Stereoselective total synthesis of goniothalesdiol A via chiron approach

Article abstract of DOI:10.1002/hlca.200900342

The stereocontrolled synthesis of goniothalesdiol A, a dihydroxylated tetrahydropyran compound, has been accomplished using d-ribose as chiral precursor. The key steps involved are aryl Grignard reaction, stereoselective alkoxy-directed keto reduction, and intramolecular oxy-Michael addition.

Full text of DOI:10.1002/hlca.200900342

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Stereoselective Total Synthesis of Goniothalesdiol A via Chiron Approach
by Jhillu S. Yadav*, Ragam Nageshwar Rao, Ragam Somaiah, Valaboju Harikrishna, and
Basi V. Subba Reddy
Discovery Laboratory, Organic Chemistry Division-I, Indian Institute of Chemical Technology,
Hyderabad – 500007, India (phone: þ 91-40-27193535; fax: þ 91-40-27160512;
e-mail: yadavpub@iict.res.in)
The stereocontrolled synthesis of goniothalesdiol A, a dihydroxylated tetrahydropyran compound,
has been accomplished using d-ribose as chiral precursor. The key steps involved are aryl Grignard
reaction, stereoselective alkoxy-directed keto reduction, and intramolecular oxy-Michael addition.
Introduction. – Goniothalesdiol A (1) and goniothalesacetate, a new class of styryl
lactones [1], were isolated from the stems of a southern Taiwan tree Goniothalamus
amuyon. The styryl lactones and acetogenins are two major types of bioactive
compounds isolated from the Goniothalamus (Annonaceae) species. The structure and
relative configuration of 1 were determined on the basis of NMR spectroscopy, and the
absolute configuration was predicted by biosynthesis [2] (Fig.).
Figure. Chemical structures of goniothalesdiol A and goniothalesacetate
Recently, we have reported the first stereoselective total synthesis of goniotha-
lesdiol A [3] employing the Sharpless kinetic resolution to construct the stereogenic
center C(2) and the C(3)/C(4) syn-diol arrangement. In the present study, we wish to
report the stereocontrolled total synthesis of natural goniothalesdiol A utilizing
inexpensive and readily available d-ribose (2) via the chiron approach. The
retrosynthetic analysis is presented in Scheme 1. Our synthetic approach began with
enantiomerically pure d-ribose (2) which was converted into the pyran moiety through
a series of stereocontrolled chemical transformations, which include Grignard addition
and C1 Wittig reaction for extending a C-chain by incorporating the C¼C bond in the
final precursor, which in turn permits the intramolecular oxy-Michael reaction.
ꢀ 2010 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Scheme 1. Retrosynthetic Analysis of Goniothalesdiol A
Results and Discussion. – Our synthesis started with compound 3, which was
prepared from d-ribose (2) according to reported procedures [4][5]. The olefin
derivative 3 was converted to the corresponding primary alcohol 4 by hydroboration
with a dicyclohexyl borane – dimethyl sulfide (DMS) complex in dry THF, followed by
oxidation with H2O2 to give product 4 in 81% yield [6] (Scheme 2). The chemoselective
protection of 4 with benzyl bromide (BnBr) in the presence of NaH afforded benzyl
ether 5 in 97% yield. Deprotection of the (t-Bu)Me2Si (TBS) ether 5 using Bu4NF
(TBAF) gave the diol in 95% yield [4]. Oxidative cleavage of the diol with silica gel-
supported NaIO4 furnished the aldehyde 6 in 95% [7]. Addition of PhMgBr to the
aldehyde in Et2O gave the secondary alcohol 7 in 63% yield as inseparable mixture of
diastereoisomers [8]. To obtain the required diastereoisomer as the major product, 7
was oxidized with IBX (¼1-hydroxy-1l3,2-benziodoxol-3(1H)-one 1-oxide) in DMSO/
CH2Cl2 1:3 to give a keto product, which was subsequently subjected to stereoselective
alkoxy-directed keto reduction with Zn(BH4)2 in THF at ꢀ 208 to afford compound 8
as the major isomer in 57% yield in two steps [9]. The chiral precursor 8 was protected
as TBS ether 9 in 95% yield using (t-Bu)Me2SiCl (TBSCl) and 1H-imidazole. Oxidative
cleavage of 9 with DDQ gave the primary alcohol 10 in 95% yield. The Swern oxidation
of 10 gave the corresponding aldehyde in quantitative yield, which was further
subjected to Horner– Wadsworth – Emmons olefination with methyl (diethoxyphos-
phoryl)acetate ((EtO)2P(O)CH2COOMe) to furnish the a,b-unsaturated ester 11 in
93% yield [10]. Deprotection of the TBS ether with TBAF in dry THF at room
temperature afforded the hydroxy ester 12 in 95% yield. Compound 12 was treated
with TsOH in benzene at room temperature to form the pyran skeleton in 13 by means
of intramolecular oxy-Michael addition of OH at C(2) onto the (E)-configured
C(6)¼C(7) bond. Eventual deprotection of acetonide using TsOH in MeOH at room
temperature afforded the target molecule goniothalesdiol A (1) in 78% yield
(Scheme 2) [11].

