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Titanium-Catalyzed Hydroaminoalkylation of Vinylsilanes and a One-Pot Procedure for the Synthesis of 1,4-Benzoazasilines

Abstract

Vinylsilanes undergo intermolecular alkene hydroaminoalkylation with secondary amines in the presence of a titanium mono(aminopyridinato) catalyst to give the branched hydroaminoalkylation products with high regioselectivity. Corresponding reactions of a suitable (2-bromophenyl)vinylsilane combined with a subsequent intramolecular Buchwald–Hartwig amination result in the development of an elegant one-pot procedure for the synthesis of 1,4-benzoazasilines.

Key words

amination - amines - palladium - silicon - titanium

• References and Notes


For reviews on the hydroaminoalkylation of alkenes, see:
• 1a Roesky PW. Angew. Chem. Int. Ed. 2009; 48: 4892 ; Angew. Chem. 2009, 121, 4988
• 1b He T.-Q. Zheng X.-J. Cai H. Xue Z.-L. Chin. J. Inorg. Chem. 2014; 30: 53
• 1c Chong E. Garcia P. Schafer LL. Synthesis 2014; 46: 2884

Group 5 metal catalysts:
• 2a Clerici MG. Maspero F. Synthesis 1980; 305
• 2b Nugent WA. Ovenall DW. Holmes SJ. Organometallics 1983; 2: 161
• 2c Herzon SB. Hartwig JF. J. Am. Chem. Soc. 2007; 129: 6690
• 2d Herzon SB. Hartwig JF. J. Am. Chem. Soc. 2008; 130: 14940
• 2e Eisenberger P. Ayinla RO. Lauzon JM. P. Schafer LL. Angew. Chem. Int. Ed. 2009; 48: 8361 ; Angew. Chem. 2009, 121, 8511
• 2f Eisenberger P. Schafer LL. Pure Appl. Chem. 2010; 82: 1503
• 2g Zi G. Zhang F. Song H. Chem. Commun. 2010; 46: 6296
• 2h Reznichenko AL. Emge TJ. Audörsch S. Klauber EG. Hultzsch KC. Schmidt B. Organometallics 2011; 30: 921
• 2i Reznichenko AL. Hultzsch KC. J. Am. Chem. Soc. 2012; 134: 3300
• 2j Garcia P. Lau YY. Perry MR. Schafer LL. Angew. Chem. Int. Ed. 2013; 52: 9144 ; Angew. Chem. 2013, 125, 9314
• 2k Zhang Z. Hamel J.-D. Schafer LL. Chem. Eur. J. 2013; 19: 8751
• 2l Dörfler J. Doye S. Eur. J. Org. Chem. 2014; 2790
• 2m Chong E. Brandt JW. Schafer LL. J. Am. Chem. Soc. 2014; 136: 10898

Ruthenium catalysts:
• 3a Jun C.-H. Hwang D.-C. Na S.-J. Chem. Commun. 1998; 1405
• 3b Chatani N. Asaumi T. Yorimitsu S. Ikeda T. Kakiuchi F. Murai S. J. Am. Chem. Soc. 2001; 123: 10935
• 4 Iridium catalysts: Pan S. Endo K. Shibata T. Org. Lett. 2011; 13: 4692
• 5 Zirconium catalysts: Bexrud JA. Eisenberger P. Leitch DC. Payne PR. Schafer LL. J. Am. Chem. Soc. 2009; 131: 2116

Titanium catalysts:
• 6a Müller C. Saak W. Doye S. Eur. J. Org. Chem. 2008; 2731
• 6b Kubiak R. Prochnow I. Doye S. Angew. Chem. Int. Ed. 2009; 48: 1153 ; Angew. Chem. 2009, 121, 1173
• 6c Prochnow I. Kubiak R. Frey ON. Beckhaus R. Doye S. ChemCatChem. 2009; 1: 162
• 6d Kubiak R. Prochnow I. Doye S. Angew. Chem. Int. Ed. 2010; 49: 2626 ; Angew. Chem. 2010, 122, 2683
• 6e Prochnow I. Zark P. Müller T. Doye S. Angew. Chem. Int. Ed. 2011; 50: 6401 ; Angew. Chem. 2011, 123, 6525
• 6f Jaspers D. Saak W. Doye S. Synlett 2012; 23: 2098
• 6g Dörfler J. Doye S. Angew. Chem. Int. Ed. 2013; 52: 1806 ; Angew. Chem. 2013, 125, 1851
• 6h Preuß T. Saak W. Doye S. Chem. Eur. J. 2013; 19: 3833
• 6i Chong E. Schafer LL. Org. Lett. 2013; 15: 6002
• 6j Dörfler J. Preuß T. Schischko A. Schmidtmann M. Doye S. Angew. Chem. Int. Ed. 2014; 53: 7918 ; Angew. Chem. 2014, 126, 8052
• 6k Dörfler J. Preuß T. Brahms C. Scheuer D. Doye S. Dalton Trans. 2015; 44: 12149
• 6l Dörfler J. Bytyqi B. Hüller S. Mann NM. Brahms C. Schmidtmann M. Doye S. Adv. Synth. Catal. 2015; 357: 2265
• 6m Lühning LH. Brahms C. Nimoth JP. Schmidtmann M. Doye SZ. Anorg. Allg. Chem. 2015; 641: 2071
• 6n Manßen M. Lauterbach N. Dörfler J. Schmidtmann M. Saak W. Doye S. Beckhaus R. Angew. Chem. Int. Ed. 2015; 54: 4383 ; Angew. Chem. 2015, 127, 4458
• 6o Weers M. Lühning LH. Lührs V. Brahms C. Doye S. Chem. Eur. J. 2017; 23: 1237
• 6p Lühning LH. Strehl J. Schmidtmann M. Doye S. Chem. Eur. J. 2017; 23: 4197
• 7 Elkin T. Kulkarni NV. Tumanskii B. Botoshansky M. Shimon LJ. W. Eisen MS. Organometallics 2013; 32: 6337

