A new and efficient route to derivatives of (R)-4-hydroxycyclohex-2-enone

Article abstract of DOI:10.1039/b107085a

A new and efficient route has been developed to four derivatives of (R)-4-hydroxycyclohex-2-enone (7-10) from one intermediate, 6. These derivatives are useful chiral building blocks in the synthesis of natural products and in asymmetric reactions. The key step is a stereoselective intramolecular ene reaction with 4 A MS as the Lewis acid and catalyst.

Full text of DOI:10.1039/b107085a

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A new and efficient route to derivatives of (R)-4-hydroxycyclohex-
2-enone
Libing Yu, Ruzhou Zhang*† and Zhiqin Wang
1
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road,
Shanghai 200032, China
Received (in Cambridge, UK) 7th August 2001, Accepted 26th September 2001
First published as an Advance Article on the web 30th October 2001
A new and efficient route has been developed to four derivatives of (R)-4-hydroxycyclohex-2-enone (7–10) from
one intermediate, 6. These derivatives are useful chiral building blocks in the synthesis of natural products and
in asymmetric reactions. The key step is a stereoselective intramolecular ene reaction with 4 Å MS as the Lewis
acid and catalyst.
Introduction
Since polyoxygenated carbocyclic fragments are abundant in a
variety of natural products, there is a constant need for the
development of a general method for the stereoselective
synthesis of these compounds with a view to natural product
total synthesis and the development of efficient routes to new
pharmaceuticals. The title compounds are considered to be very
useful chiral starting materials and are found to be structural
units in many natural products with biological activity, such as
ML-236A,1 compactin,1 FK-506,2 koninginin3 and rapamycin,4
etc. (Fig. 1). Furthermore, the compounds (R)- and (S)-4-
hydroxycyclohex-2-enone can be used with excellent diastereo-
selectivity in Diels–Alder reactions as the dienophile and in
1,2- or 1,4-conjugate additions as the Michael acceptor. This
has encouraged organic chemists to develop syntheses of (R)-
and (S)-4-hydroxycyclohex-2-enone and their derivatives.
Winterfeldt and co-workers developed a simple approach to
(S)-4-hydroxycyclohex-2-enone by using the reversibility of the
Diels–Alder reaction with the configurationally well-defined
cyclopentadiene as a chiral template.5 To complete their syn-
thesis of (R)- and (S)-4-hydroxycyclohex-2-enone, Solladié and
co-workers applied a chiral sulfoxide as the auxiliary, which was
eliminated in the final step to form the conjugated double
bond.6 Danishefsky and co-workers developed a multistep
procedure starting from (Ϫ)-quinic acid in the total synthesis of
FK-506,7 and emphasised the importance of the configuration
of 4-hydroxycyclohex-2-enone because “all stereochemistry
is introduced by communication from the single stereogenic
center at C-4 of this compound” in the syntheses of ML-236A
and compactin with racemic 4-hydroxycyclohex-2-enone as the
starting material.1 Yamamoto and co-workers reported a cycliz-
ation approach to this kind of compound, which involved
a stereocontrolled intramolecular ene reaction with methyl-
aluminium bis(4-bromo-2,6-di-tert-butylphenoxide) (MABR)
as the Lewis acid.8 In the present paper, we describe an econom-
ical and stereospecific route to the synthesis of derivatives of
(R)- and (S)-4-hydroxycyclohex-2-enone; the key step is a
stereocontrolled intramolecular ene reaction.
Results and discussion
The synthesis started with (2R,3R,4R,5R)-1,2:5,6-dianhydro-
3,4-isopropylidene--mannitol 1, which had been obtained in
Fig. 1
† Present address: LEDSS 3—Chimie Recherches, Université Joseph
four easy steps from -mannitol by known procedures.9 After
the carbon chain had been extended at both terminals of 1 by
treatment of 1 with 2-methylallylmagnesium chloride to give 3
Fourier, B. P. 53X—38041 Grenoble Cedex, France; E-mail:
zhangrz_1999@yahoo.com; Fax: 00 33 4 76635754; Tel: 00 33 4
76514688.
