Rhodium(III)-Catalyzed C–H Activation/Alkylation of Diazabicyclic Olefins with Aryl Ketones: Facile Synthesis of Functionalized Cyclopentenes

Abstract

A facile synthesis of biologically important trans-functionalized cyclopentenes by a mild Rh(III)-catalyzed alkylation of strained ­diazabicyclic olefins with aryl ketones in the presence of ammonium ­acetate has been developed. The reaction proceeds through C–H bond activation of the aryl ketone groups by transforming them in to an ­autocleavable directing group, such as in situ-formed imine.

Key words

C–H activation - aryl ketones - diazabicyclic olefins - cyclopentenes - stereoselectivity

• References and Notes

• 1a Jia C. Kitamura T. Fujiwara Y. Acc. Chem. Res. 2001; 34: 633
• 1b Miura M. Nomura M. Top. Curr. Chem. 2002; 219: 211
• 1c Handbook of C–H Transformations: Applications in Organic Synthesis. Dyker G. Wiley-VCH; Weinheim: 2005
• 2a Murai S. Kakiuchi F. Sekine S. Tanaka Y. Kamatani A. Sonoda M. Chatani N. Nature 1993; 366: 529
• 2b Chatani N. Asaumi T. Ikeda T. Yorimitsu S. Ishii Y. Kakiuchi F. Murai S. J. Am. Chem. Soc. 2000; 122: 12882
• 2c Padala K. Jeganmohan M. Org. Lett. 2011; 13: 6144
• 2d Muralirajan K. Parthasarathy K. Cheng C.-H. Angew. Chem. Int. Ed. 2011; 50: 4169
• 2e Tsuchikama K. Kasagawa M. Endo K. Shibata T. Synlett 2010; 97
• 2f Gandeepan P. Parthasarathy K. Cheng C.-H. J. Am. Chem. Soc. 2010; 132: 8569
• 3 Patureau FW. Besset T. Kuhl N. Glorius F. J. Am. Chem. Soc. 2011; 133: 2154
• 4a Bournaud C. Chung F. Pérez Luna A. Pasco M. Errasti G. Lecourt T. Micouin L. Synthesis 2009; 869
• 4b Sajisha VS. Anas S. John J. Radhakrishnan KV. Synlett 2009; 2885
• 5a Yao M.-L. Adiwidjaja G. Kaufmann DE. Angew. Chem. Int. Ed. 2002; 41: 3375
• 5b Radhakrishnan KV. Sajisha VS. Anas K. Krishnan KS. Synlett 2005; 2273
• 5c John J. Sajisha VS. Mohanlal S. Radhakrishnan KV. Chem. Commun. 2006; 3510
• 5d John J. Anas S. Sajisha VS. Viji S. Radhakrishnan KV. Tetrahedron Lett. 2007; 48: 7225
• 5e Joseph N. Rajan R. John J. Devika NV. Chand SS. Suresh E. Pihko PM. Radhakrishnan KV. RSC Adv. 2013; 3: 7751
• 5f Pérez Luna A. Cesario M. Bonin M. Micouin L. Org. Lett. 2003; 5: 4771
• 5g Bournaud C. Falciola C. Lecourt T. Rosset S. Alexakis A. Micouin L. Org. Lett. 2006; 8: 3581
• 5h Palais L. Mikhel IS. Bournaud C. Micouin L. Falciola CA. Augustin M.-V. Rosset S. Bernardinelli G. Alexakis A. Angew. Chem. Int. Ed. 2007; 46: 7462
• 5i Martins A. Lemouzy A. Lautens M. Org. Lett. 2009; 11: 181
• 6a John J. Indu U. Suresh E. Radhakrishnan KV. J. Am. Chem. Soc. 2009; 131: 5042
• 6b Bhanu Prasad BA. Buechele AE. Gilbertson SR. Org. Lett. 2010; 12: 5422
