Rhodium(III)-Catalyzed C–H Activation: An Oxidative Intramolecular Heck-Type Reaction Directed by a Carboxylate

Abstract

Carboxylates effectively direct C–H activation for rhodium(III)-catalyzed intramolecular Heck-type reactions. A catalytic amount of Cu(OAc)₂ is used as the external oxidant with oxygen likely acting as the terminal oxidant. Additionally, a novel electron-deficient rhodium(III) catalyst was found to be more effective than [RhCp*Cl₂]₂ with some substrates. A wide variety of complex dihydrobenzofurans, dihydrobenzopyrans, and other bicycles that can be easily further functionalized are now accessible through relatively mild reaction conditions.

Key words

C–H activation - Heck reaction - rhodium(III) catalysis - cyclization - dihydrobenzofurans

• References and Notes


For recent reviews on Rh(III) C–H activation, see:
• 1a Satoh T, Miura M. Chem. Eur. J. 2010; 16: 11212
• 1b Song G, Wang F, Li X. Chem. Soc. Rev. 2012; 41: 3651

Examples of Rh(III)-catalyzed amidoarylations with alkynes:
• 2a Guimond N, Gouliaras C, Fagnou K. J. Am. Chem. Soc. 2010; 132: 6908
• 2b Hyster TK, Rovis T. J. Am. Chem. Soc. 2010; 132: 10565

Amidoarylations with alkenes:
• 2c Rakshit S, Grohmann C, Besset T, Glorius F. J. Am. Chem. Soc. 2011; 133: 2350
• 2d Hyster TK, Rovis T. Synlett 2013; 24: 1842

Olefinations:
• 2e Patureau FW, Besset T, Glorius F. Angew. Chem. Int. Ed. 2011; 50: 1064
• 2f See ref. 2c.

Halogenations:
• 2g Schröder N, Wencel-Delord J, Glorius F. J. Am. Chem. Soc. 2012; 134: 8298

Allylations:
• 2h Wang H, Schröder N, Glorius F. Angew. Chem. Int. Ed. 2013; 52: 5386

For examples of enantioselective Rh(III)-catalyzed reactions, see:
• 3a Hyster TK, Knörr L, Ward TR, Rovis T. Science 2012; 338: 500
• 3b Ye B, Cramer N. Science 2012; 338: 504
• 3c Ye B, Donets PA, Cramer N. Angew. Chem. Int. Ed. 2014; 53: 507
• 4 For a recent review on carboxylate-directed C–H activation, see: Shi G, Zhang Y. Adv. Synth. Catal. 2014; 356: 1419
• 5 Satoh and Miura have described a Rh(III)-catalyzed carboxylic acid directed olefination and subsequent conjugate addition of the carboxylate to form lactones from benzoic acids and acrylates: Ueura K, Satoh T, Miura M. Org. Lett. 2007; 9: 1407
• 6 Rh(III) oxidative coupling of alkynes and benzoic acid to form isocoumarins: Ueura K, Satoh T, Miura M. J. Org. Chem. 2007; 72: 5362
• 7a Maehara A, Tsurugi H, Satoh T, Miura M. Org. Lett. 2008; 10: 1159
• 7b Mochida S, Hirano K, Satoh T, Miura M. Org. Lett. 2010; 12: 5776
• 7c Cornella J, Righi M, Larossa I. Angew. Chem. Int. Ed. 2011; 50: 9429
• 7d Neely JM, Rovis T. J. Am. Chem. Soc. 2014; 136: 2735
• 7e Zhang Y, Zhao H, Zhang M, Su W. Angew. Chem. Int. Ed. 2015; 54: 3817
• 8 Davis TA, Hyster TK, Rovis T. Angew. Chem. Int. Ed. 2013; 52: 14181
• 9 For a discussion of issues of regioselectivity with the use of alkenes as partners for heterocycle forming reactions, see: Thakur K, Sharma R, Sharma U. Synlett 2015; 26: 137
• 10 Reported simple benzamide-directed Rh(III) C–H olefination reactions (no internal oxidant) involve harsh reaction conditions, see ref. 2e.
• 11 In subsequent studies, no discernible difference in reactivity was found between reactions conducted in air and reactions conducted under an atmosphere of O₂.

Examples of new or improved reactivity from the variation of Rh(III) Cp ligands:
• 12a Hyster TK, Rovis T. Chem. Sci. 2011; 2: 1606
• 12b Hyster TK, Rovis T. Chem. Commun. 2011; 47: 11846
• 12c Piou T, Rovis T. J. Am. Chem. Soc. 2014; 136: 11292
• 12d Shibata Y, Tanaka K. Angew. Chem. Int. Ed. 2011; 50: 10917
• 12e Hoshino Y, Shibata Y, Tanaka K. Adv. Synth. Catal. 2014; 356: 1577
• 12f Hyster TK, Dalton DM, Rovis T. Chem Sci. 2015; 6: 254
• 13 Use of Z-disubstituted alkene substrates led to low conversions and poor Z/E ratios of the products.
• 14 A screen of different Cp catalysts revealed [RhCp^(CF3)2ArCl₂]₂ to be the most selective in terms of di- vs. trisubstituted alkene selectivity and E/Z selectivity.
• 15 General Procedure for the Synthesis of 2a A 1.5 dram vial was charged with a stir bar, the acid substrate (0.1 mmol, 1 equiv), [RhCp*Cl₂]₂ (1.5 mg, 2.5 μmol, 0.025 equiv) or [RhCp^(CF3)2ArCl₂]₂ (2.5 mg, 2.5 μmol, 0.025 equiv), Cu(OAc)₂ (8.0 mg, 40 μmol, 0.4 equiv), and K₂CO₃ (38.4 mg, 200 μmol, 2 equiv), followed by addition of DCE–H₂O (1:1, 500 μL, 0.2 M). The vial was flushed with oxygen, sealed, and stirred at 60 °C for the indicated time. The reaction mixture was allowed to cool and was quenched with 1 M aq HCl until fully precipitated (pH ca. 1). The suspension was then extracted twice with EtOAc. The combined organic layers were washed once with H₂O and once with sat. aq NaCl before drying over MgSO₄. The solution was filtered and concentrated by rotary evaporation. The crude residue was purified by column chromatography (EtOAc–hexanes). Compound 2a: R_f = 0.29 (25% EtOAc–hexanes). IR (film): 3082, 2962, 2925, 2879, 1696 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.56 (d, J = 7.6 Hz, 1 H), 7.25 (dd, J = 7.6 Hz, 1 H), 7.05 (d, J = 8.0 Hz, 1 H), 6.17 (dd, J = 17.6, 10.8 Hz, 1 H), 5.14 (d, J = 10.4 Hz, 1 H), 5.09 (d, J = 17.6 Hz, 1 H), 4.40 (d, J = 8.4 Hz, 1 H), 4.27 (d, J = 8.4 Hz, 1 H), 1.64 (s, 3 H); acid proton signal too broadened to assign. ¹³C NMR (100 MHz, CDCl₃): δ = 171.4, 160.9, 142.0, 135.6, 128.6, 127.0, 123.6, 115.0, 113.6, 84.1, 49.4, 23.3. MS (ESI + APCI): m/z calcd for C₁₂H₁₁O₃ [M – H]^–: 203.1; found: 203.1.