title: Hydroheteroarylation of Unactivated Alkenes Using N-Methoxyheteroarenium Salts.
abstract: We report the first reductive coupling of unactivated alkenes with N-methoxy pyridazinium, imidazolium, quinolinium, and isoquinolinium salts under hydrogen atom transfer (HAT) conditions, and an expanded scope for the coupling of alkenes with N-methoxy pyridinium salts. N-Methoxy pyridazinium, imidazolium, quinolinium, and isoquinolinium salts are accessible in 1-2 steps from the commercial arenes or arene N-oxides (25-99%). N-Methoxy imidazolium salts are accessible in three steps from commercial amines (50-85%). In total 36 discrete methoxyheteroarenium salts bearing electron-donating, electron-withdrawing, alkyl, aryl, halogen, and haloalkyl substituents were prepared (several in multigram quantities) and coupled with 38 different alkenes. The transformations proceed under neutral conditions at ambient temperature, provide monoalkylation products exclusively, and form a single alkene addition regioisomer. Preparatively useful and complementary site selectivities in the addition of secondary and tertiary radicals to pyidinium salts are documented: harder secondary radicals favor C-2 addition (2->10:1), while softer tertiary radicals favor bond formation to C-4 (4.7->29:1). A diene possessing a 1,2-disubstituted and 2,2-disubstituted alkene undergoes hydropyridylation at the latter exclusively (61%) suggesting useful site selectivities can be obtained in polyene substrates. The methoxypyridinium salts can also be employed in dehydrogenative arylation, borono-Minisci, and tandem arylation processes. Mechanistic studies support the involvement of a radical process.
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: Xiaoshen
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: Hester
authors.initials: H
authors.lastname: Dang
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: John A
authors.initials: JA
authors.lastname: Rose
authors.affiliation: Department of Chemistry and Biochemistry, Swarthmore College , Swarthmore, Pennsylvania 19081, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Rablen
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520, United States.|Department of Pharmacology, Yale School of Medicine , New Haven, Connecticut 06520, United States.
authors.forename: Seth B
authors.identifier: 0000-0001-5940-9853
authors.initials: SB
authors.lastname: Herzon