A catalytic multicomponent coupling reaction for the enantioselective synthesis of spiroacetals

Abstract

The first multicomponent catalytic asymmetric synthesis of spiroacetals has been described. Hybrid molecules comprising a spiroacetal scaffold (a natural-product inspired scaffold) and an α-amino acid motif (a privileged fragment) are easily available through a gold phosphate-catalysed one-pot three component coupling reaction of alkynols, anilines and glyoxylic acid.

Enantioselective Gold-Catalyzed Synthesis of Heterocyclic Compounds

“…Also using an in situ-generated gold phosphate, an enantioselective three-component synthesis of spiroacetals was reported in 2013. Attack of an iminium phosphate ion pair by the preformed enol ether was proposed to be the stereodetermining step [122]. A study also published by Gong and coworkers shows similar reactivity, although addition of excess phosphoric acid resulted in slight improvements to yield and ee [123].…”

Enantioselective synthesis of spiroacetals: the conquest of a long-sought goal in asymmetric catalysis

“…23 Under the appropriate conditions involving the use of a catalytic system formed by the combination of (JohnPhos)AuMe (5 mol%) and chiral BINOL-derived phosphoric acid E (5 mol%) in toluene at room temperature, we were able to obtain the [5,5]-spiroacetals 29 in high yield and enantiomeric excess.…”

Multicomponent and Multicatalytic Reactions – A Synthetic Strategy Inspired by Nature

“…[24] The products obtained through this multicomponent reaction could be considered as hybrid molecules comprising a spiroacetal unit (a natural-product-inspired scaffold) and an α-amino acid motif (a "privileged fragment"). The proposed mechanism for this reaction is similar to that described above for the reaction with salicylaldehyde, and the Scheme 15.…”