Synthesis of Azaphilones and Related Molecules by Employing Cycloisomerization of o‐Alkynylbenzaldehydes

Total Synthesis of Chlorofusin, Its Seven Chromophore Diastereomers, and Key Partial Structures

“…Sonogashira coupling of aryl bromide 22 and alkyne 23 provided the azaphilone precursor 24 (Pd(Cl) 2 (PPh 3 ) 2 , CuI, Et 3 N, DMF, 70 °C, 16 h, 73%). Oxidative cyclization of 24 using Porco's methodology38 generated the azaphilone 25 in good yield (Au(OAc) 3 , CF 3 COOH, dichloroethane, 4 min; IBX, Bu 4 NI, 4 h, 72%). Acylation of the tertiary alcohol of 25 to give 26 (butyric anhydride, DMAP, CH 2 Cl 2 , 24 h, 91%), regioselective C6-chlorination yielding 27 (NCS, AcOH, 36 h, 89%) and removal of the TBDPS protecting group (HF—pyridine, THF, 2 h, 72%) proceeded smoothly to provide azaphilone 28 .…”

Six‐Membered Rings with One Oxygen: Pyrylium Ion, Related Systems and Benzo‐Derivatives

“…The reaction can be promoted by different electrophilic reagents [22], but gold salts have been found to be the best catalysts to promote this type of transformation [23]. For instance, o-alkynyl aldehyde 59 is quantitatively converted into benzopyrylium salt 60 in just 1 min (Scheme 18.14) [24].…”

Silver‐Catalyzed Cycloisomerization Reactions

“…53 Starting from p-methoxybenzyl-protected 3,5-dichloropyrazine-2(1H)-ones 26 (Scheme 5.13), after a regioselective microwave-assisted Sonogashira reaction with various terminal alkynes, the cycloisomerization reaction could occur using AgOTf (2 mol%) with trifluoroacetic acid (TFA, 5 equiv) to yield 18 Porco's team reported the formation of benzopyrylium salts 29 (Scheme 5.14) from the action of silver and gold catalysts on o-alkynylbenzaldehydes 28. 54 Although this reaction proceeds much faster with gold than with silver, the benzopyrylium formation is of interest and will be discussed further. Belmont et al worked on a variety of quinoline derivatives bearing a substituted alkynyl group on position 2 of the ring and a carbonyl function on position 3 (e.g., 30, Table 5.1).…”