Synthesis of Amides and Esters by Palladium(0)-Catalyzed Carbonylative C(sp3 )-H Activation.

The 1,4-palladium shift strategy allows the functionalization of remote C-H bonds that are difficult to reach directly. Reported here is a domino reaction proceeding by C(sp3 )-H activation, 1,4-palladium shift, and amino- or alkoxycarbonylation, which generates a variety of amides and esters bearing a quaternary ß-carbon atom. Mechanistic studies showed that the aminocarbonylation of the σ-alkylpalladium intermediate arising from the palladium shift is fast using PPh3 as the ligand, and leads to the amide rather than the previously reported indanone product.

Redox-Neutral Coupling between Two C(sp3 )-H Bonds Enabled by 1,4-Palladium Shift for the Synthesis of Fused Heterocycles.

The intramolecular coupling of two C(sp3 )-H bonds to forge a C(sp3 )-C(sp3 ) bond is enabled by 1,4-Pd shift from a trisubstituted aryl bromide. Contrary to most C(sp3 )-C(sp3 ) cross-dehydrogenative couplings, this reaction operates under redox-neutral conditions, with the C-Br bond acting as an internal oxidant. Furthermore, it allows the coupling between two moderately acidic primary or secondary C-H bonds, which are adjacent to an oxygen or nitrogen atom on one side, and benzylic or adjacent to a carbonyl group on the other side. A variety of valuable fused heterocycles were obtained from easily accessible ortho-bromophenol and aniline precursors. The second C-H bond cleavage was successfully replaced with carbonyl insertion to generate other types of C(sp3 )-C(sp3 ) bonds.

1,4-Palladium Shift/C(sp3)-H Activation Strategy for the Remote Construction of Five-Membered Rings.

1, n-Metal shift is an elegant alternative approach enabling the functionalization of remote C-H bonds from simple precursors. In this work, we report a novel and simple Pd0-catalyzed domino reaction involving 1,4-palladium shift and C(sp3)-H activation and leading to (fused) five-membered rings. This method allowed access to a broad range of valuable arylidene γ-lactams and indanones and was applied to the formal synthesis of (-)-pyrrolam.

Domino Pd0 -Catalyzed C(sp3 )-H Arylation/Electrocyclic Reactions via Benzazetidine Intermediates.

The Pd0 -catalyzed C(sp3 )-H arylation of 2-bromo-N-methylanilides leads to unstable benzazetidine intermediates that rearrange to benzoxazines through 4π electrocyclic ring-opening and 6π electrocyclization. The introduction of a bulky, non-activatable amide group on the nitrogen atom was key to favor the challenging reductive elimination step and disfavor undesired reaction pathways.

A Four-Step Synthesis of (±)-γ-Lycorane via Pd0-Catalyzed Double C(sp2)-H/C(sp3)-H Arylation.

An expedient synthesis of lycorine alkaloids is reported using a palladium(0)-catalyzed double C-X/C-H arylation as the key step. The selectivity of this reaction was controlled through the judicious choice of the two halogen atoms, and its generality was demonstrated through the construction of various substituted pyrrolophenanthridinones. A selective arene hydrogenation allowed for the completion of the synthesis of (±)-γ-lycorane in just four steps from commercially available precursors.

Synthesis of ß-Lactams by Palladium(0)-Catalyzed C(sp3 )-H Carbamoylation.

A general and user-friendly synthesis of ß-lactams is reported that makes use of Pd0 -catalyzed carbamoylation of C(sp3 )-H bonds, and operates under stoichiometric carbon monoxide in a two-chamber reactor. This reaction is compatible with a range of primary, secondary and activated tertiary C-H bonds, in contrast to previous methods based on C(sp3 )-H activation. In addition, the feasibility of an enantioselective version using a chiral phosphonite ligand is demonstrated. Finally, this method can be employed to synthesize valuable enantiopure free ß-lactams and ß-amino acids.