Design, Synthesis And Applications Of New Tetraphosphorus Ligands In Regioselective Hydroaminomethylation Of Linear Olefins

Hydroaminomethylation, the one-pot synthesis of amines from olefins, amines （ammonia）and synthesis gas （CO and H2）, consists of an initial regioselective hydroformylation followedby a reductive amination, is an efficient atom-economic and environmental friendly processcomparing with the classical synthetic methods of amines. Since discovered in1949by Reppe,this reaction has been paid close attention, and greatly achievement has been obtained byscientists’ dedication to the design and synthesis of highly regioselective ligands forhydroaminomethylation. By now, only handful of references about hydroaminomethylationcan be found, Beller’s group has contributed a lot to the regioselectivehydroaminomethylation of terminal olefins and internal olefins, and abtained the amineproduct with high reactivity and regioselectivity using the ligands Xantphos and itsderivatives. However, only several ligands can be applied effectively in regioselectivehydroaminomethylation, thus, the regioselective catalytic activity of this reaction could beimproved to some extent. In our research, two series of tetraphosphorus ligands have beenapplied successfully in the regioselective hydroaminomethylation. To investigate the catalyticactivity of these tetraphosphorus ligands, our studies achieved two results as below:1. Two new pyrrole-based tetraphosphorus ligands L8{1,1’,1’’,1’’’,1’’’’,1’’’’’,1’’’’’’,1’’’’’’’-（（（4,4’’’-di-tert-butyl-5’,5’’-bis（4-（tert-butyl）phenyl）-[1,1’:3’,1’’:3’’,1’’’-quaterphenyl]-2’,2’’,4’,6’’-tetrayl）tetrakis（oxy））tetrakis（phosphinetriyl））octakis（¹H-pyrrole）}and L9{1,1’,1’’,1’’’,1’’’’,1’’’’’,1’’’’’’,1’’’’’’’-（（（4,4’-dimethyl-[1,1’-biphenyl]-2,2’,6,6’-tetrayl）tetrakis-（oxy））tetrakis（phosphinetriyl））octakis（¹H-pyrrole）} were designed and synthesized. Thestructures were determined by¹H,¹³C,31P NMR and the original synthetic route ofpyrrole-based type ligands were improved. The exact improved prodess were:（1） the couplingreaction of dipyrrolchlorophosphine and4,4’’’-di-tert-butyl-5’,5’’-bis（4-（tert-butyl）phenyl）-[1,1’:3’,1’’:3’’,1’’’-quaterphenyl]-2’,2’’,4’,6’’-tetraol. We introduced n-BuLi as the activatingagent of tetranol, and greatly increased the yield of this process from original30-40%to60-70%. This improvement would give suggestions for the synthesis of other pyrrole-based tetraphosphorus ligands.（2） preparation of3,3’,5,5’-tetraiodo-2,2’,6,6’-tetramethoxy-1,1’-biphenyl. Small amount of ethyl acetate were used as the recrystallized solvent in the finaltreatment of the crude product, replacing the original large amount of hot acetone. Thisimprovement made this process easily prepared, and enhanced the yield at the same time.These improvements would give new options for the preparation of other known similarpyrrole-based tetraphosphorus ligands.Furthermore, we have optimized the synthetic route of known tetraphosphorus ligandTetrabi （Tb1）. The optimized synthetic route starts from pyrene to prepare tetraacid usingRuCl3/NaIO4as the catalyst system, then react with SOCl2to obtain tetraacylchloride, afterreduction with LiAlH4to get the tetranol, react with SOCl2to obtain the tetramethylchloride.The advantage of this route were:（1） the RuCl3/NaIO4catalytic reaction was easily operated,and the yield has been improved half more than original process.（2） Two reactions withSOCl2were easily operated, and the yield were all achieved more than95%. This optimizedsynthetic route was easily operated, and the yields of each step were enhanced. Theseimprovements have increased the total yield of the ligand Tetrabi（Tb1） from original18%to35%. This synthetic route of frame ligand Tetabi（Tb1） would give good choice for thesythesis of other known similar Tetrabi-type phosphorus ligands. The design and synthesis ofthese two types of tetraphosphorus ligands has laid a solid foundation for subsequent research.2. The regioselective hydroaminomethylation activity of these tetraphosphorus ligandswere then investigated. Based on the study of the regioselective hydroformylation, terminalolefins and internal olefins were choosen as the standard substrates for the following test ofhydroaminomethylation, and the results are as follow:（1） The best reported regioselectivity, reactivity and linear selectivity were achieved withTetrabi ligand for the regioselective hydroaminomethylation of terminal olefins. Up to99%amine selectivity,168linear/branched amine product ratio （n/i）, and97.4%linear amine yieldhas been obtained at a substrate/rhodium ratio （S/Rh） of1000. The turnover number wasachieved6930at10000S/Rh ratio, and the n/i can reach up to>525. Several different olefinsand secondary amines have been applied successfully with high chemoselectivity （99%）, yield（>98%）, and regioselectivity （>120）.（2） The results of the hydroaminomethylation of internal olefins also showed bestactivity and regioselectivity using Tetrabi-type ligands and Rh（acac）（CO）2. A95.3%amineselectivity with36.2n/i ratio were obtained for2-octene at S/L/Rh ratio of1000/4/1, and aTON of linear amine was achieved of6837with a39.1n/i ratio of amine at S/L/Rh ratio of10000/12/1. The m-CF3-Ph substituted ligand was the best of the applied Tetrabi-type phosphorus ligands for different internal olefins, as up to a99.2%amine selectivity and95.6n/i ratio were obtained for2-pentene,98.8%amine selectivity and89.7n/i ratio for2-hexeneand98.2%amine selectivity and86.8n/i ratio for2-octene.（3） High reactivity and regioselectivity were abtained with pyrrole-based tetraphosphorusligands for the hydroaminomethylation of terminal olefins.92.4%amine selectivity and n/iratio of30.1was obtained for1-hexene with ligand L1. the3,3’,5,5’-methyl substitutedtetraphosphorus ligand L3was found to be the best ligand with up to70.9n/i ratio and99.5%amine selectivity for1-pentene and31.3n/i ratio and97.9%amine selectivity for1-hexene. The4,4’-methyl substituted ligand L9also showed excellent amine selectivity andregioselectivity to1-pentene with27.7n/i ratio and99.9%amine selectivity.In conclusion, two types of tetraphosphorus ligands have showed excellent activity forthe regioselective hydroaminomethylation. Tetrabi-type ligands have obtained the bestreactivity and regioselectivity for the regioselective hydroaminomethylation of terminalolefins and internal olefins, which are higher than the results from Beller’s Xantphos-typeligands. Therefore, these tetrabi-type ligands were among the best ligands applied in this field.Pyrrole-based tetraphosphorus ligands have achieved good amine selectivity andregioselectivity for the regioselective hydroaminomethylation of terminal olefins. Thesesuccesss of applications may give solide foundation for the exploration of the catalyticmechanism and performance of these ligands; and supplied a new kind of tetraphosphorusligands for this special reaction: regioselective hydroaminomethylation. These progress wouldstimulate the organo chemists’ interests of this reaction, and give new light to the realisticindustrial hydroaminomethylation procedure, especially for the more challengingregioselective hydroaminomethylation of ammonia, which is an effective method forproduction of linear amines by one-pot, convenient, efficient and lowest-cost way. On the onehand, it offers an economical pathway for the preparation of linear amines. On the other hand,it also set the fundamental theory for the transformation of functional groups in organicsynthesis. Obviously, the above results own very important value in scientific theory andindustrial application.