Stereoselective Pd-Catalyzed Remote Hydroamination of Skipped Dienes with Azoles

Abstract

A novel palladium-catalyzed stereoselective remote ­hydroamination reaction is disclosed. A series of azoles and skipped dienes undergo the migratory allylic C–H amination in good yields and selectivities. A desymmetric migratory azolation process is also developed to highlight the reliability of the transformation. Preliminary mechanistic experiments corroborate the designed metal walking and allylic substitution cascade strategy via Pd–H catalysis, different from prior ligand-to-ligand hydrogen transfer pathway for conjugated dienes.

Key words

skipped diene - remote hydroamination - palladium ­hydride - azoles - migratory allylic C–H functionalization

Publication History

Received: 15 July 2022

Accepted after revision: 02 August 2022

Accepted Manuscript online:
02 August 2022

Article published online:
02 September 2022

• References and Notes

• 1 Taylor RD, MacCoss M, Lawson AD. G. J. Med. Chem. 2014; 57: 5845
• 2 Markham A, Duggan S. Drugs 2019; 79: 1813
• 3 Mesa RA, Yasothan U, Kirkpatrick P. Nat. Rev. Drug Discovery 2012; 11: 103
• 4 Cameron F, Sanford M. Drugs 2014; 74: 263
• 5a Zhang M, Guo X.-W, Zheng S.-C, Zhao X.-M. Tetrahedron Lett. 2012; 53: 6995
• 5b Kim SW, Schempp TT, Zbieg JR, Stivala CE, Krische MJ. Angew. Chem. Int. Ed. 2019; 58: 7762
• 5c Kang B, Zhang Q.-Y, Qu G.-R, Guo H.-M. Adv. Synth. Catal. 2020; 362: 1955
• 6 Zhuang H, Lu N, Ji N, Han F, Miao C. Adv. Synth. Catal. 2021; 363: 5461

For selected examples on transition-metal-catalyzed asymmetric 1,2-hydroaminations, see:
• 7a Kawatsura M, Hartwig JF. J. Am. Chem. Soc. 2000; 122: 9546
• 7b Löber O, Kawatsura M, Hartwig JF. J. Am. Chem. Soc. 2001; 123: 4366
• 7c Lutete LM, Kadota I, Yamamoto Y. J. Am. Chem. Soc. 2004; 126: 1622
• 7d Adamson NJ, Hull E, Malcolmson SJ. J. Am. Chem. Soc. 2017; 139: 7180
• 7e Long J, Wang P, Wang W, Li Y, Yin G. iScience 2019; 22: 369
• 8a Haydl AM, Xu K, Breit B. Angew. Chem. Int. Ed. 2015; 54: 7149
• 8b Hilpert LJ, Sieger SV, Haydl AM, Breit B. Angew. Chem. Int. Ed. 2019; 58: 3378
• 9a Bernar I, Fiser B, Blanco-Ania D, Gómez-Bengoa E, Rutjes FP. J. T. Org. Lett. 2017; 19: 4211
• 9b Alonso JM, Muñoz MP. Org. Lett. 2019; 21: 7639
• 10 Jiu AY, Slocumb HS, Yeung CS, Yang X.-H, Dong VM. Angew. Chem. Int. Ed. 2021; 60: 19660

