Stereoselective total syntheses of (+)-exo- and (-)-exo-brevicomins, (+)-endo- and (-)-endo-brevicomins, (+)- and (-)-cardiobutanolides, (+)-goniofufurone

Article abstract of DOI:10.1016/j.tet.2011.04.014

Stereoselective total syntheses of aggregation pheromones (+)-exo-brevicomin (9a), (-)-exo-brevicomin (9b), (+)-endo-brevicomin (9c), (-)-endo-brevicomin (9d) and styryllactones (+)-cardiobutanolide (14a), (-)-cardiobutanolide (14b), and (+)-goniofufurone

Full text of DOI:10.1016/j.tet.2011.04.014

Tetrahedron 67 (2011) 4036e4047
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Stereoselective total syntheses of (þ)-exo- and (ꢀ)-exo-brevicomins,
(þ)-endo- and (ꢀ)-endo-brevicomins, (þ)- and (ꢀ)-cardiobutanolides,
(þ)-goniofufurone
*
Pinki Pal, Arun K. Shaw
Division of Medicinal and Process Chemistry, Central Drug Research Institute (CDRI), CSIR, Lucknow 226 001, Uttar Pradesh, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Stereoselective total syntheses of aggregation pheromones (þ)-exo-brevicomin (9a), (ꢀ)-exo-brevicomin
(9b), (þ)-endo-brevicomin (9c), (ꢀ)-endo-brevicomin (9d) and styryllactones (þ)-cardiobutanolide (14a),
(ꢀ)-cardiobutanolide (14b), and (þ)-goniofufurone (19a) were achieved in good yields from enantio-
merically pure highly functionalized furanoid glycal building blocks (1aed) involving similar synthetic
strategies, thus making these furanoid glycals highly useful building blocks in diversity-oriented syn-
thesis (DOS).
Received 22 February 2011
Received in revised form 31 March 2011
Accepted 6 April 2011
Available online 12 April 2011
Keywords:
Brevicomin
Ó 2011 Elsevier Ltd. All rights reserved.
Chiral building blocks
Cardiobutanolide
Goniofufurone
Vinylbutyrolactone
1. Introduction
of stereochemically pure four different furanoid glycals 1aed (Fig. 1)
synthesized from our earlier reported easily accessible enantio-
The chiral building blocks (CBBs) derived from commercially
available carbohydrates are most important chiral synthons for total
synthesis of functionally and stereochemically simple and complex
natural products. This approach of synthesis utilizing the stereo-
chemistry of the starting material is customarily known as the ‘chi-
ron’ approach synthesis1a,b and it becomes very cost effective if
starting material is derived from inexpensive carbohydrate or amino
acid. The stereoselective synthesis of small molecule natural prod-
ucts with multiple chiral centers starting from easily accessible
starting material of choice is a challenging task to an organic chemist.
However, their synthesis could be possible starting from inexpensive
stereochemically pure building blocks or CBBs that should be either
commercially available or synthesized in the laboratory. The prepa-
ration of attractive building blocks from carbohydrates and their use
for the synthesis of various biologically active simple or complex
natural products has received considerable attention from organic
chemists. Therefore, the stereocontrolled synthesis of CBBs is an
important objective in organic chemistry. Since last few years we are
working toward the synthesis of enantiomerically pure sugar derived
building blocks and their utilization to accomplish the total synthesis
of target natural products1d,f and natural product like molecule-
s.1c,e,g,h,j Recently, we disclosed an efficient protocol for the synthesis
merically pure 2,3,4-trisubstituted THF scaffolds.1i Now, to continue
our ongoing programme and also to show the synthetic applications
of these furanoid glycals or in other way their precursor THF scaf-
folds, we have identified few natural products with different bi-
ological activities, such as aggregation pheromones brevicomins
(9aed), styryllactones cardiobutanolides (14a,b) and (þ)-goniofu-
furone (19a) (Fig. 2) whose syntheses can be possible from furanoid
glycal building blocks (1aed).
Fig. 1. Structures of furanoid glycals 1aed.
2. Results and discussion
2.1. Synthesis of brevicomins (9aed)
The 6,8-dioxabicyclo[3.2.1]octane skeleton is a structural sub-
unit in complex natural products like palytoxin2a and pinnatoxin
A,2b and also in simpler insect pheromones, such as exo- and
* Corresponding author. E-mail address: akshaw55@yahoo.com (A.K. Shaw).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.04.014

P. Pal, A.K. Shaw / Tetrahedron 67 (2011) 4036e4047
4037
(þ)-endo-brevicomin 9c and its optical isomer 9d could similarly be
possible from enantiomerically pure erythro-furanoid glycals 1c
and 1d, respectively.
Our synthetic strategy to synthesize (þ)-exo-brevicomin from
furanoid glycal 1a (1,4-anhydro-2-deoxy-5,6-O-isopropylidene-3-
O-benzyl-D-arabino-hex-1-enitol) is shown in Scheme 2. The glycal
1a was converted into 2a by oxymercurationedemercuration7 se-
quence in 98% yield. The anomeric OH was oxidized with PDC in dry
DCM at refluxing temperature for 2 h to obtain lactone 3a as
a white solid in 75% yield. Deprotection of the acetonide in 3a was
carried out smoothly with 60% aqueous AcOH at room temperature
for 18e20 h to give diol 4a as a white solid, which was without
further purification, mesylated with MsCl in pyridine at 0 ꢁC for 3 h
to afford dimesyl derivative 5a. The diester 5a as such was imme-
diately subjected to undergo reductive elimination8 with NaI in
butan-2-one at reflux temperature for 12 h to give vinyl-
butyrolactone derivative 6a in 71% yield for three steps. Its re-
duction with DIBALH was carried out at ꢀ78 ꢁC in dry toluene to
obtain lactol 7a in 86% yield. While Wittig olefination of lactol 7a
with Ph3PCHCOCH3 in dry acetonitrile to furnish an intermediate
7a0 by the literature method5h did not produce any result, per-
forming the same reaction in dry toluene followed by Raney-Ni
hydrogenation of the resulting product with two double bonds
afforded column purified ketone 8a in 52% yield in two steps.
Finally, the simultaneous hydrogenolysis of OBn in 8a in the pres-
ence of Pd/C in MeOH and intramolecular acetalization with a trace
of 3 N HCl (Scheme 2) delivered the target (þ)-exo-brevicomin 9a
in 44% yield.5h,6i,k The physical and spectroscopic data of our syn-
thetic sample 9a are identical to those of the reported natural and
synthetic product.2c
Fig. 2. Structures of brevicomins (9aed), (þ)-cardiobutanolide (14a), (ꢀ)-car-
diobutanolide (14b), and (þ)-goniofufurone (19a).
endo-brevicomins (9aed, Fig. 2). Alkylated 6,8-dioxabicyclo[3.2.1]
octanes are well-known aggregation pheromones isolated from
several species of the bark beetles and play an important role in the
system of chemical communication amongst them. These beetles
infect pine trees causing great ecological and economic damage.
Brevicomin and frontalin were some of the earliest alkylated 6,8-
dioxabicyclo[3.2.1]octanes to be identified important head space
volatiles obtained from different Dendroctonus species.2cee The exo-
and endo-isomers of brevicomin are component of the volatiles of
several economically important bark beetles in the genera Den-
droctonus and Dryocoetes.2cee,3,4 Amongst various alkyl derivatives,
(þ)-exo-brevicomin was identified as a key component of aggre-
gation pheromone from the frass of the females of western pine
beetle, Dendroctonus brevicomis, which is a principal pest in the
timber regions on the western coast of North America.2cee,3
(þ)-endo-Brevicomin is an aggregation pheromone of Dryocoetes
autographus, a damaging pest of Norway spruce.2d,4b (þ)-endo-
Brevicomin also acts as an aggregation pheromone of southern pine
beetles, Dendroctonus frontalis, to the female-produced pheromone
frontalin, while (ꢀ)-endo-brevicomin acts as an antiaggregation
pheromone for this insect.4d,f
Encouraged by biological activities of brevicomins, various
synthetic approaches have been devised for their synthesis.5,6
Herein, we report the synthesis of two pairs of enantiomer of
brevicomins viz. (þ)-exo-, (ꢀ)-exo-brevicomins and (þ)-endo-,
(ꢀ)-endo-brevicomins from similar type of furanoid glycals (1aed),
respectively.
The general retrosynthetic prospective of brevicomins 9aed is
delineated in Scheme 1. Here, we realized that the selection of the
furanoid glycal building blocks could rely upon the two contiguous
stereocenters of immediate precursors 8 of the target brevicomins.
Thus, in the case of synthesis of (þ)-exo-brevicomin 9a, the C-6 and
C-7 stereocenters of threo-alcohol 8a could be derived from C-3 and
C-4 of threo-furanoid glycal 1a. Similarly, its optical antipode
(ꢀ)-exo-brevicomin 9b could be synthesized from threo-furanoid
glycal 1b via the intermediates threo-alcohol 8b and threo-lactone
6b. Further, based on the above argument the synthesis of
Scheme 2. Synthesis of (þ)-exo-brevicomin 9a.
After having completed the total synthesis of (þ)-exo-brevico-
min 9a from furanoid glycal 1a, the similar reaction sequence was
successfully followed for the synthesis of (ꢀ)-exo-brevicomin 9b
from 1b (1,4-anhydro-2-deoxy-5,6-O-isopropylidene-3-O-benzyl-
L
-arabino-hex-1-enitol) (Scheme 3), (þ)-endo-brevicomin 9c from
1c (1,4-anhydro-2-deoxy-5,6-O-isopropylidene-3-O-benzyl- -ribo-
L
hex-1-enitol) (Scheme 4) and (ꢀ)-endo-brevicomin 9d from 1d
(1,4-anhydro-2-deoxy-5,6-O-isopropylidene-3-O-benzyl-D-ribo-
hex-1-enitol) (Scheme 5).
2.2. Synthesis of cardiobutanolides (14a,b)
For a long time Asian trees of the genus Goniothalamus of the
plant family Annonaceae have been the subject of extensive in-
vestigation most particularly due to its proven use in folk medicine
as well as the diverse and potent polyketide constituents it offers.9
Scheme 1. General retrosynthetic strategy for brevicomins (9aed) from enantio-
merically pure similar furanoid glycals 1aed.

4038
P. Pal, A.K. Shaw / Tetrahedron 67 (2011) 4036e4047
Fig. 3. Naturally occurring representative styryllactones.
9% overall yield reported by Murga et al.14 six more total synthesis
and one formal synthesis of this molecule have been reported.15
Encouraged by the pharmacological activity and complex struc-
ture of (þ)-cardiobutanolide 14a endowed with five contiguous
chiral centers each bearing oxygen functionality, we became also
interested to take up the ‘chiron’ approach to synthesis of both the
enantiomers of this molecule.
Scheme 3. Synthesis of (ꢀ)-exo-brevicomin 9b.
Based on the retrosynthetic plan as described in Scheme 6, we
realized that while the stereocenters C-3 and C-4 of (þ)-car-
diobutanolide 14a could be translated from furanoid glycal 1a, the
remaining three stereocenters have to be created. Thus, the syn-
thesis of (þ)-cardiobutanolide 14a could be initiated from furanoid
glycal 1a. The key intermediate 6a was prepared from the furanoid
glycal 1a as described in Scheme 2. The olefin cross metathesis
reaction15e between 6a and (S)-1-phenyl-2-propene-1-ol with
Grubbs’ second generation catalyst (2.8 mol %) in refluxing DCM
furnished allylic alcohol 10a in 74% yield. It was silylated with TBSCl
in the presence of imidazole in dry DCM at 0 ꢁC to afford silyl ether
11a in 93% yield. Its asymmetric dihydroxylation with AD-mix-b in
1:1 tBuOH/H2O afforded a separable mixture of diastereomers in 5%
and 67% yield. Our desired compound identified as 12a was
obtained in 67% yield, which was utilized to complete the synthesis
of the title compound. The silyl ether deprotection of 12a with
amberlyst 15 resin in dry acetonitrile produced 13a in 94% yield.
Finally, its O-benzyl deprotection by Pd(OH)2 catalyzed hydro-
genolysis in dry MeOH furnished the desired natural product
(þ)-cardiobutanolide 14a in 67% yield (Scheme 7). The physical and
spectroscopic data of our synthetic sample 14a are identical to
those of the reported natural and synthetic product.14,15
Scheme 4. Synthesis of (þ)-endo-brevicomin 9c.
Scheme 5. Synthesis of (ꢀ)-endo-brevicomin 9d.
The leaves and extracts of Goniothalamus are traditionally used for
the treatments of edema and rheumatism,9a and also as a pain
killer, mosquito repellent,9b and an abortifacient.9c The research
group of McLaughlin have reported the isolation and character-
ization of a series of styryllactones from several species of the genus
Goniothalamus (Annonaceae). These molecules were shown to
possess various important biological activities like pesticidal,
ratogenic, embryotoxic. The significant to marginal cytotoxic ac-
tivity against human tumor cell lines were also found in these
styryllactones (Fig. 3).10e12 Hisham et al. have reported the isolation
of (þ)-cardiobutanolide 14a, a pharmacologically active natural
product from the stem bark of Goniothalamus cardiopetalus, along
with other known styryllactones in 2003.13 Its structural com-
plexity owing to five contiguous chiral centers and potential
pharmacological activity attracted the attention of synthetic or-
ganic chemists in recent years. After its first synthesis employing
Scheme 6. General retrosynthetic strategy for cardiobutanolides (14a,b) from enan-
tiomerically pure furanoid glycals 1a,b.
anti selective boronate aldol reaction of L-erythrulose derivative in
Scheme 7. Synthesis of (þ)-cardiobutanolide 14a.

