Rhodium(III)-Catalyzed C–H Activation Mediated Synthesis of Isoquinolones from Amides and Cyclopropenes

Abstract

We have developed a synthesis of 4-substituted isoquinolones from the rhodium(III)-catalyzed, C–H activation mediated coupling of O-pivaloyl benzhydroxamic acids and 3,3-disubstituted cyclopropenes. Experiments suggest the formation of a [4.1.0] bicyclic system, which can open under acidic conditions to generate the desired isoquinolone.

Key words

C–H activation - heterocycles - isoquinolone - cyclopropene - donor–acceptor cyclopropane

• References and Notes

• 1 For a review of isoquinolone synthesis; see: Glushkov VA, Shklyaev YV. Chem. Heterocycl. Compd. 2001; 37: 663
• 2a Guimond N, Gouliaras C, Fagnou K. J. Am. Chem. Soc. 2010; 132: 6908
• 2b Mochida S, Umeda N, Hirano K, Satoh T, Miura M. Chem. Lett. 2010; 39: 744
• 2c Hyster TK, Rovis T. J. Am. Chem. Soc. 2010; 132: 10565
• 2d Song G, Chen D, Pan C.-L, Crabtree RH, Li X. J. Org. Chem. 2010; 75: 7487
• 2e Guimond N, Gorelsky SI, Fagnou K. J. Am. Chem. Soc. 2011; 133: 6449
• 2f Wang H, Grohmann C, Nimphius C, Glorius F. J. Am. Chem. Soc. 2012; 134: 19592
• 3a Reissig H.-U, Zimmer R. Chem. Rev. 2003; 103: 1151
• 3b Yu M, Pagenkopf BL. Tetrahedron 2005; 61: 321
• 3c Rubin M, Rubina M, Gevorgyan V. Chem. Rev. 2007; 107: 3117
• 3d Carson CA, Kerr MA. Chem. Soc. Rev. 2009; 38: 3051
• 3e De Simone F, Waser J. Synthesis 2009; 3353
• 3f Campbell MJ, Johnson JS, Parsons AT, Pohlhaus PD, Sanders SD. J. Org. Chem. 2010; 75: 6317
• 4a De Simone F, Waser J. Synlett 2009; 593
• 4b De Simone F, Gertsch J, Waser J. Angew. Chem. Int. Ed. 2010; 49: 5767
• 4c de Nanteuil F, Waser J. Angew. Chem. Int. Ed. 2011; 50: 12075
• 4d Benfatti F, de Nanteuil F, Waser J. Org. Lett. 2012; 14: 386
• 4e Benfatti F, de Nanteuil F, Waser J. Chem. Eur. J. 2012; 18: 4844
• 5a Rakshit S, Grohmann C, Besset T, Glorius F. J. Am. Chem. Soc. 2011; 133: 2350
• 5b Wang H, Glorius F. Angew. Chem. Int. Ed. 2012; 51: 7318
• 6 Hyster TK, Knörr L, Ward TR, Rovis T. Science 2012; 338: 500
• 7 Ye B, Cramer N. Science 2012; 338: 504
• 8 Presset M, Oehlrich D, Rombouts F, Molander GA. Org. Lett. 2013; 15: 1528
• 9 General Procedure for the Synthesis of 3a A 1.5 dram vial was charged with a stir bar, 1a (0.2 mmol), [RhCp*Cl₂]₂ (1 mol %), CsOAc (0.4 mmol), and MeOH (1 mL). After stirring for 30 s, cyclopropene 2a (0.22 mmol) was added, and the reaction mixture was allowed to stir for 8 h at 23 °C. Upon completion, as determined by TLC, the reaction mixture was concentrated. The crude residue was purified via column chromatography (2:1 hexanes–EtOAc with 1% Et₃N) to provide the isoquinolone 3a as a white solid (99% yield).