Pictet–Spengler反応を利用した1位置換isoindolinesの合成

抄録

The synthesis of 3,4-dihydro-1H-isoindoles (isoindolines) was achieved via modified Pictet–Spengler reaction of arylmethylamines and aryl- or cycloalkylaldehyde. The condensation of arylmethylamine and aldehyde followed by formylation with acetic-formic anhydride of resulting imines gave effective intermediate acyliminium ions. Treatment of acyliminium ion with trifluoroacetic acid, after removal of the acylating reagent, yielded the 1-substituted isoindolines in excellent yields. The cyclization is able to proceed via the 5-exo-trig process of enamines produced from the isomerization of acyliminium ion under acidic condition, not the 5-endo-trig process of acyliminium ion. This Pictet–Spengler type cyclization was carried out under one pot procedure, providing an effective method for preparing 1-substituted isoindolines.

Scheme 1