Design And Synthesis Of Novel Organocatalysts Based On Ferrocene And Study On The Applications Of Asymmetric Michael Additions

The Michael addition has been playing an important role in the field of organic synthesis.Chemists have synthesized numerous organocatalysts used in the Michael additions of different substrates in the past decade.However,there are few reports of organocatalysts based on ferrocene.The first ferrocene-based thiourea organocatalyst 51 was synthesized by our group in 2014 and presented excellent catalytic performances in the asymmetric Michael addition of acetylacetone to nitroolefins with high enatioselectivities(up to 96% ee).Based on this work,in this thesis we designed and synthesized other novel ferrocene-based chiral bifunctional catalysts,which are more rigid and stable and show better catalytic activities.The catalysts were applied to a variety of Michael additions of various different substrates,and the best catalytic results were obtained after screening the conditions.The main contents of the thesis include the following parts:Based on our previous work,the first ferrocene-based novel sulfoamide catalyst 81 was synthesized using Ugi's amine as starting material with lithium reaction/hydrogention reduction and condensation etc.;the other three kinds of ferrocene-based novelbifunctional [3]-ferrocenophane thiourea catalysts 86/87 and 88 were synthesized using ferrocene as starting material,the three catalysts are more rigid and stable than the catalyst51,better catalytic results should be obtained in the asymmetric Michael additions.The structure of iminophosphorane is strongly Br?nsted basic group,and the catalysts containing iminophosphorane(BIMP)have been developed and applied to the organic catalytic reactions in recent years.In this thesis,we use ferrocene as skeleton to synthesize ferrocene-based novel iminophosphorane thiourea catalysts 95/96 and 97,which combine the structure of iminophosphorane and thiourea unit;The thiourea unit in the catalysts is hydrogen bond donor,and the structure of iminophosphorane is a super strong base group providing basic environment.Therefore,the catalysts should have a good application prospects in asymmetric Michael additions.Based on previous studies,we applied the newly designed catalysts to the asymmetric Michael addition of acetylacetone to nitroolefins.Finally,we selected thiourea 86 as the best catalyst,toluene as solvent,and a catalyst loading of 10 mol% at room temperature to get the corresponding Michael addition products,and showed excellent catalytic results in up to 95% yield and 99% ee.In addition,in the reaction of malonates to nitroolefins,in previous studies,catalyst 51 showed low reactivity,but with 86 as catalyst,we obtained good results,the highest yield and enantioselectivity were 75% and 76% ee,respectively.The experimental results showed that in the asymmetric Michael additions of nitroolefins to the activated methylene compounds,the newly designed and more rigid thiourea catalyst 86 has better catalytic activity than the first ferrocene-based thiourea catalyst 51.Nitroalkenes,a kind of very classic Michael receptors,can participate in a variety of different types of Michael additions.We applied the newly designed ferrocene-based chiral catalysts to the asymmetric Michael addition of nitroalkenes to acetophenones.Finally,we also selected thiourea 86 as the best catalyst,DCM as solvent,and a catalyst loading of 10 mol% at room temperature to get the products with good catalytic activities and stereoselectivities in up to 82% yield and 71% ee.Pyran derivatives are important intermediates for the synthesis of some natural products and medicines.In this thesis,we tried to synthesize a series of pyran compounds via theone-pot asymmetric Michael addition-cyclizations.Keto-esters and malononitrile were used as starting materials,newly designed iminophosphorane thiourea 96 as the best catalyst,toluene as solvent,and a catalyst loading of 15 mol%,at room temperature,to give the corresponding pyran derivatives.Although only medium yields and enantioselectivities are obtained,this provides a new way of thinking and reference for the synthesis of those compounds.The experimental results showed that the novel chiral catalysts based on ferrocene can be applied to Michael additions of various different substrates and exhibited good catalytic activities and stereoselectivities.It also proved that ferrocene can not only be used as the skeleton of ligands in metal catalysis,but also an ideal skeleton for building organocatalysts.In this work,we successfully expand the structural types of organocatalysts.