Palladium(II)‐Catalyzed Enantioselective Aminotrifluoromethoxylation of Unactivated Alkenes using CsOCF₃ as a Trifluoromethoxide Source

Abstract

Asymmetric Pd II -catalyzed intramolecular aminotrifluoromethoxylation of unactivated alkenes using readily accessible and stable CsOCF 3 as at rifluoromethoxide source has been developed, which affords aw ide variety of enantiomerically enriched b-substituted OCF 3 -containing piperidines in good yields.I ntroducing as terically bulky group into pyridine-oxazoline (Pyox) ligands is crucial to increasing both reactivity and enantioselectivity for the reaction. Additionally, the reaction features good functional group compatibility and mild reaction conditions. Scheme 1. Catalytic asymmetric trifluoromethoxylation.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

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

“…Palladium‐catalyzed intramolecular oxidative amination of alkenes has been regarded as a powerful and efficient tool for the synthesis of pyrrolidines; however, the reaction efficiency is remarkably varied from the protecting groups on the nitrogen atom . As part of our continuous efforts on oxidative fluorination of alkenes, we have developed a Pd‐catalyzed oxidative trifluoromethoxylation of alkenes via endo ‐cyclization for the synthesis of OCF 3 ‐containing piperidines; [10a] and this process could be remarkably accelerated by sterically bulky Py‐Box ligands, realizing asymmetric endo ‐aminotrifluoromethoxylation . Notably, the alkyl C—Pd(II) bond in the intermediate proved to be converted into a new C—OCF 3 bond efficiently by using SelectFluor/ AgOCF 3 .…”

“…The palladium‐catalyzed asymmetric 5‐ exo aminotrifluoromethoxylation reaction of alkenes yielding the enantiomerically enriched 2c was also investigated. When a chiral ligand was subjected to the standard conditions, the reaction of 1c gave the product 2c in good yield (64%) but with low enantioselectivity (<5% ee), which was similar to our previous studies . However, when the sterically bulky Pyox L1 as a chiral ligand and the easily prepared and stable CsOCF 3 as a trifluoromethoxylation reagent instead of AgOCF 3 were employed for the palladium‐catalyzed regio‐ and enantioselective 5‐ exo aminotrifluoromethoxylation of alkene 1c , the reaction gave the desired product 2c in 78% yield with 93 : 7 enantiomeric ratio (eq.…”

Enantioselective Benzylation and Allylation of α-Trifluoromethoxy Indanones under Phase-Transfer Catalysis

“…[46,47] Very recently, Liu and co-workers reported the Pd-catalyzed enantioselective intramolecular trifluoromethoxylation reaction of alkenes using CsOCF3 to furnish OCF3-compounds with a chiral stereogenic center (Scheme 1d). [48] While these methods have broad substrate scopes with high enantioselectivity, all the methods require transition metal catalysts. Herein, we report the first example of constructing molecules with an OCF3 chiral center under non-metallic, organocatalytic conditions.…”