• 6c Joseph N. John J. Rajan R. Thulasi S. Mohan A. Suresh E. Radhakrishnan KV. Tetrahedron 2011; 67: 4905
• 6d Prakash P. Jijy E. Preethanuj P. Pihko PM. Sarath Chand S. Radhakrishnan KV. Chem. Eur. J. 2013; 19: 10473
• 6e Sarath Chand S. Jijy E. Prakash P. Szymoniak J. Preethanuj P. Dhanya BP. Radhakrishnan KV. Org. Lett. 2013; 15: 3338
• 6f John J. Rajan R. Chand SS. Prakash P. Joseph N. Suresh E. Radhakrishnan KV. Tetrahedron 2013; 69: 152
• 6g Santhini PV. Smrithy S. Jesin CP. I. Varughese S. John J. Radhakrishnan KV. Chem. Commun. 2018; 54: 2982
• 7a Zhang Y. Wu QF. Cui S. Chem. Sci. 2014; 5: 297
• 7b Praveen P. Jijy E. Aparna PS. Viji S. Radhakrishnan KV. Tetrahedron Lett. 2014; 55: 916
• 7c Aparna PS. Prabha B. Prakash P. Jijy E. Varma RL. Radhakrishnan KV. Tetrahedron Lett. 2014; 55: 865
• 7d Santhini PV. Nimisha G. John J. Suresh E. Varma RL. Radhakrishnan KV. Chem. Commun. 2017; 53: 1848
• 8a Jun C.-H. Moon CW. Hong J.-B. Lim S.-G. Chung K.-Y. Kim Y.-H. Chem. Eur. J. 2002; 485
• 8b Zheng L. Ju J. Bin Y. Hua R. J. Org. Chem. 2012; 77: 5794
• 8c Lee H. Sim Y.-K. Park J.-W. Jun C.-H. Chem. Eur. J. 2014; 20: 323
• 8d Yi Y. Lee H. Jun C.-H. Chem. Commun. 2016; 52: 10171
• 9a Wang H. Schröder N. Glorius F. Angew. Chem. Int. Ed. 2013; 52: 5386
• 9b Sakiyama N. Noguchi K. Tanaka K. Angew. Chem. Int. Ed. 2012; 51: 5976
• 10 Diethyl 1-[(1S*,2R*)-2-(2-Acetylphenyl)cyclopent-3-en-1-yl]hydrazine-1,2-dicarboxylate (4); Typical Procedure Azabicyclic olefin 1a (100 mg, 0.42 mmol), acetophenone (2a; 50 mg, 0.42 mmol), NH₄OAc (64 mg, 0.83 mmol), [RhCp*Cl₂]₂(10 mg, 3 mol%), and Cu(OAc)₂ (150 mg, 0.83 mmol) were weighed into a Schlenk tube, and the mixture was degassed for 10 min. Anhyd DCE (1 mL) was added, and the mixture was purged with argon and stirred at 80 °C for 24 h. The solvent was evaporated in vacuo and the residue was purified by column chromatography [silica gel (100–200 mesh); Ethyl acetate-Hexane polarities] to give a viscous liquid; yield: 121 mg (81%); TLC (silica gel): R_f = 0.43 (25% EtOAc–hexane). ¹H NMR (500 MHz, CDCl₃, TMS): δ = 7.64 (d, J = 7.5 Hz, 1 H), 7.54 (br s, 1 H), 7.50–7.47 (m, 1 H), 7.43–7.42 (m, 1 H), 7.31–7.28 (m, 1 H), 5.89–5.88 (m, 1 H), 5.54–5.52 (m, 1 H), 4.94–4.69 (m, 2 H), 4.26–4.22 (m, 2 H), 4.06–3.76 (m, 2 H), 2.72–2.60 (m, 2 H), 2.59 (s, 3 H), 1.32–1.26 (m, 4 H), 1.15 (br s, 1 H), 0.71 (br s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 201.8, 156.1, 152.9, 143.8, 137.8, 132.8, 132.2, 130.6, 129.3, 129.1, 126.2, 67.9, 61.9, 61.8, 47.2, 34.8, 29.8, 14.5, 13.9. HRMS (ESI-Orbitrap): m/z [M + Na]⁺ calcd for C₁₉H₂₄N₂NaO₅: 383.1583; found: 383.1573.