Total synthesis of phytotoxic herbarumin-I from d-mannitol

Article abstract of DOI:10.1016/j.tetasy.2009.03.039

A simple carbohydrate-based convergent approach towards the total synthesis of herbarumin-I, a 10-membered lactone is described. The key features of the synthetic strategy include Grignard reaction and ring-closing metathesis reaction for the formation of the 10-membered ring and E-olefinic moiety. d-Mannitol has been used as a chiral pool material for the construction of the key fragment.

Full text of DOI:10.1016/j.tetasy.2009.03.039

Tetrahedron: Asymmetry 20 (2009) 1120–1124
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Total synthesis of phytotoxic herbarumin-I from D-mannitol
*
Ahmed Kamal , P. Venkat Reddy, S. Prabhakar
Chemical Biology Laboratory, Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple carbohydrate-based convergent approach towards the total synthesis of herbarumin-I, a 10-
membered lactone is described. The key features of the synthetic strategy include Grignard reaction
and ring-closing metathesis reaction for the formation of the 10-membered ring and E-olefinic moiety.
Received 12 February 2009
Accepted 10 March 2009
Available online 22 May 2009
D
-Mannitol has been used as a chiral pool material for the construction of the key fragment.
Ó 2009 Published by Elsevier Ltd.
1. Introduction
Retrosynthetically herbarumin-I can be obtained from bis-al-
kene 11 via the ring-closing metathesis, a key reaction strategy
that has been widely used for the synthesis of 10-membered lac-
tones possessing similar carbon skeletons. Moreover, this bis-al-
kene 11 is accessible by the esterification of 10 with 5-hexenoic
acid, whereas 10 in turn can be obtained from the commercially
In recent years naturally occurring 10-membered lactones com-
monly known as decanolides have attracted synthetic as well as
bioorganic chemists, due to their interesting structural properties
and biological activities.1 Some examples, such as herbarumin-I
1, herbarumin-II 2, herbarumin-III 3,2 microcarpalide 4,3 letha-
loxin 5,4 and decarestrictine D 65 belong to this class of molecules
as shown in Figure 1. Mata et al. have extracted three phytotoxic
lactones namely herbarumin-I 1, herbarumin-II 2 and herbaru-
min-III 3,2a,b from the culture broth and mycelium of the fungus
Phoma herbarum. Amongst these lactones herbarumin-I 1 shows
promising phytotoxic effects with IC50 (M) values as low as
5.43 ꢀ 10ꢁ5. These lactones exhibit significant phytotoxic effects
when tested against the seedlings of Amaranthus hypochondriacus
at very low concentrations,6 thus making this class of compounds
promising new lead structures in the search for novel herbicidal
agents.
available
1,2:3,4:5,6-Tri-O-isopropylidene-
-mannitol was treated with H5IO6 according to the reported lit-
D-mannitol (Scheme 1).
D-mannitol, a fully protected
D
erature procedure9 to afford the aldehyde, which without further
purification was taken up for reduction with NaBH4 to provide
the primary alcohol 2. Then treatment of alcohol 2 with PPh3
and NaHCO3 in CCl4 at reflux for 1 h gave the chloride 3 in
89% yield, which on further treatment with Na in dry ether
afforded the allylic alcohol 4 in 92% yield. Protection of the
resulting secondary alcohol with BnBr and NaH, in THF afforded
5, which on subsequent acetonide deprotection with TFA (THF/
H2O 9:1) gave the diol 6. Selective protection of the primary
hydroxyl group of 6 as the TBDMS ether provided 7, which
was followed once again by protection of the resulting secondary
alcohol with BnBr, NaH and TBAI (cat) in THF to give the diben-
zylated compound 8. Treatment of this dibenzyl ether 8 with
TBAF in THF afforded the primary alcohol 9, which is the key
intermediate for the synthesis of herbarumin-I 1. Thus, 9 was
subjected to Swern oxidation to provide the aldehyde, which
then without further purification was taken up for the Grignard
addition using propyl magnesium chloride in dry toluene
(8.78 mL, 17.56 mmol, 2 M in diethyl ether) at ꢁ78 °C to afford
the corresponding anti- and syn-diastereomeric alcohols in 7:3
ratio as separable diastereomers 10 and 10a. Formation of major
diastereomeric alcohol 10 can be explained on the basis of
non-chelation-controlled addition of Grignard nucleophile to
the aldehyde (see Scheme 2).
