Synthesis of N-Acyl Pyrroles and Isoindoles from Oxime Ester Precursors via Transition-Metal-Catalyzed Iminocarboxylation

Abstract

We describe Pt(II)- and Fe(III)-catalyzed iminocarboxylations of oxime esters conjugated with 1,3-enyne and an ortho-alkynylarene moiety, followed by a spontaneous O→N acyl migration of the enol carboxylate intermediate to generate N-acyl pyrroles and isoindoles. The reaction scope for pyrrole synthesis is general, whereas the formation of isoindoles has a relatively narrow scope because of their instability.

Key words

iminocarboxylation - pyrroles - isoindoles - platinum catalysis - iron catalysis - oxime esters

Publication History

Received: 10 September 2022

Accepted after revision: 26 September 2022

Article published online:
03 November 2022

• References and Notes

• 1a Donohoe TJ, Callens CK. A, Flores A, Lacy AR, Rathi AH. Chem. Eur. J. 2011; 17: 58
• 1b Hemric BN. Org. Biomol. Chem. 2021; 19: 46
• 2a Michaelis DJ, Shaffer CJ, Yoon TP. J. Am. Chem. Soc. 2007; 129: 1866
• 2b Michaelis DJ, Ischay MA, Yoon TP. J. Am. Chem. Soc. 2008; 130: 6610
• 2c Fuller PH, Kim J.-W, Chemler SR. J. Am. Chem. Soc. 2008; 130: 17638
• 2d Hemric BN, Shen K, Wang Q. J. Am. Chem. Soc. 2016; 138: 5813
• 2e Liu R.-H, Wei D, Han B, Yu W. ACS Catal. 2016; 6: 6525
• 2f Wu F, Stewart S, Ariyarathna JP, Li W. ACS Catal. 2018; 8: 1921
• 2g Hemric BN, Chen AW, Wang Q. ACS Catal. 2019; 9: 10070
• 3a Williamson KS, Yoon TP. J. Am. Chem. Soc. 2010; 132: 4570
• 3b Williamson KS, Yoon TP. J. Am. Chem. Soc. 2012; 134: 12370
• 3c Liu G.-S, Zhang Y.-Q, Yuan Y.-A, Xu H. J. Am. Chem. Soc. 2013; 135: 3343
• 3d Lu D.-F, Zhu C.-L, Jia Z.-X, Xu H. J. Am. Chem. Soc. 2014; 136: 13186
• 3e Legnani L, Morandi B. Angew. Chem. Int. Ed. 2016; 55: 2248
• 4a de Haro T, Nevado C. Angew. Chem. Int. Ed. 2011; 50: 906
• 4b Shaikh AC, Ranade DS, Rajamohanan PR, Kulkarni PP, Patil NT. Angew. Chem. Int. Ed. 2017; 56: 757
• 5 Muñiz K, Iglesias A, Fang Y. Chem. Commun. 2009; 5591
• 6a Bäckvall JE, Bjoerkman EE. J. Org. Chem. 1980; 45: 2893
• 6b Bäckvall JE, Bystroem SE. J. Org. Chem. 1982; 47: 1126
• 6c Alexanian EJ, Lee C, Sorensen EJ. J. Am. Chem. Soc. 2005; 127: 7690
• 6d Liu G, Stahl SS. J. Am. Chem. Soc. 2006; 128: 7179
• 6e Desai LV, Sanford MS. Angew. Chem. Int. Ed. 2007; 46: 5737
• 6f Shen H.-C, Wu Y.-F, Zhang Y, Fan L.-F, Han Z.-Y, Gong L.-Z. Angew. Chem. Int. Ed. 2018; 57: 2372
• 7a Dequirez G, Ciesielski J, Retailleau P, Dauban P. Chem. Eur. J. 2014; 20: 8929
• 7b Escudero J, Bellosta V, Cossy J. Angew. Chem. Int. Ed. 2018; 57: 574
• 7c Thornton AR, Blakey SB. J. Am. Chem. Soc. 2008; 130: 5020
• 7d Mace N, Thornton AR, Blakey SB. Angew. Chem. Int. Ed. 2013; 52: 5836
• 7e Pan D, Wei Y, Shi M. Org. Lett. 2018; 20: 84
• 8a Lei H, Conway JH. Jr, Cook CC, Rovis T. J. Am. Chem. Soc. 2019; 141: 11864
• 8b Hong SY, Chang S. J. Am. Chem. Soc. 2019; 141: 10399
• 8c Kim S, Kim D, Hong SY, Chang S. J. Am. Chem. Soc. 2021; 143: 3993
• 9a Sharpless KB, Patrick DW, Truesdale LK, Biller SA. J. Am. Chem. Soc. 1975; 97: 2305
• 9b Rudolph J, Sennhenn PC, Vlaar CP, Sharpless KB. Angew. Chem. Int. Ed. Engl. 1996; 35: 2810
• 9c Bruncko M, Schlingloff G, Sharpless KB. Angew. Chem. Int. Ed. Engl. 1997; 36: 1483
• 9d Donohoe TJ, Johnson PD, Cowley A, Keenan M. J. Am. Chem. Soc. 2002; 124: 12934
• 9e Donohoe TJ, Chughtai MJ, Klauber DJ, Griffin D, Campbell AD. J. Am. Chem. Soc. 2006; 128: 2514
• 10 Kitamura M, Moriyasu Y, Okauchi T. Synlett 2011; 643
• 11 Zhao P, Wang F, Han K, Li X. Org. Lett. 2012; 14: 3400
• 12 Gao H, Zhang J. Adv. Synth. Catal. 2009; 351: 85
• 13a Yeom H.-S, Lee Y, Lee J.-E, Shin S. Org. Biomol. Chem. 2009; 7: 4744
• 13b Kim WS, Espinoza Castro VM, Abiad A, Ko M, Council A, Nguyen A, Marsalla L, Lee V, Tran T, Petit AS, de Lijser HJ. P. J. Org. Chem. 2021; 86: 693

