Chemoenzymatic synthesis of deoxy analogues of the DNA topoisomerase II inhibitor eleutherin and the 3C-protease inhibitor thysanone

Article abstract of DOI:10.1016/j.tet.2008.01.112

The asymmetric synthesis of (-)-9-demethoxyeleutherin 6, (+)-9-demethoxyeleutherin 7 and (+)-7,9-deoxythysanone 8 has been achieved using a microwave assisted kinetic resolution of racemic alcohol 11 with Novozyme 435 as the key step.

Full text of DOI:10.1016/j.tet.2008.01.112

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 4827e4834
www.elsevier.com/locate/tet
Chemoenzymatic synthesis of deoxy analogues of the
DNA topoisomerase II inhibitor eleutherin and
the 3C-protease inhibitor thysanone
*
Prabhakar Bachu, Jonathan Sperry, Margaret A. Brimble
Department of Chemistry, The University of Auckland, 23 Symonds Street, Auckland, New Zealand
Received 26 June 2007; received in revised form 13 August 2007; accepted 27 August 2007
Available online 2 February 2008
Abstract
The asymmetric synthesis of (ꢀ)-9-demethoxyeleutherin 6, (þ)-9-demethoxyeleutherin 7 and (þ)-7,9-deoxythysanone 8 has been achieved
using a microwave assisted kinetic resolution of racemic alcohol 11 with Novozyme 435Ò as the key step.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Eleutherin; Thysanone; Topoisomerase II inhibitor; 3C-protease inhibitor; Novozyme 435Ò (Candida antarctica lipase); Microwave assisted lipase
kinetic resolution; Intramolecular cyclization
1. Introduction
addition of an oxygenated diene to a bromobenzoquinone
unit containing a functionalized pyran ring.12
The pyranonaphthoquinone family of antibiotics is isolated
from plants, fungi and aphid pigments and has been shown to
exhibit activity against various Gram-positive bacteria, patho-
genic fungi and yeasts, as well as antiviral activity.1 This
class of compounds has been postulated to act as bioreductive
alkylating agents and hence is important structural leads for
cancer therapy.2 Monomeric members of the pyranonaphtho-
quinone family that contain a 1,3-disubstitution pattern on
the pyran ring include eleutherin 1, thysanone 2, isoeleutherin
3, ventiloquinone E 4 and 6-hydroxy-7-methoxyeleutherin 5
(Fig. 1).
Eleutherin 1 was isolated3 from the tubers of Eleutherine
bulbosa (Iridaceae) and was identified as a catalytic inhibitor
of topoisomerase II.4 A number of racemic syntheses of eleu-
therin 1 have been reported6e11 and recently, an enantioselec-
tive total synthesis of eleutherin 1 was disclosed in which the
(S)-stereochemistry at C-3 was derived from ethyl (S)-lactate.
The strategy adopted involved a poor yielding late stage
Thysanone 2 was isolated from Thysanophora penicil-
loides5 and is one of few effective inhibitors of human
rhinovirus 3C-protease, thus providing a lead compound for
development of chemotherapeutic agents for the common
cold. We have previously reported the enantioselective syn-
thesis of (þ)-7,9-deoxythysanone in which the stereochemistry
at C-3 was controlled by using a Sharpless asymmetric
MeO
9
O
Me
1
OH
O
OH
1
9
O
O
3
7
3
Me
Me
HO
Me
Me
O
O
eleutherin 1
thysanone 2
MeO
O
Me
MeO
O
Me
O
O
MeO
O
R
O
isoeleutherin 3
R=OMe ventiloquinone E 4
R=OH 6-hydroxy-7-methoxyeleutherin 5
* Corresponding author. Tel.: þ64 9 3737599; fax: þ64 9 3737422.
E-mail address: m.brimble@auckland.ac.nz (M.A. Brimble).
Figure 1. Pyranonaphthoquinone family of antibiotics.
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.112

4828
P. Bachu et al. / Tetrahedron 64 (2008) 4827e4834
dihydroxylation of an allylnaphthalene. Its enantiomer was
accessible via a chiral oxazaborolidine reduction of methyl
ketone.13 In addition, several lengthy syntheses of analogues
of thysanone 2 have been reported14e16 as well as an asym-
metric synthesis confirming the relative stereochemistry of
thysanone.17
Given the significant biological activity combined with our
continuing interest in the synthesis of pyranonaphthoquinone
antibiotics,18 we herein report the efficient asymmetric syn-
thesis of (ꢀ)-9-demethoxyetheutherin 6, (þ)-9-demethoxy-
etheutherin 7 and 7,9-deoxythysanone 8, whereby the C-3
stereocentre is obtained using a microwave assisted kinetic
resolution.
pyran ring, delivering (ꢀ)-demethoxyeleutherin 6 after oxida-
tive demethylation. Similarly, (þ)-9-demethoxyeleutherin 7
could be accessed in the same fashion from (S)-alcohol 10,
which is also available from racemic alcohol 11 using the mi-
crowave assisted lipase kinetic resolution protocol. Using the
same intermediate (S)-alcohol 10, (þ)-7,9-deoxythysanone 8
could also be accessed via lithiumehalogen exchange fol-
lowed by trapping of the resulting aryllithium with a formyl
equivalent, thus triggering intramolecular cyclization.
It was decided that allylbromonaphthalene 12, a key interme-
diate previously used for the synthesis of several pyranonaph-
thoquinones,13,20,21 could serve as a suitable starting material
for the synthesis of racemic alcohol 11 (Scheme 2). Thus,
oxidative bromination of 1-naphthol 13 delivered 2-bromo-
1,4-naphthoquinone 1422 that underwent radical allylation
using a silver persulfate-catalyzed oxidative decarboxylation
of vinylacetic acid, furnishing allylnaphthoquinone 15.20
Reductive methylation23 delivered allylnaphthalene 12 that un-
derwent ozone mediated oxidative cleavage24 of the allyl group
affording aldehyde 1625 in excellent yield. Finally, Grignard
addition of methylmagnesium iodide to aldehyde 16 furnished
the desired racemic secondary alcohol 11 in 60% yield.
