Formal synthesis of natural 1,3-polyol/α-pyrone diastereoisomers

Article abstract of DOI:10.1002/hlca.200890243

A stereoselective formal synthesis of diastereoisomers of 1,3-polyol/α-pyrone antifungal natural products isolated from Ravensara anisata has been achieved involving epoxide opening and asymmetric allylation as key steps.

Full text of DOI:10.1002/hlca.200890243

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Helvetica Chimica Acta – Vol. 91 (2008)
Formal Synthesis of Natural 1,3-Polyol/a-Pyrone Diastereoisomers
by Gowravaram Sabitha*, Peddabuddi Gopal, and Jhillu S. Yadav
Organic Division-I, Indian Institute of Chemical Technology, Hyderabad – 500007, India
(fax: þ 91-40-27160512; e-mail: gowravaramsr@yahoo.com)
A stereoselective formal synthesis of diastereoisomers of 1,3-polyol/a-pyrone antifungal natural
products isolated from Ravensara anisata has been achieved involving epoxide opening and asymmetric
allylation as key steps.
Introduction. – Natural products containing the 5,6-dihydro-2H-pyran-2-one
moiety display a wide range of biological activities [1], such as antifungal activity,
cytotoxicity against human tumor cells [2], and inducing apoptosis [3]. Because of their
manifold biological properties, these compounds are of marked interest not only from a
chemical, but also from a pharmacological perspective. The 1,3-polyol/pyrones 1 and 2
[4] belong to this class of compounds, they have been isolated from Ravensara anisata
and possess inhibitory activity against C. Cucumerinum. Shibasaki and co-workers [5]
reported the enantioselective syntheses of these pyrones, and recently, a carbohydrate
based approach [6] has been reported. In continuation of our interest on the synthesis
of lactone containing natural products [7], we herein report our studies towards the
total synthesis of 1,3-polyol/a-pyrones.
Results and Discussion. – Our synthesis (see Scheme) started from the known
epoxide 3 [7h]. Epoxide opening with the Grignard reagent prepared from (3-
bromopropyl)benzene (4) and Mg in the presence of CuI in THF at 08 for 2 h afforded
the alcohol 5 in 92% yield. The secondary OH group was protected as (t-Bu)Me2Si
(TBS) ether to give compound 6 in 90% yield. Debenzylation of 6 was achieved using
Li in liquid NH3 to afford a primary alcohol 7, which was oxidized to the aldehyde 8
using 2-(iodooxy)benzoic acid (IBX) in 95% yield. Aldehyde 8 gave hydroxy protected
b-ketoester 9 on treatment with ethyl diazoacetate in the presence of SnCl2 in dry
CH2Cl2 in 80% yield.
ꢀ 2008 Verlag Helvetica Chimica Acta AG, Zꢁrich

Helvetica Chimica Acta – Vol. 91 (2008)
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Scheme
a) Mg/THF, CuI, 08, 2 h, 86%. b) 1H-Imidazole, (t-Bu)Me2Si (TBS-Cl), dry CH2Cl2, 2 h, 95%. c) Li/liq.
NH3, 87%. d) 2-(Iodooxy)benzoic acid (IBX), DMSO, CH2Cl2, 2 h, 94%. e) Ethyl diazoacetate, SnCl2,
dry CH2Cl2, 30 min, 83%. f) THF/Bu4NF (TBAF), 0.5 h, 85%. g) Catecholborane, dry THF, 5 h, 70%. h)
2,2-Dimethoxypropane, CH2Cl2, PPTS, 12 h, 90%. i) DIBAL-H, dry CH2Cl2, ꢀ 788, 70%. j) (R)-(þ)-
1,1’-Binaphthalene-2,2’-diol, (i-PrO)4Ti, 08 – r.t., CH2Cl2, 3 h. k) Acryloyl chloride/EtN(i-Pr)2, 08 ꢀ r.t.,
3 h, 89%. l) Grubbsꢂ generation I, dry CH2Cl2, 08 – r.t., 6 h, 95%. m) PPTS, MeOH, r.t., 4 h, 81%.

