Construction Of C-P And C-S Bonds Via Enantioselective Benzylation And Ortho C-H Functionalization

This thesis mainly focuses on developing different strategies for construction of carbon-heteroatom bonds,enabling the synthesis of heteroatom-containing compounds which are not easily accessible by traditional methods.Among them,Organophosphorus and aryl sulfide compounds have wide applications in synthesis,pharmaceuticals and material science.We have devoted to study on valuable P-and Scontaining compounds.The thesis includes the following two aspects:the first part was nickel-catalyzed enantioselective benzylation of secondary phosphine oxide;the second part was selective ortho thiolation of aryl halide via Pd/norbornene catalysis.The first chapter introduces the development of synthetic methods to access Pstereogenic compounds.Comparing with traditional method involving resolution of racemates or induction by chiral auxiliaries,the catalytic asymmetric synthesis has gained considerable development in the past decades.Amid these methodologies,the transition-metal catalyzed coupling of phosphorus nucleophile with electrophile proved to be most straightforward.Nevertheless,the approaches for construction of Pstereogenic compounds are still rather limited.With the goal of developing diversified chiral organophosphorus scaffold,we realized the nickel-catalyzed enantioselective benzylation reaction by using air-stable,easily-handled secondary phospine oxide as substrate,affording optically active tertiary phosphine oxide.The reaction was performed in mild conditions and bears a good functional group tolerance for both secondary phosphine oxide and benzyl chloride,delivering the products in moderate to good yields and high enantioselectivities.Studies on racemization of secondary phosphine oxide revealed the partial dynamic kinetic resolution phenomena in this catalytic system,it provides insights for further development of new synthetic methods.Apart from common cross-coupling reactions,the construction of complex molecules through cascade reaction also attracts people’s attention.The second chapter has reviewed the development of Catellani reaction in the past decades,predominantly progress in discovering electrophiles and nucleophiles.Most of the ortho functionalization reactions based on Catellani reaction focused on C-C bond formation,only ortho amination could result in C-N formation.Thus,it’s quite challenging and necessary to introduce heteroatom to the ortho position.We reanalyzed the previous work on ipso thiolation of aryl halide via C(O)-S cleavage and realized the selective ortho thiolation reaction by utilizing thiosulfonate as electrophile in Pd/norbornene catalysis.This strategy enables synthesis of complex aryl sulfide compounds in a threecomponent one-step manner.Both the aryl and alkyl thiosulfonates were compatible in this reaction.Besides,we observed the unprecedent E/Z isomerization in the olefinic sulfide product and sulfur atom plays the pivotal role in the transformation.The key of the success relies on the tautermerization of sulfonate to sulfite anion,leading to enhanced leaving ability,which gave the enlightenment for future development of suitable electrophiles.