2. Results and discussion
The retrosynthetic analysis adopted is outlined in Scheme
1. It was envisaged that (ꢀ)-9-demethoxyeleutherin 6 would
be available from (R)-bromoacetate 9 in which the stereo-
chemistry at C-3 is introduced by incorporating our recently
disclosed microwave assisted lipase kinetic resolution19 of
racemic secondary alcohols. Racemic alcohol 11 can then be
accessed from allylbromonaphthalene 12 by oxidative cleav-
age followed by Grignard addition. Halogenemetal exchange
of (R)-bromoacetate 9 followed by concomitant intramolecular
cyclization of the resulting aryllithium would furnish the
With alcohol 11 in hand, its microwave assisted lipase
kinetic resolution could be considered. Thus, a mixture of
alcohol 11, p-chlorophenyl acetate (as the acyl donor) and
Novozyme 435Ò (Candida antarctica lipase) in toluene was
O
Me
OMe
O
Br
Me
O
O
Me
Me
OMe
O
(-)-6
OMe
OMe
(R)-9
Br
Br
OH
Me
OMe
( )-11
OMe
12
O
R2
OMe
R1
Br
O
OH
Me
Me
OMe
O
R1=Me, R2=H (+)-7
R1=H, R2=OH (+)-8
(S)-10
Scheme 1. Retrosynthetic analysis of (ꢀ)-9-demethoxyeleutherin 6, (þ)-9-demethoxyeleutherin 7 and 7,9-deoxythysanone 8.
O
O
OMe
OH
Br
Br
Br
(ii)
(i)
(iii)
+
HO2C
O
14
O
15
OMe
12
13
OMe
OMe
OMe
OMe
OMe
O
Br
Br
Br
Br
(iv)
(v)
OH
OH
Me
(vi)
Me
O
+
CHO
Me
Me
OMe
OMe
OMe
16
( )-11
(R)-9
(S)-10
Scheme 2. Reagents and conditions: (i) NBS, AcOHeH2O, 1 h, 45 ꢁC, 87%; (ii) AgNO3, (NH4)2S2O8, MeCNeH2O, 2 h, 60 ꢁC, 67%; (iii) Na2S2O4, THF, TBAI,
aqueous KOH, Me2SO4, 4 h, 95%; (iv) O3, Sudan IIIÒ, CH2Cl2, 15 min, ꢀ60 ꢁC, 72%; (v) MeMgI, Et2O, 18 h, ꢀ78 ꢁC to rt, 60%; (vi) Novozyme 435Ò, p-chloro-
phenyl acetate, toluene, 60 ꢁC, 70 W, microwave, 6 h, (S)-alcohol 10 (40%, 93% ee), (R)-ester 9 (45%, 99% ee).

P. Bachu et al. / Tetrahedron 64 (2008) 4827e4834
4829
heated to 60 ꢁC in a microwave reactor (CEM Discover
systemÒ) at 70 W for 6 h, gratifyingly affording the desired
(R)-bromoester 9 in 45% yield with 99% ee and (S)-alcohol
1013 in 40% yield with 93% ee. The enantiomeric excess of
both products was established by HPLC using chiralcel
ODeH chiral column. The absolute configuration of (S)-alco-
hol 10 obtained was confirmed by comparison of its optical
rotation with the value reported in the literature.13 The as-
signed (R)-configuration of bromoester 9 and (S)-configuration
of alcohol 10 were also in agreement with Kazlauskas’ rule26
(Scheme 2).
Given the successful synthesis of (ꢀ)-9-demethoxyeleu-
therin 6 and in order to demonstrate the versatility of this
approach, attention next turned to the synthesis of the enantio-
mer (þ)-9-demethoxyeleutherin 7. Thus, (S)-bromoacetate 19
was prepared in excellent yield from (S)-alcohol 10 using ace-
tic anhydride in dichloromethane in the presence of a catalytic
amount of perchloric acid. In a similar fashion to that de-
scribed above, lithiumehalogen exchange followed by con-
comitant intramolecular cyclization delivered lactol 20 that
upon immediate deoxygenation afforded the stable naphtha-
lene 21. Finally, oxidative demethylation furnished (þ)-9-
demethoxyeleutherin 7 in 93% ee (Scheme 4).
Having established a protocol for the synthesis of enantio-
pure (R)-bromoester 9 and (S)-alcohol 10, their conversion to
our desired pyranonaphthoquinone targets was investigated.
Initially, (R)-bromoester 9 was treated with tert-butyllithium
at ꢀ78 ꢁC to generate the aryllithium triggering concomitant
intramolecular cyclization onto the adjacent acetate. Initially,
unstable lactol 17 that was formed was immediately converted
to the (ꢀ)-naphthopyran 18 in 70% yield over two steps using
the silane promoted reduction reported by Kraus.27 The
NOESY spectra recorded for (ꢀ)-naphthopyran 18 confirmed
the cis-stereochemistry between 1-H and 3-H. Finally, CAN-
mediated oxidative demethylation gratifyingly delivered
(ꢀ)-9-demethoxyeleutherin 6 in 75% yield. The enantiomeric
excess was calculated by HPLC using a chiralcel ADeH chiral
column, and was established to be >99%. The 1H NMR
data for (ꢀ)-9-demethoxyeleutherin 6 compared well to that
reported for the natural eleutherin 13d and synthetic (þ)-
eleutherin 1.12 The cis-relationship between the two methyl
groups at C-1 and C-3 was confirmed by correlation in the
NOESY spectra between 1-H and 3-H (Scheme 3).
With a view to examine a further use of (S)-alcohol 10,
attention next focused on the synthesis of (þ)-7,9-deoxythy-
sanone 8. Following our previously reported procedure,13
(S)-alcohol 10 was treated with n-butyllithium and the result-
ing aryllithium quenched with dimethylformamide. Unfortu-
nately, this procedure did not furnish lactol (ꢀ)-23, with
only debrominated product being isolated from the reaction.
This result was attributed to the C-2 position of the (S)-alcohol
10 undergoing protonation after lithiumehalogen exchange,
presumably via internal quenching of the anion by the acidic
hydroxyl group proton. In order to circumvent this problem,
it was decided to mask the alcohol as its formate, with the
hope that lithiation would trigger concomitant intramolecular
cyclization in a fashion to that described above. Thus, (S)-for-
mate 22 was prepared in excellent yield from (S)-alcohol 10
using dicyclohexylcarbodiimide and formic acid in the pres-
ence of a catalytic quantity of DMAP. Next, (S)-formate 22
gratifyingly underwent cyclization to afford the desired (ꢀ)-
lactol 23 in 76% yield upon treatment with tert-butyllithium.
