A Catalytic Asymmetric Three‐Component 1,4‐Addition/Aldol Reaction: Enantioselective Synthesis of the Spirocyclic System of Vannusal A

Abstract

Three's not always a crowd: A three‐component reaction involving α,β‐unsaturated enones 1, aldehydes 2, and alkenyl zirconium species 3 in the presence of a Rh–binap catalyst leads, sequentially, to aldols 4, enones 5, and 2,3‐disubstituted cycloalkanones 6 in good yields and with high ee values.

Asymmetric Synthesis of the Epimeric (3S)-3-((E)-Hex-1-enyl)-2-methylcyclohexanones

“…Among several known enantioselective 1,4-additions of organometallic reagents to α,β-unsaturated ketones, we obtained the best results with the recently reported rhodium(I)-catalysed addition of alkenylzirconocene chlorides with BINAP as chiral ligand [3,4]. This result also follows Nicolaou's report of the tandem reaction of the rhodium-catalysed asymmetric additions of alkenylzirconium reagents followed by trapping of the zirconium enolate by aldehydes [5]. In our case, the 1,4-addition was performed on 2-cyclohexenone using (E)-1-hexenylzirconocene chloride [6], prepared from 1-hexyne and bis(cyclopentadienyl)zirconium chloride hydride (Cp 2 Zr(H)Cl or Schwartz reagent) in the presence of a catalytic amount of the Rh(I)-complex [Rh(cod)Cl] 2 and (R)-BINAP as a chiral ligand.…”

Rhodium‐ and Palladium‐Catalyzed Asymmetric Conjugate Additions

“…An analogous zirconium-based three-component coupling reaction was reported by Nicolaou and coworkers [196]. Krische and coworkers reported the intramolecular trapping of a chiral Rh-enolate by an electrophile [212].…”

“…Alkenyl zirconium species, derived from the hydrozirconation [194] of primary alkynes by Schwartz reagent ([Cp 2 Zr(H)(Cl)]), are useful reagents in Rh-catalyzed ECAs [59,195,196]. Aryl-lead [197], -tin [54,57,198], and triarylbismuth [199] compounds are also competent aryl-transfer agents in Rh-catalyzed conjugate additions, even in the presence of air and water [200].…”

Peptidic Amidomonophosphane Ligand for Copper‐Catalyzed Asymmetric Conjugate Addition of Diorganozincs to Cycloalkenones

“…[16] These phosphorus ligands were shown to be applicable in the conjugate addition reaction of nitroalkenes [17][18][19][20][21] and a,b-unsaturated lactones. [22,23] Copper-catalyzed conjugate arylation, [24,25] vinylation [26] and kinetic resolution [27] have been the topics of the recent brilliant studies. [28] It is natural for us to apply the amidophosphane 1 in the copper-catalyzed asymmetric conjugate addition of diorganozincs, because 1 was really effective in the conjugate alkylation of Grignard reagents [6] as well as the Rh(I)-catalyzed conjugate arylation of arylboronic acids.…”