Synthesis of Medium and Large Cyclic Amines in Rhodium-Catalysed Reactions of Aminoalkenes with H2/CO

Abstract

Rhodium-catalysed reactions of N-benzyl- or N-alkyl-aminoalkenes (6) with H2/CO can give cyclic amines (7) (7–13 ring size) in good to excellent yields when BIPHEPHOS is used as a ligand. Hydrogenation of the aminoalkene becomes a competing reaction for the smaller rings but can be overcome by using a H2/CO gas ratio of 1 : 5. Reactions of 2-alkenyloxybenzylamines (13) gave 9-, 12- and 17-membered rings (14) in 30–40% yield, but dimer formation (16) and/or hydrogenation were competing reactions. Similar reactions of alkenylamides and ortho-alkenylanilines gave only non-cyclized amino aldehydes as products in low isolated yields.

Tandem Reaction of Arynes with Tertiary Amines and Aldehydes: Formation of 9‐ and 10‐Membered Dibenzo[1,5]oxaza Heterocycles

“…[1] Methods for the synthesis of nitrogen-containing medium-sized heterocycles are rare; examples include transition-metal-catalyzed (e.g., Pd-catalyzed) ringexpansion reactions, [2] silver-mediated macrocyclic lactonization, [3] rhodium-catalyzed hydroformylation of N-alkylaminoalkenes, [4] and SmI 2 -mediated cyclization. [5] However, to the best of our knowledge, there is no report on the synthesis of dibenzo-1,5-oxazonines.…”

Construction of the Azocane (Azacyclooctane) Moiety of the Lycopodium Alkaloid Lycopladine H via an Intramolecular Hydroaminomethylation Strategy

“…Thus, transition-metal-catalyzed hydroformylation of the amino alkene, followed by in situ reductive amination, has been shown to be an efficient method to form cyclic amines of various ring systems. Although this transformation has primarily been used to produce pyrrolidines, piperidines, and azepines, there are also a few examples in the literature of the synthesis of medium-sized rings . Indeed, one example exists of the formation of an azocane in moderate yield .…”

“…Although this transformation has primarily been used to produce pyrrolidines, piperidines, and azepines, there are also a few examples in the literature of the synthesis of medium-sized rings. 7 Indeed, one example exists of the formation of an azocane in moderate yield. 8 However, this powerful methodology has not yet been widely applied to complex molecule synthesis.…”