OMe
MeO
Me
O
Me
O
Me
MeO
OH
O
Br
CH3
O
(ii)
O
O
(iii)
(i)
Me
Me
Me
Me
OMe
(R)-9
O
MeO
MeO
17
(-)-18
(-)-6
Scheme 3. Reagents and conditions: (i) t-BuLi, THF, 2 h, ꢀ78 ꢁC to rt; (ii) Et3SiH, CF3CO2H, CH2Cl2, 2 h, ꢀ78 ꢁC to rt, 70% (over two steps); (iii) CAN,
MeCNeH2O, 10 min, rt, 75%, 99% ee.
OMe
O
O
Me
OMe Me
MeO
Me
OH
O
Br
(i)
CH3
O
(ii)
(iii)
O
O
(iv)
(S)-10
Me
Me
Me
Me
OMe
O
OMe
MeO
(S)-19
(+)-21
(+)-7
20
H
4
2
O
Me
H
1
Me
(+)-7
3
H
H
4.84, m
3.59, m
nOe observed
Scheme 4. Reagents and conditions: (i) Ac2O, CH2Cl2, HClO4, 2 h, rt, 94%; (ii) t-BuLi, THF, 1 h, ꢀ78 ꢁC; (iii) Et3SiH, CF3CO2H, 2 h, rt, 82% (over two steps);
(iv) CAN, MeCNeH2O, 10 min, rt, 72%.

4830
P. Bachu et al. / Tetrahedron 64 (2008) 4827e4834
OH
OH
O
OMe
MeO
O
Br
(ii)
(iii)
(i)
O
H
O
O
(S)-10
Me
Me
Me
O
(+)-8
OMe
MeO
(+)-23
(S)-22
Scheme 5. Reagents and conditions: (i) HCO2H, DCC, 4-DMAP, CH2Cl2, 24 h, 0 ꢁC to rt, 85%; (ii) t-BuLi, THF, 1 h, ꢀ78 ꢁC, 76%; (iii) CAN, MeCNeH2O,
10 min, 0 ꢁC, 74%.
1
Finally, CAN-mediated oxidative demethylation of (ꢀ)-lactol
23 provided (þ)-7,9-deoxythysanone 8 in 74% yield (Scheme
5). The enantiomeric excess was established to be 95% ee by
reported as chemical shift d, multiplicity and assignment. H
NMR shift values are reported as chemical shift d, relative in-
tegral, multiplicity (s, singlet; d, doublet; t, triplet; q, quartet;
m, multiplet), coupling constant (J in hertz) and assignment.
Assignments are made with the aide of DEPT 135, COSY,
NOESY and HSQC experiments. High resolution mass spectra
were recorded on a VG-70SE mass spectrometer at a nominal
accelerating voltage of 70 eV.
1
HPLC using a chiralcel ODeH chiral column. The H NMR
data for (þ)-7,9-deoxythysanone 8 compared well to that re-
ported for natural thysanone 25 and synthetic thysanone 2.17
This data clearly established that the lactol ring system in
(þ)-7,9-deoxythysanone 8 possesses the same relative stereo-
chemistry as both natural and synthetic thysanone 2.
4.2. 2-Bromo-1,4-naphthoquinone 1422
3. Conclusions
To a solution of N-bromosuccinimide (14.24 g, 80 mmol) in
acetic acid (200 mL) and water (400 mL) at 45 ꢁC was added
a solution of 1-naphthol 13 (2.90 g, 20 mmol) in acetic acid
(200 mL) dropwise. The mixture was stirred for 1 h at 45 ꢁC
then cooled to rt and water (200 mL) was added. The mixture
was extracted with chloroform (4ꢂ100 mL), the combined
organic layers were washed with saturated NaHCO3 (100 mL)
solution, water (2ꢂ100 mL) and brine (100 mL). The organic
layer was dried over anhydrous MgSO4 and the solvent was
removed at reduced pressure. The crude product was purified
by flash chromatography using hexaneseethyl acetate (8:2) as
eluent to afford the title compound 14 (4.17 g, 17.7 mmol,
87%) as a bright yellow solid, mp 132e133 ꢁC (lit.22 mp
131e132 ꢁC); nmax (film) 1679, 1658, 1590, 1570, 1377,
1246, 1117 cmꢀ1; m/z 237 (M[81Br]þ, 100), 235 (M[79Br]þ,
100), 209 (M[81Br]ꢀO, 40), 207 (M[79Br]ꢀO, 40), 181
(30), 179 (30); HRMS (EI) m/z calcd for C10H759BrO2,
C10H851BrO2 (Mþ) 235.9473, 237.9452, found 235.9474,
237.9457. The spectroscopic data were in agreement with
that reported in the literature.22
In conclusion, we have developed a concise, simple and
flexible enantioselective synthetic route for the preparation
of (ꢀ)-9-demethoxyeleutherin 6, (þ)-9-demethoxyeleutherin
7 and (þ)-7,9-deoxythysanone 8 using a microwave assisted
kinetic resolution of racemic alcohol 11 with Novozyme
435Ò as the key step. Studies directed towards the synthesis
of complex pyranonaphthoquinones using this methodology
are ongoing.
4. Experimental
4.1. General details
All reactions were carried out in oven-dried or flame-dried
glassware under a nitrogen atmosphere unless otherwise
stated. Analytical thin layer chromatography was performed
using 0.2 mm Kieselgel F254 (Merck) silica plates and com-
pounds were visualized under 365 nm ultraviolet irradiation
followed by staining with either alkaline permanganate or
ethanolic vanillin solution. Infrared spectra were obtained us-
ing a PerkineElmer spectrum One Fourier Transform Infrared
spectrometer as a thin film between sodium chloride plates.
Absorption maxima are expressed in wavenumbers (cmꢀ1).
Optical rotations were measured using a PerkineElmer 341
4.3. 2-Allyl-3-bromo-1,4-naphthoquinone 1520
To a solution of 2-bromo-1,4-naphthoquinone 14 (500 mg,
2.10 mmol) in acetonitrile (50 mL) were added silver nitrate
(110 mg, 1.05 mmol) and vinylacetic acid (270 mg, 3.15 mmol)
then the mixture was heated to 65 ꢁC. To the reaction mixture
was added dropwise a solution of ammonium persulfate
(910 mg, 4 mmol) in water (25 mL) over 30 min and stirring
continued for 2 h at 65 ꢁC. The mixture was cooled to rt and
water (50 mL) was added. The product was extracted with
ethyl acetate (3ꢂ40 mL), washed with saturated NaHCO3
(25 mL), water (25 mL) and brine (25 mL). The combined
organic layers were dried over anhydrous MgSO4 and concen-
trated under reduced pressure. The crude mixture was purified
by flash chromatography using hexaneseethyl acetate (96:4)
as eluent to afford the title compound 15 (389 mg, 1.4 mmol,
polarimeter at l¼598 nm and are given in 10ꢀ1 deg cm2 gꢀ1
.
