Catalytic Asymmetric Alkynylation Of Ketones And Aldimines With Terminal1,3-Diynes And3-En-1-ynes

Chiral propargylic alcohols, propargylic amines are widely found in manybiologically active natural products, as well as important synthetic precursors of chiraldrugs. Their synthetic method has attracted attention of many researchers. Theasymmetric addition of alkynes to aldehydes, ketones and imines represents the mostconvergent and efficient approach to the synthesis of such optically activecompounds.1,3-diynes are potentially intriguing building blocks due to the unique behavior ofacetylenes. Furthermore, diyne carbinols are presence in many natural products. Themost direct method for the construction of diyne carbinols involves a diynylation ofcarbonyl compounds. Despite some progress made in this area, the use of ketones aselectrophiles in this1,2-addition reaction is still untapped, which could be ascribed tothe lower reactivity of ketones and instability of diynes. In the first part of thisdissertation, the catalytic enantioselective addition of terminal1,3-diynes to aromaticketones was achieved by using Cu(OTf)2-Camphorsulfonamide catalyst. Withsystematic screening on the copper salts, ligands, solvents and reaction temperatures,a series of optically active quaternary carbon-containing diyne carbinols weresuccessfully synthesized in moderate to high yields (up to92%) andenantioselectivities (up to90%). The absolute configuration of the major enantiomerwas identified by a single-crystal X-ray structural analysis of transformed product.Subsequently, we developed an enantioselective diynylation of N-Sulfonylaldimines. With the induction of3,3’-substituted chiral binaphthol, the firstasymmetric addition of terminal1,3-diynes to N-Sulfonyl aldimines was realized inhigh yields (88%–98%) with excellent enantioselectives (90%–99%). The catalyticsystem exhibited excellent substrate scope with respect to the aromatic ketones, aryland alkyl1,3-diynes used. Furthermore, the adducts can be readily transformed intofunctionalized amine derivatives that are otherwise difficult to access.Finally, we designed and synthesized a series of terminal3-en-1-ynes, andinvestigated their applications in the alkynylation of N-Sulfonyl aldimines. With thescreened optimal reaction conditions,28propargylic amines were synthesized in highyields and enantioselectivities (up to95%ee). Additionally, we found that the aromatic ring of aldimine is essential for the high enantioselectivity of the addition.