Asymmetric Synthesis And Transformation Of Allenes Based On Sulfinamide Phosphine Ligands

In recent decades,despite the field of asymmetric catalysis has developed rapidly,the search for new,efficient,and practical asymmetric catalytic transformations to facilitate the green synthesis of chiral natural products and drugs will continue to become the research hotspot of organic chemistry.Phosphine ligands have played an important role in transition-metal-catalyzed asymmetric transformations.The ligands as the core component of asymmetric metal catalysts which are the key to the reactivity and stereoscopic control.Therefore,it is very significant to design and synthesize novel phosphine ligands for discovering new reactions and improving the efficiency and practicability of existing reactions.In this thesis,a new type of ferrocene-derived sulfinamide phosphine ligand(WJ-Phos)was designed and synthesized by introducing diphenylphosphine and sulfonyamide groups into the ferrocene scaffold.And they are applied in copper-catalyzed three-component asymmetric tandem reaction of allenes.The optically active trisubstituted chiral allenes was synthesized via palladium-catalyzed asymmetric?-hydride elimination of fully substituted enol triflates with the use of Xu-Phos as the chiral ligand.The specific contents include the following three aspects:(1)The design and synthesis of a new type of sulfinamide phosphine ligand(WJ-Phos)Ferrocene ligands have unique planar chirality,and have been extensively studied in asymmetric catalytic reactions as catalysts or chiral ligands(eg:Josiphos and PPFA).We used inexpensive available ferrocenecarboxaldehyde as the starting materials.The aldehyde functionality required protection with 1,3-propanediol prior to ortho-directed lithiation and subsequent treatment with Cl PPh₂.After the deprotection of the acetal furnished the respective desired ortho-diphenylphosphinyl-ferrocenecarboxaldehyde.Next,the condensation with tert-butanesulfinamide efficiently converted to chiral sulfinyl imine based on ferrocene skeleton.Finally,the nucleophilic addition of series of Grignard reagents and lithium reagents furnished a new type of ferrocene-derived sulfinamide phosphine ligand(WJ-Phos)in high yields with good diastereoselectivity.(2)Cu-catalyzed three-component asymmetric tandem reaction of allenesOrganoboron compounds are versatile reactive intermediates in organic synthesis,typically in cross-coupling reactions.Thus,the development of novel methods for efficient construction of organoboron compounds have received extensive attention of organic chemists.In this context,much progress has been made in Cu-catalyzed three-component boro-functionalization of allenes to efficiently furnish various functionalized organoboron compounds.Based on our developed WJ-Phos,we have successfully realized copper-catalyzed three-component asymmetric tandem reaction of allenes,delivering various functionalized organoboron compounds bearing an all-carbon stereocente.Further investigation demonstrated that WJ-Phos have showed excellent catalytic activity,stereoselective control and broad substrate scope in intermolecular three-component reaction of 1,1-disubstituted allenes with B₂(pin)₂and aroyl fluorides,leading to?-boryl-?,?-unsaturated ketones in up to 88%yield and94%ee.The salient features of this reaction include moderate to good yields,high enantioselectivities,gram-scale synthesis,and diverse synthetic transformations.(3)Pd-catalyzed asymmetric?-H elimination reaction to form allenesAllenes were extensively studied in synthetical methods,such as cycloaddition,cyclization,cycloisomerization,oxidation,cross-coupling,and boroacylation.Therefore,it is very important to develop a simple and efficient method for synthesis of allenes.The?-H elimination of the alkenyl palladium species leading to allene is an energetically unfavored process,therefore,to make this process in enantioselective manner has been a long-standing challenge.We realized the synthesis of trisubstituted chiral allenes via sulfinamide phosphine ligand Xu-Phos catalyzed asymmetric?-hydride elimination of fully substituted enol triflates.Excellent asymmetric induction of this transformation is the fine-tuning of the different chiral carbon group and N-substituent of Xu-Phos.A series of chiral allene compounds were produced in up to 89%and 93%ee value.It is worth noting that the Pd-catalyzed asymmetric?-H elimination from disubstituted enol triflates to form disubstituted chiral allenoates is well-established,but the studies on fully substituted enol triflates are still remains unexplored.There are many competitive reactions and side reactions,and we have successfully solved these problems with sulfinamide phosphine ligand.