Rational Ligand Design for Potential Applications in Transition Metal Catalysis

University of Missouri, St. Louis IRL @ UMSL Dissertations UMSL Graduate Works 10-25-2011 Rational Ligand Design for Potential Applications in Transition Metal Catalysis Sergey L. Sedinkin University of Missouri-St. Louis Follow this and additional works at: https://irl.umsl.edu/dissertation Part of the Chemistry Commons Recommended Citation Sedinkin, Sergey L., "Rational Ligand Design for Potential Applications in Transition Metal Catalysis" 2011). Dissertations. 410. https://irl.umsl.edu/dissertation/410 This Dissertation is brought to you for free and open access by the UMSL Graduate Works at IRL @ UMSL. It has been accepted for inclusion in Dissertations by an authorized administrator of IRL @ UMSL. For more information, please contact marvinh@umsl.edu.

RationalLigandDesignforPotentialApplicationsin TransitionMetalCatalysis SergeyL.Sedinkin M.S.inChemistry,UniversityofMissouriBSt.Louis,2009 M.S.inChemistry,HigherChemicalCollegeoftheRussianAcademyofSciences, 2006 A Thesis Submitted to The Graduate School at the University of Missouri St. Louis in partial fulfillment of the requirements for the degree Doctor of Philosophy in Chemistry August 2011 Advisory Committee EikeBauer,Ph.D. Chairperson ChristopherSpilling,Ph.D. JamesChickos,Ph.D. KeithStine,Ph.D.

Sedinkin,Sergey,2011,UMSL,p. I Table&of&Contents! LIST%OF%ABBREVIATIO%...%V% LIST%OF%FIGURES%...%VI% LIST%OF%TABLES%...%III% ABSTRACT%...%IX% CHAPTER%I%Rational%Ligand%Design%for%Transition%Metal%Catalysis% 1.1.%%ITRODUCTIO%...%1% 1.2.%%IFLUECE%OF%THE%METAL%COMPLEX%O%THE%CATALYTIC%EFFICIECY%...%2% 1.3.%%LIGAD%DESIG%...%3% 1.3.1.STERICADELECTROICEFFECTS...5 1.3.1.1.$$Steric$tuning$of$ligands$...$5 1.3.1.2.$$Electronic$tuning$of$ligands$...$7 1.4%%GOALS%OF%THE%CURRET%PROJECT%...%10% 1.5.%%COCLUSIO%...%11% 1.6.%%REFERECES%...%11% CHAPTER%II%Investigation%of%AminoOdithiaphospholanes%as%a%ew%Class%of% Ligands% 2.1.%%AIM%OF%THE%CHAPTER%...%16% 2.2.%%ITRODUCTIO%...%16% I

Sedinkin,Sergey,2011,UMSL,p. II 2.3.%%SYTHESIS%AD%STUDIES%OF%THE%LIGADS%...%18% 2.3.1.ELECTROICPROPERTIESADCHEMICALSTABILITY...20 2.3.2.STERICPROPERTIESADCHEMICALSTABILITY...23 2.3.3.OVERVIEWOFTHECHEMICALSTABILITYOFTHESYTHESIZEDAMIOG DITHIAPHOSPHOLAES...28 2.4.%%AALYSIS%OF%PROPERTIES%OF%THE%EW%AMIOODITHIAPHOSPHOLAES %...%30% 2.4.1.PREPARATIOOFSELEIUMDERIVATIVES...31 2.4.2.AALYSISOFTHEMRDATA...33 2.4.3.AALYSISOFTHESPECTROSCOPICDATAOFAMIOGDITHIAPHOSPHOLAESIMETAL COMPLEXES...35 2.5.%%COCLUSIO%...%40% 2.6.%%REFERECES%...%40% CHAPTER%II%Experimental%Section GEERAL%METHODS%...%44% SYTHESES%...%44% CHAPTER%III%Investigation%of%Steric%and%Electronic%Tuning%of% Phosphinooxazoline%Ligands% 3.1.%%AIM%OF%THE%CHAPTER%...%49% 3.2.%%ITRODUCTIO%...%49% 3.3.%%SYTHESIS%OF%PHOSPHIOOXAZOLIES%...%51% II

Sedinkin,Sergey,2011,UMSL,p. III 3.4.%%AALYSIS%OF%THE%LIGADS %PROPERTIES%...%63% 3.4.1.EWIROPHOSPHIOOXAZOLIECOMPLEXES...64 3.4.2.ELECTROICPROPERTIESOFTHELIGADS...67 3.4.3.STERICPROPERTIESOFTHELIGADS...72 3.5.%%COCLUSIO%...%74% 3.6.%%REFERECES%...%75% CHAPTER%III%Experimental%Section GEERAL%METHODS%...%79% SYTHESES%...%79% CHAPTER%IV%Investigation%of%ew%onOHeme%Complexes%for%Iron%Catalyzed% Oxidation%Reactions 4.1.%%AIM%OF%THE%CHAPTER%...%97% 4.2.%%ITRODUCTIO%...%97% 4.3.%%SYTHESIS%OF%THE%LIGADS%...%99% 4.4.%%APPLICATIO%OF%THE%EW%LIGADS%I%CATALYSIS%...%111% 4.4.1.PREPARATIOOFTHEIROBASEDCATALYTICSYSTEMS...112 4.4.1.1.$$Characterization$of$the$new$iron$complexes$...$115$ 4.4.2.STUDIESOFTHEACTIVITIESOFTHECATALYSTS...119 4.4.2.1.$$Comparison$of$catalytic$activities$of$the$complexes$...$120$ 4.4.2.2.$$Mechanistic$considerations$of$the$oxidation$reactions$...$123$ 4.4.2.3.$$Determination$of$isolated$yields$...$124$ III

Sedinkin,Sergey,2011,UMSL,p. IV 4.5.%%COCLUSIO%...%127% 4.6.%%REFERECES%...%128% CHAPTER%IV%Experimental%Section GEERAL%METHODS%...%132% SYTHESES%...%132% CATALYTIC%EXPERIMETS%...%141% GEERALPROCEDUREFORCOMPARATIVECATALYTICOXIDATIOS...141 DETERMIATIOOFISOLATEDYIELDS...141 IV

Sedinkin,Sergey,2011,UMSL,p. V List%of%Abbreviation% Bn...Benzyl DCM...Dichloromethane DMAP...4CDimethylamino)pyridine DMF...,CDimethylformamide DMSO...DimethylSulfoxide Et3...Triethylamine Et2O...DiethylEther FAB...FastAtomBombardment IR...Infrared Me...Methyl MeC...Acetonitrile MS...Massspectrometry 3CBA...3CitrobenzylAlcohol MR...uclearMagneticResonance OTf...TriflateOSO2CF3) Ph...Phenyl PhMe...Toluene ppm...partspermillion THF...Tetrahydrofuran TLC...ThinLayerChromatography TsCl...mCToluenesulfonylChloride V

Sedinkin,Sergey,2011,UMSL,p. VI List%of%Figures% Figure'1.1...6 Figure'1.2...7 Figure'1.3...8 Figure'2.1...17 Figure'2.2...18 Figure'2.3...20 Figure'2.4...21 Figure'2.5...24 Figure'2.6...24 Figure'2.7...26 Figure'2.8...27 Figure'2.9...29 Figure'2.10...32 Figure'2.11...35 Figure'2.12...36 Figure'3.1...50 Figure'3.2...51 Figure'3.3...52 Figure'3.4...52 Figure'3.5...53 Figure'3.6...55 VI

