Total synthesis of a mevinic acid analog

Article abstract of DOI:10.1002/hlca.201000062

Total synthesis of mevinic acid analog 1 has been achieved efficiently starting from chiral 2,3-O-isopropylidene-D-glyceraldehyde (2). The synthesis involves Mitsunobu reaction and Evans' intramolecular oxa-Michael syn-addition reactions as key steps. Cop

Full text of DOI:10.1002/hlca.201000062

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Total Synthesis of a Mevinic Acid Analog
by Thummalapally Srikanth Reddy, Dorigondla Kumar Reddy, Manchala Narasimhulu, Dasari Ramesh,
and Yenamandra Venkateswarlu*
Natural Products Laboratory, Organic Chemistry Division – I, Indian Institute of Chemical Technology,
Hyderabad – 500007, India (phone: þ 91-40-27193167; fax: þ 91-40-27160512;
e-mail: luchem@iict.res.in)
Total synthesis of mevinic acid analog 1 has been achieved efficiently starting from chiral 2,3-O-
isopropylidene-d-glyceraldehyde (2). The synthesis involves Mitsunobu reaction and Evansꢀ intra-
molecular oxa-Michael syn-addition reactions as key steps.
Introduction. – Fungal metabolites such as mevinic acid derivatives mevinoline
(A), compactin (B), and simvastatin (C) are potent inhibitors of 3-hydroxy-3-
methylglutayl coenzyme A (HMGCo A) reductase [1]. The enzyme reduces
cholesterol levels in blood by involving in the rate-limiting step of cholesterol
biosynthesis in humans. The simplified structural analog of these inhibitors is b-
hydroxy-d-lactone, which is essential for biological activity [2]. b-Hydroxy-d-lactone is
the common structural feature of all mevinic acids [3]. The lactone moiety, in its
(4R,6R)-configuration, closely resembles the HMG portion of the enzyme and acts as
inhibitor by blocking the enzyme [4]. Thus, the synthesis of many analogs of the lactone
has been reported in literature [5]. In continuation of our interest in synthesis of
biologically active natural products [6], here we report an efficient and practical total
synthesis of mevinic acid analogue 1 from commonly available d-mannitol.
Our planned approach to mevinic acid analogue 1 involved Mitsunobu reaction and
Evansꢀ intramolecular oxa-Michael syn-addition reaction as the chirality-transferring
steps starting from commonly available d-mannitol (Scheme 1).
Results and Discussion. – The synthesis of mevinic acid analogue 1 (Scheme 2) was
started from the readily available d-mannitol diacetonide, which was oxidized
ꢁ 2010 Verlag Helvetica Chimica Acta AG, Zꢂrich

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Scheme 1. Retrosynthetic Approach to Mevinic Acid Analog
Scheme 2
a) [Ph3PCH2Ph]Br (1 equiv.), BuLi (1 equiv.), THF, 08, 2 h; 90%. b) H2, 10% Pd/C, MeOH, r.t., 6 h;
98%. c) 2m HCl, MeOH, 1 h, r.t.; 95%. d) PPh3 (2 equiv.), Diisopropyl azodicarboxylate (DIAD; 2
equiv.), 4-NO2ꢀC6H4COOH (2 equiv.), THF, r.t., 2 h; 93%. e) Cat. Na, MeOH, r.t., 1 h; 94%. f) TsCl
(1.1 equiv.), Bu2SnO (0.1 equiv.), Et3N (2.5 equiv.), 08 to r.t., 4 h; 76%. g) KCN (1.5 equiv.), r.t.,
12 h; 87%. h) (t-Bu)Ph2SiCl (TBDPS-Cl; 1 equiv.), 1H-imidazole (2.5 equiv.), dry CH2Cl2; 96%.
i) 1. Diisobutylaluminum hydride (DIBAL-H;
1
equiv.), dry CH2Cl2, ꢀ 788, 0.5 h; 71%; 2.
Ph3P¼CHCOOEt, benzene, reflux, 1 h. j) Bu4NF (TBAF), THF, 30 min; 83%. k) PhCHO, t-BuOK,
THF, pH 7 buffer, 1 h; 51%. l) 80% aq. AcOH, 608, 4 h; TsOH, CH2Cl2, 4 h; 61%.
following a known procedure [7], to give (R)-2,3-O-isopropylidene-d-glyceraldehyde
(2), which was subjected to a Wittig reaction to give compound 3 in 90% yield.

