Macrolactam Synthesis via Ring-Closing Alkene–Alkene Cross-Coupling Reactions

Abstract

Reported herein is a practical method for macrolactam synthesis via a Rh­(III)-catalyzed ring closing alkene–alkene cross-coupling reaction. The reaction proceeded via a Rh-catalyzed alkenyl sp2 C–H activation process, which allows access to macrocyclic molecules of different ring sizes. Macrolactams containing a conjugated diene framework could be easily prepared in high chemoselectivities and Z,E stereoselectivities.

Recent Advances in Alkenyl sp2 C–H and C–F Bond Functionalizations: Scope, Mechanism, and Applications

“…273 Later in 2020, Loh's group substantially extended their intramolecular oxidative annulation strategy to α,β-unsaturated ketone fragments and successfully reported an expeditious method for macrolactams synthesis through a Cp*Rh(III)catalyzed alkene−alkene cross-coupling (Scheme 158). 274 The ring-closing reaction proceeded via a Rh(III)-catalyzed vinylic C−H activation process, which opens a new pathway to access diverse macrocyclic molecules of different ring sizes in satisfactory yields (33−72%). Moreover, macrolactams featuring a conjugated 1,3-diene moiety could be easily prepared with high chemoselectivities and Z,E-stereoselectivities.…”

Transition metal-catalyzed double Cvinyl–H bond activation: synthesis of conjugated dienes

“…The Loh research group 95 Loh and co-workers later extended their methodology to synthesize macrolactams 132 via rhodium-catalyzed intramolecular cross dehydrogenative coupling between acrylamide-directed alkene 130 and the α,β-unsaturated ketone 130 fragments (Scheme 56). 96 In this coupling reaction, only 2.5 mol% of [RhCp*Cl 2 ] 2 as the catalyst was employed. A broad range of substrates containing different functional groups was utilized to synthesize desired macrolactams in excellent chemo-and stereo-selective fashion.…”

K2CO3-promoted synthesis of amides from 1-aryl-2,2,2-trifluoroethanones and amines under mild conditions

“…9 The coupling of amines with pre-activated carboxylic acids or carboxylic acid derivatives (esters, aldehydes, acyl halides and acid anhydrides) is an effective method for constructing amide bonds. [10][11][12][13][14][15][16][17][18] In recent years, alcohols, [19][20][21] olens, [22][23][24][25] and alkynes [26][27][28] have also been used as carboxylic acid substitutes to synthesize amides.…”