Sedinkin,Sergey,2011,UMSL,p. VII Figure'3.7...57 Figure'3.8...58 Figure'3.9...60 Figure'3.10...61 Figure'3.11...64 Figure'3.12...66 Figure'4.1...98 Figure'4.2...100 Figure'4.3...100 Figure'4.4...103 Figure'4.5...104 Figure'4.6...106 Figure'4.7...107 Figure'4.8...108 Figure'4.9...111 Figure'4.10...114 Figure'4.11...115 Figure'4.12...118 Figure'4.13...119 Figure'4.14...120 Figure'4.15...120 Figure'4.16...125 VII

Sedinkin,Sergey,2011,UMSL,p. VIII List%of%Tables% Table'2.1...33 Table'2.2...37 Table'3.1...67 Table'3.2...69 Table'3.3...71 Table'3.4...73 Table'4.1...122 Table'4.2...126 VIII

Sedinkin,Sergey,2011,UMSL,p. IX Abstract% Strategiestoinfluencethestericandelectronicpropertiesofthreeclassesofligands wereinvestigated.first,acompoundclassknownasaminocdithiaphospholanes wasstudied.itisstructurallyrelatedtophosphoramidites,whichhavebeen successfullyappliedincatalysis.thesynthesisofaminocdithiaphospholaneswas envisagedasanapproachtoelectronicallytunedphosphoramidites.generalaccess toavarietyofstructurallymodifiedaminocdithiaphospholanesfromcommercially availablestartingmaterialswasdeveloped.theinvestigationoftheirchemical reactivitiesindicatedthatacombinationofelectronic,stericandphysicalproperties determinedthestabilityofthetargetligands.theelectrondonatingpropertiesof thenewligandswerecharacterizedbymr.theywerefoundtobemorebasicand, thus,moreelectrondonatingthanthecorrespondingphosphoramidites.the coordinationchemistryofaminocdithiaphospholaneswasinvestigatedbysynthesis ofaseriesofiridiumandrhodiumcomplexes.analysisofthephysicaldataobtained forthecomplexesconfirmedtheincreaseintheelectrondensityatthemetal centersasaconsequenceoftheincreasedbasicityoftheligands. Second,aseriesofnew,aswellasknown,phosphinooxazolinePHOX)ligandswas synthesized.asystematicstudyofstructurecpropertyrelationshipswasperformed withthephoxligands.itwasshownthatelectronictuningoftheligandsispossible byvaryingthesubstituentsonthephenylring.however,thetuningwasseento haveunexpected,andoftenonlyminorinfluenceontheelectronicpropertiesofthe metalcomplexesfromthoseligandsduetothestructuraldiversityandthebackc IX

Sedinkin,Sergey,2011,UMSL,p. X bondingabilitiesofthephoxligands.theefficiencyofsterictuningwas investigatedbyevaluationofxcraystructureanalysisdataofnewironphox complexessynthesizedforthestudy.itwasshownthatthepresenceofsubstituents inthepositionαtothenitrogenatomoftheoxazolineringhadthemostprofound impactonthegeometriesofthecorrespondingmetalcomplexes. Finally,fivenewmultidentate,OdonatingligandsL)weresynthesizedand characterized.theircoordinationchemistrywasinvestigatedbypreparationof newironcomplexesmimickingnaturallyoccurringnonchemeenzymes.thegeneral formulation[fel)2]otf)2,[fel)otf)2]or[fel)otf)]otf)wasestablishedfor thenewcomplexes,andformationofonlyoneisomerwasconfirmedforoneofthe complexes.thecatalyticactivityofthenewcompoundswasdemonstratedinthe oxidationofactivatedmethylenegroupsandalcoholstothecorrespondingketones. X

ChapterI! RationalLigandDesignforTransitionMetalCatalysis

Sedinkin,Sergey,2011,UMSL,p. 1 1.1.##Introduction# Withthesociety sdrivingneedtoestablishandpracticeenvironmentallybenign chemicalprocesses,catalyticreactionshavebecomeahighlydynamicfieldin chemicalresearch.indeed,thethreatofglobalwarminghasescalatedthe requirementofglobalindustriestodevelopcatalyticreactionsfortheregioeand enantioselectivesynthesisofsophisticatedtargetsfromsimplestartingmaterials. Thisisduetoastrongandoverridingbeliefthatthedevelopmentofefficient catalystsforindustrialescalereactionswillsignificantlyreduceenergyconsumption andwasteproduction. Stoichiometricandcatalyticreactionsoftransitionmetals,inparticular,have generatedconsiderableinterestduetotheirversatileandnumerousapplicationsin industrialandpharmaceuticalsettings.withtheexpandingutilityoftransition metalcatalysisinthepharmaceuticalandpetrochemicalindustries,amajordriving forcewasprovidedforthestudyanddevelopmentoftransitionmetalecatalyzed reactions.catalystsofthistypeprovidecriticalassistanceinthermodynamically feasibleprocessesbyopeningaloweractivationenergypathway,oftenonethatwas symmetryforbidden. 1 ThesemetalEcenteredreactionsaremostlycharacterizedby oneormoreelementaryreactions,i.e.ligandsubstitution,oxidativeaddition, reductiveelimination,migratoryinsertion,hydrogenexchange,βehydrogentransfer, σebondmetathesis,andnucleophilicaddition. 2 Thereareseveralreasonswhytransitionmetalcomplexeshavebecomepopularin thisfield.first,manyofthemarestableandeasytohandleonanyscale.for 1

Sedinkin,Sergey,2011,UMSL,p. 2 example,theledopasynthesis,discoveredbyknowles, 3 wastakentoacommercial processin1974bythemonsantocorporation.itutilizesastablerhodiumcomplex, whichisrequiredinlargequantitiesforbulksyntheses.secondly,byemploying chiralligands,thesecatalystscanpromotehighlystereoselectivereactions.agood exampleistheuseofchiralbiapligandsinrutheniumcomplexesforthe hydrogenationofβeketocarboxylicesters.thereportedenantiomericexcesswas nearly100%. 4 Thirdly,transitionmetalcatalystscanbestericallyandelectronically fineetuned byappropriatechoiceofthemetalcenterandbymanipulatingthetype andstructureoftheligands.finally,understandingofthemechanismsofthe catalytictransformationandtheinfluenceoftheligandsonthepropertiesofthe metalcentercanbeusedtoimprovetheperformanceofthecatalysts. 1.2.##Influence#of#the#metal#complex#on#the#catalytic#efficiency# Theeffectivenessofacatalyticreactiondependsonthefollowingconsiderations: 1)theselectivityofthetransformationchemoE,regioE,andstereoE),2)therateof theconversion,and3)theyieldofthedesiredproduct.oneofthemainadvantages oforganometalliccatalystsistheabilitytobe tuned tothedesiredlevelofactivity andselectivity.thiscanbeaccomplishedintwomainways.first,thechoiceofthe metalforthecomplexheavilyinfluenceswhatkindofchemicaltransformationsthe complexcouldcatalyzeefficiently.thus,rhodiumandiridiumarecommonchoices forhomogeneoushydrogenation; 5 manganese, 6,7 titanium 8,9 andrecentlyiron 10E14 arewidelyemployedinoxidationreactions;palladiumisthemostprevalentmetal forcatalyzingcarbonecarbonbondformationincrosscouplingreactions; 15 and 2