For examples of pyrrole synthesis from oxime derivatives, see:
• 14a Yoshida M, Kitamura M, Narasaka K. Bull. Chem. Soc. Jpn. 2003; 76: 2003
• 14b Portela-Cubillo F, Scott JS, Walton JC. Chem. Commun. 2007; 4041
• 14c Cai Y, Jalan A, Kubosumi AR, Castle SL. Org. Lett. 2015; 17: 488
• 14d Yang H.-B, Selander N. Chem. Eur. J. 2017; 23: 1779
• 15a Pino-Rios R, Solà M. J. Phys. Chem. A 2021; 125: 230
• 15b Heugebaert TS. A, Roman BI, Stevens CV. Chem. Soc. Rev. 2012; 41: 5626
• 15c Shields JE, Bornstein J. J. Am. Chem. Soc. 1969; 91: 5192
• 16a Shimbayashi T, Okamoto K, Ohe K. Chem. Eur. J. 2017; 23: 16892

For a review on reactions of metal nitrenoids with alkynes, see:
• 16b Ren M, Wang Y.-C, Ren S, Huang K, Liu J.-B, Qiu G. ChemCatChem 2022; 14: e202200008
• 17 N-Acylpyrroles 2a–r; General Procedure (Conditions A) A Schlenk tube was charged with a solution of the appropriate oxime ester 1 (0.15 mmol) in freshly distilled MeCN (2.5 mL). FeCl₃ (0.075 mmol, 5 mol%) was added, the tube was sealed, and the mixture was heated at 45 °C until the reaction was complete. The crude product was concentrated in vacuo and purified by chromatography (silica gel). Conditions B A Schlenk tube was charged with a solution of the appropriate oxime ester 1 (0.15 mmol) in freshly distilled toluene (3 mL). PtCl₂ (0.075 mmol, 5 mol %) was added, and CO was gradually bubbled into the solution for 10 min. The Schlenk tube was then carefully sealed and heated at 65–70 °C until the reaction was complete. The crude product was concentrated in vacuo and purified by chromatography (silica gel). 1-(2-Benzoyl-3-methyl-4,5,6,7-tetrahydro-2H-isoindol-1-yl)pentan-1-one (2a) Light-yellow solid; yield: 78% (Conditions A); 87% (Conditions B). ¹H NMR (500 MHz, CDCl₃): δ = 7.56 (d, J = 7.6 Hz, 2 H), 7.51 (t, J = 7.5 Hz, 1 H), 7.37 (t, J = 7.7 Hz, 2 H), 2.85 (t, J = 6.2 Hz, 2 H), 2.53 (t, J = 7.5 Hz, 2 H), 2.49 (t, J = 6.2 Hz, 2 H), 2.10 (s, 3 H), 1.89–1.82 (m, 2 H), 1.82–1.74 (m, 2 H), 1.46 (p, J = 7.6 Hz, 2 H), 1.18 (h, J = 7.4 Hz, 2 H), 0.81 (t, J = 7.3 Hz, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 188.61, 171.65, 135.32, 133.61, 133.12, 130.56, 129.45, 129.13, 128.51, 120.47, 39.47, 26.52, 24.47, 23.41, 22.83, 22.36, 21.41, 13.88, 10.08. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₁H₂₆NO₂: 324.1964; found: 324.1962.