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Scheme 2
a) BH3 – DMS (dimethyl sulfide), cyclohexene, then H2O2, 08 to r.t, 12 h; 81%. b) NaH, BnBr, Bu4NI
(TBAI), dry THF, reflux, 3 h; 97%. c) 1. Bu4NF (TBAF), dry THF; 95%; 2. NaIO4 – silica gel, CH2Cl2,
30 min, 95%. d) PhMgBr, THF, ꢀ 788 to r.t., overnight; 63% (inseparable mixture of diastereoisomers).
e) 1. 1-Hydroxy-1l3,2-benzodioxol-3(1H)-one 1-oxide (IBX), CH2Cl2/DMSO 3 :1, 180 – 2008, 12 h; 67%;
2. Zn(BH4)2, THF, ꢀ 208, 12 h; 85% (de 90%). f) (t-Bu)Me2SiCl (TBSCl), 1H-imidazole, CH2Cl2,
0 – 258, 4 h; 95%. g) 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), CH2Cl2, 258, 2 h; 95%. h) 1.
Oxalyl chloride, dry DMSO, dry CH2Cl2, ꢀ 788, Et3N; quant.; 2. (EtO)2P(O)CH2COOMe, tBuOK, THF,
ꢀ 78 to 08; 93% ((E)/(Z) 8 :1). i) TBAF, dry THF, 258, 2 h; 95%. j) TsOH, benzene, 4 h. k) TsOH,
MeOH, 258, 2 h; 78% (for 2 steps).
In conclusion, we have described a concise synthesis of goniothalesdiol A (1) from
d-ribose (2) in a highly stereoselective manner. Goniothalesdiol A has been
synthesized in nine steps using an oxy-Michael reaction for the construction of the

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cis-tetrahydropyran-2,6-diyl moiety. The two key reactions, i.e., a Grignard addition to
aldehyde 6, followed by a stereoselective alkoxy-directed keto reduction, are involved
in the formation of the precursor 8 as the major product, which is a key intermediate for
the total synthesis of goniothalesdiol A (1).
Experimental Part
General. Solvents were dried over standard drying agents and freshly distilled prior to use. The
reagents were purchased from Aldrich and Acros, and were used without further purification unless
otherwise stated. All moisture-sensitive reactions were carried out under N2. Org. solns. were dried over
anh. Na2SO4 and concentrated in vacuo below 408. Column chromatography (CC): silica gel (SiO2;
Acmeꢂs 60 – 120 mesh). Optical rotations: Horiba high sensitive polarimeter SEPA-300 at 258. IR
Spectra: Perkin-Elmer IR-683 spectrophotometer with NaCl optics. 1H- (200 and 300 MHz) and
13C-NMR (50 and 75 MHz) spectra: Varian Gemini FT-200 and Bruker Avance 300 instruments with
TMS as internal standard in CDCl3; J values in Hz. MS: Agilent Technologies 1100 Series (Agilent
Chemistation Software).
6-O-[(tert-Butyl)(dimethyl)silyl]-1,2-dideoxy-3,4-O-(1-methylethylidene)-d-ribo-hex-1-enitol (3).
To a stirred suspension of d-ribose (2; 8 g, 53.29 mmol) in acetone (100 ml) was added dropwise conc.
H2SO4 (0.24 ml) at r.t., and the mixture was stirred at r.t. for 3 h. The mixture was neutralized with solid
NaHCO3 (5 g), filtered, and evaporated under reduced pressure to give a colorless syrup. The resulting
syrup was purified by CC (SiO2; hexane/AcOEt 1:2) to give acetonide-protected ribose (9.42 g, 93%) as
a colourless syrup.