2958
J. Chem. Soc., Perkin Trans. 1, 2001, 2958–2961
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b107085a

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in 83% yield, both hydroxy groups of 3 were protected with
benzoyl chloride to afford benzoate 4 (97% yield).10 Treatment
of 4 with a catalytic amount of toluene-p-sulfonic acid (PTSA)
in methanol resulted in deprotection furnishing 5 (81%), which,
upon oxidation with lead tetraacetate in CH2Cl2, afforded 6 in
91% yield (Scheme 1).
at C-4 comes from -mannitol and is (R), so the new chiral
center at C-3 of 7 should also possess the (R)-configuration.
The O-benzyl compound 7 has already been synthesized by an
intramolecular ene reaction with MABR as the Lewis acid,
which was then transformed to a chiral building block of
FK-506.8
With 7 in hand, the next transformation was easily accom-
plished with O3 or OsO4 (cat.)–NaIO4 as the oxidizing agent
to give 8 in excellent yield. Subsequent dehydration of 8
catalyzed by PTSA in benzene gave (R)-4-benzoyloxycyclohex-
2-enone 9 ([α]2D0 = ϩ201 (c = 0.85, CHCl3); lit. [α]D = Ϫ197 (c =
1.9, CH2Cl2) for (S)-914) in 91% yield. The other important
compound (R)-6-benzoyloxy-4-methylcyclohex-2-enone 10
was synthesized from 7 in one step by oxidation with Jones
reagent (80% yield). Since (2S,3R,4R,5S)-1,2:5,6-dianhydro-
3,4-isopropylidene--mannitol 2 may be easily prepared from
-mannitol9 and subjected to the same reaction sequences, this
route potentially also provides access to the enantiomers of
compounds 7–10.
In conclusion, we have presented a new and efficient route
to four derivatives of (R)-4-hydroxycyclohex-2-enone, 7–10,
from one intermediate, 6, using the simple, readily available
-mannitol as the chiral starting material. Such compounds are
useful chiral building blocks that are widely used in the total
synthesis of natural products and in asymmetric reactions.
Experimental
Mps were determined on an X4 micro-melting point instrument
and are uncorrected. IR spectra were obtained on Shimadzu
IR-440 and Perkin-Elmer 983 spectrometers. NMR spectra
1
were recorded on an XL-300 spectrometer (300 MHz for H)
in CDCl3 solution using TMS as the internal reference. MS
were recorded on Finnigan-4921 and HP-5989 instruments.
Optical rotations were obtained on Perkin-Elmer 241C and are
reported in units of 10Ϫ1 deg cm2 gϪ1. All reactions were moni-
tored by TLC with Huanghai 60F254 silica-gel-coated plates.
Flash column chromatography was carried out with 300–400
mesh silica gel.
Scheme
1
Reagents and conditions: (a) 2-methylallylmagnesium
chloride, 83%; (b) BzCl–Py, 97%; (c) PTSA (cat.)–MeOH, reflux, 81%;
(d) Pb(CH3COO)4–CH2Cl2, 91%; (e) method A: ZnBr2–4 Å MS, 81%;
method B: 4 Å MS, 95%; (f ) method A: O3–Me2S, 95%; method B:
OsO4–NaIO4, 91%; (g) PTSA (cat.)–benzene, 91%; (h) Jones reagent,
80%.
(5R,6R,7R,8R)-2,11-Dimethyl-5,8-dihydroxy-6,7-
isopropylidenedioxydodeca-1,11-diene 3
To a stirred solution of 2-methylallylmagnesium chloride
[84 mmol in dry THF (30 mL), prepared from 3-chloro-2-
methylpropene (84 mmol, 8.2 mL), magnesium ribbon (2.2 g,
6.6 equiv.), and dry THF (30 mL)] was added a solution of
1 (2.6 g, 37 mmol) in dry THF (10 mL) dropwise at 0 ЊC. The
resulting mixture was then allowed to warm to room temper-
ature. Stirring was continued for 1 h at this temperature. The
mixture was quenched with MeOH (5 mL), and then poured
into H2O (200 mL) and extracted with EtOAc (150 mL). The
combined organic solution was washed with H2O and brine,
dried over Na2SO4, and concentrated in vacuo. The residue was
purified by flash column chromatography on silica gel (20%
acetone in hexane) to give 3 (3.68 g, 83%) as a white solid. Mp
51–52 ЊC; [α]2D0 = ϩ27.3 (c = 1.50, CHCl3); νmax(KBr)/cmϪ1 3300,
The next step was a stereocontrolled cyclization of 6 by an
intramolecular ene reaction, which is the key step in this work.
