 10, 12, 14); Ar = 6ꢀmethoxynaphthꢀ2ꢀyl (3, 9, 10), 4ꢀMe2CHCH2C6H4 (4, 11, 12), Ph (5, 13, 14)

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Chulakov et al.
Table 2. The ratio of diastereomers (dr) in the acylation products
of racemic amines 1 and 2 with racemic acyl chlorides 3—5
came well resolute and suitable for the quantitative deꢀ
termination of diastereomeric composition (Table 1).
Such a phenomenon has been observed earlier20,21 for the
diastereomeric amides of naproxen with heterocyclic
amines.
Amine
Acylating
agent
Solꢀ
vent
T
dr*
/°C
To evaluate selectivity of acylation, the dr values for
amides 9—14 were determined by HPLC from the ratio of
areas under the peaks of (S,S)—(R,R)ꢀ and (R,S)—(S,R)ꢀ
diastereomers. The averaged values from two—four paralꢀ
lel determinations are given in Table 2.
For all the acyl chlorides studied, the highest selectiviꢀ
ty of acylation was observed in toluene at –20 °C; the
selectivity decreased in more polar solvents (see Table 2).
1
3
3
3
3
3
3
4
4
4
4
4
4
5
5
5
5
5
5
PhCH3
PhCH3
CH2Cl2
CH2Cl2
MeCN
MeCN
PhCH3
PhCH3
CH2Cl2
CH2Cl2
MeCN
MeCN
PhCH3
PhCH3
CH2Cl2
CH2Cl2
MeCN
MeCN
+20
–20
+20
–20
+20
–20
+20
–20
+20
–20
+20
–20
+20
–20
+20
–20
+20
–20
97.8 : 2.2
98.5 : 1.5
96.0 : 4.0
96.6 : 3.4
91.0 : 9.0
89.7 : 10.3
97.9 : 2.1
99.0 : 1.0
95.5 : 4.5
97.9 : 2.1
91.0 : 9.0
94.1 : 5.9
96.9 : 3.1
98.6 : 1.4
94.5 : 5.5
94.5 : 5.5
88.4 : 11.6
89.2 : 10.8
1
Table 1. Diagnostic signals in the H NMR spectra of amides
11—14 (400 MHz, DMSOꢀd6, 100 °C)
2
3
3
3
3
3
3
4
4
4
4
4
4
5
5
5
5
5
5
PhCH3
PhCH3
CH2Cl2
CH2Cl2
MeCN
MeCN
PhCH3
PhCH3
CH2Cl2
CH2Cl2
MeCN
MeCN
PhCH3
PhCH3
CH2Cl2
CH2Cl2
MeCN
MeCN
+20
–20
+20
–20
+20
–20
+20
–20
+20
–20
+20
–20
+20
–20
+20
–20
+20
–20
97.0 : 3.0
98.2 : 1.8
93.7 : 6.3
95.5 : 4.5
87.2 : 12.8
87.9 : 12.1
98.2 : 1.8
99.0 : 1.0
95.9 : 4.1
96.8 : 3.2
91.6 : 8.4
96.6 : 3.4
97.0 : 3.0
97.2 : 2.8
92.2 : 7.8
91.0 : 9.0
83.2 : 16.8
85.5 : 14.5
Comꢀ
poundꢀ
δ (J/Hz)
Amine fragment
Me HX
Acyl fragment
Me
CH
(S,S)ꢀ11
(R,S)ꢀ11
(S,S)ꢀ12
0.71 (d,
J = 6.7)
4.76 (qdd,
JM,X = 6.7,
JB,X = 2.8,
JA,X = 1.5)
4.65 (qdd,
JM,X = 6.7,
JB,X = 2.8,
JA,X = 1.5)
4.69 (qdd,
JM,X = 6.9,
JB,X = 3.0,
JA,X = 1.7)
4.64 (m)
1.37 (d,
J = 6.7)
4.34 (q,
J = 6.7)
1.14 (d,
J = 6.7)
1.39 (d,
J = 6.7)
4.17 (q,
J = 6.7)
0.73 (d,
JM,X = 6.9)
1.39 (d,
J = 6.8)
4.37 (q,
J = 6.8)
* dr = ((S,S)—(R,R))/((R,S)—(S,R)) (from the HPLC data
(Reprosil 100 Si); see Experimental).
(R,S)ꢀ12
(S,S)ꢀ13
1.11 (d,
JM,X = 6.9)
0.72 (d,
1.38 (d,
J = 6.7)
1.39 (d,
J = 6.6)
4.18 (q,
J = 6.7)
4.38 (q,
J = 6.6)
4.77 (qdd,
JM,X = 6.8,
JB,X = 2.8,
JA,X = 1.4)
4.66 (qdd,
JM,X = 6.9,
JB,X = 2.8,
JA,X = 1.5)
4.71 (qdd,
JM,X = 6.8,
JB,X = 3.0,
JA,X = 1.7)
4.65 (m)
The acylation of amine 1 was more stereoselective when
ibuprofen acyl chloride (4) was used as compared
to naproxen acyl chloride (3) and 2ꢀphenylpropionyl
chloride (5). In the case of acylation with acyl chlorꢀ
ides 3 and 5 in dichloromethane and acetonitrile,
the reaction temperature affected little the stereochemiꢀ
cal result of the reaction. Stereoselectivity of acylaꢀ
tion with acyl chloride 4 noticeably depended on the
temperature (for instance, dr for amides 11 were
95.0 : 5.0 and 97.9 : 2.1 in CH2Cl2 at +20 and –20 °C,
respectively).
