Oxidative Diamination of Alkenes with Ureas as Nitrogen Sources:  Mechanistic Pathways in the Presence of a High Oxidation State Palladium Catalyst

Abstract

A first palladium-catalyzed intramolecular diamination of unfunctionalized terminal alkenes has recently been reported. This study investigates the details of its mechanistic course based on NMR titration, kinetic measurements competition experiments, and deuterium labeling. It concludes a two-step procedure consisting of syn-aminopalladation with an unligated palladium(II) catalyst state followed by oxidation to palladium(IV) and subsequent C-N bond formation to give the final products as cyclic diamines. Related reactions employing sulfamides give rise to aminoalkoxy-functionalization of alkenes. This process was investigated employing deuterated alkenes and found to follow an identical mechanism where stereochemistry is concerned. It exemplifies the importance of cationic palladium(IV) intermediates prior to the final reductive elimination from palladium and proves that the nucelophile for this step stems from the immediate coordination sphere of the palladium(IV) precursor. These results have important implications for the general development of alkene 1,2-difunctionalization and for the individual processes of aminopalladation and palladium-catalyzed C(alkyl)-N bond formation.

High‐Oxidation‐State Palladium Catalysis: New Reactivity for Organic Synthesis

“…A detailed mechanistic investigation revealed the overall sequence to be a syn aminopalladation followed by anti alkyl-nitrogen bond formation from a Pd IV intermediate. [66] This mechanism is in agreement with that found by Liu and Stahl for related aminoacetoxylation reactions. [62] The postulated involvement of a Pd IV catalyst state resulting from the oxidation of the s- alkyl palladium intermediate formed by aminopalladation was recently confirmed by theoretical calculations.…”

“…Thus, this anion is introduced into the palladium(IV) coordination sphere prior to reductive elimination. [66] Palladium(IV) catalysis also proved key to the development of a catalytic diamination of alkenes. [67] Initially, robust tosyl ureas were used as nitrogen sources for intramolecular vicinal alkene oxidation.…”

Iridium-Catalyzed, Intermolecular Hydroetherification of Unactivated Aliphatic Alkenes with Phenols

“…Palladium-catalyzed amination reactions now thought to occur by a migratory insertion step include carboaminations, [83][84][85][86] oxidative aminations, [87][88][89] chloroaminations, [90] aminoacetoxylations, [91] diaminations, [92] and hetero-Heck-type transformations. [93] In some cases, stereochemical evidence for syn aminopalladation by migratory insertion has been gained.…”

Palladium-Catalysed Intermolecular 1,2-Diamination of Alkenes

“…[1][2][3] Within this context, the application of suitable high oxidation state palladium catalysis 4 represents a key methodology.…”