Alderkoss

Ab-CarboneliminationstrategyforconvenientinsituaccesstocyclopentadienylmetalcomplexesG.
Smits,aB.
Audic,aM.
D.
Wodrich,bC.
Corminboeuf*bandN.
Cramer*aTheelectronicandstericpropertiesoftailoredcyclopentadienyl(Cp)ligandsarepowerfulhandlestomodulatethecatalyticpropertiesoftheirmetalcomplexes.
Thisrequirestheindividualpreparation,puricationandstorageofeachligand/metalcombination.
Alternative,ideallyinsitu,complexationprotocolswouldbeofhighutility.
WediscloseanewapproachtoaccessCpmetalcomplexes.
Commonmetalprecursorsrapidlyreactwithcyclopentadienylcarbinolsviab-carboneliminationstodirectlygivetheCp-metalcomplexes.
Anadvantageofthisisthedirectandexibleuseofstorablepre-ligands.
NoauxiliarybaseisrequiredandtheCpcomplexescanbepreparedinsituinthereactionvesselforsubsequentcatalytictransformations.
IntroductionCyclopentadienyl(Cp)-coordinatedtransition-metalcomplexesareubiquitousandmanyofthemareecientcatalystsforabroadrangeofversatile,atom-economictransformations.
1Manyofthesereactionshavehighlyoptimizedconditions,butusecommerciallyavailablecomplexeswithaconservedCp*orCpligand.
Onlyrecently,themodulationoftheelectronicandstericpropertiesoftailoredCpligandswasrecognizedasapowerfultooltoovercomesluggishreactivity,2toaddressregio-andpositionalissues,3andprovideentrytoenantiose-lectiveprocesses.
4Inrapidreactiondiscoveryandoptimization,theabilitytocombinealibraryofligandswithalibraryofmetalcomplexes,performinganinsitucomplexationtogivethedesiredcatalystspeciesisarelevantadvantage.
Whilethisapproachisverycommonforreactionsinvolving,forinstance,phosphineligands,itisstillelusiveforCpligands.
Inthiscase,eachligand/metalcombinationhastobesynthesizedindivid-ually,puriedandstockedpriortoanyuseincatalysis.
ThetypicalcomplexationofcommonCp*andCpcomplexesinvolvesthemetalasalimitingreagent.
5However,highlyelaborateCporchiralCpxligandsrequiretheuseoftheCpHderivativeasthelimitingreactant.
InparticularforchiralCpxligands,onehastorelyonundesirablereactionconditions,forexampleinvolvingthalliumalkoxideinbenzene.
4d,6Theseshortcomingsmakethedevelopmentofcomplementarycomplexationstrategiesapriority.
Ideally,suchtechnologyproceedsrapidlyandinaquantitativemanner,withoutthegenerationofinhibitingreactionbyproducts.
Itshouldalsobeuseablewitharangeofdierenttransition-metals.
b-Carboneliminationhasbeenreportedasacomplementarymethodtoaccessorganometallicspeciesincatalysis.
7Normallytheforwardreaction–theadditionacrossacarbonylgroup–isfavoredandreversingthispathwayrequiressomeadditionaldrivingforce.
Thiscouldbeacombinationofusingtherighttransition-metalandtheuseofsubstratesleadingtotheformationofstrongerCsp–[M]8orCsp2–[M]bonds.
9Thegener-ationofCsp3–[M]bondsrequiresenergy-richstartingmaterials,suchastert-cyclobutanols10,releasingstrainuponb-Celimi-nation.
11Aparticularclassofsubstrateisthatofhomoallylicalcoholsthatcangivep-boundallyl-metalspeciesbyretro-allylation.
12Alongthesamelines,acyclopentadienylcarbinolwouldgiveaCp–[M]speciesuponC–Cbondcleavage.
Theverystrongbondofthecyclopentadienylaniontothetransition-metalwouldbeaverystrongdrivingforce.
Sofar,theb-Celiminationmethodologyhasbeenusedexclusivelyasanelementarystepincatalytictransformations.
HereinweexploititspotentialforthepreparationofCp-metalcomplexes(Scheme1).
ResultsanddiscussionTherequiredcyclopentadienylcarbinolsubstratesforthepre-ligandsareaccessedinastraightforwardmannerbydeproto-nationandadditionacrossthedesiredaldehydeorketone(Scheme2,seeESIfordetails).
13IncontrasttomanylightlysubstitutedcyclopentadieneswhichfrequentlyundergoDiels–Alderdimerization,allpreparedCp-carbinolsarestableanddonotdimerizeuponstorage.
Exemplarilyfor[Rh(cod)OH]2,ligandexchangeofthehydroxyligandby2wouldbreakuptheaLaboratoryofAsymmetricCatalysisandSynthesis,EPFLSBISICLCSA,BCH4305,CH-1015Lausanne,Switzerland.