ZnBr2 was chosen as the Lewis acid for the reaction of 6 in
1
anhydrous CH2Cl2, but a H NMR spectrum showed that the
product was a mixture of 7 and the species obtained by a shift
of the double bond to the ring. The reason for this maybe
that the reaction system was not absolutely anhydrous and
Hϩ is produced by hydrolysis of ZnBr2. When 4 Å MS were
added to the reaction system (a widely used dehydrating agent
and co-catalyst in asymmetric reactions),11 compound 7 was
obtained in 81% yield and no products of the double bond shift
were found. When 4 Å MS and a catalytic amount of ZnBr2
were used, similar results were obtained to those using equiv-
alent amounts of ZnBr2.12 It was interesting that compound 7
could be obtained in 95% yield when only 4 Å MS were used in
this ene reaction, which demonstrated that the 4 Å MS acted
not only as a dehydrating agent, but also as a catalyst. The
absolute configuration of the new chiral center in the structure
of 7 was determined by the CD exciton chirality method to be
that shown in Scheme 1, after transformation of 7 to 8. The
hydroxy group at C-3 of compound 8 was protected as a
benzoyloxy group by treatment with benzoyl chloride. The CD
spectrum of this benzoate shows negative chirality. According
to the CD exciton chirality method, only when both vicinal
groups are in the anti conformation in the six-membered ring
is negative chirality obtained.13 As the absolute configuration
2920, 1650, 1450, 1380, 1230, 1070; δ 4.14 (4H, s, 2 × ᎐CH ),
᎐
H
2
3.80–3.50 (4H, m, 4CH), 2.35–1.93 (8H, m, 4CH2), 1.76 (6H, s,
2CH3), 1.30 (6H, s, 2 CH3); m/z 299 (Mϩ ϩ 1), 283 (Mϩ Ϫ 15),
59 (100%) (Found: C, 68.67; H, 10.36. C17H30O4 requires C,
68.46; H, 10.07%).
(5R,6R,7R,8R)-2,11-Dimethyl-5,8-bis(benzoyloxy)-6,7-
isopropylidenedioxydodeca-1,11-diene 4
Benzoyl chloride (23.4 mmol, 2.7 mL) was added slowly to a
solution of 3 (3.0 g, 10.0 mmol) in dry pyridine (30 mL) at 0 ЊC
and then stirred overnight at room temperature. The reaction
mixture was poured into H2O (300 mL) and extracted with
diethyl ether (200 mL). The combined organic layer was washed
J. Chem. Soc., Perkin Trans. 1, 2001, 2958–2961
2959

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fully with saturated CuSO4 and then with H2O and brine,
respectively. The resulting solution was dried over Na2SO4, con-
centrated under reduced pressure and purified by flash column
chromatography on silica gel (10% ethyl acetate in hexane) to
provide 4 (5.2 g, 97%). [α]2D0 = ϩ22.0 (c = 1.5, CHCl3); νmax(KBr)/
cmϪ1 2960, 1725, 1650, 1600, 1580, 1450, 1380, 1270; δH 7.60–
7.37 (4H, m), 7.30–7.00 (6H, m), 5.45–5.30 (2H, m, 2CH), 4.66
(1H, m), 7.30–7.15 (2H, m), 5.02 (1H, td, J 8.1, 4.2 Hz), 4.93
(1H, s), 3.86 (1H, td, J 8.1, 4.0 Hz), 2.75 (1H, dd, J 14, 5.5 Hz),
2.30–1.60 (7H, m); m/z 233 (Mϩ ϩ 1) (Found: C, 72.27; H, 6.81.
C14H16O3 requires C, 72.39; H, 6.94%).
(3R,4R)-3-Hydroxy-4-benzoyloxycyclohexanone 8
Method A. A solution of 7 (125 mg, 0.54 mmol) in CH2Cl2
(5 mL) and methanol (3 mL) was cooled to Ϫ78 ЊC in dry ice–
acetone and then ozone was introduced to the reaction mixture.
After the solution had turned blue, the flow of ozone was
ceased and nitrogen was introduced to drive away the ozone
dissolved in CH2Cl2. Me2S (0.5 mL) was added to the reaction
mixture and stirred for 1 h at Ϫ78 ЊC, and then overnight at
room temperature. The solution was concentrated in vacuo and
purified by flash column chromatography on silica gel (5%
acetone in hexane) to afford 8 (120 mg, 95% yield).
