Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Chemodivergent Oxidative Annulation of Benzamides and Enynes via 1,4-Rhodium Migration Jiaqiong Sun,† Dachang Bai,‡ Peiyuan Wang,† Kuan Wang,† Guangfan Zheng,† and Xingwei Li*,†,‡ †
School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an 710062, China School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China
‡
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ABSTRACT: Chemodivergent annulative couplings have been realized between N-methoxy benzamides and 1,3-enynes via Rh-catalyzed C−H activation and 1,4-Rh migration. Under Rh/copper catalyzed aerobic conditions, the nitrogen annulation occurred as the major pathway. The chemoselectivity was switched to the oxygen annulation under proper condition control with stoichiometric amounts of Cu(II) oxidant and NaOAc. Both coupling systems proceeded with a broad scope and functional group tolerance.
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Scheme 1. Annulation via NH-Directed C−H Activation
renes are ubiquitous and represent ideal substrates for synthesis of value-added products via catalysis. Consequently, C−H bond activation has been established as an increasingly important strategy to access complex structures.1 Among the various transition metals, Cp*Rh(III) catalysts stand out with high efficiency, selectivity, tunability, and compatibility.2 In order to achieve structural diversity and molecular versatility of C−H activation, various strategies have been developed. In this context, with respect to the arene substrates, multifunctional directing groups have been introduced,3 including nucleophilic, electrophilic, oxidizing,3d,f and 1,3-dipolar directing groups.3a,b On the other hand, bifunctional coupling partners have been employed to allow compatibility and streamlining of several distinct processes.4 Regarding the catalyst, unique properties such as Lewis acidity and steric sensitivity have been invoked,5 which allowed realization of complementary transformations. Alkynes are powerful C2 coupling partners in most C−H activation systems.2a,f,g,6 On the other hand, 1,4-migration of metals in catalysis has opened an important avenue toward construction of new platforms.7−10 Lam and co-workers pioneered in Rh(III)-catalyzed C−H activation of arenes and coupling with enynes with 1,4-migration as a key elementary step (Scheme 1).8 This migration creates an η 3-allyl intermediate that is susceptible to attack by a nucleophilic directing group, leading to [4 + 1],8b [5 + 1],8b,f and [3 + 3]8e annulation. In addition, 1,4-migration of Rh(I)8a,c,g,10a−h and Ir(I)10i,j has also been accommodated in catalysis. Despite the great progress, the nucleophilic directing group has been limited to amide, carboxylic acid, phenol, and enolate. Thus, such coupling assisted by a NH directing group remains limited, and only one example documented the coupling of a special class of benzamide with dienes via 1,4-Rh migration.8b Moreover, no chemodivergence has been realized starting from the same substrates under catalyst or condition control.5a,11 We now report chemodivergent annulative coupling of N© XXXX American Chemical Society
methoxy benzamides12 and 1,3-enynes, where both N and O nucleophiles13 can participate in [4 + 1] annulation under condition control (Scheme 1c). We initiated our studies with optimization of the reaction conditions of the coupling of N-methoxybenzamide (1a) and an alkyl-terminated enyne (2a). To our delight, a coupling occurred with Cp*Rh(OAc)2 as a catalyst in the presence of a stoichiometric amount of Cu(OAc)2, affording lactam 3aa as a major product together with an iminolactone 4aa (Table 1, entry 1). The structures of these products have been assigned based on NMR spectroscopy and mass spectrometry. In addition, product 4aa has been characterized by X-ray crystallography (CCDC 1888533). Screening of the solvent revealed that alcohols seemed to be the more suitable media for 3aa formation, and an improved yield was reached when methanol was used. Significantly, an excellent yield was realized when the reaction temperature was lowered to rt, and a comparably high yield was still obtainable when a Received: January 28, 2019
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DOI: 10.1021/acs.orglett.9b00363 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Table 1. Optimization of the Reaction Conditionsa,b
Scheme 2. Substrate Scope of N-Annulationa,b
yield (%) entry
oxidant
solvent
T (°C)
3aa
4aa
1 2 3 4 5 6 7 8 9c 10
Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 Cu(OAc)2 −
TFE DCE THF HFIP i-PrOH MeOH t-AmOH MeOH MeOH MeOH
60 60 60 60 60 60 60 rt rt rt
70 56 37 42 64 78 36 91 90 (88)d 0
7 14 47
