1. INTRODUCTION
Arenes are one of the most extensively used substrates to access important products in the pharmaceutical and agrochemical industry. Much efforts have been devoted to their functionalization in the few decades.[1-11] Among of them, alkynes are often employed as the powerful C2 coupling partners.[12-14] Rhodium-catalyzed C−H functionalization of arenes has been established as an effective strategy to synthesize desired functional structures.[15-32] However, the multitudinous C−H bonds in arenes would lead to diverse regioselectivity. In the previous reports, many multifunctional directing groups have been introduced to improve the desired regioselectivity. Despite great progress has been achieved, the nucleophilic directing group was limited to amide, carboxylic acid, phenol, and enolate. Thus, such coupling assisted by a NH directing group still remains rare.
Recently, Li group[33] reported the Cp*Rh(OAc)2-catalyzed coupling of N-methoxybenzamide R1 and alkyl-terminated enyneR2 (Scheme 1). As shown in Scheme 1, by employing Cu(OAc)2as additive and ethanol as solvent, the major product is lactam P1 (reaction A). While the major product becomes iminolactone P2 in the presence of Cu(OAc)2 and NaOAc, with 1,4-dioxane as the solvent (reaction B).
SCHEME 1Cp*Rh(OAc)2-catalyzed coupling of N-methoxybenzamide with alkyl-terminated enyne reported by Li group
To account for the distinct regioselectivity, Li group postulated possible reaction mechanisms that are summarized in Scheme 2. Theortho arene C−H bond activation firstly occurs to afford rhodacycle complex I catalyzed by Cp*Rh(OAc)2(1cat ). Then the enyneR2’ migratory inserts into the alkyne unit selectively to afford Rh(III) alkenyl II . Subsequent 1,4-Rh migration gives a Rh(III) π-allyl species III . In reaction A, III then rearranges to form allyl complex IV , which is followed by the nucleophilic attack of the softer amide nitrogen at theη 3 position to produce P1 together with a Rh(I) complex 2cat . The Rh(I) complex could then be re-oxidized by Cu(II) salt to regenerate the active catalyst1cat for the next cycle. For comparison, in the presence of an excess of NaOAc (reaction B), acetate coordination triggers allyl rearrangement to theη 1 intermediate V , which is followed by the C−O reductive elimination to deliver product P2 .
SCHEME 2 Plausible reaction pathways for the Cp*Rh(OAc)2-catalyzed coupling of N-methoxybenzamide with alkyl-terminated enyne proposed by Li et al
Although the plausible mechanistic pathway has been proposed by the Li group, some key issues still need to be further discussed. (1) Which steps are rate- and regioselectivity-determining in both of the two reactions? (2) By using Cu(OAc)2 as additive and ethanol as solvent, the product is P1 , while the product becomesP2 in the presence of Cu(OAc)2 and NaOAc, with 1,4-dioxane as the solvent. Why? (3) What is the role of NaOAc in reaction B. To address these questions, a theoretical investigation for detailed reaction mechanisms is needed. Herein, we report our detailed density functional theory (DFT) calculations on the reaction mechanisms, in order to gain insight into the interesting experimental observations and distinct selectivity. We expect this work would help understand the detailed mechanisms and design new related reactions.