2. Results and discussion
Some approaches have been developed in the literature for the
synthesis of these 10-membered lactones starting from various
sugars as chiral pool templates,7 such as
D-ribose,
L-arabinose, D-
glucose and
L-ascorbic acid. However, the interesting structural
properties, especially the presence of oxygen substituents at C7,
C8 and C9 positions in the ring and the trans relationship between
any two oxygens in its scaffold make herbarumin-I an attractive
and challenging synthetic target. As part of our studies directed to-
wards the synthesis of lactones and other biologically active mol-
ecules,8 we herein report an efficient convergent approach for
the total synthesis of herbarumin-I 1 by employing D-mannitol, a
cost-effective and readily available starting material.
Esterification of diastereomer 10 with 5-hexenoic acid in the
presence of DCC and DMAP at 0 °C to ambient temperature pro-
vides the diene 11 in 81%. This has allowed the stage to be set
for the macrolactonization via ring-closing metathesis.
* Corresponding author. Tel.: +91 40 27193157; fax: +91 40 27193189.
E-mail address: ahmedkamal@iict.res.in (A. Kamal).
0957-4166/$ - see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2009.03.039

A. Kamal et al. / Tetrahedron: Asymmetry 20 (2009) 1120–1124
1121
HO
HO
HO
HO
HO
O
O
O
OH
O
O
O
Herbarumin III 3
Herbarumin II 2
Herbarumin I 1
O
O
OH
HO
OH
O
HO
OH
HO
O
OH
O
O
OH
O
Dacarestrictine D 6
(+) Lethaloxin 5
Microcarpalide 4
Figure 1.
OBn
OBn
HO
HO
O
O
OBn OH
O
OBn
O
10
Herbarumin-I 1
11
OBn
HO
D- mannitol
OBn
9
Scheme 1. Retrosynthetic analysis of 1.
O
O
O
O
Ref. 9
Cl
b
OH
a
O
O
D-mannitol
O
O
3
2
OR
HO
O
O
g
e
d
TBDMSO
f
HO
OBn
OR
OBn
4
R = H
R = Bn 5
7
6
c
R = H
R = Bn 8
BnO
BnO
OBn
h
HO
+
:
OBn
OBn
10a
OBn
OH
OH
7
3
10
9
Scheme 2. Reagents and conditions: (a) Ph3P, NaHCO3, CCl4, reflux, 1 h, 89%; (b) Na, dry ether, 0 °C to rt, 15 h, 92%; (c) NaH, BnBr, THF, 0 °C to rt, 6 h, 93%; (d) TFA (THF/H2O
9:1) 84% (e) TBDMSCl, imidazole, CH2Cl2, 0 °C to rt, 6 h, 82%; (f) NaH, BnBr, TBAI (cat), THF, 0 °C to rt, 6 h; (g) TBAF, THF, rt, 2 h, 85%; (h) (i) (COCl)2, DMSO, Et3N, CH2Cl2, ꢁ78 °C,
0.5 h; (ii) propylmagnesium chloride, dry toluene, ꢁ78 °C, 3 h, 62%.

1122
A. Kamal et al. / Tetrahedron: Asymmetry 20 (2009) 1120–1124
PCY3
Ph
Cl
Ru
Cl
PCY3
BnO
O
Ru-I
BnO
BnO
BnO
OH
a
b
O
OBn
OBn
O
O
10
11
12
N
N
Ar
Cl
Cl
Ar
c
Ru
Ph
PCY3
HO
HO
BnO
BnO
d
Ru-II
O
O
O
O
12
1
Scheme 3. Reagents and conditions: (a) 5-hexenoic acid, DCC, DMAP, CH2Cl2, 0 °C to rt, 3 h, 81%; (b) 20 mol% Ru-I, benzene, 12 h; (c) 20 mol % Ru-II, benzene, 12 h, 62%; (d)
TiCl4, CH2Cl2, 0 °C, 0.5 h, 82%.
