Concise synthesis of α-substituted 2-benzofuranmethamines and other 2-subsituted benzofurans via α-substituted 2-benzofuranmethyl carbocation intermediates

摘要

Propargyl amines 4, where R~3 is aryl, undergo 5-exo-dig cyclization reactions under relatively mild conditions (AgNO_3, DMF, 60 C, 1 h) to give 3-amino-2,3-dihydro-2-arylmethylidenebenzofurans 5 (R~ 3 = aryl). In contrast, substrates where R~3 is alkyl undergo competing 6-endo-dig and 5-exo-dig cyclization processes. The hydroxymethyl substrate 4 (R~3 = CH_2OH), however, was smoothly converted to its corresponding 5-exo-dig cyclization product 5, likely due to the assistance of the primary hydroxyl group in the 5-exo-dig cyclization process by silver cation coordination. Under more enforcing conditions (AgNO_3, DMF, 100 C, 18 h), the initially formed products 5 undergo a 1,3-allylic rearrangement to their corresponding 2-substituted benzofuran derivatives 6. This rearrangement can also be effected by treating 5 with AgNO_3 in DMF at 100 C for 18 h or BF_3·Et_2O at rt. 2-(3-Butenyl)benzofurans 7 (Nu = allyl) can be prepared by treatment of 5 with BF_3·Et_2O and allyltributylstannane. Furan and MeOH could also be employed as external nucleophiles in these BF_3·Et_2O-promoted reactions.