Oxidative Coupling of 1-(2,6-Dichlorobenzoyl)pyrroles and -pyrazoles and Alkyl Acrylates by Palladium(II) Acetate

Abstract

Treatments of 1-(2,6-dichlorobenzoyl)-, 3-acetyl-1-(2,6-dichlorobenzoyl)-, 1-(2,6-dichlorobenzoyl)-2-formyl-, and 1-(phenylsulfonyl)pyrroles with palladium acetate and alkyl acrylates gave the corresponding α-alkenyl-substituted pyrroles in good yields, while the reaction of 1-(2,6-dichlorobenzoyl)-2,5-dimethylpyrrole gave small amounts of β-alkenyl-substituted pyrroles. Under similar conditions, 1-(2,6-dichlorobenzoyl)pyrazole and 1-(2,6-dichlorobenzoyl)-3,5-dimethylpyrazole reacted with palladium acetate and alkyl acrylates to give the corresponding 4-alkenyl-substituted pyrazoles. The reaction of 1-(2,6-dichlorobenzoyl)-4-methylpyrazole gave 5-alkenyl-substituted pyrazole

Increasing synthetic efficiency via direct C–H functionalization: formal synthesis of an inhibitor of botulinum neurotoxin

“…4 Contrastingly, Itahara developed a method for oxidatively coupling heteroarenes such as indoles, pyrroles and furans with benzene in the early 1980's. [8][9][10] These original reactions required superstoichiometric amounts of palladium acetate.…”

Palladium‐Catalysed Cross‐Coupling and Related Reactions Involving Pyrroles

“…For example, in connection with efforts to prepare porphobilinogen from pyrrole, Anderson and co‐workers established that the C4‐halogenated compound 27 reacts with ethyl acrylate in the presence of Pd(OAc) 2 and triethylamine to give the β‐substituted acrylate 28 and its debenzoylated counterpart 29 (Scheme ) 44. Related conversions involving less heavily substituted and non‐halogenated pyrroles were reported by Itahara at about the same time 45. More recently, Wong and his group demonstrated46 that highly regioselective syntheses of 3,4‐disubstituted pyrroles can be achieved through manipulation of 3,4‐bis(trimethylsilyl)pyrrole.…”

The Role of Design, Serendipity, and Scientific Competition in the Development of Oxidative Coupling Reactions

“…This oxidative cross-coupling was reminiscent of the Scholl reaction 16,17 and of the work of van Helden, Verberg, 18 Itahara, [19][20][21][22] and Fujiwara, 23 who used stoichiometric Pd(II) salts for the synthesis of biaryls and styrenes. At the time that we were acquiring these data, one example of a palladiumcatalyzed oxidative cross-coupling had was reported for the synthesis of a biaryl (the synthesis of 1-phenylnapthalene), 24 so we decided to explore this new chemical territory.…”