Stereoselective formal synthesis of (-)-centrolobine

Article abstract of DOI:10.1016/j.tet.2006.11.062

Stereoselective formal synthesis of (-)-centrolobine was achieved from naturally occurring l-(+)-tartaric acid, employing a facile FeCl₃ mediated stereoselective formation of a tetrahydropyran as the key step.

Full text of DOI:10.1016/j.tet.2006.11.062

Tetrahedron 63 (2007) 1089–1092
Stereoselective formal synthesis of (L)-centrolobine
*
Kavirayani R. Prasad and Pazhamalai Anbarasan
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
Received 4 October 2006; revised 9 November 2006; accepted 23 November 2006
Available online 15 December 2006
Abstract—Stereoselective formal synthesis of (ꢀ)-centrolobine was achieved from naturally occurring L-(+)-tartaric acid, employing a facile
FeCl3 mediated stereoselective formation of a tetrahydropyran as the key step.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
O
H
H
Tetrahydropyrans, tetrahydrofurans, and oxepanes are ubiq-
uitous structural sub-units present in a number of bio-active
natural products such as Annonaceae acetogenins,1 iono-
phores,2 etc. Centrolobine 1, a diarylheptanoid natural prod-
uct, containing a cis-2,6-disubstituted tetrahydropyran, was
isolated from the heart wood of Centrolobium robustum and
from the stem of Brosimum potabile in the Amazon Forest.3
Centrolobine was shown to be antileishmanial agent against
Leishmania amazonensis promastigotes.4 Although the
structure of centrolobine was confirmed by racemic synthe-
sis in 1964,3a absolute configuration of centrolobine was
confirmed only recently, in 2002 through an enantioselective
synthesis by Solladie et al.5a,c The bio-activity associated
with centrolobine and related tetrahydropyran containing
natural products, resulted in the enantioselective synthesis
of (ꢀ)-centrolobine by different groups in recent years.5
Herein, we report an efficient stereoselective synthesis of
(ꢀ)-centrolobine based on Lewis acid mediated cyclization
of a 1,5-diol to form a tetrahydropyran.
HO
OMe
( )-Centrolobine (1)
−
2. Results and discussion
Continuing efforts from our group in the stereoselective syn-
thesis of natural products from chiral pool L-(+)-tartaric acid
culminated in the syntheses of several bio-active phero-
mones6 and styryl lactones.7 Key approach in our methodol-
ogy is the enantioselective synthesis of a-hydroxy aldehydes,
which serves as excellent building blocks for a number of
natural products. As shown in the retrosynthesis (Scheme 1),
we envisaged the synthesis of centrolobine 1 through the
known intermediate aldehyde 2. Synthesis of the aldehyde
2wasanticipatedfromthe1,2-diol3.Stereoselectiveiron(III)
chloride mediated cyclization of a 1,5-diol 4 was considered
HO
O
O
Ar
Ar
O
H
H
H
O
Ar
H
H
HO
HO
OMe
O
2
( )-Centrolobine (1)
−
Ar = p-methoxyphenyl
OH
3
Me
OMe
N
OH OH
O
O
O
Ar
3
O
O
3
Ar
O
O
O
3
OH 3OH
4
N
OH
Me
OMe
5
6
Scheme 1. Retrosynthesis of (ꢀ)-centrolobine (1).
Keywords: (ꢀ)-Centrolobine; Stereoselective reduction; FeCl3; Tartaric acid.
* Corresponding author. Tel.: +91 80 22932578; fax: +91 80 23600529; e-mail: prasad@orgchem.iisc.ernet.in
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.11.062

1090
K. R. Prasad, P. Anbarasan / Tetrahedron 63 (2007) 1089–1092
for the tetrahydropyran unit formation. 1,5-Diol 4 can be ob-
tained from the elaboration of C2-symmetric diol 5, the syn-
thesis of which has already been established in our laboratory
from the bis-Weinreb amide 6 derived from L-(+)-tartaric
acid.
cleanly furnished the tetrahydropyran aldehyde 2.10 Since
the conversion of aldehyde 4 to (ꢀ)-centrolobine 1 through
Wittig olefination followed by hydrogenation has already
been reported in the literature, the present sequence con-
stitutes a formal synthesis of (ꢀ)-centrolobine (Scheme 3).
