Synthesis and Application of Chiral Phosphorus Ligands Derived from TADDOL for the Asymmetric Conjugate Addition of Diethyl Zinc to Enones

Abstract

Asymmetric conjugate addition of diethylzinc to cyclohexen‐2‐one, chalcone, and benzalacetone has been found to occur with 0.5% copper(II) triflate and 1% chiral phosphite. Cyclic phosphites derived from TADDOL gave excellent to moderate enantiomeric excesses. The nature of the exocyclic substituent of the dioxaphospholane ring is important, but the chiral induction is imposed by the TADDOL framework. Syntheses of all the TADDOL ligands are described.

Enantioselective Copper-Catalysed Conjugate Addition

“…[13] Although a radical pathway for diethylzinc addition is known, [4c,14] copper-catalysed experiments in the presence of added isopropyl iodide do not show any trace of isopropyl adduct, thus ruling out such a mechanism. [15] The typical experiment in most studies is the reaction, in toluene, between diethylzinc and cyclohexenone or chalcone Ϫ taken as representatives of cyclic and acyclic enones, respectively Ϫ in the presence of 0.5Ϫ5% Cu(OTf) 2 and 1Ϫ10% chiral ligand (Scheme 2).…”

“…[27a] When an exocyclic chiral alcohol is attached, however, high enantioselectivity has been attainable. With 2-phenylcyclohexanol L108, for example, a 96% ee was obtained with cyclohexenone S6, [15,37] whilst a 73% ee Ϫ the highest so far reported for these substrates Ϫ was obtained with 2-[2-naphthyl]cyclohexanol L112 and alkylidenemalonates. [38] These ligands with two chiral moieties (the TADDOL part and the exocyclic part) show strong matched/mismatched character.…”

“…Such ligands bear a TADDOL (L65Ϫ71), [15,32] a binaphthol (L51Ϫ60) [33] or a chiral diamine (L72,73) [34] unit. The TADDOL-based ligand (R ϭ Ph) L65 gave the best reported ee values with aryl nitro olefins, [32] although its behaviour with cyclic or acyclic enones is poor to moderate.…”

“…The TADDOL-based ligand (R ϭ Ph) L65 gave the best reported ee values with aryl nitro olefins, [32] although its behaviour with cyclic or acyclic enones is poor to moderate. [15] On the other hand, the binaphthol-based phosphonites (R ϭ Ph) L51 gave poor results with cyclic enones but moderate ee values with chalcone. [33] However, the bidentate diphosphonite L63 (Reetz) was reported to afford a 96% ee on cyclohexenone.…”

Bulky Monodentate Phosphoramidites in Palladium‐Catalyzed Allylic Alkylation Reactions: Aspects of Regioselectivity and Enantioselectivity

“…[45] (1 R,7 R)-4-Diethylamino-9,9-cyclohexyl-2,2,6,6-tetra(3,5-dimethylphen- 148.2, 147.9, 147.9, 143.1, 143.0, 138.1, 137.7, 137.4 …”