P. Pal, A.K. Shaw / Tetrahedron 67 (2011) 4036e4047
4039
Similarly, the (ꢀ)-cardiobutanolide 14b was synthesized from
1b, an optical antipode of 1a by adopting the reaction sequence
similar to that employed for the synthesis of its enantiomer 14a.
The olefin cross metathesis reaction between compound 6b de-
rived from 1b (Scheme 3) and (R)-1-phenyl-2-propene-1-ol with
Grubbs’ second generation catalyst (2.8 mol %) furnished allylic
alcohol 10b in 74% yield. Its silylated derivative 11b on asymmetric
The acetonide protection of two free OH in 12a afforded globally
OH protected derivative 15a in 83% yield. Its hydrogenolysis in the
presence of Pd(OH)2 in dry EtOAc gave O-benzyl deprotected de-
rivative 16a in 87% yield, which on mesylation with MsCl/Et3N at
0 ꢁC in dry DCM for 1 h followed by elimination18of MsOH under
basic condition furnished the a,b-unsaturated lactone 17a in 92%
yield. Its treatment with THF/AcOH/2 N HCl (1:1:1) at room tem-
perature delivered the triol 18a in 56% yield.17t Finally, it was sub-
jected to DBU catalyzed bicyclic ring formation by the participation
of its 6-OH to furnish the title natural product (þ)-goniofufurone
19a as a white solid in 64% yield (Scheme 10). The physical and
spectroscopic data of 19a are identical to those of the reported
natural and synthetic product.12c,16,17
dihydroxylation with AD-mix-a
in 1:1 tBuOH/H2O afforded a sepa-
rable mixture of diastereomers. The desired isomer 12b (enantio-
mer of 12a) was obtained in 58% yield along with its other
diastereomer in 8% yield. After having 12b in hand, the remaining
two synthetic steps similar to that employed for the synthesis of
(þ)-cardiobutanolide 14a (vide supra) were followed to complete
the synthesis of (ꢀ)-cardiobutanolide 14b (Scheme 8). The spectral
data of 14b are in complete agreement with the reported natural
product (þ)-cardiobutanolide 14a.14,15
Scheme 10. Synthesis of (þ)-goniofufurone 19a.
Scheme 8. Synthesis of (ꢀ)-Cardiobutanolide 14b.
3. Conclusion
In conclusion, this paper reports the stereoselective total synthe-
ses of four isomeric aggregationpheromones, (þ)-exo-brevicomin 9a,
(ꢀ)-exo-brevicomin 9b, (þ)-endo-brevicomin 9c, (ꢀ)-endo-brevico-
min 9d, two enantiomeric styryllactones (þ)-cardiobutanolide 14a,
(ꢀ)-cardiobutanolide 14b, and another styryllactone (þ)-goniofu-
furone 19a by utilizingour earlier reported stereochemically different
furanoid glycal key building blocks (1aed) derived from commer-
ciallyavailable sugars.1i The selection offuranoid glycals(1aed) in the
present work was done on the basis of the stereochemistries of the
chiral centers of the above mentioned target molecules. The impor-
tance of the work, described in this paper, lies in the fact that the
strategiesemployedforthesynthesisofallthetitlecompoundscanbe
followed to access some other unnatural diastereoisomers of car-
diobutanolides, which are hitherto unreported and also natural and
unnatural goniofufurones by using these furanoid glycals more effi-
ciently compared to the synthetic routes previously reported in the
literature. To the best of our knowledge the synthesis of unnatural
(ꢀ)-cardiobutanolide 14b has not yet been reported. Earlier, we have
shown the importance of all the precursors (THF scaffolds) of these
furanoid glycals by utilizing them as a source of chirality for the
syntheses of natural products1d,f and different molecules of various
biological properties as well.1e,h,j Therefore, it is worth mentioning
that these enantiomerically pure furanoid glycals and their pre-
cursors, which can be prepared in multi gram scale have proven to be
versatile building blocks for diversity-oriented synthesis (DOS) of
variety of natural products and molecules of biological importance.
2.3. Synthesis of (D)-goniofufurone 19a
(þ)-Goniofufurone (19a), a cytotoxic styryllactone that was
isolated from the stem bark of Goniothalamus giganteus Hook. f.,
Thomas (Annonaceae), obtained from Thailand in 1990.12c The
absolute configuration was significantly established independently
€
by Shing and Jager by synthesis of the unnatural ent-(ꢀ)-goniofu-
furone.16 Owing to significant cytotoxic activity toward several
human tumors cell lines and moderate toxicity to brine shrimp
(BS), as well as the interesting heterocyclic skeletons, (þ)-gonio-
fufurone 19a and its stereoisomers have been synthesized by many
groups from different starting materials.17 After successfully com-
pleting the total syntheses of isomeric four brevicomins and two
cardiobutanolides from furanoid glycals, herein we wish to report
the total synthesis of cytotoxic natural (þ)-goniofufurone 19a.
The retrosynthetic strategy of (þ)-goniofufurone 19a as shown
below (Scheme 9) revealed that its synthesis could also be possible
from furanoid glycal 1a as we envisaged in the case of (þ)-car-
diobutanolide 14a. Here, we visualized that the immediate pre-
cursor 18a of the target natural product 19a could easily be
accessed from 12a, which in turn could be obtained by the exten-
sion of furanoid glycal 1a via the intermediates 2a/11a as de-
scribed in the synthesis of (þ)-cardiobutanolide 14a (Scheme 7).
4. Experimental section
4.1. General
Organic solvents were dried by standard methods. All the
products were characterized by 1H, 13C, two-dimensional
Scheme 9. Retrosynthetic strategy for (þ)-goniofufurone (19a) from enantiomerically
pure furanoid glycal 1a.

4040
P. Pal, A.K. Shaw / Tetrahedron 67 (2011) 4036e4047
homonuclear COSY (correlation spectroscopy), heteronuclear sin-
gle quantum coherence (HSQC), heteronuclear multiple bond cor-
relation spectroscopy (HMBC), IR, DARTeHRMS, and EI-HRMS (C, H,
O). Analytical TLC was performed using 2.5ꢂ5 cm plates coated
with a 0.25 mm thickness of silica gel (60F-254), visualization was
accomplished with CeSO4 or 10% H2SO4/MeOH and subsequent
charring over hot plate. Column chromatography was performed
using silica gel (60e120 mesh) and silica gel (230e400 mesh). NMR
spectra were recorded on Bruker Avance 200 MHz spectrometer at
200 MHz (1H) and 50 MHz (13C), Bruker Avance 300 MHz spec-
trometer at 300 MHz (1H) and 75 MHz (13C), 400 MHz spectrome-
ter at 400 MHz (1H) and 100 MHz (13C), and Bruker Avance
600 MHz spectrometer at 600 MHz (1H). Experiments were recor-
ded in CDCl3 or CDCl3þCCl4 1:1 mixture, methanol-d4 and acetone-
127.7, 127.9, 128.3, 128.4 (ArC, ArCD), 137.4 (ArqC), 138.1 (ArqCD); EI-
HRMS: [M]þꢃ, found 294.1457. C16H22O5 requires 294.1467.
4.2.2. (4S,5R)-4-(Benzyloxy)-5-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)
tetrahydrofuran-2-ol (2b). Pale yellow syrup; yield: 82% (
(450 mg). Eluent for column chromatography: EtOAc/hexane (4/21,
v/v); Rf¼0.40 (1/2 EtOAc/hexane); IR (neat): ¼761, 1072, 1216, 1617,
1711, 2360, 2931, 3443 cmꢀ1; 1H NMR (300 MHz, CDCl3):
1.37e1.39
a:b¼1:1)
n
d
(6H, m, J¼4.8 Hz, Me, MeD), 1.42 (6H, br s, Me, MeD), 1.96e2.07 (2H,
m), 2.21e2.31 (2H, m), 3.79e3.83 (1H, m), 3.87 (1H, dd, J¼3.5,
7.8 Hz), 3.93e4.09 (3H, m), 4.14e4.26 (4H, m), 4.36e4.47 (2H, m),
4.49 (1H, d, J¼11.9 Hz), 4.56 (1H, d, J¼11.9 Hz), 4.61e4.69 (2H, m),
5.37 (1H, dd, J¼5.0, 11.5 Hz), 5.64e5.66 (1H, m), 7.26e7.36 (10H, m);
13C NMR (75 MHz, CDCl3):
d 25.3 (CH3D), 25.4 (CH3), 26.6 (CH3D), 26.7
d6 at 25 ꢁC. Chemical shifts are given on the
d
scale and are refer-
(CH3), 39.4 (CH2), 40.5 (CH2D), 66.7 (CH2D), 67.4 (CH2), 71.5 (CH2D),
72.2 (CH2), 73.4 (CHD), 73.8 (CH), 77.9 (CH), 78.6 (CHD), 80.9 (CHD),
83.9 (CH), 98.1 (CHD), 99.1 (CH), 108.6 (qCD), 108.9 (qC), 127.4, 127.5,
127.7, 127.9, 128.3, 128.4 (ArC, ArCD), 137.4 (ArqC), 138.1 (ArqCD); EI-
HRMS: [MꢀCH3]þꢃ, found 279.1221. C15H19O5 requires 279.1232.
enced to the TMS at 0.00 ppm for proton and 0.00 ppm for carbon.
For 13C NMR reference CDCl3 appeared at 77.00 ppm. For 13C NMR
in CDCl3þCCl4 mixture CCl4 appeared at 96.2 ppm. For 1H NMR
spectra methanol-d4 appeared at 3.35 ppm and for 13C NMR spectra
methanol-d4 appeared at 49.00 ppm. For 1H NMR spectra acetone-
d6 appeared at 2.83 ppm and for 13C NMR spectra acetone-d6
appeared at 206.4 ppm. For IR spectra were recorded on Per-
kineElmer 881 and FTIR-8210 PC Shimadzu Spectrophotometers.
Mass spectra were recorded on a JEOL JMS-600H high resolution
spectrometer using EI mode at 70 eV. DARTeHRMS were recorded
on a JEOL-AccuTOF, JMS-T100LC spectrometer. Optical rotations
were determined on an Autopol III polarimeter using a 1 dm cell at
25e32 ꢁC in chloroform and methanol as the solvents; concentra-
tions mentioned are in g/100 mL. Systematic (IUPAC) names of all
the compounds have been given based on THF derivative.
4.2.3. (4R,5R)-4-(Benzyloxy)-5-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)
tetrahydrofuran-2-ol (2c). Pale yellow syrup; yield: 73% (
(400 mg). Eluent for column chromatography: EtOAc/hexane (4/21,
v/v); Rf¼0.38 (1/2 EtOAc/hexane); IR (neat): ¼670, 761, 1216, 1636,
2361, 3022, 3427 cmꢀ1 1H NMR (300 MHz, CDCl3):
1.33 (6H, s,
a
:b
¼1:1)
n
;
d
Me, MeD), 1.44 (6H, s, Me, MeD), 2.01e2.29 (4H, m), 3.70e3.80 (3H,
m), 3.86e3.94 (2H, m), 4.06e4.12 (3H, m), 4.17e4.31 (4H, m),
4.52e4.65 (4H, m), 5.42 (1.4H, dd, J¼4.6, 10.9 Hz), 5.56e5.61 (0.5H,
m) 7.28e7.38 (10H, m); 13C NMR (75 MHz, CDCl3):
d 24.9 (CH3D),
25.0 (CH3), 26.5 (CH3D), 26.7 (CH3), 38.8 (CH2), 41.0 (CH2D), 66.5
(CH2D), 67.1 (CH2), 71.3 (CH2, CH2D), 75.2 (CH), 76.2 (CHD), 79.3
(CHD), 79.6 (CH), 84.8 (CH), 84.9 (CHD), 99.3 (CHD), 99.4 (CH), 109.7
(qC), 109.8 (qCD), 127.7, 127.8, 127.9, 128.4, 128.5 (ArC, ArCD), 137.3
(ArqC), 137.8 (ArqCD); EI-HRMS: [M]þꢃ, found 294.1451. C16H22O5
requires 294.1467.
4.2. General procedure for the synthesis of compounds 2aed
To the glycal 1a (515 mg, 1.86 mmol) in THF/H2O (1:1, 10 mL)
Hg(OAc)2 (654 mg, 2.05 mmol) was added at 25 ꢁC. The reaction
mixture was stirred at the same temperature for 30 min and af-
terward the solution was kept at 0 ꢁC for 15 min. To this reaction
mixture 1.7 mL aqueous solution of KI (4.38 g, 0.026 mol in 5 mL
water) was added and the reaction mixture was stirred for another
15 min. To the resulting reaction mixture at 0 ꢁC, 4.4 mL aqueous
solution of NaBH4 (80 mg, 2.11 mmol in 5 mL water) was added
drop wise over 15 min and it was stirred for 1.5 h. The insoluble
part was removed by filtration through a bed of Celite and washed
with EtOAc (3ꢂ5 mL). The filtrate was separated and the organic
layer was washed successively with saturated aqueous solutions of
KI, Na2S2O7 and brine. The organic layer was separated and dried
over anhydrous Na2SO4. The solvent was evaporated under reduced
pressure to a residue, which was purified by column chromatog-
raphy (60e120 mesh silica gel) to obtain furanose 2a (538 mg, 98%,
4.2.4. (4S,5S)-4-(Benzyloxy)-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)
tetrahydrofuran-2-ol (2d). Pale yellow syrup; yield: 98% (
(538 mg). Eluent for column chromatography: EtOAc/hexane (4/21,
a
:
b
¼1:1)
v/v); Rf¼0.39 (1/2 EtOAc/hexane); IR (neat): ¼765, 1217, 1597, 2361,
n
2858, 2926, 3409 cmꢀ1; 1H NMR (300 MHz, CDCl3þCCl4):
d 1.31, 1.34
(6H, 2s, Me, MeD),1.42 (6H, s, Me, MeD), 1.98e2.24 (4H, m), 3.62e3.74
(3H, m), 3.84e3.91 (2H, m), 3.98e4.27 (7H, m), 4.49e4.64 (4H, m),
5.37 (1.4H, dd, J¼4.5, 10.7 Hz), 5.53e5.54 (0.6H, m), 7.23e7.36 (10H,
m); 13C NMR (75 MHz, CDCl3þCCl4):
d 25.2 (MeD), 25.2 (Me), 26.7
(MeD), 26.9 (Me), 38.9 (CH2), 40.9 (CH2D), 66.7 (CH2D), 67.2 (CH2), 71.3
(CH2, CH2D), 75.3 (CH), 76.3 (CHD), 79.6 (CHD), 79.7 (CH), 84.8 (CH),
85.0 (CHD), 99.2 (CHD), 99.3 (CH), 109.6 (qC), 109.7 (qCD), 127.7, 127.8,
127.9, 128.0, 128.4, 128.5 (ArC, ArCD), 137.4 (ArqC), 138.0 (ArqCD); EI-
HRMS: [M]þꢃ, found 294.1465. C16H22O5 requires 294.1467.
a
:
b
¼1:1) as a pale yellow syrup. Analogous protocol was adopted
for the synthesis of 2bed.
4.3. General procedure for the synthesis of compounds 3aed
4.2.1. (4R,5S)-4-(Benzyloxy)-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)
tetrahydrofuran-2-ol (2a). Pale yellow syrup; yield: 98%
PDC (640 mg, 1.70 mmol) was added to a stirred solution of
(
a
:
b
¼1:0.6) (538 mg). Eluent for column chromatography: EtOAc/
hexane (4/21, v/v); Rf¼0.39 (1/2 EtOAc/hexane); IR (neat): ¼761,
1072, 1216, 1617, 1711, 2360, 2931, 3022, 3443 cmꢀ1 1H NMR
(300 MHz, CDCl3):
1.40e1.42 (5.4H, m, J¼3.6 Hz, Me, MeD),
compound 2a (500 mg, 1.70 mmol) in dry DCM (15 mL) containing
4 A molecular sieves. The reaction mixture was refluxed for 2 h.
ꢀ
n
;
After completion of the reaction (TLC control), it was filtered
through Celite bed, which was rinsed with DCM (3ꢂ5 mL). After
removal of the organic solvent, the crude product was purified by
column chromatography (60e120 mesh silica gel) to obtain lac-
tones 3a in 75% yield (374 mg). Similar reaction protocol was
adopted for the synthesis of 3bed.
d
1.45e1.46 (5.2H, m, J¼4.4 Hz, Me, MeD), 1.99e2.12 (2H, m),
2.25e2.29 (2H, m), 3.75 (1H, d, J¼11.8 Hz, eOH), 3.89 (1H, dd, J¼3.5,
7.9 Hz), 3.97e4.28 (5.8H, m), 4.39e4.62 (2.8H, m), 4.69 (2H, s), 5.39
(1H, dd, J¼4.7, 11.5 Hz), 5.67e5.73 (0.6H, m), 7.29e7.37 (8H, m); 13C
NMR (75 MHz, CDCl3):
d 25.3 (CH3D), 25.4 (CH3), 26.6 (CH3D), 26.7
(CH3), 39.4 (CH2), 40.5 (CH2D), 66.7 (CH2D), 67.4 (CH2), 71.5 (CH2D),
72.2 (CH2), 73.4 (CHD), 73.9 (CH), 78.0 (CH), 78.5 (CHD), 80.9 (CHD),
84.0 (CH), 98.1 (CHD), 99.1 (CH), 108.6 (qCD), 108.9 (qC), 127.4, 127.5,
4.3.1. (4R,5S)-4-(Benzyloxy)-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)
dihydrofuran-2(3H)-one (3a). White solid; yield: 75% (374 mg); mp
57e60 ꢁC. Eluent for column chromatography: EtOAc/hexane (3/22,

