Pd‐Catalyzed Csp²H Functionalization of Heteroarenes via Isocyanide Insertion: Concise Synthesis of Di‐(Hetero)Aryl Ketones and Di‐(Hetero)Aryl Alkylamines

Abstract

We report herein an efficient Pd-catalyzed direct C-H bond functionalization of heteroarenes via an isocyanide insertion strategy for the synthesis of di-(hetero)aryl ketones and di-(hetero)aryl alkylamines. The methodology involves a three component reaction between an azole, a haloarene and an isocyanide resulting in the formation of an imine, which in turn is either hydrolyzed or reduced to get the desired product.

Synthesis of Diversely Functionalized Oxindoles Enabled by Migratory Insertion of Isocyanide to a Transient σ‐Alkylpalladium(II) Complex

“…Hydrolysis of (S)-7gd under acidic conditions (2.0 NH Cl, THF,R T) afforded the ester 4g whose absolute configuration was determined to be S by comparison of its optical rotation value with that reported in the literature. [23] (S)-4g is ak nown precursor of (À)-physovenine (14), (À)-esermethole (15,a nd (À)-physostigmine (16). [23] We note that previous efforts on the palladium-catalyzed carbonylative Heck reaction of 1a with CO afforded 4 with an e.r.…”

“…Thef ormation of 10 a could be accounted for by migratory insertion of isocyanide from B followed by direct imidoylation of oxadiazole. [14] It is interesting to note that the ligand plays ak ey role in the product distribution. Using dppp as ligand under otherwise identical reaction conditions, 5a and 10 a were formed in aone to one ratio (for details,see Table S2 in the Supporting Information).…”

Pd/PTABS: Catalyst for Efficient C−H (Hetero)Arylation of 1,3,4‐Oxadiazoles Using Bromo(Hetero)Arenes

“…Although, Pd/PTAPS system showed considerable improvement in the yield of the product (55%, Entry 8, Table ) with the best result obtained with PTABS providing the arylated product in 70% yield (Entry 9, Table ). As we have not explored the addition of an additive (acid such as trifluoroacetic acid or pivalic acid), it is predicted that the presence of a sulfonate (for PTABS and PTAPS system) could be responsible for providing assistance in the efficient functionalisation of the 1,3,4‐oxadiazoles. Furthermore, base study was conducted with Cs 2 CO 3 proving to be the most effective amongst the inorganic bases as the Li and K salts proved to be less effective (Entries 10–13, Table ).…”

Synthesis of Diversely Functionalized Oxindoles Enabled by Migratory Insertion of Isocyanide to a Transient σ‐Alkylpalladium(II) Complex

“…After extensive screening of reaction conditions, the desired ketone 5 a was isolated in 72 % yield together with 10 a (12 %) by performing the reaction in MeCN in the presence of Pd(OAc) 2 (0.1 equiv), t Bu‐Davephos (0.2 equiv), and Cs 2 CO 3 (2.0 equiv) at 100 °C. The formation of 10 a could be accounted for by migratory insertion of isocyanide from B followed by direct imidoylation of oxadiazole . It is interesting to note that the ligand plays a key role in the product distribution.…”