1.
The checkers received (SS)-N-tert-butanesulfinamide (2) as a gift from AllyChem (>99% ee by chiral HPLC on a Chiracel AS column, 90:10 hexanes/i-PrOH, 1mL/min, λ = 222 nm). Indium powder (>99%) was purchased from Alfa Aesar. The submitters received (SS)-N-tert-butanesulfinamide (2) as a gift from Medalchemy. (SS)-N-tert-butanesulfinamide (2) is also available from many commercial suppliers.
2.
THF (HPLC grade, 99.9% purity) was purchased from Scharlau and used as received. A new bottle of decanal (1) (96 %, Alfa Aesar) was used without further purification. Titanium(IV) tetraethoxide (33-35% TiO2) was purchased from Across Organics.
3.
At this point, a sample was removed and submitted to 1H NMR analysis, confirming full conversion of 2 into the corresponding N-tert-butanesulfinyl imine 6 intermediate. 1H NMR (300 MHz, CDCl3) d: 0.88 (t, J = 6.6 Hz, 3 H), 1.20 (s, 9 H), 1.23-1.39 (m, 12 H), 1.56-1.69 (m, 2 H), 2.52 (td, J = 7.4, 4.8 Hz, 2 H), 8.07 (t, J = 4.8 Hz, 1 H),
4.
Allyl bromide (3), 99% was purchased from Alfa Aesar and filtered through a short plug (0.7 × 2.5 cm) of alumina (activity 1).
5.
Caution: Approximately 5 min after the addition of allyl bromide (3), upon beginning to heat the reaction mixture, the reaction became very exothermic with the internal temperature rapidly rising to ~65 ºC. It was therefore necessary to remove the heating bath for about 5 min.
6.
It is important to control the temperature in the reaction mixture. At 40 ºC the reaction is significantly slower.
7.
The reaction progress can be monitored by TLC analysis on Merck silica gel 60 F254 plates and visualization with phosphomolybdic acid (5% in EtOH). Using hexanes:ethyl acetate (3:1) as eluent, compound 2 has an Rf = 0, N-tert-butanesulfinyl imine 6 has an Rf = 0.77, diastereomer (4R,SS)-4 (minor) has an Rf = 0.32, diastereomer (4R,SS)-4 (major) has an Rf = 0.26, and the homoallyl alcohol by-product 7 has an Rf = 0.85.
8.
The crude oil contained a 10:1 mixture of (4R,SS)-4 : (4S,SS)-4 with the diastereomeric purity determined by 1H-NMR pdf analysis based on the NH signals: major diastereomer 3.22 (d, J = 6.1 Hz); minor diastereomer 3.07 (d, J = 5.9 Hz) (see attached NMR).
9.
Silica gel 60, 230-400 mesh (Sorbent Technologies) was used.
10.
The column fractions were checked by TLC analysis on Merck silica gel 60 F254 plates with hexanes:ethyl acetate (3:1) as eluent and visualization with phosphomolybdic acid. Rf values are given in Note 7.
11.
The minor diastereomer (4R,SS)-4 elutes before the major one. Concentration of fractions 58-94 furnished 2.18 g (36%) of a 78:22 mixture of (4R,SS)-4/(4S,SS)-4 (according to 1H NMR). Concentration of fractions 95-168 furnished 3.21 g (53%) of (4S,SS)-4 (>99:1 according to 1H NMR).
12.