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Hydrogenation of compound 3 on 10% Pd/C in MeOH gave acetonide 4, followed on
treating with 2n HCl in MeOH, to afford diol 5 in 95% yield. At this stage, the
stereogenic center of the secondary OH group in 5 was inverted by a Mitsunobu
reaction1) [9] to give diol 7 in order to match the configuration at C(6) in compound 1.
The primary OH group in 7 was protected with TsCl using Et3N and a catalytic amount
of Bu2SnO to give tosylated compound 8 in 76% yield with minor tosylation at the
secondary OH group of 7 [10]. p-Toluenesulfonate 8 was converted to the
corresponding nitrile 9 in 87% yield by reaction with KCN in EtOH/H2O 3 :2 at room
temperature. The secondary OH group in 9 was protected with (t-Bu)Ph2SiCl (TBDPS-
Cl)/1H-imidazole to give TBDPS ether 10 in 96% yield. The CN function was reduced
with DIBAL-H in dry CH2Cl2 at ꢀ 788 to afford the aldehyde in 71% yield, which was
just subjected to a C2-Wittig reaction using Ph3P¼CHCOOEt to afford 11 (E/Z 95 :5)
as colorless syrup. The geometrical isomers were separated with a silica-gel column to
give the pure (E)-form in 76% yield. The TBDPS group in 11 was removed using
Bu4NF (TBAF) to afford homoallylic alcohol 12 in 83% yield. Later, the homoallylic
alcohol was subjected to Evansꢀ intramolecular oxa-Michael syn-addition reaction
using PhCHO and t-BuOK at 08 in anhydrous THF to furnish benzylidene acetal 13 in
51% yield [11]. Finally, 13 on treatment with 80% aqueous AcOH and TsOH, afforded
lactone 1 in 61% yield. The physical ([a]2D5 ¼ þ46.8 (c ¼ 0.7, CHCl3)) and spectroscopic
data (1H- and 13C-NMR) of 1 were in good agreement with those reported for
compound 1 [5].
In conclusion, an efficient and practical total synthesis of a mevinic acid analogue, 1,
has been achieved involving Mitsunobu reaction and Evansꢀ intramolecular oxa-
Michael syn-addition reaction as key steps starting from commonly available d-
mannitol. The protocol described here has significant potential for the synthesis of a
variety of other biologically important substituted b-hydroxy-d-lactones.
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. solvents were dried
over anh. Na2SO4 and concentrated in vacuo below 408. All column chromatographic (CC) separations
were performed using silica gel (SiO2; Acmeꢀs 60 – 120 mesh). Optical rotations: Horiba high-sensitive
polarimeter SEPA-300 at 258. IR Spectra: Perkin-Elmer IR-683 spectrophotometer with NaCl optics. 1H-
(300 MHz) and 13C-NMR (75 MHz) spectra: Bruker-Avance-300 instrument with TMS as internal
standard in CDCl3; J values are given in Hz. MS: Agilent Technologies 1100 Series (Agilent Chemistation
Software).
(4S)-2,2-Dimethyl-4-[(E)-2-phenylethenyl]-1,3-dioxolane (3). To a suspension of [Ph3PCH2Ph]Br
(9.96 g, 23.03 mmol) in dry THF (100 ml) was added BuLi (1.6m in hexane; 14.16 ml, 22.65 mmol) at 08
and stirred for 15 min. Then, a soln. of ketal 2 (3 g, 23.07 mmol) in THF (20 ml) was added dropwise, and
the mixture was stirred for an additional 0.5 h at 08. After completion, the reaction was quenched with
sat. NH4Cl soln. (30 ml), and the mixture was extracted with Et2O (3 ꢁ 30 ml). The Et2O soln. was
washed with brine and dried (Na2SO4). After removal of the solvent, the crude product was purified by
flash CC (hexane/AcOEt 98 :2) to afford pure 3 (4.24 g, 90%). [a]2D5 ¼ þ3.2 (c ¼ 1, CHCl3). IR (neat):
3062, 3024, 2986, 2929, 2860, 1610, 1498, 1296, 1060. 1H-NMR: 7.38 – 7.23 (m, 5 H); 6.67 (d, J ¼ 11.8, 1 H);
1
)
For a review on the Mitsunobu reaction, see [8].

