Notes
P r ep a r a tion of Su bstr a tes. All substrates of â-substituted
J . Org. Chem., Vol. 63, No. 22, 1998 8065
En zym a tic Resolu tion of Ra cem ic γ-La cton es: Enzyme
LPS (3.0 mass equiv) was added to a stirred solution of
â-substituted methyl-γ-butyrolactone (0.72 mmol) in the speci-
fied solvent (15 mL). The resulting solution was stirred well at
35 °C while pH of the solution was maintained to 7.2 by adding
NaOH solution (0.1 M). After the conversion of the reaction
reached at certain percentage according to NaOH consumption,
the reaction was quenched by adding Celite and ice. The cake
was filtered through Celite with water and EtOAc. The com-
bined organic layer was washed with water twice, dried over
anhydrous MgSO4, filtered, and concentrated under reduced
pressure. Hydrolyzed product and starting substrate were
isolated and purified by flash chromatography on silica gel in
more than 95% of combined yield. ee values were measured by
either 200 or 400 MHz 1H NMR of γ-((acetyloxy)methyl)-γ-
butyrolactone in the presence of 12-15 mol % of tris[3-((trifluo-
romethyl)hydroxymethylene)-D-camphorato]europium(III) [Eu-
(hfc)3]. HPLC also was used with CHIRALPAK-AS (0.46 cm i.d.
× 25 cm) and the eluent of ethanol.
γ-((acetyloxy)methyl)-γ-butyrolactones (1a -7a ) were prepared
from acetylation by AgOAc of the corresponding â-substituted
γ-(iodomethyl)-γ-butyrolactones except 8a which came from
commercially available 4,4-dimethyl-5-(hydroxymethyl)tetrahy-
drofuran-2-one with AcCl and pyridine. â-Substituted γ-(io-
domethyl)-γ-butyrolactones were easily prepared from acyclic
olefin through reported method of stereoselective iodolactoniza-
tion.6,7
(4R *,5R *)-4-E t h yl-5-(iod om e t h yl)t e t r a h yd r ofu r a n -2-
on e: 1H NMR δ 0.94 (t, 3H, J ) 7.2 Hz), 1.33-1.70 (m, 2H),
2.14-2.33 (m, 2H), 2.79 (dd, 1H, J ) 19.8, 11.2 Hz), 3.31 (dd,
1H, J ) 10.8, 4.8 Hz), 3.41 (dd, 1H, J ) 10.8, 5.4 Hz), 4.10 (dd,
1H, J ) 10.2, 5.0 HZ); 13C NMR δ 7.08, 11.3, 26.2, 34.3, 42.1,
82.9, 175.5. Anal. Calcd for C7H11O2I: C, 33.1; H, 4.36.
Found: C, 33.2; H, 4.57.
(4R *,5S *)-4-E t h yl-5-(iod om e t h yl)t e t r a h yd r ofu r a n -2-
on e: 1H NMR δ 0.92 (t, 3H, J ) 7.2 Hz), 1.21-1.33 (m, 1H),
1.51-1.64 (m, 1H), 2.34-2.65 (m, 3H), 3.15-3.32 (m, 2H), 4.64
(dd, 1H, J ) 12.8, 6.8 Hz); 13C NMR δ 1.0, 11.5, 19.7, 33.8, 39.6,
81.6, 175.6. Anal. Calcd for C7H11O2I: C, 33.1; H, 4.36.
Found: C, 33.4; H, 4.18.
(4R*,5R*)-4-Meth yl-5-((a cetyloxy)m eth yl)tetr a h yd r ofu -
r a n -2-on e (2a ). 1H NMR δ 1.19 (d, 3H, J ) 6.6 Hz), 2.09 (s,
3H), 2.21 (dd, 1H, J ) 16.8, 8.6 Hz), 2.32-2.43 (m, 1H), 2.74
(dd, 1H, J ) 16.8, 8.0 Hz), 4.09-4.37 (m, 3H); 13C NMR δ 17.2,
20.2, 31.8, 36.1, 63.6, 83.5, 170.4, 175.7.
(4R*,5S*)-4-Meth yl-5-((a cetyloxy)m eth yl)tetr a h yd r ofu -
r a n -2-on e (3a ): 1H NMR δ 1.08 (d, 3H, J ) 7.0 Hz), 2.07 (s,
3H), 2.26 (dd, 1H, J ) 16.4, 6.4 Hz), 2.59-2.81 (m, 2H), 4.16
(dd, 1H, J ) 12.2, 6.0 Hz), 4.32 (dd, 1H, J ) 12.2, 3.6 Hz), 4.60-
4.68 (m, 1H); 13C NMR δ 13.5, 20.4, 31.6, 36.2, 62.7, 79.4, 170.3,
176.1.
