Beyond Tertiary Amines: Introducing Secondary Amines by Palladium/Norbornene-Catalyzed Ortho Amination.

Since the discovery of the palladium/norbornene (Pd/NBE)-catalyzed ortho amination in 2013, escaping the limitation of only yielding tertiary anilines has been a long-standing challenge. Here, we describe that, by carefully choosing the phosphine ligand and NBE mediator, the installation of a N-mono-alkylamino group becomes feasible. The reaction tolerates a wide range of aryl iodide substrates and various N-mono-tertiary alkylamine-derived electrophiles. Both ipso alkenylation and alkynylation can be realized. The synthetic utility of this method is exemplified by the formation of primary amino group via selective deprotection and streamlined access to N-heterocycles. Preliminary success of installing a bulky N-secondary alkylamino group and a mechanistic understanding of the decomposition pathways of mono N-alkylamine electrophiles have been obtained.

Difunctionalization of Alkenes and Alkynes via Intermolecular Radical and Nucleophilic Additions.

Popular and readily available alkenes and alkynes are good substrates for the preparation of functionalized molecules through radical and/or ionic addition reactions. Difunctionalization is a topic of current interest due to its high efficiency, substrate versatility, and operational simplicity. Presented in this article are radical addition followed by oxidation and nucleophilic addition reactions for difunctionalization of alkenes or alkynes. The difunctionalization could be accomplished through 1,2-addition (vicinal) and 1,n-addition (distal or remote) if H-atom or group-transfer is involved in the reaction process. A wide range of moieties, such as alkyl (R), perfluoroalkyl (Rf), aryl (Ar), hydroxy (OH), alkoxy (OR), acetatic (O2CR), halogenic (X), amino (NR2), azido (N3), cyano (CN), as well as sulfur- and phosphorous-containing groups can be incorporated through the difunctionalization reactions. Radicals generated from peroxides or single electron transfer (SET) agents, under photoredox or electrochemical reactions are employed for the reactions.

Allyl-Palladium-Catalyzed Ketone Dehydrogenation Enables Telescoping with Enone α,ß-Vicinal Difunctionalization.

The telescoping of allyl-palladium catalyzed ketone dehydrogenation with organocuprate conjugate addition chemistry allows for the introduction of aryl, heteroaryl, vinyl, acyl, methyl, and other functionalized alkyl groups chemoselectively to a wide variety of unactivated ketone compounds via their enone counterparts. The compatibility of the dehydrogenation conditions additionally allows for efficient trapping of the intermediate enolate with various electrophiles. The utility of this approach is demonstrated by comparison to several previously reported multistep sequences.