Regiodivergent Synthesis of 1,3‐ and 1,4‐Enynes through Kinetically Favored Hydropalladation and Ligand‐Enforced Carbopalladation

Abstract

Pd-catalyzed hydroalkynylations were developed that involve ligand-enabled regiodivergent addition of an alkyne to an allenamide, giving branched and linear products stereoselectively and facilitated by the neighboring amide group. Regioselectivity was achieved with the use of (o-OMePh) P and BrettPhos, which allowed the functionalization of various alkynes, including steroids, carbohydrates, alkaloids, chiral ligands, and vitamins. Based on the experimental results, it was proposed that hydro- and carbopalladation processes operated during the formations of the branched and linear products, respectively.

Highly Chemoselective Esterification from O‐Aminoallylation of Carboxylic Acids: Metal‐ and Reagent‐Free Hydrocarboxylation of Allenamides

“…Specifically, for compound 3 l , we first performed base‐mediated deacylation, smoothly affording γ‐hydroxyenamide 4 a , which can be manipulated further, in 91 % yield. Lewis acid mediated S N 2‐type functionalizations such as alkynylation [14] using a Zn‐acetylide and arylation using an indole afforded ynenamide 4 b and enamide‐tethered indoles 4 c , respectively. We also sought methods to construct modifiable three‐carbon synthetic building blocks via electrophile‐induced difunctionalization of the enamide unit under metal‐free conditions.…”

Silaborative Assembly of Allenamides and Alkynes: Highly Regio‐ and Stereocontrolled Access to Bi‐ or Trimetallic Skipped Dienes

“…Realization of this process is a formidable challenge because of 1) chemoselectivity issues due to unselective interception of silylboranes by either an allene [17] or alkyne; [16a, 18] 2) the regioselectivity of the allene‐alkyne coupling [19] (e.g., 5 or 5′ , Table 1) through hydroalkynylation; [19b] 3) the chemoselectivity of the allenamide, which can react through, for example, a hydroalkynylation/silaboration [20] or silaboration/alkyne coupling [16, 17e] pathway (Scheme S1); and 4) regioselectivity issues due to ligands [18d] or additives [17c] …”

Ligand‐Controlled Regiodivergence for Catalytic Stereoselective Semireduction of Allenamides

“…These processes are highly desirable as they would enable more efficient and rapid access to isomeric alkene products from the same starting allenes. [18] A major challenge in enabling the ligand-controlled divergence is closely associated with the substrate and metal dependence of the transformations. As a key intermediate, the metal allyl species are extensively known to react in different regiomeric preferences originated from the reactants' steric patterns, [19] electronic properties, [20] the types of nucleophiles, [21] and the metal species.…”