Melting points were recorded on an Electrothermal melting
point apparatus and are uncorrected. NMR spectra were re-
corded as indicated on either a Bruker DRX-400 spectrometer
operating at 400 MHz for 1H nuclei and 100 MHz for 13C nu-
clei or on a Bruker Avance 300 spectrometer operating at
1
300 MHz and 75 MHz for H and 13C nuclei, respectively.
Chemical shifts are reported in parts per million (ppm) relative
to the tetramethylsilane peak recorded as d 0.00 ppm in
CDCl3/TMS solvent, or the residual chloroform peak at
d 7.25 ppm. The 13C NMR values were referenced to the resi-
dual chloroform peak at d 77.0 ppm. 13C NMR values are

P. Bachu et al. / Tetrahedron 64 (2008) 4827e4834
4831
67%) as orange/yellow crystals, mp 77e79 ꢁC (lit.20 mp 79 ꢁC);
nmax (film) 1677, 1665, 1596, 1424, 1277, 1265, 738 cmꢀ1
HRMS (EI) m/z calcd for C13H891BrO2, C13H799BrO2 (Mþ)
277.9765, 275.9786, found 277.9772, 275.9787. The spectro-
scopic data were in agreement with that reported in the
literature.20
308 (M[79Br]þ, 100), 295 (M[81Br]ꢀMe, 15), 293 (M[79Br]ꢀ
Me, 15), 200 (55), 185 (76); HRMS (EI) m/z calcd for
;
81
79
C14H BrO3, C14H BrO3 (Mþ) 310.0028, 308.0048, found
13 13
310.0021, 308.0049. The spectroscopic data were in agree-
ment with that reported in the literature.25
4.6. 3-Bromo-2-(2-hydroxypropyl)-1,4-dimethoxy-
naphthalene 1113
4.4. 2-Allyl-3-bromo-1,4-dimethoxynaphthalene 1220
To a mixture of 2-allyl-3-bromo-1,4-napthoquinone 15
(340 mg, 1.23 mmol) and tetrabutylammonium iodide (46 mg,
0.11 mmol) in THF (17 mL) under nitrogen was added a solu-
tion of sodium dithionite (1.28 g, 7.3 mmol) in water (7 mL)
with vigorous stirring. After 30 min, potassium hydroxide
(1.58 g, 28.2 mmol) in water (7 mL) was added and the mix-
ture stirred for 1 h followed by the addition of dimethyl sulfate
(2.45 mL, 25.2 mmol). The mixture was stirred for 4 h then
quenched with aqueous ammonia (8.5 mL, 1.5 M) and water
(250 mL). The crude product was extracted with ethyl acetate
(3ꢂ40 mL). The organic extracts were washed with hydro-
chloric acid (50 mL, 2 M), water (3ꢂ60 mL) and dried over
anhydrous MgSO4. The solvent was removed under reduced
pressure and the crude mixture was purified by flash chroma-
tography using hexaneseethyl acetate (9:1) as eluent to yield
the title compound 12 (361 mg, 1.2 mmol, 95%) as an off-
white solid, mp 56e57 ꢁC (lit.20 mp 57 ꢁC); nmax (film)
1733, 1577, 1455, 1359, 1265, 1079, 1006 cmꢀ1; MS (EI, %)
m/z 308 (M[81Br]þ, 100), 306 (M[79Br]þ, 100), 293
(M[81Br]ꢀMe, 40), 291 (M[79Br]ꢀMe, 40), 212 (55), 197
A solution of aldehyde 16 (50 mg, 0.16 mmol) in dry
diethyl ether (10 mL) was flushed with nitrogen for about
2 min and cooled to ꢀ78 ꢁC. An ethereal stock solution of
methylmagnesium iodide (0.18 mL, 1.0 M, 0.18 mmol) was
added dropwise to the above aldehyde solution. The reaction
mixture was allowed to warm to rt overnight. The reaction
was quenched with H2O (10 mL) and stirred for 5 min. The
mixture was extracted into ethyl acetate (3ꢂ20 mL), dried
over MgSO4 and the solvent removed under reduced pressure.
The resulting residue was purified by column chromatography
using hexaneseethyl acetate (8:2) as eluent to afford the title
compound 11 (32 mg, 0.01 mmol, 60%) as a white solid, mp
118e120 ꢁC (lit.13 mp 118e120 ꢁC); nmax (film) 3433, 2103,
1644, 1453, 1358, 1086, 1004 cmꢀ1; HRMS (EI) m/z calcd
79
81
for C15H BrO3, C15H BrO3 (Mþ) 324.0361, 326.0341,
17
17
found 324.0360, 326.0347. The spectroscopic data were in
agreement with that reported in the literature.13
4.7. (S)-3-Bromo-2-(2-hydroxypropyl)-1,4-dimethoxy-
naphthalene 1013 and (R)-3-bromo-2-(2-acetoxypropyl)-
1,4-dimethoxynaphthalene 9
81
79
(65); HRMS (EI) m/z calcd for C15H BrO2, C15H BrO2
15
15
(Mþ) 308.0235, 306.0255, found 308.0238, 306.0261. The
spectroscopic data were in agreement with that reported in
the literature.20
A mixture of alcohol (ꢃ)-11 (200 mg, 0.6 mmol) and
p-chlorophenyl acetate (340 mg, 2.0 mmol) in toluene (5 mL)
was flushed with argon for 1 min followed by the addition of No-
vozyme 435Ò (SigmaeAldrich) (33 mg). The resulting mixture
was stirred at 60 ꢁC in a microwave reactor (single mode CEM
DiscoverÒ Focused Microwave Synthesis System) at 70 W for
6 h. When the reaction was complete (as indicated by TLC anal-
ysis) the mixture was filtered through cotton wool to remove the
enzyme and washed with dichloromethane (2ꢂ3 mL). The com-
bined organic extracts were concentrated under reduced pres-
sure and the residue purified by flash chromatography using
hexaneseethyl acetate (9:1) as eluent to yield the corresponding
alcohol 10 and ester 9.
