1.
Diethyl L-tartrate (99%) was obtained from Janssen Chimica, Brüggen, Germany or Aldrich Chemical Company, Inc.
2.
Benzaldehyde (99+%) from Aldrich Chemical Company, Inc., was used as received.
3.
p-Toluenesulfonic acid monohydrate (99%) was obtained from Fluka Feinchemikalien GmbH, Neu-Ulm, Germany or from Aldrich Chemical Company, Inc.
4.
The mixture becomes homogeneous at reflux temperature. The reaction usually takes about 16 hr at an 0.5 mole-scale as indicated by the amount of water separated.
5.
Diethyl ether (technical grade) was distilled over potassium hydroxide.
6.
The spectral properties of diethyl (−)-2,3-O-benzylidene-L-tartrate are as follows: 1H NMR (250 MHz, CDCl3) δ: 1.32, 1.35 (2 t, 6 H, J = 7.1, 2 CH2CH3), 4.23, 4.28 (2 q, 4 H, J = 7.1, 2 CH2CH3), 4.83, 4.95 (2 d, 2 H, J = 4.0, 2 CHO), 6.16 (s, 1 H, CHPh), 7.40, 7.58 (2 m, 5 H, C6H5),4 [α]D20 −30.7° (CHCl3, c 2.20),5 mp 45°C.4,5
7.
Lithium aluminum hydride was obtained in 25-g samples (98%) from Merck-Schuchardt, Hohenbrunn, Germany or Aldrich Chemical Company, Inc.
8.
Diethyl ether was dried first by distillation over potassium hydroxide, then by distillation from lithium aluminum hydride.
9.
In order to dissolve aluminum chloride in dry diethyl ether, a flask is charged with the aluminum chloride and the diethyl ether is added in 10-mL portions with vigorous mechanical stirring to give a dark solution. The flask must be cooled in an ice bath.
10.
Dichloromethane (technical grade) was distilled over phosphorus pentoxide.
11.
If lithium aluminum hydride and aluminum chloride are not of high purity, an excess of 10% of each should be used. Otherwise a mixture with products of incomplete reduction is obtained.
12.
The reaction mixture is heated to reflux with 200 mL of tetrahydrofuran; the precipitate then obtained is very easy to filter off.
13.
The spectral properties of (+)-2-O-benzyl-L-threitol are as follows: 1H NMR (250 MHz, CDCl3) δ: 2.58, 2.76, 2.98 (bs, 3 H, 3 OH), 3.44–3.88 (m, 6 H, 2 CH2OH, H-2, H-3), 4.56, 4.69 (AB, 2 H, J = 11.6, CH2C6H5), 7.16–7.34 (m, 5 H, C6H5), [α]D25 +17.5° (EtOH, c 1.14).5
14.
In several experiments it was found that the yield of (−)-2-O-benzyl-L-glyceraldehyde is somewhat lower when the reaction is performed on a larger scale.
15.
Sodium periodate (98%) was obtained from Fluka Feinchemikalien GmbH, Neu-Ulm, Germany or from Fisher Scientific Company.
16.
The pH was controlled with Merck Universal-Indikatorpapier or pHydrion Vivid 1–11 Jumbo pH paper, Micro Essential Laboratory, Brooklyn, NY, USA.
17.
A silicone-oil bath is preheated to 160°C (the checkers used a sand bath). The flask of the evacuated apparatus filled with the crude product is immersed totally in the bath until no more distillate is collected. For optimum results, the distillation should be performed within 10 to 15 min. Slower distillation leads to lower yields because of thermal decomposition.
18.
It is not possible to give exact spectral properties of (−)-2-O-benzyl-L-glyceraldehyde because of rapid di- and/or oligomerization. In order to check the optical purity of the product, it is convenient to compare the equilibrium value of specific rotation, as obtained after 6 days in ethanol solution at room temperature; [α]D22 −33.2° (EtOH, c 0.083). In succeeding reactions (see Discussion and Step D), it was determined from NMR shift experiments that these products [e.g., (i) the Z-selective Wittig enoate product (with ethoxycarbonylmethylene-triphenylphosphorane) and the penten-5-olide therefrom (after acid-catalyzed lactonization,4,6] and (ii) the E-enoate (Horner product)4,6 contained enantiomers in ratios of >96:4.
19.
Nitrogen was dried by means of a Sicapent® (E. Merck) drying tube. The checkers used argon.
20.
The checkers used hexanes (technical grade) distilled over 3 Å molecular sieves. The submitters used pentane distilled from sodium.
21.
Tetrahydrofuran was purified by distillation under nitrogen from a purple solution of sodium and benzophenone.
22.
Triethyl phosphonoacetate was purified by distillation (bp 143°C, 9 mm). The checkers obtained this compound (99%) from Aldrich Chemical Company, Inc., and used it as received.
23.
The submitters used 28 g of Kieselgel 60, E. MERCK, 0.040–0.063 mm (250–400 mesh); column: 28 cm × 2.5 cm. The checkers used 100 g of silica gel, 0.032–0.063 mm, Selecto Scientific, Norcross, GA, USA, catalog # 162824; column: 40 cm × 5.5 cm.
24.
Ethyl acetate and petroleum ether (technical grade; boiling range 40–80°C) were purified by distillation. The checkers used ethyl acetate/hexanes 10/90 followed by ethyl acetate/hexanes 35/65 as eluent; ethyl acetate (HPLC grade) was obtained from Mallinckrodt Specialty Chemicals Company, Paris, KY, USA and hexanes (technical grade) were distilled over 3 Å molecular sieves.
25.
The analytical data (after chromatography) were as follows: Calcd. for C14H18O4 (250.29): C, 67.18; H, 7.25. Found: C, 67.00; H. 7.20. The E/Z ratio was found to be >97:3 (determined by HPLC). RtE = 3.72 min; RtZ = 4.28 min, eluent petroleum ether/ethyl acetate 6/4 (LiChrosorb Si 60 column, E. Merck]. TLC: Rf = 0.34 (petroleum ether/ethyl acetate 1/1). GLC analysis: Column PS086/.32 mm × 20 m glass capillary, 95:5 methyl/phenylsilicone. Program: T1, 40°C/(1 min), rate 10°C/min, T2, 300°C, 0.5 bar hydrogen pressure; RtZ = 16.47 min; RtE = 17.25 min. E/Z ratio was found to be >97:3 (determined by GLC). [α]D22 −75.8° (CHCl3, c 1.192, E/Z >97:3), bp 125–130°C (0.001 mm). 13C NMR (63 MHz, CDCl3) δ: 14.2 (OCH2CH3), 60.7 (OCH2CH3), 64.6 (C-5), 71.5 (CH2Ph), 79.0 (C-4), 123.9 (C-2), 127.9, 128.0, 128.3, 128.6, 137.6 (C6H5), 144.3 (C-3), 165.9 (C-1); 1H NMR (250 MHz, CDCl3), δ: 1.30 (t, 3 H, J = 7.1, CH3), 2.32 (dd, 1 H, J = 5.2, 7.9, OH), 3.65 (m, 2 H, CH2OH), 4.14 (m, 1 H, 4-H), 4.22 (q, 2 H, J = 7.1, OCH2CH3), 4.41, 4.45 (AB, 2 H, J = 11.6, CH2Ph), 6.11 (dd, 1 H, J = 1.3, 15.8, 2-H), 6.85 (dd, 1 H, J = 6.1, 15.8, 3-H), 7.34 (m, 5 H, C6H5).