JM,X = 6.8)
(R,S)ꢀ13
(S,S)ꢀ14
(R,S)ꢀ14
1.15 (d,
JM,X = 6.9)
1.42 (d,
J = 6.6)
4.21 (q,
J = 6.6)
0.75 (d,
JM,X = 6.9)
1.41 (d,
J = 6.8)
4.42 (q,
J = 6.8)
1.12 (d,
1.41 (d,
4.22 (q,
Acylation of nonfluorinated amine 2 was characterꢀ
ized by the same regularities. Thus, in the case of the
JM,X = 6.9)
J = 6.8)
J = 6.8)

2ꢀArylpropionyl chlorides in kinetic resolution
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
951
chemical ionization at atmospheric pressure (APCI), the
source temperature was 400 °C. Elemental analysis was perꢀ
formed on a PE 2400 II elemental analyzer (Perkin—Elmer Inꢀ
struments, USA).
2ꢀArylpropionyl chlorides 3—5 (general procedure). Oxalyl
chloride (175 μL, 2.0 mmol) was added to a suspension of acid
6—8 (1.0 mmol) in benzene (5 mL) with stirring. The reaction
mixture was stirred for 6 h at room temperature, concentrated
in vacuo, and dried over P2O5.
reaction of amine 2 with acyl chloride 4 at reduced temꢀ
peratures, a somewhat increase in stereoselectivity was
observed (dr for amides 12 were 98.2 : 1.8 and 99.0 : 1.0 in
toluene at +20 and –20 °C, respectively), while the stereoꢀ
chemical result of acylation of amine 2 with acyl chloride
5 virtually did not depend on temperature (dr for amides
14 were 97.0 : 3.0 and 97.2 : 2.8 in toluene at +20 and
–20 °C, respectively).
In conclusion, it was found that among compounds
studied, ibuprofen acyl chloride (4) is an acylating reagent
the most selective and sensitive to the changes in the reacꢀ
tion temperature as compared to naproxen acyl chloride
(3) and 2ꢀphenylpropionyl chlorides (5).
At the present, we continue our studies on the search
for the new efficient agents for resolution among 2ꢀarylꢀ
propionic acid derivatives and on the prospects for their
practical use in the resolution of racemic amines.
(RS)ꢀ2ꢀ(6ꢀMethoxynaphthꢀ2ꢀyl)propionyl chloride (3). The
yield was 97%, pale yellow crystals, m.p. 76 °C. 1H NMR
(CDCl3), δ: 1.67 (d, 3 H, Me, J = 6.9 Hz); 3.92 (s, 3 H, OMe);
4.24 (q, 1 H, CH, J = 6.9 Hz); 7.10—7.80 (m, 6 H, Ar).
(S)ꢀ2ꢀ(4ꢀIsobutylphenyl)propionyl chloride ((S)ꢀ4). The yield
was 95%, colorless oil. 1H NMR (CDCl3), δ: 0.91 (d, 6 H,
CH2CH(CH3)2, J = 6.7 Hz); 1.59 (d, 3 H, CH3, J = 7.1 Hz);
1.86 (m, 1 H, CH2CH(CH3)2); 2.57 (d, 2 H, CH2CH(CH3)2,
J = 7.5 Hz); 4.10 (q, 1 H, CH, J = 7.1 Hz); 7.15, 7.20 (both m,
4 H, Ar).
(RS)ꢀ2ꢀ(4ꢀIsobutylphenyl)propionyl chloride (4). The yield
was 95%, colorless oil. 1H NMR spectrum is identical to that of
compound (S)ꢀ4.
Experimental
(S)ꢀ2ꢀPhenylpropionyl chloride ((S)ꢀ5). The yield was 95%,
colorless oil. 1H NMR (CDCl3), δ: 1.60 (d, 3 H, Me, J = 6.8 Hz);
4.13 (q, 1 H, CH, J = 6.8 Hz); 7.28—7.41 (m, 5 H, Ph).
(RS)ꢀ2ꢀPhenylpropionyl chloride (5). The yield was 95%,
colorless oil. 1H NMR spectrum is identical to that of comꢀ
pound (S)ꢀ5.
Kinetic resolution (general procedure). A solution of acyl chloꢀ
ride 3—5 (0.15 mmol) in the corresponding solvent (toluene,
dichloromethane, or acetonitrile) (1.5 mL) was added in one
portion to a thermostated solution of amine 1 or 2 (0.3 mmol) in
the same solvent (1.5 mL) at a given temperature. The reaction
mixture was thermostated for 6 h at the given temperature,
washed with aqueous HCl (1 M, 2×3 mL) (in the case of the
reaction in acetonitrile, aq. HCl (1 M, 5 mL) was added to the
reaction mixture, followed by extraction the amide with benꢀ
zene); the organic layer was washed with brine (4×3 mL), 5% aq.
NaHCO3 (2×3 mL), water (2×3 mL), dried with MgSO4, and
concentrated. The residue was dried in vacuo over P2O5. Diasteꢀ
reomeric composition of amides 9—14 was determined by HPLC
(ReproSil 100Si).
