Photoredox-mediated Minisci C–H alkylation of N-heteroarenes using boronic acids and hypervalent iodine

Abstract

A photoredox-mediated Minisci C–H alkylation of N-heteroarenes with easily accessible primary and secondary alkyl boronic acids has been developed.

Visible‐Light Photocatalysis as an Enabling Tool for the Functionalization of Unactivated C(sp3)‐Substrates

“…Hypervalent iodine reagents have also been utilized as oxidants in coupling of alkyltrifluoroborates with alkynes (Scheme 27) [64] and with vinylcarboxylic acids 45 (Scheme 28), [65] as well as in Minisci-type C-H alkylation with alkylboronic acids 46 (Scheme 29). [66] In the coupling of alkyltrifluoroborates with alkynylbenziodoxoles, mechanistic investigations were performed, and 1-hydroxy-1,2-benziodoxol-3-(1H)-one (BI-OH, 47) or the benziodoxole radical were proposed to oxidize the photoexcited Ru II * to Ru III (Scheme 27). [64] Subsequent oxidation of the alkyltrifluoroborate formed the alkyl radical and regenerated the photocatalyst.…”

“…[67,68] Typically, alkylcarboxylic acids are employed as carbon radical precursors; however, Li and co-workers have developed a photocatalytic method in which primary and secondary alkylboronic acids are used as radical-forming substrates. [66] Alkylation of various Nheteroarenes was accomplished with the aid of the photocatalyst Ru(bpy) 3 Cl 2 and BI-OAc (44) as the oxidant (Scheme 29). Here, DFT calculations supported an initial SET from the excited-state Ru II * species to BI-OAc, forming an oxygen-centered radical that reacted with the alkylboronic acid to form the key alkyl radical.…”

Visible‐Light‐Initiated Manganese Catalysis for C−H Alkylation of Heteroarenes: Applications and Mechanistic Studies

“…[1,2] Owing to increasing interest in alkyl-functionalized heterocycles in drug discovery,C À H alkylation of heteroarenes has impacted medicinal chemistry strategies. [2,[4][5][6][7] Non-photomediated Minisci approaches often involve the use of an excess oxidant, peroxide,e xcess acid, and high temperature. [2,[4][5][6][7] Non-photomediated Minisci approaches often involve the use of an excess oxidant, peroxide,e xcess acid, and high temperature.…”

Alkinylierung von C(O)‐H‐Bindungen durch Photoredox‐vermittelten Wasserstoffatomtransfer

“…[17] Solche Verfahren erfordern jedoch eine vorherige Substratfunktionalisierung,s odass eine niedrige Atom-und Stufençkonomie resultiert. [15d, 18] Zum Te sten dieser Hypothese wählten wir Cyclohexancarbaldehyde (A)a ls Substrat unter Verwendung der katalytischen Bedingungen unserer vorherigen Arbeit: [9] 10 Mol-%d es HAT-Katalysators Natrium-2-iodbenzoat, [19] 2M ol-% [Ir(dF(CF 3 )ppy) 2 (dtbbpy)]PF 6 ((dF(CF 3 )ppy) = 2-(2,4-Difluorphenyl)-5-(trifluormethyl)pyridin, dtbbpy = 4,4'-Di-tertbutyl-2,2'-bipyridin), PC I (Ir III* /Ir II = 1.21 Vg egen SKE) in Anwesenheit von EBX-Reagenz B.Das gewünschte Produkt wurde in einer Ausbeute von lediglich 10 %g ebildet (Tabelle 1, Nr.1). [15d, 18] Zum Te sten dieser Hypothese wählten wir Cyclohexancarbaldehyde (A)a ls Substrat unter Verwendung der katalytischen Bedingungen unserer vorherigen Arbeit: [9] 10 Mol-%d es HAT-Katalysators Natrium-2-iodbenzoat, [19] 2M ol-% [Ir(dF(CF 3 )ppy) 2 (dtbbpy)]PF 6 ((dF(CF 3 )ppy) = 2-(2,4-Difluorphenyl)-5-(trifluormethyl)pyridin, dtbbpy = 4,4'-Di-tertbutyl-2,2'-bipyridin), PC I (Ir III* /Ir II = 1.21 Vg egen SKE) in Anwesenheit von EBX-Reagenz B.Das gewünschte Produkt wurde in einer Ausbeute von lediglich 10 %g ebildet (Tabelle 1, Nr.1).…”