Palladium Catalysis Featuring Attractive Noncovalent Interactions Enabled Highly Enantioselective Access to β-Quaternary δ-Lactams

Abstract

Described herein is a highly enantioselective route to β-quaternary δ-lactams by palladium/pyridine-dihydroisoquinoline (PyDHIQ)-catalyzed conjugate arylations. Notably, the effect of π-interactions on the high enantioselectivity was elucidated by DFT calculations and noncovalent interaction (NCI) analysis. The skeleton of the PyDHIQ ligand plays a key role in the formation of attractive noncovalent interactions with substrates in an enantioselectivity-determining step. The developed methodology was successfully applied to the asymmetric formal synthesis of (−)-picenadol.

Asymmetric Hydrogenation of Oximes Synergistically Assisted by Lewis and Brønsted Acids

“…For decades, our group has focused on the design and synthesis of chiral diphosphine ligands as well as their applications in asymmetric catalysis. − Ferrocene–thiourea bisphosphine ligands such as Zhaophos, which combined planar chirality, central chirality, and noncovalent interactions exhibited high reactivity and enantioselectivity for the hydrogenation of iminium and oxocarbenium salts via H-bonding or ion-pairing interactions. − It should be noted that the introduction of a suitable additive to a specific catalytic system has emerged as a powerful tool to enhance the reactivity and control the enantioselectivity. − Thus, we envisioned that Brønsted acid will protonate the oxime to produce a more activated oxime sulfonate and the conjugate base combined with thiourea to facilitate dihydrogen coordination and its subsequent heterolytic cleavage into a proton and a hydride source according to our previous research. , Concomitantly, the intervention of Lewis acid can further fine-tune the chiral environment of hydrogenation through weak interaction with thiourea. This promising strategy seems to catch up with the tremendous development of noncovalent catalysis with hydrogen bonding and ion-pairing interactions. − Here, we report Ir/Zhaophos-catalyzed asymmetric hydrogenation of oximes for the preparation of the chiral hydroxylamines (up to 95% yield and 96% ee) via synergistic assistance by Lewis and Brønsted acid (Figure c).…”

Enantioselective Reductive Conjugate Alkenylation of α,β-Unsaturated Ketones and Amides via Nickel Catalysis

“…In asymmetric conjugate addition of benchtop-stable aryl boronates and silanes, chiral complexes of Rh and Pd were well studied. Similarly, chiral Rh complexes have been applied to catalytic addition of alkenyl boronic acids, boronates, trifluoroborates, and silanes (Figure b). , The conjugate addition of alkenyl boronic acids was also promoted by chiral BINOL or tartaric acid derivatives, but high catalyst loadings were often needed (10–25 mol %).…”

Dynamic Kinetic Reductive Conjugate Addition for Construction of Axial Chirality Enabled by Synergistic Photoredox/Cobalt Catalysis

“…Nevertheless, the use of highly active organometallic reagents (ArMgX or ArLi) requires harsh reaction conditions and is poorly functional group-compatible. Subsequently, air-stable soft nucleophiles (arylborons and arylsilicons) were used in asymmetric conjugate addition chemistry involving Rh, Pd, and Cu catalysis. In particular, Rh-catalyzed Hayashi–Miyaura reactions, which realize the asymmetric additions of a variety of conjugated alkenes, are widely used to synthesize natural products .…”