Efficient resolution of some monoprotected derivatives of Corey lactone

Article abstract of DOI:10.1016/j.mencom.2012.05.002

Racemic monoprotected at primary hydroxy group Corey lactones were resolved using (1S,2R,5R)-6,6-dimethyl-4-oxo-3-oxabicyclo-[3.1.0]hexan-2-ol as a chiral auxiliary reagent of hemiacylal chemotype.

Full text of DOI:10.1016/j.mencom.2012.05.002

Mendeleev
Communications
Mendeleev Commun., 2012, 22, 125–126
Efficient resolution of some monoprotected
derivatives of Corey lactone
Vladimir V. Loza, Nikolay S. Vostrikov and Mansur S. Miftakhov*
Institute of Organic Chemistry, Ufa Scientific Centre of the Russian Academy of Sciences, 450054 Ufa,
Russian Federation. Fax: +7 347 235 6066; e-mail: bioreg@anrb.ru
DOI: 10.1016/j.mencom.2012.05.002
Racemic monoprotected at primary hydroxy group Corey lactones were resolved using (1S,2R,5R)-6,6-dimethyl-4-oxo-3-oxabicyclo-
[3.1.0]hexan-2-ol as a chiral auxiliary reagent of hemiacylal chemotype.
(–)-Lactone diol 1 (the Corey lactone) and its monoprotected
derivatives such as 2 are widely used as key synthons in the non-
O
O
cuprate ‘linear’synthesis of natural prostaglandins and their ana-
i, 1.1 equiv. RCl
logues.1,2 The syntheses of ( )-1,2 have already been reported.3–6
( )-1
Imidazole, CH2Cl2,
room temperature
The main problem in these syntheses is producing the corre-
sponding enantiopure form. The known procedures involve the use
of enzymatic methods,7 the separation of suitable diastereomeric
derivatives of ( )-18 and resolution of the ( )-1 precursors.9
However, each of these methods suffers from shortcomings: the
necessity of the tedious search for appropriate enzymes, of the
repeated crystallization of diastereomeric derivatives and so on.
a R = SiMe2But, 94%
b R = SiPr3i , 85%
c R = Bz, 80%
OR
HO
O
( )-2a–c
HO
O
0.01 equiv. TsOH
C6H6, heat, 1 h
+
2a–c
H
H
O
3
O
O
O
O
O
O
O
OH
HO
+
+
OR
OBz
(–)-1
OR
O
O
O
O
H
O
O
In this communication, we report a simple and practical method
for the production of both enantiomers of ( )-2 via an easy
separation of their diastereomeric derivatives obtained with the
readily available homochiral hemiacylal 310 (Scheme 1). It seemed
reasonable to facilitate the resolution by firstly transforming the
primary hydroxy group in compound 1 to obtain derivatives 2a–c
with bulky silane or benzoate protective groups followed by chiral
derivatization of the secondary hydroxyl. Derivatives 2a–c were
easily prepared by selective reaction of ( )-1 with the corre-
sponding RCl under standard conditions.11,†
H
H
H
O
O
O
H
H
6c (for 2c), 11%
4a, 30%
4b, 33%
4c, 40%
5a, 26%
5b, 30%
5c, 37%
Scheme 1
General protocol for acylales 4–6. A solution of ( )-2a,b (1.0 mmol),
3 (1.05 mmol) and anhydrous TsOH (0.01 mmol) in dry benzene (20 ml)
was stirred and refluxed for 1 h with continuous removal of water with a
Dean–Stark trap. The solution was concentrated under reduced pressure,
and the residue was diluted with CH2Cl2 (5 ml) and washed with water
(2×3 ml) and brine, and then dried over Na2SO4. Removal of the solvent
under reduced pressure produced oil, which was fractionated by column
chromatography.
General protocol for enantiomeric silanes 2a,b and benzoates 2c. A solu-
tion of a diastereomer 4 or 5 (0.5 mmol) and PPTS (5 mg, 0.02 mmol) in
10 ml of MeOH was stirred at 60°C for 1 h. The solvent was evaporated
in vacuo. The residue was dissolved in water (10 ml) and extracted with
CH2Cl2 (3×5 ml). The combined organic phases were washed with water
and brine. Removal of the solvent under reduced pressure and column
chromatography of the residue on silica gel afforded the required products
as well as recovered chiral auxiliary 3 (~50%), dimer 7 (~5–7%) and methyl
acetal 8 (~25%). The spectral features of the enantiomeric 2a–c were
identical with spectral features of the corresponding racemic mixtures.
For characteristics of compounds synthesized, see Online Supplementary
Materials.
The TsOH-catalyzed reaction of alcohols 2a–c with hemiacylal
3 proceeded equally well in refluxing benzene with azeotropic
removal of water. Note that catalysis with camphorsulfonic acid
†
General protocol for silane derivatives 2a,b. Imidazole (0.87 g,
