Synthesis of chiral phosphites and their application in the asymmetric Addition of Dimethylzinc to Alkylidenmalonates

The asymmetric conjugate addition of dimethylzinc to α,β-unsaturated carbonyl compounds is an efficient and direct method to obtain a methyl substituted stereogenic centre, a structural motif which often plays an important role in determining the biological activity of numerous natural compounds [1]. Acyclic -unsaturated esters are generally not reactive towards dialkylzinc reagents but, in any case, chiral 3-methylesters can be achieved by asymmetric addition of dimethylzinc to alkylidenmalonates followed by direct demethoxycarbonylation of the addition products [2]. We decided to prepare herein new chiral phosphites [3] and to explore their efficiency as ligands in the copper-catalyzed asymmetric conjugate addition of dimethylzinc to diethyl 3-phenylpropylidenmalonate with the aim to disclose new synthetic applications of this procedure. In particular we focused our attention on the development of new route to some floral fragrances like Phenoxanol, Citralis and Nitrile Citralis, in optically active form, choosing 3-phenylpropylidenmalonate as starting substrate on which to test the asymmetric addition. . [1] (a) A.Alexakis, J.E.Bäckvall, N.Krause, O.Pàmies, M.Diéguez, Chem Rev, 108, 2008, 2796. (b) B.L.Feringa, Acc. Chem. Res., 33, 2000, 346. [2] J.Schuppan, A.J.Minnaard, B.L.Feringa, Chem. Comm. 2004, 792. [3] P.Scafato, S.Labano, G.Cunsolo, C.Rosini, Tetrahedron:Asymmetry, 14, 2003, 3873.