Initial attempts for the ring-closing metathesis of diene 11 using
Grubbs’ first generation catalyst (Ru-I) were not successful, but this
reaction, under varying conditions such as different solvents and
temperatures, showed some traces of dimer formation along with
the recovered starting material. However, use of Grubbs’ second
generation catalyst (Ru-II, 20 mol %) in benzene under argon at
70 °C for 12 h, resulted in the ring-closing metathesis10 of 11 which
led to the exclusive formation of lactone 12 (in E-form) bearing the
trans geometry at the newly formed double bond and interest-
ingly no cis-form was detected. The doublet of a doublet at
5.88–5.97 ppm in the 1H NMR spectrum with a coupling constant
of JH-5, H-6 = 15.6 Hz allowed us to assign the E-stereochemistry for
12. After the lactone formation, the bis-benzyl-protected diol groups
at 7 and 8 positions need to be deprotected. Accordingly, bis-benzyl-
protected diol was treated with TiCl4 in dichloromethane11at 0 °C to
afford the target molecule 1 (see Scheme 3). The spectral and analyt-
ical data were comparable to the previously reported data in the
literature.2,7b
per million with respect to the internal TMS. Mass spectra were re-
corded on VG micromass-7070H (70 Ev).
4.2. 1,2:3,4-Di-O-isopropylidine-(2R,3R,4S)-5-chloropentane-
1,2,3,4-tetraol 3
To a stirred solution of compound 2 (7 g, 30.17 mmol), in
dry CCl4 (15 mL), Ph3P (11.8 g, 45.25 mmol) and NaHCO3
(5.06 g, 60.34 mmol) were added and heated at reflux for 1 h.
CCl4 was evaporated under reduced pressure and the residue
that was obtained was extracted with CHCl3 (2 ꢀ 100 ml), dried
over anhydrous Na2SO4, evaporated and purified by column
chromatography (silica gel, 60–120 mesh, EtOAc–hexane 6:94)
to afford 3 (6.72 g, 89%) as a liquid. ½a D25
¼ þ12:9 (c 1.1, CHCl3);
ꢂ
IR (neat):
840 cmꢁ1
cmax: 3443, 2987, 2936, 2882, 1215, 1155, 1065,
;
1H NMR (300 MHz, CDCl3): d 1.34 (s, 3H), 1.39 (s,
3H), 1.42 (s, 3H), 1.44 (s, 3H), 3.65 (dd, J = 5.35 Hz, 1H), 3.79
(t, J = 7.56 Hz, 1H), 3.80–3.85 (m, 1H), 3.90–4.05 (m, 2H),
4.10–4.15 (m, 2H); 13C NMR (75 MHz, CDCl3): d 25.1, 26.5,
26.9, 27.1, 44.6, 67.4, 76.8, 78.1, 79.7, 109.6, 109.9; MS-EIMS:
m/z 273.5 (M+Na)+.
3. Conclusion
In conclusion, we have developed a simple, convenient and effi-
cient approach for the synthesis of naturally occurring herbaru-
4.3. (1S)-1-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]-2-propen-1-
ol 4
min-I 1 by employing
D-mannitol as a chiral template. This
protocol involves the use of a Grignard reaction and ring-closing
metathesis as key steps. The synthesis of related compounds of this
family is underway in our laboratory.
