1.
Reagent-grade tetrahydrofuran was purchased from Fisher Scientific Company and either freshly distilled from sodium metal and benzophenone or dried at least 3 days over activated Linde 4A molecular sieves before use in Reaction A. It was used as received for reaction C.
2.
Butyllithium in hexane was purchased from Aldrich Chemical Company, Inc. and titrated prior to use.4
3.
Propionyl chloride (d, 1.065) was obtained from Aldrich Chemical Company, Inc., and distilled prior to use.
4.
Trituration by the checkers gave 21.2–22.3 g (91–96%) of acylated product of somewhat higher purity: mp 45–46°C; [α]D22 +99.5° (ethanol, c 1.01). Alternatively, the acylated oxazolidinone can be isolated by distillation (Kugelrohr, 125°C, 12 mm). Isolated yields were 97–99%.
5.
The product has the following spectroscopic properties: IR (solution in dichloromethane) cm−1: 3030, 2980, 1780, 1705, 1455, 1385, 1245, 1210, 1080; 1H NMR (CDCl3) δ: 1.2 (t, 3 H, J = 7.2, CH3), 2.8 (dd, 1 H, J = 13.3, 9.6, CH2C6H5), 2.9 (m, 2 H, CH2CH3), 3.3 (dd, 1 H, J = 13.4, 3.3, CH2C6H5), 4.1 (m, 2 H, CHCH2O), 4.7 (m, 1 H, NCH), 7.1–7.5 (m, 5 H, ArH); [α]D +92.9° (ethanol, c 1.01).
6.
Dichloromethane was distilled from calcium hydride.
7.
Dibutylboron triflate was prepared according to the method of Mukaiyama.5 It is also available from Aldrich Chemical Company, Inc. as a solution in dichloromethane or diethyl ether, but results with this material are inconsistent. It should be used within 2 weeks of preparation or after redistillation. Triethylamine (Fisher Scientific Company) was distilled from calcium hydride immediately prior to use.
8.
The entire reaction can be carried out at 0°C if desired. The ratio of diastereomers in the unpurified product mixture falls slightly to 97.6 : 0.2 : 2.2 (Note 10).
9.
The checkers isolated a colorless viscous oil that crystallized on addition of 1 : 2 ethyl acetate–hexane. Care must be taken to avoid an excess of hexane, since oiling of the product can occur under these circumstances.
10.
Diastereomer ratios were determined by gas chromatography. Since the aldol adduct undergoes retroaldol reaction on the column, it must be silylated prior to injection. Approximately 5 mg of the crude adduct is filtered through a short plug of silica gel to remove any trace metals. The material is taken up into 1–2 mL of dichloromethane in a 2-mL flask or small test tube. To this solution are added 4–5 drops of N,N-diethyl-1,1,1-trimethylsilylamine and a small crystal of 4-(N,N-dimethylamino)pyridine (Note 11). The solution is stirred for 2 hr and injected directly onto the column. (Column conditions: 30-m × 0.32-mm fused-silica column coated with DB 5, 14-psi hydrogen carrier gas, oven temperature 235°C.)
11.
N,N-Diethyl-1,1,1-trimethylsilylamine and 4-(N,N-dimethylamino)pyridine were purchased from Aldrich Chemical Company, Inc.
12.
The product has the following spectroscopic characteristics: IR (solution in dichloromethane) cm−1: 3520, 3040, 2980, 1780, 1695, 1455, 1385, 1210, 1110; 1H NMR (CDCl3) δ: 1.2 (d, 3 H, J = 7.0, CH3), 2.8 (dd, 1 H, J = 13.4, 9.5, 1 H CH2C6H5), 3.1 (d, 1 H, J = 2.7, OH), 3.3 (dd, 1 H, J = 13.4, 3.4, CH2C6H5), 4.1 (m, 3 H, CHCH2O, CHCH3), 4.6 (m, 1 H, NCH), 5.1 (m, 1 H, HOCH), 7.1–7.5 (m, 10 H, ArH); [α]D +75.7° (dichloromethane, c 1.00).
13.
Kieselgel 60 was purchased from EM Science, Cherry Hill, NJ, an affiliate of E. Merck, Darmstadt.
14.
Hydrogen peroxide was obtained from Mallinckrodt, Inc.
15.
The following spectroscopic characteristics were observed: IR (solution in dichloromethane) cm−1: 3600, 3400–2300 broad hump, 3040, 3000, 1710, 1455, 1230; 1H NMR (CDCl3) δ: 1.2 (d, 3 H, J = 7.1, CH3), 2.9 (m, 1 H, CHCH3), 5.2 (d, 1 H, J = 3.9, C6H5CH), 7.2–7.4 (m, 5 H, ArH); [α]D22 −26.4° (CH2Cl2, c 1.04). No epimerization was detected by NMR.