转自：康龙化成

Enantiospecific Synthesis of α‑Tertiary Amines: Ruthenium-Catalyzed Allylic Amination with Aqueous Ammonia

Sven M. Papidocha,‡ Henrik R. Wilke,‡ Kacper J. Patej,‡ Mayuko Isomura, Tim J. Stucky, Lukas Rothenbühler, and Erick M. Carreira*

ETH Zürich, Department of Chemistry and Applied Biosciences, Laboratory of Organic Chemistry, 8093 Zürich, Switzerland

—J. Am. Chem. Soc.,2025,https://doi.org/10.1021/jacs.5c01928

Recommended by Murong Xu_MC3

KEYWORDS: asymmetric synthesis, Allylic substitution, amination, Ru catalysis (反应类型), allylic carbonates, ammonia (原料), α‑Tertiary Amines, amino acids (产物),C(sp3)-N(成键类型)

ABSTRACT: Ammonia stands out as the most available, cost-effective, and atom-economical source of nitrogen for organic synthesis. In the laboratory, it is safely and most conveniently handled in aqueous solution. Despite the advantages, the direct application of aqueous ammonia in the field of transition-metal catalysis remains a significant challenge. In this study, we report the first ruthenium-catalyzed allylic substitution using ammonia. The catalytic system, consisting of [Cp*Ru(MeCN)3]PF6and aphenoxythiazoline ligand, enables the enantiospecific amination of tertiary allylic carbonates in aqueous media and affords enantioenriched primary amines as single regioisomers in high yields.

Selected Asymmetric Allylic Substitutions

Optimization Study and Controls

Scope of Tertiary, Allylic Electrophiles for the Ruthenium-Catalyzed  Allylic Amination

Application: Preparation of Enantioenriched Cyclic Building Block 4 and Amino Acid Derivative 8

Prof. Erick M. Carreira et alhave observed that the combination of [Cp*Ru(MeCN)3]PF6with a phenoxythiazoline ligand is compatible with and exhibits catalytic activity in aqueous ammonia. This enabled development of the first enantiospecific allylic substitution of tertiary allylic carbonates to directly furnish optically activeα-tertiary amines. Importantly, exclusive monoallylation was observed for all examples investigated. Additionally,the method was applied to a range of drug- and natural product derived substrates. The reaction demonstrated broad tolerance toward functional groups, including ketones, lactones, ureas, (allylic) alcohols, and thioethers. The resulting allylic amines were obtained in up to 78% yield as single regioisomers in a highly stereospecific manner. The findings underscore the opportunities for ruthenium catalysis in allylic substitution reactions using aqueous ammonia for the stereo controlled synthesis of valuable building blocks for organic synthesis.

（转自：康龙化成）