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5.67 (dd, J ¼ 8.0, 11.8, 1 H); 4.83 – 4.71 (m, 1 H); 3.71 (t, J ¼ 8.0, 1 H); 3.53 (t, J ¼ 8.0, 1 H); 1.46 (s, 3 H);
1.38 (s, 3 H). 13C-NMR: 136.1; 133.2; 128.4; 127.8; 126.3; 126.6; 109.8; 77.0; 69.3; 26.6; 25.7. LC/MS: 227
([M þ Na]þ).
(4S)-2,2-Dimethyl-4-(2-phenylethyl)-1,3-dioxolane (4). To a soln. of 3 (4.10 g, 20.09 mmol) in MeOH
(30 ml) was added 10% Pd/C (0.33 g) and stirred under H2 for 6 h at r.t. After completion of the reaction,
the catalyst was removed by filtration, the solvent was evaporated, and the crude product was purified by
flash CC (hexane/AcOEt 50 :1) to afford 4 (4.05 g, 98%). Colorless oil. [a]2D5 ¼ ꢀ4.6 (c ¼ 1.2, CHCl3). IR
(neat): 3059, 3028, 2934, 2860, 1615, 1478, 1216, 1061, 968, 753. 1H-NMR: 7.25 – 7.12 (m, 5 H); 4.08 – 3.99
(m, 1 H); 3.94 (t, J ¼ 7.5, 1 H); 3.46 (t, J ¼ 7.5, 1 H); 2.80 – 2.57 (m, 2 H); 1.97 – 1.71 (m, 2 H); 1.39 (s,
3 H); 1.32 (s, 3 H). 13C-NMR: 141.5; 128.37; 128.32; 125.9; 108.7; 75.3; 69.3; 35.3; 31.9; 26.9; 25.6. LC/MS:
207 ([M þ H]þ).
(2S)-4-Phenylbutane-1,2-diol (5). To a soln. of 4 (3.9 g, 18.93 mmol) in MeOH (30 ml) was added
HCl (2m, 10 ml), and the mixture was stirred for 1 h at r.t. After completion of the reaction, the mixture
was neutralized with solid K2CO3, MeOH was removed, and the mixture was diluted with H2O (15 ml)
and extracted with AcOEt (3 ꢁ 30 ml). The combined org. layer was dried (Na2SO4), and the solvent was
removed under vacuum to obtain crude 5, which was purified by flash CC (hexane/AcOEt 1:1) to afford
5 (2.98 g, 95%). Colorless oil. [a]2D5 ¼ ꢀ31.8 (c ¼ 1, CHCl3). IR (neat): 3425, 3028, 2985, 2930, 1637, 1608,
1
1486, 1453. H-NMR: 7.26 – 7.14 (m, 5 H); 4.02 (br. s, 2 H); 3.67 – 3.56 (m, 2 H); 3.43 – 3.37 (m, 1 H);
2.81 – 2.57 (m, 2 H); 1.75 – 1.64 (m, 2 H). 13C-NMR: 141.6; 128.33; 128.31; 125.8; 71.5; 66.5; 34.5; 31.7. LC/
MS: 189 ([M þ Na]þ).
(2R)-4-Phenylbutane-1,2-diyl Bis(4-nitrobenzoate) (6). To a stirred soln. of PPh3 (8.84 g,
33.73 mmol), 5 (2.8 g, 13.91 mmol), and 4-nitrobenzoic acid (5.63 g, 33.73 mmol) in dry THF (50 ml)
was added DIAD (95%, 6.62 ml, 33.73 mmol) dropwise at 08. The mixture was stirred for 2 h at r.t. After
the completion of reaction, the mixture was diluted with H2O (20 ml) and extracted with AcOEt (3 ꢁ
30 ml). The combined org. layer was washed with NaHCO3 and brine solns., and dried (Na2SO4).
Evaporation of the solvent gave a crude product, which was purified by flash CC (hexane/AcOEt 9 :1), to
afford 6 (7.27 g, 93%). Light yellow viscous liquid. [a]2D5 ¼ ꢀ6.3 (c ¼ 1, CHCl3). IR (neat): 3028, 2978,
1734, 1715, 1528, 1336, 1278. 1H-NMR: 8.31 – 8.24 (m, 4 H); 8.20 – 8.12 (m, 4 H); 7.28 – 7.15 (m, 5 H); 5.55
(m, 1 H); 4.65 (dd, J ¼ 3.2, 12.0, 1 H); 4.52 (dd, J ¼ 6.9, 12.0, 1 H); 2.63 (t, J ¼ 7.5, 2 H); 1.92 – 1.76 (m,
2 H). 13C-NMR: 164.2; 164.1; 150.5; 141.8; 135.1; 134.8; 130.6; 128.2; 125.7; 123.5; 73.0; 66.2; 32.4; 30.8.
LC/MS: 464 (Mþ).
