| Methodology discovery and natural product total synthesis are two main branches of organic chemistry research.The exploration of novel methodology can simplify the synthetic route of complex natural product.Only the practical methods with general substrate scope could be involved in natural product total synthesis.In view of this,this thesis focuses on investigating novel methodology aiming at divergent syntheses of alkaloids.A regiodivergent C1 insertion multicomponent reaction was established to construct the scaffolds of phenanthridinone and acridone.To further improve atom/step economy of the method,an aryne involoved Pd-catalyzed C-H activation MCR was developed to synthesize phenanthridinone.The method for stereo alkaloids construction was also investigated,in which an asymmetric synthetic strategy for constructing the divergent-synthesis monomer of ETP natural products has been successfully achieved.(1)Ligand Controlled Regiodivergent C-1 Insertion on Arynes for Construction of Phenanthridinone and Acridone AlkaloidsPalladium-catalyzed regiodivergent C-1 insertion multicomponent reaction,involving aryne,CO and 2-iodoaniline,is established to construct the scaffolds of phenanthridinone and acridone alkaloids.Predominant regioselectivity control is achieved under the guidance of selective ligands.The phenanthridinones are solely obtained under ligand-free condition.Meanwhile,application of electron-abundant bidentate ligand dppm afforded the acridones highly efficiently.The releasing rate of aryne from precursor assisted the regioselectivity of its insertion as well,which was revealed through the interval NMR tracking.A plausible mechanism was suggested based on the control experiments.Representative natural products and two types of natural product analogues were synthesized divergently through this tunable manner.(2)Collective Synthesis of Phenanthridinone through C-H Activation Involving Pd-Catalyzed Aryne Multicomponent ReactionPalladium-catalyzed multicomponent reaction(MCR),involving aryne,CO and aniline,is established for straightforward assembling of phenanthridinone scaffold through C-H bond activation.Free combination with multiple kinds of readily available anilines and arynes,is facilely achieved for phenanthridinone construction without prefunctionalization.Representative natural products were subsequently synthesized through this MCR strategy highly efficiently.Control experiments and interval NMR tracking revealed the mechanism,particularly the key role from CuF2 determining aryne releasing rate from precursor in this transformation.(3)Stereoselective Construction of the Key Monomer of ETP Natural ProductsAn asymmetric synthetic strategy for constructing the divergent-synthesis monomer of ETP natural products has been successfully achieved.The functionalized 2,3,3a,4,7,7a-hexahydroindole scaffold was constructed by a diastereoslective IEDDA reaction.Both diene and dienophile are derived from naturally abundant starting materials.A new method to open the bridged-lactone ring via an SN2’ process was firstly reported,affording the bridged-ring-opened intermediate in 20 gram-scale.The conversion to the key monomer was proven to be practical by several functional group transformations. |
