Direct synthesis of γ‐substituted phthalides via ortho‐aryl benzoic acid mediated benzyl radical cyclization

Abstract

Direct synthesis of γ‐substituted phthalids from related ortho‐aryl benzoic acids with 48–85% yield are covered. The direct oxidation in the presence of peroxydisulphate‐copper (II) chloride in aqueous medium was applied. The reaction is highly regioselective and leads exclusively to γ‐butyrolactone, through very stable benzylic radical intermediate.

Synthesis of Annulated Anthracenes, Carb­azoles, and Thiophenes Involving Bradsher‐Type Cyclodehydration or Cycli­zation–Reductive‐Dehydration Reactions

“…As a representative case, 2‐[(9‐hexyl‐carbazol‐3‐yl)methyl]benzaldehyde ( 6a ) was first prepared from the corresponding keto acid (i.e., 4a ) 17. The reduction of the ketone group of 4a under Clemmensen conditions following the published procedure17b led to benzyl acid 5a . The benzyl acid was reduced with LiAlH 4 , and the resulting alcohol was oxidized with PCC (pyridinium chlorochromate) to give benzyl aldehyde 6a as a thick liquid (Scheme ).…”

“…We planned to test the generality of the BF 3 · OEt 2 ‐mediated cyclodehydration reaction, and so we prepared various 2‐arylmethyl benzaldehydes. Known keto acids 4b – 4q 17a,18a and 4r – 4u 18b led, upon Clemmensen reduction,17b to the formation of the respective 2‐benzyl benzoic acids (i.e., 5b – 5q ) and 2‐naphthyl benzoic acids (i.e., 5r – 5u ), respectively. LiAlH 4 reduction followed by PCC oxidation of the benzoic acids ( 5b – 5n and 5r – 5u ) gave the respective benzaldehydes (i.e., 6b – 6n and 6r – 6u ) in good to excellent yields (Scheme ).…”

“…HCl (1.8 mL) was added every 6 h. Usual work‐up following a procedure similar to that described for 5a gave benzyl acid 5b (1.72 g, 75 %) as a colourless solid, m.p. 112–114 °C (ref 19. 111–112 °C).…”

Versatile Reactivity and Catalytic Effects of Copper(II) Halides in Organic Syntheses

“…The reaction was highly regioselective and led exclusively to the butyrolactone through a very stable benzylic radical intermediate [106,107].…”

Peroxydisulfate‐Mediated Transition‐Metal‐Free Oxidative C(sp3)−H Bond Lactonization

“…For instance, Nikishin et al . and Mahmoodi et al . reported the copper‐mediated transformation of linear alkanoic acids to lactones using peroxydisulfate.…”