Compound 3 (6.5 g, 25.94 mmol) was dissolved in dry ether
(75 mL) at ꢁ10 °C and shining Na pieces (1.79 g, 77.84 mmol) were
added under nitrogen atmosphere. After complete addition, the
reaction mixture was allowed to stir at room temperature for
12 h. Then the reaction mixture was carefully quenched with
MeOH at 0 °C, diluted with brine, dried over anhydrous Na2SO4
and concentrated under reduced pressure. The residue was puri-
fied by column chromatography (silica gel, 60–120 mesh, EtOAc–
4. Experimental
4.1. General experimental
Reagents and chemicals were purchased from Aldrich. All sol-
vents and reagents were purified by standard techniques. THF
was freshly distilled from LiAlH4. Crude products were purified
by column chromatography on 60–120 silica gel. IR spectra were
recorded on a Perkin–Elmer 683 spectrometer. Optical rotations
were obtained on a Horiba 360 digital polarimeter. 1H and 13C
NMR spectra were recorded in CDCl3 solution on a Varian Gemini
200, Brucker Avance 300. Chemical shifts are reported in parts
hexane 15:85) to afford 4 (3.77 g, 92%) as a liquid. ½a D25
¼ þ2:9 (c
ꢂ
1.1, CHCl3); IR (neat): cmax: 3442, 2925, 2854, 1649, 1022, 754;
1H NMR (300 MHz, CDCl3): d 1.36 (s, 3H), 1.44 (s, 3H), 2.07 (d,
J = 3.05 Hz, 1H), 3.83–3.95 (m, 2H), 4.05 (q, J = 4.53, 6.80 Hz, 1H),
4.25 (m, 1H), 5.22–5.42 (m, 2H), 5.76–5.86 (m, 1H); 13C NMR
(75 MHz, CDCl3): d 25.04, 26.33, 64.77, 71.87, 78.05, 109.33,
116.72, 136.23; MS-EIMS: m/z 181 (M+Na)+.

A. Kamal et al. / Tetrahedron: Asymmetry 20 (2009) 1120–1124
1123
4.4. (4R)-4-[(1S)-1-(Benzyloxy)-2-propenyl]-2,2-dimethyl-1,3-
dioxolane 5
CHCl3 (2 ꢀ 30 ml), dried over anhydrous Na2SO4 and concentrated
under reduced pressure to afford crude 8. This was dissolved in dry
THF, cooled to 0 °C and TBAF (19.56 mL, 19.56 mmol, 1 M in THF)
was added slowly. The reaction mixture was stirred for 1 h at room
temperature. After completion of the reaction, the reaction mixture
was quenched with water, THF was evaporated, extracted with
CHCl3 (2 ꢀ 25 ml), dried over anhydrous Na2SO4 and concentrated
under reduced pressure. The residue was purified by column chro-
matography (silica gel, 60–120 mesh, EtOAc–hexane 1:3) to afford
To a stirred solution of the compound 4 (3.5 g, 22.15 mmol) in
dry THF (40 mL), sodium hydride (1.06 g, 44.30 mmol) and benzyl
bromide (2.63 mL, 22.15 mmol) were added at 0 °C and stirred at
room temperature for 4 h. After completion of the reaction, THF
was evaporated, extracted with CHCl3 (2 ꢀ 75 ml), dried over
anhydrous Na2SO4 and concentrated under reduced pressure. The
residue was purified by column chromatography (silica gel, 60–
120 mesh, EtOAc–hexane 5: 95) to afford 5 (5.10 g, 93%) as a yel-
9 (2.50 g, 85% from two steps) as a liquid. ½a D25
¼ þ60:4 (c 1.1,
ꢂ
CHCl3); IR (neat):
cmax: 3456, 2954, 2930, 2858, 1466, 1254,
low oil. ½a 2D5
ꢂ
¼ þ49:5 (c 1.1, CHCl3); IR (neat):
c
max: 3405, 2925,
1110, 1069, 838, 777, 698; 1H NMR (300 MHz, CDCl3): 2.04 (br s,
1H), 3.51–3.56 (m, 1H), 3.71–3.73 (m, 2H), 3.93–3.98 (m, 1H),
4.41–4.70 (m, 4H), 5.33–5.39 (m, 2H), 5.82–5.94 (m, 1H), 7.25–
7.35 (m, 10H); 13C NMR (75 MHz, CDCl3): 61.84, 70.54, 72.61,
73.31, 80.68, 119.25, 127.55, 127.59, 127.64, 127.70, 127.84,
128.33, 134.91, 135.5, 138.06; MS-EIMS: m/z 321.0 (M+Na)+.