The alcohol (S)-10 (80 mg, 0.25 mmol, 40%) was obtained
as a white solid, mp 118e120 ꢁC (lit.13 mp 118e120 ꢁC); [a]2D0
þ40.8 (c 0.001, CHCl3) {lit.13 [a]D þ8.1 (c 2.05, CHCl3)},
93% ee. The enantiomeric excess (ee) was determined by
high performance liquid chromatography (Waters-600) using
a chiral column (chiralcel ODeH, 0.43ꢂ1 cm, Daicel Chem-
ical Ind. Ltd.) using 2-propanolehexanes (1:99) as eluent
with a flow rate of 0.5 mL/min. The retention time for the
major peak was 32 min and the retention time for the minor
4.5. 2-(3-Bromo-1,4-dimethoxynaphthalen-2-yl) ethanol 1625
To a stirred solution of 2-allyl-3-bromo-1,4-dimethoxy-
naphthalene 12 (986 mg, 3.21 mmol) in dichloromethane
(120 mL) under nitrogen was added 0.1% solution of Sudan
III (three drops) in dichloromethane and the mixture was
cooled to ꢀ30 ꢁC. Ozone gas was bubbled into the reaction
mixture at ꢀ60 ꢁC and the reaction mixture turned from
pink to pale yellow. Nitrogen gas was flushed into the reaction
mixture for 15 min then dimethylsulfide (3.0 mL, 40.80 mmol)
was added at ꢀ60 ꢁC. The reaction mixture was warmed to rt
and stirring was continued for 1 h. The solvent was removed
under reduced pressure and the crude mixture was purified
by flash chromatography (20% ethyl acetate/hexanes) to yield
the title compound 16 (840 mg, 2.7 mmol, 85%) as a pale pink
solid, mp 68e70 ꢁC; Rf (20% ethyl acetate/hexanes) 0.56; nmax
(film) 1724, 1579, 1455, 1359, 1265, 1083, 1006 cmꢀ1; dH
NMR (300 MHz, CDCl3) 9.84 (1H, t, J1,2¼1.5 Hz, CHO),
8.10e8.01 (2H, m, 50-H and 80-H), 7.54e7.49 (2H, m, 60-H
and 70-H), 4.12 (2H, d, J2,1¼1.5 Hz, 2-H), 3.95 (3H, s,
10-OMe), 3.82 (3H, s, 40-OMe); dC (75 MHz, CDCl3) 198.4,
151.7, 150.2, 128.6, 127.5, 127.0, 126.8, 122.8, 122.5, 122.5,
115.7, 62.3, 61.2, 45.0; MS (EI, %) m/z 310 (M[81Br]þ, 98),
peak was 41 min; nmax (film) 3433, 2103, 1644, 1453, 1358,
79
17
1086, 1004 cmꢀ1; HRMS (EI) m/z calcd for C15H BrO3,
81
17
C15H BrO3 (Mþ) 324.0361, 326.0341, found 324.0360,

4832
P. Bachu et al. / Tetrahedron 64 (2008) 4827e4834
326.0347. The spectroscopic data were in agreement with that
reported in the literature.13
reduced pressure to afford the crude lactol 17 (100 mg) which
was not purified due to its ready decomposition upon exposure
to silica gel.
Ester (R)-9 (100 mg, 0.27 mmol, 44%) was also obtained as
a colourless liquid; [a]D20 þ17.8 (c 0.17, CHCl3), 99% ee. The
enantiomeric excess (ee) was determined by high performance
liquid chromatography (Waters-600) using a chiral column
(chiralcel ODeH, 0.43ꢂ1 cm, Daicel Chemical Ind. Ltd.) us-
ing 2-propanolehexanes (0.25:99.75) as eluent with a flow
rate of 0.5 mL/min. The retention time for the minor peak
was 47 min and the retention time for the major peak was
55 min; Rf (10% ethyl acetate/hexanes) 0.41; nmax (film)
2938, 1732, 1567, 1454, 1356, 1239, 1001 cmꢀ1; dH NMR
(400 MHz, CDCl3) 8.09e8.01 (2H, m, 5-H and 8-H), 7.56e
7.49 (2H, m, 6-H and 7-H), 5.46e5.34 (1H, m, 2-H), 3.96
To a solution of the crude lactol 17 (100 mg) in dry di-
chloromethane (10 mL) at ꢀ78 ꢁC was added trifluoroacetic
acid (0.07 mL, 0.96 mmol) dropwise and the mixture stirred
for 15 min. Triethylsilane (0.15 mL, 0.96 mmol) was then added
dropwise at ꢀ78 ꢁC and the mixture stirred for 2 h then allowed
to warm to rt over 1 h. The reaction mixture turned to a pale
yellow colour and was quenched with ice-water (10 mL)
then extracted with dichloromethane (3ꢂ10 mL). The com-
bined organic extracts were washed with brine solution
(10 mL) and dried over anhydrous Na2SO4. The solvent was
evaporated and the residue purified by column chromatogra-
phy (10% ethyl acetate/hexanes) to afford the title compound
18 (60 mg, 0.22 mmol, 70%) as a colourless liquid; Rf (10%
ethyl acetate/hexanes) 0.65; [a]2D0 ꢀ137.5 (c 0.02, CHCl3);
(3H, s, 1-OMe), 3.92 (3H, s, 4-OMe), 3.34 (1H, dd, Jgem
¼
13.3 Hz, J1B,2¼6.2 Hz, 1-HB), 3.19 (1H, dd, Jgem¼13.3 Hz,
J1A,2¼6.2 Hz, 1-HA), 1.94 (3H, s, OCOMe), 1.29 (3H, d,
J3,2¼6.3 Hz, 3-H); dC (75 MHz, CDCl3) 170.4, 151.6, 150.1,
128.2, 127.6, 126.9, 126.6, 126.6, 122.7, 122.5, 116.7, 70.3,
62.2, 61.3, 36.2, 21.2, 19.7; MS (EI, %) m/z 368 (Mþ, 81Br,
48), 366 (Mþ, 79Br, 48), 308 (100), 306 (100), 293 (27), 291
(30), 281 (15), 279 (20), 212 (50), 200 (45), 185 (50); HRMS
nmax (film) 2934, 2400, 1449, 1359, 1350, 1215, 1012 cmꢀ1
;
dH NMR (400 MHz, CDCl3) 8.08e8.02 (2H, m, 6-H and
9-H), 7.50e7.44 (2H, m, 7-H and 8-H), 5.24 (1H, q, J1,Me
6.3 Hz, 1-H), 3.91 (3H, s, 5-OMe), 3.86 (3H, s, 10-OMe),
¼
3.74e3.68 (1H, m, 3-H), 3.09 (1H, dd, Jgem¼16.0 Hz, J4eq,3
¼
(EI) m/z calcd for C17H BrO4, C17H BrO4 (Mþ) 366.0467,
2.0 Hz, 4-Heq), 2.63 (1H, dd, Jgem¼16.2 Hz, J4ax,3¼11.0 Hz,
4-Hax), 1.70 (3H, d, JMe,1¼6.3 Hz, 1-Me), 1.43 (3H, d,
JMe,3¼6.1 Hz, 3-Me); dC (100 MHz, CDCl3) 148.8, 148.4,
129.1, 127.4, 127.4, 125.7, 125.5, 125.2, 122.9, 121.1, 71.2,
69.6, 61.2, 60.9, 31.9, 22.4, 21.8; MS (EI, %) m/z 272 (Mþ,
80), 257 (100), 242 (35), 227 (25), 213 (30), 198 (13), 181
(10), 152 (10), 115 (9), 77 (6); HRMS (EI) m/z calcd for
C17H20O3 (Mþ) 272.1412, found 272.1406.
