Selective Demethylations in 2, 3, 4-Trimethoxyaryl Carbonyl Compounds

Lead Optimization of Second-Generation Acridones as Broad-Spectrum Antimalarials

“…The synthesis of the first series of acridones 18 – 58 with various mono- and disubstitutions on ring A and aryloxy, arylamino, and aryl moieties at the 6-position of ring B started from commercially available methyl 4-iodo-2-methoxybenzoate ( 1 ) and methyl 4-bromo-2-methoxybenzoate ( 2 ). Initially, the copper-catalyzed arylation of 1 with phenols 3a – e delivered the corresponding diaryl ether intermediates 4a – e , which were then converted into 2-hydroxy-diaryl ethers 5a – e by selective deprotection of the methoxy (OMe) group with boron trichloride (BCl 3 ) . Intermediates 5a – e were treated with triflic anhydride (Tf 2 O) in the presence of pyridine to give the triflates 6a – e , which were further subjected to Buchwald–Hartwig cross-coupling with various substituted anilines 7a–l to give the key anthranilate intermediates 8a – q (Scheme ).…”

“…Initially, the copper-catalyzed arylation 15 of 1 with phenols 3a−e delivered the corresponding diaryl ether intermediates 4a−e, which were then converted into 2hydroxy-diaryl ethers 5a−e by selective deprotection of the methoxy (OMe) group with boron trichloride (BCl 3 ). 16 Intermediates 5a−e were treated with triflic anhydride (Tf 2 O) in the presence of pyridine to give the triflates 6a−e, which were further subjected to Buchwald−Hartwig crosscoupling with various substituted anilines 7a−l to give the key anthranilate intermediates 8a−q (Scheme 1). 14,17 Conversely, the synthesis of anthranilate intermediates 12a−j and 17a−f, key synthons in the synthesis of acridones 43−52 and 53−58, commenced with the coupling of 2 with corresponding anilines 7m−q and boronic acids 13a−d under standard Buchwald− Hartwig and Suzuki cross-coupling reaction conditions to derive intermediates 9a−e and 14a−d, respectively.…”

Improved Auxiliary for the Synthesis of Medium‐Sized Bis(lactams)

“…Auxiliary 3c was obtained from commercially available 2,3,4‐trimethoxybenzaldehyde ( 3a ). Selective “BCl 3 ‐mediated” demethylation of 3a 16 was followed by alkylation with isopropyl bromide 17. Besides 3c , a mixture derived from alkylation on the ortho position and alkylation on both phenols was obtained.…”

Oxazole‐Bridged Combretastatin A Analogues with Improved Anticancer Properties

“…Catechol 7, an oxazole derivative of combretastatin A-1 (CA-1), was made via the dibenzyl ether 6 from 1 and 2,3-dibenzoxy-4-methoxy-benzaldehyde 2 c. The latter was prepared in two steps starting from 2,3,4-trimethoxybenzaldehyde, which was selectively demethylated with BCl 3 in dichloromethane. [10] The resulting 2,3-dihydroxy-4-methoxybenzaldehyde was then benzylated with benzyl bromide in the presence of potassium carbonate yielding 2 c. The debenzylation of 6 using H 2 gas and Pd/C catalyst gave catechol 7 in 48 % yield. In this case, the protocol used for the conversion of 3 to 4 afforded only 37 % of catechol 7.…”