(RS)ꢀ7,8ꢀDifluoroꢀ3ꢀmethylꢀ2,3ꢀdihydroꢀ4Hꢀ[1,4]benzꢀ
oxazine (1) and (RS)ꢀ3ꢀmethylꢀ2,3ꢀdihydroꢀ4Hꢀ[1,4]benzꢀ
oxazine (2) were obtained according to the known procedure.32
(S)ꢀ7,8ꢀDifluoroꢀ3ꢀmethylꢀ2,3ꢀdihydroꢀ4Hꢀ[1,4]benzoxazine
and (S)ꢀ3ꢀmethylꢀ2,3ꢀdihydroꢀ4Hꢀ[1,4]benzoxazine were obꢀ
tained as described earlier.20 (S)ꢀNaproxen, ibuprofen, (2RS)ꢀ
phenylpropionic and (2S)ꢀphenylpropionic acids are commerꢀ
cially available reagents. (S)ꢀIbuprofen was synthesized by resoꢀ
lution of a racemate by fractional crystallization of diastereoꢀ
meric salts with quinine from the acetone—methanol solvent
mixture and subsequent crystallization of the sodium salt accordꢀ
ing to the known method.33 (RS)ꢀNaproxen was obtained
by racemization of (S)ꢀnaproxen by melting with DBU acꢀ
cording to the described method.34 All the solvents were puriꢀ
fied using standard procedures just before use. Column flashꢀ
chromatography was performed on silica gel 60 (230—400 mesh)
(Lancaster). Melting points were determined on a SMP3 instꢀ
1
rument (Barloworld Scientific). H and 19F NMR spectra were
recorded on a Bruker DRXꢀ400 spectrometer (400 and 376 MHz,
respectively) with Me4Si and hexafluorobenzene as internal
The mixtures of amides and individual (S,S)ꢀdiastereomers
9 and 10 have been described earlier.20
1
standards. H NMR spectra of chlorides 3—5 were recorded in
CDCl3 at room temperature, 1H NMR spectra of amides
11—14, in DMSOꢀd6 at 100 °C. Specific rotation was deterꢀ
mined on a Perkin—Elmer M 341 polarimeter (the units are
(deg mL) (g dm)–1; the units for concentration of solutions are
g (100 mL)–1).
Analysis of diastereomeric composition of amides 9—14 by
HPLC was performed on a Knauer Smartlineꢀ1000 chromatoꢀ
graph (Germany) using a 4.6×250ꢀmm column filled with Reproꢀ
Sil 100 Si, 5 μm sorbent (Elsiko, Russia); the rate of elution was
1 mL min–1; detection was at 220 nm, the hexane—propanꢀ2ꢀol
was a liquid phase (80 : 1 for 9, 100 : 1 for 10, and 200 : 1 for
11—14). Mass spectra were recorded after chromatographic
resolution on a Shimadzu LCMSꢀ2010 instrument (a Phenomeꢀ
nex Luna C18(2) column, 150×2.0 mm, 3 μm, 100 Å, the acetoꢀ
nitrile—water (75 : 25) mixture was a liquid phase, the rate of
elution was 1.0 mL min–1, the column temperature was 60 °C)
with a quadrupole analyzer (in the positive or negative modes);
Synthesis of (S,S)ꢀamides 11—14 (general procedure). A soluꢀ
tion of (S)ꢀacyl chloride 4 or 5 (1 mmol) in toluene (10 mL) was
added to a solution of (S)ꢀamine 1 or 2 (2 mmol) in toluene
(10 mL) at +20 °C. The reaction mixture was thermostated for 6 h
at +20 °C; washed with aq. HCl (1 M, 2×3 mL), brine (4×3 mL),
5% aq. NaHCO3 (2×3 mL), water (2×3 mL), dried with MgSO4,
and concentrated. The residue was dried in vacuo over P2O5.
(S,S)ꢀAmides 11 and 12 were isolated by flashꢀchromatography
on silica gel (eluent, benzene), (S,S)ꢀamides 13 and 14, by reꢀ
crystallization from the EtOH—water solvent mixture.
Nꢀ[(2S)ꢀ2ꢀ(4ꢀIsobutylphenyl)propionyl]ꢀ7,8ꢀdifluoroꢀ(3S)ꢀ
3ꢀmethylꢀ2,3ꢀdihydroꢀ4Hꢀ[1,4]benzoxazine ((S,S)ꢀ11). The yield
was 68%, colorless oil, [α]D20 +96.0 (c 1.06, CHCl3), de ≥ 99.9%.
HPLC (ReproSil 100 Si, hexane—propanꢀ2ꢀol (200 : 1)):
1
τ = 8.6 min. H NMR (DMSOꢀd6), δ: 0.71 (d, 3 H, Me benzꢀ
oxazine, J = 6.7 Hz); 0.83 (d, 6 H, CH2CH(CH3)2, J = 6.8 Hz);
1.37 (d, 3 H, Me ibuprofen, J = 6.7 Hz); 1.80 (m, 1 H,

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Chulakov et al.