79
19
81
19
368.0446, found 366.0466, 368.0447.
4.8. (S)-3-Bromo-2-(2-acetoxypropyl)-1,4-dimethoxy-
naphthalene 19
To a solution of alcohol (S)-10 (81 mg, 0.25 mmol) in di-
chloromethane (10 mL) was added dropwise acetic anhydride
(0.03 mL, 0.29 mmol) with stirring. After 10 min perchloric
acid (one drop) was added to the reaction mixture and the re-
sulting violet solution was stirred for 2 h. The reaction was
quenched with saturated NaHCO3 solution (20 mL), extracted
with dichloromethane (3ꢂ10 mL). The combined organic ex-
tracts were washed with saturated NH4Cl solution (20 mL) and
dried over anhydrous Na2SO4. The solvent was removed at
reduced pressure and the crude product purified by column
chromatography using hexaneseethyl acetate (9:1) as eluent
to yield the title compound 19 (86 mg, 0.24 mmol, 94%) as a
4.10. (þ)-(1R,3S)-5,10-Dimethoxy-1,3-dimethyl-3,4,5,10-
tetrahydro-1H-naphtho[2,3-c]pyran 21
Compound 21 (52 mg, 0.19 mmol, 82%) was obtained from
(S)-19 (86 mg, 0.23 mmol) using the same procedure for the
preparation of (ꢀ)-18 from (R)-9; colourless liquid, mp 74e
76 ꢁC; [a]D20 þ94.5 (c 0.11, CHCl3). The spectroscopic data
were identical to the (ꢀ)-naphthopyran 18.
1
colourless liquid; [a]D20 ꢀ19.2 (c 0.03, CHCl3). The H NMR
4.11. (ꢀ)-(1S,3R)-1,3-Dimethyl-3,4-dihydro-1H-naphtho-
[2,3-c]pyran-5,10-dione 6
spectrum was identical to that obtained for (þ)-(R)-acetate 9
as reported above.
4.11.1. [(ꢀ)-9-Demethoxyeleutherin]
4.9. (ꢀ)-(1S,3R)-5,10-Dimethoxy-1,3-dimethyl-3,4,5,10-
tetrahydro-1H-naphtho[2,3-c]pyran 18
To the stirred solution of naphthopyran (ꢀ)-18 (30 mg,
0.11 mmol) in acetonitrile (10 mL), was added dropwise a
solution of ceric ammonium nitrate (149 mg, 0.27 mmol) in
water (4 mL) at rt. The reaction mixture was poured into ice-
water (10 mL) and extracted with ethyl acetate (3ꢂ15 mL).
The combined organic extracts were washed with brine
(15 mL) and dried over Na2SO4. The solvent was removed un-
der reduced pressure and the crude mixture purified by flash
chromatography (10% ethyl acetate/hexanes) to afford the title
compound 6 (20 mg, 0.08 mmol, 75%) as a yellow needles,
mp 122e124 ꢁC (lit.9 mp 122e125 ꢁC); [a]2D0 ꢀ256.5 (c
0.11, CHCl3), 99% ee. The enantiomeric excess (ee) was
determined by high performance liquid chromatography
Bromoester (R)-9 (117 mg, 0.33 mmol) was dissolved in
dry THF (5 mL) under nitrogen and the solution cooled to
ꢀ78 ꢁC. A solution of tert-butyllithium in pentane (0.48 mL,
1.6 M, 0.69 mmol) was added dropwise to the above solution
until the reaction mixture turned to a pale red colour and the
reaction was stirred for 1 h. The reaction was quenched at
ꢀ78 ꢁC with H2O (10 mL) followed by gradual warming to
rt then extracted with ethyl acetate (3ꢂ10 mL). The combined
organic extracts were washed with brine (10 mL) and dried
over anhydrous Na2SO4. The solvent was evaporated under

P. Bachu et al. / Tetrahedron 64 (2008) 4827e4834
4833
(Waters-600) using a chiral column (chiralcel ADeH,
0.43ꢂ1 cm, Daicel Chemical Ind. Ltd.), with 2-propanolehex-
ane (1:99) as eluent with a flow rate of 0.5 mL/min. The reten-
tion time for the minor peak was 21 min and the retention time
for the major peak was 24 min; Rf (10% ethyl acetate/hexanes)
0.60; nmax (film) 2935, 1660, 1623, 1595, 1295, 1215,
1055 cmꢀ1; dH NMR (400 MHz, CDCl3) 8.08e8.00 (2H, m,
6-H and 9-H), 7.67e7.73 (2H, m, 7-H and 8-H), 4.87e4.81
3.41 (1H, dd, Jgem¼13.4 Hz, J1B,2¼6.1 Hz, 1-HB), 3.21 (1H,
dd, Jgem¼13.4 Hz, J1A,2¼6.1 Hz, 1-HA), 1.35 (3H, d, J3,2
¼
6.3 Hz, 3-H); dC (75 MHz, CDCl3) 160.5, 151.7, 150.2,
128.2, 127.6, 126.7, 126.6, 126.4, 122.8, 122.6, 116.4, 70.4,
62.3, 61.3, 36.2, 19.8; MS (EI, %) m/z 354 (Mþ, 81Br, 100),
352 (Mþ, 79Br, 100), 308 (75), 306 (75), 293 (25), 291 (25),
267 (20), 265 (20), 230 (45), 212 (70), 200 (50), 185 (65),
171 (20), 127 (20), 115 (20); HRMS (EI) m/z calcd for
81
79
(1H, m, 1-H), 3.63e3.55 (1H, m, 3-H), 2.77 (1H, dt, Jgem
¼
C16H BrO4, C16H BrO4 (Mþ) 354.0290, 352.0310, found
17 17
18.2 Hz, J4eq,3¼2.6 Hz, 4-Heq), 2.25 (1H, ddd, Jgem¼18.6 Hz,
354.0298, 352.0314.
