Palladium‐Catalyzed Highly Regioselective Arylation of Allylamines with Thiophenes and Furans

Abstract

A palladium‐catalyzed highly regioselective and stereoselective direct arylation of allylamine derivatives with a wide range of thiophenes and furans has been developed. In the presence of palladium(II) acetate [Pd(OAc)2] catalyst and appropriate oxidants, the coupling reaction proceeded with excellent group compatibility and high efficiency, leading exclusively to γ‐arylated linear (E)‐allylamines. It was found that the choice of solvent, olefin substrate and oxidant had an important influence on reaction efficiency, and the use of sterically demanding N,N‐diprotected allylamines bearing a carbamate moiety is crucial for securing high regioselectivity and stereoslectivity. This method provides a straightforward approach for the efficient synthesis of various γ‐heteroarylated, linear (E)‐allylamines.

Palladium‐Catalyzed Regioselective and Stereoselective Oxidative Heck Arylation of Allylamines with Arylboronic Acids

“…It is believed that the strong coordination of the nitrogen atom of allylic amine 2m to Pd could cause catalyst poisoning, thereby inhibiting the arylation. Similar poor performance of N , N ‐dialkylallylic amines has been reported recently 4b,5k,10b,c. It appears that the presence of a carbamate group in allylic amine substrates is necessary for high catalytic activity.…”

“…The viability of the current catalyst system was further demonstrated in the highly regioselective and stereoselective arylation of α‐substituted allylic amine 2j (Table 3, entries 25 and 26). The frequently encountered partial deprotection in the arylation of N,N ‐diprotected allylic amines did not take place in our case 5j,10b,c…”

S,O‐Ligand‐Promoted Pd‐Catalyzed C–H Olefination of Thiophenes

“…In the particular case of palladium‐catalyzed C–H functionalization of thiophenes, the vast majority of the reported reactions take place at the most acidic C‐2 position. However, when 3‐substituted thiophenes are used, addressing selective C–H functionalization at the more hindered C‐2 position remain challenging . For instance, the C–H olefination of 3‐methylthiophene with butyl acrylate have been reported to preferentially occur at the C‐2 position albeit with low selectivity (C2/C5 = 1.25:1) (Scheme a).…”

Regioselective Olefination of 3‐Substituted Five‐Membered Heteroarenes

“…[ 8 ] Shortly thereafter, the group of Xiao reported a slightly improved selectivity (C2/C5 = 2.5:1) for the olefination of 3‐methylthiophene ( 1a , 3 equiv) enabled by exploring a series of oxidants and solvents. [ 9 ] A decisive finding towards addressing this challenge was made by Liu and his co‐workers: As part of a study focusing on 2‐substituted thiophenes, 3‐methylthiophene ( 1a , 3 equiv) was also tested and the C2‐olefinated product was isolated in 58 % yield as a mixture of double bond isomers ( E/Z /branched = 93:6:1) but without the respective C5‐isomer. [ 10 ] While exploring possible reaction conditions, the authors found that a significant improvement of reactivity and selectivity could be induced through the addition of 5 vol.‐% of DMSO.…”