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Removal of the TBS group using Bu4NF (TBAF) in THF yielded d-hydroxy-b-
ketoester 10, and enantioselective reduction of the keto group with catecholborane
furnished 1,3-syn-diol 11 in 70% yield. Acetonide protection of the diol followed by
DIBAL-H reduction gave aldehyde 13. We envisioned that a chiral asymmetric
allylation [8] of aldehyde 13 could be achieved using allyltributylstannane and a chiral
Lewis acid. Thus treatment of aldehyde 13 with allyl(tributyl)stannane and (R)-
BINOL afforded the chiral homoallyl alcohol 14 in good yield with high enantiose-
lectivity. With this reaction we had achieved the extension of the 1,3-syn polyol system.
Next, acrylation of the secondary OH group in 14 was carried out efficiently with
acryloyl chloride in the presence of Et3N to yield a diene 15, a precursor for the ring-
closing metathesis, in 95% yield. The diene was reacted with the 10 mol-% of Grubbsꢂ
catalyst [bis(tricyclohexylphosphine)benzylidene ruthenium(IV) dichloride] in CH2Cl2
under N2 atmosphere to furnish lactone 16, cleavage of the acetonide with pyridinium
p-toluenesulfonate (PPTS) in MeOH yielded dihydroxylactone 17 in 81% yield. The
spectral data of the 17 matched with the reported data [6]. Since the monoacetylation
of lactone 17 to the target molecules 1 and 2 has already been reported [5], the present
sequence constitutes
a formal synthesis of pyrones (6R,2’S,4’S(OAc))-1 and
(6R,2’S(OAc)),4’S)-2.
It is important to mention that the natural product isolated by Hostettmann [4] was
shown to be the (6R,2’S,4’R) isomer, whereas the (6S,2’R,4’R) isomer has been
prepared by Shibasaki et al. [5]; later the (6R,2’S,4’S) isomer was also synthesized using
a carbohydrate-based approach [6].
In conclusion, a formal approach for the stereoselective synthesis of 1,3-polyol/a-
pyrones ((6R,2’S,4’S) isomers) was achieved involving epoxide opening and asymmet-
ric allylation as key steps.
Experimental Part
Commercial reagents were used without further purification. All solvents were purified by standard
techniques. Column chromatographic (CC) separations were carried out on silica gel (SiO2; 60 – 120
mesh). M.p.: Fisher Johns apparatus; uncorrected. Optical rotation: Jasco Dip 360 digital polarimeter. IR
Spectra: Perkin-Elmer 683 spectrometer. NMR Spectra: in CDCl3; Varian Gemini 200, Bruker 300, or
Varian Unity 400 NMR spectrometers; chemical shifts (d) are given in ppm and are referenced to Me4Si
as internal standard; coupling constants (J) are given in Hz. MS: Finnigan MAT 1020B or micro mass VG
70-70 H spectrometers operating at 70 eV using a direct inlet system.
(3S)-1-(Benzyloxy)-7-phenylheptan-3-ol (5). To a suspension of Mg (1.3 g, 56.11 mmol) in dry THF
(20 ml), (3-bromopropyl)benzene (4; 8.5 g, 56.11 mmol) was added dropwise under N2 at 08. The mixture
was allowed to stir for about 1 h at r.t. A cat. amount of CuI was then added at 08 to the suspension of the
Grignard reagent and allowed to stir at the same temp. for ca. 0.5 h. (2R)-2-[2-(Benzyloxy)ethyl]oxirane
(3; 5 g, 28.05 mmol) in dry THF (15 ml) was added dropwise at 08 and stirred at r.t. for ca. 30 min. After
completion of the reaction, sat. aq. NH4Cl soln. was added, and the mixture extracted with AcOEt. The
org. layer was washed with brine, dried over anh. Na2SO4, and concentrated under reduced pressure. CC
(SiO2) afforded 5 (7.2 g, 83%) as a viscous liquid. [a]2D5 ¼ ꢀ6.3 (c ¼ 0.015, CHCl3). IR (neat): 3435, 3061,
3027, 2930, 2856, 1721, 1602, 1494, 1454, 1363, 1267, 1206, 1094, 1028, 798, 741. 1H-NMR (200 MHz,
CDCl3): 7.43 – 7.07 (m, 10 H); 4.52 (s, 2 H); 3.85 – 3.55 (m, 3 H); 2.62 (t, J ¼ 7.8, 2 H); 1.77 – 1.31 (m, 8 H).
13C-NMR (75 MHz CDCl3): 142.7; 137.9; 128.4; 128.2; 127.7; 127.6; 125.6; 96.1; 73.3; 72.3; 69.2; 37.3; 36.4;
35.9; 31.5; 25.2. LC-MS: 321 ([M þ Na]þ). HR-ESI-MS: 321.183 ([M þ Na]þ, C20H26NaOþ2 ; calc.
