Concise Synthesis of α-Substituted 2-Benzofuranmethamines and Other 2-Subsituted Benzofurans via α-Substituted 2-Benzofuranmethyl Carbocation Intermediates

Abstract

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.

Hierarchically Porous Sphere-Like Copper Oxide (HS-CuO) Nanocatalyzed Synthesis of Benzofuran Isomers with Anomalous Selectivity and Their Ideal Green Chemistry Metrics

“…As a result, enormous synthetic strategies and methodologies have been developed for the construction of benzo­[b]­furan scaffolds such as decarboxylation of o-acylphenoxyacetic acids or esters, − dehydrative cyclization of (α-(phenoxy)-alkyl ketones, , palladium catalyzed cyclization of 2-(1-alkynyl)­phenols, , [3,3]-sigmatropic rearrangement of arenes etc . Recently, A3 coupling strategy, is a three-component coupling of an aldehyde, an alkyne and an amine, has been considered to be a sustainable tool with high atom economy to afford N-heterocyclic natural products and O-heterocycles including 2,3-disubstituted benzo­[b]­furans. − However, most of the reported catalytic conditions generate excess waste along with desired product due to the usage of extra additives and base reagents, toxic organic solvents and nonrecyclable catalysts which limit their applications at industrial scale production. There is a need of developing an efficient and sustainable method to afford these biologically significant benzofuran heterocycles.…”

One‐Pot Three‐Component Synthesis of 2‐Methyl‐3‐aminobenzofurans Using Calcium Carbide as a Concise Solid Alkyne Source

“…F is further hydrolyzed to afford intermediate G . [ 15 ] The hydroxyl in G attacks intramolecular triple bond to produce intermediate H , [ 16‐17 ] followed by isomerizing into the more stable 3a as a final product.…”

Aldo‐X Bifunctional Building Blocks for the Synthesis of Heterocycles

“…Dihydrobenzofurans can also be synthesized by tuning combinations of substrates . The A 3 reaction product of salicylaldehyde, phenylacetylene, and secondary amine has also been used as a starting material for the synthesis of 3‐amino‐2,3‐dihydro‐2‐arylmethylidenebenzofurans by using AgNO 3 as a catalyst …”