Enantioselective synthesis of N-heterocycles via intramolecular Pd(0)-catalysed allylic amination

Diastereoselective synthesis of 2-vinylpyrrolidines and 2-vinylpiperidines by the palladium-catalysed cyclization of amino-allylic carbonates containing a chiral protecting group

“…This type of transformation frequently occurs under mild conditions, tolerates a broad array of functional groups, and proceeds with high stereoselectivity. Extending our previous work on the use of allylic carbonates in the synthesis of O-and N-heterocycles, [35][36][37][38][39][40] in this paper we report new results on diastereoselective intramolecular Pd(0)-catalysed allylic aminations. Herein, we present the first examples of asymmetric palladium catalysis in which the starting amino carbonates contain a chiral protecting group with known and specified absolute configuration which can act as a chiral auxiliary and also enable one to perform the cyclization reaction in a stereoselective way, without the presence of any chiral ligands.…”

Allylic Aminations with Hindered Secondary Amine Nucleophiles Catalyzed by Heterobimetallic Pd–Ti Complexes

“…Due to the importance of piperidine and pyrrolidine structures in natural products and pharmaceuticals, we next investigated the ability of hindered amine nucleophiles to undergo intramolecular cyclization to generate cyclic products (Figure ). Hindered substrates of this type have previously been shown to require forcing conditions and in certain cases (R = t Bu) to fail altogether . Under our standard optimized conditions with 3 mol % catalyst, we found that intramolecular amination occurred rapidly at room temperature to generate the desired heterocycles in high yield over two steps from the corresponding alcohols (Figure ).…”

Recent Developments in Asymmetric Allylic Amination Reactions

“…Alternatively, Zawisza and coworkers prepared pyrrolidines and piperidines in excellent yield using chiral palladium complexes. 103 The tendency of palladium complexes to furnish achiral linear allylic amines in the intermolecular variant is presumably tempered by the strain associated with the formation of seven-and eight-membered rings in the corresponding intramolecular process. Interestingly, the palladium catalyst derived from the phosphine-amine ligand PPM (170) delivers the highest enantioselectivity for the pyrrolidine, whereas the palladium complex with the phosphoramidite ligand ent-118 imparts the best enantioselectivity for the piperidine product (entries 7 and 8).…”

“…In contrast, the construction of the tosyl-protected piperidine was accomplished in high yield and with excellent enantioselectivity using the chiral palladium complex with ent-118 as the ligand (entry 11). 103…”