To a stirred soln. of acetonide-protected ribose (7.0 g , 36.8 mmol) in dry CH2Cl2 (50 ml) were added
1H-imidazole (6.26 g, 88.0 mmol) and TBSCl (6.44 g, 42.8 mmol) at r.t., and the mixture was stirred for
3 h at r.t. The reaction was quenched with ice-cold H2O, and the mixture was diluted with AcOEt. The
org. layer was extracted with AcOEt, and the org. layers were washed with brine, dried (Na2SO4), and
evaporated under reduced pressure. The resulting syrup was purified by CC (SiO2; hexane/AcOEt 7:3)
to give TBS protected ribose acetonide (10.0 g, 89%) as a colorless oil (9 :1 anomeric mixture).
To a mixture of methyl(triphenyl)phosphonium iodide (52 g, 130 mmol) and tBuOK (7.4 g, 64 mmol)
was added dry THF (240 ml), and the mixture was stirred at r.t. under N2 for 4 h. Then, the stirring was
stopped, and the solid was allowed to settle down. The clear supernatant orange-yellow liquid was
transferred into the soln. of TBS-protected ribose acetonide (10 g, 32 mmol) in dry THF (40 ml) at ꢀ 788.
The mixture was then slowly allowed to attain r.t. After 3 h, the reaction was quenched with crushed ice,
and the mixture was diluted with AcOEt. The org. layer was separated and dried (Na2SO4), filtered, and
evaporated under reduced pressure. The resulting syrup was purified by CC (SiO2; hexane/AcOEt 3 :2)
to give 3 (9.2 g, 82%). Pale-yellow syrup. [a]2D8 ¼ ꢀ3.5 (c ¼ 1.0, CHCl3). IR (neat): 3557, 2931, 2858, 1746,
1
1641, 1466, 1376, 1254, 1217, 1117, 1060, 838, 779, 671. H-NMR (300 MHz, CDCl3): 5.99 (ddd, J ¼ 6.0,
10.5, 17.0, 1 H); 5.38 (td, J ¼ 1.5, 17.0, 1 H); 5.23 (td, J ¼ 1.5, 10.5, 1 H); 4.64 (t, J ¼ 6.0, 1 H); 3.98 (dd, J ¼
6.7, 9.8, 1 H); 3.77 (dd, J ¼ 3.0, 9.8, 1 H); 3.71 – 3.52 (m, 2 H); 2.34 (d, J ¼ 6.0, 1 H); 1.44 (s, 3 H); 1.33 (s,
3 H); 0.91 (s, 9 H); 0.08 (s, 6 H). 13C-NMR (75 MHz, CDCl3): 134.2; 117.5; 108.7; 78.81; 77.4; 69.4; 64.4;
27.8; 25.4; 18.3. HR-ESI-MS: 325.1812 ([M þ Na]þ, C15H30NaO4Siþ; calc. 325.1811).
6-O-[(tert-Butyl)(dimethyl)silyl]-2-deoxy-3,4-O-(1-methylethylidene)-d-ribo-hexitol (4). To the stir-
red soln. of cyclohexene (12.03 ml, 11.9 mmol) in dry THF (15 ml) was added BH3 · DMS (5.65 ml,
59.6 mmol) dropwise at 08, and stirring was continued for 1 h at 08. At the same temp., a soln. of 3 in dry
THF (100 ml) was added to the mixture, and, after 1 h, the mixture was allowed to warm to r.t. and stirred
for further 12 h. The mixture was cooled to 08, then H2O2 (20 ml, 30%) and NaOH (20%, 63 ml) were
added, and the mixture was stirred for 4 h. Then, the mixture was extracted with AcOEt (2 ꢁ 500 ml).
