Functionalized fluoroalkyl heterocycles by 1,3-dipolar cycloadditions with γ-fluoro-α-nitroalkenes

The integration of flow reactors into synthetic organic chemistry

“…We have used such a system to help evolve a flow route to various butane‐2,3‐diacetals (BDAs) which are key building block in many natural product syntheses. The flow approach allowed the BDA units to be prepared generally in higher yields and with higher reproducibility than the corresponding batch processes . For example, the BDA protected tartrate was obtained from a mixed stream of dimethyl‐ l ‐tartrate and trimethyl orthoformate and a stream containing butane‐2,3‐dione together with catalytic quantities of camphorsulfonic acid (CSA).…”

“…A functionalized heterocycle that is becoming increasingly common in medicinal chemistry projects is the 3‐nitropyrrolidine. This versatile motif can be readily prepared using TFA (trifluoroacetic acid) or a fluoride source to generate a dipolar structure from N ‐(methoxymethyl)‐ N ‐(trimethylsilyl)benzylamine which will undergo cycloaddition with an alkene . Under flow conditions a stream of the nitroalkene with TFA can be combined with a second stream containing the coupling partner (Scheme ) .…”

Recent progress in the field of cycloaddition reactions involving conjugated nitroalkenes

“…Bigotti et al 23 carried out the reaction with the participation of γ-fluoro-α-nitroalkenes in the [3+2] cycloaddition reactions with nitrones. These reactions leads to isoxazolidines in good to excellent yields, with total regiocontrol and nearly complete diastereocontrol in favor of the isomers with 3,4cis configuration (Table 6).…”

Regioselectivity, stereoselectivity, and molecular mechanism of [3 + 2] cycloaddition reactions between 2-methyl-1-nitroprop-1-ene and (Z)-C-aryl-N-phenylnitrones: a DFT computational study

“…These reactions have been also explored in detail using various theoretical approaches [21,22,26]. Additionally, similar cycloadditions of 1-substituted nitroethenes (such as 2nitroprop-1-ene [27], 1-chloronitroethene [28,29], and 1bromonitroethene [27]) and 2-substituted nitroethenes (e.g., (E)-2-arylnitroethenes [30,31], (E)-1-nitroprop-1-ene [32], (E)-3,3,3-trichloro-1-nitroprop-1-ene [27,33,34], (E)-3,3,3trifluor-1-nitroprop-1-ene [35], and (E)-3-nitroacrylate [27]) analogs have been explored. Recently, preliminary studies of 32CA processes between 1,2-disubstituted nitroethenes and (Z)-(3,4,5-trimethoxyphenyl)-N-methylnitrone have also been published [28,36].…”