Desulfinative Alkylation of Heteroarenes via an Electrostatic Electron Donor–Acceptor Complex

Abstract

Functionalized pyridine and quinoline rings are important components of numerous bioactive molecules and natural products; however, diversification of these rings often requires de novo heterocycle ring synthesis or demanding reaction conditions. We report a method for desulfinative alkylation of pyridine and quinoline N-methoxide salts that operates under both photocatalytic and electrostatic electron donor–acceptor-mediated pathways. Unlike most EDA-mediated processes, this reaction operates in the absence of light and with the desulfination of the donor compound.

Synthesis of Quinoline Silyloxymethylsulfones as Intermediates to Sulfonyl Derivatives

“…The color change that occurs upon addition of 1 is indicative of the formation of an electron donor–acceptor complex (EDA). EDA complexes are known to form between quinolinium N -methoxides and various anions. , We observe a red shift in the UV–vis spectrum of 2a and 1 upon exposure to TsCl consistent with the formation of an EDA complex (Figure S1). Of note, no red shift occurs on exposure of solely 2a to 1 .…”

Late-Stage C–H Functionalization of Azines

“…The Niu group reported a glycosidation reaction of fasudil 111 . In addition, the Moschitto group developed an α-heteroatom alkylation reaction shown in Scheme ( 112 ) . Because the synthesis of the N -alkoxy and N -amino activating groups occurs before the reaction, derivatization cannot arise directly from the C–H azine.…”

“…90 In addition, the Moschitto group developed an α-heteroatom alkylation reaction shown in Scheme 24 (112). 91 Because the synthesis of the N-alkoxy and N-amino activating groups occurs before the reaction, derivatization cannot arise directly from the C−H azine. However, the broad scope, impressive regioselectivity, and wide range of amenable coupling partners of these reactions will allow practitioners to rapidly access azine analogues for LSF applications.…”

Silyloxymethylation of Aryl Halides via Metallaphotoredox Catalyzed Desulfinative Cross‐Coupling with Silyl Rongalite

“…In particular, we sought to probe functionalized C1 sulfinates for their potential to work as a progenitor of an oxymethyl radical under dual catalytic conditions (Scheme 1B). Although alkyl sulfinates have been exploited extensively in Minisci arylation reactions [14] including oxymethylation, [15] their application as cross‐coupling partners has been much less explored [16] . Moreover, the entries relevant to the use of a C1 sulfinate for desulfinative cross‐coupling are presently absent in the literature [17] .…”