2874, 1719, 1643, 1555, 1394, 1275, 1211, 1066, 933, 698; 1H
NMR (300 MHz, CDCl3): d 1.36 (s, 3H), 1.41 (s, 3H), 3.75 (t,
J = 5.85, 7.30 Hz, 1H), 3.84–3.93 (m, 1H), 4.01–4.17 (m, 2H), 4.36–
4.65 (m, 2H), 5.30–5.42 (m, 2H), 5.75–5.92 (m, 1H); 7.24–7.34
(m, 5H); 13C NMR (75 MHz, CDCl3): d 25.14, 26.38, 65.77, 70.37,
77.65, 80.85, 109.53, 119.42, 127.44, 127.63, 128.18, 135.10,
137.89; MS-EIMS: m/z 271.2 (M+Na)+.
4.8. (4R,5R,6S)-5,6-Di(benzyloxy)-7-octen-4-ol 9
4.5. (2R,3S)-3-(Benzyloxy)-4-pentene-1,2-diol 6
To a stirred solution of oxalyl chloride (0.87 mL, 10.06 mmol), in
dry CH2Cl2 (20 mL), DMSO (1.42 mL, 20.12 mmol), was added at
ꢁ78 °C and stirred at the same temperature for 30 min. Compound
9 (1.5 g, 5.03 mmol) in dry CH2Cl2 (10 mL), was added at ꢁ78 °C to
the reaction mixture and stirred for 2 h at the same temperature.
DIPEA (3.05 mL, 20.08 mmol) was added at ꢁ78 °C and the reaction
mixture was allowed to warm room temperature for 30 min. The
reaction mixture was diluted with water (20 mL) and extracted
with CHCl3 (2 ꢀ 25 mL). The combined organic layers were washed
with brine (20 mL), dried over anhydrous Na2SO4 and concentrated
under reduced pressure to afford crude aldehyde as a yellow syrup.
The crude aldehyde was dissolved in toluene (20 mL) and was
cooled to ꢁ78 °C. To this n-propyl magnesium chloride (8.78 mL,
17.56 mmol, 2 M in di ethyl ether) was added slowly and stirred
at the same temperature for 3 h. After completion of the reaction,
the reaction mixture was treated with saturated aqueous NH4Cl
solution (20 mL) and extracted with CH2Cl2 (2 ꢀ 30 ml), dried over
anhydrous Na2SO4 and concentrated under reduced pressure. The
residue was purified by column chromatography (silica gel, 60–
120 mesh, EtOAc–hexane 10:90) to afford 10 (0.92 g, 62%) as a yel-
Compound 5 (4.8 g, 19.35 mmol) was dissolved in THF/H2O
(9:1; 30 mL) and was treated with trifluoroacetic acid (2.87 mL,
38.70 mmol) at 0 °C and further stirred for 4 h at room tempera-
ture. After completion of the reaction, the reaction mixture was
quenched with aqueous sodium bicarbonate solution, THF was
evaporated, extracted with EtOAc (2 ꢀ 60 ml), dried over anhy-
drous Na2SO4 and concentrated under reduced pressure. The resi-
due was purified by column chromatography (silica gel, 60–120
mesh, EtOAc–hexane 3:7) to afford 6 (3.38 g, 84%) as a syrup.
½
a 2D5
ꢂ
¼ þ54:5 (c 1.1, CHCl3); IR (neat):
cmax: 3412, 2965, 2931,
2877, 1718, 1274, 1068, 1022, 700; 1H NMR (200 MHz, CDCl3): d
2.13–2.23 (br s, 1H), 2.57–2.62 (br s, 1H), 3.53–3.75 (m, 3H),
3.84–3.95 (m, 1H), 4.31–4.67 (m, 2H), 5.27–5.44 (m, 2H), 5.70–
5.92 (m, 1H) 7.24–7.35 (m, 5H); 13C NMR (75 MHz, CDCl3): d
63.17, 70.47, 73.35, 81.75, 119.73, 127.59, 127.69, 128.28, 134.95,
137.85; MS-EIMS: m/z 231.1 (M+Na)+.