CH2CH(CH3)2); 2.40 (d, 2 H, CH2CH(CH3)2, J = 7.1 Hz);
4.01 (dd, 1 H, C(2)HB benzoxazine, J = 11.1 Hz, J = 2.8 Hz);
4.22 (dd, 1 H, C(2)HA benzoxazine, J = 11.1 Hz, J = 1.5 Hz);
4.34 (q, 1 H, CH ibuprofen, J = 6.8 Hz); 4.76 (qdd, 1 H, C(3)H
benzoxazine, J = 6.7 Hz, J = 2.8 Hz, J = 1.5 Hz); 6.82 (ddd, 1 H,
C(6)H benzoxazine, J = 10.1 Hz, J = 9.4 Hz, J = 8.1 Hz); 7.04
(m, 4 H, C6H4 ibuprofen); 7.54 (ddd, 1 H, C(5)H benzoxazine,
J = 9.4 Hz, J = 5.3 Hz, J = 2.5 Hz). 19F NMR (DMSOꢀd6), δ:
1.69 (ddd, 1 F, C(8)F, J = 21.2 Hz, J = 8.1 Hz, J = 2.5 Hz); 20.5
(m, 1 F, C(7)F). Found (%): C, 67.89; H, 5.33; N, 4.36.
C18H17F2NO. Calculated (%): C, 68.13; H, 5.40; N, 4.41. MS
(APCI), m/z (Irel (%)): 374 [M + H]+ (100), 415 [M + H +
+ CH3CN]+ (5.99).
J = 8.2 Hz, J = 7.3 Hz, J = 1.6 Hz); 7.10—7.28 (m, Ph); 6.77
(dd, 1 H, C(5)H benzoxazine, J = 8.2 Hz, J = 1.4 Hz). Found (%):
C, 76.77; H, 6.75; N, 4.85. C18H19NO2. Calculated (%):
C, 76.84; H, 6.81; N, 4.98.
Synthesis of amides 11—14 (a mixture of diastereomers).
A solution of (RS)ꢀacyl chloride 4 or 5 (1 mmol) in toluene
(10 mL) was added to a solution of (S)ꢀamine 1 or 2 (2 mmol) in
toluene (10 mL) at +20 °C. The reaction mixture was thermoꢀ
stated for 6 h at +20 °C; washed with aq. HCl (1 M, 2×3 mL),
brine (4×3 mL), 5% aq. NaHCO3 (2×3 mL), water (2×3 mL),
dried with MgSO4, and concentrated. The residue was dried
in vacuo over P2O5. Diastereomers 11—14 were isolated by flashꢀ
chromatography on silica gel (eluent, benzene).
Nꢀ[(2S)ꢀ2ꢀ(4ꢀIsobutylphenyl)propionyl]ꢀ(3S)ꢀ3ꢀmethylꢀ2,3ꢀ
dihydroꢀ4Hꢀ[1,4]benzoxazine ((S,S)ꢀ12). The yield was 70%,
colorless oil, [α]D +84.25 (c 1.0, CHCl3), de ≥ 99.9%. HPLC
Nꢀ[(2RS)ꢀ2ꢀ(4ꢀIsobutylphenyl)propionyl]ꢀ7,8ꢀdifluoroꢀ(3S)ꢀ
3ꢀmethylꢀ2,3ꢀdihydroꢀ4Hꢀ[1,4]benzoxazine (11). The yield was
55%, colorless oil, de 0. HPLC (ReproSil 100 Si, hexane—proꢀ
20
(ReproSil 100 Si, hexane—propanꢀ2ꢀol (200 : 1)): τ = 6.8 min.
1H NMR (DMSOꢀd6), δ: 0.73 (d, 3 H, Me benzoxazine,
J = 6.9 Hz); 0.83 (d, 6 H, CH2CH(CH3)2, J = 6.6 Hz); 1.39
(d, 3 H, Me ibuprofen, J = 6.8 Hz); 1.80 (m, 1 H, CH2CH(CH3)2);
2.40 (d, 2 H, CH2CH(CH3)2, J = 7.1 Hz); 3.91 (dd, 1 H, C(2)HB
benzoxazine, J = 10.8 Hz, J = 3.0 Hz); 4.06 (dd, 1 H, C(2)HA
benzoxazine, J = 10.8 Hz, J = 1.7 Hz); 4.37 (q, 1 H, CH ibuproꢀ
fen, J = 6.8 Hz); 4.69 (qdd, 1 H, C(3)H benzoxazine, J = 6.9 Hz,
J = 3.0 Hz, J = 1.7 Hz); 6.78 (dd, 1 H, C(8)H benzoxazine,
J = 8.1 Hz, J = 1.6 Hz); 6.86 (ddd, 1 H, C(7)H benzoxazine,
J = 8.1 Hz, J = 7.2 Hz, J = 1.3 Hz); 7.00 (ddd, 1 H, C(6)H
benzoxazine, J = 8.3 Hz, J = 7.2 Hz, J = 1.6 Hz); 7.03 (m, 4 H,
C6H4 ibuprofen); 7.65 (dd, 1 H, C(5)H benzoxazine, J = 8.3 Hz,
J = 1.3 Hz). MS (APCI), m/z (Irel (%)): 338 [M + H]+ (100), 379
[M + H + CH3CN]+ (4.3).
