Diastereoselective Synthesis of N-tert-Butanesulfinylamines through Addition of p-Nitrobenzyl Chloride to N-tert-Butanesulfinimines Using a TDAE ­Strategy

Abstract

An easy and efficient method of diastereoselective synthesis of N-tert-butanesulfinylamines using a TDAE strategy was developed. Good yields and diastereoselectivities were achieved using readily available N-tert-butanesulfinimines and commercially available p-nitrobenzyl chloride.

Key words

N-tert-butanesulfinimines - diastereoselectivity - TDAE - addition - chiral auxiliary

• References and Notes

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• 9 General Procedure To a stirred solution of N-sulfinimine 2 (0.24 mmol) in DMF (1 mL) at –20 °C was added TDAE (0.2 mmol) followed by dropwise addition of a solution of p-nitrobenzyl chloride (1) in DMF (1 mL). The solution was vigorously stirred at –20 °C for 1 h and then maintained at r.t. for 2 h. H₂O (5 mL) was added, and the aqueous solution was extracted with CH₂Cl₂ (3 × 15 mL). The combined organic layer was washed with H₂O (20 mL) and dried over MgSO₄. Filtration and evaporation of the solvent furnished the crude product. Purification by silica gel chromatography (EtOAc–PE: from 6:4 to 8:2 depending on the polarity of substrates) allowed pure amine products 3 as a mixture of diastereoisomers. N-[1,2-Bis(4-nitrophenyl)ethyl]-2-methylpropane-2-sulfinamide (3b) Major Diastereoisomer (R,R) Yellow solid; mp 171–174 °C. ¹H NMR (200 MHz, CDCl₃): δ = 8.16 (d, J = 8.6 Hz, 2 H), 8.08 (d, J = 8.5 Hz, 2 H), 7.40 (d, J = 8.6 Hz, 2 H), 7.18 (d, J = 8.5 Hz, 2 H), 4.80–4.70 (m, 1 H), 3.67 (d, J = 4.7 Hz, 1 H), 3.48 (dd, J = 13.5, 6.2 Hz, 1 H), 3.13 (dd, J = 13.5, 7.7 Hz, 1 H), 1.17 (s, 9 H). ¹³C NMR (50 MHz, CDCl₃): δ = 48.2, 147.8, 147.1, 144.3, 130.5, 128.3, 124.2, 123.8, 60.1, 56.6, 43.0, 22.6. ESI-HRMS: m/z [M + Na]⁺ calcd for [C₁₈H₂₁N₃O₅SNa]⁺: 414.10941; found: 414.10979. Minor Diastereoisomer (R,S) Yellow solid; mp 145–148 °C. ¹H NMR (200 MHz, CDCl₃): δ = 8.18 (d, J = 8.8 Hz, 2 H), 8.12 (d, J = 8.7 Hz, 2 H), 7.39 (d, J = 8.8 Hz, 2 H), 7.19 (d, J = 8.7 Hz, 2 H), 4.86–4.79 (m, 1 H), 3.58 (br s, 1 H), 3.24 (dd, J = 7.3, 3.6 Hz, 2 H), 1.19 (s, 9 H). ¹³C NMR (50 MHz, CDCl₃): δ = 148.0, 147.7, 147.4, 143.3, 130.5, 128.7, 124.11, 124.08, 59.0, 56.3, 44.7, 22.6. ESI-HRMS: m/z [M + Na]⁺ calcd for [C₁₈H₂₁N₃O₅SNa]⁺: 414.10941; found: 414.10982.
• 10 CCDC 929478 contains the supplementary crystallographic data of compound (R,R)-3b for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif.
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• 12 Deprotection of Amine (R,R)-3b To a stirred solution of N-protected amine (R,R)-3b (47 mg, 0.12 mmol) in MeOH (4 mL) was added 4 M HCl in dioxane (180 μL, 0.72 mmol), and the solution was stirred at r.t. for 2 h. The reaction mixture was then concentrated under reduced pressure, diluted with EtOAc (20 mL), and washed with sat. aq NaHCO₃ (20 mL). The aqueous layer was extracted twice more with EtOAc (2 × 20 mL). The combined organic layers were dried over MgSO₄, filtered, and concentrated under reduced pressure Solvents were evaporated under vacuum. Purification by silica gel chromatography (CH₂Cl₂–MeOH = 95:5) allowed pure primary amine 4b (26 mg, 75%). (R)-1,2-Bis(4-nitrophenyl)ethylamine (R)-(4b) Yellow solid; mp 141–144 °C. ¹H NMR (200 MHz, CD₃OD): δ = 8.20 (d, J = 8.7 Hz, 2 H), 8.11 (d, J = 8.7 Hz, 2 H), 7.56 (d, J = 8.7 Hz, 2 H), 7.35 (d, J = 8.7 Hz, 2 H), 4.55–4.45 (m, 1 H), 3.27–3.14 (m, 2 H). ¹³C NMR (50 MHz, CD₃OD): δ = 149.0, 148.4, 146.2, 146.2, 131.7, 129.3, 124.8, 124.6, 57.7, 44.4. ESI-HRMS: m/z [M + Na]⁺ calcd for [C₁₄H₁₃N₃O₄Na]⁺: 310.07983; found: 310.07965.