The synthetic sequence for the pivotal 1,5-diol 4 commenced
with the controlled addition of 4-pentenylmagnesium bro-
mide to the bis-Weinreb amide 6, furnishing the 1,4-diketone
7 in excellent yield. Under conditions optimized by us for the
reduction of such diketones,8 stereoselective reduction of
1,4-diketone 7 with L-Selectride afforded the 1,4-diol 5 as
a single diastereomer in 94% yield. Protection of the 1,4-
diol 5 as the corresponding bis-silylether utilizing standard
conditions resulted in the bis-silylether 8 in 94% yield.
Ozonolysis of the terminal olefins in 8 furnished the bis-
aldehyde, which without further purification, was subjected
to the Grignard reaction with p-methoxyphenylmagnesium
bromide to yield 9 as mixture of diastereomers at the benzylic
position in 90% combined yield for two steps (Scheme 2).
Since Lewis acid mediated cyclization of a 1,5-diol involving
a benzylic carbocation was envisaged, no effort was made to
separate the diastereomers. Deprotection of the silyl ethers
in 9 with tetrabutylammonium fluoride afforded the 1,5-
diol 4 in 89% yield.
In summary, a formal approach for the stereoselective
synthesis of (ꢀ)-centrolobine was achieved from the bis-
Weinreb amide derived from L-(+)-tartaric acid. The tetrahy-
dropyran framework in (ꢀ)-centrolobine was accomplished
through a facile FeCl3 mediated cyclization of a 1,5-diol.
3. Experimental
3.1. General procedures
Column chromatography was performed on silica gel, Acme
grade 100–200 mesh. TLC plates were visualized either with
UV, in an iodine chamber, or with phosphomolybdic acid
spray, unless noted otherwise. Unless stated otherwise, all
reagents were purchased from commercial sources and used
without additional purification. THF was freshly distilled
over Na-benzophenone ketyl. Melting points were uncor-
rected. Unless stated otherwise, all the reactions were per-
formed under an inert atmosphere. Optical rotations were
measured on a JASCO DIP-370 digital polarimeter at
25 ꢁC. IR spectra were recorded on a Jasco FTIR 410 spec-
Reaction of 1,5-diol 4 with FeCl3 furnished a separable
mixture of tetrahydropyrans 3 and 3a in 70% and 10%,
respectively, formed through the cyclization of 1,5-diol
with concomitant deprotection of the acetonide.9 The major
C2-symmetric diastereomer 3 on treatment with Pb(OAc)4
1
trophotometer. H and 13C NMR spectra were recorded on
JNM l-300 spectrometer. The chemical shifts and coupling
constants are reported in the standard fashion with reference
Me
OMe
N
OTBS
O
O
1) L-Selectride, THF
−78 °C, 2.5 h, 94%
MgBr
O
O
O
O
3
O
O
3
3
THF, 0 °C, 1h
96%
2) TBSCl, Imidazole
O
DMAP, DMF, 80 °C
3 h, 94%
O
3
3
N
OTBS
Me
OMe
6
7
8
Ar = p-OMeC6H4
TBSO
OH
Ar
Ar
OH OH
1) O3/O2, Me2S, NaHCO3
DCM : MeOH, 0 °C, 5h
O
O
TBAF, THF
Ar
rt, 8 h, 89%
3
3
Ar
2) p-OMeC6H4MgBr
THF, 0 °C, 1 h
90% for 2 steps
O
O
TBSO 3OH
OH 3OH
4
9
Scheme 2. Synthesis of key inetermediate 1,5-diol 4.
