Synthetic approaches to N- and 4-substituted 1,4-dihydro-3(2H)-isoquinolinone derivatives

Reaction of methyl-2-(2-formylphenyl)acetate with primary amines in a reductive amination/cyclisation process resulted N-substituted 1,4-dihydro-3(2H)-isoquinolinones. With H2NCH2R sodium borohyride is suitable reductant (11 examples), but H2NCHR1R2 required transfer hydrogenation using ammonium formate catalysed by palladium on carbon (9 examples). 4-Substituted-1,4-dihydro-3(2H)-isoquinolinones were synthesised deprotonation (n-butyllithium) and addition R3CH2Br (12 examples R3 = alkyl, Ar, CHCH2, CCH). Modest diastereoselectivity was achieved 1,4-dihydro-3(2H)-isoquinolinones derived from H2NCHMeR2 [R2 (η5-C5H4)Co(η4-C4Ph4) - max. dr 1.9 : 1], use H2NCHMeFc (Fc ferrocenyl) provided new method 1,4-dihydro-3(2H)-isoquinolinone N-deprotection formic acid.