panꢀ2ꢀol (200 : 1)): τ
5.6 min, τ
8.6 min. 1H NMR
(R,S)
(S,S)
(DMSOꢀd6), δ: 0.71 (d, 0.5×3 H, Me benzoxazine, J = 6.7 Hz);
0.83 (d, 0.5×6 H, CH2CH(CH3)2, J = 6.8 Hz); 0.87 (d, 0.5×6 H,
CH2CH(CH3)2, J = 6.8 Hz); 1.14 (d, 0.5×3 H, Me benzoxazine,
J = 6.7 Hz); 1.37 (d, 0.5×3 H, Me ibuprofen, J = 6.8 Hz); 1.39
(d, 0.5×3 H, Me ibuprofen, J = 6.7 Hz); 1.80 (m, 0.5×1 H,
CH2CH(CH3)2); 1.85 (m, 0.5×1 H, CH2CH(CH3)2); 2.40
(d, 0.5×2 H, CH2CH(CH3)2, J = 7.1 Hz); 2.44 (d, 0.5×2 H,
CH2CH(CH3)2, J = 6.9 Hz); 3.58 (dd, 0.5×1 H, C(2)HB benzꢀ
oxazine, J = 11.0 Hz, J = 2.8 Hz); 4.01 (dd, 0.5×1 H, C(2)HB
benzoxazine, J = 11.0 Hz, J = 2.8 Hz); 4.16 (dd, 0.5×1 H,
C(2)HA benzoxazine, J = 11.0 Hz, J = 1.5 Hz); 4.17 (q, 1 H, CH
ibuprofen, J = 6.7 Hz); 4.22 (dd, 0.5×1 H, C(2)HA benzoxazine,
J = 11.1 Hz, J = 1.5 Hz); 4.34 (q, 0.5×1 H, CH ibuprofen,
J = 6.8 Hz); 4.65 (qdd, 1 H, C(3)H benzoxazine, J = 6.7 Hz,
J = 2.8 Hz, J = 1.5 Hz); 4.76 (qdd, 0.5×1 H, C(3)H benzꢀ
oxazine, J = 6.7 Hz, J = 2.8 Hz, J = 1.5 Hz); 6.82 (ddd, 1 H,
C(6)H benzoxazine, J = 10.1 Hz, J = 9.4 Hz, J = 8.1 Hz); 7.04
(m, 0.5×4 H, C6H4 ibuprofen); 7.12, 7.23 (both m, 0.5×4 H,
C6H4 ibuprofen); 7.55 (m, 1 H, C(5)H benzoxazine). 19F NMR
(DMSOꢀd6), δ: 1.69 (ddd, 0.5×1 F, C(8)F, J = 21.2 Hz, J = 8.1 Hz,
J = 2.5 Hz); 2.08 (ddd, 0.5×1 F, C(8)F, J = 22.2 Hz, J = 9.4 Hz,
J = 2.8 Hz); 20.50 (m, 1 F, C(7)F). Found (%): C, 70.48; H, 6.89;
N, 3.91. C22H25F2NO2. Calculated (%): C, 70.76; H, 6.75;
N, 3.75.
Nꢀ[(2RS)ꢀ2ꢀ(4ꢀIsobutylphenyl)propionyl]ꢀ(3S)ꢀ3ꢀmethylꢀ
2,3ꢀdihydroꢀ4Hꢀ[1,4]benzoxazine (12). The yield was 62%, colꢀ
orless oil, de 70%. HPLC (ReproSil 100 Si, hexane—propanꢀ2ꢀ
ol (200 : 1)): τ(R,S) 4.8 min, τ(S,S) 6.8 min. 1H NMR (DMSOꢀd6),
δ: 0.73 (d, 0.85×3 H, Me benzoxazine, J = 6.9 Hz); 0.83
(d, 0.85×6 H, CH2CH(CH3)2, J = 6.6 Hz); 0.87 (d, 0.15×6 H,
CH2CH(CH3)2, J = 6.6 Hz); 1.11 (d, 0.15×3 H, Me benzoxazine,
J = 6.9 Hz); 1.38 (d, 0.15×3 H, Me ibuprofen, J = 6.7 Hz); 1.39
(d, 0.85×3 H, Me ibuprofen, J = 6.8 Hz); 1.80 (m, 1 H,
CH2CH(CH3)2); 2.40 (d, 0.85×2 H, CH2CH(CH3)2, J = 7.1 Hz);
2.44 (d, 0.15×2 H, CH2CH(CH3)2, J = 7.1 Hz); 3.61 (dd, 0.15×1 H,
C(2)HB benzoxazine, J = 10.8 Hz, J = 2.1 Hz); 3.91 (dd, 0.85×1 H,
C(2)HB benzoxazine, J = 10.8 Hz, J = 3.0 Hz); 4.02 (dd, 0.15×1 H,
C(2)HA benzoxazine, J = 10.8 Hz, J = 1.7 Hz); 4.06 (dd, 0.85×1 H,
C(2)HA benzoxazine, J = 10.8 Hz, J = 1.7 Hz); 4.18 (q, 0.15×1 H,
CH ibuprofen, J = 6.7 Hz); 4.37 (q, 0.85×1 H, CH ibuprofen,
J = 6.8 Hz); 4.64 (m, 0.15×1 H, C(3)H benzoxazine); 4.69 (qdd,
0.85×1 H, C(3)H benzoxazine, J = 6.9 Hz, J = 3.0 Hz, J = 1.7 Hz);
6.78 (dd, 0.85×1 H, C(8)H benzoxazine, J = 8.1 Hz, J = 1.6 Hz);
6.82 (m, 0.15×1 H, C(8)H benzoxazine); 6.80 (m, 0.15×1 H,
Nꢀ[(2S)ꢀ2ꢀPhenylpropionyl]ꢀ7,8ꢀdifluoroꢀ(3S)ꢀ3ꢀmethylꢀ
