background and overview[1]
currently, many natural products and drug molecules contain halogens. the halogen cyclization reaction of alkenes is a very important method to introduce halogens. optically active hydroxylamine compounds exist in many drug molecules, such as sphingosin anti-aging agent 4020e and its analogues. the commercially available d-sphingosine has this type of structure and is an effective and highly selective pkc. inhibitors. phosphorus oxygen ligand (1s, 2s)-(-)-1,2-diaminocyclohexane-n,n’-bis(2′-diphenylphosphorobenzoyl) is an intermediate for the synthesis of this type of compound. .
preparation[1]
(1s, 2s)-(-)-1,2-diaminocyclohexane-n,n’-bis(2′-diphenylphosphonobenzoyl) is prepared as follows:
under nitrogen conditions, add (r, r)-cyclohexanediamine (1.26g, 11.0mmol), 2-diphenylphosphine benzoic acid (6.74g), and dcm (100.0ml) to the reactor in sequence. , then add edci (4.22g, 22.0mmol) and dmap (1.34g, 11.0mmol) in sequence, stir at room temperature for 6 hours, quench with 1n hydrochloric acid aqueous solution, extract the aqueous phase with dcm (3 × 50.0ml), and combine the organic phases , dried over anhydrous magnesium sulfate, spin-dried and column chromatographed to obtain the product trostligand shown; dissolve trostligand (4.84g, 7.0mmol) in dcm (100.0ml), add hydrogen peroxide (17.5ml, 35%w) at 0°c /w), stir for 4 hours at 0°c, add water (100.0ml) to dilute, extract the aqueous phase with dcm (3×50.0ml), combine the organic phases, dry over anhydrous magnesium sulfate, spin dry and then column chromatography to obtain the result the product shown is a white solid product represented by formula a (1s, 2s)-(-)-1,2-diaminocyclohexane-n,n’-bis(2′-diphenylphosphorus benzoyl) 4.34g, 86% yield.
the structure confirmation results are as follows: 1hnmr (non-foaming surfactant hz, cdcl3) δ8.17 (s, 2h), 7.66-7.64 (m, 2h), 7.60-7.55 (m, 6h), 7.49-7.41 ( m, 12h), 7.39-7.34 (m, 4h), 7.33-7.28 (m, 4h), 3.38 (s, 2h), 1.75 (d, j=6.4hz, 2h), 1.56 (s, 2h), 1.14 (d, j=4.8hz, 4h); 13cnmr (100hz, cdcl3) δ168.61.168.58, 141.53, 141.45, 134.3, 134.1, 133.3, 132.8, 132.6, 132.5, 132.4, 132.3, 132.2, 132.1, 132.0 3,132.01 , 131.7, 130.5, 129.9, 129.83, 129.76, 129.6, 129.5, 128.62, 128.56, 128.5, 128.4, 54.5, 31.5, 24.5.
