Sustainable Palladium-Catalyzed Tsuji–Trost Reactions Enabled by Aqueous Micellar Catalysis

Abstract

Palladium-catalyzed allylic substitution, or “Tsuji–Trost” reactions, can be run under micellar catalysis conditions featuring not only chemistry in water but also numerous combinations of reaction partners that require low levels of palladium, typically on the order of 1000 ppm (0.1 mol %). These couplings are further characterized by especially mild conditions, leading to a number of cases not previously reported in an aqueous micellar medium. Inclusion of diverse nucleophiles, such as N–H heterocycles, alcohols, dicarbonyl compounds, and sulfonamides is described. Intramolecular cyclizations further illustrate the broad utility of this process. In addition to recycling studies, a multigram scale example is reported, indicative of the prospects for scale up.

Allylation of C‐, N‐, and O‐Nucleophiles via a Mechanochemically‐Driven Tsuji–Trost Reaction Suitable for Late‐Stage Modification of Bioactive Molecules

“…However, primary amines showed diminished yields due to the challenging prevention of over-alkylation (22). Secondary amines, on the other hand, gave excellent allylation yields without overalkylation concerns (23,27,(32)(33)(34)(35).…”

“…The sulfonamide moiety in Celecoxib was fully bis-allylated as its high nucleophilicity hampers a monoselective reaction (36). This mild protocol successfully facilitated the allylation of several complex N-containing small molecule drugs (30)(31)(32)(33)(34)(35)(36), highlighting its potential in late-stage modifications.…”

Cascade Processes with Micellar Reaction Media: Recent Advances and Future Directions

“…Multistep, one-pot reactions were also demonstrated. Pd-catalyzed allylic substitution formation was followed by cobalt (salen)-catalyzed dehydrogenation to the N -allylated indole with 54% isolated yield [ 118 ].…”

Recent Progress of Metal Nanoparticle Catalysts for C–C Bond Forming Reactions

“…One of the most effective catalytic systems is micellar catalytic systems, which have been developed and expanded by Lipshutz and Handa groups. In their reaction systems, several reactions proceed at room temperature by designing an appropriate surfactant which form a micellar reaction field in water (Scheme 30) [315][316][317][318][319][320][321][322][323][324][325][326][327][328]. Scheme 30.…”