Catalytic asymmetric formation of delta-lactones from unsaturated acyl halides.
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 delta-lactones, subunits of numerous bioactive products. The dienolates were generated in situ from E/Z mixtures of alpha,beta-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 alpha,beta-unsaturated delta-lactones with excellent enantioselectivities. Mechanistic studies confirmed the formation of the dienolate intermediates for both catalytic systems. The active Er(III) 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 Sc(III) and Y(III) 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-CCl(3)- or 4-silyl-substituted alpha,beta-unsaturated delta-lactones, giving access to a number of valuable delta-lactone building blocks, were investigated.
Tiseni
Paolo S
PS
ETH Zürich, Hönggerberg, Laboratory of Organic Chemistry, Wolfgang-Pauli-Strasse 10, 8093 Zürich, Switzerland.
Peters
René
R
D000143:Acids / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D006846:Hydrocarbons, Halogenated / Q000737:chemistry*; D007477:Ions / Q000737:chemistry; D007783:Lactones / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D000143:Acids; D000447:Aldehydes; D006846:Hydrocarbons, Halogenated; D007477:Ions; D007783:Lactones