A Pd-Catalyzed [4 + 2] Annulation Approach to Fluorinated N-Heterocycles

Abstract

3-Fluoro- and trifluoromethylthio-piperidines represent important building blocks for discovery chemistry. We report a simple and efficient method to access analogs of these compounds that are armed with rich functionality allowing them to be chemoselectively derivatized with high diastereocontrol.

Advances in Palladium‐Catalyzed Decarboxylative Cycloadditions of Cyclic Carbonates, Carbamates and Lactones

“…Next, the enantioselective variant of the reaction was achieved with excellent stereocontrol by replacing phosphoramidite L30 with chiral ligand L31 . In their continuous efforts, a palladium‐catalyzed decarboxylative [4+2] annulation of cyclic carbamate 148 with β ‐ketoester containing fluoro or trifluoromethylthio group at α position was also achieved with the same catalytic system, [58b] delivering a number of 3‐fluoro‐ and trifluoromethylthio‐piperidines in high yields (up to 99 %).…”

Concise One-Pot Multicomponent Reaction Approach to Mono­fluo­rinated Spiro-pyrazole-pyridine Derivatives without Additional Catalyst

“…5 Therefore, the synthesis of fluorine-containing N-heterocyclic compounds is particularly important. 6 Recently, the synthesis of polyheterocyclic compounds by one-pot, multicomponent reactions (MCRs) has attracted significant interest. 7 MCRs are generally considered to be one of the most important and useful methods in conventional chemical reactions, because they reduce operative steps and enhance synthetic efficiency.…”

“…5 Therefore, the synthesis of fluorine-containing N -heterocyclic compounds is particularly important. 6…”

“…However, to the best of our knowledge, protocols using ethyl 2-fluoroacetoacetate as a monofluorinated building block with pyrazolidine-3,5-diones to construct monofluorinated spiro-pyrazole-pyridine derivatives via one-pot MCRs has not been explored systematically in the literature. Considering the importance of 3-fluoropiperidine derivatives, 6 and in continuation of our interest in the synthesis of various fluorinated polyheterocyclic compounds based on the MCR strategy, 16 herein, we wish to report our recent studies on the efficient synthesis of monofluorinated functionalized spiro-pyrazole-pyridine derivatives via one-pot four-component reactions of 1,2-diphenylpyrazolidine-3,5-dione ( 1 ), ethyl 2-fluoroacetoacetate ( 2 ), aromatic aldehydes 3 , and ammonium acetate ( 4 ) without need for additional catalyst.…”

“…

3,6,3,7triazaspiro [4.5]dec-7-ene-9-carboxylate derivatives were efficiently synthesized from readily available 1,2-diphenylpyrazolidine-3,5-dione, ethyl 2-fluoroacetoacetate, aromatic aldehyde and ammonium acetate via one-pot four-component reactions in the absence of additional catalyst. In this protocols, ammonium acetate served not only as the fourth component but also as the catalyst.

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