P. Pal, A.K. Shaw / Tetrahedron 67 (2011) 4036e4047
4041
v/v); ½a 2D5
ꢄ
þ40.9 (c 0.43, MeOH); Rf¼0.55 (3/7 EtOAc/hexane); IR
water to separate the organic layer. The aqueous layer was washed
with DCM (2ꢂ5 mL) and the combined organic layer was dried over
anhydrous Na2SO4 and concentrated to obtain the crude product,
which was used as such for next step without further purification.
To the mesylated crude compound 5a in butan-2-one (15 mL), NaI
(418 mg, 2.78 mmol) was added and the reaction mixture was stirred
for 12 h under refluxing condition. Solvent was removed under vac-
uum after completion of the reaction. Saturated aqueous Na2S2O7
solution (10 mL) was added to the residue and the mixture was
extracted with diethyl ether (3ꢂ5 mL). The combined organic extract
was dried over anhydrous Na2SO4, concentrated under vacuum and
purified by column chromatography (60e120 mesh silica gel) to ob-
tain a white solid 6a (214 mg, 77% for three steps). The synthesis of
6bed was completed by adopting the similar reaction sequences.
(KBr):
n
¼690, 773, 1041, 1272, 1382, 1778, 2364, 2929, 3406 cmꢀ1
;
1H NMR (300 MHz, CDCl3):
d 1.39 (3H, s), 1.44 (3H, s), 2.66e2.67
(2H, m), 4.02 (1H, dd, J¼5.3, 8.9 Hz), 4.15 (1H, dd, J¼6.2, 8.9 Hz),
4.30e4.33 (1H, m), 4.39 (1H, dd, J¼3.8, 7.2 Hz), 4.47e4.51 (1H, m),
4.56 (1H, d, J¼11.9 Hz), 4.63 (1H, d, J¼11.9 Hz), 7.27e7.38 (5H, m);
13C NMR (75 MHz, CDCl3):
d 25.3 (CH3), 26.7 (CH3), 36.1 (CH2), 66.7
(CH2), 71.8 (CH2), 72.4 (CH), 74.4 (CH), 83.5 (CH), 109.4 (qC), 127.6,
128.0, 128.5 (ArC), 137.2 (ArqC), 174.6 (C]O); EI-HRMS: [M]þ
,
ꢃ
found 292.1312. C16H20O5 requires 292.1311.
4.3.2. (4S,5R)-4-(Benzyloxy)-5-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)
dihydrofuran-2(3H)-one (3b). White solid; yield: 87% (434 mg); mp
55e57 ꢁC. Eluent for column chromatography: EtOAc/hexane (3/22,
v/v); ½a 2D5
ꢀ34.1 (c 0.57, MeOH); Rf¼0.55 (3/7 EtOAc/hexane); IR
ꢄ
(KBr):
n
¼762, 1045, 1216, 1521, 1639, 1781, 2360, 2400, 2929,
4.4.1. (4R,5R)-4-(Benzyloxy)-5-((R)-1,2-dihydroxyethyl)dihy-
3406 cmꢀ1
;
1H NMR (300 MHz, CDCl3þCCl4):
d
1.38 (3H, s), 1.43
drofuran-2(3H)-one (4a). White solid. Rf¼0.21 (1/1 EtOAc/hexane);
(3H, s), 2.56e2.69 (2H, m), 4.01 (1H, dd, J¼5.3, 8.9 Hz), 4.14 (1H, dd,
J¼6.2, 8.9 Hz), 4.26e4.34 (2H, m), 4.45e4.52 (1H, m), 4.56 (1H, d,
J¼11.9 Hz), 4.63 (1H, d, J¼11.9 Hz), 7.28e7.36 (5H, m); 13C NMR
IR (KBr):
NMR (300 MHz, CD3OD):
n
¼690, 771, 1168, 1209, 1339, 1781, 2365, 3434 cmꢀ1
;
1H
d
2.62e2.68 (1H, m), 2.81 (1H, dd, J¼4.5,
17.7 Hz), 3.65 (1H, dd, J¼5.1, 11.7 Hz), 3.79 (1H, dd, J¼2.6, 11.7 Hz),
(75 MHz, CDCl3þCCl4):
d 25.5 (CH3), 26.9 (CH3), 36.1 (CH2), 66.8
4.03e4.09 (1H, m), 4.41e4.45 (2H, m), 4.57e4.66 (2H, m), 7.24e7.38
(CH2), 71.8 (CH2), 72.3 (CH), 74.3 (CH), 83.4 (CH), 109.4 (qC), 127.7,
(5H, m); 13C NMR (75 MHz, CD3OD):
d 37.1 (CH2), 64.8 (CH2), 69.5
128.1, 128.5 (ArC), 137.2 (ArqC), 173.9 (C]O); EI-HRMS: [M]þ
,
(CH), 72.7 (CH2), 76.4 (CH), 83.8 (CH),128.8, 128.9, 129.4 (ArC),139.3
(ArqC), 177.8 (C]O); EI-HRMS: [M]þꢃ, found 252.0996. C13H16O5
requires 252.0998.
ꢃ
found 292.1320. C16H20O5 requires 292.1311.
4.3.3. (4R,5R)-4-(Benzyloxy)-5-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)
dihydrofuran-2(3H)-one (3c). White solid; yield: 77% (384 mg); mp
84e86 ꢁC. Eluent for column chromatography: EtOAc/hexane (3/22,
4.4.2. (4R,5R)-4-(Benzyloxy)-5-vinyldihydrofuran-2(3H)-one
(6a). White solid; yield: 77% for three steps (214 mg); mp
52e54 ꢁC. Eluent for column chromatography: EtOAc/hexane (3/22,
v/v); ½a 3D2
ꢀ3.35 (c 0.30, MeOH); Rf¼0.52 (3/7 EtOAc/hexane); IR
ꢄ
(KBr):
n
¼699, 764, 1071, 1158, 1258, 1377, 1782, 2340, 2368, 2928,
v/v); ½a 2D5
ꢀ2.17 (c 0.50, MeOH); Rf¼0.40 (3/7 EtOAc/hexane); IR
ꢄ
3040 cmꢀ1
;
1H NMR (300 MHz, CDCl3):
d
1.34 (3H, s), 1.44 (3H, s),
(KBr):
n
¼698, 738, 1023, 1157, 1208, 1773, 2366, 2857, 2943 cmꢀ1
;
2.61 (1H, dd, J¼2.0, 18.3 Hz), 2.81 (1H, dd, J¼6.9, 18.3 Hz), 3.83e3.92
(1H, m), 4.06e4.15 (2H, m), 4.29e4.32 (1H, m), 4.44 (1H, dd, J¼1.4,
6.2 Hz), 4.55 (2H, br s), 7.28e7.39 (5H, m); 13C NMR (75 MHz,
1H NMR (300 MHz, CDCl3):
d
2.60 (2H, d, J¼4.4 Hz), 4.21 (1H, dd,
J¼4.5, 8.9 Hz), 4.42 (1H, d, J¼12.0 Hz), 4.49 (1H, d, J¼12.0 Hz),
4.80e4.84 (1H, m), 5.37 (2H, dd, J¼17.3, 21.1 Hz), 5.95e6.07 (1H, m),
CDCl3):
d
24.6 (CH3), 26.4 (CH3), 34.9 (CH2), 66.1 (CH2), 71.1 (CH2),
7.18e7.30 (5H, m); 13C NMR (75 MHz, CDCl3):
d 35.6 (CH2), 71.7
74.4 (CH), 74.7 (CH), 85.1 (CH), 110.3 (qC), 127.7, 128.1, 128.5 (ArC),
136.9 (ArqC), 174.9 (C]O); EI-HRMS: [MꢀCH3]þꢃ, found 277.1063.
C15H17O5 requires 277.1076.
(CH2), 75.9 (CH), 83.9 (CH), 120.0 (CH2), 127.5, 127.9, 128.5 (ArC),
131.2 (CH), 137.0 (ArqC), 174.6 (C]O); DARTeHRMS: [MþH]þ
,
ꢃ
found 219.1037. C13H15O3 requires 219.1021.
4.3.4. (4S,5S)-4-(Benzyloxy)-5-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)
dihydrofuran-2(3H)-one (3d). White solid; yield: 77% (384 mg); mp
85e87 ꢁC. Eluent for column chromatography: EtOAc/hexane (3/22,
4.4.3. (4S,5S)-4-(Benzyloxy)-5-((S)-1,2-dihydroxyethyl)dihydro-fu-
ran-2(3H)-one (4b). White solid. Rf¼0.20 (1/1 EtOAc/hexane); IR
(neat):
n
¼766, 1044, 1216, 1522, 1648, 1779, 2361, 3021, 3423 cmꢀ1
;
v/v); ½a 3D2
ꢄ
þ1.95 (c 0.13, CHCl3); Rf¼0.55 (3/7 EtOAc/hexane); IR
1H NMR (300 MHz, CD3OD):
d 2.58e2.64 (1H, m), 2.78 (1H, dd,
(KBr):
n
¼761, 1216, 1597, 1784, 2360, 2926, 3020 cmꢀ1
;
1H NMR
J¼4.6, 17.7 Hz), 3.61 (1H, dd, J¼5.1, 11.7 Hz), 3.75 (1H, dd, J¼2.6,
(300 MHz, CDCl3þCCl4):
d 1.32 (3H, s), 1.42 (3H, s), 2.56 (1H, dd,
11.7 Hz), 3.99e4.08 (1H, m), 4.34e4.41 (2H, m), 4.52e4.67 (2H, m),
J¼2.1, 18.2 Hz), 2.75 (1H, dd, J¼6.9, 18.2 Hz), 3.84 (1H, dd, J¼4.4,
8.2 Hz), 3.99e4.12 (2H, m), 4.25e4.28 (1H, m), 4.38 (1H, dd, J¼1.1,
6.3 Hz), 4.53 (2H, br s), 7.25e7.33 (5H, m); 13C NMR (75 MHz,
7.23e7.35 (5H, m); 13C NMR (75 MHz, CD3OD):
d 37.1 (CH2), 64.8
(CH2), 69.5 (CH), 72.7 (CH2), 76.4 (CH), 83.7 (CH), 128.8, 128.9, 129.2,
129.4 (ArC), 139.3 (ArqC), 177.8 (C]O); EI-HRMS: [M]þꢃ, found
252.0988. C13H16O5 requires 252.0998.
CDCl3þCCl4):
d 24.8 (CH3), 26.6 (CH3), 34.9 (CH2), 66.4 (CH2), 71.1
(CH2), 74.6 (CH), 74.8 (CH), 85.0 (CH), 110.3 (qC), 127.8, 128.1, 128.6
(ArC), 137.1 (ArqC), 174.1 (C]O); EI-HRMS: [M]þꢃ, found 292.1287.
C16H20O5 requires 292.1311.
4.4.4. (4S,5S)-4-(Benzyloxy)-5-vinyldihydrofuran-2(3H)-one
(6b). Pale yellow solid; yield: 72% for three steps (200 mg); mp
54e56 ꢁC. Eluent for column chromatography: EtOAc/hexane (3/22,
4.4. General procedure for the synthesis of compounds 6aed
v/v); ½a 2D5
þ1.0 (c 0.30, MeOH); Rf¼0.40 (3/7 EtOAc/hexane); IR
ꢄ
(KBr):
n
¼763, 1216, 1522, 1645, 1777, 2359, 3021, 3430 cmꢀ1
;
1H
Compound 3a (374 mg, 1.28 mmol) was dissolved in 60% aque-
ous AcOH solution (10 mL) and it was stirred at room temperature
for 18e20 h. After completion of the reaction (TLC control), the
reaction mixture was concentrated in vacuum. Toluene was added
to it and co-evaporated under reduced pressure to obtain diol 4a as
a white solid (295 mg), which was used for mesylation without
further purification.
NMR (300 MHz, CDCl3):
d
2.62 (2H, d, J¼4.5 Hz), 4.22 (1H, dd, J¼4.6,
9.2 Hz), 4.44 (1H, d, J¼12.0 Hz), 4.51 (1H, d, J¼12.0 Hz), 4.82e4.86
(1H, m), 5.34e5.44 (2H, m), 5.97e6.08 (1H, m), 7.19e7.32 (5H, m);
13C NMR (75 MHz, CDCl3):
d 35.6 (CH2), 71.7 (CH2), 75.9 (CH), 83.9
(CH), 120.1 (CH2), 127.5, 128.0, 128.5 (ArC), 131.2 (CH), 137.0 (ArqC),
174.6 (C]O); DARTeHRMS: [MþNH4]þ
,
found 236.1319.
ꢃ
C13H18NO3 requires 236.1287.
To a stirred solution of compound 4a (295 mg, 1.17 mmol) in
pyridine at 0 ꢁC, methanesulfonyl chloride (MsCl) (0.27 mL,
3.51 mmol) was added drop wise over 15 min and stirring was
continued at 0 ꢁC for 3 h. The reaction mixture was diluted with
4.4.5. (4R,5S)-4-(Benzyloxy)-5-((S)-1,2-dihydroxyethyl)dihy-
drofuran-2(3H)-one (4c). White solid. Rf¼0.21 (1/1 EtOAc/hexane);
IR (KBr):
n
¼675, 770, 1218, 1778, 2361, 3432 cmꢀ1
;
1H NMR