The org. extracts were washed with H2O and brine, and dried (Na2SO4). Evaporation of the solvent,
followed by purification of the crude product by CC (SiO2; hexane/AcOEt 95 :5), afforded 4 (7.2 g,
81%). Pale liquid. [a]3D3 ¼ ꢀ18.1 (c ¼ 1.0, CHCl3). IR (neat): 3447, 2932, 2853, 1641, 1473, 1376, 1254,
1
1110, 1055, 835. H-NMR (300 MHz, CDCl3): 4.92 – 4.87 (m, 1 H); 4.40 – 4.29 (m, 2 H); 3.92 – 3.77 (m,
4 H); 2.28 (br. s, 1 H); 1.83 – 1.60 (m, 2 H); 1.45 (s, 3 H); 1.35 (s, 3 H); 0.90 (s, 9 H); 0.05 (s, 3 H); 0.04 (s,

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Helvetica Chimica Acta – Vol. 93 (2010)
3 H). 13C-NMR (50 MHz, CDCl3): 108.4; 75.7; 74.5; 72.1; 62.2; 60.5; 31.7; 27.7; 25.7; 25.5; 21.2; 18.5. HR-
ESI-MS: 343.4888 ([M þ Na]þ, C15H32NaO5Siþ; calc. 343.1917).
1-O-Benzyl-6-O-[(tert-butyl)(dimethyl)silyl]-2-deoxy-3,4-O-(1-methylethylidene)-d-ribo-hexitol
(5). To a mixture of NaH (0.55 g, 60 wt.-% in mineral oil, 13.7 mmol) in dry THF (80 ml) was added a
soln. of 4 (4 g, 12.5 mmol) in dry THF (20 ml) at 08. After 20 min, BnBr (1.65 ml, 13.7 mmol) was added,
and the stirring was continued for 2 h at r.t. The reaction was quenched by the addition of a sat. soln. of
NH4Cl (20 ml), and the mixture was extracted with AcOEt. The org. extracts were washed with H2O and
brine, and dried (Na2SO4). Evaporation of the solvent, followed by purification of the crude product by
CC (SiO2; hexane/AcOEt 95 :5) afforded 5 (4.97 g, 92%). Pale-yellow liquid. [a]3D3 ¼ ꢀ10 (c ¼ 0.5,
1
CHCl3). IR (neat): 3547, 2932, 2853, 1746, 1641, 1464, 1376, 1254, 1210, 1110, 1060, 838, 756. H-NMR
(300 MHz, CDCl3): 7.39 – 7.17 (m, 5 H); 4.83 (d, J ¼ 11.3, 1 H); 4.42 (d, J ¼ 11.3, 1 H); 4.31 – 4.23 (m,
1 H); 4.06 (dd, J ¼ 5.7, 9.0, 1 H); 3.99 (dd, J ¼ 1.9, 11.3, 1 H); 3.77 – 3.63 (m, 2 H); 3.49 (ddd, J ¼ 2.1, 5.1,
9.0, 1 H); 2.0 (br. s, 1 H); 1.79 – 1.64 (m, 2 H); 1.36 (s, 3 H); 1.24 (s, 2 H); 0.84 (s, 9 H); 0.01 (s, 6 H).
13C-NMR (50 MHz, CDCl3): 138.5; 128.3; 127.6; 108.0; 76.9; 72.7; 67.5; 64.5; 29.9; 28.2; 25.8; 25.7;18.3;
ꢀ 5.5; ꢀ 5.4. HR-ESI-MS: 433.6126 ([M þ Na]þ, C22H38NaO5Siþ; calc. 433.2386).
1-O-Benzyl-2-deoxy-3,4-O-(1-methylethylidene)-5-C-phenyl-d-erythro-pentitol (7). To a well-stirred
soln. of 5 (4.5 g, 10.9 mmol) in anh. THF (50 ml) was added 1m Bu4NF (13.2 ml, 13.2 mmol) at 08. Then,
the reaction was quenched with ice flakes, and the mixture was concentrated under reduced pressure. The
mixture was extracted with AcOEt (3 ꢁ 50 ml). The combined org. layers were washed with H2O and
brine, and dried (Na2SO4). After removing the volatiles under reduced pressure, the crude product was
purified by CC (SiO2; hexane/AcOEt 85 :15) to afford the pure vicinal diol (3.06 g, 95%). Colorless
liquid. [a]3D3 ¼ þ4.8 (c ¼ 0.15, CHCl3). IR (neat): 3650, 3554, 2952, 1744, 1464, 1377, 1254, 1210, 1060, 840,
1
757. H-NMR (300 MHz, CDCl3): 7.41 – 7.26 (m, 5 H); 4.67 (d, J ¼ 11.7, 1 H); 4.48 (d, J ¼ 10.7, 1 H);
4.41 – 4.35 (m, 1 H); 4.21 (dd, J ¼ 5.8, 8.8, 1 H); 3.93 (dd, J ¼ 3.9, 11.7, 1 H); 3.84 (dd, J ¼ 1.9, 11.7, 1 H);
3.82 – 3.71 (m, 2 H); 3.57 – 3.52 (m, 1 H); 2.05 (br. d, J ¼ 14.6, 1 H); 1.84 – 1.76 (m, 2 H); 1.44 (s, 3 H); 1.35
(s, 2 H). 13C-NMR (50 MHz, CDCl3): 138.6; 128.5; 128.4; 127.7; 108.1; 76.8; 72.7; 71.1; 67.4; 64.3; 29.8;
28.0; 25.8; 25.7. HR-ESI-MS: 297.5447 ([M þ H]þ, C16H24O5þ ; calc. 297.5449).
