Hydroaminoalkylation of Allenes

Abstract

The first examples of early-transition-metal-catalyzed hydroaminoalkylation reactions of allenes are reported. Initial studies performed with secondary aminoallenes led to the identification of a suitable titanium catalyst and revealed that under the reaction conditions, the initially formed hydroaminoalkylation products undergo an unexpected titanium-catalyzed rearrangement to form the thermodynamically more stable allylamines. The assumption that this rearrangement involves a reactive allylic cation intermediate provides a simple explanation of the fact that no successful early-transition-metal-catalyzed hydroaminoalkylations of allenes have previously been reported. As a result of the generation of the corresponding cation, the titanium-catalyzed intermolecular hydroaminoalkylation of propa-1,2-diene unexpectedly gives an aminocyclopentane product formed by incorporation of two equivalents of propa-1,2-diene.

Key words

allenes - amines - C–H activation - homogeneous catalysis - titanium - hydroaminoalkylation

• References and Notes


For selected reviews on the hydroaminoalkylation of alkenes, see:
• 1a Chong E, Garcia P, Schafer LL. Synthesis 2014; 46: 2884
• 1b Hannedouche J, Schulz E. Organometallics 2018; 37: 4313
• 1c Edwards PM, Schafer LL. Chem. Commun. 2018; 54: 12543
• 2 Manßen M, Lauterbach N, Dörfler J, Schmidtmann M, Saak W, Doye S, Beckhaus R. Angew. Chem. Int. Ed. 2015; 54: 4383

For group-3-metal-catalyzed hydroaminoalkylation reactions of alkenes with tertiary amines, see:
• 3a Nako AE, Oyamada J, Nishiura M, Hou Z. Chem. Sci. 2016; 7: 6429
• 3b Liu F, Luo G, Hou Z, Luo Y. Organometallics 2017; 36: 1557
• 3c Gao H, Su J, Xu P, Xu X. Org. Chem. Front. 2018; 5: 59

For selected examples of late-transition-metal-catalyzed hydroaminoalkylation reactions of alkenes, see:
• 4a Tran AT, Yu J.-Q. Angew. Chem. Int. Ed. 2017; 56: 10530
• 4b Spettel M, Pollice R, Schnürch M. Org. Lett. 2017; 19: 4287
• 4c Thullen SM, Rovis T. J. Am. Chem. Soc. 2017; 139: 15504
• 4d Lahm G, Opatz T. Org. Lett. 2014; 16: 4201
• 4e Schinkel M, Wang L, Bielefeld K, Ackermann L. Org. Lett. 2014; 16: 1876
• 4f Kulago AA, Van Steijvoort BF, Mitchell EA, Meerpoel L, Maes BU. W. Adv. Synth. Catal. 2014; 356: 1610

For selected examples of group 4 metal catalysts for hydroaminoalkylation reactions, see:
• 5a Kubiak R, Prochnow I, Doye S. Angew. Chem. Int. Ed. 2009; 48: 1153
• 5b Kubiak R, Prochnow I, Doye S. Angew. Chem. Int. Ed. 2010; 49: 2626
• 5c Dörfler J, Doye S. Angew. Chem. Int. Ed. 2013; 52: 1806
• 5d Dörfler J, Preuß T, Schischko A, Schmidtmann M, Doye S. Angew. Chem. Int. Ed. 2014; 53: 7918
• 5e Lühning LH, Brahms C, Nimoth JP, Schmidtmann M, Doye S. Z. Anorg. Allg. Chem. 2015; 641: 2071
• 5f Dörfler J, Preuß T, Brahms C, Scheuer D, Doye S. Dalton Trans. 2015; 44: 12149
• 5g Chong E, Schafer LL. Org. Lett. 2013; 15: 6002

For selected examples of group 5 metal catalysts for hydroaminoalkylation reactions, see:
• 6a Clerici MG, Maspero F. Synthesis 1980; 305
• 6b Nugent WA, Ovenall DW, Holmes SJ. Organometallics 1983; 2: 161
• 6c Herzon SB, Hartwig JF. J. Am. Chem. Soc. 2007; 129: 6690
• 6d Eisenberger P, Ayinla RO, Lauzon JM. P, Schafer LL. Angew. Chem. Int. Ed. 2009; 48: 8361
• 6e Reznichenko AL, Hultzsch KC. J. Am. Chem. Soc. 2012; 134: 3300
• 6f Garcia P, Lau YY, Perry MR, Schafer LL. Angew. Chem. Int. Ed. 2013; 52: 9144
• 6g Chong E, Brandt JW, Schafer LL. J. Am. Chem. Soc. 2014; 136: 10898
• 6h Brandt JW, Chong E, Schafer LL. ACS Catal. 2017; 7: 6323
• 6i Edwards PM, Schafer LL. Org. Lett. 2017; 19: 5720
• 6j DiPucchio RC, Roşca S.-C, Schafer LL. Angew. Chem. Int. Ed. 2018; 57: 3469

