Lithium Sulfondiimidoyl Carbanions

Abstract

The trapping of sulfondiimine-based α-lithiated carbanions with aldehydes leads to unprecedented β-hydroxy sulfondiimines in good yields. An alkylation has been achieved by treatment of the metalated species with methyl iodide. Of special interest, N-monosubstituted β-hydroxy sulfondiimines can be accessed without protection of the free nitrogen.

Key words

sulfur compound - sulfondiimine - lithium - carbanion - ­alkylation

• References and Notes


For recent examples, see:
• 1a Lücking U. Angew. Chem. Int. Ed. 2013; 52: 9399 ; and references cited therein
• 1b Lücking U, Scholz A, Lienau P, Siemeister G, Bohlmann R, Bömer U. WO 2015150273, 2015
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For recent preparative approaches towards sulfondiimines, see:
• 5a Candy M, Guyon C, Mersmann S, Chen J.-R, Bolm C. Angew. Chem. Int. Ed. 2012; 51: 4440
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For selected applications of sulfondiimines, see:
• 6a Diederich WE, Haake M. J. Org. Chem. 2003; 68: 3817
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• 7 The attempt to deprotonate 2a with 2.0 equiv of the superbase generated from KOH in DMSO (at 20 °C for 15 min followed by treatment with 5a at the same temperature), which recently proved effective in N-alkylations of NH-sulfondiimines (comp. ref. 5d), remained unsuccessful coming along with partial decomposition of 2a.
• 8 General Experimental Procedure Under an atmosphere of argon, in a flame-dried Schlenk tube equipped with magnetic stirrer and septum, the sulfondiimine (1.0 equiv, 0.163 mmol) was dissolved in dry THF (2 mL). TMEDA (2.0 equiv) was added, and the resulting solution was cooled to –78 °C. Then, n-BuLi (1.05 equiv or 2.10 equiv, depending on the substrate) was added dropwise at –78 °C within 5 min, and the resulting solution was stirred for 30 min at –78 °C. The electrophilic reagent (see each case for details) was then added by syringe, and the reaction mixture was stirred at –78 °C. The conversion of the reaction was monitored by TLC. In case of an incomplete conversion, the reaction mixture was slowly warmed to room temperature (see each case for details). Upon complete conversion sat. NH₄Cl solution (15 mL) was added. The mixture was extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layers were dried over anhydrous MgSO₄, and the solvents were removed under reduced pressure. Purification by flash column chromatography using n-pentane–EtOAc gradient elution (see each case for details) afforded the desired product.
• 9 Analytical Data for Selected Products 1-(N,N′-Diphenyl-S-phenylsulfondiimidoyl)-2-phenylethan-2-ol (3a) 94% yield. ¹H NMR (600 MHz, CDCl₃): δ = 8.24 (d, J = 7.7 Hz, 2 H), 7.69–7.65 (m, 1 H), 7.63–7.58 (m, 2 H), 7.27–7.14 (m, 13 H), 7.02 (br s, 1 H, OH), 7.96–7.91 (m, 2 H), 5.00 (d, J = 10.4 Hz, 1 H), 4.00 (dd, J = 14.1, 10.4 Hz, 1 H), 2.99 (d, J = 14.1 Hz, 1 H). ¹³C NMR (151 MHz, CDCl₃): δ = 144.6, 114.4, 140.9, 136.4, 133.5, 129.8 (2 C), 129.3 (2 C), 129.2 (2 C), 129.2 (2 C), 128.6 (2 C), 128.0, 125.6 (2 C), 123.4 (2 C), 122.8 (2 C), 122.1, 121.8, 69.2, 62.8. MS (EI): m/z (%) = 412 (6) [M]⁺, 320 (15), 199 (100), 197 (33), 181 (22), 180 (25), 167 (31), 165 (45), 123 (29), 106 (22), 105 (24), 103 (27), 93 (17), 77 (41). IR (neat): ν = 3269, 3061, 2863, 1590, 1483, 1446, 1284, 1247, 1176, 1068, 974, 906, 856, 832, 792, 747, 690 cm^–1. ESI-HRMS: m/z calcd for C₂₆H₂₅ON₂S: 413.1682; found: 413.1682. N,N′-Diphenyl-S-ethyl-S-phenyl-sulfondiimine (7) 94% yield; mp 125–126 °C. ¹H NMR (600 MHz, CDCl₃): δ = 8.21–8.28 (m, 2 H), 7.61–7.52 (m, 3 H), 7.20–7.12 (m, 8 H), 6.88–6.84 (m, 2 H), 3.64 (q, J = 7.4 Hz, 2 H), 1.07 (t, J = 7.4 Hz, 3 H). ¹³C NMR (151 MHz, CDCl₃): δ = 145.9 (2 C), 136.1, 132.8, 129.5 (2 C), 129.4 (2 C), 129.1 (4 C), 123.0 (4 C), 121.0 (2 C), 50.2, 7.8. MS (EI): m/z (%) = 320 (26) [M]⁺, 229 (59), 200 (100), 182 (20), 167 (17), 105 (10), 97 (17), 77 (15). IR (KBr): ν = 3054, 1590, 1480, 1445, 1285, 1251, 1174, 1067, 1023, 964, 797, 747, 692. ESI-HRMS: m/z calcd for C₂₀H₂₁N₂S: 321.1420; found: 321.1420.
• 10 To our surprise, neither acetone nor acetophenone (2.0 equiv in each case) could be employed as electrophile. Even after 48 h at 20 °C no addition product of type 3 was observed. Only partial degradation of 2a had occurred.
• 11 Here, both 2b and 1a were applied as racemates. For accessing enantiopure sulfondiimines, see ref. 5a and references cited therein.
• 12 Attempts to separate the diastereomers of 3k remained unsuccessful.

For selected syntheses and applications of structurally analogous NH-β-hydroxy sulfoximines that have been studied extensively, see:
• 13a Hwang K.-J, Logusch EW, Brannigan LH, Thomson MR. J. Org. Chem. 1987; 52: 3435
• 13b Bolm C, Felder M. Tetrahedron Lett. 1993; 34: 6041
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• 13e Shen X, Zhang W, Ni C, Gu Y, Hu J. J. Am. Chem. Soc. 2012; 134: 16999
• 13f Shen X, Miao W, Ni C, Hu J. Angew. Chem. Int. Ed. 2014; 53: 775
• 14 When the corresponding NH-sulfoximine was applied as starting material under the same conditions, no conversion was observed.
• 15 Notably, this behavior is in analogy to observations made in sulfoximine chemistry where the diastereomers of β-hydroxy sulfoximines stemming from ketone additions proved readily separable, while products from reactions with aldehydes were difficult to isolate in diastereomerically pure form. For a representative report, see: Johnson CR, Stark CJ. J. Org. Chem. 1982; 47: 1193