(2R)-4-Phenylbutane-1,2-diol (7). To a soln. of 6 (7.1 g, 15.30 mmol) in MeOH (50 ml) was added
Na (0.07 g, 3.06 mmol), and the mixture was stirred for 1 h. After completion of the reaction, solid NH4Cl
(0.5 g) was added to the mixture, and MeOH was removed under vacuum, and the mixture was diluted
with H2O (50 ml), extracted with AcOEt (3 ꢁ 25 ml), washed with brine, dried (Na2SO4), and
evaporated. The crude product was purified by flash CC (hexane/AcOEt 1:1), to afford 7 (2.18 g, 94%).
Colorless oil. Its spectroscopic data were identical to those of 5, except that the optical rotation value was
opposite.
(2R)-2-Hydroxy-4-phenylbutyl 4-Methylbenzenesulfonate (8). To an ice-cold soln. of 7 (2.2 g,
13.2 mmol), cat. amount of Bu2SnO (0.005 g), and Et3N (4.5 ml, 33 mmol) in dry CH2Cl2 (20 ml) was
added dropwise a soln. of TsCl (2.52 g, 13.2 mmol) in CH2Cl2 (10 ml), and the mixture was stirred for 4 h
at r.t. After completion of reaction, the mixture was diluted with H2O and extracted with CH2Cl2 (3 ꢁ
30 ml). The org. layer was washed with brine soln., dried (Na2SO4), and concentrated under reduced
pressure to yield the crude residue, which was purified by CC (hexane/AcOEt 7:3) to afford 8 (3.22 g,
76%). Viscous liquid. IR (neat): 3445, 3063, 2933, 2858, 1636, 1454, 1358, 1212, 1083, 699. 1H-NMR: 7.75
(d, J ¼ 8.6, 2 H); 7.30 (d, J ¼ 8.6, 2 H); 7.22 – 7.08 (m, 5 H); 4.02 – 3.75 (m, 3 H); 2.83 – 2.54 (m, 2 H); 2.44
(s, 3 H); 1.75 – 1.63 (m, 2 H). 13C-NMR: 145.0; 141.0; 132.5; 129.9; 128.4; 128.3; 127.9; 126.0; 73.8; 68.6;
34.1; 31.3; 21.6. LC/MS: 320 (Mþ).
(3R)-3-Hydroxy-5-phenylpentanenitrile (9). To a cooled (08) soln. of 8 (3.1 g, 9.56 mmol) in 60% aq.
EtOH (50 ml) was added KCN (0.94 g, 14.46 mmol). The mixture was stirred at r.t. for 12 h. After
completion of the reaction, the solvent was removed under vacuum, and the mixture was diluted with
H2O (20 ml), extracted with AcOEt (3 ꢁ 30 ml). The combined org. layer was washed with brine, dried
(Na2SO4), and the solvent was removed under reduced pressure to obtain crude product, which was

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purified by flash CC (hexane/AcOEt 7:3) to afford 9 (1.47 g, 87%). Colorless solid. [a]2D5 ¼ ꢀ21.3
(c ¼ 1.5, CHCl3). IR (neat): 3454, 3061, 2954, 2252, 1634, 1492. 1H-NMR: 7.32 – 7.18 (m, 5 H); 3.98 – 3.90
(m, 1 H); 2.86 – 2.66 (m, 2 H); 2.45 (t, J ¼ 4.9, 2 H); 2.08 (br. s, 1 H); 1.95 – 1.86 (m, 2 H). 13C-NMR:
140.6; 128.5; 128.3; 126.2; 117.5; 66.9; 37.8; 31.5; 26.2. LC/MS: 176 ([M þ H]þ).
(3R)-3-{[(tert-Butyl)(diphenyl)silyl]oxy}-5-phenylpentanenitrile (10). To a stirred soln. of 9 (1.3 g,
7.42 mmol) and 1H-imidazole (1.51 g, 22.28 mmol) in CH2Cl2 (20 ml) at 08 was added (t-Bu)Ph2SiCl
(1.92 ml, 7.40 mmol) dropwise. After completion of the reaction, the mixture was diluted with H2O
(10 ml) and extracted with CH2Cl2 (3 ꢁ 15 ml). The org. layer was washed with brine soln. (10 ml) and
dried (Na2SO4). The solvent was removed under vacuum to furnish the crude residue, which was purified
by flash CC (hexane/AcOEt 9 :1) to afford 10 (2.94 g, 96%). Colorless oil. [a]2D5 ¼ þ4.2 (c ¼ 1, CHCl3).