Sedinkin,Sergey,2011,UMSL,p. 3 rutheniumcarbenecomplexescatalizeolefinmetathesis. 16 Thesecondimportant partofametalcomplexareitsligands.mostofthecomplexes characteristics, includingcatalyticactivity,aredefinedthroughthenatureoftheligandattached i.e.thestericandelectronicpropertiesofaligandareusuallytranslatedtothe complexes.thus,sincethecatalyticpropertiesofmetalcomplexesarehighly dependentonthenatureoftheligand,itistherebyreasonabletoassumethatthe designofaligandthatexhibitsthedesiredstericandelectronicpropertywillleadto anefficientcatalystforaparticularprocess.consequently,itisimportanttorealize thattheoutcomeofreactionscatalyzedbyorganometalliccomplexescanbe influencedbythenatureofametalcomplexandtheselectionanddesignofthe chiralligand. 1 Therefore,thetargeteddesignofligandscanleadtosynthesisof metalcomplexeswithdesiredproperties,whichisespeciallybeneficialfor applicationinorganometalliccatalysis. 1.3.##Ligand#design# Thereareseveralcharacteristicstobeconsideredforthestructureofaligandtobe employedinsynthesisofametalcomplex.thedesignofaligandstartswiththe selectionofanatomthatwouldparticipateinformationofacoordinationbondto themetal.typicalchoicesarephosphorus,nitrogen,oxygenorsulfur.theseatoms typicallyarepartofstructurallycomplexligandsunlikehalogensthatareligandson theirown.thecoordinatingatomplaysanimportantroleintheoverallbehaviorof amoleculeasaligand.theenergyofthecoordinationbonddependsoninteraction ofthemetalcenterwiththecoordinatingatom.the hardandsoftacidandbase 3

Sedinkin,Sergey,2011,UMSL,p. 4 conceptcanbeusedtodescribethatdependency. 17 Itwasshownthat softer transitionmetalsplatinum,palladium,ruthenium,rhodium,etc.)formstronger bondswithligandsbearing softer coordinatingatomsphosphorus,sulfur)rather than harder oxygenornitrogenatoms.theoppositeholdstrueforthe harder alkalimetals. 18 extfactoristhenumberofatomsthatparticipateinformationofcoordination bondswithametalcenter.ligandswithonlyoneofsuchanatomarecalled monodentate.ligandswithtwoormoreatomscapableofformingcoordination bondstoametalarecalledpolydentate.uponformationofacomplex,theseligands generatechelatingringsincludingthemetalcenter. 19 Chelationcomplexesare thermodynamicallymorestablemainlyduetoanoverallincreaseinentropyduring theirformation. 20 Thestabilizationisknownas chelateeffect. 21 Thatisusuallya beneficialoutcomeforcomplexsynthesisbecauseitoftenallowsthepreparationof compoundsthataremorestableandthuseasiertohandlewithoutspecial precautions.however,insomecasesthestabilityofacomplexcanlimititspractical applications.thus,forcatalysis,acomplexinacatalyticcycleshouldbeableto openacoordinationsitethroughoneofthemechanismsmentionedabove, 2 but stronglybondedligandscanpotentiallyinhibitthatprocess. Withtypeandnumberofcoordinatingatomsselected,thenextaspectofthedesign istheorganiccorestructurethatwouldcontaintheseatoms.thechoiceofthe organiccompoundclassultimatelydefinesthemolecule sperformanceasaligand andthekindofstericandelectronicpropertiesthatwouldbetranslatedtothe metalcomplex. 4

Sedinkin,Sergey,2011,UMSL,p. 5 1.3.1.##Steric#and#electronic#effects# Asmentionedabove,ligandsexertstericandelectronicinfluencesonthemetal center.thus,theynotonlyinfluencethestereoeandregioselectiveoutcomeofthe reactiontobecatalyzed,theyalsoaffectthecatalyticefficiency.metaleligand interactionshaveabiginfluenceontheelectrondensityofthemetalcenterandthus impactthecatalyticbehaviorofthemetalcomplex. 22 LigandEmetalbondsconsistofσEusuallydonorinteraction)andπEusually acceptorinteraction)components.thecontributionofeachcomponenttobonding dependsontheelectroniccharacteristicsoftheligand. 23E25 Consequently, considerableresearcheffortshavebeendevotedtothefineetuningoftheelectronic characteristicsofaligandbyincorporatingavarietyofelectronwithdrawingor electrondonatinggroups.ontheotherhand,bulkygroupsonaligandexertsteric effectsonthemetalcenter.thesetherebyinfluencecatalyticactivitybychanging thegeometryofthecomplexandbycontrollingtheaccessibilityofthemetalcenter. 1.3.1.1.##Steric#tuning#of#ligands# Varyingthestericpropertiesofligandsismostcommonlyemployedstrategyin improvingtheperformanceofmetalcomplexes. 26 Oneofthefirstsystematic investigationsofstericpropertieswasperformedbytolmanwhointroducedhis conceptofaconeangleθforphosphoruscontainingligandsfigure'1.1,i). 27 Later, anadditionalprobeforassessingstericpropertieswasdevelopedbycaseyand WhitekerforbidentateligandsFigure'1.1,II).Theyintroducedtheconceptofa biteangleβn. 28 However,itwasshownthateffectsofthebiteangleofligandsare 5

Sedinkin,Sergey,2011,UMSL,p. 6 notexclusivelystericbutcouldhaveanelectroniccomponent. 29 Whilethese conceptsareapplicableforrelativelysimplesystems,mostofthemorecomplex ligandscannotbeanalyzedbytheseconcepts. Θ R R P R R 2 P β n M PR 2 M I II Figure'1.1.''The'cone'angle'Θ'I)'and'bite'angle'β n'ii)'concepts' Fundamentalstericpropertiesofligandsaredefinedbytheirskeletalcorestructure, butminoralternationscanbeachievedbyvaryingsubstituents,usuallyalkyl groups,onthebasicconfiguration.placementofthesubstituentsplaysan importantrolewiththemostlogicalpositionsbeingnearbythecoordinatingatom oratomsincaseofmultidentateligands).forexample,thechromiumbased complexiiifigure'1.2)employedinasymmetricepoxidationoftranseβe methylstyrenewasshowntoinducehigherenantioselectivitywhensubstituentsin orthoepositionstothecoordinatinggroupsr 1 andr 4,Figure'1.2)were present. 30,31 Onthecontrary,ashiftofthesubstitutiontotheR 2 andr 3 positions withr 1 andr 4 beinghydrogensresultedinadropoftheselectivity.thisfinding wasascribedtogreaterinfluenceonthepropertiesofthecomplexbystericeffects, whenthesubstituentsaresituatedclosertothecoordinatingoxygenandnitrogen atoms.steric finetuning ofthecatalystiiiwasperformedbyvaryingthesizeof 6

Sedinkin,Sergey,2011,UMSL,p. 7 thesubstituentsr 1.VerybulkytEbutylgroupswereshowntoprovidethehighest stereoselectivity. 30 X - R 3 R 4 O O Cr L O R 4 R 3 R 2 R 1 R 1 R 2 III Figure'1.2.''Sterically'tuned'chromium'complex'III' Severalapproachestostudystericpropertiesofligandsandtheireffectsonthe metalcenterofcomplexesareknowninliterature. 27,32E34 Analysisoftheoretical modelsisoftenemployedinordertodescribestericcharacteristicsofknown ligandsandpossiblypredictstericinfluenceofnewcompounds. 33,34 While molecularmechanicsmethodswereemployedintheliteraturetoassist investigationofpotentiallypracticalcatalysts, 35 employmentofxeraystructural analysisremainedamorecommontechnique. 36E38 1.3.1.2.##Electronic#tuning#of#ligands# Modificationsoftheelectronicpropertiesofligandsforknowncatalyticsystemsare notaswidelyemployedas adjustments ofthestericenvironmentcausedby ligands.thisisgenerallyduetomorechallengingelectronictuningofmost practicallyusedligands,whichoftendonotallowaconvenientmodificationoftheir structure. 26 evertheless,studiesofnewcatalyticsystemsandtheinfluenceofthe electronicpropertiesofligandsontheirefficiencyhavebeenreportedinthe literature. 22,39 7

