Study towards selective synthesis of highly conjugated oligoene and oligoyne compounds via palladium -catalyzed cross -coupling

Qian Hu, Purdue University

Abstract

Pd-catalyzed cross coupling reaction is widely used in organic synthesis. In the first chapter, the discussion focused on the synthesis of amphotericin B "South"-"West" fragment. The "West" fragment was prepared in 5 steps from commercially available starting compound. And the "South" fragment was also synthesized in 5 steps with high stereoselectivity by Pd-catalyzed cross coupling. Finally, the "South"-"West" fragment was assembled in less than 10 steps via Heck reaction and Horner-Wadsworth-Emmons olefination. The literature reported synthesis of diyne or oligoyne suffers from the formation of undesired homo-coupling products. As discussed in chapter 2, iteration of Pd-catalyzed reaction of alkynyl- and oligoynylzincs with ( E)ICH=CHCl followed by metalation-termination with electrophiles(E) has provided a linear route to conjugated tri- and tetraynes, while Pd-catalyzed monoalkynylation of 1,1-dibromoenynes accompanied by dehydrobromination has provided a convergent route to conjugated tri-, tetra-, and pentaynes. Both display unprecedentedly high efficiency and selectivity. In the last chapter, the focus is Pd-catalyzed second-step substitution following the well-known trans-selectively monosubstitution of 1,1-dibromo-1-alkenes. Both (1E)- and (1Z)-2-methyl-1,3-dienes can be selectively synthesized by using Pd-catalyzed trans-selective monoalkenylation of 1,1-dibromo-1-alkenes followed by the second sunstitution catalyzed by either E-selective ligands, i.e., tBu 3P and NHC, or Z-selective ligands, i.e., PPh 3, TFP, dppf, and DPEphos. Although the detailed mechanism is still not fully established yet, it is believed a mechanism involving palladacarbene should be operating, and the investigation of mechanism is an ongoing project in Prof. Negishi group.

Degree

Ph.D.

Advisors

Negishi, Purdue University.

Subject Area

Organic chemistry

COinS