Bimetallic Gold(I)/Chiral N,N′‐Dioxide Nickel(II) Asymmetric Relay Catalysis: Chemo‐ and Enantioselective Synthesis of Spiroketals and Spiroaminals

Abstract

A highly efficient asymmetric cascade reaction between keto esters and alkynyl alcohols and amides is reported. The success of the reaction was attributed to the combination of chiral Lewis acid N,N'-dioxide nickel(II) catalysis with achiral π-acid gold(I) catalysis working as an asymmetric relay catalytic system. The corresponding spiroketals and spiroaminals were synthesized in up to 99 % yield, 19:1 d.r., and more than 99 % ee under mild reaction conditions. Control experiments suggest that the N,N'-dioxide ligand was essential for the formation of the spiro products.

Triple zirconocene/brønsted acid/CuO cooperative and relay catalysis system for tandem Mannich addition/C–C formative cyclization/oxidation

“…At rst, simple copper salts such as CuCl 2 , CuBr 2 , Cu(acac) 2 , Cu(OAc) 2 , CuSO 4 $5H 2 O, CuO, Cu(OTf) 2 and Cu(ClO 4 ) 2 were used as catalysts in the presence of both Cp 2 -TiCl 2 and PhCOOH (Table 1, entries 1-8). Among these metal salts, CuO was found to be the most effective catalyst and the desired product 4aa was obtained in 31% yield (Table 1, entry 6).…”

A Silver‐Catalyzed Modular Intermolecular Access to 6,6‐Spiroketals

“…[8] This method uses alkynes as less reactive surrogates for a ketone, which enables the use in late stage steps in a complex molecular environment and has been used in several total synthesis, e. g. involving gold catalysis. [12] Independently, Jiang et al developed an analogous synthetic cut, using silver and scandium synergistic catalysis yielding racemic products. [10] Despite these advances, only a limited number of intermolecular spiroketal formations have been reported, which often require highly reactive compounds such as organolithium compounds or Grignard reagents, accompanied by a low functional group tolerance.…”

“…[10] Despite these advances, only a limited number of intermolecular spiroketal formations have been reported, which often require highly reactive compounds such as organolithium compounds or Grignard reagents, accompanied by a low functional group tolerance. [14] In this light, we set out to develop a mild transition metal-catalyzed synthesis of the spiroketal substructure via an intramolecular cyclization and an intermolecular addition to yield the desired scaffold. Jiang et al introduced a silver salt-mediated transformations using an 1-(2ethynylphenyl)ethenone and Michael acceptors.…”

“…[11] The bimetallic and modular approach of Feng et al is also of note, combining a gold-catalyzed cyclization with an enantioselective [4 + 2] cycloaddition to unsaturated keto esters. [12] Independently, Jiang et al developed an analogous synthetic cut, using silver and scandium synergistic catalysis yielding racemic products. [13] Beyond its appearance in natural products and biologically active compounds of interest, the 6,6spiroketal motif has been used as skeleton for chiral ligands, enabling various transition-metal-catalyzed asymmetric reactions.…”

“…[13] Beyond its appearance in natural products and biologically active compounds of interest, the 6,6spiroketal motif has been used as skeleton for chiral ligands, enabling various transition-metal-catalyzed asymmetric reactions. [14] In this light, we set out to develop a mild transition metal-catalyzed synthesis of the spiroketal substructure via an intramolecular cyclization and an intermolecular addition to yield the desired scaffold.…”