949568-55-2Relevant academic research and scientific papers
Catalytic asymmetric formation of δ-Lactones from Unsaturated acyl halides
Tiseni, Paolo S.,Peters, Rene
, p. 2503 - 2517 (2010)
Previously unexplored enantiopure zwitterionic ammonium dienolates have been utilized in this work as reactive intermediates that act as diene components in hetero-Diels-Alder reactions (HDAs) with aldehydes to produce optically active δ-lactones, subunits of numerous bioactive products. The dienolates were generated in situ from E/Z mixtures of a,b- unsaturated acid chlorides by use of a nucleophilic quinidine derivative and Sn (OTf)2 as co-catalyst. The latter component was not directly involved in the cycloaddition step with aldehydes and simply facilitated the formation of the reactive dienolate species. The scope of the cycloaddition was considerably improved by use of a complex formed from Er- (OTf)3 and a simple commercially available norephedrine-derived ligand that tolerated a broad range of aromatic and heteroaromatic aldehydes for a cooperative bifunctional Lewis-acid-/ Lewis-base-catalyzed reaction, providing a,b-unsaturated d-lactones with excellent enantioselectivities. Mechanistic studies confirmed the formation of the dienolate intermediates for both catalytic systems. The active ErIII complex is most likely a monomeric species. Interestingly, all lanthanides can catalyze the title reaction, but the efficiency in terms of yield and enantioselectivity depends directly on the radius of the Ln III ion. Similarly, use of the pseudolanthanides ScIII and YIII also resulted in product formation, whereas the larger La III and other transition metal salts, as well as main group metal salts, proved to be inefficient. In addition, various synthetic transformations of 6- CCl3- or 4-silyl-substituted α,β-unsaturated d-lactones, giving access to a number of valuable δ-lactone building blocks, were investigated.