12.78 mmol) and chlorosilane R3SiCl (6.39 mmol) were added (in case
of 2b, 15 mg of DMAP were also added) to a stirred solution of ( )-1
(1.0 g, 5.81 mmol) in 10 ml of anhydrous CH2Cl2 under argon at 0°C.
Stirring at room temperature was continued overnight. The imidazole
hydrochloride was removed by filtration through a short pad of Celite
and washed with CH2Cl2 (2×5 ml). The combined filtrates were washed
with water and aqueous NaHCO3 (2×3 ml), brine and dried. Removal of
the solvent under reduced pressure afforded the required silanes.
General protocol for 2c. A solution of benzoyl chloride (6.39 mmol)
in 5 ml of pyridine was added to a stirred solution of ( )-1 (1.0 g, 5.81 mmol)
in 10 ml of anhydrous pyridine under argon at 0°C. The reaction mixture
was stirred at room temperature for 24 h. After removal of pyridine
and pyridine hydrochloride, the crude product was purified by silica gel
chromatography.
© 2012 Mendeleev Communications. All rights reserved.
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Mendeleev Commun., 2012, 22, 125–126
(CSA) led to intense hydrolysis of the silane protective group in
Online Supplementary Materials
the case of 2a, whereas pyridinium-p-toluenesulfonate (PPTS)
was not effective.
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.mencom.2012.05.002.
Diastereomeric products 4a–c and 5a–c were formed in the
reaction in nearly equal quantities in 56–77% overall yields.†
Epimerization of chiral centre in reagent 3 occurred to a negligible
extent only in the case of 2c, when anomeric product 6c was
isolated (although in insignificant amounts) along with the major
products 4c and 5c. The configuration of 6c follows from the
doublet (J 4.2 Hz) character of the anomeric H-2' signal in the
1H NMR spectrum, whereas compounds 4 and 5 display the cor-
responding signal as a singlet.
Diastereomeric pairs of 4a–c and 5a–c differed significantly
in their mobility during chromatography on silica gel (DRf =
= 0.04–0.10) and could be easily thus separated. The regenera-
tion of (–)-2a–c and their corresponding (+)-enantiomers from
the individual diastereomers 4a–c and 5a–c was achieved by short
heating with a catalytic amount of PPTS in MeOH (Scheme 2).
The chiral auxiliary 3 was recovered in 50% yield along with
dimer 7 (~5–7%) and methyl derivative 8 (~25%) (cf. ref. 18).
Compounds 7 and 8 can be transformed into lactol 3 by acidic
hydrolysis.
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O
O
O
O
O
O
O
MeOH, heat
PPTS
4a–c
+
H
H
H
H
OR
O
HO
(–)-2a–c
7, ~5–7%
O
HO
MeO
O
O
+
+
H
H
H
H
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8, ~25%
3, ~50%
O
O
MeOH, heat
PPTS
+
8
3
+
+
7
5a–c
~50%
~5–7%
~25%
OR
HO
11 P. J. Kocien´ski, Protecting Groups, Thieme, Stuttgart, 1994, p. 260.
(+)-2a–c
12 O
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,
(–)-2a, 68% (>98% ee) (+)-2a, 64% (>98% ee)
(–)-2b, 70% (>97% ee) (+)-2b, 71% (>97% ee)
(–)-2c, 85% (>96% ee) (+)-2c, 86% (>96% ee)
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Scheme 2
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1982, 23, 4057.
In summary, we have elaborated a three-step protocol that
produces enantiomers of the Corey lactone derivatives 2a–c from
racemic lactone ( )-1 in overall yields 20–25%. This protocol
provides an additional example of the hemiacylal 3 [(–)-3 or (+)-3]
efficacy as a reagent for the resolution of racemic alcohols, in
addition to the published resolutions of alletrolone,13 4-hydroxy-
2-cyclopenten-1-one,14 lineatine,15 2-allyl-4-hydroxycyclo-
pentenone16 etc.17 Taking into consideration the importance and
prevalence of the Corey strategy in the prostaglandin synthesis, we
hope the protocol described above could find an application in
the chemistry of prostaglandins and other cyclopentanoids as well.
15 K. Mori, T. Uematsu, M. Minobe and K. Vanagi, Tetrahedron, 1983, 39,
1735.
16 Jpn. Kokai Tokkyo Koho, Jpn. Patent 58041836, Teijin (Chem. Abstr.,
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17 J. Salaün, Chem. Rev., 1989, 89, 1247.
Received: 28th December 2011; Com. 11/3856
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