Transition-metal Catalyzed P-C Bond-forming Reactions Via Cross Couplings Of P(O)-H Compounds

Organo phosphorus compounds are of significant importance in organic synthesis,which can be used as the ligand or catalyst of the reactions.Traditionally,these compounds are prepared by the reaction of toxic phosphoryl halides with organolithiums or Grignard reagents,which requires air and moisture sencitive starting materials and suffers from low functional group tolerance.Compared to the unstable phosphoryl halides,P(O)-H compounds are greener,safer and stable.Using P(O)-H compounds in place of the toxic phosphoryl halides as the starting materials is of great significance in the history of organo phosphorus synthesis.In 1980,Hirao and co-workers disclosed a palladium-catalyzed coupling of organo halides with P(O)-H compounds under mild conditions.This reaction is now widely used as a reliable method for the construction of C-P bonds because of its high efficiency and good tolerance to functionalities.However,the electrophilic coupling reagents of these reactions are dependent on the toxic organo halides which are partly difficult to prepare,expensive and environmentally unfriendly.In comparison with the traditional coupling reactions,using the readily avalible starting materials(such as C-H,C-O,C-S compounds)as coupling reagents for the construction of chemical bond is of high atom economy,step economy and environmental friendliness.These compounds are mostly natural abundant and easily obtained,but the utilization of those compounds still remains chanllengeable due to their low reactivity.The studies on activation and functionalization of such compounds will benefit greatly the utilization of simple petrochemicals and biomass and would be highly of significance.This paper focuses on the cross coupling reactions of green and stable P(O)-H compounds with readily available C-H,C-O or C-S compounds over the transition metal catalysis.A series of facile and efficient methods for the construction of P-C bonds have been developed.The research contents come as follows:1.Preparation of alkynylphosphine oxides via the palladium-catalyzed P(O)-H/spC-H cross coupling reactions.A facile and efficient palladium-catalyzed cross dehydrogenative coupling of tenimal alkynes with secondary phosphine oxides under mild conditions was developed.This transformation has a good functional-group tolerance.Various functional groups,such as methyl,ester,trifluoromethy,halogen atom,carboxyl and alkenyl were tolerated well under this reaction conditions.In addition to the secondary phosphine oxides,other two kinds of P(O)-H compounds(phosphonates and phosphites)can also react with terminal alkynes,producing the corresponding alkynphosphonates.2.Mechanistic studies on the palladium-catalyzed corss dehydrogenative coupling of P(O)-H compounds with terminal alkynes and first catalytic synthesis of P-chiral alkynylphosphoryl compounds via cross dehydrogenative coupling reacitonsThe mechanism of the palladium catalyzed cross dehydrogenative coupling of P(O)-H compounds with terminal alkynes was studied.Successive ligand exchange reactions of Pd(OAc)2 with a hydrogen phosphoryl compound and a terminal alkyne took place readily to replace the two acetate on palladium producing the corresponding(phosphoryl)(alkynyl)palladium complexes,which upon heating decomposed to the corresponding alkynylphosphorus compound.It is also confirmed that in the stoichiometric reactions of the complexes,the configuration at phosphorus keeps retention.On the basis of these stoichoiometric reactions,an efficient synthesis of P-chiral alkynylphosphoryl compounds via palladium catalyzed stereoselective cross dehydrogenative coupling of P-chiral P(O)-H compounds with terminal alkynes was developed.The key palladium complexes and the stereochemistry of the chiral phosphorus compounds are all unambiguously determined by single crystal X-ray analysis..3.Nickel-catalyzed C-O/P-H cross coupling forming sp2/sp3C-P bond.The first Ni-catalyzed C-O/P-H cross coupling of phenolic and benzylic alcohol derivatives(pivalates,carbonates and carbamates)with various P-H compounds is described.This method fetures wide generality in regard to both C-0 and P-H compounds,the readily available alcohol derivatives of aryl,alkenyl,and allyl are applicable,and for P-H compounds,both>PV(O)H compounds(secondary phosphine oxide,H-phosphinate and H-phosphonate)and hydrogen phosphines(>P?H)can be used as the substrates.Thus,a variety of valuable compounds bearing C(sp2)-P or C(sp3)-P bonds can be readily obtained in good to excellent yields by using this new strategy.4.Nickel-catalyzed cross coupling of phenol esters with P-H compounds forming C-P bondAn efficient nickel-catalyzed phosphorylation of phenol derivatives with P(O)-H compounds via C-O/P-H cross coupling is described.Under the reaction conditions,various phenyl pivalates coupled readily with hydrogen phosphoryl compounds to afford the corresponding coupling products aryl phosphonates and aryl phosphine oxides in good to high yields.In addition to pivalates,triflates can also be used as the substrates in the cross coupling reactions with P-H compounds catalyzed by nickel.5.Efficient Nickel-catalyzed C-S/P-H cross coupling forming C-P bondsThe first nickel-catalyzed phosphinylation of C-S bonds forming C-P bonds is developed.This transformation can proceed readily with the simple Ni(cod)2 at a loading down to 0.1 mol%at 10 mmol scale.A variety of aryl sulfur compounds,i.e.sulfides,sulfoxides and sulfones all coupled with P(O)-H compounds to produce the corresponding organophosphorus compounds in high yields,which provides an efficient new method for C-P bonds construction.