IR (neat): 3085, 3026, 2925, 2858, 2250, 1635, 1496, 1464, 1255. 1H-NMR: 7.70 – 7.64 (m, 5 H); 7.47 – 7.35
(m, 5 H); 7.23 – 7.11 (m, 5 H); 3.98 – 3.92 (m, 1 H); 2.63 – 2.53 (m, 2 H); 2.39 (dd, J ¼ 5.6, 8.8, 2 H); 1.98 –
1.89 (m, 2 H); 1.09 (s, 9 H). 13C-NMR: 140.7; 135.7; 134.7; 133.1; 130.0; 129.9; 129.4; 128.3; 128.2; 127.8;
127.7; 125.9; 117.2; 68.3; 37.8; 31.0; 26.8; 25.3; 19.1. LC/MS: 436 ([M þ Na]þ).
Ethyl (2E,5R)-5-{[tert-Butyl(diphenyl)silyl]oxy}-7-phenylhept-2-enoate (11). To a stirred soln. of 10
(2.8 g, 6.7 mmol) in dry CH2Cl2 (30 ml) was added DIBAL-H (1m in toluene; 6.7 ml, 6.7 mmol) slowly for
1
15 min at ꢀ 788, and the mixture was stirred for ꢃ2 h at ꢀ 788. The reaction was quenched with sat.
sodium potassium tartrate soln. (50 ml), and the mixture was stirred vigorously at r.t. for an additional h,
and extracted with CH2Cl2 (3 ꢁ 25 ml). The combined org. layer was washed with brine soln. (20 ml) and
dried (Na2SO4), and the solvent was removed under vacuum to give a crude product, which was purified
by flash CC (hexane/AcOEt 50 :2) to afford the aldehyde (2.08 g, 71%) as colorless oil. To a soln. of the
aldehyde in benzene (20 ml) was added Ph3P¼CH2COOEt (1.9 g, 5.5 mmol), and the mixture was stirred
at reflux for 1 h. After completion of the reaction, the solvent was removed under reduced pressure, and
the residue was purified by CC (hexane/AcOEt) to afford 11 as a colorless syrup (mixture of geometrical
isomers (E)/(Z) 95 :5), and the geometrical isomers were separated by CC to give 11 (1.77 g, 76%).
[a]2D5 ¼ ꢀ9.2 (c ¼ 1, CHCl3). IR (neat): 3064, 2953, 1728, 1625, 1495, 1256. 1H-NMR: 7.69 – 7.54 (m, 5 H);
7.41 – 7.21 (m, 5 H); 7.15 – 6.81 (m, 5 H); 6.98 – 6.84 (m, 1 H); 5.88 (d, J ¼ 17.2, 1 H); 4.25 – 4.19 (m, 1 H);
4.11 (q, J ¼ 7.4, 2 H); 2.59 – 2.51 (m, 4 H); 1.81 – 1.75 (m, 2 H); 1.29 (t, J ¼ 7.4, 3 H); 1.05 (s, 9 H).
13C-NMR: 164.3; 146.4; 135.8; 134.9; 133.1; 130.2; 129.8; 129.6; 128.4; 128.0; 127.9; 127.8; 127.6; 126.3;
125.8; 73.1; 65.4; 41.0; 36.6; 35.6; 19.1; 14.5. LC/MS: 509 ([M þ Na]þ).
Ethyl (2E,5R)-5-Hydroxy-7-phenylhept-2-enoate (12). To a cooled (08) soln. of 11 (1.6 g, 3.29 mmol)
in dry THF (10 ml) was added Bu4NF (TBAF; 1.05 ml, 3.62 mmol, 1m soln. in THF) dropwise, and the
mixture was stirred for 30 min. After completion of the reaction, H2O (5 ml) was added to the mixture,
and the mixture was extracted with AcOEt (3 ꢁ 15 ml). The combined org. extract was washed with
brine, dried (Na2SO4), and concentrated to give the crude product, which was purified by CC (hexane/
AcOEt 4 :6) to afford pure 12 (0.67 g, 83%). Liquid. [a]2D5 ¼ ꢀ14.2 (c ¼ 1, CHCl3). IR (neat): 3380, 1721,
1
1639, 1254. H-NMR: 7.21 – 7.09 (m, 5 H); 6.91 – 6.82 (m, 1 H); 5.85 (d, J ¼ 17.4, 1 H); 4.21 – 4.18 (m,
1 H); 4.13 (q, J ¼ 7.5, 2 H); 2.39 – 2.07 (m, 4 H); 1.76 – 1.75 (m 2 H); 1.29 (t, J ¼ 7.5, 3 H). 13C-NMR:
164.1; 146.1; 139.3; 129.6; 128.1; 128.0; 126.7; 72.8; 62.1; 40.8; 36.4; 35.7; 14.2. LC/MS: 248 ([M þ H]þ).
