Stereoselective synthesis of multisubstituted alkenes via ring opening reactions of cyclopropenes : enantioselective copper catalysed asymmetric reduction of alkenylheteroarenes

A catalytic organometallic addition-ring opening sequence of cyclopropenes that enables the efficient and highly stereoselective synthesis of multisubstituted alkenes has been developed. A possible mechanism of organoaluminium reaction is proposed. The metalloenolate resulting from ring opening can be trapped with various electrophiles, enabling a rapid increase in molecular complexity in a one-pot operation. Also, in the presence of stoichiometric magnesium halides, a range of bis-activated cyclopropenes undergo highly stereoselective ring-opening reactions to produce multisubstituted alkenyl halides. The halogen nucleophile promotes Lewis-acid mediated regioselective SNVσ attack at the sp2-carbon of cyclopropene, resulting in the formation of acyclic conjugate enolate, which can be trapped with enones to furnish more highly functionalised products. At last, copper-catalysed asymmetric conjugate reductions of β,β'-disubstituted 2-alkenylheteroarenes are reported. A range of nitrogen-containing aromatic heterocycles are able to provide effective activation of an adjacent alkene for highly enantioselective catalytic conjugate reduction reactions. Extension of the general concept to other classes of heteroarenes has been proven successful. Further manipulation of the condition is required to tolerate more hindered heteroarene substrates.