Sedinkin,Sergey,2011,UMSL,p. 8 Thepurposeofelectronictuningofligandsistoinfluencetheabilityofthe coordinatingatomtodonateelectrondensitytothemetalcenterofacomplex. Electronictuningeffectscanbedividedintotwoaspects:1)selectionofthe compoundsclasstobearprincipalelectronicpropertiesand2)electronicfinee tuning. Similarlytosterics,thekeyelectronicpropertiesofligandsaredefinedbytheinitial choiceofthecompoundclass.thesubstitutionpatternaroundthecoordinating atomshowsthelargestinfluenceontheelectronicpropertiesoftheligand.for example,inaseriesofphosphoruscontainingligands,achangefromstrong electronedonationtomoderateelectronewithdrawwasobservedwhenthe increasingnumberofoxygenatomswasattachedtothephosphorusfigure'1.3). 23 Amongnitrogenbasedligands,aminesperformasσEdonorsbutpresenceofa doublebondatanitrogenimines,pyridines,etc.)makesthemalsoeffectiveπe acceptors. 40,41 R P R R RO P R R RO P R OR RO P OR OR Decrease of electron donating properties Figure'1.3.''Influence'of'the'substitution'pattern'around'a'phosphorus'atom'on' the'donating'properties'of'the'ligands' Atthepointwhenthegeneralelectronicpropertieshavebeenset,fineelectronic tuningcanbeperformedbyplacingelectronedonatingorelectronewithdrawing groupsinthebackbonewhilethecoreskeletalstructureremainsthesame. Propertiesofthesesubstituentstranslatetoelectronicchangesatthecoordinating 8

Sedinkin,Sergey,2011,UMSL,p. 9 atomthrougheitherinductiveorresonanceeffects. 42 Therefore,thetypeand positionofasubstituentinamoleculeplaysanimportantroleintheoverall outcomeoftheelectronictuning.theinductiveeffectstronglydependsonthe numberofbondsseparatingthecoordinatingatomandthesubstituent.itdecreases veryrapidwithincreasingdistance.hence,thepositionofthesubstituentshouldbe closetothecoordinatingatomtohaveaneffectonitselectrondensity.however, thatplacementcaninterferewiththestericpropertiesofthemolecule. 30,31 Onthe modelmetalcomplexiiifigure'1.2)itwasshownthatitscatalyticactivity significantlydecreasedwithmovingtheelectronwithdrawingchloridesubstituent fartherfromthecoordinatingoxygenatomfromr 1 =CltoR 3 =Cl). 31 Thereareseveralwayshowtheeffectsofelectronictuningofligandscanbe studied.oneofthemostcommonproceduresisbasedonemployingtheligandsin thesynthesisofaseriesofrelatedmetalcomplexescarryingacarbonylligand. AnalysisoftheIRspectragivesinformationabouttheelectrondensityatthemetal, asincreasingstretchingfrequenciesofthecarbonylligandindicateincreasing electrondonatingpropertiesoftheligands. 41,43E46 Applicationsofcyclicvoltammetrymethodforidentificationofoxidationpotentials weredescribedformetalcomplexesandligands.acorrelationbetweendonating propertiesofligandsandνc=ostretchingfrequencieswasfound.alinearincreaseof theoxidationpotentialswasshowntoresultinthedecreaseofνc=ostretching frequenciesinasimilarlinearmannerthatwasconnectedtothedeclineofthe electrondonatingabilitiesoftheligands. 23 9

Sedinkin,Sergey,2011,UMSL,p. 10 uclearmagneticresonancewasemployedtodeterminecouplingconstants betweenmagneticallyactivecoordinatingatomsusually 31 P)andametalcenter Rh,W,Hg). 47E51 Adecreaseinthecouplingconstant 31 PEM)valueswasobserved withincreasingdonatingpropertiesofligands.also,extensiveapplicationwas foundforvaluesof 31 PE 77 Secouplingsduetotheirgoodcorrelationwithdonating propertiesofthephosphorusatoms. 43,52E58 1.4.##Goals#of#the#current#project# Themaingoalstatedforthisprojectistoinvestigatepathwaystoinfluencesteric andelectronicpropertiesofthreeclassesofligands.thefirsttargetofthe investigationisaclassofcompoundsknownasaminoedithiaphospholanes. 59 They arestructurallyrelatedtophosphoramidites,whichhavesuccessfullybeenapplied incatalysis. 60 Therefore,aminoEdithiaphospholanescanbeseenaselectronically tunedphosphoramidites.however,verylittleisknownabouttheirpropertiesand theircoordinationchemistryhasnotbeenreportedintheliterature.thesecond objectiveistosystematicallyinvestigatethepossibilityofstericandelectronic tuningofthephosphinooxazolines. 61 Whiletheyareaknownclassofligands,a comprehensivestudyoftheirstructureepropertiesrelationshipcannotbefoundin theliterature.thefinalpartoftheprojectisdedicatedtothesynthesisofseveral newmultidentateligandsandtheircorrespondingironcomplexesmimicking naturallyaccruingnonehemeenzymes. 62 Aprobeofthecatalyticactivityofthenew complexesisgoingtobeperformedusingoxidationreactionsofactivated methylenegroupsandalcohols. 10

Sedinkin,Sergey,2011,UMSL,p. 11 1.5.##Conclusion# Irrespectiveoftheapplication,thesyntheticpathwaytoametalcomplexconsistsof severalstages.ligandsdesignisoneofthemostsubstantialstepsintheprocess. Itsimportanceisoftenunderestimated.However,theligandisasignificantpartofa metalcomplexanddefinesmanyofitsprincipalproperties.abetterunderstanding ofstericandelectronicpropertiesexertedbyknownligandshelpstodevelop complexeswithdesiredcharacteristics.ontheotherhand,introductionofnew classesofcompoundsaspotentialligandsbroadenstheselectionofbuildingblocks thatcanbeusedfordesigningnewmetalcomplexes.thesearethemainwaysfor theexpansionandimprovementofpracticalimplementationofmetalcomplexes thatwillleadtothecontinuousevolutionofcoordinationchemistry. 1.6.##References# 1) iu,s.;hall,m.b.chem.,rev.2000,100,353. 2) Crabtree,R.H.The,Organometallic,Chemistry,of,the,Transition,Metals; JohnWiley&Sons:ewYork,1988. 3) Knowles,W.S.Acc.,Chem.,Res.1983,16,106. 4) oyori,r.;ohkuma,t.;kitamura,m.;takaya,h.;sayo,.; Kumobayashi,H.;Akutagawa,S.J.,Am.,Chem.,Soc.1987,109,5856. 5) Vries,J.G.d.;Elsevier,C.J.Handbook,of,Homogeneous,Hydrogenation; WILEYEVCHVerlagGmbH&Co.KGaA:Weinheim,Germany,2007. 11

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ChapterII! Investigation+of+Amino/dithiaphospholanes+as+a+ew+Class+of+Ligands+

