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

• Main Authors: Nikhom Wongsa, Ubonta Sommart, Thunwadee Ritthiwigrom, Arife Yazici, Somdej Kanokmedhakul, Kwanjai Kanokmedhakul, Anthony C. Willis, Stephen G. Pyne
• Format: Journal
• Published: 2018
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84873325933&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/48139
• Institution: Chiang Mai University

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 2 OH), 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 2 O at rt. 2-(3-Butenyl)benzofurans 7 (Nu = allyl) can be prepared by treatment of 5 with BF 3 ·Et 2 O and allyltributylstannane. Furan and MeOH could also be employed as external nucleophiles in these BF 3 ·Et 2 O-promoted reactions. © 2013 American Chemical Society.