(4R*,5R*)-4-Eth yl-5-((acetyloxy)m eth yl)tetr ah ydr ofu r an -
2-on e (4a ): 1H NMR δ 0.77 (t, 3H, J ) 7.2 Hz), 1.24-1.83 (m,
2H), 1.89 (s, 3H), 1.97-2.21 (m, 2H), 2.46-2.62 (m, 1H), 3.94
(dd, 1H, J ) 12.6, 6.0 Hz), 3.89-4.16 (m, 2H); 13C NMR δ 11.0,
20.0, 25.4, 33.7, 38.0, 46.0, 81.8, 170.1, 175.7. Anal. Calcd for
C9H14O4: C, 58.1; H, 7.58. Found: C, 58.2; H,7.64.
(4R*,5S*)-4-Eth yl-5-((acetyloxy)m eth yl)tetr ah ydr ofu r an -
2-on e (5a ): 1H NMR δ 0.97 (t, 3H, J ) 0.97 Hz), 1.28-1.64 (m,
2H), 2.08 (s, 3H), 2.21-2.66 (m, 3H), 4.14 (dd, 1H, J ) 12.4, 5.2
Hz), 4.36 (dd, 1H, J ) 12.6, 1.8 Hz), 4.69 (dd, 1H, J ) 10.2, 5.4
Hz); 13C NMR δ 12.4, 20.7, 21.7, 33.8, 39.4, 63.0, 79.2, 170.5,
176.3. Anal. Calcd for C9H14O4: C, 58.1; H, 7.58. Found: C,
57.9; H, 7.78.
(4R,5R)-4-Meth yl-5-(h yd r oxym eth yl)tetr a h yd r ofu r a n -2-
on e (2b): 1H NMR δ 1.09 (d, 3H, J ) 6.8 Hz), 2.14 (dd, 1H, J
) 17.0, 8.4 Hz), 2.37-2.62 (m, 1H), 2.42 (bs, 1H), 2.68 (dd, 1H,
J ) 17.0, 8.4 Hz), 3.54-3.85 (m, 2H), 4.08 (dd, 1H, J ) 6.8, 4.4
Hz); 13C NMR δ 17.5, 30.8, 36.8, 62.1, 87.4, 177.4.
(4R,5R)-4-Meth yl-5-((tosyloxy)m eth yl)tetr a h yd r ofu r a n -
2-on e (2c). This was prepared by the reported method starting
from the hydrolyzed product 2b: [R]20 -61.3 (c 2.7, CHCl3);
D
lit.9a [R]21 -60.9 (c 1.25, dioxane).
D
(4R,5S)-4,5-Dim eth yltetr a h yd r ofu r a n -2-on e (9). The to-
sylated product of 2c (446 mg, 1.57 mmol) and NaBH3CN (394
mg, 6.28 mmol) were dissolved in 10 mL of HMPA. The
resultant solution was stirred at 100 °C for 27 h for the reaction
to be completed. The reaction chamber was cooled to the room
temperature before adding the water. The product was ex-
tracted by 20 mL of ether twice. The organic layer was
separated, washed twice with each of a NaHCO3 solution and
brine, dried over anhydrous MgSO4, filtered, and concentrated
under reduced pressure to give crude product. This was purified
by chromatography to give 84 mg of product in 47% yield: [R]20
D
-56.8 (c 0.18, CHCl3); lit.10b [R]24 -59.7 (c 2.06, CHCl3).
D
(3R,4S)-Cogn a c La cton e (10). This was prepared by the
reported method9 with di-n-butylcuprate to yield the natural
product of (3R,4S)-cognac lactone in 84% yield: {[R]20D -73.4 (c
1.45, CH2Cl2); lit.11c [R]24 +83.2 (for the enantiomer, c 0.69,
D
MeOH)}.
(4R,5S)-4-Meth yl-5-(h yd r oxym eth yl)tetr a h yd r ofu r a n -2-
on e (3b): 1H NMR δ 1.07 (d, 3H, J ) 6.8 Hz), 2.79 (dd, 1H, J
) 16.8, 8.0 Hz), 2.55 (dd, 1H, J ) 17.0, 8.4 Hz), 2.91 (q, 1H, J )
7.4 Hz), 3.44 (bs, 1H), 3.75 (d, 2H, J ) 4.6 Hz), 4.43-4.51 (m,
1H); 13C NMR δ 13.6, 32.0, 36.6, 61.5, 83.2, 177.8.
