1.
N-Sulfinamide 1 could be purchased from Aldrich Chemical Company, Inc. in optically pure form. However, (±)-1 can be obtained at much lower cost following a known procedure,11 which involves two steps from p-tolyldisulfide.
2.
Acetophenone, 99% was purchased from Aldrich Chemical company, Inc. and was used without further purification.
3.
Titanium (IV) ethoxide, technical grade was purchased from Aldrich Chemical Company, Inc. and was used without further purification.
4.
No difference in the yield was observed when using either dried CH2Cl2 (from P2O5) or the directly purchased CH2Cl2 from SDS (purex analytical grade).
5.
The reaction was monitored by TLC on silica gel using hexanes/EtOAc (2:1) as eluent and visualization with phosphomolibdic acid. The starting material 1 had Rf = 0.1 (green), acetophenone had Rf = 0.77 (green), and the final product 2 had Rf = 0.38 (brown).
6.
A double filter paper of medium porosity was used.
7.
Silica gel (230–400 mesh) from Merck was used.
8.
The physical properties of N-sulfinylketimine 2 were as follows: white solid, mp 95.0–96.0 °C (lit.2 mp 99–100 °C). 1H NMR pdf (500 MHz) δ: 2.40 (s, 3 H) 2.78 (s, 3 H), 7.32 (d, J = 8.2 Hz, 2 H), 7.39 (t, J = 8.0 Hz, 2 H), 7.47 (t, J = 6.7 Hz, 1 H), 7.72 (d, J = 8.2 Hz, 2 H), 7.88 (d, J = 7.6 Hz, 2 H), 13C NMR pdf (125.7 MHz) δ: 20.2, 21.4, 125.2, 127.5, 128.4, 129.8, 131.8, 138.2, 141.8, 143.3, 173.9; IR (KBr, cm−1): 3430, 1637, 1565, 1096; LRMS (ESI-MS) m/z 258 (M+H)+, 280 (M+Na)+; HRMS (FAB-MS) calcd for C15H16NOS (M+H)+ 258.0947, found 258.1008.
9.
N-Sulfinylketimine 2 and N-sulfonylketimine 3 are hydrolyzed upon extended contact with silica gel; therefore the flash chromatography should be carried out rapidly.
10.
In this case, dry CH2Cl2 (distilled from P2O5) was used, since traces of water can hydrolyze the starting material 2 or N-sulfonylketimine 3.
11.
This reaction was exothermic, therefore the addition should be carried out at 0 °C. Without an ice bath (0 °C) an increase in temperature from 21 to 40 °C was detected.
12.
3-Chloro-perbenzoic acid (>77 %) was purchased from Aldrich Chemical Company, Inc. (Lot number S22939 was used, which contained 18.03 % of water and 71.70 % of 3-chloroperbenzoic acid). The reagent was directly used without removal of the water, which resulted in a 78% yield. The yield of the reaction could be increased to 84% when water was removed from this reagent. The procedure for removing water was as follows: Prior to its use, water was removed by dissolving the commercial product in CH2Cl2, drying the organic solution over anhydrous Na2SO4, filtering and concentrating the reagent to dryness under vacuum. Titration following the procedure reported in the literature (McDonald, R. N.; Steppel, R. N.; Dorsey, J. E. Org. Synth. 1970, 50, 15) indicated a purity of 90% (using Na2S2O3 0.1004 N). A purity of 91% was obtained when the purity determination was carried out by HPLC: performed on ZORBAX RX-C8 (4.6 mm × 25 cm) with 50:50 water:methanol, with a flow rate of 0.5 mL/min at 210 nm (3-chlorobenzoic acid tR= 5.5 min, 3-Chloroperbenzoic acid tR= 21.5 min). When a calibration standard was used (3-chlorobenzoic acid at different concentrations) under these conditions, the purity was determined to be 90%.
13.
The reaction was monitored by TLC on silica gel using hexanes/EtOAc (2:1) as eluent and visualization with a phosphomolibdic acid. The starting material 2 has an Rf = 0.38 while Rf= 0.70 for the final product 3.
14.
N-Sulfonylketimine 3 is hydrolyzed upon extended contact with water; therefore, the washes should be carried out rapidly.
15.
The physical properties of N-sulfonylketimine 3 were as follows: white solid, mp 88.5–90.5 °C (lit.10kmp 88–90 °C). 1H NMR pdf (500 MHz) δ: 2.45 (s, 3 H) 2.99 (s, 3 H), 7.34 (d, J = 8.2 Hz, 2 H), 7.41 (t, J = 8.0 Hz, 2H), 7.53 (t, J = 7.2 Hz, 1H), 7.90 (d, J = 8.2 Hz, 2 H), 7.93 (d, J = 8.0 Hz, 2 H); 13C NMR pdf (125.7 MHz, CDCl3) δ: 21.1, 21.5, 127.0, 128.2, 128.6, 129.4, 133.1, 137.5, 138.7, 143.5, 179.8; IR (KBr, cm−1): 3435, 1590, 1570, 1286, 1180, 1083; LRMS (ESI-MS) m/z 274 (M+H)+, 296 (M+Na)+; HRMS (FAB-MS) calcd for C15H16NO2S (M+H)+ 274.0896, found 274.0775. The purity of the sample was determined by HPLC (>98%), performed on Chiral AS (Daicel) with 60:40 hexane:2-propanol and a flow rate of 0.6 mL/min.
16.
The N-sulfonylketimine 3 (0.007 mol, 2 g) could be crystallized from Et2O (80 mL). The solution was heated until the solid dissolved, and filtered through filter paper of medium porosity. The solution was kept for 12 h at −20 °C. White needles were collected using a Büchner funnel under vacuum (25 mmHg), which resulted in the isolation of 1.90 g of pure 3 (95% yield).