321.1830).

Helvetica Chimica Acta – Vol. 91 (2008)
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{[(3S)-1-(Benzyloxy)-7-phenylheptan-3-yl]oxy}(tert-butyl)dimethylsilane (6). To a stirred soln. of
alcohol 5 (5 g, 16.75 mmol) and imidazole (2.28 g, 33.51 mmol) in dry CH2Cl2 (50 ml) was added
TBDMS-Cl (3.78 g, 25.12 mmol) portionwise at 08. The mixture was stirred at the same temp. for 2 h, and
then quenched with H2O. The CH2Cl2 layer was separated, and the aq. layer extracted with additional
CH2Cl2 (2 ꢁ 50 ml). The combined org. layers were washed with H2O, brine, and dried over anh. Na2SO4.
The solvent was removed in vacuo, and the residue was purified by CC (SiO2) to afford 6 (6.57 g, 95%
yield) as a colorless liquid. IR (neat): 2925, 2854, 1740, 1632, 1456, 1318, 1264, 1077, 897, 792, 698.
1H-NMR (200 MHz, CDCl3): 7.43 – 7.01 (m, 10 H); 4.43 (s, 2 H); 3.88 – 3.70 (m, 1 H); 3.46 (t, J ¼ 6.6,
2 H); 2.57 (t, J ¼ 7.3, 2 H); 1.81 – 1.26 (m, 8 H); 0.84 (s, 9 H); 0.01 (s, 3 H). LC-MS: 435 ([M þ Na]þ). HR-
ESI-MS: 435.2666 ([M þ Na]þ, C26H40NaO2Siþ; calc. 435.2695).
(3S)-3-{[(tert-Butyl)dimethylsilyl]oxy}-7-phenylheptan-1-ol (7). Li metal (0.423 g, 60.53 mmol) was
added to freshly distilled NH3 (35 ml) and 6 (5.0 g, 12.12 mmol) in dry THF (20 ml) in a 250 ml two-neck
round bottom flask fitted with a cold finger condenser at ꢀ 338, and after 10 min quenched by the
addition of solid NH4Cl, and the NH3 was then allowed to evaporate. The residue was diluted with THF
(50 ml) and then directly filtered by using filtration flask and Buckner funnel setup and washed with
AcOEt (50 ml). The filtrate was concentrated and purified by CC (SiO2), eluted with AcOEt/PE (4 :6)
to give 7 as a colorless liquid (3.4 g, 87%). [a]D25 ¼ ꢀ35.0 (c ¼ 0.001, CHCl3). IR (neat): 3445, 2925, 2854,
1741, 1629, 1457, 1381, 1256, 1021, 765. 1H-NMR (200 MHz, CDCl3): 7.38 – 7.04 (m, 5 H); 4.04 – 3.58 (m,
3 H); 2.60 (t, J ¼ 7.5, 2 H); 1.93 – 1.04 (m, 8 H); 0.90 (s, 9 H); 0.01 (s, 6 H). 13C-NMR (75 MHz, CDCl3):
142.5; 128.4; 128.2; 125.6; 71.7; 60.2; 37.8; 36.7; 35.9; 31.5; 25.8; 25.0; 17.9; ꢀ 4.4; ꢀ 4.7. LC-MS: 345
([M þ Na]þ). HR-ESI-MS: 345.2240 ([M þ Na]þ, C19H34NaO2Siþ; calc. 345.2226).