OH OH
HO
HO
O
O
Ar
Ar
O
O
Ar
Ar
O
Ar
3
FeCl3, DCM
rt, 30 min
+
HO
HO
Ar
O
OH 3OH
4
Ar = p-OMeC6H4
3 70%
3a 10%
HO
Ref 5a
Pb(OAc)4
H
O
O
Ar
Ar
( )-Centrolobine (1)
−
O
Ar
Benzene
HO
H
H
rt, 1.5 h
O
2
3
Scheme 3. Synthesis of (ꢀ)-centrolobine (1).

K. R. Prasad, P. Anbarasan / Tetrahedron 63 (2007) 1089–1092
1091
to either an internal tetramethylsilane (for 1H) or the central
line (77.1 ppm) of CDCl3 (for 13C). NMR samples were pre-
pared in CDCl3. High-resolution mass spectra were recorded
on a Micromass Q-TOF micro mass spectrometer using an
electron spray ionization mode.
temperature and poured into water (15 mL) and extracted
with ether (3ꢂ10 mL). The combined ethereal extracts
were washed with brine and dried over Na2SO4. Evaporation
of solvent followed by column chromatography of the resul-
tant residue using ethylacetate/petroleum ether (1:9) as an
eluent yielded 8 as colorless oil in 94% (0.58 g). [a]D
ꢀ13.8 (c 1.8, CHCl3); IR (neat): 2931, 2858, 1462, 1376,
3.1.1. Preparation of (4R,5R)-4,5-bis(hex-5-enoyl)-2,2-
dimethyl-1,3-dioxolane (7). In an oven dried two necked
50-mL round-bottom flask equipped with a magnetic stir
bar and an argon inlet was placed the bis-Weinreb amide
(6) (0.5 g, 1.8 mmol) dissolved in THF (6 mL). This was
cooled to 0 ꢁC and a THF solution of 4-pentenylmagnesium
bromide (7 mL of a 1 M solution in THF, 7 mmol) was added
dropwise under argon. The reaction mixture was stirred for
1 h, quenched with satd NH4Cl (3 mL), poured into water
(10 mL), and extracted with ether (3ꢂ10 mL). The com-
bined organic layers were washed with brine and dried
over Na2SO4. The residue obtained after the evaporation of
solvent was purified by column chromatography using ethyl-
acetate/petroleum ether (1:9) as an eluent to yield 7 as color-
less oil in 96% (0.51 g). [a]D +11.6 (c 1.2, CHCl3); IR (neat):
1
1253, 835 cmꢀ1; H NMR (300 MHz, CDCl3) d 5.80 (ddt,
J¼17.4, 10.2, 6.6 Hz, 2H), 5.05–4.93 (m, 4H), 3.95 (s,
2H), 3.61 (m, 2H), 2.14–1.98 (m, 4H), 1.72–1.63 (m, 2H),
1.55–1.36 (m, 6H), 1.39 (s, 6H), 0.90 (s, 18H), 0.07 (s,
12H); 13C NMR (75 MHz, CDCl3) d 138.6, 114.6, 108.7,
79.1, 72.2, 33.8, 33.7, 27.3, 26.0, 24.9, 18.3, ꢀ4.1, ꢀ4.2;
HRMS for C29H58O4Si2+Na calcd 549.3771; found
549.3760.
3.1.4. Preparation of (4S,5S)-4,5-bis((1R)-1-(tert-butyldi-
methylsilyloxy)-5-hydroxy-5-(4-methoxyphenyl)pentyl)-
2,2-dimethyl-1,3-dioxolane(9). Ozone was bubbled through
a pre-cooled (ꢀ78 ꢁC) solution of 8 (0.5 g, 0.95 mmol) in
DCM/MeOH (4:1, 12.5 mL) containing solid NaHCO3
(10 mg) till the pale blue color persisted. Excess ozone was
flushed off with oxygen and Me2S (0.8 mL) was added and
stirred for 4.5 h at 0 ꢁC. The reaction mixture was con-
centrated under reduced pressure, filtered through a short
pad of Celite and the Celite pad was washed with ether
(20 mL). The ethereal layers were combined and evaporation
of solvent afforded the crude bis-aldehyde, which was sub-
jected to Grignard reaction without further purification.
