An integrative sustainability assessment of the Tsuji–Trost reaction simulating allylic amination under non-conventional (vs. conventional) conditions

Abstract

With allyl compounds being a valuable chemical commodity, it is important to understand the sustainability aspects of the Tsuji–Trost reaction in terms of productivity (reactivity-coupled utility), environmental impact (including health hazards), and economic burden and benefits of commercially available allylic precursors under varying conditions. However, comprehensive literature searches reveal that no such study is publicly accessible; the majority of the literature focuses only on the synthetic utility of a few allylic precursors. In this context, we undertook a study for sustainability assessment of 26 allyl precursors (with diverse ionisable partners) by simulating an allylic amination reaction in an alternative reaction medium, water (vs. an organic solvent, OS), under Earth-abundant nickel (vs. traditional palladium) catalysis. The study was accomplished through: (1) conducting reactivity-utility profiling of allylic precursors; (2) identifying the major side reactions occurring with allylic precursors (water vs. OS); and (3) determining green metrics (E-factor, atom economy, atom efficiency, RME, and EcoScale) of the amination process linked with allylic precursors. The key highlights of the study include the following: (a) water is as diverse as an organic solvent in facilitating the Tsuji–Trost allylic amination; (b) diverse allylic precursors could be employed in water as well as in an organic solvent to realize allylic amination; (c) nickel catalysis is a viable alternative to palladium for allylic amination with distinct superiority in the water medium while using an allyl alcohol and allyl amine (trans-N-allylation). Further advancing sustainability and catalysis, we demonstrated for the first time a fully catalytic ‘in-water’ allylic amination reaction using an allylic alcohol and a Ni(II)-catalyst with features like scale-up synthesis (up to 10 g), catalytic usage of a reductant, etc. The authors propose this work as a sustainability guide to steer further research and developments in academia and industry related to allylation chemistries.