(3S)-3-{[(tert-Butyl)dimethylsilyl]oxy}-7-phenylheptanal (8). To an ice-cooled soln. of 2-(iodo-
oxy)benzoic acid (4.42 g, 15.80 mmol) in DMSO (4.5 ml, 63.22 mmol) was added a soln. of alcohol 7
(3.4 g, 10.53 mmol) in anh. CH2Cl2 (10 ml). The mixture was stirred at r.t. for 2 h and then filtered
through a Celite pad and washed with Et2O. The combined org. filtrates were washed with H2O and brine,
dried (anh. Na2SO4), and concentrated in vacuo. The crude product was purified by CC (SiO2) to afford
aldehyde 8 as a viscous liquid (3.2 g, 94%). [a]D25 ¼ þ0.92 (c ¼ 1.85, CHCl3). IR (neat): 3445, 2925, 2854,
1
1741, 1629, 1457, 1381, 1256, 1021, 765. H-NMR (200 MHz, CDCl3): 9.76 (s, 1 H); 7.36 – 7.01 (m, 5 H);
4.28 – 4.05 (m, 1 H); 2.60 (t, J ¼ 7.3, 2 H); 2.52 – 2.40 (m, 2 H); 1.93 – 1.45 (m, 6 H); 0.86 (s, 9 H); 0.03 (s,
6 H). 13C-NMR (75 MHz, CDCl3): 202.1; 142.3; 128.4; 128.3; 125.7; 68.1; 50.8; 37.7; 35.8; 31.4; 25.7; 24.8;
17.9; ꢀ 4.5; ꢀ 4.7. LC-MS: 359 ([M þ K]þ).
Ethyl (5S)-5-{[(tert-Butyl)dimethylsilyl]oxy}-3-oxo-9-phenylnonanoate (9). Ethyl diazoacetate
(1.08 ml, 10.29 mmol) was added to a soln. of anh. tin(II)chloride (0.12 g, 0.93 mmol) in dry CH2Cl2
(15 ml) at r.t. To this suspension, a few drops of 8 (3 g, 9.36 mmol) in dry CH2Cl2 were added slowly at 08.
When N2 evolution started, the remaining soln. of 8 was added dropwise over 10 min. After N2 evolution
had stopped (30 min), the mixture was transfered to a separatory funnel with sat. brine (NaCl, 30 ml)
and extracted with Et2O (2 ꢁ 20 ml). The org. layers were combined and dried over anh. Na2SO4. The
solvent was removed in vacuo, and the residue was purified by CC (SiO2) to afford 9 (3.15 g, 83% yield)
as a viscous liquid. [a]2D5 ¼ þ18.0 (c ¼ 0.01, CHCl3). IR (neat): 2928, 2855, 1744, 1719, 1633, 1463, 1379,
1
1252, 1149, 1094, 1033, 835, 772, 699. H-NMR (200 MHz, CDCl3): 7.31 – 6.95 (m, 5 H); 4.29 – 4.04 (m,
3 H); 3.35 (s, 2 H); 2.75 – 2.38 (m, 4 H); 1.69 – 1.16 (m, 11 H); 0.81 (s, 9 H); 0.02 (s, 6 H). 13C-NMR
(75 MHz CDCl3): 201.9; 167.3; 142.4; 128.4; 128.3; 125.6; 68.8; 68.4; 61.2; 50.8; 50.1; 39.3; 37.4; 35.8; 31.4;
29.8; 25.8; 24.6; 17.9; 14.1; ꢀ 4.5. LC-MS: 429 ([M þ Na]þ). HR-ESI-MS: 429.2443 ([M þ Na]þ,
C23H38NaO4Siþ; calc. 429.2437).
Ethyl (5S)-5-Hydroxy-3-oxo-9-phenylnonanoate (10). To 9 (3 g, 7.37 mmol) in dry THF (10 ml) was
added TBAF (11.06 ml, 11.06 mmol, 1m soln. in THF) dropwise at 08, and the mixture was stirred for
30 min. H2O (2 ml) was added, and the mixture was extracted with AcOEt. The org. extracts were
washed with brine and dried over anh. Na2SO4. After evaporation of the solvent, the residue was purified
by CC (SiO2) to afford 10 (1.83 g, 85%) as a liquid. [a]2D5 ¼ þ19.2 (c ¼ 1, CHCl3). IR (neat): 3446, 2988,
2930, 2364, 1737, 1631, 1455, 1379, 1260, 1027. 1H-NMR (200 MHz, CDCl3): 7.37 – 7.02 (m, 5 H); 4.18 (q,
J ¼ 7.09, 2 H); 4.09 – 3.96 (m, 1 H); 3.41 (s, 2 H); 2.90 – 2.48 (m, 4 H); 1.90 – 1.17 (m, 9 H). LC-MS: 315
([M þ Na]þ). HR-ESI-MS: 315.1584 ([M þ Na]þ, C17H24NaOþ4 ; calc. 315.1572).

