Palladium‐Catalyzed/Norbornene‐Mediated CH Activation/ N‐Tosylhydrazone Insertion Reaction: A Route to Highly Functionalized Vinylarenes

Abstract

A straightforward method for the synthesis of highly functionalized vinylarenes through palladium-catalyzed, norbornene-mediated C-H activation/carbene migratory insertion is described. Extension to a one-pot procedure is also developed. Furthermore, this method can also be used to generate polysubstituted bicyclic molecules. The reaction proceeds under mild conditions to give the products in satisfactory yields using readily available starting materials. This is a Catellani-Lautens reaction that incorporates different types of coupling partners. Additionally, this reaction is the first to demonstrate the possibility of combining Pd-catalyzed insertion of diazo compounds and Pd-catalyzed C-H activation.

Modular ipso/ortho Difunctionalization of Aryl Bromides via Palladium/Norbornene Cooperative Catalysis

“…Important contributions by Catellani, Lautens and others have demonstrated that, analogous to the cross coupling reactions, a broad range of nucleophiles can be coupled at the ipso position, which include Heck coupling, 7a,8 Suzuki coupling, 9 alkyne insertion, 10 Sonogashira coupling, 11 cyanation, 12 direct arylation, 13 amidation 14 /amination, 15 aryl ether formation, 16 hydrogenolysis, 17 enolate coupling, 18 1,2-addition to carbonyl group, 19 vinylation with hydrazone, 20 borylation, 21 thiolation, 22 and selenation 23 (Scheme 1B). However, compared to the highly versatile ipso -coupling, the scope of the electrophiles that can be introduced at the ortho position had been primarily restricted to alkyl and aryl halides since the seminal works by Catellani in 1997 7a and 2001.…”

Alkylating Reagents Employed in Catellani‐Type Reactions

“…Recently, diazo compounds have been utilized as a new type of terminating reagent for the Catellani‐type reactions . The first example was reported by Liang and co‐workers in 2014, utilizing N ‐tosylhydrazones as the terminating reagents; this demonstrated the feasibility of combining Pd‐catalyzed carbene insertion with Pd‐catalyzed C−H activation . Interestingly, it was found that the addition of water greatly improved the reaction efficiency (Scheme A).…”

“…[33] The first example wasr eported by Liang and co-workersi n2 014, utilizing N-tosylhydrazones as the terminating reagents;t his demonstrated the feasibility of combining Pd-catalyzed carbene insertion with Pd-catalyzed CÀHa ctivation. [34] Interestingly,i tw as found that the addition of water greatlyi mproved the reaction efficiency (Scheme 15 A). In addition, the authors also developed ao ne-potp rocedure:t he in situ formed tosylhydrazones from simple carbonyl compounds could be directly used for the Catellani reaction without purification,a nd comparable yields were obtained to those of the two-stepp rocess (Scheme 15 B).…”

Catellani Reaction: An Enabling Technology for Vicinal Functionalization of Aryl Halides by Palladium(0)/Norbornene Cooperative Catalysis

“…Many other types of ipso functionalization were also developed by combining the ortho alkylation (Scheme 9). For example, the ipso hydrogenation (17) [29] with alkyl boronic acid and the ipso vinylation (18) [30] with N-tosylhydrazones were realized by Lautens and Liang, respectively. In 2015, the Zhou group found that the direct construction of aryl−heteroaryl bond (19) could be achieved by coupling different heteroaromatics at the ipso position of aryl iodides.…”

“…[33] The reaction preferentially undergoes an ortho alkylation of aryl iodides followed by intramolecular Heck reaction to realize the synthesis of polysubstituted bicyclic molecules 21. Besides ipso Heck reaction, the ipso vinylation (22) [30,34] via the insertion of carbene and the ipso cyanation reaction (23) [26] could be achieved as well. Similarly, Liang synthesized polyfluoroarenesubstituted benzofuran derivatives 24 under a Pd/Cu co-catalyzed system, and it was the first time that electron-deficient arenes were directly introduced into a Catellani-type reaction.…”