Abstract
Selectivity control of varied C–H bonds in a complex molecule is a long-standing goal and still a great challenge in C–H activation field. Most often, such selectivity is achieved by the innate reactivity of different C–H bonds. In this context, the classic Mannich reaction of acetophenone derivatives and imines is ascribed to the more reactive C(sp3)–H bonds α to the carbonyl, with the much less reactive aromatic C(sp2)–H bonds remaining intact. Herein we report an aromatic C(sp2)–H addition of ketones to imines enabled by manganese catalysis, which totally reverses the innate reactivity of C–H bonds α to the carbonyl and those on the aromatic ring. Diverse products of ortho-C–H aminoalkylated ketones, cyclized exo-olefinic isoindolines, and three-component methylated isoindolines can be successfully accessed under mild reaction conditions, which significantly expands the synthetic utilities of ketones as simple bulk chemicals.
Highlights
Selectivity control of varied C–H bonds in a complex molecule is a long-standing goal and still a great challenge in C–H activation field
We evaluated the reaction chemoselectivity by using acetophenone 1v bearing α-C–H bonds as a substrate which was commonly used in the Mannich reaction (Fig. 2)
When the reaction was carried out in the absence of MnBr(CO)[5], the Mannich reaction took place overwhelmingly followed by elimination of an amine of the β-amino carbonyl intermediate to afford chalcone 6 in 46% gas chromatography–mass spectrometry (GC-MS) yield
Summary
Selectivity control of varied C–H bonds in a complex molecule is a long-standing goal and still a great challenge in C–H activation field. Diverse products of ortho-C–H aminoalkylated ketones, cyclized exo-olefinic isoindolines, and three-component methylated isoindolines can be successfully accessed under mild reaction conditions, which significantly expands the synthetic utilities of ketones as simple bulk chemicals Ketones such as acetophenone are considered among the most accessible and practically useful building blocks in both laboratories and chemical industries. Developments of earth-abundant base metal catalyzed site-selective aromatic C–H transformations of ketones with more challenging imine electrophiles have not been reported yet Despite of their huge synthetic interests, considerable challenges still remain in these processes, such as the formidably competitive Mannich and/or Aldol-type reactions of α-C–H bonds of ketones, the relatively inert reactivity of aromatic C–H bonds with a weakly coordinating ketone group[26], and the lower catalytic reactivity of base metals compared with the precious ones. Such diverse reactivity provides a straightforward and efficient way to access varied functionalized isoindolines from simple ketones and imines
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