4042
P. Pal, A.K. Shaw / Tetrahedron 67 (2011) 4036e4047
(300 MHz, CD3OD):
d
2.54e2.60 (1H, m), 2.95 (1H, dd, J¼6.8,
nitrogen. The reaction was quenched with water (20 mL) and
allowed to warm to bring it at room temperature. Saturated
aqueous sodium/potassium tartrate solution (2 mL) was added and
the resulting mixture was stirred for 1 h after which the product
was extracted with EtOAc (3ꢂ5 mL). The combined organic extract
was dried over Na2SO4, concentrated in vacuo. The residue
obtained was purified by flash column chromatography
(230e400 mesh) to afford the protected lactol 7a (173 mg, 86%).
Similar reaction protocol was adopted for the synthesis of 7bed.
18.2 Hz), 3.64 (2H, d, J¼5.8 Hz), 3.82 (1H, dd, J¼5.6, 10.3 Hz), 4.46
(1H, d, J¼6.8 Hz), 4.62 (2H, br s), 4.69 (1H, d, J¼3.9 Hz), 7.33e7.40
(5H, m); 13C NMR (75 MHz, CD3OD):
d 36.7 (CH2), 63.6 (CH2), 71.8
(CH2), 72.5 (CH), 75.7 (CH), 87.6 (CH), 128.9, 129.0, 129.5 (ArC), 139.1
(ArqC), 178.5 (C]O); EI-HRMS: [MþH]þꢃ, found 253.1078. C13H17O5
requires 253.1076.
4.4.6. (4R,5S)-4-(Benzyloxy)-5-vinyldihydrofuran-2(3H)-one
(6c). Pale yellow syrup; yield: 73% for three steps (203 mg). Eluent
for column chromatography: EtOAc/hexane (3/22, v/v); ½a D25
ꢄ
ꢀ82.9
4.5.1. (4R,5R)-4-(Benzyloxy)-5-vinyltetrahydrofuran-2-ol
(c 0.50, MeOH); Rf¼0.30 (1/4 EtOAc/hexane); IR (neat):
n
¼670, 762,
(7a). Brown syrup; yield: 86% (
column chromatography: EtOAc/hexane (7/43, v/v); Rf¼0.39 (3/7
EtOAc/hexane); IR (neat):
¼696, 770, 1107, 1219, 1636, 2362,
3421 cmꢀ1 1H NMR (300 MHz, (CD3)2C]O):
1.91e2.00 (2H, m,
a:
b¼1:0.3) (173 mg). Eluent for
1216, 1636, 1782, 2364, 3023 cmꢀ1 1H NMR (300 MHz, CDCl3):
;
d
2.58 (1H, dd, J¼3.3, 17.9 Hz), 2.74 (1H, dd, J¼6.4, 17.9 Hz),
n
4.04e4.09 (1H, m), 4.57 (2H, br s), 4.97e4.98 (1H, m), 5.29 (1H, d,
J¼10.6 Hz), 5.41 (1H, d, J¼17.2 Hz), 5.77e5.88 (1H, m), 7.31e7.40
;
d
1Hþsolvent), 2.03e2.05 (0.2H, m), 2.09e2.21 (1.3H, m), 4.05e4.09
(0.3H, m), 4.13e4.18 (1H, m), 4.27e4.31 (0.3H, m), 4.36e4.54 (3.5H,
m), 5.07e5.30 (3.8H, m), 5.48e5.50 (1H, m), 5.88e6.10 (1.3H, m),
(5H, m); 13C NMR (75 MHz, CDCl3):
d 34.3 (CH2), 71.5 (CH2), 78.2
(CH), 84.5 (CH), 117.9 (CH2), 127.7, 128.1, 128.6 (ArC), 133.2 (CH),
136.9 (ArqC), 174.6 (C]O); DARTeHRMS: [MþH]þꢃ, found 219.1040.
C13H15O3 requires 219.1021.
7.14e7.26 (6.4H, m); 13C NMR (75 MHz, (CD3)2C]O):
d 40.1 (CH2D),
41.3 (CH2), 71.8 (CH2), 72.0 (CH2D), 80.5 (CHD), 81.3 (CH), 81.9 (CH),
83.8 (CHD), 98.0 (CH), 98.9 (CHD), 117.0 (CH2, CH2D), 128.1, 128.2,
4.4.7. (4S,5R)-4-(Benzyloxy)-5-((R)-1,2-dihydroxyethyl)-dihy-
128.25, 128.29, 128.9, 129.1 (ArC, ArCD), 136.2 (CH), 137.2 (CHD),
139.4 (ArqCD), 139.7 (ArqC); DARTeHRMS: [MꢀOH]þ
, found
ꢃ
drofuran-2(3H)-one (4d). White solid; Rf¼0.21 (1/1 EtOAc/hexane);
IR (KBr):
NMR (300 MHz, CD3OD):
n
¼762, 1216, 1348, 1597, 1783, 2361, 3021, 3409 cmꢀ1
;
1H
203.1058. C13H15O2 requires 203.1072.
d
2.51e2.57 (1H, m), 2.92 (1H, dd, J¼6.8,
18.2 Hz), 3.60 (2H, d, J¼5.8 Hz), 3.78 (1H, dd, J¼5.8, 10.1 Hz), 4.43
4.5.2. (4S,5S)-4-(Benzyloxy)-5-vinyltetrahydrofuran-2-ol (7b). Pale
yellow syrup; yield: 82% (
¼1:0.3) (165 mg). Eluent for column
(1H, d, J¼6.7 Hz), 4.59e4.67 (3H, m), 7.29e7.37 (5H, m); 13C NMR
a:b
(75 MHz, CD3OD):
d
36.7 (CH2), 63.6 (CH2), 71.8 (CH2), 72.5 (CH), 75.7
chromatography: EtOAc/hexane (7/43, v/v); Rf¼0.37 (3/7 EtOAc/
(CH), 87.6 (CH), 128.9, 129.0, 129.5 (ArC), 139.1 (ArqC), 178.5 (C]O);
hexane); IR (neat):
n
¼763, 1216, 1636, 2361, 2931, 3021, 3429 cmꢀ1
;
EI-HRMS: [M]þꢃ, found 252.1002. C13H16O5 requires 252.0998.
1H NMR (300 MHz, (CD3)2C]O):
d
1.91e2.00 (1.7H, m,
1Hþsolvent), 2.03e2.05 (0.2H, m), 2.09e2.21 (1.3H, m), 4.05e4.09
(0.3H, m), 4.13e4.18 (1H, m), 4.27e4.31(0.3H, m), 4.36e4.53 (3.6H,
m), 5.06e5.11 (2H, m), 5.19e5.30 (1.6H, m), 5.49e5.53 (1H, m),
5.89e6.11 (1.2H, m), 7.13e7.28 (6.3H, m); 13C NMR (75 MHz,
4.4.8. (R)-1-((2S,3S)-3-(Benzyloxy)-5-oxotetrahydrofuran-2-yl)eth-
ane-1,2-diyl dimethanesulfonate (5d). Purification of
a small
amount of crude product by column chromatography for data
afforded pure mesylated-ester 5d (350 mg, 65% yield, for two steps)
as a white solid; mp 120e122 ꢁC. Eluent for column chromatogra-
(CD3)2C]O): d 40.2 (CH2D), 41.3 (CH2), 71.8 (CH2), 72.1 (CH2D), 80.6
(CHD), 81.4 (CH), 81.9 (CH), 83.8 (CHD), 98.0 (CH), 98.9 (CHD), 117.0
(CH2, CH2D), 128.0, 128.1, 128.2, 128.3, 128.9, 129.0 (ArC, ArCD), 136.2
(CH), 137.3 (CHD), 139.4 (ArqCD), 139.8 (ArqC); DARTeHRMS:
[MꢀOH]þꢃ, found 203.1068. C13H15O2 requires 203.1072.
phy: MeOH/CHCl3 (1/49, v/v); ½a D25
ꢄ
þ11.5 (c 0.26, CHCl3); Rf¼0.45
(1/1 EtOAc/hexane); IR (KBr):
n
¼761, 1216, 1361, 1793, 2360,
3020 cmꢀ1; 1H NMR (300 MHz, CDCl3þCCl4):
d
2.63 (1H, dd, J¼3.4,
18.4 Hz), 2.82 (1H, dd, J¼7.0, 18.2 Hz), 3.06 (3H, s), 3.09 (3H, s), 4.35
(1H, dd, J¼5.6, 11.7 Hz), 4.42e4.52 (2H, m), 4.57e4.62 (3H, m),
4.82e4.87 (1H, m), 7.31e7.39 (5H, m); 13C NMR (75 MHz, CDCl3):
4.5.3. (4R,5S)-4-(Benzyloxy)-5-vinyltetrahydrofuran-2-ol
(7c). Colorless oil; yield: 94% (
umn chromatography: EtOAc/hexane (7/43, v/v); Rf¼0.40 (2/3
EtOAc/hexane); IR (neat):
¼670, 763, 1216, 1631, 2364, 2927, 3021,
3432 cmꢀ1 1H NMR (300 MHz, (CD3)2C]O):
1.81e1.88 (1H, m),
a:b
¼1:1) (189 mg). Eluent for col-
d
34.8 (CH2), 37.7 (CH3), 38.8 (CH3), 66.5 (CH2), 71.9 (CH2), 74.1 (CH),
76.0 (CH), 81.2 (CH), 128.0, 128.4, 128.7 (ArC), 136.4 (ArqC), 173.4
(C]O); EI-HRMS: [M]þꢃ, found 408.0544. C15H20O9S2 requires
408.0549.
n
;
d
1.95e2.00 (4H, m, 1HDþsolvent), 2.18e2.27 (1H, m), 3.77e3.82 (1H,
m), 3.95e4.00 (1H, m), 4.25e4.28 (1H, m), 4.48 (5H, d, J¼8.7 Hz),
4.79e4.87 (1H, m, eOH), 4.97e5.03 (2H, m), 5.17e5.29 (2H, m),
5.33e5.39 (2H, m), 5.46 (1H, dd, J¼3.9, 8.1 Hz), 5.71e5.94 (2H, m),
4.4.9. (4S,5R)-4-(Benzyloxy)-5-vinyldihydrofuran-2(3H)-one
(6d). Pale yellow syrup; yield: 92% (160 mg) (starting dimesyl de-
rivative was 325 mg). Eluent for column chromatography: EtOAc/
7.17e7.29 (10H, m); 13C NMR (75 MHz, (CD3)2C]O):
d 39.9 (CH2),
hexane (3/22, v/v); ½a D25
ꢄ
þ14.4 (c 0.17, MeOH); Rf¼0.32 (1/4 EtOAc/
40.4 (CH2D), 71.9 (CH2), 72.1 (CH2D), 83.4 (CH), 83.6 (CHD), 83.8 (CH),
85.2 (CHD), 98.8 (CH), 99.4 (CHD), 115.8 (CH2), 115.9 (CH2D), 128.2,
128.3, 128.4, 128.5, 129.06, 129.09 (ArC, ArCD), 138.3 (CH), 139.4
(ArqC), 139.6 (ArqCD), 140.3 (CHD); DARTeHRMS: [MꢀOH]þꢃ, found
203.1085. C13H15O2 requires 203.1072.
hexane); IR (neat):
n
¼760, 1216, 1354, 1782, 2361, 3020 cmꢀ1
;
1H
NMR (300 MHz, CDCl3):
d
2.58 (1H, dd, J¼3.3, 17.8 Hz), 2.73 (1H, dd,
J¼6.4, 17.9 Hz), 4.04e4.08 (1H, m), 4.57 (2H, br s), 4.96e4.97 (1H,
m), 5.29 (1H, d, J¼10.6 Hz), 5.41 (1H, d, J¼17.1 Hz), 5.77e5.88 (1H,
m), 7.30e7.36 (5H, m); 13C NMR (75 MHz, CDCl3):
d 34.3 (CH2), 71.5
(CH2), 78.2 (CH), 84.5 (CH), 118.0 (CH2), 127.7, 128.2, 128.6 (ArC),
133.2 (CH), 136.8 (ArqC), 174.7 (C]O); EI-HRMS: [M]þꢃ, found
218.0930. C13H14O3 requires 218.0943.
4.5.4. (4S,5R)-4-(Benzyloxy)-5-vinyltetrahydrofuran-2-ol
(7d). Colorless oil; 90% (181 mg) (
a
:
b
¼1:1). Eluent for column
chromatography: EtOAc/hexane (7/43, v/v); Rf¼0.40 (2/3 EtOAc/
hexane); IR (neat):
n
¼762, 1216, 1637, 1711, 2361, 3021, 3442 cmꢀ1
;
4.5. General procedure for the synthesis of compounds 7aed
1H NMR (300 MHz, (CD3)2C]O):
d 1.82e1.88 (1H, m), 1.94e2.00
(3H, m, 1HDþsolvent), 2.17e2.26 (1H, m), 3.77e3.82 (1H, m),
3.95e4.00 (1H, m), 4.25e4.28 (1H, m), 4.48 (5H, d, J¼8.6 Hz), 4.69
(1H, d, J¼6.8 Hz, eOH), 4.97e5.03 (2H, m), 5.17e5.29 (3H, m),
5.35e5.39 (1H, m), 5.46 (1H, dd, J¼4.2, 8.5 Hz), 5.71e5.92 (2H, m),
Diisobutylaluminum hydride (1.0 M) in toluene (1.37 mL,
1.37 mmol) was added drop wise to a stirred solution of lactone 6a
(200 mg, 0.92 mmol) in dry toluene (2 mL) at ꢀ78 ꢁC. The reaction
mixture was stirred for 2 h at ꢀ78 ꢁC under an atmosphere of
7.16e7.29 (10H, m); 13C NMR (75 MHz, (CD3)2C]O):
d 40.0 (CH2),