NaIO4 (25.7 g, 120.0 mmol) was dissolved in 50 ml of hot H2O (708) in a 250-ml round-bottomed
flask. To the hot soln. was added SiO2 (230 – 400 mesh, 100 g) with vigorous swirling and shaking. The
resulting SiO2 coated with NaIO4 was in a powder form and was free-flowing. The reagent can be kept in
a bottle for 1 month with negligible loss of activity. To a vigorously stirred suspension of SiO2-supported
NaIO4 reagent (23.6 g) in CH2Cl2 (75 ml) in a 25-ml round-bottomed flask was added a soln. of the vicinal
diol (3.5 g, 11.8 mmol) in CH2Cl2 (75 ml). The reaction was monitored by TLC until disappearance of the
starting material (generally 10 – 30 min). The mixture was filtered through a sintered glass funnel, and
the filter cake was thoroughly washed with CHCl3 (45 – 150 ml). Removal of solvents from the filtrate
afforded the aldehyde 6, which was directly used for the next reaction.
A suspension of PhMgBr was generated in situ with Mg turnings (0.95 g, 39 mmol) and PhBr
(2.78 ml, 26 mmol) in dry THF at r.t. under N2. Then, a soln. of 6 (3.5 g, 13 mmol) in THF (15 ml) was
added slowly at ꢀ 788 under inert atmosphere. After 2 h, the mixture was warmed to r.t. and left
overnight until completion of the reaction, and then the reaction was quenched by addition of sat. aq.
NH4Cl (25 ml), and the mixture extracted with AcOEt (3 ꢁ 100 ml). The combined org. layers were
washed with H2O and brine, and dried (Na2SO4). Removal of solvent, followed by CC (SiO2; hexane/
AcOEt 95 :5) gave 7 (3.0 g, 63%). Colorless oil. IR (neat): 3434, 2924, 2855, 1718, 1603, 1492, 1455, 1377,
1
1205, 1074, 889, 755. H-NMR (300, CDCl3): 7.42 – 7.22 (m, 10 H); 4.58 – 4.53 (m, 1 H); 4.53 (s, 2 H);
3.93 – 3.7 (m, 1 H); 3.68 – 3.55 (m, 2 H); 3.30 – 3.20 (m, 1 H); 2.85 (d, J ¼ 9.0, 1 H); 2.20 – 1.92 (m, 1 H);
1.90 – 1.76 (m, 1 H); 1.56 (s, 3 H); 1.39 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 139.3; 137.5; 128.3; 127.7;
127.4; 127.1; 98.8; 73.0; 72.5; 66.6; 34.1; 29.6. HR-ESI-MS: 365.1731 ([M þ Na]þ, C21H26NaO4þ ; calc.
365.1728).
(5R)-1-O-Benzyl-2-deoxy-3,4-O-(1-methylethylidene)-5-C-phenyl-d-erythro-pentitol (8). To a stir-
red soln. of IBX (4.6 g, 16.4 mmol) in DMSO (2.33 ml, 32.8 mmol) was added 7 (3.0 g, 8.21 mmol) in anh.
CH2Cl2 (50 ml) dropwise at r.t. The mixture was kept under reflux at 180 – 2008 for 12 h; then it was
cooled to r.t., extracted with Et2O (3 ꢁ 100 ml), and filtered through a Celite pad. The filtrate was washed
with sat. NaHCO3 and brine. The org. layer was dried (Na2SO4). The evaporation of solvent, followed by

Helvetica Chimica Acta – Vol. 93 (2010)
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purification of the crude product by flash-CC (SiO2; hexane/AcOEt 6 :4) yielded the pure ketone (2 g,
67%), which was directly used for the next reaction.
