Catalyst- and Solvent-Dependent Stereodivergence in the Intramolecular Et sub(2)Zn/Pd super(0)-Promote d Carbonyl Propargylation: Mechanistic Implications

• Published in: Chemistry : a European journal 2013-10, Vol.19 (41), p.13893-13900
• Main Authors: Arrate, Monica, Durana, Aritz, Lorenzo, Paula, deLera, Angel R, Alvarez, Rosana, Aurrecoechea, Jose M
• Format: Article
• Language: English
• Subjects: Aldehydes; Carbonyls; Catalysts; Formations; Ligands; Palladium; Phosphines; Solvents
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201301170

Carbonyl-tethered propargylic benzoates undergo intramolecular carbonylpropargylation upon treatment with Et sub(2)Zn in the presence of a catalytic amount of Pd super(0) with the formation of 2-alkynylcyclopentanol products. A ligand/solvent effect on the cis/trans selectivity (referring to the relative positions of alkynyl and OH groups) of ring-closure has been found. In a non-coordinating solvent (benzene), increasing the electron-donating ability of the phosphine ligand (while decreasing its dissociation ability) leads to an increased tendency towards the trans product. On the other hand, the combination of a coordinating solvent (THF) and PPh sub(3), an easily dissociated phosphine, results in the exclusive formation of cis products. Experimental and computational results are compatible with a divergent behavior of an allenylethylpalladium intermediate that partitions between competitive carbonyl-addition and transmetalation pathways, each leading to a different diastereoisomer. These results also suggest that the dissociating ability of the phosphine regulates that behavior. Transmetalate or cyclize? Pronounced changes in the diastereoselectivity of ring closure are observed in the Pd super(0)-catalyzed, Et sub(2)Zn-mediated intramolecular coupling between propargylic esters and aldehydes or ketones depending on the selection of solvent and Pd ligand (see scheme).