P. Pal, A.K. Shaw / Tetrahedron 67 (2011) 4036e4047
4043
40.5 (CH2D), 71.9 (CH2), 72.1 (CH2D), 83.5 (CH), 83.6 (CHD), 83.8 (CH),
85.2 (CHD), 98.9 (CH), 99.4 (CHD), 115.8 (CH2), 115.9 (CH2D), 128.2,
128.3, 128.4, 128.5, 129.06, 129.1 (ArC, ArCD), 138.3 (CH), 139.5
(ArqC), 139.6 (ArqCD), 140.3 (CHD); DARTeHRMS: [M]þꢃ, found
220.1087. C13H16O3 requires 220.1099.
4.6.4. (6S,7R)-6-(Benzyloxy)-7-hydroxynonan-2-one (8d). Pale yel-
low syrup; yield: 40% for two steps (70 mg). Eluent for column
chromatography: EtOAc/hexane (1/9, v/v); ½a D25
ꢄ
ꢀ9.81 (c 0.33,
¼763, 1216, 1636,
2363, 3021, 3429 cmꢀ1 1H NMR (300 MHz, CDCl3):
; d 0.98 (3H, t,
CHCl3); Rf¼0.40 (3/7 EtOAc/hexane); IR (neat):
n
J¼7.4 Hz), 1.45e1.61 (6H, m), 2.11 (3H, s), 2.39e2.43 (2H, m),
3.33e3.37 (1H, m), 3.69e3.75 (1H, m), 4.53 (1H, d, J¼11.4 Hz), 4.61
(1H, d, J¼11.4 Hz), 7.29e7.35 (5H, m); 13C NMR (75 MHz, CDCl3):
4.6. General procedure for the synthesis of compounds 8aed
To the lactol 7a (146 mg, 0.66 mmol) in dry toluene (20 mL),
1-(triphenylphosphoranylidene)-2-propanone (Ph3PCHCOCH3) (317
mg, 0.99 mmol) was added and the solution was heated to reflux till
the completion of reaction (TLC viewed by UV light), which took 2 h.
The reaction mixture was cooled to room temperature and solvent
was removed under vacuum. The resulting residue was used as such
for next step without further purification.
d 10.5 (CH3), 19.9 (CH2), 25.1 (CH2), 27.9 (CH2), 29.9 (CH3), 43.6
(CH2), 71.8 (CH2), 72.9 (CH), 81.7 (CH),127.8,127.9,128.5 (ArC),138.3
(ArqC), 208.9 (C]O); DARTeHRMS: [MþH]þꢃ, found 265.1775.
C16H25O3 requires 265.1804.
4.7. General procedure for the synthesis of compounds 9aed
The above residue in 50 mL round bottomed flask was imme-
diately dissolved in absolute ethanol. Raney-Ni as a catalyst was
added to this solution. A vacuum was created in the round bot-
tomed flask containing the above reaction mixture with the help of
pump and the mixture was stirred under H2 in a balloon at 1 atm.
After the completion of the reaction (TLC, 2 h) catalyst was re-
moved by filtration, washed with methanol twice and the com-
bined filtrate was concentrated and purified by silica gel
(230e400 mesh) column chromatography to afford 8a as a pale
yellow syrup (91 mg, 52% for two steps). The synthesis of 8bed was
achieved by adopting the similar reaction protocol.
To a round bottomed flask containing the compound 8a (19 mg,
0.072 mmol) in methanol (5 mL) were added catalytic amount of
10% Pd/C (5 mg) and 0.02 mL of 3 N HCl at room temperature.
A vacuum was created in this flask containing the above reaction
mixture with the help of pump and was stirred under H2 in a bal-
loon at 1 atms. After the completion of the reaction (TLC, 24 h)
catalyst was removed by filtration, washed with methanol twice
and the combined filtrate was concentrated on a rotary evaporator
at 20 ꢁC to afford (þ)-exo-brevicomin 9a (5 mg, 44%). It was im-
mediately submitted for recording the data due to its volatile na-
ture. Analogous reaction protocol was adopted for the synthesis
of 9bed.
4.6.1. (6R,7R)-6-(Benzyloxy)-7-hydroxynonan-2-one (8a). Pale yel-
low syrup; yield: 52% for two steps (91 mg). Eluent for column
4.7.1. (þ)-exo-Brevicomin (9a). Yield: 44% (5 mg). ½a D29
ꢄ
þ16.0 (c
¼770, 1091,
chromatography: EtOAc/hexane (1/9, v/v); ½a D25
ꢄ
ꢀ8.54 (c 1.02,
0.17, CHCl3) [lit. ½a D27
ꢄ
þ59.0 (c 2.5, CHCl3)]5i; IR (neat):
n
CHCl3) [lit. ½a 2D7
ꢄ
ꢀ12.8 (c 1.3, CHCl3)]6i,k; Rf¼0.60 (3/7 EtOAc/hex-
1218, 1461, 2857, 2922 cmꢀ1 1H NMR (300 MHz, CDCl3):
;
ane); IR (neat):
n
¼767, 1088, 1218, 1639, 1706, 2363, 2925,
d 0.90e0.98 (3H, m), 1.26 (3H, s), 1.41e1.78 (6H, m), 2.17e2.29 (2H,
3422 cmꢀ1
;
1H NMR (300 MHz, CDCl3):
d
1.00 (3H, t, J¼7.4 Hz),
m), 3.93e4.02 (2H, m); DARTeHRMS: [MþH]þꢃ, found 157.1224.
1.56e1.74 (6H, m), 2.16 (3H, s), 2.47 (2H, t, J¼6.7 Hz), 3.31e3.36 (1H,
C9H17O2 requires 157.1229.
m), 3.50e3.51 (1H, m), 4.54 (1H, d, J¼11.4 Hz), 4.68 (1H, d,
J¼11.3 Hz), 7.30e7.44 (5H, m); 13C NMR (75 MHz, CDCl3):
d
10.2
4.7.2. (ꢀ)-exo-Brevicomin (9b). Yield: 36% (4 mg). ½a D29
ꢄ
ꢀ31.9 (c
(CH3), 19.3 (CH2), 26.3 (CH2), 29.7 (CH2), 29.9 (CH3), 43.6 (CH2), 72.5
(CH2), 73.9 (CH), 81.6 (CH), 127.8, 127.9, 128.5 (ArC), 138.3 (ArqC),
208.7 (C]O); DARTeHRMS: [MꢀOH]þꢃ, found 247.1699. C16H23O2
requires 247.1698.
0.40, Et2O)[ lit. ½a D29
ꢄ
ꢀ60.0 (c 2.57, Et2O)]5l; IR (neat):
n
¼770, 1090,
1218, 1461, 2857, 2922 cmꢀ1
;
1H NMR (300 MHz, CDCl3):
d
0.90e0.98 (3H, m), 1.26 (3H, s), 1.41e1.78 (6H, m), 2.17e2.29 (2H,
m), 3.93e4.02 (2H, m); DARTeHRMS: [MþH]þꢃ, found 157.1243.
C9H17O2 requires 157.1229.
4.6.2. (6S,7S)-6-(Benzyloxy)-7-hydroxynonan-2-one (8b). Pale yel-
low syrup; yield: 67% for two steps (117 mg). Eluent for column
4.7.3. (þ)-endo-Brevicomin (9c). Yield: 44% (5 mg). ½a D30
þ20.4 (c
ꢄ
chromatography: EtOAc/hexane (1/9, v/v); ½a D25
ꢄ
þ10.48 (c 0.85,
0.23, CHCl3) [lit. ½a D25
ꢄ
þ64.2 (c 2.3, Et2O), ½a D22
þ39.5 (c 1.00,
ꢄ
CHCl3) [lit. ½a 2D0
ꢄ
þ13.0 (c 1.7, CHCl3)]5q; Rf¼0.60 (3/7 EtOAc/hexane);
Et2O)]4e,f
;
IR (neat):
n
¼768, 1045, 1114, 1218, 1464, 2854,
IR (neat):
NMR (300 MHz, CDCl3):
2.12 (3H, s), 2.44 (2H, t, J¼6.8 Hz), 3.28e3.33 (1H, m), 3.45e3.51
(1H, m), 4.51 (1H, d, J¼11.3 Hz), 4.65 (1H, d, J¼11.3 Hz), 7.31e7.35
n
¼761, 1072, 1216, 1617, 1711, 2360, 2931, 3443 cmꢀ1; 1H
2923 cmꢀ1 1H NMR (300 MHz, CDCl3):
; d 0.90e0.98 (3H, m), 1.46
d
0.97 (3H, t, J¼7.4 Hz), 1.49e1.69 (6H, m),
(3H, s), 1.82e2.02 (6H, m), 2.13e2.34 (2H, m), 3.76e3.85 (1H, m),
4.15e4.21 (1H, m); DARTeHRMS: [MþH]þ
, found 157.1233.
ꢃ
C9H17O2 requires 157.1229.
(5H, m); 13C NMR (75 MHz, CDCl3):
d 10.2 (CH3), 19.3 (CH2), 26.4
(CH2), 29.7 (CH2), 29.9 (CH3), 43.6 (CH2), 72.5 (CH2), 73.9 (CH), 81.7
(CH), 127.8, 127.9, 128.5 (ArC), 138.3 (ArqC), 208.7 (C]O); EI-HRMS:
[M]þꢃ, found 264.1723. C16H24O3 requires 264.1726.
4.7.4. (ꢀ)-endo-Brevicomin (9d). Yield: 36% (4 mg). ½a D30
ꢄ
ꢀ42.1 (c
0.28, CHCl3) [lit. ½a D25
ꢄ
ꢀ78.9 (c 0.99, Et2O)]5p; IR (neat):
n
¼768, 1045,
1114, 1218, 1464, 2854, 2923 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d
0.90e0.98 (3H, m), 1.46 (3H, s), 1.82e2.02 (6H, m), 2.13e2.34 (2H,
m), 3.76e3.85 (1H, m), 4.15e4.21 (1H, m); DARTeHRMS: [MþH]þ
,
ꢃ
4.6.3. (6R,7S)-6-(Benzyloxy)-7-hydroxynonan-2-one
(8c). Yellow
syrup; yield: 35% for two steps (61 mg). Eluent for column chro-
found 157.1222. C9H17O2 requires 157.1229.
matography: EtOAc/hexane (1/9, v/v); ½a D25
ꢄ
þ9.81 (c 0.46, CHCl3);
Rf¼0.28 (2/3 EtOAc/hexane); IR (neat):
n
¼670, 761, 1631, 2362,
4.8. General procedure for the synthesis of compound 10a,b
3021, 3425 cmꢀ1; 1H NMR (300 MHz, CDCl3): 0.98 (3H, t, J¼7.4 Hz),
1.49e1.68 (6H, m), 2.11 (3H, s), 2.39e2.43 (2H, m), 3.33e3.38 (1H,
m), 3.72e3.77 (1H, m), 4.53 (1H, d, J¼11.4 Hz), 4.61 (1H, d,
To a 50 mL two necked oven dried round bottomed flask fitted
with a reflux condenser and septum was added Grubbs’ second
generation catalyst (50 mg, 0.058 mmol) under argon atmosphere.
Dry degassed DCM (3 mL) was then added to the above solution
through a syringe and it was kept for stirring. Compound 6a
(500 mg, 2.29 mmol) and (S)-1-phenyl-2-propene-1-ol (282 mg,
2.10 mmol) in DCM (2 mL each) were added simultaneously
J¼11.5 Hz), 7.29e7.35 (5H, m); 13C NMR (75 MHz, CDCl3):
d 10.6
(CH3), 19.9 (CH2), 25.1 (CH2), 27.9 (CH2), 29.9 (CH3), 43.6 (CH2), 71.8
(CH2), 72.9 (CH), 81.6 (CH), 127.8, 127.9, 128.5 (ArC), 138.3 (ArqC),
209.0 (C]O); DARTeHRMS: [MꢀOH]þꢃ, found 247.1701. C16H23O2
requires 247.1698.