2937, 1725, 1455, 1375, 1259, 1153, 995, 914, 860 cmꢀ1
;
1H NMR (300 MHz, CDCl3) d 5.77 (ddt, J¼17.1, 10.2,
6.6 Hz, 2H), 5.06–4.96 (m, 4H), 4.55 (s, 2H), 2.75–2.56
(m, 4H), 2.12–2.05 (m, 4H), 1.77–1.67 (m, 4H), 1.42 (s,
6H); 13C NMR (75 MHz, CDCl3) d 208.4, 137.8, 115.3,
112.4, 81.4, 38.2, 32.9, 26.1, 22.1; HRMS for
C17H26O4+Na calcd 317.1729; found 317.1742.
3.1.2. Preparation of (4S,5S)-4,5-bis((R)-1-hydroxyhex-
5-enyl)-2,2-dimethyl-1,3-dioxolane (5). To a solution of 7
(0.4 g, 1.36 mmol) in THF (4 mL) at ꢀ78 ꢁC was added
L-Selectride (5 mL of a 1 M solution in THF, 5 mmol) drop-
wise over 10 min, under argon. The reaction mixture was
stirred for 2.5 h. After the reaction was complete (TLC), it
was quenched with 2 M NaOH (5 mL) and then H2O2
(30% w/v in water, 2.5 mL) was added at the same temper-
ature and stirred for 3 h at room temperature. (H2O2 treat-
ment is necessary to remove residual boron impurities
resulting from Selectride). The reaction mixture was filtered
through a short pad of Celite and the Celite pad was washed
with ether (20 mL). Combined ethereal layers were washed
with brine and dried (Na2SO4). Residue obtained after
evaporation of solvent was purified by column chromato-
graphy using ethylacetate/petroleum ether (3:7) as an eluent
to yield 5 in 94% (0.38 g) as colorless oil. [a]D ꢀ7.5 (c 1.1,
CHCl3); IR (neat): 3446, 2985, 2861, 1457, 1415, 1380,
The bis-aldehyde obtained above was dissolved in THF
(5 mL) under argon. This was cooled to 0 ꢁC and a THF
solution of p-methoxyphenylmagnesium bromide (3.5 mL,
1 M solution in THF, 3.5 mmol) was added dropwise over
a period of 5 min. The reaction mixture was stirred for 1 h
at the same temperature. After the reaction was complete
as indicated by TLC, it was quenched with satd NH4Cl
(3 mL), poured into water (15 mL), and extracted with
ether (3ꢂ10 mL). The combined ethereal extracts were
washed with brine and dried (Na2SO4). The residue obtained
after evaporation of solvent was purified by column chroma-
tography using ethylacetate/petroleum ether (1:3) as an
eluent to yield 9 as colorless oil in 90% (0.64 g). IR (neat):
3407, 2929, 2856, 1612, 1511, 1461, 1247, 1035, 833,
775 cmꢀ1
;
1H NMR (300 MHz, CDCl3) d 7.23 (d,
J¼8.4 Hz, 4H), 6.85 (d, J¼8.4 Hz, 4H), 4.62–4.55 (m,
2H), 3.92–3.84 (m, 2H), 3.78 (s, 6H), 3.72–3.54 (m, 2H),
2.31 (br s, 2H), 1.80–1.20 (m, 12H), 1.37 (s, 3H), 1.36 (s,
3H), 0.86 (br s, 18H), 0.04 (br s, 12H); 13C NMR
(75 MHz, CDCl3) d 158.9, 136.8, 128.6, 127.7, 127.1,
127.0, 113.9, 113.8, 108.7, 79.0, 74.1, 74.0, 72.2, 72.1,
65.0, 55.2, 39.0, 34.0, 27.3, 27.2, 25.9, 22.1, 22.0,
18.2, ꢀ4.2; HRMS for C40H70O8Si2+Na calcd 769.4507;
found 769.4503.