(4R*,5R*)-4-P h en yl-5-((a cetyloxy)m eth yl)tetr a h yd r ofu -
r a n -2-on e (6a ): 1H NMR δ 2.03 (s, 3H), 2.74 (dd, 1H, J ) 17.8,
9.8 Hz), 3.00 (dd, 1H, J ) 17.8, 9.0 Hz), 3.49 (dd, 1H, J ) 17.8,
9.0 Hz), 4.15 (dd, 1H, J ) 12.4, 5.4 Hz), 4.32 (dd, 1H, J ) 12.4,
2.8), 4.64 (ddd, 1H, J ) 7.4, 5.4, 2.8 Hz), 7.21-7.40 (m, 5H); 13
C
(5S)-4-Met h yl-5-((ter t-b u t yld im et h ylsilyl)oxy)m et h yl)-
2,5-d ih yd r ofu r a n -2-on e (11). tert-Butyldimethylsilyl chloride
(1.29 g, 8.6 mmol) in CH2Cl2 (7 mL) was added to a solution of
3b (91 mg, 7.9 mmol) and imidazole (0.79 mg, 11.7 mmol) in
CH2Cl2 (7 mL). The resultant suspension was stirred at room
temperature for 4 h and diluted with CH2Cl2, washed with 2 M
HCl solution, water, and NaHCO3 solution, dried, and concen-
trated to give an oily product. This crude product dissolved in
8 mL of THF was added at -78 °C to the reaction flask
containing HMDS (0.32 g, 1.51 mmol) and n-BuLi (0.60 mL of
2.5 M solution, 1.51 mmol) that was premixed at 0 °C for 30
min. The resultant solution was stirred for 45 min. Into this
reaction flask was added phenylseleniun bromide (0.15 g, 0.81
mol), and the mixture was stirred for 2 h before 35 mL of
NH4Cl solution was added. The reaction product was extracted
with EtOAc three times. The organic layer was washed suc-
cessively with NaHCO3 solution and brine, dried over anhydrous
MgSO4, filtered, and concentrated under reduced pressure to
give oily product. This crude phenyl selenide was dissolved in
16 mL of EtOAc. Into the solution was added H2O2 (30%, 2.5
mL), and the resultant reaction mixture was stirred in 45 min.
After the reaction was completed the organic layer was sepa-
rated, washed twice with each of a NaHCO3 solution and brine,
dried over anhydrous MgSO4, filtered, and concentrated under
reduced pressure to give crude product. This was purified by
column chromatography to give 0.15 g of product in 91% yield:
1H NMR δ 0.10 (s, 6H), 0.69 (s, 9H), 1.95 (s, 3H), 3.79 (dd, 1H,
NMR δ 20.4, 36.7, 43.1, 63.4, 83.2, 127.0, 127.9, 129.2, 138.4,
170.4, 172.0. Anal. Calcd for C13H14O4: C, 66.7; H, 6.02.
Found: C, 66.6, 5.93.
(4R*,5S*)-4-P h en yl-5-((a cetyloxy)m eth yl)tetr a h yd r ofu -
r a n -2-on e (7a ): 1H NMR δ 1.94 (s, 3H), 2.88 (d, 2H, J ) 9.0
Hz), 3.66 (dd, 1H, J ) 12.6, 6.6 Hz), 3.83-4.00 (m, 2H), 4.87
(td, 1H, J ) 6.3, 3.4 Hz), 7.11-7.35 (m, 5H); 13C NMR δ 20.4,
34.2, 42.5, 63.4, 80.0, 127.3, 128.0, 129.0, 136.2, 170.1, 176.0.
Anal. Calcd for C13H14O4: C, 66.7; H, 6.02. Found: C, 66.8,
6.11.
4,4-Dim et h yl-5-((a cet yloxy)m et h yl)t et r a h yd r ofu r a n -2-
on e (8a ). Acetyl chloride (0.22 g, 2.8 mmol) and Et3N (0.28 g,
2.8 mmol) were added to the solution of 4,4,-dimethyl-5-(hy-
droxymethyl)tetrahydrofuran-2-one (0.20 g, 1.4 mmol) in 5 mL
of CH2Cl2 under N2 atmosphere at room temperature. The
resultant solution was stirred until all starting material was
consumed checking by TLC in 1 h. Water was added, and the
reaction product was extracted with CH2Cl2 three times. The
organic layer was combined, washed in water and brine, dried
over anhydrous MgSO4, and filtered. The filterate was concen-
trated under reduced pressure and purified by distillation to
yield 0.24 g of 4,4,-dimethyl-5-((acetyloxy)methyl)tetrahydrofu-
ran-2-one in 92% yield: 1H NMR δ 1.06 (s, 3H), 1.20 (s, 3H),
2.05 (s, 3H), 2.34 (d, 2H, J ) 4.8 Hz), 4.09 (dd, 1H, J ) 13.0, 8.2
Hz), 4.21-4.31 (m, 2H); 13C NMR δ 20.6, 21.3, 26.1, 38.2, 43.9,
62.5, 84.8, 170.6, 175.5.