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

Abstract

Catalyst-free addition of ketone enolate to nonactivated multiple CÀCb onds involves non-complementary reaction partners and typically requires super-basic conditions. On the other hand, highly aggregated or solvated enolates are not reactive enough to undergo direct addition to alkenes or alkynes.Herein, we report an ew anionic cascade reaction for one-step assembly of intriguing molecular scaffolds possessing contiguous six-, five-, and four-membered rings,r epresenting af ormal [2+ +2] enol-allene cycloaddition. Reaction proceeds under very mild conditions and with excellent diastereoselectivity.D eeper mechanistic and computational studies revealed unusually slow proton transfer phenomenon in cyclic ketone intermediate and explained peculiar stereochemical outcome.

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

“…This is likely related to significant racemization of carboanion stereogenic center before isomerization to allene as the reaction proceeded at relatively high temperature.Indeed, by using more basic KHMDS,the reaction temperature could be lowered to À40 8 8Ca nd the ee of the product drastically increased to 80 %; the value is within arange of ee suitable for potential further enrichment by crystallization. Thea bsolute configuration of the major enantiomer of 3c was predicted based on the computationally derived mechanism (Figure 3) and verified by single-crystal X-ray analysis [32] of the derived 3,5-dinitrobenzoate (Supporting Information, page S128).…”

“…Thec ompound 3a was obtained as as ingle diastereomer as indicated by NMR and its structure was secured by X-ray crystallography. [32] Ther eaction scope was further evaluated as outlined in Figure 2. Thereaction is compatible with various substituents Tabelle 1: Screening of reaction conditions.…”

“…Exploration of substrate scope. [32] [a] Yield based on recovered starting material. Standard reaction conditions:…”

Triton B-promoted regioselective intramolecular addition of enolates to tethered ynamides for the construction of 8-membered O-heterocycles

“…14 Recently Orentas et al proposed an elegant anionic cascade reaction, affording unique polycyclic ring-fused systems via a formal [2 + 2] enolallene cycloaddition (Scheme 2b). 15 Reported Conia-ene reactions of ene-ynamides are scarce. 16 In connection with our ongoing research on ynamides and intrigued by the possibility to explore the reactivity of those substrates, the reactivity of unique ynamides equipped with propargylic ethers in basic media was considered.…”

“…14 Recently Orentas et al proposed an elegant anionic cascade reaction, affording unique polycyclic ring-fused systems via a formal [2 + 2] enol-allene cycloaddition (Scheme 2b). 15…”