E-mail:nicolai.
cramer@ep.
chbLaboratoryforComputationalMolecularDesign,EPFLSBISICLCMD,BCH5312,CH-1015Lausanne,Switzerland.
E-mail:clemence.
corminboeuf@ep.
chElectronicsupplementaryinformation(ESI)available:Experimentalproceduresandcharacterisationofallnewcompounds.
SeeDOI:10.
1039/c7sc02986aPresentaddress:LaboratoryofCNSActiveCompounds,LatvianInstituteofOrganicSynthesis,Aizkraukles21,LV-1006,Riga,Latvia.
Citethis:Chem.
Sci.
,2017,8,7174Received7thJuly2017Accepted24thAugust2017DOI:10.
1039/c7sc02986arsc.
li/chemical-science7174|Chem.
Sci.
,2017,8,7174–7179ThisjournalisTheRoyalSocietyofChemistry2017ChemicalScienceEDGEARTICLEdimerandreleaseamoleculeofwatertogiveintermediate3.
Inturn,3ispredisposedforthenalb-CeliminationsteptoyieldtheCpmetalcomplex4aandketone1.
Aselectionofcarbinolswithstericallyandelectronicallydierentsubstituents,R1andR2,wereinitiallyevaluated(Table1).
Avarietyoffactorsinuencedthereactionperformance.
AnaromaticsubstituentR1orR2wasfoundtobebenecialforyieldandreactivity.
Atertiaryhydroxylgroupisbetterthanasecondaryone.
Strainedketonederived2fand2g(entries6–7)partiallyunderwentthealternativestrain-releasepathway,10openingthefour-memberedringinsteadofleadingtotheCp-metalspecies.
Mostsubstratesrequiredtheadditionofcesiumcarbonateforshorterreactiontimes.
Withouttherhodiumcomplex,carbinols2arestableandnoconversiontofreeCp*Hwasobserved.
Notably,somesubstratesdisplayedsignicantlyincreasedreactivityanddidnotrequiretheaddi-tionofanybase(entries8,10,13,and15).
Thetwofastestreactionswere2h(Ph/CO2Me)and2m(Ph/Me).
Amongthetestedsubstrates,thedimethyl-typecarbinolmoietywasfurtherinvestigated,despiteitslowerreactivity,asitreleasesonlyvolatileacetoneasabyproduct(Table2).
Itprovidesacleancomplexationgivingarangeofcomplexes4withdierentbulks,rangingfromMe3Cp(entry1)totBuMe4Cp(entry5).
Whilesubstrateswithbulkygroupsreactverysmoothly,lesssubstitutedoneslikethetrimethylCpprecursor5breactlessecientlyduetosomefulvenebyproductforma-tion.
Indenylcomplexescanbepreparedwithsimilareciency(entries6–7).
Methylphenylglyoxylateandacetophenonederivedpre-ligands5iand5jareeasiertoaccessandbettersuitedinthecomplexationgiving,asbefore,fastandcleantransformationswithouttherequirementofabasicadditive(entries8–9).
Importantly,thiscomplexationstrategyisequallysuccessfulforchiralCp*ligandsequippedwithouratropchiralbackbone.
4f–iImportantly,theb-Celiminativecomplexationisnotlimitedtorhodium.
Forinstance,using[Ir(cod)OH]2asthemetalsaltprovidedaccesstoindenylIr(cod)andcyclo-pentadienylcomplexes6g–6jincomparableyields(entries6–9).
ExposureofthechiralCpx*pre-ligand5ktothereactionconditionsinducedasmoothcomplexation,providingrhodiumcomplex4kin93%yield(entry10).
Thisisparticularlynote-worthyasclassicalcomplexationmethods4d,fforadi-substitutedchiralCpxligandfailedcompletelyforthischiralpenta-substitutedanalog.
Analogously,thechiraliridiumcomplex6kcouldbeobtainedin87%yield.
Moreover,wecouldextendthemethodforthepreparationofachiralCpx*CoIIIcomplex7k(entry11).
Forthersttime,chiralfullypenta-substitutedcyclopentadienylrhodium,iridiumandcobaltcomplexesarenowaccessible.
Thissetsthestageforfutureapplicationsinasymmetriccatalysis,especiallyfortransformationswherepreviouslyreportedcomplexeswiththedisubstitutedchiralvariants4a,bfailedtoprovideadequatereactivity.
Besidesthehydroxylbridgeddimer,other[Rh(cod)X]2complexes(XOMe,OAc,andCl)canbeused(Table3,entriesScheme1Generationoforganometallicsusingtheb-carbonelimi-nationstrategy.
Scheme2(a)SynthesisofCppre-ligandcarbinols2.
