Substrate Structural Effects in Yttrium(III)-Catalyzed Hydroamination/Cyclizations of 1,2-Disubstituted and 1,1,2-Trisubstituted Aminoalkenes ­Terminated by 2-(Phenyl) and 2-(2-Heteroarenyl) Groups

Abstract

A series of 2-phenyl- and 2-(2-heteroarenyl)-bearing amines possessing 1,2-disubstituted and 1,1,2-trisubststuted ­alkenes have been evaluated in intramolecular hydroaminations catalyzed by Y[N(TMS)₂]₃ (1_Y ). Aminoalkenes possessing a terminal 2-(5-trimethylsilyl)thienyl group exhibited substantially enhanced reactivity compared to their 2-(phenyl)-containing counterparts. Cyclization efficiencies imparted by the 2-[(5-trimethylsilyl)furanyl] substituent were comparable or only slightly better than those obtained with the simple the 2-(phenyl) group.

Key words

hydroamination - cyclization - yttrium - heteroarenes

• References and Notes

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• 7a General Cyclization/Hydroamination Procedure: In an argon-filled glove box, Y[N(TMS)₂]₃ (5.70 mg, 0.010 mmol) and benzene-d ₆ (0.5 mL) were added into a J. Young NMR tube equipped with a Teflon screw cap. (E)-2,2,4-Trimethyl-5-[5-(trimethylsilyl)-2-thienyl]pent-4-enylamine (3f; 28 mg, 0.10 mmol) and p-xylene (10 µL) were then added and the reactant mixture was subsequently held at 60 °C in an oil bath for 4 h until cyclization/hydroamination was judged complete (≥95% by ¹H NMR integration).
• 7b Synthesis of p-Toluenesulfonamide; 2,4,4-Trimethyl-1-(toluene-4-sulfonyl)-2-[5-(trimethylsilyl)thiophene-2-ylmethyl]tetrahydropyrrole (4f_Ts): Tetrahydropyrrole 4f was prepared from (E)-2,2,4-trimethyl-5-[5-(trimethylsilyl)-2-thienyl]pent-4-enylamine (3f; 28 mg, 0.10 mmol) by the general hydroamination procedure. The Teflon screw cap was then removed and the crude product was diluted with anhydrous CH₂Cl₂ (3 mL). TsCl (22 mg, 0.12 mmol) and pyridine (9.70 μL, 0.12 mmol) were added in succession. The reactant mixture was stirred at room temperature for 12 h, then the reactant mixture was diluted with Et₂O (10 mL), washed with saturated NaHCO₃ (3 mL) and brine (3 mL), and the organic phase was subsequently dried with Na₂SO₄. Concentration in vacuo followed by flash chromatography on silica gel (hexane–EtOAc, 15:1) afforded 2,4,4-trimethyl-1-(toluene-4-sulfonyl)-2-[5-(trimethylsilyl)thiophene-2-ylmethyl]tetrahydropyrrole (4f_Ts ; 33.2 mg, 76%). ¹H NMR (500 MHz, CDCl₃): δ = 7.75 (d, J = 8.0 Hz, 2 H, 2Ar-H), 7.26 (d, J = 8.0 Hz, 2 H, 2Ar-H), 7.07 (d, J = 3.0 Hz, 1 H, Ar-H), 6.98 (d, J = 3.0 Hz, 1 H, Ar-H), 3.57 (d, J = 14.0 Hz, 1 H, CH), 3.29 (d, J = 14.0 Hz, 1 H, CH), 3.06 (d, J =9.5 Hz, 1 H, CH), 2.98 (d, J = 10.0 Hz, 1 H, CH), 2.40 (s, 3 H, ArCH₃), 2.15 (d, J = 13.0 Hz, 1 H, CH), 1.51 (s, 3 H, CH₃), 1.42 (d, J = 13.5 Hz, 1 H, CH), 0.97 (s, 3 H, CH₃), 0.90 (s, 3 H, CH₃), 0.27 (s, 9 H, 3 SiCH₃); ¹³C NMR (500 MHz, CDCl₃): δ = 145.2, 142.8, 138.4, 133.9, 129.4, 129.3, 127.3, 68.7, 61.8, 52.6, 42.3, 36.2, 27.6, 27.2, 27.1, 21.5, −0.02; IR (film): 2957, 1439, 1342, 1251, 1209, 1154, 1092, 1055, 984, 840, 814, 759, 714, 659, 592, 548 cm⁻¹; HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₃₃NO₂S₂Si: 436.1816; found: 436.1897.