4044
P. Pal, A.K. Shaw / Tetrahedron 67 (2011) 4036e4047
through a syringe to the stirring solution. The septum was
replaced with a glass stopper while the stirring was continued.
The solution was refluxed for 8 h. The temperature of the mixture
was cooled slowly to room temperature. The organic solvent was
evaporated under reduced pressure to give a brown residue, which
was purified by column chromatography (230e400 mesh) to give
10a as a white solid (557 mg, 74%). Similar reaction protocol was
adopted for the synthesis of 10b. In this case metathesis was
performed between compound 6b and (R)-1-phenyl-2-propene-1-
ol in dry DCM.
4.9.2. (4S,5S)-4-(Benzyloxy)-5-((R,E)-3-(tert-butyldimethyl-sily-
loxy)-3-phenylprop-1-enyl)dihydrofuran-2(3H)-one (11b). White
solid; yield: 66% (480 mg); mp 85e88 ꢁC. Eluent for column chro-
matography: EtOAc/hexane (3/22, v/v); ½a D31
ꢄ
þ33.1 (c 0.33, CHCl3);
¼769, 1215, 1651, 1780,
ꢀ0.09
Rf¼0.60 (2/3 EtOAc/hexane); IR (KBr):
n
2358, 2857, 2926, 3025 cmꢀ1 1H NMR (300 MHz, CDCl3):
; d
(3H, s), 0.00 (3H, s), 0.85 (9H, s), 2.61 (2H, d, J¼4.5 Hz), 4.17 (1H, dd,
J¼4.5, 8.5 Hz), 4.42e4.50 (2H, m), 4.84 (1H, dd, J¼4.6, 6.9 Hz), 5.21
(1H, d, J¼4.3 Hz), 5.89e6.06 (2H, m), 7.17e7.28 (10H, m); 13C NMR
(75 MHz, CDCl3):
d
ꢀ4.9 (CH3), ꢀ4.8 (CH3), 25.8 (3CH3), 35.8 (CH2),
71.7 (CH2), 74.4 (CH), 76.1 (CH), 83.7 (CH), 121.4 (CH), 125.9, 127.3,
127.5, 127.9, 128.3, 128.5 (ArC), 137.1 (ArqC), 139.6 (CH), 143.0
(ArqC), 174.7 (C]O); DARTeHRMS: [MþH]þꢃ, found 439.2309.
C26H35O4Si requires 439.2305.
4.8.1. (4R,5R)-4-(Benzyloxy)-5-((S,E)-3-hydroxy-3-phenylprop-1-
enyl)dihydrofuran-2(3H)-one (10a). White solid; yield: 74%
(557 mg); mp 95e98 ꢁC. Eluent for column chromatography:
EtOAc/hexane (4/21, v/v); ½a D31
þ1.00 (c 0.32, MeOH); Rf¼0.27 (2/3
ꢄ
EtOAc/hexane); IR (KBr):
n
¼771, 1217, 1461, 1543, 1651, 1750, 2359,
4.10. General procedure for the synthesis of compound 12a,b
2924, 3021, 3441 cmꢀ1
;
1H NMR(300 MHz, CDCl3):
d
2.68 (2H, d,
t
J¼4.3 Hz), 4.27 (1H, dd, J¼4.5, 8.9 Hz), 4.48 (1H, d, J¼12.0 Hz), 4.57
(1H, dd, J¼12.0 Hz), 4.92e4.95 (1H, m), 5.29e5.30 (1H, m),
6.01e6.14 (2H, m), 7.26e7.38 (10H, m); 13C NMR (75 MHz, CDCl3):
To a stirred solution of BuOH (5 mL) and water (5 mL) were
added AD-mix-
b (4.0 g) and methanesulfonamide (CH3SO2NH2)
(0.100 g, 1.05 mmol) at room temperature. The mixture was vig-
orously stirred at room temperature until both phases were clear
and then cooled to 0 ꢁC. A solution of compound 11a (500 mg,
d
35.7 (CH2), 71.7 (CH2), 73.9 (CH), 75.9 (CH), 83.4 (CH), 123.3 (CH),
126.3, 127.6, 127.9, 128.0, 128.5, 128.6 (ArC), 137.0 (ArqC), 137.9 (CH),
141.9 (ArqC), 174.6 (C]O); DARTeHRMS: [MꢀOH]þ
,
found
1.14 mmol) in BuOH (5 mL) and catalytic amount of OsO4 were
t
ꢃ
307.1333. C20H19O3 requires 307.1334.
added simultaneously at 0 ꢁC to the above reaction mixture. It
was stirred at the same temperature for 24 h. The reaction was
quenched at 0 ꢁC by the addition of sodium sulfite (1.2 g),
warmed to room temperature, and further stirred for 30 min. The
resulting mixture was extracted with EtOAc (3ꢂ10 mL). The
organic layer was dried over anhydrous Na2SO4, filtered, and
concentrated in vacuo. Purification of the crude product by silica
gel (230e400 mesh) column chromatography afforded 12a
(362 mg, 67%) as a white solid. Similar reaction procedure
was adopted for the synthesis of 12b from 11b by using AD-
4.8.2. (4S,5S)-4-(Benzyloxy)-5-((R,E)-3-hydroxy-3-phenylprop-1-
enyl)dihydrofuran-2(3H)-one (10b). White solid; yield: 74%
(557 mg); mp 98e100 ꢁC. Eluent for column chromatography:
EtOAc/hexane (4/21, v/v); ½a D31
ꢀ2.8 (c 0.27, MeOH); Rf¼0.27 (2/3
ꢄ
EtOAc/hexane); IR (KBr):
n
¼765, 1215, 1456, 1543, 1777, 2363, 2856,
2924, 3021, 3449 cmꢀ1
;
1H NMR(300 MHz, CDCl3):
d
2.71 (2H, d,
J¼4.3 Hz), 4.29 (1H, dd, J¼4.5, 8.9 Hz), 4.51 (1H, d, J¼11.9 Hz), 4.59
(1H, d, J¼12.0 Hz), 4.96 (1H, t, J¼4.7 Hz), 5.33 (1H, br s), 6.04e6.16
(2H, m), 7.28e7.38 (10H, m); 13C NMR (75 MHz, CDCl3):
d
35.7
mix-a.
(CH2), 71.8 (CH2), 73.9 (CH), 75.9 (CH), 83.3 (CH), 123.4 (CH), 126.3,
127.6, 127.9, 128.0, 128.6, 128.7 (ArC), 137.1 (ArqC), 137.9 (CH), 142.0
(ArqC), 174.5 (C]O); DARTeHRMS: [MꢀOH]þꢃ, found 307.1328.
C20H19O3 requires 307.1334.
4.10.1. (4R,5R)-4-(Benzyloxy)-5-((1S,2S,3R)-3-(tert-butyldimethyl-
silyloxy)-1,2-dihydroxy-3-phenylpropyl)dihydrofuran-2(3H)-one
(12a). White solid; yield: 67% (362 mg); mp 102e105 ꢁC. Eluent for
column chromatography: EtOAc/hexane (1/4, v/v); ½a D31
ꢄ
ꢀ46.5 (c
4.9. General procedure for the synthesis of compound 11a,b
0.73, MeOH); Rf¼0.38 (1/2 EtOAc/hexane); IR (KBr):
n
¼767, 1216,
1590, 1777, 2359, 2857, 2928, 3021, 3462 cmꢀ1; 1H NMR (300 MHz,
CDCl3):
To the stirring solution of compound 10a (540 mg, 1.67 mmol) in
dry DCM (10 mL) at 0 ꢁC imidazole (239 mg, 3.31 mmol) and TBSCl
(275 mg, 1.82 mmol) were added. The temperature of the reaction
mixture was raised to room temperature. After 8 h, a saturated
aqueous solution of NH4Cl (15 mL) was added and the resulting so-
lution was extracted with DCM (3ꢂ10 mL). The combined organic
phases were dried over Na2SO4 and the solvent was removed under
reduced pressure. The residue was purified by column chromatog-
raphy (230e400 mesh) to furnish 11a (676 mg, 93%) as a white solid.
Similar reaction protocol was adopted for the synthesis of 11b.
d
ꢀ0.10 (3H, s), 0.09 (3H, s), 0.89 (9H, s), 2.34 (1H, d,
J¼7.6 Hz, eOH), 2.62 (1H, dd, J¼5.6, 17.5 Hz), 2.74e2.81 (1H, m),
3.66 (1H, t, J¼6.6 Hz), 4.29e4.33 (2H, m), 4.49e4.60 (3H, m), 4.85
(1H, d, J¼6.4 Hz), 7.21e7.34 (10H, m); 13C NMR (75 MHz, CDCl3):
d
ꢀ5.3 (CH3), ꢀ4.7 (CH3), 25.7 (3CH3), 35.2 (CH2), 67.9 (CH), 71.1
(CH2), 73.9 (CH), 74.1 (CH), 76.7 (CH), 84.5 (CH), 126.7, 127.8, 127.9,
128.1, 128.4, 128.6 (ArC), 136.4 (ArqC), 141.1 (ArqC), 174.5 (C]O);
DARTeHRMS: [MþH]þ
, found 473.2349. C26H37O6Si requires
ꢃ
473.2359.
4.10.2. (4S,5S)-4-(Benzyloxy)-5-((1R,2R,3S)-3-(tert-butyldimethyl-
silyloxy)-1,2-dihydroxy-3-phenylpropyl)dihydrofuran-2(3H)-one
(12b). White solid; yield: 58% (313 mg); mp 100e102 ꢁC. Eluent
for column chromatography: EtOAc/hexane (1/4, v/v); ½ ꢄD þ47.2
4.9.1. (4R,5R)-4-(Benzyloxy)-5-((S,E)-3-(tert-butyldimethyl-silyl-
oxy)-3-phenylprop-1-enyl)dihydrofuran-2(3H)-one
(11a). White
a 31
solid; yield: 93% (676 mg); mp 90e92 ꢁC. Eluent for column chro-
matography: EtOAc/hexane (3/22, v/v); ½a D30
ꢄ
ꢀ37.1 (c 0.80, CHCl3);
¼771, 1216, 1578, 1781,
ꢀ0.10
(c 0.23, MeOH); Rf¼0.38 (1/2 EtOAc/hexane); IR (KBr):
n
¼772,
Rf¼0.60 (2/3 EtOAc/hexane); IR (KBr):
n
1217, 1645, 1750, 2360, 2859, 2927, 3423 cmꢀ1
(300 MHz, CDCl3):
;
1H NMR
2360, 2860, 2933, 3027 cmꢀ1
;
1H NMR (300 MHz, CDCl3):
d
d
ꢀ0.14 (3H, s), 0.09 (3H, s), 0.89 (9H, s), 2.62
(3H, s), 0.00 (3H, s), 0.84 (9H, s), 2.59 (2H, d, J¼4.2 Hz), 4.15 (1H, dd,
J¼4.4, 8.4 Hz), 4.40e4.49 (2H, m), 4.82 (1H, dd, J¼4.7, 6.9 Hz), 5.20
(1H, d, J¼4.2 Hz), 5.88e6.06 (2H, m), 7.15e7.29 (10H, m); 13C NMR
(1H, dd, J¼5.6, 17.5 Hz), 2.75e2.81 (1H, m), 3.65 (1H, br s),
4.29e4.32 (2H, m), 4.49e4.59 (3H, m), 4.86 (1H, d, J¼6.3 Hz),
7.21e7.34 (10H, m); 13C NMR (75 MHz, CDCl3):
d
ꢀ5.2 (CH3), ꢀ4.7
(75 MHz, CDCl3):
d
ꢀ4.9 (CH3), ꢀ4.8 (CH3), 25.8 (3CH3), 35.8 (CH2),
(CH3), 25.7 (3CH3), 35.2 (CH2), 67.9 (CH), 71.2 (CH2), 74.0 (CH),
74.2 (CH), 76.7 (CH), 84.5 (CH), 126.8, 127.9, 128.0, 128.2, 128.4,
128.6 (ArC), 136.5 (ArqC), 141.1 (ArqC), 174.3 (C]O);
DARTeHRMS: [MþH]þꢃ, found 473.2353. C26H37O6Si requires
473.2359.
71.7 (CH2), 74.4 (CH), 76.1 (CH), 83.7 (CH), 121.4 (CH), 125.9, 127.2,
127.5, 127.9, 128.3, 128.4 (ArC), 137.1 (ArqC), 139.5 (CH), 142.9
(ArqC), 174.7 (C]O); DARTeHRMS: [MþH]þꢃ, found 439.2299.
C26H35O4Si requires 439.2305.

P. Pal, A.K. Shaw / Tetrahedron 67 (2011) 4036e4047
4045
4.11. General procedure for the synthesis of compound 13a,b
mp 189e190 ꢁC; lit. ½a 2D4
ꢄ
þ6.4 (c 0.28, MeOH)]13; Rf¼0.37 (EtOAc);
IR (KBr):
n
¼762, 1186, 1369, 1703, 2339, 2369, 2932, 2976,
To a stirred solution of compound 12a (122 mg, 0.26 mmol) in
dry acetonitrile Amberlyst 15 resin (150 mg) was added at 0 ꢁC. The
mixture was vigorously stirred at room temperature for 5 h to
complete the reaction. After that, the reaction mixture was filtered
through a Celite pad and then concentrated in vacuo to give a white
solid 13a (87 mg, 94%). The product did not require any purification.
Similar reaction protocol was adopted for the synthesis of 13b.
3452 cmꢀ1 1H NMR (400 MHz, (CD3)2C]O):
; d 2.38 (1H, d,
J¼17.1 Hz), 2.79e2.82 (1Hþsolvent, m), 3.79 (1H, d, J¼8.4 Hz,
eOH), 3.93 (1H, t, J¼7.0 Hz), 4.31 (1H, d, J¼5.2 Hz, eOH), 4.38e4.39
(1H, m), 4.57 (1H, dd, J¼2.8, 7.5 Hz), 4.63e4.67 (2H, m), 4.79e4.84
(1H, m), 7.21e7.25 (1H, m), 7.29e7.32 (2H, m), 7.45 (2H, d,
J¼7.3 Hz); 13C NMR (100 MHz, (CD3)2C]O):
d 40.4 (CH2), 68.7 (CH),
70.3 (CH), 74.2 (CH), 75.6 (CH), 86.7 (CH), 127.9, 128.0, 128.6 (ArC),
144.3 (ArqC), 176.2 (C]O); DARTeHRMS: [MꢀH]þ
, found
ꢃ
4.11.1. (4R,5R)-4-(Benzyloxy)-5-((1S,2R,3R)-1,2,3-trihydroxy-3-phe-
nylpropyl)dihydrofuran-2(3H)-one (13a). White solid; yield: 94%
(87 mg); mp 160e162 ꢁC. Eluent for column chromatography:
267.0893. C13H15O6 requires 267.0869.
4.13. Synthesis of (4R,5S)-4-(benzyloxy)-5-((4S,5S)-5-((R)-
(tert-butyldimethylsilyloxy)(phenyl)methyl)-2,2-dimethyl-
1,3-dioxolan-4-yl)dihydrofuran-2(3H)-one (15a)
EtOAc/hexane (2/3, v/v); ½a D27
ꢄ
ꢀ33.5 (c 0.43, MeOH); Rf¼0.24 (4/1
EtOAc/hexane); IR (KBr):
n
¼765, 1216, 1602, 1765, 2364, 2858, 2925,
2.77e2.78 (2H, m),
3.71e3.74 (1H, m), 4.32e4.67 (5H, m), 4.74 (1H, d, J¼7.9 Hz),
7.19e7.42 (10H, m); 13C NMR (75 MHz, CD3OD):
36.7 (CH2), 69.9
3022, 3426 cmꢀ1; 1H NMR (300 MHz, CD3OD):
d
To a stirred solution of 12a (200 mg, 0.42 mmol) in acetone
(3 mL) was added 2,2-dimethoxypropane (DMP) (0.08 mL,
0.63 mmol) followed by camphorsulfonic acid (CSA) (10 mg,
0.043 mmol). The reaction mixture was stirred till the consump-
tion of starting material (2 h). Afterward, the reaction mixture was
concentrated under reduced pressure to colorless oil, which was
dissolved in EtOAc (5 mL) and extracted with the same solvent
(3ꢂ10 mL). The organic layer was dried over anhydrous Na2SO4,
filtered, and concentrated in vacuo. Purification of the crude
product by silica gel column chromatography (230e400 mesh)
afforded pure 15a (180 mg, 83%) as a yellow gum. Eluent for
d
(CH), 71.9 (CH2), 74.4 (CH), 75.5 (CH), 76.0 (CH), 87.5 (CH), 128.3,
128.4, 128.9, 129.1, 129.3, 129.5 (ArC), 138.7 (ArqC), 144.2 (ArqC),
177.9 (C]O); DARTeHRMS: [MꢀOH]þꢃ, found 341.1408. C20H21O5
requires 341.1389.
4.11.2. (4S,5S)-4-(Benzyloxy)-5-((1R,2S,3S)-1,2,3-trihydroxy-3-phe-
nylpropyl)dihydrofuran-2(3H)-one (13b). White solid; yield: 90%
(84 mg); mp 160e164 ꢁC. Eluent for column chromatography:
EtOAc/hexane (2/3, v/v); ½a D31
þ33.3 (c 0.27, MeOH); Rf¼0.24 (4/1
ꢄ
EtOAc/hexane); IR (KBr):
n
¼763, 1216, 1632, 1766, 2371, 2857, 2927,
column chromatography: EtOAc/hexane (1/24, v/v); ½a D27
ꢄ
ꢀ10.73
¼770,
;
1H NMR
3022, 3418 cmꢀ1; 1H NMR (300 MHz, CD3OD):
d
2.86e2.87 (2H, m),
(c 0.60, MeOH); Rf¼0.58 (1/4 EtOAc/hexane); IR (neat):
n
3.83 (1H, d, J¼6.7 Hz), 4.44e4.78 (6H, m), 7.31e7.47 (10H, m); 13C
1219, 1369, 1589, 1661, 1791, 2338, 2370, 2930 cmꢀ1
(300 MHz, CDCl3):
NMR (75 MHz, CD3OD):
d
36.8 (CH2), 70.1 (CH), 72.0 (CH2), 74.5
d
ꢀ0.08 (3H, s), 0.13 (3H, s), 0.93 (9H, s), 1.28
(CH), 75.6 (CH), 76.1 (CH), 87.5 (CH), 128.4, 128.5, 129.0, 129.2, 129.4,
129.6 (ArC), 138.8 (ArqC), 144.3 (ArqC), 178.1 (C]O); DARTeHRMS:
[MꢀH]þꢃ, found 357.1321. C20H21O6 requires 357.1338.
(3H, s), 1.35 (3H, s), 2.50 (1H, dd, J¼8.6, 16.8 Hz), 2.80 (1H, dd,
J¼10.0, 16.9 Hz), 3.77 (1H, d, J¼7.7 Hz), 4.22e4.32 (2H, m),
4.57e4.59 (3H, m), 4.99 (1H, d, J¼4.5 Hz), 7.28e7.40 (10H, m); 13C
NMR (75 MHz, CDCl3):
d
ꢀ4.8 (CH3), ꢀ4.7 (CH3), 25.9 (3CH3), 26.2
4.12. General procedure for the synthesis of compound 14a,b
(CH3), 27.7 (CH3), 34.1 (CH2), 72.3 (CH2), 73.9 (CH), 74.1 (CH), 74.3
(CH), 78.0 (CH), 80.6 (CH), 110.2 (qC), 126.2, 127.5, 127.8, 128.0,
A catalytic amount of Pd(OH)2 (5 mg) was added to a solution of
13a (20 mg, 0.056 mmol) in methanol (5 mL). A vacuum was cre-
ated in a round bottomed flask containing the above reaction
mixture with the help of pump and the mixture was stirred under
H2 in a balloon at 1 atms. After the completion of the reaction (TLC,
24 h) catalyst was removed by filtration, washed with methanol
twice and the combined filtrate was concentrated and purified by
silica gel (230e400 mesh) column chromatography to afford
(þ)-cardiobutanolide 14a (10 mg, 67%) as a white solid. Analogous
procedure was adopted for the synthesis of (ꢀ)-cardiobutanolide
14b from 13b.
128.4, 128.6 (ArC), 137.2 (ArqC), 141.0 (ArqC), 174.4 (C]O);
DARTeHRMS: [MþH]þ
, found 513.2673. C29H41O6Si requires
ꢃ
513.2672.
4.14. Synthesis of (4R,5S)-5-((4S,5S)-5-((R)-(tert-
butyldimethyl-silyloxy)(phenyl)methyl)-2,2-dimethyl-1,3-
dioxolan-4-yl)-4-hydroxydihydrofuran-2(3H)-one (16a)
To a solution of 15a (136 mg, 0.26 mmol) in dry EtOAc (5 mL)
taken in a round bottomed flask was added a catalytic amount of
Pd(OH)2 (10 mg). A vacuum was created in this flask containing the
above reaction mixture with the help of pump and was stirred
under H2 in a balloon at 1 atms. After the completion of the reaction
(TLC, 24 h) catalyst was removed by filtration, washed with EtOAc
twice and the combined filtrate was concentrated to afford a col-
orless oil, which on column chromatographic (230e400 mesh silica
gel) purification gave the pure compound 16a (97 mg, 87%) as
a yellow gum. Eluent for column chromatography: EtOAc/hexane
4.12.1. (þ)-Cardiobutanolide (14a). White solid; yield: 67%
(10 mg); mp 192e194 ꢁC; Eluent for column chromatography:
EtOAc/hexane (9/11, v/v);
½
a 2D9
ꢄ
þ6.1 (c 0.4, MeOH) [lit. mp
189e190 ꢁC; lit. ½a 2D4
ꢄ
þ6.4 (c 0.28, MeOH)]13; Rf¼0.37 (EtOAc); IR
(KBr):
n
¼769, 1218, 1590, 1772, 2340, 2858, 2927, 3371 cmꢀ1
;
1H
NMR (600 MHz, (CD3)2C]O):
d
2.38 (1H, d, J¼17.4 Hz), 2.86e2.89
(1Hþsolvent, m), 3.93 (1H, dd, J¼1.2, 7.8 Hz), 4.40 (1H, dd, J¼1.2,
7.2 Hz), 4.57 (1H, dd, J¼3.6, 7.8 Hz), 4.62e4.64 (1H, m), 4.80 (1H, d,
J¼7.8 Hz), 7.21e7.24 (1H, m), 7.31 (2H, t, J¼7.8 Hz), 7.45 (2H, d,
(7/43, v/v); ½a 2D8
ꢄ
þ4.58 (c 0.50, MeOH); Rf¼0.21 (1/4 EtOAc/hex-
ane); IR (neat):
n
¼770, 1219, 1374, 1462, 1727, 1784, 2340, 2369,
2856, 2926, 3486 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d
ꢀ0.06 (3H, s),
J¼7.8 Hz); 13C NMR (100 MHz, (CD3)2C]O):
d
40.4 (CH2), 68.7 (CH),
0.11 (3H, s), 0.93 (9H, s), 1.39 (3H, s), 1.49 (3H, s), 2.54 (1H, dd, J¼5.5,
17.8 Hz), 2.69 (1H, dd, J¼7.6, 17.8 Hz), 3.68 (1H, d, J¼6.3 Hz), 4.36
(1H, dd, J¼4.4, 7.9 Hz), 4.48e4.55 (2H, m), 4.93e5.03 (1H, m),
70.4 (CH), 74.2 (CH), 75.6 (CH), 86.6 (CH), 127.9, 128.0, 128.6 (ArC),
144.3 (ArqC), 176.1 (C]O); DARTeHRMS: [M]þꢃ, found 268.0947.
C13H16O6 requires 268.0946.
7.28e7.37 (5H, m); 13C NMR (75 MHz, CDCl3):
d
ꢀ4.8 (CH3), ꢀ4.7
(CH3), 25.9 (3CH3), 26.3 (CH3), 27.5 (CH3), 38.5 (CH2), 69.1 (CH), 73.7
(CH), 75.3 (CH), 80.1 (CH), 80.7 (CH), 110.5 (qC), 126.1, 127.9, 128.4
(ArC), 140.4 (ArqC), 174.6 (C]O); DARTeHRMS: [MþH]þꢃ, found
423.2208. C22H35O6Si requires 423.2203.
4.12.2. (ꢀ)-Cardiobutanolide (14b). White solid; yield: 60% (9 mg);
mp 194e195 ꢁC. Eluent for column chromatography: EtOAc/hexane
(9/11, v/v); ½a 2D8
ꢀ2.72 (c 0.2, MeOH) [for (þ)-cardiobutanolide lit.
ꢄ