4.6. (2R,3S)-3-(Benzyloxy)-1-[1-methyl-1-(1,1,1-
trimethylsilyl)ethoxy]-4-penten-2-ol 7
low liquid. ½a 2D8
ꢂ
¼ þ62:1 (c 1.1, CHCl3); IR (neat):
cmax: 3423, 3015,
2987, 1455, 1378, 1085 cmꢁ1; 1H NMR (200 MHz, CDCl3): d 0.89 (t,
J = 6.7 Hz, 3H), 1.36 (m, 2H), 1.52 (m, 2H), 3.39 (t, J = 11.5, 5.6 Hz,
1H), 3.69 (br s, 1H), 3.99 (t, J = 13.0, 6.6 Hz, 1H), 4.42 (q,
J = 11.8 Hz, 2H), 4.69 (q, J = 11.7 Hz, 2H), 5.34 (m, 2H), 5.92 (m,
1H), 7.26 (m, 10H); 13C NMR (75 MHz, CDCl3): 14.6, 18.7, 34.7,
70.2, 72.3, 74.1, 81.8, 83.7, 119.3, 127.60, 127.62, 127.7, 127.9,
128.2, 128.3, 135.9, 137.9, 138.2; MS-EIMS: m/z 363.1 (M+Na)+.
To a cooled (0 °C) solution of 6 (3.2 g, 15.38 mmol) in CH2Cl2
(35 mL), imidazole (1.56 g, 23.07 mmol) was added followed by
TBDMSCl (2.32 g, 15.38 mmol) and stirred for 4 h at room temper-
ature. The reaction mixture was treated with 20 mL of saturated
aqueous NH4Cl solution and extracted with CH2Cl2 (2 ꢀ 30 ml),
dried over anhydrous Na2SO4 and concentrated under reduced
pressure. The residue was purified by column chromatography (sil-
ica gel, 60–120 mesh, EtOAc–hexane 15:85) to afford 7 (4.06 g,
4.9. 2-[(1R,2S,3S)-2,3-Di(benzyloxy)-1-propyl-4-pentenyl]oxy-
1,6-heptadiene 10
82%) as a liquid. ½a D25
ꢂ
¼ þ26:5 (c 1.1, CHCl3); IR (neat): cmax
:
3471, 2954, 2930, 2858, 1466, 1254, 1110, 1069, 838, 776, 698;
1H NMR (300 MHz, CDCl3): 0.10 (s, 6H), 0.92 (s, 9H), 2.30 (br s,
1H), 3.66–3.72 (m, 3H), 3.81–3.85 (m, 1H), 4.37–4.66 (m, 2H),
5.31–5.41 (m, 2H), 5.82–5.94 (m, 1H), 7.26–7.35 (m, 5H); 13C
NMR (75 MHz, CDCl3): ꢁ5.44, 18.2, 25.82, 63.45, 70.33, 73.32,
80.62, 119.58, 127.53, 127.73, 128.29, 135.25, 138.20; MS-EIMS:
m/z 345.8 (M+Na)+.
To a stirred solution of the compound 10 (0.7 g, 2.06 mmol) in
dry CH2Cl2 (15 mL), DCC (0.84 g, 4.12 mmol), 1-hexenoic acid
(0.244 mL, 2.06 mmol) and DMAP (catalytic amount) were added
at 0 °C and stirred at room temperature for 3 h. After completion
of the reaction, the reaction mixture was filtered through Celite
and extracted with CH2Cl2 (2 ꢀ 20 ml), dried over anhydrous
Na2SO4 and concentrated under reduced pressure. The residue
was purified by column chromatography (silica gel, 60–120 mesh,
4.7. (2R,3S)-2,3-Ddi(benzyloxy)-4-penten-1-ol 8
EtOAc–hexane 4:96) to afford 11 (0.73 g, 81%) as
¼ þ68:2 (c 1.1, CHCl3); IR (neat): max: 3067, 2959, 2931,
2871, 1735, 1455, 1170, 1096, 915, 738, 698 cmꢁ1 1H NMR
(200 MHz, CDCl3): d 0.84 (t, J = 15.1, 7.5 Hz, 3H), 1.15–1.32 (m,
2H), 1.44–1.71 (m, 4H), 2.05 (m, 2H), 2.19 (m, 2H), 3.58 (t, J = 9.8,
4.5 Hz, 1H), 3.75 (t, J = 13.5, 6.04 Hz, 1H), 4.46 (m, 4H), 4.98 (m,
a liquid.
