Evaluation of Palladacycles as a Non‐Rhodium Based Alternative for the Asymmetric Conjugate 1,4‐Addition of Arylboronic Acids to α,β‐Unsaturated Enones

Abstract

The asymmetric conjugate 1,4-addition of arylboronic acids to a,b-unsaturated carbonyl compounds is an extremely versatile and widely used organic transformation. While the rhodium(I)-catalysed reaction has been thoroughly explored, the asymmetric palladium-catalysed protocol is far less developed and understood, particularly with acyclic enones as substrates. Herein, we report the systematic evaluation of a series of metallacycles for this re-action and the conjugate addition of arylboronic acids to a wide range of a,b-unsaturated enones, catalysed by an easily accessible and robust chiral phosphapalladacycle in high yields and enantioselectivities.

Protodepalladation as a Strategic Elementary Step in Catalysis

“…Similar results were obtained with BINAM-based NHC ligands 56 and pre-formed palladacycles bearing chiral naphylphosphine ligands. 57 Chiral pyridinooxazoline (PyOX) (Scheme 21ii) 58 and bisoxazoline (BOX) 59 ligands were effectively used to construct chiral quaternary centres. Miyaura and co-workers found that addition of a silver salt greatly enhanced the enantioselectivity in linear substrates, presumably by accelerating the transmetalation step of the arylboronic acid onto palladium (Scheme 21iii).…”

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

“…On the other hand, the addition of phenylboronic acid to six and seven-membered cycles as well as linear substrates provided the products with high yields (72-97%) and enantioselectivities (78-92% ee; 12). In reactions with substituted arylboronic acids and selected acyclic enones comparable enantioselectivities were observed, while the yields were slightly lower in most cases (56-93% ee, 47-97%; entries 13-21, Table 12) [43].…”

“…Furthermore, the authors proposed a catalytic cycle (Scheme 8) [43] and stated that the rate-determining step (RDS) was the protonolysis of the O-bound enolate in the presence of PPh 3 that leads to the regeneration of the catalytically active hydroxopal-ladium species and the addition product (Scheme 8) [43]. The presence of PPh 3 ensures the preference of hydrolysis instead of a β-hydride elimination, which would lead to an oxidative Heck-type product.…”

“…The presence of PPh 3 ensures the preference of hydrolysis instead of a β-hydride elimination, which would lead to an oxidative Heck-type product. The authors stated that as a result of the coordination with PPh 3 , there is a steric hindrance disfavouring the β-hydride elimination [43].…”

Palladacyclus‐katalysierte, hoch enantioselektive Arylierung von Iminen mit Arylboroxinen ohne Verwendung einer exogenen Base

“…[13] Unter Verwendung eines planar-chiralen Palladacyclus nahmen wir aufgrund dieser bevorzugten Anordnung hohe Enantioselektivitäten an. [14] Um unsere Hypothese zu belegen, wurde die Addition von Ph-B(OH) 2 (2a)a nN-Tosylimin 1a untersucht (Tabelle 1). Das Produkt 4awurde bereits als nützliche Vorstufe von Cetirizin identifiziert.…”