Ligand-Controlled Asymmetric Induction at a Transition Metal-Bonded α-Carbon in Ester and Amide Enolates. Diastereoselective Formation of Oxapalladacycles Applied to the Synthesis of a Chiral Nonracemic 2H-1-Benzopyran

Abstract

Stable benzannelated oxapalladacycles [−(P−P)Pd-1-C6H4-2-OCHY−] possessing chiral nonracemic bidentate phosphine ligands, (P−P) = (4S,5S)-(+)-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane ((S,S)-DIOP) or (2S,4S)-(−)-2,4-bis(diphenylphosphino)pentane ((S,S)-BDPP), and a palladium-bonded stereogenic carbon representing an α-carbon in ester (Y = COOEt) or amide (Y = CONEt2) enolates, have been synthesized in diastereomeric excess 46−80% exploiting asymmetric induction from the chiral ligands. The stereoselective event involved an intramolecular displacement of the iodide in complexes (P−P)IPd-1-C6H4-2-OCH2Y by an in situ generated lithium or potassium ester or amide enolate. Only one enantiomer of each ligand was used, and the absolute sense of stereoinduction could be controlled by the choice of the base (t-BuOK or LDA) to afford both diastereomers of each palladacycle in a diastereomerically enriched form. Treatment of the palladacycles with an excess of t-BuOK allowed for further enrichment in the content of “thermodynamic” diastereomers. An X-ray structure of the complex [−((S,S)-BDPP)Pd-1-C6H4-2-(R)-OCHCOOEt−] was obtained. Ligand exchange reactions of the palladacycles with an achiral 1,2-bis(diphenylphosphino)ethane (dppe) ligand afforded enantiomerically enriched palladacycles [−(dppe)Pd-1-C6H4-2-OCHCOOEt−] in the corresponding enantiomeric purities without a loss of the stereochemical information. Reaction of dimethyl acetylenedicarboxylate (dmad) with complex [−((S,S)-DIOP)Pd-1-C6H4-2-OCHCONEt2−], enriched via chromatography to 96% de, afforded (−)-2-N,N-diethylcarbonyl-3,4-bis(methoxycarbonyl)-2H-1-benzopyran in 88.4% ee with only a minimal (8%) racemization of the metal-bonded stereocenter.