High Regio- And Stereoselective Reactions Of Fluorine-containing Allenes Catalyzed By Metal Palladium

Fluorinated phosphonates area class of effective natural phosphate mimics.Introduction of fluorine atoms makes these mimics having unique physicochemical and biological properties.This strategy has been widely used in the drug design.Among them,vinyldifluoromethylenephosphonates andα-monofluorovinylphosphonates were already recognized as excellent phosphate mimics.Although a number of efficient protocols were developed,achieving high degrees of regio-and stereoselectivity was still a challenging task.In this paper,using α,α-difluoromethylene-β-allenylphosphonates as substrate and palladium as a catalyst,we successfully developed efficient methods for the synthesis of two kinds of novel fluorinated phosphonates with high regio-and stereoselectivity.This paper is divided into two parts:1.We studied for the first time the cross-coupling reaction of α,α-difluoromethylene-β-allenylphosphonates with terminal alkynes.Under Pd(OAc)2/PPh3 catalyst,without any base,4-nonsubstituted allenes gave the Evinyldifluoromethylenephosphonates.On the other hand,under Pd(OAc)2/SPhos catalyst with cesium carbonate as base,4,4-disubstituted allenes gave(Z)-α-monofluorovinylphosphonates.These reactions feature mild reaction conditions,inexpensive catalytic system,highly regio-and stereo-selectivity and show excellent tolerance toward functional groups.2.We studied the coupling reaction of α,α-difluoromethylene-β-allenyl phosphonates with aryl trifluoroborate.Under Pd(OAc)2/SPhos catalyst,another kind(E)-α-monofluorovinylphosphonates were synthesized with high regio-and stereoselectivity.