Transcription of ORGANOMETALLIC CHEMISTRY
1 ORGANOMETALLICCHEMISTRY1 OrganometallicChemistry(Prelude)2 What is ORGANOMETALLIC CHEMISTRY ?Organometallicchemistryreferst oreactionsthatusetheclassesofcompounds(R -M) (metallation)orbyreplacementofametalinan organometalliccompoundwithanothermetal(t ransmetallation).12:44 PMOrganometallicChemistry3 WhyGoOrganometallicChemistryWhatissospec ialabouttheOrganometallicapproachtoorgan icsynthesis? , :44 , :44 PMOrganomagnesiumor grignard Reagents5 TheGrignardreagentsprovedtobeveryreactiv ecarbanionnucelophilesandstrongbasescapa bleofabstractinghighlyacidicprotonsattac hedtoheteroatomssuchasO,NandS, :44 PMReactions of grignard Reagents6 TheGrignardreagentsreactasnucleophileswi thvariouselectrophilesGrignardreagentsre actasbaseswhentreatedwithcompoundswithan acidichydrogenattacheddirectlytoaheteroa tomsuchaswater,alcohols,aminesorthiols:E xampleExampleReactionswithaldehydes,keto nesandestersprovidealcoholsTerminal alkynes are also.
2 44 PMReactions of grignard Reagents7 Reactionswithcarbondioxidefollowedbyacid ificationprovidecarboxylicacidsReactions withnitrilestoiminiumsaltsfollowedbyhydr olysisprovideketonesExampleExampleReacti onswithorthoformatesfollowedbyhydrolysis providealdehydesExample12:44 :(sp>>sp2>>sp3)Notethatspcarbonsbyvirtue ofhavingmorescharacteraremoreelectronwit hdrawingandthereforecapableofstabilizing acarbanion-chargemuchmoreeffectivelythan sp3carbons,whichhavegreaterpcharacter.(a )Lithium-HalogenexchangeOrganolithiumRea gents9 Lithium-halogenexchangereactionsproceedi nthedirectionofformingthemorestableorgan olithiumreagent,thatis, , :44 (transmetalation) (stereospecific) (b)MetalationExample(c)TransmetalationAl thoughorganolithiumreagentsaremorereacti vethanGrignardreagents, :44 PMOrganozincReagents11 Organozinchalidescanbepreparedbyeitherth ereactionofanactivatedhalidewithzincmeta l(dust)oraGrignardororganolithiumreagent withazincsalt(commonlyZnCl2).
3 Anattractivefeatureoforganozinccompounds isthatmanyofthefunctionalgroups(suchases ters) , :44 PMOrganozincReagents12 ExampleOrganozincreagentsare,however, ,ketonesandesters,organozincreagentsreac treadilywithaldehydes,lessreadilywithket ones, (zinc-halogen) :44 PMSimmons-Smith Reaction13 Averyeffectivemeansforcyclopropanationof alkenesbytransferofaCH2unitemploysanorga nozincreagentderivedfromamixtureofmethyl eneiodide(CH2I2)andazinc-coppercouple, :(i)Aconcertedreactionmechanismispresume dtoapply(ii)Thecyclopropanationoccurssyn stereospecifically(iii)Electron-richalke nessuchasthosewithhigheralkylsubstitutio nreactfaster(iv)Electron-donatingsubstit uents(enolethersandenamines)alsoacceller atereaction.
4 (v) (Et2Zn)anddiidomethane(methyleneiodide). ByexaminingthepolarityoftheC-IandC-Znbon ds, ,itdoesn't, :44 PMOrganozincReagents(Simmons-Smith Reaction)14 Examples12:44 PMOrganocuprateReagents15 TheGilmanreagents(lithiumdialkylcuprates )arepreparedbyaddingaCu(i)salttoanorgano lithium(2equiv).Therearetwotypesoforgano cupratereagentsthatarecommonlyencountere d:(a)Lowerorderorganocuprates(homocuprat esandmixedcuprates)(b)Higherorderorganoc upratesLowerorderorganocuprates(Gilmanre agents)ExampleOrganocuprateReagents16 HigherorderorganocupratesThehighorderorg anocuprates(lithiumdialkylcyanocuprates) arepreparedbyaddingCuCNtoanorganolithium (2equiv).
5 ExampleThehigherorderorganocupratesarequ alitativelysimilartothelowerorderorganoc uprates, :44 PMReactions of OrganocuprateReagents17 Themostimportantreactionsoforganocuprate sarethecouplingreactionswithhalides,conj ugateadditionstoa,b-unsaturatedcarbonylc ompoundsandadditionstoalkynes.(a)Lithium dialkylcupratesdisplacebromidesandiodide sfromavarietyofsubstrates(alkyl,arylanda lkenyl). of OrganocuprateReagents19(b) ,butnotthatofthelesserreactivecarbonylof analdehyde, Additions of (d)Althoughorganocupratesdonotreactwiths aturatedaldehydesandketones,theyundergoc onjugate-additionwitha, (III)species, , :44 PMConjugate Addition of ,theproductsofconjugateadditiontoa,b-uns aturatedcarbonylcompoundsareenolatesand, therefore, :44 PMConjugate Additions of Organocuprates22 Example(f) reactions of Organocuprates23 Example(f) reactions of :Example12:44 PMPalladium-CatalysedReactions of :Suzuki-MiyauraReactionWhat is its synthetic potential?
6 27 Considertheoptionsavailableinthesyntheti cproblemhighlightedbelow:Weighingtheopti ons:12:44 PMSuzuki-MiyauraReaction28 Mostarylhalidesarecommerciallyavailable, :44 (a)Transmetallationoforganolithiumororga nomagnesiumreagentswithtrimethylborateal lowsaccesstovariousboronateesters:Exampl eSynthesisoftheBoronateEstersforSuzukiRe action12:44 PMSuzuki-MiyauraReaction30 ExampleExample(b)Palladium-catalysedreac tionofarylhalidesorvinylichalideswithbis (pinacolato)diboron:(c)Hydroborationofte rminalalkyneswithcatecholborane12:44 PMSuzuki-MiyauraReaction31 Although,Pd(PPh3)4,isthemostreactivecata lyst, ;Consequently,itisusedinconjunctionwithP Ph3togeneratethemorereactivePd(PPh3) (PPh3)4inwhichPd(0) (II)salts,whichserveasprecatalysts;being reducedtotheactivePd(0) :44 PMMechanism of Suzuki-MiyauraReaction32 Thebasicstepsinthecross-couplingreaction include:(i)oxidativeadditionofthearylorv inylhalidetoPd(0),followedby(ii)Transmet allation(thetransferofanorganicligandfro mtheorganometallicreagenttotheresultingP d(II)intermediate).
7 (iii)ThedisubstitutedPd(II)intermediatet henundergoesareductiveelimination,whichg eneratesthecarbon-carbonbondcouplingprod uctandregeneratesthecatalyticallyactiveP d(0) :44 PMGeneral Reaction33 SchematicReactionMechanismExample:Quinol ineresiduesarecommoninmanyDrugs12:44 PMMechanism of Suzuki-MiyauraReactionOlefin Ring Closing Metathesis (RCM) Ring Closing Metathesis (RCM)35 Althoughallcatalyticsystemsareinprincipl ereversible, :44 PMOlefin Ring Closing Metathesis (RCM)36 Scope of RCME xamplesFive,six, (formationoflargeringcyclicesters) of Ring Closing Metathesis (RCM)37 AplausiblereactionmechanismforthisRCMiss hownbelow:ConsideratypicalRCMofhepta-1,6 - :44 PM