Ethyl [(4R,6R)-2-Phenyl-6-(2-phenylethyl)-1,3-dioxan-4-yl]acetate (13). To a cooled (08) soln. of 12
(0.50 g, 2.0 mmol) in THF (10 ml) was added PhCHO (0.23 g, 2.17 mmol) and t-BuOK (0.022 g,
0.20 mmol), and the resulting yellow soln. was stirred for 15 min. This sequence (addition/stirring) was
repeated twice, and the reaction was quenched with pH 7 buffer phosphate soln. (20 ml). The layers were
separated, and the aq. layer was extracted with AcOEt (3 ꢁ 20 ml). The combined org. layer was washed
with brine (20 ml), dried (Na2SO4), and the solvent was removed under reduced pressure. Crude product
was purified by CC (petroleum ether/AcOEt 7:3) to afford 13 (0.36 g, 51%). [a]2D5 ¼ ꢀ5.8 (c ¼ 1, CHCl3).
IR (neat): 2857, 1735, 1268,1205, 1151. 1H-NMR: 7.64 – 7.58 (m, 2 H); 7.48 – 7.26 (m, 5 H); 7.24 – 7.18 (m,
3 H); 5.58 (s, 1 H); 4.31 – 4.20 (m, 1 H); 4.13 (q, J ¼ 6.6, 2 H); 3.86 – 3.77 (m, 1 H); 2.75 (t, J ¼ 7.5, 2 H);
2.69 (dd, J ¼ 14.9, 6.3, 1 H); 2.44 (dd, J ¼ 14.9, 6.1, 1 H); 1.98 – 1.48 (m, 4 H); 1.23 (t, J ¼ 6.5, 3 H).
13C-NMR: 170.7; 141.9; 138.7; 128.4; 128.3; 128.1; 128.0; 125.9; 125.5 100.4; 77.1; 74.1; 60.7; 40.5; 37.8;
36.7; 36.1; 14.2. LC/MS: 377 ([M þ Na]þ).
(4R,6R)-Tetrahydro-4-hydroxy-6-(2-phenylethyl)-2H-pyran-2-one (1). A soln. of 13 (0.40 g,
1.82 mmol) in 80% aq. AcOH (3 ml) was stirred for 3 h at 608. After completion of the reaction,

Helvetica Chimica Acta – Vol. 93 (2010)
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AcOH was removed under reduced pressure, and the mixture was extracted with AcOEt (3 ꢁ 10 ml).
The combined org. layer was washed with H2O and brine soln., dried (Na2SO4), and the solvent was
evaporated under reduced pressure. The residue obtained was dissolved in CH2Cl2 (5 ml), and TsOH
(cat.) was added. The mixture was stirred for 4 h. The reaction was quenched with aq. NaHCO3 (2 ml),
and the mixture was extracted with CH2Cl2 (3 ꢁ 5 ml). The combined org. layer was washed with brine,
dried (Na2SO4), concentrated in vacuo, and purified by CC (hexane/AcOEt 1:1) to afford 1 (0.15 g,
61%). [a]2D5 ¼ þ46.8 (c ¼ 0.7, CHCl3). IR (neat): 3442, 2980, 1730, 1650, 1435, 1370, 1135, 1036. 1H-NMR:
7.36 – 7.18 (m, 5 H); 4.74 – 4.61 (m, 1 H); 4.37 – 4.32 (m, 1 H); 2.95 – 2.52 (m, 4 H); 2.07 – 1.67 (m, 4 H);
1.5 – 1.3 (br. s, 1 H). 13C-NMR: 170.5; 141.1; 128.5; 128.3; 126.0; 77.0; 75.0; 38.6; 37.5; 36.0; 32.0. LC/MS:
243 ([M þ Na]þ).
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Received January 24, 2010