For examples of titanium-catalyzed intramolecular hydroaminoalkylation reactions of aminoalkenes, see:
• 7a Prochnow I, Kubiak R, Frey ON, Beckhaus R, Doye S. ChemCatChem 2009; 1: 162
• 7b Prochnow I, Zark P, Müller T, Doye S. Angew. Chem. Int. Ed. 2011; 50: 6401
• 7c Dörfler J, Bytyqi B, Hüller S, Mann NM, Brahms C, Schmidtmann M, Doye S. Adv. Synth. Catal. 2015; 357: 2265
• 8 Lehmkuhl H, Fustero S. Liebigs Ann. Chem. 1980; 1371
• 9 Elkin T, Kulkarni NV, Tumanskii B, Botoshansky M, Shimon LJ. W, Eisen MS. Organometallics 2013; 32: 6337
• 10 4-Methyl-N-(2-methylenecyclohexyl)aniline (4)In a glovebox under N₂, amine 1 (101 mg, 0.5 mmol) and catalyst IV (27 mg, 0.05 mmol, 10 mol%) were dissolved in p-cymene (15 mL) in a 25 mL ampoule equipped with magnetic stirrer bar. The ampoule was then sealed and heated at 160 °C for 2.5 h. The product was purified by chromatography [silica gel (250 g, length = 1 m, diam. = 20 mm), PE–Et₂O (20:1, R_f = 0.36)] to give 4 as a colorless liquid [yield: 50 mg (0.25 mmol, 50%)], together with the byproduct N-(cyclohex-1-en-1-ylmethyl)-4-methylaniline [5; yield: 5 mg (0.02 mmol, 5%)] as a yellow oil. Crystals of 4 were obtained by slow evaporation of a solution in hexane.4Colorless liquid [yield: 50 mg (0.25 mmol, 50%)]; mp: = 59 °C. IR (ATR) λ^-1 3410, 2936, 2854, 1612, 1519, 1441, 1398, 1315, 1302, 1259, 1180, 1156, 1140, 1123, 1108, 1086, 908, 804 cm⁻¹. ¹H NMR (500 MHz, CDCl₃): δ = 1.38-1.46 (m, 2 H), 1.55–1.63 (m, 1 H), 1.79 (dq, J = 16.9, 4.0 Hz, 1 H), 1.88 (dq, J = 16.9, 4.1 Hz, 1 H), 2.03–2.13 (m, 2 H), 2.25 (s, 3 H), 2.44 (dt, J = 13.3, 3.8 Hz, 1 H), 3.71 (dd, J = 10.3, 4.3 Hz, 1 H), 3.75 (br. s, 1 H), 4.77 (s, 1 H), 4.84 (s, 1 H), 6.54 (d, J = 8.3 Hz, 2 H), 6.98 (d, J = 8.1 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃, DEPT): δ = 20.5 (CH₃), 25.4 (CH₂), 28.4 (CH₂), 34.5 (CH₂), 35.7 (CH₂), 57.1 (CH), 106.7 (CH₂), 113.6 (CH), 126.5 (C), 129.7 (CH), 145.3 (C), 149.6 (C). MS (EI, 70 eV): m/z (%) = 201 (100) [M]⁺, 172 (15), 133 (15), 107 (61), 91 (11). HRMS (EI, 70 eV): m/z [M⁺] calcd. for C₁₄H₁₉N: 201.1512; found: 201.1511.
• 11 For details, see the Supporting Information.
• 12 CCDC 1871667 contains the supplementary crystallographic data for compound 4. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
• 13 Allylamines have been used as substrates for nickel-catalyzed cross-coupling reactions that involve cationic π-allyl metal intermediates, see: Trost BM, Spagnol MD. J. Chem. Soc., Perkin Trans. 1 1995; 2083

For selected examples of titanium-catalyzed allene hydroamination with primary amines, see:
• 14a Johnson JS, Bergman RG. J. Am. Chem. Soc. 2001; 123: 2923
• 14b Ackermann L, Bergman RG. Org. Lett. 2002; 4: 1475

For selected examples of hydroamination reactions with secondary amines achieved with neutral group 4 metal catalysts, see:
• 15a Stubbert BD, Marks TJ. J. Am. Chem. Soc. 2007; 129: 6149
• 15b Majumder S, Odom AL. Organometallics 2008; 27: 1174
• 15c Müller C, Saak W, Doye S. Eur. J. Org. Chem. 2008; 2731
• 15d Leitch DC, Payne PR, Dunbar CR, Schafer LL. J. Am. Chem. Soc. 2009; 131: 18246
• 15e Mukherjee A, Nembenna S, Sen TK, Pillai Sarish S, Ghorai PK, Ott H, Stalke D, Mandal SK, Roesky HW. Angew. Chem. Int. Ed. 2011; 50: 3968
• 15f Leitch DC, Platel RH, Schafer LL. J. Am. Chem. Soc. 2011; 133: 15453
• 16 Cabezas JA, Poveda RR, Brenes JA. Synthesis 2018; 50: 3307