(2H, s, ᎐CH ), 4.61 (2H, s, ᎐CH ), 4.41–4.30 (2H, m, 2CH),
᎐
᎐
2
2
2.20–1.95 (8H, m, 4CH2), 1.66 (6H, s, 2CH3), 1.39 (6H, s,
2CH3); m/z 507 (Mϩ ϩ 1), 106 (100%) (Found: C, 73.13; H,
7.42. C31H38O6 requires C, 73.52; H, 7.51%).
(5R,6R,7R,8R)-2,11-Dimethyl-5,8-bis(benzoyloxy)-6,7-
dihydroxydodeca-1,11-diene 5
To a stirred solution of 4 (470 mg, 0.93 mmol) in methanol
(20 mL), PTSA (50 mg) was added and then the reaction
mixture was refluxed for 8 h. After removal of the solvent under
reduced pressure, the residue was diluted with diethyl ether
(20 mL) and washed with NaHCO3 (aq.), H2O and brine. The
organic solution was dried over Na2SO4 and concentrated
in vacuo. The residue was purified by flash column chrom-
atography on silica gel (20% acetone in hexane) to afford 5 (260
mg, 81% yield and 74% conversion of 4). [α]2D0 = ϩ62.2 (c = 1.06,
CHCl3); νmax(KBr)/cmϪ1 3400, 2930, 1710, 1650, 1600, 1580,
1450, 1270; δH 8.10–7.97 (4H, m), 7.65–7.50 (2H, m), 7.50–7.40
Method B. OsO4 (1.3 mg) and NaIO4 (350 mg) were dissolved
in 1,4-dioxane–H2O (5 mL, v/v, 3 : 1). After stirring for 0.5 h,
compound 7 (100 mg, 0.43 mmol) was added and the reaction
mixture was stirred overnight. Na2SO3 (500 mg) was added to
the reaction mixture and stirred for 15 min at room temper-
ature. The solution was diluted with H2O (20 mL) and then
extracted with diethyl ether. The combined organic solution
was washed with water and brine, and dried over Na2SO4. The
solvent was removed under reduced pressure and purified by
flash column chromatography on silica gel to afford 8 (92 mg,
91% yield). [α]2D0 = Ϫ21.3 (c = 0.55, CHCl3); νmax(KBr)/cmϪ1
3450, 2950, 1710, 1600, 1580, 1280, 1110, 930, 710; δH 8.13–8.00
(2H, m), 7.67–7.55 (1H, m), 7.55–7.43 (2H, m), 5.33–5.20 (1H,
m), 4.40–4.27 (1H, m), 2.90 (1H, dd, J 15, 4 Hz), 2.65–2.43 (5H,
m), 2.15–1.93 (2H, m); m/z, 235 (Mϩ ϩ 1) (Found: C, 66.24; H,
5.70. C13H14O4 requires C, 66.60; H, 5.98%).
(4H, m), 5.20–5.05 (2H, m, 2CH), 4.66 (2H, s, CH ᎐), 4.62 (2H,
᎐
2
s, CH ᎐), 3.61 (2H, d, J 8 Hz, 2CH), 3.30 (OH, s), 2.20–1.90
᎐
2
(8H, m, 4CH2), 1.69 (6H, s, 2CH3); m/z 467 (Mϩ ϩ 1), 449 (Mϩ
Ϫ 18) (Found: C, 72.34; H, 7.53. C28H34O6 requires C, 72.10; H,
7.30%).
(2R)-2-Benzoyloxy-5-methylhex-5-enal 6
A solution of lead tetraacetate (190 mg) in CH2Cl2 (10 mL) was
cooled to Ϫ20 ЊC and diol 5 (115 mg, 0.50 mmol) was added.
