Asymmetric preparation of polysubstituted cyclopentanes by synergistic Pd(0)/amine catalyzed formal [3+2] cycloadditions of vinyl cyclopropanes with enals

Abstract

We report herein a novel diastereo- and enantiocontrolled preparation of polysubstituted cyclopentanes by the formal [3+2] cycloadditions of vinyl cyclopropanes with enals. In constrast with previously developed strategies, our original approach is based on the synergistic merger of iminium/enamine organocatalysis with palladium(0) catalysis.

Synergistic formal ring contraction for the enantioselective synthesis of spiropyrazolones

“…Lately several groups have reported several synergistic cycloadditions for the formation of bicyclic and spiro products. Michelet, 5 Jørgensen, 6 Wei Wang 7 and Rios 8 reported a formal ring expansion of vinyl cyclopropanes with enals for the formation of spiro compounds under Pd(0) and secondary amine catalysis. Later on, Jørgensen reported vinyl aziridine opening 9 and [4 + 2] decarboxylation 10 ( Scheme 1 top) using a synergistic approach with excellent results.…”

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

“…To test the feasibility of the designed [3 + 2] annulation process [ 79 – 94 ], we started our investigation by carrying out the reaction between the commonly used D–A system dimethyl 2-vinylcyclopropane-1,1-dicarboxylate ( 1a ) and trans -cinnamaldehyde ( 2a ) catalyzed in the presence of a LA and chiral amine I in CH 2 Cl 2 at rt for 48 h ( Table 1 ). A series of Lewis acids were initially screened.…”

Recent Developments in Enantioselective Multicatalyzed Tandem Reactions

“…The synthesis of polysubstituted chiral cyclopentanes has received great attention from the chemical community because of the prominent presence of these scaffolds in many biologically active products . In this context, Ratovelomanana‐Vidal, Michelet and Vitale described in 2016 a novel diastereo‐ and enantioselective formal [3+2] cycloaddition of vinylcyclopropanes 19 with α,β‐unsaturated aldehydes 2 catalyzed by a combination of 5 mol% of Pd 2 (dba) 3 ⋅CHCl 3 associated to 10 mol% of dppe as ligand and 20 mol% of proline‐derived chiral amine catalyst 3 . The process was performed at room temperature in the presence of p‐ nitrobenzoic acid as an additive in benzotrifluoride as the solvent, evolving through a domino Michael/cyclization reaction that afforded the corresponding enantiopure functionalized cyclopentanes 20 (>99% ee ) with moderate to high yields (54–88%) and diastereoselectivities (72–80% de ) when starting from 1,1‐dicyano‐2‐vinylcyclopropane [Z=C(CN) 2 ], as illustrated in Scheme .…”