Ligand-Regulated Palladium-Catalyzed Regiodivergent Hydroarylation of the Distal Double Bond of Allenamides with Aryl Boronic Acid

Abstract

The ligand-regulated regiodivergent hydroarylation of the distal double bond of allenamides with aryl boronic acid was achieved in the presence of palladium­(II) catalysts, delivering a variety of functionalized enamide with excellent E selectivity and Markovnikov/anti-Markovnikov selectivity. Two possible coordination intermediates were proposed to be responsible for the regiodivergent hydroarylation: (1) The coordination Intermediate I, which was proposed to be formed through the coordination of MeCN, distal double bond, phenyl to palladium, led to the aryl group away from the Intermediate I, inducing excellent E selectivity and anti-Markovnikov selectivity. (2) A switch of regioselectivity to 1,2-Markovnikov hydroarylation was obtained using bidentate phosphine ligand (dppf or Xantphos). The formed coordination Intermediate II led to the N-tether away from the Intermediate II and at the trans position of aryl, resulting in excellent E selectivity and Markovnikov selectivity. Meanwhile, tentative investigation on the mechanism proved that the hydron source of this hydroarylation is more likely to be boronic acid. The transmetallation between aryl boronic acid and palladium catalyst was the initial step of this transformation.

Selective Hydrofunctionalization of N-Allenyl Derivatives with Heteronucleophiles Catalyzed by Brønsted Acids

“…While the formation of C−C bonds was not a primary objective of our study, it is worth noting that only one example is reported in the literature describing the γ-addition of anisole to allenamides. 31 This protocol is limited to allenyl-N-sulfonamides and its sustainability is penalized by the use of boronic acids, a Pd-based catalyst, and 1,4-dioxane as the solvent. In all other protocols, anisole was unreactive, since many more electron-rich compounds must be used to ensure an acceptable reactivity.…”

“…Furthermore, HFIP is characterized by a certain acidity (p K a ∼ 17.9 in DMSO, p K a ∼ 9.3 in water). While the formation of C–C bonds was not a primary objective of our study, it is worth noting that only one example is reported in the literature describing the γ-addition of anisole to allenamides . This protocol is limited to allenyl- N -sulfonamides and its sustainability is penalized by the use of boronic acids, a Pd-based catalyst, and 1,4-dioxane as the solvent.…”

Transition Metal‐Catalyzed Intermolecular Hydroarylation of Allenes

“…In 2021, Liu and coworkers disclosed a palladium‐catalyzed hydroarylation of monosubstituted N‐ tosyl allenamides (Scheme 49). [52] The use of acetonitrile as a ligand mainly led to the addition of the aryl moiety onto the terminal carbon of the allene (Scheme 49, eq. 1) whereas the use of the bulkier dppf or Xantphos ligand instead afforded the product resulting from the addition on the central carbon of the allene (Scheme 49, eq.…”

Palladium‐Catalyzed Cycloisomerization of 1,6‐Allene‐Ene via [1,8]‐Sigmatropic Hydrogen Shift of Allylic C−H

“…On the basis of our recently developed cyclization of allenamides, [52][53][54][55][56][57][58][59][60] we envisioned a plausible Csp 3 -H bond activation of the allylic position, which might undergo hydrogen atom transfer to deliver pyrroline derivates as shown in Scheme 1D. However, the chemo-and regio-selectivity and low BDE distinction between the old and new CÀ H bond are the main challenging.…”