Synthesis of 3-Amino-5-fluoroalkylfurans by Intramolecular Cyclization

Abstract

A synthesis to access rarely described 3-amino-5-fluoroalkylfurans has been developed by cyclization of easily accessible fluorovinamides. This method is rapid and simple and affords the desired furans as hydrochloride salts in quantitative or nearly quantitative yields. It is compatible with four different fluorinated groups (-CF3, -CF2CF3, -CHF2, and -CF2Cl) and a wide range of substituents on the amine.

New Chemical Transformations Involving SO2F2‐Mediated Alcohol Activation

“…Very recently, our group reported on the SO 2 F 2 -mediated synthesis of polyfluoroalkyl aryl ethers from fluorinated alcohols. [83] While most previously reported, processes for the polyfluoroalkylation of phenols require harsh conditions (high temperature, strong base, metal catalyst), the present method involves mild conditions and a short reaction time (30 min). There was only one example of SO 2 F 2 -mediated alkylation of a phenol reported by Sammis and co-workers, using a nonfluorinated alcohol.…”

Synthesis of Polysubstituted Furans: An Update Since 2019

“…Synthesis of fluoromethylated enones was reported by Gerus et al [113] Leroux et al in 2021 explored the synthetic potential of fluoro methylated enones for the synthesis of 3amino-5-fluoroalkylfurans 210 by cyclization of fluoromethylated enones 206 in good to excellent yields. [114] The mechanism involves the activation of the alcohol by thionyl chloride. The alcohol is probably activated only by protonation under acidic conditions without SOCl 2 .…”

“…Leroux et al. in 2021 explored the synthetic potential of fluoro methylated enones for the synthesis of 3‐amino‐5‐fluoroalkylfurans 210 by cyclization of fluoromethylated enones 206 in good to excellent yields [114] . The mechanism involves the activation of the alcohol by thionyl chloride.…”

Biomass to Aromatic Amine Module: Alkali Catalytic Conversion of N‐Acetylglucosamine into Unsubstituted 3‐Acetamidofuran by Retro‐Aldol Condensation

“…Lingham and co‐workers [17] synthesized a series of 3‐ N ‐substitued and 5‐alkyl −3‐ N ‐substituted furan derivatives via enaminones derived from the Michael addition of amines to acyclic keto alkynol precursors. The groups of Li [18] and Leroux [19] both developed this method to prepare polysubstituted 3‐amino furans and 3‐amino‐5‐fluoroalkylfurans in quantitative or nearly quantitative yields (Scheme 1a). Guguloth and co‐workers [20] obtained 3‐aminofuran derivatives with substituent groups at the 2, 3 and 5 positions in yields greater than 80 % through the tandem Mannich‐Grignard addition and intramolecular cyclization of ketoaldehydes, secondary amines and terminal alkyne (Scheme 1b).…”