Alkali Base-Initiated Michael Addition/Alkyne Carbocyclization Cascades

Abstract

A new cascade reaction involving an intramolecular Michael addition followed by an alkyne carbocyclization is presented. The reaction is promoted by a substoichiometric amount of KHMDS and represents one of the rare examples where the carbocyclization of an unactivated alkyne is mediated by an alkali metal base, under mild conditions. The reaction allows the generation of functionally dense, stereochemically defined, tricyclic structures possessing three adjacent stereocenters in good yields and with high stereoselectivity.

A Conia‐Ene‐Type Cyclization under Basic Conditions Enables an Efficient Synthesis of (−)‐Lycoposerramine R

“…The reaction also worked well when cyclic ketones without α‐substituents were used. In this case, the exocyclic double bonds isomerized under the basic conditions to yield conjugated enones, as had been observed previously by Dixon (Table ) . Overall, this transformation is reminiscent of an intramolecular aldol condensation, but it can be carried out with acid‐sensitive substrates such as 34 .…”

An Enolate‐Structure‐Enabled Anionic Cascade Cyclization Reaction: Easy Access to Complex Scaffolds with Contiguous Six‐, Five‐, and Four‐Membered Rings

“…Much earlier,s imilar intramolecular addition of sodium enolate to tethered alkyne in 2-hydroxyacetonaphthone derivatives has been described by Schmid and co-workers [8] ( Figure 1a)a nd later expended to other intramolecular variations by Dixon [9] and Tr auner. [10] Although the isomerization of propargylic ether into the corresponding allene under basic conditions seems very plausible,t he reaction is believed to proceed via direct addition of an enolate to at riple bond as judged from the configuration of exocyclic double bond and nearly stoichiometric amount of the base used.…”

Eine Conia‐En‐artige Cyclisierung unter basischen Bedingungen ermöglicht die effiziente Synthese von (−)‐Lycoposerramin R

“…Die Reaktion funktionierte ebenso mit cyclischen Ketonen ohne α‐Substitution. In diesem Fall isomerisierte die exocyclische Doppelbindung unter den basischen Bedingungen zum konjugierten Enon, wie es bereits von Dixon beobachtet worden war (Tabelle ) . Ingesamt erinnert die Transformation an eine Aldolkondensation, kann aber auch mit säurelabilen Substraten wie 34 durchgeführt werden.…”