From Highly Enantioselective Catalytic Reaction of 1,3-Diynes with Aldehydes to Facile Asymmetric Synthesis of Polycyclic Compounds

摘要

(S)-1,1'-Binaphth-2-ol (BINOL) in combination with ZnEt_2, Ti(O'Pr_)4, and biscydohexylamine was found to catalyze the highly enantioselective (83-95% ee) addition of various 1,3-diynes to aldehydes of diverse structures. This method provides a convenient pathway to generate a number of optically active dienediynes as the acyclic precursors to polycyclic compounds. The chiral dienediynes undergo highly chemoselective Pauson-Khand (PK) cycloaddition in benzaldehyde by using [Rh(cod)C1]_2 as the catalyst in the presence of rac-BINAP. High diastereoselectivity (up to >20:l) has also been achieved with the chiral dienediyne substrates containing a bulky substituent adjacent to the chiral center. In the presence of the Grubbs II catalyst, ring-closing enyne metathesis of the PK cycloaddition products led to the formation of the desired 5,5,7- and 5,5,8-fused tricyclic compounds. Further highly diastereoselective Diels-Alder reaction of a 5,5,7-tricyclic compound with maleic anhydride produced a 5,5,7,6-polycyclic product. The asymmetric synthesis of polycyclic compounds from optically active dienediynes has established a novel and efficient synthetic route to the structural framework of many biologically significant molecules.