A soln. of ketone (2.0 g, 7.25 mmol), obtained from the oxidation of alcohol 7 (2 g, 7.25 mmol) in
THF (20 ml) under N2, was cooled to ꢀ 208, and Zn(BH4)2 (2.8 ml of a 2m soln. in THF, 5.45 mmol) was
added slowly during 10 min. After stirring for 12 h at the same temp., the reaction was quenched by
addition of sat. aq. NH4Cl. The resulting mixture was extracted with AcOEt. The combined org. layers
were washed with brine, dried (Na2SO4), and evaporated in vacuo. The residue was subjected to CC
(SiO2; hexane/AcOEt 9 :1) to give 8 (1.68 g, 85%). Colorless oil. [a]2D5 ¼ ꢀ51.4 (c ¼ 0.7, CHCl3). IR
(neat): 3434, 2924, 2855, 1718, 1603, 1492, 1455, 1377, 1205, 1074, 889, 755. 1H-NMR (300 MHz, CDCl3):
7.42 – 7.23 (m, 10 H); 4.56 (d, J ¼ 3.0, 1 H); 4.53 (s, 2 H); 3.92 – 3.80 (m, 1 H); 3.69 – 3.56 (m, 2 H); 3.30 –
3.20 (t, J ¼ 9.1, 1 H); 2.93 (d, J ¼ 2.3, 1 H); 2.0 – 1.90 (m, 1 H); 1.90 – 1.77 (m, 1 H); 1.60 (s, 3 H); 1.40 (s,
3 H). 13C-NMR (75 MHz, CDCl3): 139.3; 137.5; 128.3; 127.7; 127.4; 127.1; 98.8; 73.0; 72.5; 66.6; 34.1; 29.6.
HR-ESI-MS: 365.1729 ([M þ Na]þ, C21H26NaOþ4 ; calc. 365.1728).
(5R)-1-O-Benzyl-5-O-[(tert-butyl)(dimethyl)silyl]-2-deoxy-3,4-O-(1-methylethylidene)-5-C-phenyl-
d-erythro-pentitol (9). To a stirred soln. of 8 (1.50 g, 4.37 mmol) and 1H-imidazole (0.357 g, 5.25 mmol)
in anh. CH2Cl2 (800 ml) was added TBSCl (0.65 g, 4.8 mmol) dropwise at 08, and stirring was continued
for 4 h at r.t. The reaction was quenched with ice flakes, and the mixture was extracted with CH2Cl2 (3 ꢁ
500 ml). The combined org. layers were washed with H2O and brine, and dried (Na2SO4). Removal of
solvent, followed by CC (SiO2; hexane/AcOEt 95 :5), furnished 9 (1.89 g, 95%). Colorless liquid. [a]D31
¼
ꢀ4.1 (c ¼ 1, CHCl3). IR (neat): 3031, 2925, 2854, 1719, 1603, 1452, 1377, 1205, 1075, 899, 755. 1H-NMR
(300 MHz, CDCl3): 7.26 – 7.19 (m, 10 H); 4.53 (s, J ¼ 8.7, 1 H); 4.47 (s, 2 H); 4.28 (qd, J ¼ 2.3, 5.5, 1 H);
4.32 – 4.24 (m, 1 H); 4.11 (dd, J ¼ 5.5, 8.5, 1 H); 3.66 – 3.52 (m, 2 H); 2.12 – 2.02 (m, 1 H); 1.86 – 1.74 (m,
1 H); 1.28 (s, 3 H); 1.15 (s, 3 H); 0.78 (s, 9 H); ꢀ 0.5 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 141.6; 140.5;
128.4; 127.7; 126.7; 108.5; 85.4; 77.4; 74.0; 72.5; 69.0; 34.3; 29.7; 27.2; 26.3; 18.5; ꢀ 4.4. HR-ESI-MS:
479.2592 ([M þ Na]þ, C27H40NaOþ4 ; calc. 479.2596).
