The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• relationships in this chemotype. Keywords: acyl Pictet–Spengler reaction; alkaloids; antiproliferative activity; benzyltetrahydroisoquinolines; ion channels; protective group; total synthesis; Introduction The benzylisoquinoline alkaloids are a large and diverse class of plant secondary metabolites including

• [15]. In this work we took advantage of the hitherto less explored N-acyl-Pictet–Spengler reaction and related chemistry based on the seminal work of Speckamp [16], where an N-acyl residue at the arylethylamine building block leads to enhanced cyclization rates due to the acid-mediated formation of

• by lithium alanate reduction [18][19]. In a novel total synthesis of the racemic alkaloid N-methylcoclaurine (1) performed in this course we also used the ethoxycarbonyl group successfully for protection of two phenolic groups at two different rings during the N-acyl-Pictet–Spengler reaction [15

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• participating directly as the nucleophile. First proposed anion-binding mechanism in the thiourea-catalyzed acetalization of benzaldehyde. a) Thiourea-catalyzed enantioselective acyl-Pictet–Spengler reaction of tryptamine-derived imines 4. b) Equilibrium between the ionic (SN1-type mechanism) and neutral form