Synthesis of N-Tosyl-2-methylaziridineTetrahedron: Asymmetry 8(15), 2655-2662 (1997)(S)-N,O-Ditosylalaninol 6cTosyl chloride (9.53 g, 40 mmol) was added in portions over 40 min to (S)-alaninol (
5a, 1.50 g, 20 mmol) in pyridine (50 mL) at 0°C. Stirring was continued for another 3 h, then the flask was placed at -30°C overnight. Ice (200 g) was added followed by concd HCl (60 mL). The water/pyridine solution was extracted twice with EtOAc. The combined organic phases were washed with saturated aqueous NaHCO3, water and brine, and finally dried (MgSO
4). The solvent was evaporated, leaving a sticky yellow substance. Recrystallisation from hot ethanol yielded 4.77 g (62%) of
6c as a yellow powder.
(S)-N-Tosyl-2-methylaziridine 7cSulfonamide
6c (4.77 g, 12.4 mmol) in dry THF (40 mL) was added dropwise to a suspension of washed (hexane) sodium hydride (18.6 mmol) in dry THF (10 mL). The resulting mixture was stirred for 2 h at room temperature, with a lot of foaming. The reaction was quenched by adding water (50 mL) and brine (50 mL). The aqueous phase was extracted 3 times with diethyl ether, the combined ether phases were washed with 2 M NaOH and dried (MgSO
4), and the solvent evaporated, leaving a yellow liquid. The liquid was filtered through silica (6 cm column, eluent: hexane:EtOAc 80:20). Evaporation left 1.24 g (47%) of
7c as a white solid.
Synthesis of N-Tosyl-2-methylaziridineOrg. Lett. 4(6), 949-952 (2002)(S)-N-Tosyl-2-methylaziridine 7cTo a solution of L-alaninol (8 mmol) and triethylamine (3.5 equiv) in dry acetonitrile (80 mL) was slowly added p-TsCl (2 equiv) and DMAP (0.1 equiv) at 0°C with stirring for 30 min. The reaction mixture was stirred at room temperature for 4-5 h. The solvent was removed under reduced pressure and dissolved with EtOAc (100 mL). The organic layer was washed with brine (2x40 mL). The organic layer was dried over anhydrous MgSO
4 and filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified on a silica gel column chromatography to give white solid
13 (1.62 g, 82% yield).
A Convenient Method for the Preparation of Enantiomerically Pure 2-Substituted N-TosylaziridinesMalcolm B. Berry, Donald CraigSynlett (1) 41-44 (1992) DOI:
10.1055/s-1992-21259
AbstractA three-step procedure for the synthesis of enantiomerically pure 2-substituted N-tosylaziridines
4 is described. The method involves N-tosylation of (S)-2-amino acids
1, followed by reduction to give N-tosyl-2-amino alcohols
3 and O-tosylation with in situ aziridine ring closure.
Tosylation of 2-Methylaziridine (TsCl/Et
3, 65%)
J. Chem. Soc. Perkin Trans. 1 2015-2020 (1991)(+)-(2S)-2-Methyl-1-(p-tolylsulfonyl)aziriridine (17) Helv. Chim. Acta. 83, 2594-2606 (2000)A 50-ml pear-shaped flask was charged with a mixture of TsCl (4.19 g, 22 mmol), pyridine (3.5 ml), and CH
2Cl
2 (6.5 ml). The mixture was cooled to 0°C, and (-)-(2S)-2aminopropan-1-ol (0.751 g, 10.0 mmol) was added dropwise. The mixture was allowed to warm to RT. and stirred for 16 h. The mixture was then poured into a separatory funnel containing 50 ml of cold 1N HCl and 25 ml of CH
2Cl
2. After extraction, the org. layer was separated and washed with saturated CuSO
4 solution (1x25 ml) and brine (1x25 ml); each aqueous layer was back-extracted with CH
2Cl
2 (2x25 ml). The organic fractions were combined, dried (MgSO
4), and concentrated in vacuo to give 3.9 g of a greenish oil, which was taken up in dry acetone (50 ml) and stirred over 5.0 g of K
2CO
3 for 14 h. This mixture was filtered through a plug of Celite and concentrated in vacuo to give 3.4g of a yellow oil, which was purified by flash chromatography hexane) to give 1.99 g of a white solid, which was recrystallized from refluxing petroleum ether to give 1.86 g (8.8 mmol, 88%) of
17 Colorless needles, mp 57-58°C.
Formation of Sodium Naphthalide SolutionTo a stirred solution of naphthalene (190 mg, 1.5 mmol) in 10 ml of dry 1,2-dimethoxyethane was added Na metal (125 mg, 5.5 mmol). This mixture was stirred vigorously for 2 h at RT prior to use.
Deprotection of p-Toluenesulfonate A solution of 0.2 mmol of an N-Tosylamide in 5 ml of dry 1,2-dimethoxyethane (DME) was cooled to -50°C, and the above naphthalide solution was added dropwise with vigorous stirring. Addition (ca. 5 ml) was continued until a persistent green color was achieved. The mixture was allowed to warm to 0° and then quenched by addition of 1 ml of EtOH. The mixture was concentrated at reduced pressure to give a solid white residue, which was purified by flash chromatography to afford the deprotected amine (90%+ yield) as a slightly yellow oil.