Catalytic Allylic Amination versus Allylic Oxidation:  A Mechanistic Dichotomy

Abstract

Allylic oxidation of hydrocarbon substrates is the foundation of many industrial and fine-chemical production processes. Direct allylic oxidation of cycloalkenes (C5 - 8) has been widely discussed in the chemical literature. However, certain mechanistic details related to the presence of allylic free radicals have yet to be fully resolved. The corresponding copper-catalyzed allylic amination reaction has not been previously achieved. We report the first examples of this class of amination reaction using saccharin and bis-p-toluenesulfonamide as nitrogen sources and t-BuOOH and PhI(saccharinate)2 as oxidants. Kinetic studies on stoichiometric model reactions demonstrate that the oxidant is not involved in the RDS of the transformation, and studies with 3,3,6,6-tetradeuteriocyclohexene conclusively show a mechanistic dichotomy between the catalytic oxidation and amination reactions. Both oxidative processes involve η1-allyl intermediates, and regiochemical results are a consequence of discrete copper complexes. A mechanistic rationale involving allylic transpositions explains this mechanism dichotomy.

Theoretical Insights into Enantioselective Catalysis: The Mechanism of the Kharasch–Sosnovsky Reaction

“…[61] It can be stated that a Curtin-Hammett situation would lead to a complete scrambling between vinylic and allylic carbon atoms, whereas no scrambling should be expected for the anti-Curtin-Hammett hypothesis. Thus, our results (indicating partial scrambling) show an intermediate behavior between experimental results corresponding to two related Kharasch-Sosnovsky reactions (suggesting full [9] or scarce scrambling). [25] Evidently, the complexity of the experimental reaction conditions (role of counterion, specific solvent interactions, different catalyst ligand, isotope labeling, etc.)…”

“…Interestingly, the comparison between the activation barriers of Beckwith-Zavitsas and Slough mechanisms shows that the hydrogen abstraction of cyclohexene by tert-butoxyl radical must occur preferably by a naked molecule, in contrast with the conclusions of a related experimental study. [9] Proposal of a new reaction mechanism: B3 LYP/6-31G* results corresponding to the OÀO bond dissociation of the perester-catalyst complex to yield the allyl-copperA C H T U N G T R E N N U N G (III) key reaction intermediate show that such a reaction is thermodynamically favored (by 21.9 kcal mol À1 ).…”

“…In Kharasch-Sosnovsky reactions by using a non-coordinating solvent in the presence of a large excess of olefin, most catalyst ions must be present in the reaction mixture as a copper(I)-alkene complex, [8] a situation consistent with kinetic data on a closely-related allylic amination reaction. [9] The first step of the catalytic cycle is the formation of a perester-catalyst complex through the ligand exchange of the alkene-copper(I) complex with tert-butyl perbenzoate.…”

“…A different reaction mechanism has recently been proposed by Slough for the Kharasch–Sosnovsky reaction 9. Accordingly, hydrogen abstraction takes place between the tert ‐butoxyl radical and the ligand‐bound benzoate‐cyclohexene‐copper(I) ion to yield a CuC σ‐bond in an intermolecular reaction, a process that involves formal π‐bond migration in the organometallic species.…”

Gold versus Silver‐Catalyzed Intermolecular Hydroaminations of Alkenes and Dienes

“…Nevertheless, when MW heating was used, very poor results were obtained (Table 3, entry 41), again the silver-catalyzed reactions failed (Table 3, entries 40 and 42). For other terminal acyclic alkenes, such as oct-1-ene (1k), the HA took place in high yield only under solvent-free conditions using the gold complex as catalyst (Table 3, entries [43][44][45][46]. In this case, product 3ka was obtained together with regioisomeric sulfonamides at the 3-and 4-positions of the aliphatic skeleton, in 2/1.5/1 ratio.…”