Catalytic Enantioselective Alkylations of Tetrasubstituted Olefins. Synthesis of All-Carbon Quaternary Stereogenic Centers through Cu-Catalyzed Asymmetric Conjugate Additions of Alkylzinc Reagents to Enones

Abstract

A method for Cu-catalyzed asymmetric conjugate addition (ACA) of dialkylzinc reagents to tetrasubstituted five- and six-membered cyclic enones that afford quaternary all-carbon stereogenic centers in up to 95% ee is reported. Catalytic ACAs are practical and efficient. Reactions proceed to >98% conversion in undistilled commercial grade toluene in the presence of 2 mol % of an air-stable Cu salt (CuCN) and a readily available chiral ligand. Enantioselective ACA reactions deliver products that can be readily functionalized to afford a variety of synthetically versatile compounds in high optical purity.

Cu‐ and Ni‐Catalyzed Conjugated Additions of Organozincs and Organoaluminums to α,β‐Unsaturated Carbonyl Compounds

“…Also worthy of mention with respect to asymmetric induction are peptide-based ligands L55 (Figure 2.17), as introduced by Hoveyda et al [136], that are related to the phosphine-peptide ligands L13. Fine-tuning of the peptide backbone resulted in the development of L55a, which was used in the asymmetric conjugated addition of organozincs to tetrasubstituted activated cycloenones (Table 2.19); in this case, the asymmetric induction was up to 95% ee.…”

2-Quinoxalinol salen ligands incorporated into functionalized resins for selective solid-phase extraction of copper(II)

“…An overabundance of copper in the environment is of concern due to possible harmful effects to agriculture, fish, or wildlife. [18][19][20][21][22] SPE technology for the selective recovery of copper has not previously been described in the literature. Such technology has considerable potential and would allow many catalytic or coupling reactions commonly used in the synthetic laboratory to be more accessible for use in combinatorial processes or in industrial applications, where excess or trace metal ions are likely to complicate subsequent reactions.…”

A Multicomponent Ni‐, Zr‐, and Cu‐Catalyzed Strategy for Enantioselective Synthesis of Alkenyl‐Substituted Quaternary Carbons

“…Among the underdeveloped approaches are those that involve the less reactive acyclic a,b-unsaturated carbonyl compounds and furnish products with all-carbonsubstituted quaternary stereogenic centers. [3,4] Of the limited number of reported instances, [5] only a few pertain to linear substrates, and most involve highly activated electrophiles (e.g., nitroalkenes or Meldrums acid derivatives). [6,7] As far as we are aware, none of the existing approaches deal with the addition of alkenyl units, readily functionalizable moieties that allow access to a variety of useful enantiomerically enriched derivatives.…”