Opening the Way to Catalytic Aminopalladation/Proxicyclic Dehydropalladation: Access to Methylidene γ-Lactams

Abstract

A new aerobic intramolecular palladium(II)-based catalytic system that triggers aminopalladation/dehydropalladation of N-sulfonylalkenylamides to give the corresponding methylidene γ-lactams has been identified. Use of triphenylphosphine and chloride anion as ligands is mandatory for optimal yields, and molecular oxygen can be used as the sole terminal oxidant. Scope and limitations of the methods are described. A mechanism is proposed on the basis of experimental results as well as density functional theory calculations.

Catalytic Aza-Wacker Annulation: Tuning Mechanism by the Activation Mode of Amide and Enantioselective Syntheses of Melinonine-E and Strychnoxanthine

“…Under the optimal conditions, the N-Ts amide performed a nucleophilic anti addition to the activated alkene by Pd species and subsequent β-D cis -elimination to result in a cyclized product 2a as a major product (92%), while the deuterated 2a - d was only 8%. This scenario is consistent with previous mechanistic studies on the aza-Wacker cyclization with the similar functionalized amide. , Interestingly, the cyclization of the N-OMe amide would largely go through syn-amidopalladation to afford 2g - d in a 83% D-incorporation (only 17% of the Hb signal was integrated in the NMR spectra) . Notwithstanding, further mechanistic investigation is warranted to understand the profound effect of the N substituent, this scenario would be advantageous for the diverted synthesis of cyclized products by tuning the activation mode of the amide.…”

“…This scenario is consistent with previous mechanistic studies on the aza-Wacker cyclization with the similar functionalized amide. 11,16 Interestingly, the cyclization of the N-OMe amide would largely go through syn-amidopalladation to afford 2g-d in a 83% D-incorporation (only 17% of the Hb signal was integrated in the NMR spectra). 15 Notwithstanding, further mechanistic investigation is warranted to understand the profound effect of the N substituent, this scenario would be advantageous for the HOAc (2) >99 91 (25/1) i a Reactions conditions: amide (0.1 mmol), catalyst (mol %), O 2 (1 atm), additive (equiv), and 3 Å molecular sieves (30 mg) in DMSO (1 mL) at 100 °C.…”

“…Although bipyridine-derived ligands were reported to facilitate the aza-Wacker reaction under several circumstances, in this study, these ligands were found to be less efficient to promote the cyclization (entries 10–12). Other palladium catalysts, which have been proven beneficial for selected substrates, , were less effective for the current process (entries 13 and 14). The turning point commenced with the addition of HOAc; both the reaction rate and the selectivity ( 2 / 3 ) were amended (entry 15).…”

(Diacyloxyiodo)benzenes‐Driven Palladium‐Catalyzed Cyclizations of Unsaturated N‐Sulfonylamides: Opportunities of Path Selection

“…Thus, when a distocyclic hydrogen is available ( I , R 2 =CH 3 ), the β‐H elimination path turns out to be faster than the oxidative cleavage. On the other hand, the difficulty of β‐H elimination of intermediates I and II (R 2 =H), having only a proxicyclic β‐hydrogen available has been already noticed by us ,…”

Recent Advances in Palladium-Catalyzed Oxidative Couplings in the Synthesis/Functionalization of Cyclic Scaffolds Using Molecular Oxygen as the Sole Oxidant

“…A methodology reporting access to alkylidene γ-lactams from N -sulfonylalkenylamides was presented by Poli and Oble in 2016, proceeding by way of a new aerobic approach to aminopalladation reactions via a sequential proxicyclic β-hydride elimination (Scheme 4 ). 19 The transformation was studied mechanistically by DFT calculations, together with deuterium-labeling experiments, indicating that the cyclization process occurs via an anti -aminopalladation event. A positive effect on the yield was observed using chloride ions, with the hypothesis being that these anions increase the electrophilic character of the Pd-alkene complex.…”