Sedinkin,Sergey,2011,UMSL,p. 16 2.1.$$Aim$of$the$chapter$ Electronictuningofphosphoramiditeligands. Ithasbeenourexperiencethatoneofthemostemployedligandclassinour laboratory,phosphoramidites, 1C5 lackedtheabilityofeffectiveelectronictuning, 3,4 whenperformedbyelectrondonatingoracceptingsubstituentsonthearylrings connectedtothephosphorus.therefore,adifferentapproachtoadjustthe electronicpropertieswasrequired.anewclassofligandsstructurallyrelatedto phosphoramiditeswasinvestigatedinwhichtheoxygeninphosphoramiditeswas replacedwithsulfur.theaimoftheinvestigationwastoestablishageneral procedureforthesynthesisofthenewligands,characterization,determinationof theirchemicalstabilityandinvestigationoftheirelectronicproperties. Coordinationchemistryandimpactofthenewligandsontheelectrondensityatthe metalcenterwerealsoinvestigated. 2.2.$$Introduction$ PhosphoramiditesIinFigure2.1)havebeenemployedinthesynthesisofavariety ofcatalyticallyactiveorganometalliccomplexes. 6 Ourlaboratoryhasalreadyshown thatphosphoramiditecomplexesofrutheniumcanefficientlycatalyzetheformation ofβcoxoesters 4 andthemukaiyamaaldolreaction. 3 However,itwasshownthat electronictuningofthephosphoramiditeshadonlyaslighteffectwhenperformed onthebackboneoftheligand. 3,4 Consequently,wewereinterestedininvestigating theelectronicinfluencesoftheatomsdirectlyattachedtothephosphoruscenteron 16

Sedinkin,Sergey,2011,UMSL,p. 17 thepropertiesoftheligands.wedecidedtostudythesulfuranalogsof phosphoramidites,knownintheliteratureasaminocdithiaphospholanesiii)ifthe phosphorusandthesulfuratomsareincorporatedinafivememberedring,or phosphoramidodithioitsii)inallothercasesfigure2.1). 7 Significantly,thisclass ofcompoundsisknown,butithasnotbeenappliedintransitionmetalcoordination chemistry. R 1 O R 2 R 1 S R 2 P P R 1 O R 2 R 1 S R 2 R 1 R 1 S P S R 2 R 2 I II III Figure2.1.PhosphoramiditesI,phosphoramidodithioitsIIandamino7 dithiaphospholanesiii AminoCdithiaphospholaneshavefirstbeenreportedintheliteraturebut,their syntheticapplicationshavebeenlimited. 8 Onlyafewstructureshavebeen synthesized, 7 thereforetheknowledgeoftheirchemistryandreactivityislimited. Uptonow,onlyafewapplicationsofthisclassofcompoundsinresearchgave informationabouttheirreactivity.thepcbondinaminocdithiaphospholanesis sensitivetohydrolysis 9 oralcoholysis, 7,10 apropertythathasbeenusedforthe phosphorylationofnucleotides. 7,8,11 WhiletheinstabilityofthePCbondisusefulin thesecases,forpurposesofourresearchweneededtoaccessmorestable structuresofthatcompoundclass. 17

Sedinkin,Sergey,2011,UMSL,p. 18 2.3.$$Synthesis$and$studies$of$the$ligands$ DuetothelackofliteratureexamplesforaminoCdithiaphospholanesynthesis,we appliedmodifiedmethodologiesdevelopedearlierinourlaboratoryforthe preparationofphosphoramidites. 3,4 Thegeneralprocedureconsistedofatwostep substitutionofthechlorideatomsinpcl3thatwereperformedonepotfigure2.2). Cl P Cl Cl R 2 H, Et 3 CH 2 Cl 2, 0 C, 1 h Cl R P Cl R IV R 1 SH, Et 3 CH 2 Cl 2, rt, 0.5 h R 1 R 1 S P S V R R Figure2.2.Generalmethodforamino7dithiaphospholanesynthesis AsshowninFigure2.2,theintendedsynthesisofthetargetedligandsstartedwith theexchangeofoneofthechloridesinpcl3withadisubstitutednitrogenatomthe R2unit)togivecompoundIV.Itwasperformedbyslowdropwiseadditionofone equivalentofasecondaryaminetoasolutionofpcl3inch2cl2inthepresenceof Et3asabase.Inordertopreventoverheatingofthereactionmixtureandpossible formationofdicandtricsubstitutedsideproducts,theadditionwasperformedat0 Cice/waterbath).Thereactionproceededveryfastbutinordertoensure completeconversion,themixturewasstirredforanhourintheicebath.atthat time,thenextstepwasperformedtoyieldthetargetcompoundv.afteradditionof aslightexcess2.1equivalents)ofthethiolr 1 SHat0 C,thereactionmixturewas warmedtoroomtemperatureandstirredfor30minutes.acrude 31 PMRwas recordedtocheckforthepresenceofthedesiredproduct.thereactionmixture wasquicklywashedwithaqueoussolutionsofahso4andahco3inorderto separateunreactedamineandthiolstartingmaterials,ifpresent,andpotentialbasic 18

Sedinkin,Sergey,2011,UMSL,p. 19 oracidicbyproducts.finalpurificationwasaccomplishedeitherbyprecipitationof thetargetcompoundoutofasolutioninch2cl2byadditionofaet2o/hexanes solventmixtureorbycolumnchromatography.thesynthesisoftheligandsand theircharacterizationisdetailedbelow. Forfurtherinvestigationswefirstneededtounderstandthechemicalbehaviorof thepotentialligands.therefore,anappropriateselectionoftargetstructureswas performedtoachievethatobjective.duetotheaforementionedabilityofaminoc dithiaphospholanestoundergodecompositionthroughanucleophilicattackonthe phosphorusatom,aninvestigationoftheinfluenceofthemolecularstructureonthe stabilityofthecompoundswasrequired.therearetwomainfactorsthatcanplaya roleintheabilityofthephosphorusatomtosuffernucleophilicattack.thefirst factorrelatestotheelectronicpropertiesofthepotentialreactioncenters.fora nucleophilicattack,thephosphorusatomhastoperformasanelectrophile,sothe electrondensityattheatommustbelowfortheattacktoproceed.consequently, anincreaseoftheelectrondensityatthephosphorusshouldresultinalessreactive compound,andthusamorestablemolecule.thesecondimportantfactorfor reactivityisthestericenvironmentaroundthephosphoruscenter.anucleophile hastobeabletoreachtheatominorderforanattacktotakeplace.byincreasing thestericcongestionaroundthephosphorusatom,aminocdithiaphospholanes shouldbecomelesspronetonucleophilicattack.inourtargetedligands,both effectsmainlydependonthesubstituentsonthenitrogenandthesulfuratoms. Therefore,byexploitingstructuralmodificationsoftheligands,weshouldbeableto identifyoptimalsubstituentstoincreasethestabilityofourtargets.thispartofthe 19

