Asymmetric Synthesis of Acyclic Amines Through Zr‐ and Hf‐Catalyzed Enantioselective Alkylzinc Reagents to Imines

Abstract

Readily available chiral amino acid-based ligands are used in metal-catalyzed additions of alkylzinc reagents to various aromatic and aliphatic imines; the desired amine products are formed efficiently and in high levels of optical purity. In cases where the more Lewis acidic Zr salts afford lower efficiency, Hf-based catalysts deliver significantly higher yields with similar enantioselectivities. Critical structural features of the N-activating groups as well as the optimal chiral ligands are discussed. A mechanistic working model is presented to rationalize the existing data and to serve as a predictive tool.

Nonlinear Effects in Asymmetric Catalysis

“…(61)] gave a (+)-NLE, thus suggesting the involvement of dimeric or oligomeric complexes. [164] Earlier studies [ 165] 3. Homogeneous Organocatalytic Reactions…”

“…Zhou and co-workers [147] reported a highly enantioselective hydrogenation using Rh complexes of the siphos ligand (164) [Eq. (51); cod = cyclooctadiene].…”

Nichtlineare Effekte in der asymmetrischen Katalyse

“…Eine Zirconium‐katalysierte Dreikomponentenreaktion von Diethylzink mit einem in situ gebildeten Imin unter Verwendung des Liganden 197 [Gl. (61)] ergab einen (+)‐NLE, der auf die Beteiligung dimerer und oligomerer Komplexe schließen ließ 164. In früheren Untersuchungen fand man, dass der an einen festen Polystyrolträger gebundene Ligand 197 eine ähnliche Effizienz und Selektivität zeigt wie das homogene System, was als Hinweis für eine monomere Struktur der katalytischen Spezies gewertet wurde.…”

Stereoselective Synthesis of α‐Branched Amines by Nucleophilic Addition of Unstabilized Carbanions to Imines

“…To extend this methodology to N-aryl imines derived from alkyl-substituted aldehydes, they developed a three-component approach involving in situ imine formation from an appropriate aldehyde and o-anisidine followed by the alkylation 3-ClC 6 H 4 5 9 9 9 3 . While the more Lewis acidic zirconium alkoxide afforded lower yields, higher yields with equally good or slightly lower enantioselectivities were obtained using hafnium tetraisopropoxide [83]. These conditions using the same family of chiral ligands have been recently applied to the enantioselective synthesis of N-substituted quaternary carbon centers derived from ketoimines (Scheme 1.20) [84,85].…”