J4ax,3¼10.2 Hz, J4ax,1¼3.9 Hz, 4-Hax), 1.54 (3H, d, JMe,1
¼
6.4 Hz, 1-Me), 1.36 (3H, d, JMe,3¼6.4 Hz, 3-Me); dC
(100 MHz, CDCl3) 184.0, 183.9, 146.8, 142.6, 133.7, 133.5,
132.4, 131.8, 126.19, 126.18, 70.0, 68.7, 30.4, 21.2, 20.8;
MS (EI, %) m/z 242 (Mþ, 100), 227 (45), 224 (10), 213
(25), 209 (20), 198 (30), 181 (20), 152 (10), 115 (20), 76
(25); HRMS (EI) m/z calcd for C15H14O3 (Mþ) 242.0943,
found 242.0943. This spectroscopic data were in agreement
with racemic compound that reported in the literature.9
4.14. (ꢀ)-(1R,3S)-9,10-Dimethoxy-1-hydroxy-3-methyl-3,4-
dihydro-1H-naphtho[2,3-c]pyran 2313
Formate (S)-22 (46 mg, 0.13 mmol) was dissolved in dry
THF (7 mL) under nitrogen and the solution cooled to ꢀ78 ꢁC.
tert-Butyllithium in pentane (0.17 mL, 1.6 M, 0.27 mmol) was
added dropwise to the above solution. The colourless reaction
mixture turned to dark red and the mixture was stirred for 1 h
at the same temperature. The reaction was quenched with H2O
(5 mL) at ꢀ78 ꢁC then left to warm to rt. The crude mixture
was extracted with ethyl acetate (3ꢂ10 mL). The combined
organic extracts were washed with brine (5 mL) and dried
over anhydrous Na2SO4. The solvent was evaporated under
reduced pressure to give a residue that was purified by flash
chromatography using hexaneseethyl acetate (7:3) as eluent
to afford the title compound 23 (27 mg, 0.01 mmol, 76%) as
colourless crystals, mp 145e146 ꢁC (lit.13 mp 146e147 ꢁC);
[a]2D0 ꢀ39.2 (c 1.19, CHCl3); HRMS (EI) m/z calcd for
C16H18O4 (Mþ) 274.1205, found 274.1202. The spectroscopic
data were in agreement with that reported in the literature.13
4.12. (þ)-(1R,3S)-1,3-Dimethyl-3,4-dihydro-1H-naphtho-
[2,3-c]pyran-5,10-dione 7
4.12.1. [(þ)-9-Demethoxyeleutherin]
Compound 7 (14 mg, 0.06 mmol, 72%) was obtained from
(þ)-21 using the same procedure for the preparation of 6 from
(ꢀ)-18; yellow needles, mp 122e124 ꢁC (lit.9 mp 122e
125 ꢁC); [a]D20 þ227.2 (c 0.10, CHCl3), 93% ee. The enantio-
meric excess (ee) was determined by high performance liquid
chromatography (Waters-600) using a chiral column (chiralcel
ADeH, 0.43ꢂ1 cm, Daicel Chemical Ind. Ltd.) using 2-prop-
anolehexanes (1:99) as eluent with a flow rate of 0.5 mL/min.
The retention time for the major peak was 21 min and the
4.15. (þ)-(1R,3S)-1-Hydroxy-3-methyl-3,4,5,10-tetrahydro-
1H-naphtho[2,3-c]pyran-5,10-dione 8
1
retention time for the minor peak was 24 min. The H NMR
spectrum was identical to the (ꢀ)-9-demethoxyeleutherin 6
reported above.
4.15.1. [(þ)-7,9-Deoxythysanone]13
A stirred solution of lactol (ꢀ)-23 (11.5 mg, 0.04 mmol) in
acetonitrile (5 mL) was cooled to 0 ꢁC and a solution of ceric
ammonium nitrate (46 mg, 0.08 mmol) in water (5 mL) was
added dropwise. The reaction mixture was warmed to rt then
poured into water (10 mL) and extracted with ethyl acetate
(3ꢂ15 mL). The combined organic extracts were washed
with brine (15 mL) and dried over anhydrous Na2SO4. After
concentration under reduced pressure, the residue was purified
by column chromatography using hexaneseethyl acetate (7:3)
as eluent to afford the title compound 8 (7.5 mg, 0.03 mmol,
74%) as a pale yellow solid, mp 161e162 ꢁC (lit.13 mp 161e
162 ꢁC); [a]D20 þ139.3 (c 0.76, CH2Cl2) {lit.9 [a]D þ29.5
(c 0.80, CH2Cl2)}, 95% ee. The enantiomeric excess (ee)
was determined by high performance liquid chromatography
(Waters-600) using a chiral column (chiralcel ODeH,
0.43ꢂ1 cm, Daicel chemical Ind. Ltd.) using 2-propanole
hexanes (1:99) as eluent, and a flow rate of 0.5 mL/min. The
retention time for the major peak was 77 min and the retention
time for the minor peak was 97 min; MS (EI, %) m/z 244 (Mþ,
20), 243 (25), 226 (50), 200 (100), 172 (60), 115 (50), 105
(20), 76 (28); HRMS (EI) m/z calcd for C14H12O4 (Mþ)
4.13. (S)-3-Bromo-2-(2-formylpropyl)-1,4-dimethoxy-
naphthalene 22
To a solution of bromoalcohol (S)-10 (50 mg, 0.15 mmol)
in dry dichloromethane (5 mL) was added formic acid
(45 mg, 0.32 mmol). The reaction mixture was cooled to 0 ꢁC
under nitrogen, 4-dimethylaminopyridine (2 mg) was added
and the reaction mixture stirred for 2 min followed by the
addition of dicyclohexylcarbodiimide (40 mg, 0.195 mmol).
