Highly Regio-,Diastereo-and Enantioselective Gold(I)-Catalyzed Cyclization Or Cycloaddition Reaction With N-allenamides

The development of gold-catalyzed intermolecular cycloadditions,in particular an asymmetric version,still pose a considerable challenge,because of the inherent liner binding mode of gold(I)complexes.N-allenamides,which are more electron-rich than simple allenes,have showed the unique reactivity and selectivity.Although significant achievements were achieved in this field,the reactive mode of N-allenamides is still scanty.Meanwhile,the catalytic enantioselective version is less developed.The main works of this thesis were focused on the novel asymmetric gold catalyzed reaction of N-allenamides and development of novel type of chiral phosphine ligands.The detailed research contents mainly include the following five aspects:1.Asymmetric gold-catalyzed intermolecular[2+2]versus[4+2]cycloadditions of N-allenamides with 3-styrylindolesA highly enantioselective[2+2]versus[4+2]-cycloaddition of 3-styrylindoles to N-allenamides catalyzed by identical gold(I)/chiral phosphoramidite complexes is presented.The cycloaddition mode unexpectedly depends on the electronic nature of the N-substituent 3-styrylindoles,the origin of which could be well rationalized using DFT calculations and experimental results.To the best of our knowledge,the present work represents the first example of such an impressive substituent effect in tuning the reaction mode with high chemo-,regio-and enantioselectivity in asymmetric gold catalysis.2.Asymmetric Gold(I)-Catalyzed Intermolecular[3+2]cycloaddition with N-Allenamides at the Proximal C=C BondThe present work represents the first example of a gold-catalyzed annulation with the proximal C=C bond of an N-allenamide,and is distinctly different from the previously observed annulations at the distal C=C bond.Interestingly,both enantiomers of the products could be obtained in good yields with high regio-,diastereo-,and enantioselectivity by using either diastereomer of a binolderived phosphoramidite as a chiral ligand.3.Asymmetric Gold-Catalyzed Intramolecular Hydroindolation of N-AllenamidesThe highly enantioselective gold-catalyzed intramolecular hydroindolation of N-allenamides was implemented utilizing a designed novel chiral sulfinamide phosphine ligand(PC-Phos),which,of note,represents the first example of a highly enantioselective intramolecular cyclization of N-allenamides.The practicality of this Au(I)-catalyzed transformation was validated in the total synthesis of(R)-desbromoarborescidine A which was accomplished in only 5 steps.Moreover,the catalyst system PC-Phos/AuNTf2 proved to be specifically efficient to promote the desymmetrizastion of N-allenamides in excellent yields with satisfactory ees.4.Asymmetric Gold(?)-Catalyzed Intermolecular Tandem Cyclization/[3+2]Cycloadditions of 2-(1-Alkynyl)-2-alken-1-ones with 3-StyrylindolesA highly enantioselective gold(?)-catalyzed intermolecular tandem cyclization/[3+2]cycloadditions of 2-(1-alkynyl)-2-alken-l-ones with 3-stylindoles was achieved by using Ming-Phos as a chiral ligand.A variety of chiral highly-substituted cyclopenta[c]furans were obtained in good yields(up to 99%)with excellent diastereoselectivities(>20:1)and enantioselectivities(up to 97%ee).5.Design and synthesis of chiral phosphine ligand named Dong-PhosBased on the chiral ligand Ming-Phos developed by our group,we design to control the chiral environment of catalyst by varying the substituent group of the phosphine.A new type of chiral sulfonamide monophosphine ligand,named Dong-Phos,could be obtained efficiently in a short step.