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Ethyl (3S,5S)-3,5-Dihydroxy-9-phenylnonanoate (11). The soln. of 10 (1.8 g, 6.15 mmol) in dry THF
was chilled in a MeOH-ice bath (ꢀ108) and charged with freshly distilled catecholborane (1.64 ml,
15.38 mmol). After 5 h, the mixture was quenched by the addition of 1 ml of anh. MeOH and 2 ml of a
sat. aq. soln. of sodium potassium tartrate. This mixture was allowed to stir at r.t. for 1 h, and the desired
product was isolated by CC (SiO2) to afford the diol 11 (1.74 g, 70%) as a liquid. [a]2D5 ¼ þ12.0 (c ¼ 1.15,
CHCl3). IR (neat): 3434, 2978, 2924, 2364, 1743, 1626, 1449, 1370, 1264, 1037. 1H-NMR (200 MHz,
CDCl3): 7.30 – 7.05 (m, 5 H); 4.35 – 4.10 (m, 1 H); 4.13 (q, J ¼ 7.3, 2 H); 3.98 – 3.76 (m, 1 H); 2.59 (t, J ¼
7.5, 2 H); 2.54 – 2.21 (m, 2 H); 1.74 – 1.52 (m, 8 H); 1.26 (t, J ¼ 7.5, 3 H); 1.33 (s, 3 H). 13C-NMR (75 MHz,
CDCl3): 172.5; 142.5; 128.3; 128.2; 125.6; 72.0; 69.0; 60.7; 42.2; 41.7; 37.6; 35.8; 31.4; 25.0; 14.1. LC-MS:
317 ([M þ Na]þ). HR-ESI-MS: 317.1730 ([M þ Na]þ, C17H26NaO4þ ; calc. 317.1729).
Ethyl [(4S,6S)-2,2-Dimethyl-6-(4-phenylbutyl)-1,3-dioxan-4-yl]acetate (12). To a soln. of diol 11
(1.5 g, 5.09 mmol) in dry CH2Cl2 (10 ml), 2,2-dimethoxypropane (0.94 ml, 7.64 mmol) and pyridinium p-
toluenesulfonate (PPTS; 0.13 g, 0.51 mmol) were added. The mixture was stirred at ambient temp. for
12 h. NaHCO3 was added to neutralize PPTS and filtered. Removal of solvent and purification by CC
(SiO2) afforded the 12 (1.53 g, 91%) as a liquid. [a]2D5 ¼ þ5.83 (c ¼ 1.2, CHCl3). IR (neat): 3446, 2988,
1
2930, 2364, 1737, 1631, 1455, 1379, 1260, 1027. H-NMR (300 MHz, CDCl3): 7.30 – 7.05 (m, 5 H); 4.28 –
4.16 (m, 1 H); 4.12 (q, J ¼ 7.5, 2 H); 3.83 – 3.66 (m, 1 H); 2.59 (t, J ¼ 8.3, 2 H); 2.52 – 2.24 (m, 2 H);
1.68 – 1.44 (m, 8 H); 1.41 (s, 3 H); 1.33 (s, 3 H); 1.26 (t, J ¼ 7.5, 3 H). 13C-NMR (50 MHz, CDCl3): 171.1;
142.6; 128.4; 128.3; 125.8; 98.7; 68.7; 66.0; 60.4; 41.5; 36.5; 36.2; 31.4; 30.9; 24.6; 19.7; 14.2. LC-MS: 357
([M þ Na]þ). HR-ESI-MS: 357.2055 ([M þ Na]þ), C20H30NaOþ4 ; calc. 357.2042).
[(4S,6S)-2,2-Dimethyl-6-(4-phenylbutyl)-1,3-dioxan-4-yl]acetaldehyde (13). To a stirred soln. of
acetonide protected ester 12 (1.5 g, 4.48 mmol) in dry THF (10 ml) was added DIBAL-H (3.84 ml, 1.4m,
5.38 mmol in hexane) dropwise over a period of 10 min at ꢀ 788 under N2 atmosphere. After stirring for
2 h at the same temp., dry MeOH (2 ml) was added, and the mixture was allowed to warm to r.t. Sat. aq.
