Synthesis of Cyclic Guanidines Bearing N-Arylsulfonyl and N-Cyano Protecting Groups via Pd-Catalyzed Alkene Carboamination Reactions

Abstract

Palladium-catalyzed carboamination reactions of N-allylguanidines bearing cleavable N-cyano or N-arylsulfonyl protecting groups are described. The reactions afford cyclic guanidine products in good yield, and transformations of substrates bearing internal alkenes proceed with high diastereoselectivity. Deuterium labeling studies indicate these transformations proceed via anti-aminopalladation pathways.

Pd‐Catalyzed C−C, C−N, and C−O Bond‐Forming Difunctionalization Reactions of Alkenes Bearing Tethered Aryl/Alkenyl Triflates

“…[1,2] As shown below (Scheme 1a), these transformations affect the formation of one carbon-heteroatom bond, one carbon-carbon bond, and up to two stereocenters. The transformations afford an array of heterocyclic products, including tetrahydrofurans, [3] pyrazolidines, [4] pyrrolidines, [5] cyclic ureas [6] and cyclic guanidines, [7] in good yield and high diastereoselectivity.…”

Synthesis of Dihydropyrazoles via Ligand-Free Pd-Catalyzed Alkene Aminoarylation of Unsaturated Hydrazones with Diaryliodonium Salts

“…However, despite the synthetic utility and broad substrate scope of these transformations, it has not been possible to apply the above photocatalytic systems to those β,γ-unsaturated hydrazones equipped with an aryl group at the alkene terminus. On the other hand, in recent years, palladium-catalyzed alkene difunctionalization through C–N bond formation has been established as a powerful and widely applied synthetic tool for construction of diverse nitrogen heterocycles. , Among most of these processes, the initial aminopalladation typically involves amides, carbamates as well as sulfonamides as nucleophilic nitrogen sources, thus enabling selective and efficient C–N bond formation. Inspired by such a type of catalytic activation mode, we envisioned that by combining palladium-catalyzed aminopalladation of alkene with appropriate aryl sources, we might realize an intermolecular aminoarylation of β,γ-unsaturated hydrazones (Scheme b).…”

“…On the basis of the literature reports, ,,, we currently prefer the Pd­(II)/(IV) catalytic cycle for this aminoarylation reaction as depicted in Scheme , though an alternative Pd(0)/(II) catalytic cycle cannot be excluded. Taking the syn -addition pathway as an example with 1a-D and 2a , an initial coordination of the pendant alkene to the catalyst Pd­(TFA) 2 followed by deprotonation and intramolecular syn -aminopalladation leads to a alkylpalladium complex B via Pd-amido complex A . The diaryliodonium salt 2a serves not only as aryl source but also as terminal oxidant.…”

Transition Metal‐Catalyzed Carboamination of Alkenes and Allenes: Recent Progress

“…Wolfe and co‐workers, during their study on the synthesis of various cyclic guanidine derivatives form N ‐allyl guanidines, reported a Pd‐catalyzed carboamination reaction of N ‐allyl guanidines 14 with aryl bromides/triflates 8 for the diastereoselective synthesis of cyclic guanidine derivatives 15 having an easily removable N ‐protecting group (Scheme 7). [28] The developed method has a very broad substrate scope. Almost all types of alkenes, for example aliphatic/aryl alkenes and terminal and internal alkenes were used in the cascade to synthesize corresponding guanidines in good yield and good diastereoselectivity.…”