To a stirred solution of the compound 7 (3.8 g, 11.80 mmol) in
dry THF (40 mL), sodium hydride (0.56 g, 23.60 mmol), benzyl bro-
mide (1.40 mL, 11.80 mmol) and TBAI (catalytic amount) were
added at 0 °C and stirred at room temperature for 6 h. After com-
pletion of the reaction, the THF was evaporated, extracted with
½
a 2D8
ꢂ
c
;

1124
A. Kamal et al. / Tetrahedron: Asymmetry 20 (2009) 1120–1124
2H), 5.09 (m, 1H), 5.30 (m, 2H), 5.79 (m, 2H), 7.26 (m, 10H); 13C
NMR (75 MHz, CDCl3): 13.8, 18.6, 23.9, 31.2, 32.9, 33.6, 69.9,
73.5, 73.9, 80.0, 82.0, 115.2, 119.6, 127.4, 127.7, 127.8, 128.0,
128.1, 128.2, 135.2, 137.5, 138.1, 138.3, 172.7; MS-EIMS: m/z
459.25 (M+Na)+.
Acknowledgements
The authors P.V.R. and S.P.R. wish to thank UGC and CSIR, New
Delhi for the award of research fellowships.
References
4.10. (8S,9S,10R)-8,9-Di-(benzyloxy)-10-propyl-3,4,5,8,9,10-
hexahydro-2H-2-oxecinone 12
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rated under reduced pressure, affording
a dark brown oily
residue which was purified by column chromatography (silica
gel, 60–120 mesh, EtOAc–hexane 5:95) to afford 12(0.29 g, 62%)
as a liquid. ½a 2D8
ꢂ
¼ þ43:2 (c 1.0) 3069, 2970, 2871, 1738, 1450,
1170, 1080, 925, 730, 695 cmꢁ1
;
1H NMR (300 MHz, CDCl3): d
0.81 (t, J = 7.23 Hz, 3H), 1.23–1.27 (m, 4H), 1.61–1.87 (m, 2H),
1.94–2.41(m, 4H), 3.75–3.78 (m, 2H), 4.24–4.64 (dd, 2H) 4.81 (d,
1H), 4.92–4.95 (dd, 1H), 5.06 (d, 1H), 5.46–5.55 (m, 1H), 5.88 –
5.97 (dd, J = 15.6 Hz, 1H), 7.27–7.40 (m, 10H); 13C NMR (75 MHz,
CDCl3): 13.85, 18.46, 26.21, 33.61, 33.98, 34.49, 69.10, 73.36,
74.85, 79.70, 84.10, 127.23, 127.31, 127.52, 128.07, 128.21,
128.75, 129.18, 135.14, 138.49, 138.67, 178.46, MS-EIMS: m/z
431.2 (M+Na)+.
4.11. (8S,9S,10R)-8,9-Dihydroxy-10-propyl-3,4,5,8,9,10-
hexahydro-2H-2-oxecinone 1
8. (a) Kamal, A.; Krishnaji, T.; Reddy, P. V. Tetrahedron: Asymmetry 2007, 18, 1775–
1779; (b) Kamal, A.; Krishnaji, T.; Reddy, P. V. Tetrahedron Lett. 2007, 48, 7232–
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8657–8660; (d) Kamal, A.; Shaik, A. A.; Sandbhor, M.; Malik, M. S.; Kaga, H.
