Palladium(II)‐Catalyzed Aminotrifluoromethoxylation of Alkenes: Mechanistic Insight into the Effect of N‐Protecting Groups

Abstract

Summary of main observation and conclusion An efficient palladium‐catalyzed regioselective 5‐exo aminotrifluoromethoxylation of alkenes has been established herein, which provides a practical route towards the synthesis of OCF3‐containing pyrrolidines. tert‐Butyloxycarbonyl (Boc) as an amino protecting group plays a significant role in both the chemo‐ and regioselectivities. In addition, preliminary mechanistic studies reveal that the amino protecting group of substrates and the counter anion of palladium catalyst play critical roles in reaction efficiency presumably due to an isomerization of alkyl‐ Pd(II) intermediates. Moreover, the asymmetric 5‐exo aminotrifluoromethoxylation reaction has also been achieved by introducing a sterically bulky pyridinyl‐oxazoline ligand.

Ligand-Controlled Regioselective Pd-Catalyzed Diamination of Alkenes

“…Michael has reported Pd­(II)-catalyzed diamination of alkenes using N -fluorobenzenesulfonimide (NFSI) as an electrophilic aminating reagent (Scheme a, bottom) . These reactions exclusively undergo 5- exo aminopalladation of alkenes to afford the functionalized pyrrolidines, due to the coordination effect between protecting group on nitrogen and palladium . In contrast, our group reported a series of palladium-catalyzed intramolecular aminations of alkenes, such as aminofluorination, aminochlorination, aminoacetoxylation, and aminotrifluoromethoxylation, where the reactions exclusively undergo 6- endo cyclization to afford the 3-functionalized piperidines …”

“…As part of our ongoing research interest in highly selective difunctionalizations of alkenes, we recently achieved a series of asymmetric 6- endo aminations of alkenes by employing a sterically hindered pyridinyloxazoline (Pyox) ligand. In these reactions, introducing steric bulky group at the C6 position of pydinyl in chiral Pyox ligands proved to be essential for both reaction reactivity and enantioselectivity . Inspired by these studies, we chose NFSI as the oxidant and amine source to trap the alkyl-Pd­(II) species generated from 6- endo aminopalladation, which was targeted for the synthesis of 3-aminopiperidines, rather than previously reported 5- exo cyclization product.…”

Advances in the Development of Trifluoromethoxylation Reagents

“…Thus, TFMT was the first reagent which promoted the development of the field of trifluoromethoxylation and employed with fluoride anion to prepare alkyl, aryl, and heteroaryl trifluoromethyl ethers. In addition, TFMT was a precursor of trifluoromethoxide salts AgOCF 3 [117][118][119][120][121][122] and CsOCF 3 [123,124], which in turn could be used as trifluoromethoxylating reagents. However, the high volatility of TFMT (bp 19 • C) severely limits its synthetic application.…”

Palladium(II)‐Catalyzed Enantioselective Azidation of Unactivated Alkenes

“…As our ongoing research interests in difunctionalizations of alkenes, we recently disclosed several palladium-catalyzed intramolecular amination of alkenes proceeding through 6endo cyclization, giving various 3-substituted piperidines; [15] meanwhile, an asymmetric version has also been achieved by employing a sterically hindered pyridinyl-oxazoline (Pyox) ligand. [16] Notably, for these reactions, the related CÀheter-oatom bonds were generated by the reductive elimination of high-valent alkyl-Pd IV species. Inspired by these studies, we reasoned that, if an electrophilic azidating reagent can be used as an azidating source to generate high-valent alkyl-Pd IV -N 3 species, the efficient catalytic azidation of unactivated alkenes by alkyl À N 3 bond reductive elimination might be feasible (Scheme 1 b).…”

“…As our ongoing research interests in difunctionalizations of alkenes, we recently disclosed several palladium-catalyzed intramolecular amination of alkenes proceeding through 6endo cyclization, giving various 3-substituted piperidines; [15] meanwhile, an asymmetric version has also been achieved by employing a sterically hindered pyridinyl-oxazoline (Pyox) ligand. [16] Notably, for these reactions, the related CÀheter- [*] X. Li, Dr. X. Qi, C. Hou, Dr. P. Chen, Prof. Dr. G. Liu…”