Sedinkin,Sergey,2011,UMSL,p. 20 projectwasdividedintotwosections.theelectroniceffectswerestudiedfirst, followedbyaninvestigationofthestericinfluenceontheligandstabilities. 2.3.1.$$Electronic$properties$and$chemical$stability$ TheelectrondensityatthephosphorusatominaminoCdithiaphospholanescanbe tunedbyvaryingthesubstituentonthesulfurandnitrogenatoms.accordingtothe methodchosenforthegeneralsynthesisofthecompoundsfigure2.2),those variationswereimplementedbyemployingamineandthiolstartingmaterialswith differentelectronicproperties. Fivereadilyavailablethiols2.172.5wereusedforthesynthesisFigure2.3).We wereinterestedincomparingtheimpactofdifferentalkyl2.1)andaryl substituents2.272.5)ontheligandproperties.inaddition,introductionof substituentsonthearylringwereexpectedtochangetheelectroncdonating propertiesofthesulfuratom.therefore,alongwiththeparentalthiophenol2.2, thiolswithastronglyelectroncdonatingmethoxygroup2.5),aweaklyelectronc donatingmethylsubstituent2.3)andanelectroncwithdrawingchloridesubstituent 2.4)wereselectedforthesynthesisofthecorrespondingaminoC dithiaphospholanes. 2.1 SH X SH H 2.2 X = H H 2.3 X = Me 2.4 X = Cl 2.6 2.7 2.5 X = MeO Figure2.3.Electronicallymodifiedthiolandaminestartingmaterials 20

Sedinkin,Sergey,2011,UMSL,p. 21 Atthenitrogensideofthemolecule,amodificationoftheelectronicpropertieswas intendedtobeachievedbyuseofadialkylandadiarylamine.inanattempttoonly probetheelectroniceffectwithouttriggeringstericinteractions,twostructurally similarsecondaryamineswereselected,diphenylamine2.6anddibenzylamine2.7 Figure2.3).Allthecompoundschosenforthestudyarecommerciallyavailable. Withthisseriesofstartingmaterials,wemovedtoemployingtheminthesynthesis ofaminocdithiaphospholanesaccordingtothegeneralproceduredescribedabove Figure2.2).Inordertogetinsightintherelationshipsbetweenthestructureand thestabilityofaminocdithiaphospholanes,weemployedallpossiblecombinations ofthestartingmaterialsinsynthesisfigure2.4).toobtainpreliminarydata,test reactionswereperformedandthereactionmixturesanalyzedspectroscopically. Cl P Cl Cl Cl P Cl Ph Ph PhCH 2 ) 2 H, Et 3 CH 2 Cl 2, 0 C, 1 h Ph 2 H, Et 3 Cl P Cl CH 2 Ph CH 2 Ph RSH, Et 3, CH 2 Cl 2, rt, 0.5 h RSH, Et 3, CH 2 Cl 2, rt, 0.5 h R R S P S CH 2 Ph CH 2 Ph 2.13 R = Et detected in the 2.14 R = Ph reaction mixture, 2.15 R = p-meph but not isolable 2.16 R = p-clph 2.17 R = p-meoph, 85% R R S P S Ph Ph 2.8 R = Et 2.9 R = Ph 2.10 R = p-meph 2.11 R = p-clph 2.12 R = p-meoph detected in the reaction mixture, but not isolable Figure2.4.Targetsforprobingofelectroniceffects 21

Sedinkin,Sergey,2011,UMSL,p. 22 Accordingly,afterreaction,asmallaliquotofthecrudereactionmixturewastaken fromeachofthetenreactionmixtures.crude 31 PMRspectrawereobtainedand confirmedtheabsenceofeitherthepcl3startingmaterialoranychloroccontaining intermediates.eachsampleshowedamajorpeakwithvariousamountsofminor signals.thechemicalshiftsforthemainsignalinthe 31 PMRspectraranged between120and135ppm,andwereintheregionexpectedforthetarget molecules. 10 Unfortunately,evenfromthecrudeMRdataweobservedongoing decompositionformanyofthedesiredcompounds.alargenumberofsignalswith highintensities,exceedingintotaltheintensityofthemajorpeak,wasobservedin thecrudespectrafromthesynthesesofcompounds2.872.12.duetotheaniline derivative2.7)employedinthesynthesis,allthosemoleculeswereexpectedto containaph2grouponthephosphorus,whichissignificantlylesselectron donatingthanthebn2group,thereforeanucleophilicattackonthephosphorus potentiallyproceededatahigherrate.whileweobservedthatarylsubstituentson thenitrogenatomcausedfastdecompositionofthemolecules2.872.12,atrendfor theirrelativestabilitywasneverthelessnoticedbasedontheanalysisofthedata obtainedfrom 31 PMRspectraofthecrudereactionmixturesoveraperiodofa couplehours.thus,compound2.12wasfoundtodecomposeatthelowestrate amongthemoleculesintheseries. Thosefindingswereconsistentwithsimilardataobtainedforcompounds2.137 2.17.Inthatseries,overallahigherstabilitywasobservedformoleculesbearing dialkylaminosubstituentatthephosphorusatom,withtheaminoc dithiaphospholane2.17beingthemoststableone. 22

Sedinkin,Sergey,2011,UMSL,p. 23 AfteracquisitionofpreliminaryinformationaboutthestabilityoftheaminoC dithiaphospholanes2.872.17,numerousattemptstoseparateandpurifythe synthesizedcompoundsinfigure2.4wereundertaken.first,aqueousworkupof thereactionmixtureswasnecessarytoseparatetheammoniumsaltsandsomeof thesideproducts.then,precipitationofthedesiredtargetmoleculeswas attempted.forthatpurpose,thecrudematerialsobtainedfromtheaqueouswork upwereredissolvedinaminimalamountofch2cl2followedbyslowadditionof Et2O/hexanesmixtureswithvariousratiosofthetwosolvents.Column chromatographywasalsoinvestigatedforpurificationoftheproducts.several sorbentswereexamined,includingsilicagel,aluminaandflorisil.hexanes/ethyl acetateortoluene/ethylacetatesolventsystemswith3%et3wereusedfor elution.unfortunately,almostalleffortstoseparatethedesiredproductsfromthe reactionmixturesfailedduetoongoingdecompositionofthecompounds.onlythe targetmolecule2.17wasshowntobestableenoughto survive washingwithh2o, andpurificationbycolumnchromatographytoaffordtheproductin85%yieldasa colorlessoil. 2.3.2.$$Steric$properties$and$chemical$stability$ Similartoprobingtheelectronictuningeffects,investigationsoftheinfluenceofthe stericenvironmentaroundthephosphoruscenteronthestabilityoftheaminoc dithiaphospholaneswereperformedbyemployingstericallymodifiedthiolsand secondaryaminesintheirsynthesis. Duetothepresenceoftwosulfuratomsconnectedtothephosphoruscenterinthe targetmolecules,thechoiceofthesulfurcontainingstartingmaterialsallowedthe 23

Sedinkin,Sergey,2011,UMSL,p. 24 inclusionofdithiols.theirusewouldincorporatethephosphorusintoacyclic system,consequentlyprovidanuniquestericenvironment.hence,threecyclic dithiolstartingmaterials2.1872.20werechosenfigure2.5). HS SH HS SH HS 2.18 rac-2.19 2.20 2.21 2.22 SH O H H R H R 2.23 R = Et 2.24 R = i-pt Figure2.5.Stericallymodifiedthiolandaminestartingmaterials Amineswithdifferentnitrogensubstituentwereseenasgoodcandidatestoprobe theinfluenceofsterichindranceonthestabilityoftheaminocdithiaphospholanes. Fouramineswerepickedforthestudy2.2172.24inFigure2.5).Intheprevious experiments,weobservedthatdialkylaminosubstituentsgavemorestableproducts thandiarylaminosubstituents,thusalltheaminesweusedatthatpointcarried alkylgroups. Whilemostofthethiolsandtheamineswerecommerciallyavailable,theknown compound2.19hadtobeprepared.itwassynthesizedintwostepsfrom cyclohexeneoxide2.25similarlytoaproceduredescribedintheliteraturefigure 2.6). 12 O CS 2, KOH MeOH, rt, overnight Figure2.6.Synthesisofrac)7trans71,27cyclohexanedithiol2.19 Inthefirststep,theepoxide2.25wasopenedbyaxanthateanionpreformedin#situ bymixingkohwithcs2inmeoh. 13 Thereactionproceededsmoothlyatroom S S S LiAlH 4 THF, reflux, 3 h 2.25 2.26 2.19 SH SH 24