For metal-involved chain-walking, see:
• 11a Sommer H, Juliá-Hernández F, Martin R, Marek I. ACS Cent. Sci. 2018; 4: 153
• 11b Dhungana RK, Sapkota RR, Niroula D, Giri R. Chem. Sci. 2020; 11: 9757
• 11c Li Y, Wu D, Cheng H.-G, Yin G. Angew. Chem. Int. Ed. 2020; 59: 7990
• 11d Janssen-Müller D, Sahoo B, Sun S.-Z, Martin R. Isr. J. Chem. 2020; 60: 195
• 11e Mei T.-S, Patel HH, Sigman MS. Nature 2014; 508: 340
• 11f Zhu S, Niljianskul N, Buchwald SL. Nat. Chem. 2016; 8: 144
• 11g Bruffaerts J, Pierrot D, Marek I. Nat. Chem. 2018; 10: 1164
• 11h Chen X, Cheng Z, Guo J, Lu Z. Nat. Commun. 2018; 9: 3939
• 11i Zhou F, Zhang Y, Xu X, Zhu S. Angew. Chem. Int. Ed. 2019; 58: 1754
• 11j Ross SP, Rahman AA, Sigman MS. J. Am. Chem. Soc. 2020; 142: 10516
• 11k Wang W, Ding C, Yin G. Nat. Catal. 2020;  3:  951
• 11l Zhang R, Yan X, Bai S.-T, Chen C, Nan B, Ma B, Wen J, Zhang X. Green Synth. Catal. 2022; 3: 40
• 12a Larock RC, Lu YD, Bain AC, Russell CE. J. Org. Chem. 1991; 56: 4589
• 12b Larock RC, Wang Y, Lu Y, Russell CA. J. Org. Chem. 1994; 59: 8107
• 12c Han X, Larock RC. Synlett 1998; 748
• 12d Larock RC, Han X. J. Org. Chem. 1999; 64: 1875
• 12e Wang Y, Dong X, Larock RC. J. Org. Chem. 2003; 68: 3090
• 12f Pang H, Wu D, Cong H, Yin G. ACS Catal. 2019; 9: 8555
• 13 Zhang Y, Shen H.-C, Li Y.-Y, Huang Y.-S, Han Z.-Y, Wu X. Chem. Commun. 2019; 55: 3769
• 14a Zhu D, Jiao Z, Chi YR, Gonçalves TP, Huang K.-W, Zhou JS. Angew. Chem. Int. Ed. 2020; 59: 5341
• 14b Zhu D, Xu W, Pu M, Wu Y.-D, Chi YR, Zhou JS. Org. Lett. 2021; 23: 7064
• 15 Yu R, Shanmugam R, Fang X. Angew. Chem. Int. Ed. 2020; 59: 21436
• 16 Chen Y.-W, Liu Y, Lu H.-Y, Lin G.-Q, He Z.-T. Nat. Commun. 2021; 12: 5626
• 17 See Mayr’s Database of Reactivity Parameters (accessed Aug 2, 2022): https://www.cup.lmu.de/oc/mayr/reaktionsdatenbank/fe/
• 18 Yang S.-Q, Wang Y.-F, Zhao W.-C, Lin G.-Q, He Z.-T. J. Am. Chem. Soc. 2021; 143: 7285
• 19 General Procedure for Palladium-Catalyzed Remote Hydroamination with AzolesIn a nitrogen-filled glovebox, Pd(PCy₃)₂Cl₂ (7.4 mg, 0.010 mmol), L12 (4.2 mg, 0.010 mmol), NaBAr^F ₄ (9.8 mg, 0.011 mmol), and dry PhCF₃ (0.20 mL) were added to a 10 mL Schlenk tube and stirred at room temperature for 10 min. Then the remote diene 1 (0.20 mmol), nucleophile 2 (0.30 mmol), and dry Et₃N (84 μL, 0.60 mmol) were added to the solution, and the resulting mixture was stirred at 80 °C for 24 h. After this time, the crude mixture was cooled down to room temperature, diluted with EtOAc (2 mL), filtered through Celite, condensed, and purified by flash column chromatography to afford product pure 3.(E)-1-(1-Phenylhex-1-en-3-yl)-1H-pyrazole (3a)Colorless oil, 75% yield. ¹H NMR (400 MHz, CDCl₃): δ = 7.55 (d, J = 1.8 Hz, 1 H), 7.45 (d, J = 2.3 Hz, 1 H), 7.37–7.35 (m, 2 H), 7.31–7.28 (m, 2 H), 7.25–7.21 (m, 1 H), 6.47 (d, J = 15.9 Hz, 1 H), 6.39 (dd, J = 15.9, 6.8 Hz, 1 H), 6.27 (t, J = 2.1 Hz, 1 H), 4.92–4.84 (m, 1 H), 2.20–2.08 (m, 1 H), 2.00–1.89 (m, 1 H), 1.40–1.19 (m, 2 H), 0.95 (t, J = 7.4 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 139.1, 136.3, 131.9, 129.0, 128.6, 128.0, 127.8, 126.6, 105.3, 64.3, 37.3, 19.4, 13.8. HRMS (EI): m/z [M]⁺ calcd for C₁₅H₁₈N₂ ⁺: 226.1470; found: 226.1465.