soln. of sodium potassium tartarate (10 ml) was added, and the resulting mixture was stirred vigorously
until the two layers were separated. The org. layer was separated, and the aq. layer was extracted with
additional CH2Cl2 (2 ꢁ 40 ml). The combined org. layers were washed with H2O, brine and dried over
anh. Na2SO4. Removal of solvent in vacuo and purification by CC (SiO2) afforded the aldehyde 13
(0.91 g, 75% yield) as a viscous liquid. [a]2D5 ¼ þ4.1 (c ¼ 1, CHCl3). IR (neat): 3328, 2958, 2346, 1702,
1
1623, 1425, 1379, 1027. H-NMR (300 MHz, CDCl3): 9.02 (s, 1 H); 7.33 – 7.10 (m, 5 H); 4.34 – 4.19 (m,
1 H); 3.98 – 3.74 (m, 1 H); 2.56 (t, J ¼ 7.5, 2 H); 2.52 – 2.27 (m, 2 H); 1.74 – 1.52 (m, 8 H); 1.33 (s, 3 H);
1.29 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 203.7; 167.0; 142.5; 128.4; 128.3; 125.7; 67.5; 61.5; 49.9; 49.7;
36.3; 35.8; 31.3; 25.1; 14.1. LC-MS: 313 ([M þ Na]þ).
(2R)-1-[(4R,6S)-2,2-Dimethyl-6-(4-phenylbutyl)-1,3-dioxan-4-yl]pent-4-en-2-ol (14). A mixture of
(R)-(þ)-1,1’-binaphthalene-2,2’-diol (22.5 mg, 0.078 mmol), and 1m Ti(O-i-Pr)4 in CH2Cl2 (39 ml,
0.039 mmol) in CH2Cl2 (1 ml) was stirred at r.t. for 1 h. Aldehyde 13 (115 mg, 0.394 mmol) was added
to the red-brown soln., the contents were cooled to 08 and allyl(tributyl)stannane (144 mg, 0.435 mmol)
was added. After 3 h at 08, sat. NaHCO3, (0.5 ml) was added, and the contents were stirred for 1 h. The
combined org. layers were dried (Na2SO4) and filtered. The crude material was purified by CC (SiO2) to
give 14 (125 mg, 95%) as a light yellow oil with 98% ee. [a]2D5 ¼ þ5.3 (c ¼ 0.5, CHCl3). IR (KBr): 3447,
3070, 2990, 2930, 2857, 2364, 1730, 1641, 1454, 1379, 1200, 1100, 1024, 915, 746, 698. 1H-NMR (200 MHz,
CDCl3): 7.25 – 7.07 (m, 5 H); 5.92 – 5.68 (m, 1 H); 5.16 – 4.98 (m, 2 H); 4.22 – 3.65 (m, 3 H); 2.60 (t, J ¼
7.0, 2 H); 2.26 – 2.12 (m, 2 H); 1.73 – 1.13 (m, 16 H). HR-ESI-MS: 355.225 ([M þ Na]þ, C21H32NaO3þ ;
calc. 355.2249).
(2R)-1-[(4S,6S)-2,2-Dimethyl-6-(4-phenylbutyl)-1,3-dioxan-4-yl]pent-4-en-2-yl Prop-2-enoate (15).
To a stirred soln. of 14 (0.150 g, 0.45 mmol) and N-ethyl-N-(propan-2-yl)propan-2-amine (0.118 ml,
0.677 mmol) in anh. CH2Cl2 (5 ml), acryloyl chloride (0.04 ml, 0.496 mmol) was added dropwise at 08 and
stirred for 3 h at r.t. The mixture was treated with H2O (1 ꢁ 15 ml) and extracted with CH2Cl2 (2 ꢁ 15 ml).
The combined org. layers were washed with brine, dried (Na2SO4), and the solvent was evaporated under
reduced pressure. The residue was purified by CC (SiO2) (AcOEt/hexane, 1:20) to obtain the acrylate
compound 15 (0.155 g, 89%) as a light yellow oil. [a]2D5 ¼ þ4.1 (c ¼ 1.0, CHCl3). IR (KBr): 3433, 3075,
1
3026, 2989, 2993, 2859, 1723, 1638, 1405, 1269, 1196, 1125, 984, 918, 699. H-NMR (300 MHz, CDCl3):
7.24 – 7.07 (m, 5 H); 6.44 – 6.32 (m, 1 H); 6.15 – 6.01 (m, 1 H); 5.85 – 5.65 (m, 2 H); 5.27 – 4.97 (m, 2 H);

Helvetica Chimica Acta – Vol. 91 (2008)
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3.92 – 3.65 (m, 3 H); 2.59 (t, J ¼ 6.7, 2 H); 2.45 – 2.22 (m, 2 H); 1.93 – 1.20 (m, 16 H). 13C-NMR (50 MHz,
CDCl3): 168.2; 142.1; 133.4; 130.5; 130.4; 128.4; 128.3; 125.6; 118.1; 98.5; 68.8; 66.5; 40.6; 40.3; 37.2; 36.2;
35.9; 31.4; 30.2; 29.7; 24.6; 19.5. HR-ESI-MS: 409.237 ([M þ Na]þ, C24H34NaO4þ ; calc. 409.2355).