2,3ꢀdihydroꢀ4Hꢀ[1,4]benzoxazine ((S,S)ꢀ13). The yield was 65%,
20
colorless crystals, m.p. 165 °C (EtOH—water), [α]D +127.4
(c 1.0, CHCl3), de ≥ 99.9%. HPLC (ReproSil 100 Si, hexꢀ
ane—propanꢀ2ꢀol (200 : 1)): τ = 11.1 min. 1H NMR (DMSOꢀd6),
δ: 0.72 (d, 3 H, Me benzoxazine, J = 6.8 Hz); 1.39 (d, 3 H, Me
phenylpropionic acid, J = 6.6 Hz); 4.02 (dd, 1 H, C(2)HB benzꢀ
oxazine, J = 10.9 Hz, J = 2.8 Hz); 4.23 (dd, 1 H, C(2)HA benzꢀ
oxazine, J = 10.9 Hz, J = 1.4 Hz); 4.38 (q, 1 H, CH phenylproꢀ
pionic acid, J = 6.6 Hz); 4.77 (qdd, 1 H, C(3)H benzoxazine,
J = 6.8 Hz, J = 2.8 Hz, J = 1.4 Hz); 6.84 (ddd, 1 H, C(6)H
benzoxazine, J = 10.2 Hz, J = 9.0 Hz, J = 8.2 Hz); 7.12—7.30
(m, Ph); 7.55 (ddd, 1 H, C(5)H benzoxazine, J = 9.0 Hz,
J = 5.3 Hz, J = 2.5 Hz). 19F NMR (DMSOꢀd6), δ: 1.75 (ddd,
1 F, C(8)F, J = 21.2 Hz, J = 8.0 Hz, J = 2.5 Hz); 20.58 (m, 1 F,
C(7)F). Found (%): C, 67.89; H, 5.33; N, 4.36. C18H17F2NO2.
Calculated (%): C, 68.13; H, 5.40; N, 4.41.
Nꢀ[(2S)ꢀ2ꢀPhenylpropionyl]ꢀ(3S)ꢀ3ꢀmethylꢀ2,3ꢀdihydroꢀ
4Hꢀ[1,4]benzoxazine ((S,S)ꢀ14). The yield was 55%, white crysꢀ
20
tals, m.p. 76 °C (EtOH—water), [α]D +136.2 (c 1.0, CHCl3),
de ≥ 99.9%. HPLC (ReproSil 100 Si, hexane—propanꢀ2ꢀol
(200 : 1)): τ = 7.6 min. 1H NMR (DMSOꢀd6), δ: 0.75 (d, 3 H, Me
benzoxazine, J = 6.9 Hz); 1.41 (d, 3 H, Me phenylpropionic
acid, J = 6.8 Hz); 3.92 (dd, 1 H, C(2)HB benzoxazine, J = 10.8 Hz,
J = 3.0 Hz); 4.07 (dd, 1 H, C(2)HA benzoxazine, J = 10.8 Hz,
J = 1.7 Hz); 4.42 (q, 1 H, CH phenylpropionic acid, J = 6.8 Hz);
4.71 (qdd, 1 H, C(3)H benzoxazine, J = 6.9 Hz, J = 3.0 Hz,
J = 1.7 Hz); 6.77 (dd, 1 H, C(8)H benzoxazine, J = 8.2 Hz,
J = 1.4 Hz); 6.87 (ddd, 1 H, C(7)H benzoxazine, J = 8.2 Hz,
J = 7.3 Hz, J = 1.4 Hz); 7.00 (ddd, 1 H, C(6)H benzoxazine,

2ꢀArylpropionyl chlorides in kinetic resolution
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
953
C(7)H benzoxazine); 6.86 (ddd, 0.85×1 H, C(7)H benzoxazine,
J = 8.1 Hz, J = 7.2 Hz, J = 1.3 Hz); 7.00 (ddd, 1 H, C(6)H
benzoxazine, J = 8.3 Hz, J = 7.2 Hz, J = 1.6 Hz); 7.03
(m, 0.85×4 H, C6H4 ibuprofen); 7.12, 7.23 (both m, 0.15×4 H,
C6H4 ibuprofen); 7.65 (dd, 1 H, C(5)H benzoxazine, J = 8.3 Hz,
J = 1.3 Hz). Found (%): C, 78.25; H, 8.36; N, 4.13. C22H27NO2.
Calculated (%): C, 78.30; H, 8.06; N, 4.15.
Nꢀ[(2RS)ꢀ2ꢀPhenylpropionyl]ꢀ7,8ꢀdifluoroꢀ(3S)ꢀ3ꢀmethylꢀ
2,3ꢀdihydroꢀ4Hꢀ[1,4]benzoxazine (13). The yield was 60%,
colorless crystals, m.p. 160 °C, de 10%. HPLC (ReproSil 100 Si,
09ꢀPꢀ3ꢀ2001 and 09ꢀIꢀ3ꢀ2004), and the Ministry of
Education and Science of the RF (State Contract
No. 02.522.12.2011).
References
1. H. B. Kagan, J. C. Fiaud, Top. Stereochem., 1988, 18, 249.
2. J. M. Keith, J. F. Larrow, E. N. Jacobsen, Adv. Synth. Catal.,
2001, 343, 5.