The physical properties of (4S,Ss)-4 are as follows: 1H NMR pdf (400 MHz, CDCl3) δ: 0.88 (t, J = 6.9 Hz, 3 H), 1.20 (s, 9 H), 1.22-1.39 (m, 14 H), 1.43-1.53 (m, 2 H), 2.30 (dt, J = 13.9, 6.9 Hz, 1 H), 2.41 (dt, J = 12.8, 6.4 Hz, 1 H), 3.19 (d, J = 6.0 Hz, 1 H), 3.25-3.36 (m, 1 H), 5.13 (d, J = 1.7 Hz, 1 H), 5.17 (d, J = 2.0 Hz, 1 H), 5.70-5.85 (m, 1 H); 13C NMR pdf (101 MHz, CDCl3) δ: 14.2, 22.7, 25.5, 29.4, 29.56, 29.61, 29.63, 32.0, 35.0, 40.5, 54.9, 55.8, 118.9, 134.3; IR (neat, cm-1) 3208 (br), 2923, 2854, 1640, 1457, 1389, 1363, 1176, 1051. Anal. calcd. for C17H35NOS: C, 67.72; H, 11.70; N, 4.65. Found: C, 67.39; H, 11.58; N, 4.69. The submitters report the specific rotation of a 97:3 mixture of (4S,SS)-4/(4R,SS)-4 as [α]20D +45.8 (c 2.6, CH2Cl2).
13.
The diastereomeric purity was determined by 1H NMR analysis (see Note 8).
14.
The submitters further confirmed the diastereomeric purity of compound 4 by converting it to the corresponding benzamide according to the following procedure. To a solution of 4 (0.1 mmol) in MeOH (1 mL) was added 4M of HCl in dioxane (0.3 mL), and the solution was stirred 1.5 h at room temperature. After cooling to 0 °C, 2M NaOH (5 mL) was added, followed by benzoyl chloride (32 µL, 0.25 mmol), and the resulting mixture was stirred over 2 h at room temperature (23 °C). After aqueous workup, a sample [GC-MS (EI): 301 (M+, 1%), 260 ([M-C3H5]+, 39%); 105 ([M-Bz]+, 100%); 77 (18%)] was submitted to chiral HPLC analysis. The chromatography was performed on a JASCO 200-series apparatus equipped with a Chiralcel OD-H column 25 cm × 0.46 cm (isocratic elution with 10% i-PrOH in n-hexane, 1.0 mL/min, UV detection at 254 nm); tR = 6.3 min (R), tR = 7.7 min (S).
15.
Concentration of fractions 48-72 furnished 977 mg (16%) of a 66:34 mixture of (4R,SS)-4/(4S,SS)-4. Concentration of fractions 73-108 furnished 935 mg (15%) of (4S,SS)-4 (>99:1 dr).
16.
MeOH (99.8%) was purchased from J. T. Baker and distilled from magnesium.
17.
At this point the pH of aqueous phase was >12. Importantly, at pH 8-9 the corresponding ammonium hydrochloride is isolated using the same procedure.
18.
The submitters report that according to GC-MS (EI): 136 ([M]+, 0.6%); 79 ([M-C4H9]+, 5%); 57 ([C4H9]+, 23%); the main impurity is likely t-BuSO2Me (tR = 4.9 min), which is volatile. After keeping under house vacuum (0.7-3.5 mmHg) until constant weight, only the expected compound 5 was observed by GC (tR = 10.5 min). GC analyses were obtained on an Agilent 5973N equipped with an HP-5 column (30 m × 0.25 mm, ID × 0.25 µm) and an EI (70 EV) detector. The temperature program: hold at 60 °C for 3 min, ramp from 60 °C to 270 °C at 15 °C/min, hold at 270 °C for 10 min.
19.
The physical properties of 5 are as follows: 1H NMR pdf (500 MHz, CDCl3) δ: 0.86 (t, J = 6.7 Hz, 3 H), 1.20 (s, 2 H), 1.44-1.21 (m, 17 H), 1.88-2.01 (m, 1 H), 2.13-2.27 (m, 1 H), 2.75 (s, 1 H), 5.05 (s, 1 H), 5.08 (d, J = 8.3 Hz, 1 H), 5.69-5.83 (m, 1 H); 13C NMR pdf (126 MHz, CDCl3) δ: 14.4, 23.0, 26.6, 29.6, 29.86, 29.92, 30.0, 32.2, 38.0, 42.9, 50.9, 77.1, 77.3, 77.6, 117.4, 136.3; IR (neat, cm-1) 3354 (br), 3076, 2956, 2922, 2853, 1640, 1466, 1439, 1378, 1354, 1130. The submitters report the specific rotation as [α]20D -6.2 (c 1.1, CH2Cl2)