Tetrahedron Lett. 2004, 43, 8057–8059; (e) Kamal, A.; Khanna, G. B. R.; Ramu, R.;
Krishnaji, T. Tetrahedron Lett. 2003, 44, 4783–4787.
To a stirred solution of 12 (0.16 g, 0.39 mmol) in dry CH2Cl2
(10 mL), TiCl4 (0.086 mL, 0.78 mmol), was added at 0 °C for
15 min. After completion of the reaction, it was taken into dichlo-
romethane, washed with saturated aqueous sodium bicarbonate
(10 mL) and water (10 mL), dried over anhydrous Na2SO4 and con-
centrated under reduced pressure. The residue was purified by col-
umn chromatography (silica gel, 60–120 mesh, EtOAc–hexane
20:80) to afford the desired compound 1 as a colourless low melt-
9. (a) Wu, W.; Wu, Y. J. Org. Chem. 1993, 58, 3586–3588; (b) Reddy, J. S.; Kumar, A.
R.; Rao, V. B. Tetrahedron: Asymmetry 2005, 16, 3154–3159.
10. (a) Fürstner, A. Angew. Chem., Int. Ed. 2002, 39, 3012–3043; (b) Liu, D.; Kozmin,
S. S. Org. Lett. 2002, 4, 3005–3007; (c) Murga, J.; Falomir, E.; Garica-Fortanet, J.;
Carda, M.; Marco, J. A. Org. Lett. 2002, 4, 3447; (d) Prunet, J. Angew. Chem., Int.
Ed. 2003, 42, 2826–2830; (e) Gurjar, M. K.; Nagaprasad, R.; Ramana, C. V.
Tetrahedron Lett. 2003, 44, 2873–2875; (f) Davoli, P.; Spaggiari, A.; Castagnetti,
L.; Prati, F. Org. Biomol. Chem. 2004, 2, 38–47; (g) Dieters, A.; Martin, S. F. Chem.
Rev. 2004, 104, 2199–2238; (h) Chavan, S. P.; Praveen, C. Tetrahedron Lett. 2005,
46, 1939–1941; (i) Davoli, P.; Fava, R.; Morandi, S.; Spaggiari, A.; Prati, F.
Tetrahedron 2005, 61, 4427–4436; (j) Garica-Fortanet, J.; Murga, J.; Falomir, E.;
Carda, M.; Marco, J. A. J. Org. Chem. 2005, 70, 9822–9827; (k) Sharma, G. V. M.;
Cherukupalli, G. R. Tetrahedron: Asymmetry 2006, 17, 1081–1088; (l) Gradillas,
A.; Perez-Castells, J. Angew. Chem., Int. Ed. 2006, 45, 6086–6101; (m) Ghosh, S.;
Rao, R. V. Tetrahedron Lett. 2007, 48, 6937–6940.
ing solid (0.073 g, 82%). ½a D28
ꢂ
¼ þ10:6 (c 1.1, EtOH); IR (neat): cmax
:
3285, 2927, 2869, 1728, 1455, 1208, 1090 cmꢁ1
;
1H NMR
(200 MHz, CDCl3): d 0.91 (t, J = 7.5 Hz, 3H), 1.25–1.42 (m, 2H),
1.52–1.63 (m, 2H), 1.83–2.05 (m, 3H), 2.35 (m, 3H), 3.49 (d,
J = 9.8 Hz, 1H) 4.41 (br s, 1H), 4.93 (td, J = 9.8, 2.3 Hz, 1H), 5.45–
5.55 (m, 1H), 5.63 (d, J = 15.8 Hz, 1H); 13C NMR (75 MHz, CDCl3):
13.8, 17.9, 24.6, 29.3, 33.3, 33.6, 70.1, 73.2, 73.5, 124.5, 130.7,
176.3; MS-EIMS: m/z 251 (M+Na)+.
11. Hori, H.; Nishida, Y.; Ohrui, H.; Meguro, H. J. Org. Chem. 1989, 54, 1346–1353.