Multiple remote C(sp³)–H functionalizations of aliphatic ketones via bimetallic Cu–Pd catalyzed successive dehydrogenation

Abstract

The dehydrogenation-triggered multiple C(sp3)–H functionalizations at remote positions γ, δ or ε, ζ to carbonyl groups of aliphatic ketones with carboxylic acids as coupling partners have been achieved using a bimetallic Cu–Pd catalyst system.

Oxidative Dehydrogenation of Alkanes through Homogeneous Base Metal Catalysis

“…This finding leads to the development of C(sp 3 )−H functionalization at remote positions other than α, β position to carbonyl groups. Based on bimetallic Cu−Pd catalyzed successive dehydrogenation, C(sp 3 )−H functionalizations at γ, δ or ϵ, ζ position to carbonyl groups of aliphatic ketones with aryl/alkenyl carboxylic acids as coupling partners have been achieved (Scheme 11a) [18] . The carboxyl‐directed cyclopalladation intermediate 38 reacts with terminal double bond of dienone or polyenone, yielding a six‐membered lactone intermediate.…”

“…Based on bimetallic CuÀ Pd catalyzed successive dehydrogenation, C(sp 3 )À H functionalizations at γ, δ or ɛ, ζ position to carbonyl groups of aliphatic ketones with aryl/alkenyl carboxylic acids as coupling partners have been achieved (Scheme 11a). [18] The carboxyl-directed cyclopalladation intermediate 38 reacts with terminal double bond of dienone or polyenone, yielding a six-membered lactone intermediate. Final desaturation by copper/TEMPO gave the alkenylatedisocoumarin product 39.…”

Comprehensive Mechanistic Analysis of Palladium- and Nickel-Catalyzed α,β-Dehydrogenation of Carbonyls via Organozinc Intermediates

“…Specifically, our group showed that Pd- and Ni-catalyzed methods using either stoichiometric allyl or aryl oxidants could be developed to promote α,β-dehydrogenation of ketones, esters, amides, carboxylic acids, nitriles, and heterocycles (Figure E) . The development of these methodologies has enabled access to synthetically useful unsaturated molecules, as shown in Figure F. , Many transition metal-catalyzed dehydrogenation methods are still being developed, underscoring the importance of this transformation …”

Iron-Catalyzed Aerobic α,β-Dehydrogenation

“…Their preparation from the corresponding saturated substrates is the most convenient and straightforward process and is thus of great importance. Traditional methods normally required a multistep process or the involvement of stoichiometric halogen-containing oxidants. , Utilization of a transition metal as a catalyst has been proven to be the most efficient method for the single-step α,β-dehydrogenation of carbonyls, and significant advances have been achieved. − …”