The Photochemical Activity of a Halogen-Bonded Complex Enables the Microfluidic Light-Driven Alkylation of Phenols

Abstract

A mild light-driven protocol for the direct alkylation of phenols is reported. The process is driven by the photochemical activity of a halogen-bonded complex formed upon complexation of the in situ generated electron-rich phenolate anion with the α-iodosulfone. The reaction proceeds rapidly (10 min) under microfluidic conditions, delivering a wide variety of ortho-alkylated products (27 examples, up to 97% yield, >20:1 regioselectivity, on a gram scale), including densely functionalized bioactive phenol derivatives

Dual-Role Halogen-Bonding-Assisted EDA-SET/HAT Photoreaction System with Phenol Catalyst and Aryl Iodide: Visible-Light-Driven Carbon–Carbon Bond Formation

“…To explore this strategy, we focused on phenols, i.e., feedstock compounds, as a catalyst (Figure a) since their conjugate bases (phenoxides) are stable anionic species known to serve as electron donors in EDA complex formation via π–π stacking or halogen bonding . Several groups employed phenoxide/aryl halide EDA complex formation for the light-driven C–O or C–C bond formation reactions (Figure b).…”

Visible-light-mediated synthesis of β-keto sulfones using g-C3N4 as a recyclable photocatalyst under sustainable conditions

“…The sulfonyl radical attacks the intermediate ( D ) generating 1-phenyl-2-tosylethan-1-one ( 1a ), which is facilitated by the blue light-mediated C–I bond cleavage. 23 (Scheme 3). However, the possible formation of β-keto sulfone via the nucleophilic attack of the sulfonyl nucleophile to iodo-intermediate ( D ) cannot be completely ruled out.…”

Photocatalytic Late-Stage C–H Functionalization

“…Filippini and Dell'Amico devised an in flow 86−88 alkylation of phenols via halogen-bonded EDA complexes 10 between phenoxides and α-sulfonyl iodides. 140 Naturally occurring and synthetic biologically relevant phenols, salicylaldehyde, tyramine, tyrosine, and paracetamol underwent C2 selective alkylation in the absence of externally supplied photocatalyst. Transiently formed EDA complexes can, in fact, act as visiblelight photoabsorbing species and initiate chain processes without the need for external photocatalyst.…”

“…Filippini and Dell’Amico devised an in flow − alkylation of phenols via halogen-bonded EDA complexes between phenoxides and α-sulfonyl iodides . Naturally occurring and synthetic biologically relevant phenols, salicylaldehyde, tyramine, tyrosine, and paracetamol underwent C2 selective alkylation in the absence of externally supplied photocatalyst.…”