3288
A. S. Raw, E. B. Jang / Tetrahedron 56 (2000) 3285±3290
further puri®cation. All reactions were carried out under a
nitrogen atmosphere. Mention of a proprietary company or
product does not imply endorsement by the US Department
of Agriculture.
yield) of the recovered benzyloxazolidinone auxiliary. The
aqueous layer was acidi®ed to pH 1±2 with 12 M HCl and
extracted with ethyl acetate (5£300 mL). The combined
ethyl acetate extracts were dried (Na2SO4) and the volatiles
were removed in vacuo to yield an oil that was puri®ed by
¯ash chromatography (1:1 ethyl acetate/hexane, 0.3% acetic
acid) to give 5 as a solid (20.2 g, 51% overall yield from 6).
The optical purity of the methyl ester of 5 was shown to be
97% ee (30 m Chiraldex BD-A column, 708C isothermal,
25 psi, tr major 31.4 min, tr minor 33.0 min). Rf 0.40 (ethyl
acetate/hexane 1:1); mp 65±668C; 1H NMR (300 MHz,
CDCl3) d 10.2±11.8 (b, 1H), 5.61±5.69 (m, 2H). 2.12±
2.33 (m, 4H), 1.89±2.00 (m, 1H), 1.67±1.77 (m, 1H), 1.02
(d, J6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 182.3,
126.3, 124.5, 46.8, 32.9, 30.3, 28.7, 19.7; MS (EI) m/z
140 (M1, 21), 122 ([M2H2O]1, 16), 111 (14), 95 (100),
79 (75), 67 (49); [a]D299.08 (c4.89, CHCl3).
(4R)-3-((E)-2-Butenoyl)-4-(phenylmethyl)-2-oxazolidinone
(6) was synthesized according to a literature procedure.9
The product was recrystallized from ethanol to yield a
white solid (156.4 g, 90%). Rf 0.20 (ethyl acetate/hexane
1
1:9); mp 79±818C; H NMR (300 MHz, CDCl3) d 7.14±
7.35 (m, 7H), 4.67±4.75 (m, 1H), 4.10±4.21 (m, 2H), 3.30
(dd, J3.4 Hz, 13.2 Hz, 1H), 2.79 (dd, J9.5 Hz, 13.2 Hz,
1H), 1.97 (d, J5.7 Hz, 3H); 13C NMR (75 MHz, CDCl3) d
164.6, 153.2, 146.3, 135.2, 129.2, 128.6, 127.0, 121.7, 65.8,
54.9, 37.5, 18.2; MS (EI) m/z 245 (M1, 10), 230 (11), 154
(12), 133 (4), 91 (9), 69 (100), 41 (11); [a]D 278.38
(c3.83, CHCl3).
(4R)-3-((40R,50R)-Cyclohexene-40-carbonyl)-4-(phenyl-
methyl)-2-oxazolidinone (7).10 In a fume hood, a 3 L, 3-
neck round-bottomed ¯ask equipped with a dry-ice con-
denser, was charged with oxazolidinone 6 (70.0 g, 0.286
mol), galvinoxyl (500 mg, 1.2 mmol), and 400 mL of
methylene chloride. After cooling to 2788C, butadiene
(800 mL, 9.6 mol), dried by passage through Drierite was
condensed into the solution. Diethylaluminum chloride
(0.570 mol, 1.8 M in toluene) was added over 10 min and
the solution was stirred overnight at 215 to 2108C. The
reaction was quenched by addition to 1 M HCl (1000 mL),
and stirred for 60 min at room temperature to allow the
butadiene to evaporate. The layers were separated and the
aqueous layer was extracted with methylene chloride
(4£250 mL). The combined organics were neutralized by
stirring with solid NaHCO3, dried (MgSO4) and the volatiles
were removed in vacuo to give a crude oil (103.9 g, 107%
crude yield), that was carried onto the next step without
puri®cation. A portion of the sample was puri®ed by ¯ash
chromatography (1:4 ethyl acetate/hexane), to give a solid;
(1R,2R,4S,5S)-4-Iodo-2-methyl-6-oxabicyclo[3.2.1]octan-
7-one (8).14 To a solution of optically active 5 (16.8 g,
120 mmol) in methylene chloride (200 mL) and water
(400 mL), were added NaHCO3 (20.1 g, 240 mmol), KI
(120 g, 720 mmol) and iodine (91.0 g, 360 mmol). The
resulting mixture was protected from light and stirred for
24 h. The solution was cooled (08C), and sodium thiosulfate
was carefully added until the dark iodine color disappeared.
