(α-Aminoalkyl)cuprates Prepared from Soluble Copper(I) Salts:  Conjugate Additions to α,β-Unsaturated Carboxylic Acid Derivatives

Copper Cyanide-Catalyzed Palladium Coupling of N-tert-Butoxycarbonyl-Protected α-Lithio Amines with Aryl Iodides or Vinyl Iodides

“…Utilization of benzylmagnesium chloride results in transmetalation at −80 °C, but reductive elimination begins to occur at temperatures > −30 °C with a half-life of 4 min at −15 °C. We have observed that α-aminoalkyl cuprates are formed from the organolithium reagents at around −50 °C, whereas simple lithium dialkyl or diaryl cuprates form at lower temperatures (−120 to −78 °C). It seems plausible, therefore, that all three steps in the coupling of α-aminoalkyl anions with aryl iodides occur between −50 and 20 °C and that the oxidative addition and reductive elimination steps are slower than the transmetalation step (e.g., RLi to RPdAr).…”

“…The diamine employed to facilitate deprotonation of the carbamate moiety also effects the observed yield of the coupling reaction. Both TMEDA and sparteine effectively facilitate deprotonation of the carbamates, and in the α-aminoalkyl cuprate conjugate addition reactions use of sparteine afforded higher yields 5b. For these reasons the dependence of coupling yield on diamine does not appear to reflect deprotonation efficiencies.…”

“…These carbanions react with typical carbonyl electrophiles and with alkyl halides, chlorosilanes, and chlorostannanes. We have extended the range of α-aminoalkyl metal chemistry with the development of the corresponding cuprate and/or copper reagents which react with enones, 5a,b , enoates,5e allylic substrates,5f acid chlorides,5d and cyclic vinyl triflates 5c…”

Conjugate Addition Reactions of α-Aminoalkylcuprates with α,β-Alkenyl-, α,β-Alkynyl-, α,β−β,γ-Allenyl-, and α,β−γ,δ-Dienyl Carboxylic Acid Derivatives, Nitriles, and Sulfoxides

“…Successful development of dipole stabilized α-lithio amine chemistry encouraged the exploration of α-aminoalkylcuprate reagents. The first reported examples of α-aminoalkylcuprate conjugate addition reactions were limited to α,β-enones and enals and early efforts to effect conjugate addition to α,β-enoates were unsuccessful consistent with cuprate-enoate reactivity profiles . Although numerous homo and mixed organocuprates readily transfer alkyl ligands to the β-carbon atom of α,β-enones, the conjugate addition reaction is often sluggish with the less reactive enoate substrates.…”

“…Alkyl copper compounds also participate with enoates in conjugate addition reactions in synthetically useful yields in the presence of additives such as BF 3 ·Et 2 O and chloro- or iodotrimethylsilane . These tactics proved ineffective for α-aminoalkylcuprates and their conjugate addition to α,β-enoates was eventually achieved by use of the THF soluble complex CuCN·2LiCl and TMSCl . In this full report we describe the reactions of α-aminoalkylcuprates with α,β-alkenyl-, α,β-alkynyl- carboxylic acid derivatives 5 and nitriles and with α,β−γ,δ-dienoates (Scheme.…”