Alternating Current Electrolysis for Organic Electrosynthesis: Trifluoromethylation of (Hetero)arenes.

Paired electrolysis has a limited reaction scope for organic synthesis because it is often not compatible with reactions involving short-lived intermediates. We addressed this limitation using alternating current electrolysis (ACE). Using trifluoromethylation of (hetero)arenes as a model reaction, we showed that the yield was improved from 13% using paired electrolysis to 84% using ACE. We have also developed a theory for guiding the rational design of reaction parameters for future applications of ACE.

Saturated oxygen and nitrogen heterocycles via oxidative coupling of alkyltrifluoroborates with alkenols, alkenoic acids and protected alkenylamines.

Saturated heterocycles are important components of many bioactive compounds. The method disclosed herein enables a general route to a range of 5-, 6- and 7-membered oxygen and nitrogen heterocycles by coupling potassium alkyltrifluoroborates with heteroatom-tethered alkenes, predominantly styrenes, under copper-catalyzed conditions, in the presence of MnO2. The method was applied to the synthesis of the core of the anti-depressant drug citalopram. The reaction scope and observed reactivity is consistent with a polar/radical mechanism involving intermolecular addition of the alkyl radical to the alkene followed by [Cu(iii)]-facilitated C-O (or C-N) bond forming reductive elimination.

Synthesis of Spirocyclic Ethers by Enantioselective Copper-Catalyzed Carboetherification of Alkenols.

Spirocyclic ethers can be found in bioactive compounds. This copper-catalyzed enantioselective alkene carboetherification provides 5,5-, 5,6- and 6,6-spirocyclic products containing fully substituted chiral carbon centers with up to 99 % enantiomeric excess. This reaction features the formation of two rings from acyclic substrates, 1,1-disubstituted alkenols functionalized with either arenes, alkenes, or alkynes, and clearly constitutes a powerful way to synthesize chiral spirocyclic ethers.

Synthesis of 2-Aryl- and 2-Vinylpyrrolidines via Copper-Catalyzed Coupling of Styrenes and Dienes with Potassium ß-Aminoethyl Trifluoroborates.

2-Arylpyrrolidines occur frequently in bioactive compounds, and thus, methods to access them from readily available reagents are valuable. We report a copper-catalyzed intermolecular carboamination of vinylarenes with potassium N-carbamoyl-ß-aminoethyltrifluoroborates. The reaction occurs with terminal, 1,2-disubstituted, and 1,1-disubstituted vinylarenes bearing a number of functional groups. 1,3-Dienes are also good substrates, and their reactions give 2-vinylpyrrolidines. Radical clock mechanistic experiments are consistent with the presence of carbon radical intermediates and do not support participation of carbocations.