4046
P. Pal, A.K. Shaw / Tetrahedron 67 (2011) 4036e4047
4.15. Synthesis of (S)-5-((4R,5S)-5-((R)-(tert-butyldimethyl-
silyloxy)(phenyl)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-
furan-2(5H)-one (17a)
125.9, 128.5, 128.8 (ArC), 138.9 (ArqC), 175.3 (C]O); DARTeHRMS:
[MþH]þꢃ, found 251.0918. C13H15O5 requires 251.0919.
Acknowledgements
To a stirred solution of 16a (102 mg, 0.24 mmol) dissolved in dry
DCM (10 mL) was added Et3N (0.08 mL, 0.60 mmol) drop wise at
0 ꢁC and left the reaction mixture for stirring for 10 min. The
methanesulfonyl chloride (MsCl) (0.02 mL, 0.29 mmol) was added
drop wise to this reaction mixture at the same temperature and
stirring was further continued for 3 h at the same temperature for
the completion of the reaction. The reaction mixture was diluted
with water, organic layer was separated and the aqueous layer was
extracted with DCM (3ꢂ10 mL). The combined organic layer was
dried over anhydrous Na2SO4 and concentrated to obtain the crude
product which on column chromatographic purification
(230e400 mesh silica gel) gave pure 17a (90 mg, 92%) as a pale
yellow oil. Eluent for column chromatography: EtOAc/hexane (1/
We are thankful to Sophisticated Analytical Instrument Facility,
CDRI for providing spectral data, "DST (project SR/SI/OC-17/2010)
for financial support and Mr. A.K. Pandey for technical assistance.
P.P. thanks CSIR New Delhi for awarding Senior Research Fellow-
ship. CDRI Communication no. 8048.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2011.04.014. These data in-
clude MOL files and InChiKeys of the most important compounds
described in this article.
49, v/v); ½a 3D2
ꢀ14.89 (c 0.63, MeOH); Rf¼0.68 (1/4 EtOAc/hexane);
ꢄ
IR (neat):
n
¼770, 1155, 1254, 1460, 1767, 2362, 2858, 2925 cmꢀ1; 1H
NMR (300 MHz, CDCl3):
d
ꢀ0.17 (3H, s), 0.00 (3H, s), 0.82 (9H, s),
References and notes
1.21 (3H, s), 1.31 (3H, s), 4.05e4.06 (1H, m), 4.18e4.20 (1H, m), 4.32
(1H, dd, J¼4.2, 7.7 Hz), 4.90 (1H, d, J¼4.2 Hz), 5.95 (1H, dd, J¼1.9,
1. (a) Hanessian, S. Total Synthesis of Natural Products: The ‘Chiron’ Approach;
Pergamon: Oxford, 1983; (b) Ducatti, D. R. B.; Massi, A.; Noseda, M. D.; Durate,
M. E. R.; Dondoni, A. Org. Biomol. Chem. 2009, 7, 576e588; (c) Saquib, M.; Gupta,
M. K.; Sagar, R.; Prabhakar, Y. S.; Shaw, A. K.; Kumar, R.; Maulik, P. R.; Gaikwad,
A. N.; Sinha, S.; Srivastava, A. K.; Chaturvedi, V.; Srivastava, R.; Srivastava, B. S. J.
Med. Chem. 2007, 50, 2942e2950; (d) Reddy, L. V. R.; Reddy, P. V.; Shaw, A. K.
Tetrahedron: Asymmetry 2007, 18, 542e546; (e) Reddy, P. V.; Reddy, L. V. R.;
Kumar, B.; Kumar, R.; Maulik, P. R.; Shaw, A. K. Tetrahedron 2008, 64,
2153e2159; (f) Reddy, L. V. R.; Swamy, G. N.; Shaw, A. K. Tetrahedron: Asym-
metry 2008, 19, 1372e1375; (g) Saquib, M.; Hussain, I.; Kumar, B.; Shaw, A. K.
Chem.dEur. J. 2009, 15, 6041e6049; (h) Reddy, L. V. R.; Reddy, P. V.; Mishra, N.
N.; Shukla, P. K.; Yadav, G.; Srivastava, R.; Shaw, A. K. Carbohydr. Res. 2010, 345,
1515e1521; (i) Pal, P.; Kumar, B.; Shaw, A. K. Eur. J. Org. Chem. 2009, 2179e2184;
(j) Reddy, P. V.; Bajpai, B.; Kumar, B.; Shaw, A. K. Eur. J. Org. Chem. 2011,
1575e1586.
5.6 Hz), 7.16e7.27 (6H, m); 13C NMR (75 MHz, CDCl3):
d
ꢀ4.8 (CH3),
ꢀ4.7 (CH3), 25.9 (3CH3), 26.1 (CH3), 27.3 (CH3), 73.7 (CH), 74.9 (CH),
81.1 (CH), 81.8 (CH), 110.3 (qC), 122.1 (]CH), 126.0, 127.9, 128.5
(ArC), 140.5 (ArqC), 153.2 (]CH), 172.9 (C]O); DARTeHRMS:
[MþH]þꢃ, found 405. 2092. C22H33O5Si requires 405.2097.
4.16. Synthesis of (S)-5-((1S,2R,3R)-1,2,3-trihydroxy-3-phenyl-
propyl)furan-2(5H)-one (18a)
To a stirred solution of 17a (79 mg, 0.19 mmol) in 2.5 mL of THF
were added 2.5 mL AcOH and 2.5 mL 2 N HCl at room temperature.
The stirring of the reaction mixture was continued for 24 h at the
same temperature. After the reaction was completed (TLC), the
volatiles were removed under reduced pressure and the residue
obtained was purified by silica gel (230e400 mesh) column chro-
matography to give 18a (27 mg, 56%) as a white solid. Eluent for
column chromatography: EtOAc/hexane (3/7, v/v); mp 106e108 ꢁC;
2. (a) Moore, R. E. Prog. Chem. Org. Nat. Prod. 1985, 48, 81e202; (b) Chou, T.; Kamo,
O.; Uemura, D. Tetrahedron Lett. 1996, 37, 4023e4026; (c) Silverstein, R. M. J.
Chem. Educ. 1968, 45, 794e797; (d) Silverstein, R. M.; Brownlee, R. G.; Bellas, T.
E.; Wood, D. L.; Browne, L. E. Science 1968, 159, 889e891; (e) Wood, D. L.;
Browne, L. E.; Ewing, B.; Lindahl, K.; Bedard, W. D.; Tilden, P. E.; Mori, K.; Pit-
man, G. B.; Hughes, P. R. Science 1976, 192, 896e898.
3. Joshi, N. N.; Mamdapur, V. R.; Chadha, M. S. J. Chem. Soc., Perkin Trans. 1 1983,
2963e2966 and references cited therein.
4. endo-Brevicomin. (a) Minor component of volatiles of mountain pine beetle,
Dendroctonus ponderosae, and western balsam bark beetle, Dryocoetes con-
fusus Schurig, V.; Weber, R.; Nicholson, G. J.; Oehlschlager, A. C.; Pierce, H., Jr.;
Pierce, A. M.; Borden, J. H.; Ryker, L. C. Naturwissenschaften 1983, 70, 92e93; (b)
Aggregation pheromone of Dryocoetes autographus Mori, K.; Seu, Y.-B. Tetra-
hedron 1985, 41, 3429e3431; (c) (ꢅ)-Antiaggregation pheromone for southern
½
a 3D2
ꢄ
ꢀ69.8 (c 0.3, MeOH) [lit. mp 109e111 ꢁC; ½a D24
ꢄ
ꢀ68 (c 0.6,
EtOAc)]17d; Rf¼0.52 (4/1 EtOAc/hexane); IR (KBr):
n
¼769, 1047,
1218, 1461, 1656, 1744, 2366, 2856, 2925, 3404 cmꢀ1 1H NMR
;
(200 MHz, CD3OD):
d
3.64 (1H, dd, J¼2.0, 8.2 Hz), 4.07 (1H, dd,
ꢁ
pine beetle, Dendroctonus frontalis Vite, J. P.; Renwick, J. A. A. Natur-
J¼2.0, 6.0 Hz), 4.72 (1H, d, J¼8.2 Hz), 5.24e5.29 (1H, m), 6.16 (1H,
dd, J¼2.1, 5.8 Hz), 7.21e7.45 (5H, m), 7.76 (1H, dd, J¼1.5, 5.8 Hz); 13C
wissenschaften 1971, 7, 578e582; (d) (ꢀ)-Antiaggregation pheromone and (þ)
ꢁ
aggregation pheromone for D. frontalis Vite, J. P.; Billings, R. F.; Ware, C. W.;
NMR (50 MHz, CDCl3):
d 72.8 (CH), 74.9 (CH), 75.1 (CH), 87.5 (CH),
Mori, K. Naturwissenschaften 1985, 72, 99e100; (e) Oehlschlager, A. C.; John-
ston, B. D. J. Org. Chem. 1987, 52, 940e943; (f) Burke, S. D.; Muller, N.; Beaudry,
C. M. Org. Lett. 1999, 1, 1827e1829 and references cited therein.
€
122.2 (]CH), 128.4, 128.5, 129.1 (ArC), 144.0 (ArqC), 156.9 (]CH),
175.6 (C]O); DARTeHRMS: [MþH]þꢃ, found 251.0908. C13H15O5
requires 251.0919.
5. Some synthesis of brevicomins: (a) Perez, A. L.; Gries, R.; Gries, G.; Oehlschl-
ager, A. L. Bioorg. Med. Chem. 1966, 4, 445e450; (b) Wasserman, H. H.; Barber,
E. H. J. Am. Chem. Soc. 1969, 36, 3674e3675; (c) Bellas, T. E.; Brownlee, R. G.;
Silverstein, R. M. Tetrahedron 1969, 25, 5149e5153; (d) Mori, K. Tetrahedron
1974, 30, 4223e4227; (e) Kocienski, P. J.; Ostrow, R. W. J. Org. Chem. 1976, 41,
398e400; (f) Cahiez, G.; Alexakis, A.; Normant, J. F. Tetrahedron Lett. 1980, 21,
1433e1436; (g) Bernardi, R.; Fuganti, C.; Grasselli, P. Tetrahedron Lett. 1981, 22,
4021e4024; (h) Sherk, A. E.; Fraser-Reid, B. J. Org. Chem. 1982, 47, 932e935; (i)
Johnston, B. D.; Oehlschlager, A. C. J. Org. Chem. 1982, 47, 5384e5386; (j) Ferrier,
R. J.; Prasit, P. J. Chem. Soc., Perkin Trans. 1 1983, 1645e1647; (k) Asami, M.;
Mukaiyama, T. Chem. Lett. 1983, 93e96; (l) Wuts, P. G. M.; Bigelow, S. S. J. Chem.
Soc., Chem. Commun. 1984, 736e737; (m) Bhupathy, M.; Cohen, T. Tetrahedron
Lett. 1985, 26, 2619e2622; (n) Kufner, U.; Schmidt, R. R. Synth. Commun. 1985,
1060e1062; (o) Ferrier, R. J.; Schmidt, P.; Tyler, P. C. J. Chem. Soc., Perkin Trans. 1
1985, 301e303; (p) Yusufoglu, A.; Antons, S.; Scharf, H.-D. J. Org. Chem. 1986, 51,
3485e3487; (q) Mulzer, J.; Angermann, A.; Munch, W. Liebigs Ann. Chem. 1986,
825e838; (r) Mori, K.; Seu, Y.-B. Liebigs Ann. Chem. 1986, 205e209; (s) Tamao,
K.; Nakajo, E.; Ito, Y. J. Org. Chem. 1987, 52, 4412e4414; (t) Kotsuki, H.; Kadota, I.;
Ochi, M. Tetrahedron Lett. 1989, 30, 3999e4000; (u) Padwa, A.; Chinn, R. L.; Zhi,
L. Tetrahedron Lett. 1989, 30, 1491e1494; (v) Kotsuki, H.; Kadota, I.; Ochi, M. J.
Org. Chem. 1990, 55, 4417e4422; (w) Matsumoto, K.; Suzuki, N.; Ohta, H. Tet-
rahedron Lett. 1990, 31, 7163e7166; (x) Myles, D. C.; Andrulis, P. J., III; White-
sides, G. M. Tetrahedron Lett. 1991, 32, 4835e4838; (y) Kim, M.-J.; Choi, G.-B.;
Kim, J.-Y.; Kim, H.-J. Tetrahedron Lett. 1995, 36, 6253e6256; (z) Takahata, H.;
4.17. Synthesis of compound (D)-goniofufurone (19a)
A solution of unsaturated lactone 18a (0.017 g, 0.068 mmol) in
dry THF (10 mL) containing DBU (6 mL) was stirred at room tem-
perature for 24 h. The solution was then filtered through a short
pad of silica gel topped with Celite. Removal of the solvent from the
filtrate in vacuo gave a residue, which was crystallized from EtOAc/
hexane (1/20, v/v) to give a white solids 19a (11 mg, 65%); mp
€
150e152 ꢁC. Crystallized from EtOAc/hexane. ½a 3D1
þ5.1 (c 0.23,
ꢄ
ꢂ
MeOH) [lit. mp 152e154 ꢁC; lit. ½a D22
ꢄ
þ9.0 (c 0.5, EtOH)]12c; Rf¼0.57
€
(EtOAc); IR (KBr):
n
¼771, 1045, 1219, 1463, 1652, 1774, 2364, 2852,
2918, 3443 cmꢀ1; 1H NMR (300 MHz, CDCl3):
d 2.64e2.80 (2H, m),
2.99 (1H, br s, eOH), 4.11 (1H, dd, J¼2.8, 4.8 Hz), 4.21 (1H, br s,
eOH), 4.42 (1H, br s), 4.87 (1H, d, J¼4.1 Hz), 5.12 (1H, t, J¼4.3 Hz),
5.19 (1H, d, J¼4.6 Hz), 7.34e7.44 (5H, m); 13C NMR (50 MHz, CDCl3):
d
36.1 (CH2), 73.5 (CH), 74.5 (CH), 77.3 (CH), 82.9 (CH), 87.4 (CH),