(5R)-5-O-[(tert-Butyl)(dimethyl)silyl]-2-deoxy-3,4-O-(1-methylethylidene)-5-C-phenyl-d-erythro-
pentitol. (10). To a stirred soln. of 9 (1.75 g, 3.85 mmol) in 9 :1 CH2Cl2 (18 ml) and H2O (2 ml) was added
DDQ (6.75 g, 15.35 mmol) at 08. The mixture was stirred at r.t. for 4 h. The reaction was quenched with
NaHCO3, and the aq. layer was extracted with AcOEt (3 ꢁ 100 ml). The combined org. layer were
washed with brine and dried (Na2SO4). Removal of solvent followed by CC (SiO2; hexane/AcOEt
85 :15) afforded 10 (1.33 g, 95% yield). Colorless liquid. [a]3D1 ¼ þ28 (c ¼ 0.25, CHCl3). IR (neat): 3448,
1
2925, 2854, 1604, 1455, 1375, 1072, 895, 763. H-NMR (300 MHz, CDCl3): 7.38 – 7.25 (m, 5 H); 4.48 (d,
J ¼ 8.56, 1 H); 3.95 (td, J ¼ 2.4, 8.6, 1 H); 3.83 – 3.71 (m, 2 H); 3.38 (t, J ¼ 8.6, 1 H); 2.35 (br. d, 1 H);
2.11 – 1.94 (m, 1 H); 1.76 – 1.56 (m, 1 H); 1.62 (s, 3 H); 1.46 (s, 3 H); 0.75 (s, 9 H); 013 (s, 3 H); ꢀ 0.97 (s,
3 H). 13C-NMR (75 MHz, CDCl3): 137.8; 128.3; 127.5; 126.7; 109.2; 85.4; 78.4; 61.2; 34.3; 27.6; 27.4; 26.2;
18.5; ꢀ 4.5. HR-ESI-MS: 389.2125 ([M þ Na]þ, C20H34NaO4Siþ; calc 389.2124).
Methyl (2E)-4-{(4S,5S)-5-[(R)-{[(tert-Butyl)(dimethyl)silyl]oxy}(phenyl)methyl]-2,2-dimethyl-1,3-
dioxolan-4-yl}but-2-enoate (11). To a stirred soln. of oxalyl chloride (0.3 ml, 3.56 mmol) in dry CH2Cl2
(15 ml) was added DMSO (0.33 ml, 4.64 mmol) in dry CH2Cl2 (10 ml) dropwise at ꢀ 788. The mixture
was stirred for 15 min at the same temp. To this mixture was added dropwise a soln. of 10 (1.0 g,
2.73 mmol) in dry CH2Cl2 (10 ml), and stirring was continued for another 1 h at ꢀ 788. Then, Et3N
(2.28 ml, 16.4 mmol) was added to the mixture, and the mixture was warmed to r.t. After addition of H2O
(50 ml), the layers were separated, and the aq. layer was extracted with CH2Cl2 (3 ꢁ 50 ml). The
combined org. layers were washed with H2O and brine, dried (Na2SO4), and concentrated in vacuo. The
resulting residue (quant. yield) was used directly for the next step.
(EtO)2P(O)CH2COOMe (0.8 g, 8.3 mmol) was added to a suspension of tBuOK (0.47 g, 4 mmol) in
THF (10 ml) at 08 under N2. After stirring at r.t. for 30 min, the soln. was cooled to ꢀ 788, and a soln. of
aldehyde (0.8 g, 2 mmol) in THF (5 ml), obtained from 10, was added. After 30 min, the mixture was
allowed to warm to 08 and stirred for another 30 min. Then, the reaction was quenched with sat. aq.
NH4Cl (8 ml) and extracted with AcOEt (3 ꢁ 30 ml), washed with brine, and dried (Na2SO4). Filtration
and evaporation of the solvent in vacuo furnished the crude 11 (0.79 g, 93%), which was subjected to CC
(SiO2; hexane/AcOEt 9 :1). [a]2D5 ¼ ꢀ53 (c ¼ 0.3, CHCl3). IR (neat): 2925, 2854, 1727, 1657, 1463, 1437,
1
1381, 1261, 1165, 1095, 864, 836, 778. H-NMR (300 MHz, CDCl3): 7.37 – 7.20 (m, 5 H); 7.00 – 6.87 (m,

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Helvetica Chimica Acta – Vol. 93 (2010)
1 H); 5.83 (d, J ¼ 15.8, 1 H); 4.43 (d, J ¼ 9.0, 1 H); 3.80 – 3.65 (m, 1 H); 3.70 (s, 3 H); 3.31 (t, J ¼ 9.0,
1 H); 2.70 – 2.60 (m, 1 H); 2.28 – 2.15 (m, 1 H); 1.54 (s, 3 H); 1.34 (s, 3 H); 0.73 (s, 9 H); 0.14 (s, 3 H); 0.04
(s, 3 H). 13C-NMR (75 MHz, CDCl3): 145.7; 128.7; 128.3; 122.7; 78.1; 73.8; 73.1; 34.8; 29.4; 25.8; 19.4;
ꢀ 4.1; ꢀ 5.7. HR-ESI-MS: 443.2228 ([M þ Na]þ, C23H36NaO5Siþ; calc 443.2229).