Sedinkin,Sergey,2011,UMSL,p. 25 temperatureandupondilutionwithalargeamountofh2o,yellowcrystalsofthe desiredintermediateproduct2.26formed.inordertoremoveexcesscs2the mixturewaskeptataround70 Cforanhour.Thecrystallineproductwas separatedbyfiltration,wasspectroscopicallypure,andwasusedinthenextstep withoutfurtherpurification.reductionofthecyclictrithiocarbonate2.26with LiAlH4inTHFgavecompleteconversiontothedithiol2.19after3hoursofreflux. WashingofthereactionmixturewithdilutedHClwasperformedtodestroy unreactedlialh4andaluminumbyproductsofthereaction.afterextractionwith Et2Oandevaporationofthesolvent,theproduct2.19wasobtainedwithbaseline MRpurityin83%yieldandwasusedwithoutfurtherpurification. AllthestartingmaterialswerenextemployedintheaminoCdithiaphospholane synthesesaccordingtothegeneralmethodologyfigure2.2).thepreviously obtaineddatashowedthattheuseofparacmethoxythiophenol2.5and dibenzylamine2.7gavemorestableproducts.therefore,atthisphaseofthestudy, theywereusedascouplingpartnerstoobtainthecorrespondingtargetmolecules withdifferentlevelsofstericcongestion.westartedwiththesynthesisof phosphoramidodithioites2.2772.30figure2.7). 25

Sedinkin,Sergey,2011,UMSL,p. 26 R O H H H R 2.21 2.22 2.23 R = Et 2.24 R = i-pt 1. PCl 3, Et 3, CH 2 Cl 2, 0 C, 1 h 2. p-meophsh, Et 3, CH 2 Cl 2, rt, 0.5 h PhOp-Me PhOp-Me PhOp-Me PhOp-Me PhOp-Me PhOp-Me S P S S P S S P S R R O 2.27 2.28, 50% 2.29 R = Et 2.30 R = i-pr Compounds 2.27, 2.29, and 2.30 were detected in the reaction mixture, but not isolable Figure2.7.Targetsforprobingthestericeffectsofthesubstituentson nitrogenontheligandstabilities ThereactionsandworkupswereperformedasdescribedaboveFigure2.2).Upon completionofthereactions,aninvestigationofthenumberofproductswas performedby 31 PMRofthecrudemixtures.Itshowedthatthecrudecompound 2.28gavetheleastnumberof 31 Psignalsnotrelatedtotheexpectedproductand thehighestratiobetweentheintensityofthemajorproductsignalat133.2ppmand thecombinedintensitiesoftheminorpeaks.areversetrendwasseeninthe 31 P MRdataofthecompounds2.27,2.29and2.30.Thespectraforthosemixtures containedasignificantnumberofsignalsintheregionbetween40to0ppm, suggestingongoinghydrolysiswithformationofcompoundscontainingpcobond andultimatelyphosphoricacid.purificationattemptsincreasedtheintensityof thosepeaks.theaminocdithiaphospholane2.28wasseparatedfromthereaction mixturebyextractionandpurifiedbycolumnchromatographyin50%overallyield asacolorlessoil.thethreeothertargets2.27,2.29and2.30)fromfigure2.7 weretooreactiveandalleffortstoseparatethemfromhydrolysisbyproducts resultedinongoingdecomposition. 26

Sedinkin,Sergey,2011,UMSL,p. 27 OurlastsynthetictargetswerethecyclicaminoCdithiaphospholanes2.3172.33 Figure2.8).Thedithiols2.1872.20wereutilizedfortheirsynthesis. Dibenzylamine2.7,thatwasshownabovetogivepotentiallymorestableproducts, wasusedasthenitrogensource. Cl P Cl Cl PhCH 2 ) 2 H, Et 3 CH 2 Cl 2, 0 C, 1 h Cl P Cl CH 2 Ph CH 2 Ph Et 3 CH 2 Cl 2, rt, 0.5 h 2.18 2.20 2.19 S P S CH 2 Ph CH 2 Ph S P S S P S CH 2 Ph CH 2 Ph 2.31, 82% CH 2 Ph 2.32, 85% CH 2 Ph 2.33, 83% Figure2.8.Targetsforprobingthestericeffectsofsubstituentsonsulfur Thesyntheseswereperformedunderthestandardconditiondescribedabove Figure2.2).Theproducts2.3172.33werefoundtobecrystalline.Therefore,their separationwasperformedbyprecipitation.attemptstoexcludepotentially destructiveaqueousworkupandtoprecipitatetheaminocdithiaphospholanes 2.3172.33straightfromtheircorrespondingreactionmixturesdidnotresultin successfulseparations.significantamountsofhydrolysisbyproductswereobserved duringaqueousworkup,whichprecipitatedalongwiththecrystallinematerialsas oils.however,thebyproductswereseparatedbywashingwithh2oandsaturated aqueousahco3,andtheresultingcrudeproductswereredissolvedinch2cl2.the compounds2.3172.33weresuccessfullyprecipitatedoutofthesolutionsbyslow additionofet2ofollowedbyet2o/hexanesmixtures.thecrystallinematerialswere separatedfromthesolventbyfiltrationand,upondrying,affordedthe 27

Sedinkin,Sergey,2011,UMSL,p. 28 spectroscopicallypureaminocdithiaphospholanes2.3172.33in82%,85%,and83% yields,respectively,ascolorless,crystallinematerials. 2.3.3.$$Investigation$of$the$chemical$stability$of$the$synthesized$amino? dithiaphospholanes$ Overall,fiveaminoCdithiaphospholanes2.17,2.28,2.3172.33)wereisolatedin spectroscopicallypureformwithyieldsrangingfrom50to85%.ingeneral,itwas foundthatforthisclassofcompounds,acombinationoffactorsaffordedisolable productswithstabilitiessufficienttoobtainanalyticallypurematerials.increaseof theelectrondensityatthephosphorusatomproducedcompound2.17,whichisless vulnerabletohydrolysisthan2.872.12.inadditiontotheelectroncdonating substituentsonthesulfuratoms,themolecule2.28carriestwoquaternarycarbon atomsnexttothenitrogenthatwebelievecausesasignificantstericbarrierfora potentialnucleophilicattackonthephosphorusatom,thusmakingthestructure relativelystable.thephysicalstateofthedesiredproductswasalsofoundtoplay animportantroleinsuccessfulisolationandpurificationofthecompounds.the ligands2.3172.33arecrystallineandprecipitatedoutofthesolutionsofthecrude mixtures.however,allothercrudemixturesrequiredpurificationbycolumn chromatography,whichismore demanding withrespecttothestabilityofthe targetmolecules.therefore,fromthelargeseriesoftheattemptedsyntheses,only twononccrystallineproducts2.17and2.28)weresuccessfullyisolated. Therelativechemicalstabilityofthesynthesizedcompounds2.17,2.28,2.3172.33 wasinvestigatedby 31 PMRmeasurementsinpresenceofnucleophilesovertime. 28