After stirring for 1 h at this temperature, the reaction mixture
was warmed to room temperature and quenched with ethylene
glycol (0.5 mL). The upper phase was separated and the residue
was washed with CH2Cl2. The combined organic solution
was washed with water and brine, and dried over Na2SO4. The
solvent was removed under reduced pressure and then purified
by flash column chromatography on silica gel (5% ethyl acetate
in hexane) to give 6 (105 mg) in 91% yield. [α]2D0 = ϩ57.4 (c =
0.63, CHCl3); νmax(CHCl3)/cmϪ1 2930, 1725, 1650, 1600, 1580,
1270, 1120, 859, 710; δH 9.65 (1H, s, CHO), 8.13–8.00 (2H, m,
aromatic H), 7.65–7.50 (1H, m, aromatic H), 7.53–7.37 (2H, m,
aromatic H), 5.22 (1H, dd, J 7.7, 4.7 Hz, CH-OBz), 4.79 (1H, s,
(R)-4-Benzoyloxycyclohex-2-enone 9
PTSA (5 mg) was added to a solution of 8 (46 mg, 0.20 mmol)
in benzene (5 mL) and then refluxed for 20 min. After evapor-
ation of the solution, the residue was purified by flash column
chromatography on silica gel (5% ethyl acetate in hexane) to
give 9 (39 mg) in 91% yield. [α]2D0 = ϩ201 (c = 0.85, CHCl3);
νmax(KBr)/cmϪ1 2960, 1715, 1690, 1600, 1580, 1270; δH 8.15–
7.97 (2H, m), 7.42 (1H, br), 7.38 (2H, br), 7.00 (1H, dd, J 10,
4 Hz), 6.14 (1H, d, J 10 Hz), 5.90–5.80 (1H, m), 2.80–2.20 (4H,
m); m/z 216 (Mϩ) (Found: C, 72.06; H, 5.62. C13H11O3 requires
C, 72.22; H, 5.56%).
Preparation of (R)-3-methyl-6-benzoyloxycyclohex-2-enone 10
CH ᎐), 4.74 (1H, s, CH ᎐), 2.35–2.05 (4H, m, 2CH ), 1.76 (3H,
᎐
᎐
2
2
2
s, CH3); m/z 233 (Mϩ ϩ 1) (Found: C, 72.50; H, 6.93. C14H16O3
Jones reagent (0.12 mL) was added dropwise to a solution of 7
(100 mg, 0.43 mmol) in freshly distilled acetone (10 mL). The
reaction mixture was stirred for 2 h at room temperature and
then quenched with H2O (50 mL). After extraction with EtOAc,
the combined organic solution was washed with brine and
dried. The solvent was removed under reduced pressure and the
residue was purified by flash column chromatography on silica
gel (5% ethyl acetate in hexane) to afford 10 as a white solid (80
mg, 80% yield). [α]2D0 = ϩ86.4 (c = 0.78, CHCl3); νmax(KBr)/cmϪ1
1735, 1690, 1640, 1280, 1215; δH 8.20–8.05 (2H, m), 7.65–7.50
(1H, m), 7.50–7.37 (2H, m), 5.98 (1H, s), 5.90 (1H, dd, J 10, 6
Hz), 2.70–2.20 (4H, m), 2.02 (3H, s); m/z 231 (Mϩ ϩ 1) (Found:
C, 72.60; H, 5.94. C14H14O3 requires C, 73.04; H, 6.09%).
requires C, 72.39; H, 6.94%).
(1R,2R)-2-Benzoyloxy-5-methylenecyclohexanol 7
Method A. To a stirred solution of ZnBr2 (65 mg, 0.26 mmol)
in CH2Cl2 (5 mL), 4 Å MS (500 mg) were added. After stirring
for 0.5 h, compound 6 (54 mg, 0.24 mmol) was added and
stirring was continued for another hour. The solid was removed
by filtration through Celite. The filtrate was washed with satur-
ated NaHCO3, H2O and brine, and dried over Na2SO4. After
evaporation of solution, the residue was purified by flash
column chromatography on silica gel (5% acetone in hexane).
Compound 7 was obtained in 81% yield (44 mg).
Method B. To a solution of 6 (1.0 g, 4.31 mmol) in CH2Cl2
(20 mL), 4 Å MS (1.0 g) were added and stirred for two days.
After filtration through Celite, the residue was washed with
CH2Cl2. The combined organic solution was concentrated
in vacuo and then purified by flash column chromatography on
silica gel to provide 7 (950 mg) in 95% yield. [α]2D0 = Ϫ40.6 (c =
1.31, CHCl3); νmax(CHCl3)/cmϪ1 3600, 1710, 1650, 1600, 1580,
1458, 1280, 1070, 950, 720; δH 8.10–7.97 (2H, m), 7.43–7.30
References
1 S. Danishefsky and B. Simoneau, J. Am. Chem. Soc., 1989, 111,
2599.