For reviews on the Buchwald-Hartwig amination, see:
• 8a Hartwig JF. Nature (London, U.K.) 2008; 455: 314
• 8b Surry DS. Buchwald SL. Angew. Chem. Int. Ed. 2008; 47: 6338 ; Angew. Chem. 2008, 120, 6438
• 8c Schlummer B. Scholz U. Adv. Synth. Catal. 2004; 346: 1599
• 8d Elkema R. Anderson HL. Macromolecules 2008; 41: 9930

For reviews on organosilicon compounds with medicinal applications, see:
• 9a Mills JS. Showell GA. Expert Opin. Invest. Drugs 2004; 13: 1149
• 9b Franz AK. Wilson SO. J. Med. Chem. 2013; 56: 388
• 10a Aoyama T. Sato Y. Suzuki T. Shirai H. J. Organomet. Chem. 1978; 153: 193
• 10b Francois C. Boddaert T. Durandetti M. Querolle O. Van Hijfte L. Meerpoel L. Angibaud P. Maddaluno J. Org. Lett. 2012; 14: 2074
• 11 Geyer M. Karlsson O. Baus JA. Wellner E. Tacke R. J. Org. Chem. 2015; 80: 5804
• 12 General Procedure for the One-Pot Synthesis of 1,4-Benzoazasilines, as Exemplified by the Synthesis of Product 44a An oven-dried Schlenk tube equipped with a Teflon stopcock and a magnetic stirring bar was transferred into a nitrogen-filled glovebox and charged with catalyst III (154 mg, 0.20 mmol, 10 mol%) and toluene (0.5 mL). Afterwards, N-methylaniline (3, 214 mg, 2.00 mmol), (ortho-bromophenyl)dimethylvinylsilane (37, 531 mg, 2.20 mmol), and toluene (0.5 mL) were added. After the mixture had been heated to 160 °C for 24 h, the Schlenk tube was cooled to r.t. and transferred back into a nitrogen-filled glovebox. Then Pd₂(dba)₃ (46 mg, 0.05 mmol, 2.5 mol%), RuPhos (66 mg, 0.1 mmol, 7 mol%), NaOt-Bu (288 mg, 3.0 mmol), and toluene (5 mL) were added. After heating the mixture to 110 °C for additional 24 h, the crude product was purified by flash chromatography (SiO₂, PE), to give 1,4-benzoazasiline 44a (420 mg, 1.57 mmol, 79%) as a colorless oil. R_f = 0.20 (SiO₂, PE). ¹H NMR (500 MHz, CDCl₃): δ = 7.39 (dd, J= 7.2, 1.5 Hz, 1 H), 7.32 (t, J= 7.9 Hz, 2 H), 7.16 (d, J= 7.5 Hz, 2 H), 7.10–7.03 (m, 2 H), 6.83 (td, J= 7.2, 0.6 Hz, 1 H), 6.66 (d, J= 8.4 Hz, 1 H), 3.85 (dd, J= 13.1, 3.6 Hz, 1 H), 3.55 (dd, J= 13.1, 9.6 Hz, 1 H), 1.30–1.23 (m, 1 H), 1.04 (d, J= 7.5 Hz, 3 H), 0.28 (s, 3 H), 0.26 (s, 3 H) ppm. ¹³C{¹H} NMR (125 MHz, DEPT, CDCl₃): δ = 154.1 (C), 149.6 (C), 135.1 (CH), 129.5 (CH), 129.4 (CH), 124.7 (CH), 123.6 (C), 123.1 (CH), 119.2 (CH), 117.8 (CH), 57.5 (CH₂), 17.9 (CH), 13.0 (CH₃), –1.7 (CH₃), –4.4 (CH₃) ppm. ²⁹Si{¹H} NMR (99.4 MHz, INEPT, CDCl₃): δ = –8.1 ppm. GC–MS (EI, 70 eV): m/z(%) = 267 (40) [M]⁺, 225 (100) [C₁₄H₁₅NSi]⁺, 210 (40), 180 (8), 105 (11) [C₇H₇N]⁺, 91 (5) [C₆H₅N]⁺. HRMS (EI): m/z calcd for C₁₇H₂₁NSi: 267.1438; found: 267.1440 [M]⁺. IR (ATR, neat): λ ^–1 = 2948, 2864, 1585, 1557, 1494, 1472, 1431, 1340, 1248, 1175, 1129, 1088, 835, 808, 722, 750, 696, 610 cm^–1.