(6R)-6-{[(4S,6S)-2,2-Dimethyl-6-(4-phenylbutyl)-1,3-dioxan-4-yl]methyl}-5,6-dihydro-2H-pyran-2-
one (16). To a soln. of 15 (0.12 g, 0.31 mmol) in anh. CH2Cl2 (15 ml), first generation of Grubbsꢂ catalyst
(0.025 g, 0.031 mmol) was added at 08, and the resultant mixture was allowed to warm to r.t. over 6 h.
After completion of the reaction, the solvent was removed under reduced pressure, and the residue was
purified by CC (SiO2) (AcOEt/hexane, 3 :7) to yield 16 (0.105 g, 95%). [a]2D5 ¼ þ9.2 (c ¼ 1.0, CHCl3). IR
(KBr): 3449, 3025, 2933, 2858, 1726, 1602, 1494, 1456, 1382, 1248, 1199, 1039, 816, 700. 1H-NMR
(200 MHz, CDCl3): 7.25 – 7.07 (m, 5 H); 6.92 – 6.78 (m, 1 H); 6.0 (dt, J ¼ 9.3, 1.5, 1 H); 4.72 – 4.49 (br. ddt,
J ¼ 3.1, 8.5, 14.0, 1 H); 4.24 – 3.95 (m, 1 H); 3.89 – 3.63 (m, 1 H); 2.60 (t, J ¼ 7.8, 2 H); 2.48 – 2.25 (m,
2 H); 2.12 – 1.16 (m, 16 H). 13C-NMR (50 MHz, CDCl3): 164.2; 145.1; 142.6; 128.3; 128.2; 125.9; 121.6;
98.2; 74.9; 68.9; 64.9; 42.0; 40.8; 36.1; 31.2; 30.2; 29.2; 24.9; 20.0. HR-ESI-MS: 381.2051 ([M þ Na]þ,
C22H30NaOþ4 ; calc. 381.2042).
(6R)-6-[(2S,4S)-2,4-Dihydroxy-8-phenyloctyl]-5,6-dihydro-2H-pyran-2-one (17): To a soln. of 16
(0.075 g, 0.23 mmol) in MeOH (1 ꢁ 10 ml, HPLC quality), a cat. amount (pinch) of PPTS was added and
stirred for 4 h. After completion of the reaction, the mixture was quenched with solid NaHCO3 (0.06 g,
0.071 mmol) and directly concentrated under reduced pressure. The residue was purified by CC (SiO2)
(AcOEt/hexane, 3 :2) to yield 17 (0.054 g, 81%). [a]2D5 ¼ þ63.2 (c ¼ 1.0, CHCl3). IR (KBr): 3405, 3025,
2930, 2856, 1711, 1493, 1452, 1389, 1254, 1149, 1052, 746, 700. 1H-NMR (200 MHz, CDCl3): 7.30 – 7.11 (m,
5 H); 6.89 (ddd, J ¼ 9.8, 4.5, 3.8, 1 H); 6.02 (dt, J ¼ 9.8, 1.8, 1 H); 4.72 – 4.57 (br. ddt, J ¼ 8.9, 7.5, 5.5,
1 H); 4.15 – 4.03 (m, 1 H); 3.90 – 3.79 (m, 1 H); 3.50 (m, 2 H); 2.62 (t, J ¼ 7.5, 2 H); 2.45 – 2.39 (m, 2 H);
2.08 – 1.95 (m, 1 H); 1.81 – 1.32 (m, 9 H). 13C-NMR (50 MHz, CDCl3): 164.2; 145.4; 142.4; 128.3; 128.2;
125.7; 121.2; 76.2; 72.7; 69.5; 42.7; 42.3; 38.1; 35.8; 31.4; 29.4; 24.9. HR-ESI-MS: 341.1730 ([M þ Na]þ,
C19H26NaOþ4 ; calc. 341.1729).
P. G. thanks CSIR, New Delhi for financial assistance.
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Received April 1, 2008