Synthesis of 2,3-disubstituted benzofurans and indoles by π-Lewis acidic transition metal-catalyzed cyclization of ortho-alkynylphenyl O, O- and N, O-acetals

Abstract

The PtCl 2-catalyzed cyclization reaction of ortho-alkynylphenyl acetals 1 in the presence of COD (1,5-cyclooctadiene) produces 3-(α-alkoxyalkyl)benzofurans 2 in good to high yields. For example, the reaction of acetaldehyde ethyl 2-(1-octynyl)phenyl acetal ( 1a), acetaldehyde ethyl 2-(cyclohexylethynyl)phenyl acetal ( 1c), and acetaldehyde ethyl 2-(phenylethynyl)phenyl acetal ( 1f) in the presence of 2 mol % of platinum(II) chloride and 8 mol % of 1,5-cycloocatadiene in toluene at 30 °C gave the corresponding 2,3-disubstituted benzofurans 2a, 2c, and 2f in 91, 94, and 88% yields, respectively. Moreover, the reaction of N-methoxymethyl-2-alkynylanilines 3 was catalyzed by PdBr 2, affording the corresponding 2,3-disubstituted indoles 4 in moderate yields. For example, the reaction of N-methoxymethyl-2-(1-pentynyl)- N-tosylaniline ( 3a) and N-methoxymethyl-2-(phenylethynyl)- N-tosylaniline ( 3b) in the presence of 10 mol % of PdBr 2 in toluene at 80 °C gave 3-methoxymethyl-2-propyl-1-tosylindole ( 4a) and 3-methoxymethyl-2-phenyl-1-tosylindole ( 4b) in 33 and 33% yields, respectively.