Methyl (2E)-4-{(4S,5R)-5-[(R)-Hydroxy(phenyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl}but-2-
enoate (12). To a well-stirred soln. of 11 (0.7 g, 1.58 mmol) in anh. THF (15 ml) was added 1m Bu4NF
(1.9 ml, 1.9 mmol) at 08. Then, the reaction was quenched with ice flakes, and the mixture was
concentrated under reduced pressure. The mixture was extracted with AcOEt (3 ꢁ 50 ml). The combined
org. layers were washed with H2O and brine, and dried (Na2SO4). After removing the volatiles under
reduced pressure, the crude product was purified by CC (SiO2; hexane/AcOEt 85 :15) to afford 12
(0.49 g, 95%). Colorless liquid. [a]3D1 ¼ þ8.4 (c ¼ 0.4, CHCl3). IR (neat): 3434, 2924, 1728, 1657, 1464,
1437, 1380, 1260, 1166, 1096, 865, 836, 778. 1H-NMR (300 MHz, CDCl3): 7.36 – 7.20 (m, 5 H); 6.98 – 6.88
(m, 1 H); 5.83 (d, J ¼ 15.8, 1 H); 4.20 (d, J ¼ 4.5, 1 H); 4.15 – 4.08 (m, 1 H); 3.90 – 3.86 (m, 1 H); 3.70 (s,
3 H); 2.70 – 2.62 (m, 1 H); 2.28 – 2.16 (m, 1 H); 1.54 (s, 3 H); 1.36 (s, 3 H). 13C-NMR (75 MHz, CDCl3):
168.0; 145.8; 141.1; 128.3; 122.9; 78.1; 73.8; 73.1; 52.0; 34.8; 29.4. HR-ESI-MS: 329.1359 ([M þ Na]þ,
C17H22NaO5Siþ; calc 329.1360).
Goniothalesdiol A (¼ Methyl (7R)-3,7-Anhydro-2,4-dideoxy-7-phenyl-d-ribo-heptonate; 1). To a
stirred soln. of 12 (0.3 g, 0.51 mmol) in benzene (4 ml) was added TsOH (0.03g, 0.1 mmol). The mixture
was stirred at r.t. for 3 h, and the solvent was removed under reduced pressure. The crude residue 13 was
dissolved in 2 ml MeOH, and TsOH was added; the resulting mixture was stirred overnight at r.t. The
solvent was removed under reduced pressure. The crude residue was subjected to CC (SiO2; hexane/
AcOEt 6 :4) to afford 1 (0.15 g, 78%). White solid. M.p. 928. [a]2D7 ¼ ꢀ27 (c ¼ 0.3, CHCl3). IR (neat):
1
3405, 2918, 2848, 2373, 1730, 1435, 1200, 1170, 1068. H-NMR (300 MHz, CDCl3): 7.40 – 7.28 (m, 5 H);
4.54 (d, J ¼ 9.8, 1 H); 4.45 – 4.35 (m, 1 H); 4.24 – 4.19 (m, 1 H); 3.68 (s, 3 H); 3.49 (dd, J ¼ 9.8, 3.0, 1 H);
2.61 (dd, J ¼ 15.1, 7.5, 1 H); 2.45 (dd, J ¼ 15.1, 6.0, 1 H); 2.11 (ddd, J ¼ 13.5, 3.0, 2.2, 3 H); 1.76 (ddd, J ¼
12.0, 3.0, 2.2, 1 H); 1.40 (s, 1 H). 13C-NMR (75 MHz, CDCl3): 171.3; 139.2; 128.4; 128.2; 127.3; 77.7; 72.6;
68.4; 67.0; 51.6; 40.3; 37.1. HR-ESI-MS: 267.1228 ([M þ H]þ, C14H19O5þ ; calc. 267.1232).
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Received September 24, 2009