1240, 1166, 1072, 993, 883 cmꢀ1 1H NMR (300 MHz,
;
CDCl3) d 5.81 (ddt, J¼16.8, 10.2, 6.6 Hz, 2H), 5.05–4.94
(m, 4H), 3.90 (s, 2H), 3.50 (br s, 2H), 2.12–2.01 (m, 4H),
1.71–1.36 (m, 8H), 1.42 (s, 6H); 13C NMR (75 MHz,
CDCl3) d 138.5, 114.8, 109.3, 79.9, 69.9, 34.3, 33.5, 27.3,
24.9; HRMS for C17H30O4+Na calcd 321.2042; found
321.2043.
3.1.3. Preparation of (4S,5S)-4,5-bis((R)-1-(tert-butyl-
dimethylsilyloxy)-hex-5-enyl)-2,2-dimethyl-1,3-dioxo-
lane (8). To a solution of 5 (0.35 g, 1.17 mmol) in DMF
(3.5 mL) were added imidazole (0.36 g, 5.3 mmol), DMAP
(0.020 g, 0.1 mmol), and TBDMSCl (0.53 g, 3.5 mmol) at
room temperature. The reaction mixture was kept at 80 ꢁC
and stirred at the same temperature for 2 h. After the reaction
was completed (indicated by TLC), it was cooled to room
3.1.5. Preparation of (4S,5S)-4,5-bis((1R)-1,5-dihydroxy-
5-(4-methoxyphenyl)pentyl)-2,2-dimethyl-1,3-dioxolane
(4). To a solution of 9 (0.5 g, 0.67 mmol) dissolved in dry
THF (7 mL) was added TBAF (1.05 g, 4 mmol) at 0 ꢁC
under argon. It was slowly allowed to warm to room temper-
ature over a period of 30 min. After stirring for 8 h at room
temperature, it was poured into water (10 mL) and extracted
with ethylacetate (3ꢂ10 mL). Combined ethylacetate extracts

1092
K. R. Prasad, P. Anbarasan / Tetrahedron 63 (2007) 1089–1092
were washed with brine (15 mL) and dried over Na2SO4.
Evaporation of solvent followed by column chromatography
of the resultant residue using ethylacetate/petroleum ether
(9:1) as an eluent yielded 4 in 89% (0.31 g) as colorless oil.
IR (neat): 3403, 2935, 1611, 1512, 1246, 1174, 1033,
References and notes
1. Bermejo, A.; Figadere, B.; Zafra-Polo, M.-C.; Barrachina, I.;
Estornell, E.; Cortes, D. Nat. Prod. Rep. 2005, 22, 269.
2. Faul, M. M.; Huff, B. E. Chem. Rev. 2000, 100, 2407.
3. (a) de Albuquerque, I. L.; Galeffi, C.; Casinovi, C. G.; Marini-
Bettolo, G. B. Gazz. Chim. Ital. 1964, 94, 287; (b) Galeffi, C.;
Giulio Casinovi, C.; Marini-Bettolo, G. B. Gazz. Chim. Ital.
1965, 95, 95; (c) Craveiro, A. A.; Prado, A. d. C.; Gottlieb,
O. R.; Welerson de Albuquerque, P. C. Phytochemistry 1970,
9, 1869.