3. E. Vedejs, M. Jure, Angew. Chem., Int. Ed., 2005, 44, 3974.
4. M. Breuer, K. Ditrich, T. Habicher, B. Hauer, M. Keßeler,
R. Stürmer, T. Zelinski, Angew. Chem., Int. Ed., 2004,
43, 788.
5. F. van Rantwijk, R. A. Sheldon, Tetrahedron, 2004, 60, 501.
6. K. Ditrich, Synthesis, 2008, 2283.
7. S. Takayama, S. T. Lee, S.ꢀC. Hung, C.ꢀH. Wong, Chem.
Commun., 1999, 127.
8. M. Nechab, N. Azzi, N. Vanthuyne, J. Org. Chem., 2007,
72, 6918.
9. S. Arai, S. BelleminꢀLapponnaz, G. Fu, Angew. Chem., Int.
Ed., 2001, 40, 234.
10. F. Arp, G. Fu, J. Am. Chem. Soc., 2006, 128, 14264.
11. K. Arnold, B. Davies, D. Hérault, A. Whiting, Angew. Chem.,
Int. Ed., 2008, 47, 2673.
12. C. K. De, E. G. Klauber, D. Seidel, J. Am. Chem. Soc., 2009,
131, 17060.
13. B. Fowler, P. J. Mikochik, S. J. Miller, J. Am. Chem. Soc.,
2010, 132, 2870.
14. K. Kondo, T. Kurosaki, Y. Murakami, Synlett, 1998, 725.
15. N. Maezaki, A. Furusawa, S. Uchida, T. Tanaka, Tetraꢀ
hedron, 2001, 57, 9309.
16. A. Karnik, S. Kamath, Tetrahedron: Asymmetry, 2008,
19, 45.aa
17. S. Arseniyadis, A. Valleix, A. Wagner, C. Mioskowski, Anꢀ
gew. Chem., Int. Ed., 2004, 43, 3314.
18. A. G. AlꢀSehemi, R. S. Atkinson, J. Fawcett, J. Chem. Soc.,
Perkin Trans. 1, 2002, 257.
19. Z. J. Kamin´ski, B. Kolesin´ska, J. E. Kamin´ska, J. Góra,
J. Org. Chem., 2001, 66, 6276.
20. V. N. Charushin, V. P. Krasnov, G. L. Levit, M. A. Koroꢀ
lyova, M. I. Kodess, O. N. Chupakhin, M. H. Kim, H. S.
Lee, Y. J. Park, K.ꢀCh. Kim, Tetrahedron: Asymmetry, 1999,
10, 2691.
21. V. P. Krasnov, G. L. Levit, I. N. Andreeva, A. I. Grishakov,
V. N. Charushin, O. N. Chupakhin, Mendeleev Commun.,
2002, 12, 27.
22. V. P. Krasnov, G. L. Levit, I. M. Bukrina, I. N. Andreeva,
L. Sh. Sadretdinova, M. A. Korolyova, M. I. Kodess, V. N.
Charushin, O. N. Chupakhin, Tetrahedron: Asymmetry, 2003,
14, 1985.
hexane—propanꢀ2ꢀol (200 : 1)): τ
6.2 min, τ
11.1 min.
(R,S)
(S,S)
1H NMR (DMSOꢀd6), δ: 0.72 (d, 0.55×3 H, Me benzoxazine,
J = 6.8 Hz); 1.15 (d, 0.45×3 H, Me benzoxazine, J = 6.9 Hz);
1.39 (d, 0.55×3 H, Me phenylpropionic acid, J = 6.6 Hz); 1.42
(d, 0.45×3 H, Me phenylpropionic acid, J = 6.6 Hz); 3.62
(dd, 0.45×1 H, C(2)HB benzoxazine, J = 10.9 Hz, J = 2.8 Hz);
4.02 (dd, 0.55×1 H, C(2)HB benzoxazine, J = 10.8 Hz, J = 3.0 Hz);
4.17 (dd, 0.45×1 H, C(2)HA benzoxazine, J = 10.9 Hz, J = 1.5 Hz);
4.21 (q, 0.45×1 H, CH phenylpropionic acid, J = 6.6 Hz); 4.23
(dd, 0.55×1 H, C(2)HA benzoxazine, J = 10.8 Hz, J = 1.4 Hz);
4.38 (q, 0.55×1 H, CH phenylpropionic acid, J = 6.8 Hz); 4.66
(qdd, 0.45×1 H, C(3)H benzoxazine, J = 6.9 Hz, J = 2.8 Hz,
J = 1.5 Hz); 4.77 (qdd, 0.55×1 H, C(3)H benzoxazine, J = 6.8 Hz,
J = 2.8 Hz, J = 1.4 Hz); 6.84 (ddd, 1 H, C(6)H benzoxazine,
J = 10.2 Hz, J = 9.0 Hz, J = 8.2 Hz); 7.12—7.30 (m, Ph); 7.55
(ddd, 1 H, C(5)H benzoxazine, J = 9.0 Hz, J = 5.3 Hz,
J = 2.5 Hz). 19F NMR (DMSOꢀd6), δ: 1.75 (ddd, 0.55×1 F,
C(8)F, J = 21.2 Hz, J = 8.0 Hz, J = 2.5 Hz); 2.13 (ddd, 0.45×1 F,
C(8)F, J = 21.2 Hz, J = 8.0 Hz, J = 2.5 Hz); 20.58 (m, 1 F,
C(7)F). Found (%): C, 68.12; H, 5.37; N, 4.37. C18H17F2NO2.
