Chiral aziridine-2-carboxylates: versatile precursors for functionalized tetrahydroisoquinoline (THIQ) containing heterocycles

Abstract Preparation of functionalized 3,4-dihydroisoquinolines 17a – j from ( S )- N -methoxy- N -methyl-1-[( R )-1-phenylethyl]aziridine-2-carboxamide 4 is an effective route for the synthesis of 3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinolin-4-ols. Stereoselective reduction of the cyclic imines 17a – j resulted in (1 S ,3 S ,4 R )-4-( tert -butyldimethylsilyl-oxy)-3-[( tert -butyldimethylsilyloxy)methyl]-6,7-dimethoxy-1,2-disubstituted-1,2,3,4-tetrahydroisoquinolines and the desilylation of the TBS groups afforded (1 S ,3 S ,4 R )-3-(hydroxymethyl)-6,7-dimethoxy-1,2-disubstituted-1,2,3,4-tetrahydroisoquinolin-4-ols 19a – i in good yields. Also, an asymmetric synthesis of novel tetracyclic 3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinolin-4-ols 23 and 25 was successfully achieved via Pd-catalyzed N-arylation and C–C coupling reaction.