After 15 min, the mixture was warmed to rt and stirred for
24 h. The resulting precipitate was removed by filtration and
the filtrate concentrated under reduced pressure. The crude
residue was purified by flash chromatography (10% ethyl
acetate/hexanes) to afford the title compound 22 (46 mg,
0.13 mmol, 85%) as a colourless liquid; Rf (10% ethyl acetate/
hexanes) 0.50; [a]D20 ꢀ25.4 (c 0.19, CHCl3); nmax (film)
2936, 2400, 1719, 1570, 1455, 1360, 1215 cmꢀ1; dH NMR
(300 MHz, CDCl3) 8.18e8.00 (2H, m, 5-H and 8-H), 7.95
(1H, s, OCHO), 7.60e7.50 (2H, m, 6-H and 7-H), 5.57e
5.47 (1H, m, 2-H), 3.96 (3H, s, 1-OMe), 3.93 (3H, s, 4-OMe),

4834
P. Bachu et al. / Tetrahedron 64 (2008) 4827e4834
13. Brimble, M. A.; Elliott, R. J. R. Tetrahedron 2002, 58, 183.
14. Brimble, M. A.; Houghton, S. I.; Woodgate, P. D. Tetrahedron 2007,
63, 880.
244.0736, found 244.0729. The spectroscopic data were in
agreement with that reported in the literature.13
15. Bulbule, V. J.; Priti, P. S.; Deshpande, V. H.; Hanumant, B. Tetrahedron
2007, 63, 166.
References and notes
16. Kraus, A. G.; Ogutu, H. Tetrahedron 2002, 58, 7391.
17. Donner, C. D.; Gill, M. Tetrahedron Lett. 1999, 40, 3921; Donner, C. D.;
Gill, M. J. Chem. Soc., Perkin Trans. 1 2002, 938.
1. (a) Thomson, R. H. Naturally Occurring Quinones, 2nd ed.; Academic:
London, 1971; p 282; See also p 597; (b) For a review on the isolation
and structure of pyranonaphthoquinone antibiotics, see: Brimble, M. A.;
Duncalf, L. J.; Nairn, M. R. Nat. Prod. Rep. 1999, 16, 267.
2. Moore, H. W. Science 1977, 197, 527.
3. (a) Schmid, H.; Meijer, T. M.; Ebnother, A. Helv. Chim. Acta 1950, 33,
595; (b) Schmid, H.; Ebnother, A.; Meijer, T. M. Helv. Chim. Acta
1950, 33, 1751; (c) Schmid, H.; Ebnother, A. Helv. Chim. Acta 1951,
34, 561; (d) Cameron, D. W.; Kingston, D. G. I.; Sheppard, N.; Todd,
A. R. J. Chem. Soc. 1964, 98.
18. (a) Brimble, M. A.; Nairn, M. R.; Park, J. S. O. Org. Lett. 1999, 1, 1459;
Brimble, M. A.; Nairn, M. R.; Park, J. S. O. J. Chem. Soc., Perkin Trans. 1
2000, 697; (b) Brimble, M. A.; Brenstrum, T. J. Tetrahedron Lett. 2000,
41, 2991; Brimble, M. A.; Brenstrum, T. J. J. Chem. Soc., Perkin Trans.
1 2001, 1624; (c) Brimble, M. A.; Davey, R. M.; McLeod, M. D. Synlett
2002, 1318; Brimble, M. A.; Davey, R. M.; McLeod, M. D.; Murphy, M.
Org. Biomol. Chem. 2003, 1, 1690; (d) Brimble, M. A.; Neville, D.;
Duncalf, L. J. Tetrahedron Lett. 1998, 39, 5647; Brimble, M. A.;
Duncalf, L. J.; Neville, D. J. Chem. Soc., Prekin Trans. 1 1998, 4165;
(e) Brimble, M. A.; McEwan, J. F.; Turner, P. Tetrahedron: Asymmetry
1998, 9, 1257; (f) Brimble, M. A.; Lai, M. Y. H. Org. Biomol. Chem.
2003, 1, 4227; (g) Brimble, M. A.; Laita, O.; Robinson, J. E.
Tetrahedron 2006, 62, 3021.
4. (a) Krishnan, P.; Bastow, K. F. Biochem. Phramacol. 2000, 60, 1367; (b)
Hara, H.; Maruyama, N.; Yamashita, S.; Hayashi, Y.; Lee, K.-H.; Bastow,
K. F.; Chairul, R. M.; Imakura, Y. Chem. Pharm. Bull. 1997, 45, 1714.
5. Singh, S. B.; Cordingley, M. G.; Ball, R. G.; Smith, J. L.; Dombrowski,
A. W.; Goetz, M. A. Tetrahedron Lett. 1991, 32, 5279.
6. Kobayashi, K.; Uchida, M.; Uneda, T.; Tanmatsu, M.; Morikawa, O.;
Konishi, H. Tetrahedron Lett. 1998, 39, 7725.
19. Bachu, P.; Gibson, J. S.; Sperry, J.; Brimble, M. A. Tetrahedron: Asymme-
try 2007, 13, 1618.
20. Kesteleyn, B.; De Kimpe, N.; Puyvelde, L. V. J. Org. Chem. 1999, 64,
1173.
7. Uno, H. J. Org. Chem. 1986, 51, 350.
8. Naruta, Y.; Uno, H.; Maruyama, K. J. Chem. Soc., Chem. Commun. 1981,
1277.
21. Kometani, T.; Takeuchi, Y.; Yoshii, E. J. Org. Chem. 1982, 47, 4725.
22. Heinzman, S. W.; Grunwell, J. R. Tetrahedron Lett. 1980, 21, 4305.
23. Kraus, G. A.; Man, T. O. Synth. Commun. 1986, 16, 1037.
24. Veysoglu, T.; Mitscher, L. A.; Swayze, J. K. Synthesis 1980, 807.
25. Brimble, M. A.; Bachu, P.; Sperry, J. Synthesis 2007, 2887.
26. Kazlauskas, R. J.; Weissfloch, A. N.; Rapaport, A. T.; Cuccia, L. A.
J. Org. Chem. 1991, 56, 2656.
9. Kometani, T.; Yoshii, E. J. Chem. Soc., Perkin Trans. 1 1981, 1191.
10. Kometani, T.; Takeuchi, Y.; Yoshii, E. J. Chem. Soc., Perkin Trans. 1
1981, 1197.
11. Giles, G. F.; Green, I. R.; Hugo, V. I.; Mitchell, P. R. K.; York, S. C.
J. Chem. Soc., Perkin Trans. 1 1984, 2383.
12. Tewierik, L. M.; Dimitriadis, C.; Donner, C. D.; Gill, M.; Willems, B.
Org. Biomol. Chem. 2006, 4, 3311.
27. Kraus, G. A.; Molina, M. T.; Walling, J. A. J. Org. Chem. 1987, 52, 1273.