Calculated (%): C, 68.13; H, 5.40; N, 4.41.
Nꢀ[(2RS)ꢀ2ꢀPhenylpropionyl]ꢀ(3S)ꢀ3ꢀmethylꢀ2,3ꢀdihydroꢀ
4Hꢀ[1,4]benzoxazine (14). The yield was 55%, colorless crystals,
m.p. 70—71 °C, de 60%. HPLC (ReproSil 100 Si, hexꢀ
ane—propanꢀ2ꢀol (200 : 1)): τ
5.6 min, τ
7.6 min.
(R,S)
(S,S)
1H NMR (DMSOꢀd6), δ: 0.75 (d, 0.8×3 H, Me benzoxazine,
J = 6.9 Hz); 1.12 (d, 0.2×3 H, Me benzoxazine, J = 6.9 Hz); 1.41
(d, 3 H, Me phenylpropionic acid, J = 6.8 Hz); 3.65 (m, 0.2×1 H,
C(2)HB benzoxazine); 3.92 (dd, 0.8×1 H, C(2)HB benzoxazine,
J = 10.8 Hz, J = 3.0 Hz); 4.02 (m, 0.2×1 H, C(2)HA benzꢀ
oxazine); 4.07 (dd, 0.8×1 H, C(2)HA benzoxazine, J = 10.8 Hz,
J = 1.7 Hz); 4.22 (q, 0.2×1 H, CH phenylpropionic acid, J = 6.8 Hz);
4.42 (q, 0.8×1 H, CH phenylpropionic acid, J = 6.8 Hz); 4.65
(m, 0.2×1 H, C(3)H benzoxazine); 4.71 (qdd, 0.8×1 H, C(3)H
benzoxazine, J = 6.9 Hz, J = 3.1 Hz, J = 1.7 Hz); 6.77
(dd, 0.8×1 H, C(8)H benzoxazine, J = 8.2 Hz, J = 1.4 Hz); 6.82
(m, 0.2×1 H, C(8)H benzoxazine); 6.85 (m, 1 H, C(7)H benzꢀ
oxazine); 6.87 (ddd, 0.8×1 H, C(7)H benzoxazine, J = 8.2 Hz,
J = 7.3 Hz, J = 1.4 Hz); 7.00 (ddd, 1 H, C(6)H benzoxazine,
J = 8.2 Hz, J = 7.3 Hz, J = 1.6 Hz); 7.10—7.28 (m, Ph); 6.77
(dd, 1 H, C(5)H benzoxazine, J = 8.2 Hz, J = 1.4 Hz). Found (%):
C, 76.56; H, 6.97; N, 4.75. C18H19NO2. Calculated (%): C, 76.84;
H, 6.81; N, 4.98.
23. V. P. Krasnov, G. L. Levit, M. I. Kodess, V. N. Charushin,
O. N. Chupakhin, Tetrahedron: Asymmetry, 2004, 15, 859.
24. V. P. Krasnov, G. L. Levit, M. A. Koroleva, I. M. Bukrina,
L. Sh. Sadretdinova, I. N. Andreeva, V. N. Charushin, O. N.
Chupakhin, Izv. Akad. Nauk, Ser. Khim., 2004, 1203 [Russ.
Chem. Bull., Int. Ed., 2004, 53, 1253].
25. D. A. Gruzdev, G. L. Levit, V. P. Krasnov, E. N. Chulakov,
L. Sh. Sadretdinova, A. N. Grishakov, M. A. Ezhikova, M. I.
Kodess, V. N. Charushin, Tetrahedron: Asymmetry, 2010,
21, 936.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 10ꢀ03ꢀ00084),
the Council on Grants at the President of the Russian
Federation (Program of State Support for Leading Scienꢀ
tific Schools of the RF, Grant NShꢀ65261.2010.3), the
Ural Branch of the Russian Academy of Sciences (Grants

954
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
Chulakov et al.
26. H. Herlinger, H. Kleimann, I. Ugi, Liebigs Ann. Chem., 1967,
706, 37.
27. L. Leclerq, I. Suisse, F. AgbossouꢀNiedercorn, Eur. J. Org.
Chem., 2010, 2696.
28. I. Shiina, K. Nakata, K. Ono, Y. Onda, M. Itagak, J. Am.
Chem. Soc., 2010, 132, 11629.
29. A. Andreou, N. Al Shaye, H. Brown, J. Eames, Tetrahedron
Lett., 2010, 51, 6935.
32. I. Hayakawa, S. Atarashi, S. Yokohama, M. Imamura, K.ꢀI.
Sakano, M. Furukawa, Antimicrob. Agents Chemother., 1986,
29, 163.
33. T. Manimaran, G. P. Stahly, Tetrahedron: Asymmetry, 1993,
4, 1949.
34. E. J. Ebbers, G. J. Ariaans, A. Bruggink, B. Zwanenburg,
Tetrahedron: Asymmetry, 1999, 10, 3701.
30. JP Pat. 2000178265; Chem. Abstrs, 2000, 133, 43530.
31. A. Horeau, Tetrahedron, 1975, 31, 1307.
Received January 26, 2011