2 (a) T. Kino, H. Hatanaka, M. Hashimoto, M. Nishiyama, T. Goto,
M. Okuhara, M. Kohsaka, H. Aoki and H. Imanaka, J. Antibiot.,
1987, 40, 1249; (b) H. Tanaka, A. Kuroda, H. Marusawa,
H. Hatanaka, T. Kino, T. Goto, M. Hashimoto and T. Taga, J. Am.
Chem. Soc., 1987, 109, 5031.
2960
J. Chem. Soc., Perkin Trans. 1, 2001, 2958–2961

View Article Online
3 (a) R. Dunlop, A. Simon, K. Sivasithamparam and E. Ghisalberti,
J. Nat. Prod., 1989, 52, 67; (b) E. Ghisalberti and C. Rowland,
J. Nat. Prod., 1993, 56, 1799; (c) S. Parker, H. Cutler and
P. Schreiner, Biosci. Biotechnol. Biochem., 1995, 59, 1747; (d ) G. Liu
and Z. Q. Wang, Synthesis, 2001, 119.
4 (a) C. Vezina, A. Kudelski and S. N. Sehgal, J. Antibiot., 1975, 28,
721; (b) S. N. Sehgal, H. Baker and C. Vezina, J. Antibiot., 1975, 28,
727; (c) D. Swindells, P. White and J. Findlay, Can. J. Chem., 1978,
56, 2491; (d ) J. Findlay and L. Radics, Can. J. Chem., 1980, 58, 579;
(e) K. C. Nicolaou, T. Chakraborty, A. D. Piscopio, N. Minowa and
P. Bertinato, J. Am. Chem. Soc., 1993, 115, 4419.
8 Keiji Maruoka, Susumu Saito, Takashi Ooi and Hisashi Yamamoto,
Synlett, 1991, 579.
9 Y. Merrer, C. Dureault, C. Gravier, D. Languin and J. Depezay,
Tetrahedron Lett., 1985, 26, 319.
10 Wang et al. have reported the transformation of 1 to 4 in the
synthesis of (2R,2ЈR,3R,3ЈR)-3,3Ј-dihydroxy-6,6,6Ј,6Ј-tetramethyl-
3,3Ј,4,4Ј,5,5Ј,6,6Ј-octahydro-2,2Ј-bi(2H-pyran) as a letter: L. Yu,
L. Xu and Z. Wang, Chin. Chem. Lett., 1997, 8, 653.
11 (a) Catalytic Asymmetric Synthesis, ed. I. Ojima, Wiley-VCH, 2000;
(b) H. Kolb, M. VanNieuwenhze and K. B. Sharpless, Chem. Rev.,
1994, 94, 2483.
5 R. Brünjes, U. Tilstam and E. Winterfeldt, Chem. Ber., 1991, 124,
1677.
6 M. Carreño, J. Ruano, M. Garrido, M. Ruiz and G. Solladié,
Tetrahedron Lett., 1990, 31, 6653.
7 (a) A. Jones, M. Yamaguchi, A. Patten, S. Danishefsky, J. Ragan,
D. Smith and S. Schreiber, J. Org. Chem., 1989, 54, 17; (b) J. Audia,
L. Boisvert, A. Patten, A. Villalobos and S. Danishefsky, J. Org.
Chem., 1989, 54, 3738; (c) S. Danishefsky and B. Simoneau, Pure
Appl. Chem., 1988, 60, 1555.
12 Libing Yu, Dissertation, Shanghai Institute of Organic Chemistry,
1994.
13 (a) B. Ying, G. Qin and R. Xu, Chin. J. Org. Chem., 1987, 3, 165; (b)
N. Harada and K. Nakanishi, J. Am. Chem. Soc., 1969, 91, 3989.
14 Kazlauskas et al. have reported the synthesis of (S)-4-benzoyl-
oxycyclohex-2-enone, [α]D = Ϫ197 (c = 1.9, CH2Cl2), which was
obtained from (S)-4-acetoxycyclohex-2-enone (98% ee) in two steps:
R. J. Kazlauskas, A. N. E. Weissfloch, A. T. Rappaport and L. A.
Cuccia, J. Org. Chem., 1991, 56, 2656.
J. Chem. Soc., Perkin Trans. 1, 2001, 2958–2961
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