It was then extracted with diethyl ether (4£300 mL). The
combined organics were dried (MgSO4) and the volatiles
were removed in vacuo to give crude 8 as a yellowish
solid (27.8 g, 87% yield). This was carried onto the next
step without further puri®cation. Rf 0.33 (ethyl acetate/
1
hexane 1:9); mp 99±1008C; H NMR (300 MHz, CDCl3)
d 4.86 (dd, J3.6 Hz, 5.9 Hz, 1H), 4.35±4.38 (m, 1H),
2.90 (m, 1H), 2.63±2.73 (m, 1H), 2.49±2.52 (m, 1H),
2.20±2.36 (m, 2H), 1.95±2.00 (m, 1H). 1.38 (d, J
7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 178.2, 81.6,
43.8, 34.3, 29.3, 27.8, 19.5, 19.1; MS (EI) m/z 266 (M1,
4), 139 ([M2I]1, 80), 95 (100), 79 (16), 67 (26), 55 (29);
[a]D23.608 (c2.22, CHCl3).
1
Rf 0.25 (1:9 ethyl acetate/hexane); mp 79±808C; H NMR
(300 MHz, CDCl3) d 7.19±7.36 (m, 5H), 5.69±5.73 (m,
2H), 4.68±4.76 (m, 1H), 4.14±4.24 (m, 2H), 3.70 (dt,
J5.5 Hz, 10.2 Hz, 1H), 3.26 (dd, J3.2 Hz, 13.5 Hz,
1H), 2.79 (dd, J9.5 Hz, 13.5 Hz, 1H), 2.35±2.43 (m,
1H), 2.02±2.27 (m, 3H), 1.75±1.86 (m, 1H), 0.97 (d, J
6.4 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 176.4, 153.1,
135.3, 129.4, 128.9, 127.3, 126.3, 124.6, 66.0, 55.3, 44.2,
37.9, 33.0, 30.3, 29.0, 19.5; MS (EI) m/z 299 (M1, 13), 284
(1), 178 (25), 122 (100), 95 (46), 79 (30); [a]D2141.58
(c1.48, CHCl3).
(1R, 6R)-6-Methyl-3-cyclohexene-1-carboxylic acid (5).6
To a cold (08C) solution of 7 (103.9 g, 0.286 mol), in 4:1
THF/water (500 mL) was added 30% hydrogen peroxide
(160 mL, 1.40 mol), followed by addition of solid lithium
hydroxide (27.4 g, 0.652 mol). The resulting mixture was
allowed to slowly warm to room temperature, and after
4 h the reaction was complete. The solution was cooled
(08C) and sodium sul®te (202 g, 1.6 mol) was added. The
bulk of the THF was removed in vacuo, and the resulting
mixture (pH 12±13) was extracted with methylene chloride
(5£200 mL) to remove the chiral auxiliary. The combined
methylene chloride extracts were dried (MgSO4) and the
volatiles were removed in vacuo to yield 44.0 g (87%
(1R,2R,5R)-2-Methyl-6-oxabicyclo[3.2.1]octan-7-one (9).14
A solution of 8 (26.8 g, 101 mmol), tributyltin hydride
(29.8 mL, 111 mmol), and AIBN (200 mg) in benzene
(300 mL) was re¯uxed overnight. After removing the ben-
zene in vacuo, diethyl ether (250 mL) and 10% aqueous KF
(250 mL) were added. Stirring for 30 min precipitated a
tributyltin ¯ouride polymer. The polymer was removed by
®ltration, and the ®ltrate was extracted with methylene
chloride (3£100 mL). The combined organics were dried
(MgSO4) and the volatiles were removed in vacuo to yield
an oil that was puri®ed by ¯ash chromatography (using
eluent gradient 1:20 ethyl acetate/hexane to 3:7 ethyl
acetate/hexane) to give 9 as a yellowish solid (13.2 g,
94% yield). Rf 0.26 (ethyl acetate/hexane 1:9); mp 62±
638C; IR (gas phase) cm21 2975, 2888, 1811, 1347, 1156;
1H NMR (300 MHz, CDCl3) d 4.76±4.80 (m, 1H), 2.43±
2.46 (m, 1H), 2.12±2.25 (m, 2H), 2.01±2.05 (m, 1H), 1.89±
1.98 (m, 2H), 1.62±1.70 (m, 1H), 1.41±1.47 (m, 1H), 1.13
(d, J6.8 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 179.1,
78.1, 44.5, 31.0, 28.1, 24.8, 24.4, 17.5; MS (EI) m/z 140
(M1, 3), 112 ([M2CO]1, 3), 97 (28), 81 (100), 70 (38), 55
(48); [a]D131.38 (c0.968, CHCl3); Analysis calcd for
C8H12O2: C, 68.54; H, 8.63. Found: C, 68.15; H, 8.60.