Tunable Approach to Diverse Phenethylamines via Reduction of 5-Aryloxazolidines with Triethylsilane.

A rapid pathway for the synthesis of various β-phenethylamines from aromatic aldehydes has been developed. Initially, a wide range of 5-aryloxazolidines was prepared via the [3 + 2] cycloaddition reaction of -methylazomethine ylide derived from sarcosine and paraformaldehyde. The subsequent reduction of 5-aryloxazolidines with triethylsilane in trifluoroacetic acid yields three types of products: ,-dimethylphenylethanolamines, ,-dimethylphenethylamines, and tetrahydroisoquinolines, depending on the substituents in the aromatic ring and reaction conditions.

5-Aryloxazolidines as Reagents for Double Alkylation of Arenes: A Novel Synthesis of 4-Aryltetrahydroisoquinolines.

5-Aryloxazolidines react with arenes under Lewis or Brønsted acid conditions via the Friedel-Crafts/Pictet-Spengler double alkylation sequence to give alkaloid-like 4-aryltetrahydroisoquinolines in 12-94% yields. Three approaches for the controlled insertion of substituents into the target molecules and application of oxazolidine derivatives such as 1-arylethanol-2-amines or 4-hydroxytetrahydroisoquinolines in the alkylation of arenes are also described. An unprecedented two-step easily scalable synthesis of the 4-aryltetrahydroisoquinoline core from aromatic aldehyde was achieved applying oxazolidine methodology.