832 cmꢀ1
;
1H NMR (300 MHz, CDCl3) d 7.20 (d, J¼
8.4 Hz, 4H), 6.82 (d, J¼8.4 Hz, 4H), 4.57–4.51 (m, 2H),
3.84 (br s, 2H), 3.75 (s, 6H), 3.48–3.43 (m, 2H), 3.30–3.00
(br s, 4H), 1.81–1.20 (m, 12H), 1.36 (s, 6H); 13C NMR
(75 MHz, CDCl3) d 158.7, 136.9, 126.9, 113.6, 108.9, 79.6,
73.6, 73.5, 69.8, 69.7, 60.3, 55.0, 49.2, 38.6, 38.5, 34.0,
33.8, 27.1, 22.0, 20.8, 14.0; HRMS for C29H42O8+Na calcd
541.2777; found 541.2764.
4. Araujo, C. A. C.; Alefrio, L. V.; Leon, L. L. Phytochemistry
1998, 49, 751.
5. (a) Colobert, F.; Mazery, R. D.; Solladie, G.; Carreno, M. C.
Org. Lett. 2002, 4, 1723; (b) Marumoto, S.; Jaber, J. J.;
Vitale, J. P.; Rychnovsky, S. D. Org. Lett. 2002, 4, 3919; (c)
Carreno, M. C.; Mazery, R. D.; Urbano, A.; Colobert, F.;
Solladie, G. J. Org. Chem. 2003, 68, 7779; (d) Evans, P. A.;
Cui, J.; Gharpure, S. J. Org. Lett. 2003, 5, 3883; (e) Lee, E.;
Kim, H. J.; Jang, W. S. Bull. Korean Chem. Soc. 2004, 25,
1609; (f) Boulard, L.; BouzBouz, S.; Cossy, J.; Franck, X.;
Figadere, B. Tetrahedron Lett. 2004, 45, 6603; (g) Clarke,
P. A.; Martin, W. H. C. Tetrahedron Lett. 2004, 45, 9061; (h)
Chan, K. P.; Loh, T. P. Org. Lett. 2005, 7, 4491; (i) Clarke,
P. A.; Martin, W. H. C. Tetrahedron 2005, 61, 5433; (j)
Jennings, M. P.; Clemens, R. T. Tetrahedron Lett. 2005, 46,
2021; (k) Chandrasekhar, S.; Prakash, S. J.; Shyamsunder, T.
Tetrahedron Lett. 2005, 46, 6651; (l) Bohrsch, V.; Blechert,
S. Chem. Commun. 2006, 1968; (m) Lee, C. H. A.; Loh, T. P.
Tetrahedron Lett. 2006, 47, 1641.
3.1.6. Preparation of (1R,2R)-1,2-bis((2R,6S)-tetrahydro-
6-(4-methoxyphenyl)-2H-pyran-2-yl)ethane-1,2-diol (3).
In an oven dried single necked 10-mL round-bottom flask
was placed 4 (0.2 g, 0.45 mmol) dissolved in dry DCM
(3 mL) under argon. FeCl3 (72 mg, 0.45 mmol) was added
at room temperature and the reaction mixture was stirred
for 30 min. After the reaction was complete (as indicated
by TLC), it was diluted with ether (20 mL) and washed
with satd NaHCO3 (3 times), brine (10 mL), and dried
over Na2SO4. Residue obtained after evaporation of solvent
was purified by column chromatography using ethylacetate/
petroleum ether (1:1) as an eluent to yield 3 in 70% (0.12 g)
along with 3a in 10% (0.017 g) yield. Physical and spectral
data of the major isomer 3. [a]D ꢀ74.0 (c 1.5, CHCl3); IR
(neat): 3477, 2937, 2842, 1513, 1245, 1176, 1078, 1031,
811 cmꢀ1
;
