Synthesis of Vinylcyclopropane‐Fused Pyrazolone Derivatives by Sulfur Ylide‐Initiated 1,6‐Michael Addition‐Cyclization Reactions

Abstract

A highly diastereoselective cyclopropanation of α,β,γ,δ‐unsaturated pyrazolones has been disclosed. This method allows for construction of a vinylcyclopropane‐fused pyrazolone framework via a 1,6‐addition/substitution sequence providing excellent regio‐ and chemoselectivity, good yields, broad functional group tolerance and gram‐scale capacity. Moreover, the subsequent transformation of derivatives demonstrates great potential in building useful synthetic architectures.

Stereoselective Assembly of Multifunctional Spirocyclohexene Pyrazolones That Induce Autophagy-Dependent Apoptosis in Colorectal Cancer Cells

“…We designed amine-catalyzed asymmetric [4 + 2] annulation of α,β,γ,δ-unsaturated pyrazolone 1 with aldehyde 2 to produce the target framework (Scheme b). In this reaction, the α,β,γ,δ-unsaturated pyrazolone substrate 1 serves as the electron-deficient C4 building block as well as branched diene for spiro-construction whereas the aldehyde 2 is activated via a highest occupied molecular orbital-raising strategy . The resulting spirocyclohexene-pyrazolone hybrids can provide a chiral spirocycle library for bioactive screening as part of the combinatorial pharmacophore strategy, which can be effective for lead discovery.…”