P. Pal, A.K. Shaw / Tetrahedron 67 (2011) 4036e4047
4047
Kusunoki, M.; Takeda, Y.; Momose, T. Tetrahedron: Asymmetry 1996, 7,
2093e2098.
13. Hisham, A.; Toubi, M.; Shuaily, W.; Bai, M. D. A.; Fujimoto, Y. Phytochemistry
2003, 62, 597e600.
6. (a) Vettel, S.; Lutz, C.; Diefenbach, A.; Haderlein, G.; Hammerschmidt, S.;
Kuhling, K.; Mofid, M.-R.; Zimmermann, T.; Knochel, P. Tetrahedron: Asymmetry
14. Ruiz, P.; Murga, J.; Carda, M.; Marco, J. A. J. Org. Chem. 2005, 70, 713e716.
15. (a) Matsuura, D.; Takabe, K.; Yoda, H. Tetrahedron Lett. 2006, 47, 1371e1374; (b)
Krishna, P. R.; Reddy, P. V. N. Tetrahedron Lett. 2006, 47, 4627e4630; (c) Garg, A.;
Singh, R. P.; Singh, V. K. Tetrahedron 2006, 62, 11240e11244; (d) Prasad, K. R.;
Gholap, S. L. J. Org. Chem. 2008, 73, 2916e2919; (e) Krishna, P. R.; Kumar, E. S.
Tetrahedron Lett. 2009, 50, 6676e6679; (f) Yadav, J. S.; Madhavarao, B.; Rao, K. S.
Synlett 2009, 3179e3181; (g) Chandrasekhar, S.; Kiranmai, N. Tetrahedron Lett.
2010, 51, 4058e4060.
€
1997, 8, 779e800; (b) Hu, S.; Jayaraman, S.; Oehlschlager, A. C. J. Org. Chem.
1999, 64, 2524e2526; (c) Gallos, J. K.; Kyradjoglou, L. C.; Koftis, T. V. Hetero-
cycles 2001, 55, 781e784; (d) de Sousa, A. L.; Resck, I. S. J. Braz. Chem. Soc. 2002,
13, 233e237; (e) Mayer, S. F.; Mang, H.; Steinreiber, A.; Saf, R.; Faber, K. Can. J.
Chem. 2002, 80, 362e369; (f) Raghavan, S.; Joseph, S. C. Tetrahedron Lett. 2003,
44, 8237e8239; (g) Kumar, D. N.; Rao, B. V. Tetrahedron Lett. 2004, 45,
2227e2229; (h) Tyvorskii, V. I.; Astashko, D. A.; Kulinkovich, O. G. Tetrahedron
2004, 60, 1473e1479; (i) Prasad, K. R.; Anbarasan, P. Tetrahedron: Asymmetry
2005, 16, 3951e3953; (j) Kim, S.-G.; Park, T.-H.; Kim, B. J. Tetrahedron Lett. 2006,
47, 6369e6372; (k) Prasad, K. R.; Anbarasan, P. Tetrahedron: Asymmetry 2007, 18,
1419e1427; (l) Singh, S.; Guiry, P. J. J. Org. Chem. 2009, 74, 5758e5761.
7. Oishi, T.; Ando, K.; Chida, N. Chem. Commun. 2001, 1932e1933 and references
cited therein.
8. Mereyala, H. B.; Gadikota, R. R.; Krishnan, R. J. Chem. Soc., Perkin Trans. 1 1997,
3567e3571 and references cited therein.
9. (a) Wu, Y.-C.; Duh, C.-Y.; Chang, F.-R.; Chang, G.-Y.; Wang, S.-K.; Chang, J.-J.;
McPhail, D. R.; McPhail, A. T.; Lee, K.-H. J. Nat. Prod. 1991, 54, 1077e1081; (b)
Talapatra, S. K.; Basu, D.; Deb, T.; Goswami, S.; Talapatra, B. Indian J. Chem., Sect.
B 1985, 24, 29e34; (c) Sam, T. W.; Sew-Yeu, C.; Matsjeh, S.; Gan, E. K.; Razak, D.;
16. (a) Shing, T. K. M.; Tsui, H.-C. J. Chem. Soc., Chem. Commun. 1992, 432; (b) Shing,
T. K. M.; Tsui, H.-C.; Zhou, Z.-H. J. Chem. Soc., Chem. Commun. 1992, 810e811; (c)
Shing, T. K. M.; Tsui, H.-C.; Zhou, Z.-H. Tetrahedron 1992, 48, 8659e8666 and
€
references cited therein; (d) Gracza, T.; Jager, V. Synlett 1992, 191e193; (e)
€
Gracza, T.; Jager, V. Synthesis 1994, 1359e1368; (f) Bermejo, A.; Blazquez, M. A.;
Rao, K. S.; Cortes, D. Phytochemistry 1998, 47, 1375e1380.
17. (a) Prakash, K. R. C.; Rao, S. P. Tetrahedron 1993, 49, 1505e1510; (b) Ye, J.; Bhatt,
R. K.; Falck, J. R. Tetrahedron Lett. 1993, 34, 8007e8010; (c) Yang, Z.-C.; Zhou, W.-
S. Tetrahedron 1995, 51, 1429e1436; (d) Shing, T. K. M.; Tsui, H.-C.; Zhou, Z.-H. J.
Org. Chem. 1995, 60, 3121e3130; (e) Mukai, C.; Hirai, S.; Kim, I. J.; Kido, M.;
ꢃ
Hanaoka, M. Tetrahedron 1996, 52, 6547e6560; (f) Surivet, J.-P.; Vatele, J.-M.
ꢃ
Tetrahedron Lett. 1996, 37, 4373e4376; (g) Surivet, J.-P.; Vatele, J.-M. Tetrahedron
Lett. 1997, 38, 819e820; (h) Cagnolini, C.; Ferri, M.; Jones, P. R.; Murphy, P. J.
Tetrahedron 1997, 53, 4815e4820; (i) Yi, X.-H.; Meng, Y.; Hua, X.-G.; Li, C.-J. J.
Org. Chem. 1998, 63, 7472e7480; (j) Mereyala, H. B.; Gadikota, R. R.; Joe, M.;
Arora, S. K.; Dastidar, S. G.; Agarwal, S. Bioorg. Med. Chem. 1999, 7, 2095e2103;
(k) Chen, W.-P.; Roberts, S. M. J. Chem. Soc., Perkin Trans. 1 1999, 103e105; (l)
Tsubuki, M.; Kanai, K.; Nagase, H.; Honda, T. Tetrahedron 1999, 55, 2493e2514;
ꢁ
ꢃ
Mohamed, A. L. Tetrahedron Lett. 1987, 28, 2541e2544; (d) Cave, A.; Figadere, B.;
ꢁ
Laurens, A.; Cortes, D. Prog. Chem. Org. Nat. Prod. 1997, 70, 81e288; (e) Zafra-
ꢃ
ꢁ
Polo, M. C.; Figadere, B.; Gallardo, T.; Tormo, J. R.; Cortes, D. Phytochemistry
1998, 48, 1087e1117; (f) Alali, F. Q.; Liu, X.-X.; Mclaughlin, J. L. J. Nat. Prod. 1999,
62, 504e540.
€
10. On the cytotoxic activity and other bioactivity of styryllactones, see: (a)
(m) Bruns, R.; Wernicke, A.; Koll, P. Tetrahedron 1999, 55, 9793e9800; (n)
ꢁ
ꢃ
Blazquez, M. A.; Bermejo, A.; Zafra-Polo, M. C.; Cortes, D. Phytochem. Anal. 1999,
Surivet, J.-P.; Vatele, J.-M. Tetrahedron 1999, 55, 13011e13028; (o) Su, Y.-L.; Yang,
10, 161e170; (b) Mereyala, H. B.; Joe, M. Curr. Med. Chem.: Anti-Cancer Agents
2001, 1, 293e300.
11. For a review on the synthesis of styryllactones, see: Mondon, M.; Gesson, J.-P.
Curr. Org. Synth. 2006, 3, 41e75.
12. Isolation of styryllactones: (a) El-Zayat, A. A. E.; Ferrigni, N. R.; McCloud, T. G.;
McKenzie, A. T.; Byrn, S. R.; Cassady, J. M.; Chang, C.-J.; McLaughlin, J. L. Tet-
rahedron Lett. 1985, 26, 955e956; (b) Alkofahi, A.; Ma, W.-W.; McKenzie, A. T.;
Byrn, S. R.; McLaughlin, J. L. J. Nat. Prod. 1989, 52, 1371e1373; (c) Fang, X.-P.;
Anderson, J. E.; Chang, C.-J.; Fanwick, P. E.; McLaughlin, J. L. J. Chem. Soc., Perkin
Trans. 1 1990, 1655e1661 and references cited therein; (d) Fang, X.-P.; Ander-
son, J. E.; Chang, C.-J.; McLaughlin, J. L.; Fanwick, P. E. J. Nat. Prod. 1991, 54,
1034e1043 and references cited therein; (e) Fang, X.-P.; Anderson, J. E.; Chang,
C.-J.; McLaughlin, J. L. Tetrahedron 1991, 47, 9751e9758.
C.-S.; Teng, S.-J.; Zhao, G.; Ding, Y. Tetrahedron 2001, 57, 2147e2153; (p) Prasad,
K. R.; Gholap, S. L. Synlett 2005, 2260e2262; (q) Yadav, V. K.; Agrawal, D. Chem.
Commun. 2007, 5232e5234; (r) Popsavin, V.; Benedekovic, G.; Sreco, B.; Pop-
savin, M.; Francuz, J.; Kojic, V.; Bogdanovic, G. Org. Lett. 2007, 9, 4235e4238; (s)
Prasad, K. R.; Dhaware, M. G. Synthesis 2007, 3697e3705; (t) Prasad, K. R.;
Gholap, S. L. J. Org. Chem. 2008, 73, 2e11; (u) Popsavin, V.; Benedekovic, G.;
Sreco, B.; Popsavin, M.; Francuz, J.; Kojic, V.; Bogdanovic, G. Bioorg. Med. Chem.
ꢁ
€
Lett. 2008, 18, 5178e5181; (v) Hernandez-García, L.; Quintero, L.; Hopfl, H.; Sosa,
M.; Sartillo-Piscil, F. Tetrahedron 2009, 65, 139e144; (w) Popsavin, V.; Sreco, B.;
Benedekovic, G.; Francuz, J.; Popsavin, M.; Kojic, V.; Bogdanovic, G. Eur. J. Med.
Chem. 2010, 45, 2876e2883; (x) Sharma, G. V. M.; Mallesham, S. Tetrahedron:
Asymmetry 2010, 21, 2646e2658.
€
18. Mosimann, M.; Kupfer, P. A.; Leumann, C. J. Org. Lett. 2005, 7, 5211e5214.