Sedinkin,Sergey,2011,UMSL,p. 29 TheexperimentswereconductedinMRtubes.Thecompoundsweredissolvedin CDCl3andaround10volumepercentofMeOHorH2Owereaddedtothesolutions. WaterisnotmisciblewithCDCl3,thereforethetubeswereshakentoform emulsions.the 31 PMRdataforthesolutionswererecordedbeforetheadditionof thenucleophilesandafter15,30,60minutesandafteroneday.analysisofthe relativeratesofdecompositionofthemoleculesresultedinthefollowingrowof stabilityforthesynthesizedaminocdithiaphospholanesfigure2.9). p-meoph p-meoph p-meoph p-meoph S P S 2.28 S P S 2.17 CH 2 Ph CH 2 Ph S P S CH 2 Ph CH 2 Ph S P S CH 2 Ph CH 2 Ph > > > S P S 2.31 2.32 2.33 CH 2 Ph CH 2 Ph Figure2.9.Chemicalstabilityrowforthesynthesizedcompounds2.17,2.28, 2.3172.33 TheaminoCdithiaphospholane2.17wasfoundtobethemoststableamongthe synthesizedcompounds,closelyfollowedbythemolecule2.28.bothcompounds showedonlysmallamountsofdecompositionafter60minutesincdcl3solutionsin thepresenceofmeohorh2o.however,after24hourstheintensitiesofthe 31 P signalscorrespondingtothecompounds2.17and2.28weresignificantlylower thanthecombinedintensitiesoftheotherpeaksinthemrspectra.thesedata supportedincreasedstabilityoftheproducts2.17and2.28,whilestillconfirming theirsensitivitytowardshydrolysisandalcoholysisovertimeinsolution. 29

Sedinkin,Sergey,2011,UMSL,p. 30 ThethreeaminoCdithiaphospholanes2.3172.33,whichincorporatethephosphorus atomintoacyclicstructure,wereobservedtobeindefinitelystableincrystalline form,butwereseentorapidlydecomposeinsolution.themrstudyoftheir behaviorinpresenceofthenucleophilesshowedalmostcompletedisappearanceof the 31 Psignalforcompounds2.3172.3360minutesafteradditionofMeOHorH2O. Therelativedegradationrateofcompound2.33wasnoticeablyhigherthanthatof thecompounds2.31and2.32,whiletheaminocdithiaphospholane2.31wasfound tobestableinthesolutionforatleast30minutes. 2.4.$$Analysis$of$the$properties$of$the$new$amino? dithiaphospholanes$ Withthepurifiedandsufficientlystableligands2.17,2.28,2.3172.33inhand,we startedthenextpartoftheproject.asmentionedabove,thecoordination chemistryofthisclassofcompoundshaspreviouslynotbeenreported.therefore, electronicfactorsrelevantforcoordinationtoametalcenterwereinvestigatedfirst. Atfirst,theelectronCdonatingabilitiesofthenewligandswerecomparedwiththose ofstructuralyrelatedphosphoramidites,whichwasaccomplishedbymr.a relationshipbetweenthechemicalshiftandtheelectrondensityattheatomisvery complexforheavyelements,suchasphosphorus,duetothelargeinfluenceof paramagneticshieldingcomponentsonthechemicalshift.ontheotherhand, couplingconstantstoanothernucleuswereshowntocorrelatewellwiththe electrondensityatphosphorus.forphosphoruscontainingligands,analysisofthe 30

Sedinkin,Sergey,2011,UMSL,p. 31 couplingconstantswaspreviouslyperformedtoassesstheelectrondensityand basicityonthephosphorus. 14 Basicitytrendsobtainedfrom 1 J 31 PCM)coupling constantsinmetalcomplexesshowedadependencyonthemetal 14 andthe structureofthecomplexes. 15,16 Thus,itwasobservedthatwithincreaseofthe electrondonatingpropertiesofaligand,the 31 PC 195 Pt 17 and 31 PC 183 W 18,19 coupling constantsdecreased,butareversedeffectwasobservedfor 1 J 31 PC 199 Hg). 20,21 Similarrelationshipswerefoundforseleniumderivativesofphosphines.The isotope 77 SeisMRactiveandhasaspinof½,leadingtospinCspininteractionswith 31 P,whichresultsinsplittingofthephosphorussignalstoadoublet.Itwas describedthatthevalueofthe 31 PC 77 Secouplingconstantincreaseswithdecreasing basicityofthephosphorusatom. 16,22C28 Correlationsbasedonthosetrendswere foundtobemorereliableduetoonlyveryslightdeviationsofthestructuresof phosphoruscompoundsuponintroductionofselenium. 16 Thereforeweemployed seleniumderivativesinordertocharacterizetheelectronicpropertiesofthenew aminocdithiaphospholanes. 2.4.1.$$Preparation$of$selenium$derivatives$ Phosphinesandothercompoundscontainingtrivalentphosphorusreadilyreact withelementalseleniumtoformthecorrespondingselenides, 26,29 whichareanalogs ofphosphinoxidesderivatives.forthepurposeofcollecting 31 PC 77 Secoupling constants,wefoundthatmrtubeexperimentsarethefastestandeasiestwayto achievethatgoal.toperformthetests,wefollowedageneralprocedurespecifically developedtodeterminethosecouplingconstantsfigure2.10). 31

Sedinkin,Sergey,2011,UMSL,p. 32 R 1 R 1 S R 2 P S R 2 2.17 R 1 = p-meoph, R 2 = CH 2 Ph 2.28 R 1 = p-meoph, R 2 = -CCH 3 ) 2 CH 2 ) 3 CH 3 ) 2 C- 2.31 R 1 = -CH 2 CH 2 -, R 2 = CH 2 Ph 2.32 R 1 = 1,2-Cy, R 2 = CH 2 Ph 2.33 R 1 = 1,2-Ph, R 2 = CH 2 Ph Se 8, CDCl 3, 50 C, 1 h S S R 1 Se P R 2 R 1 R 2 2.34 R 1 = p-meoph, R 2 = CH 2 Ph 2.35 R 1 = p-meoph, R 2 = -CCH 3 ) 2 CH 2 ) 3 CH 3 ) 2 C- 2.36 R 1 = -CH 2 CH 2 -, R 2 = CH 2 Ph 2.37 R 1 = 1,2-Cy, R 2 = CH 2 Ph 2.38 R 1 = 1,2-Ph, R 2 = CH 2 Ph Figure2.10.Ageneralprocedureforsynthesisoftheseleniumderivativesof theamino7dithiaphospholanes2.17,2.28,2.3172.33 A20mgsampleofthephosphorusCcontainingligands2.17,2.28,2.3172.33was dissolvedincdcl3andplacedintoanmrtube.theamountofseleniumaddedto thesolutionwas15mg.themolarratiobetweenthereactantandseleniumvaried dependingonthemolecularweightofthemoleculetobetested,buttheadded amountofseleniumwasalwaysin2to4foldexcess.itwasfoundthatdifferent aminocdithiaphospholanesreactedatslightlydifferentratesatroomtemperature exceptforthecompound2.28thatdidnotgivenoticeableconversionto2.35even afterseveralhours,asassessedbymr.theotherligandsaffordedtheexpected seleniumderivativesbetween2and4hoursatroomtemperature.thesubstantial differenceinthereactivityof2.28wasascribedtotheveryhighsterichindranceof thephosphoruscenterinthatcompound.therefore,toassurecompleteconversion tothecorrespondingselenideforeachmolecule,allreactionswerecarriedoutat50 Cforonehour.Theformationoftheselenides2.3472.38wasconfirmedbyFABC 32