Enantioselective Nickel-Catalyzed Hydrocyanation of Homostilbenes

We investigated the previously unknown enantioselective Ni-catalyzed hydrocyanation of 1,3-diarylpropenes (homostilbenes). For this purpose, a series of (E)-homostilbenes were prepared by (microwave-assisted) Pd-catalyzed coupling of allylic alcohols with aryl-boronic acids. Employing our established catalyst system formed from Ni(cod)(2) and a TADDOL-derived chiral phosphine-phosphite ligand and using TMSCN as an in situ source of HCN, the hydrocyanation of various homostilbenes was studied. The synthetic usefulness of the methodology was demonstrated in a short synthesis of the new (allo-) colchicine analogue 7-cyano-11-methoxy-colchinol involving an PIDA-mediated oxidative cyclization of the corresponding hydrocyanation product to set up the 7-membered ring. The absolute configuration of 2,4-diphenylbutyronitrile was assigned by comparison of experimental and calculated ECD spectra.