1H NMR (300 MHz, CDCl3) d 7.26 (d,
J¼8.7 Hz, 4H), 6.86 (d, J¼8.7 Hz, 4H), 4.40–4.34 (m,
2H), 3.85–3.66 (m, 4H), 3.79 (s, 3H), 3.13 (br s, 2H),
1.20–1.94 (m, 2H), 1.83–1.37 (m, 10H); 13C NMR
(75 MHz, CDCl3) d 158.9, 135.2, 127.1, 113.6, 79.9, 79.7,
73.5, 55.2, 33.4, 26.5, 23.5; Anal. calcd for: C, 70.56; H,
7.74. Found: C, 70.61; H, 7.98.
6. Synthesis of bio-active pheromones: (a) Prasad, K. R.;
Anbarasan, P. Tetrahedron: Asymmetry 2005, 16, 3951; (b)
Prasad, K. R.; Anbarasan, P. Tetrahedron Lett. 2006, 47,
1433; (c) Prasad, K. R.; Anbarasan, P. Synlett 2006, 2087; (d)
Prasad, K. R.; Anbarasan, P. Tetrahedron: Asymmetry 2006,
17, 1146; (e) Prasad, K. R.; Anbarasan, P. Tetrahedron 2006,
62, 8303; (f) Prasad, K. R.; Chandrakumar, A.; Anbarasan, P.
Tetrahedron: Asymmetry 2006, 17, 1979.
7. Synthesis of styryl lactones: (a) Prasad, K. R.; Gholap, S. L.
Synlett 2005, 2260; (b) Prasad, K. R.; Gholap, S. L. J. Org.
Chem. 2006, 71, 3643.
8. Prasad, K. R.; Chandrakumar, A. Tetrahedron: Asymmetry
2005, 16, 1897.
9. Although, FeCl3 mediated cyclization of 1,4-diols to the corre-
sponding THF ethers is known in the literature (Sharma,
G. V. M.; Kumar, K. R.; Sreenivas, P.; Krishna, P. R.;
Chorghade, M. S. Tetrahedron: Asymmetry 2002, 13, 687–
690), to the best of our knowledge formation of tetrahydro-
pyrans by similar cyclization is not addressed. Formation of
the tetrahydropyran 3b in 17% yield was also observed, which
on further reaction with aq HCl furnished 3.
3.1.7. Preparation of (2S,6R)-2-(4-methoxyphenyl)-6-for-
myltetrahydropyran (2). To a solution of 1,2-diol (3)
(0.1 g, 0.22 mmol) in benzene (3 mL) at room temperature
was added Pb(OAc)4 (0.2 g, 0.4 mmol) under argon. The
reaction mixture was stirred for 1.5 h at the same tempera-
ture. After the reaction was completed (TLC), it was filtered
through short pad of Celite, the Celite pad was washed
with dichloromethane (15 mL) and dried over Na2SO4.
Evaporation of solvent under reduced pressure afforded 2
as colorless oil in quantitative yield (99 mg). [a]D ꢀ9.1 (c
3.4, CHCl3); lit.5c [a]D ꢀ6 (c 0.874, CHCl3); IR (neat):
2932, 2855, 1737, 1612, 1517, 1441, 1369, 1030, 812,
768 cmꢀ1 1H NMR (300 MHz, CDCl3) d 9.70 (s, 1H),
;
7.32 (d, J¼8.7 Hz, 2H), 6.90 (d, J¼8.7 Hz, 2H), 4.44–4.39
(m, 1H), 4.01–3.94 (m, 1H), 3.80 (s, 3H), 2.12–1.39 (m,
6H); 13C NMR (75 MHz, CDCl3) d 202.2, 159.0, 134.3,
127.2, 113.7, 82.1, 79.6, 55.2, 33.0, 25.9, 23.2.
O
O
HO
HO
aq.HCl/THF
rt, 5h, 94%
O
O
Ar
Ar
O
O
Ar
Ar
3b
3
Acknowledgements
10. Stereochemistry as well as enantiopurity of the aldehyde 2 were
further confirmed by reduction to the corresponding alcohol
([a]D ꢀ53 (c 1.3, CHCl3), lit.5c [a]D ꢀ53 (c 0.806, CHCl3)), the
spectraldataofwhichisconsistentwiththatreportedinliterature.
We thank Department of Science and Technology (DST) for
funding of this project. P.A. thanks CSIR for a research
fellowship.