(b)Envisionedb-CeliminationtoaccessCp*Rh(I)complexes.
Table1Evaluationoftheinuenceofthecarbinolsubstituentsonb-CeliminationaEntry2R1R2AdditiveTime%yieldb12aHnPentylCs2CO33h3922bHPhCs2CO31h9532cHCO2EtCs2CO33h1042dMeMeCs2CO33h9952eCH2(CH2)3CH2Cs2CO33h9362fCH2CH2CH2Cs2CO31h3072gCH2OCH2Cs2CO33h2082hCO2MePh—15min7592iCO2MeMeCs2CO33h75102jCO2MetBu—1h45112kCO2MeCF3Cs2CO31hKosslerandN.
Cramer,J.
Am.
Chem.
Soc.
,2016,138,3935;(b)B.
YeandN.
Cramer,Acc.
Chem.
Res.
,2015,48,1308forselectedexamples,see:(c)G.
ErkerandA.
A.
H.
vanderZeijden,Angew.
Chem.
,Int.
Ed.
,1990,29,512;(d)B.
YeandN.
Cramer,Science,2012,338,504;(e)T.
K.
Hyster,L.
Knorr,T.
R.
WardandT.
Rovis,Science,2012,338,500;(f)B.
YeandN.
Cramer,J.
Am.
Chem.
Soc.
,2013,135,636;(g)D.
KosslerandN.
Cramer,J.
Am.
Chem.
Soc.
,2015,137,12478;(h)G.
Song,W.
N.
O.
WylieandZ.
Hou,J.
Am.
Chem.
Soc.
,2014,136,12209;(i)M.
Dieckmann,Y.
-S.
JangandN.
Cramer,Angew.
Chem.
,Int.
Ed.
,2015,127,12317.
5(a)R.
Dubois,US4962253A,TheDowChemical,1990;(b)R.
B.
King,Inorg.
Chem.
,1963,2,528;(c)M.
D.
RauschandR.
A.
Genetti,J.
Org.
Chem.
,1970,35,3888;(d)N.
Weding,R.
Jackstell,H.
Jiao,A.
SpannenbergandM.
Hapke,Adv.
Synth.
Catal.
,2011,353,3423;(e)C.
White,A.
Yates,P.
M.
MaitlisandD.
M.
Heinekey,inInorg.
Synth.
,JohnWiley&Sons,Inc.
,2007,p.
228;(f)H.
Chen,J.
HartwigandT.
C.
Semple,WO01/64689A1,ShellInternationaleResearchMaatschappijB.
V.
,YaleUniversity,2001.
6(a)T.
E.
Bitterwolf,T.
L.
HublerandA.
L.
Rheingold,J.
Organomet.
Chem.
,1992,431,199;(b)B.
G.
ConwayandM.
D.
Rausch,Organometallics,1985,4,688;(c)P.
G.
GassmanandC.
H.
Winter,J.
Am.
Chem.
Soc.
,1986,108,4228;(d)S.
S.
Jones,M.
D.
RauschandT.
E.
Bitterwolf,J.
Organomet.
Chem.
,1993,450,27.
7Forareview,see:(a)D.
J.
MackandJ.
T.
Njardarson,ACSCatal.
,2013,3,272;(b)T.
SeiserandN.
Cramer,Synlett,2011,4,449;(c)M.
MurakamiandT.
Matsuda,Chem.
Commun.
,2011,47,1100;(d)K.
Ruhland,Eur.
J.
Org.
Chem.
,2012,14,2683;(e)M.
MiuraandT.
Satoh,inPalladiuminOrganicSynthesis,ed.
J.
Tsuji,SpringerBerlinHeidelberg,Berlin,Heidelberg,2005,pp.
1–20.
8Forselectedexamples,see:(a)R.
Shintani,K.
Takatsu,T.
Katoh,T.
NishimuraandT.
Hayashi,Angew.
Chem.
,Int.
Ed.
,2008,47,1447;(b)A.
Horita,H.
Tsurugi,A.
Funayama,T.
SatohandM.
Miura,Org.
Lett.
,2007,9,2231;(c)T.
Nishimura,T.
Katoh,K.
Takatsu,R.
ShintaniandT.
Hayashi,J.
Am.
Chem.
Soc.
,2007,129,14158;(d)R.
Shintani,K.
Takatsu,T.
Katoh,T.
NishimuraandT.
Hayashi,Angew.
Chem.
,Int.
Ed.
,2008,47,1447;(e)A.
Funayama,T.
SatohandM.
Miura,J.
Am.
Chem.
Soc.
,7178|Chem.
Sci.
,2017,8,7174–7179ThisjournalisTheRoyalSocietyofChemistry2017ChemicalScienceEdgeArticle2005,127,15354;(f)T.
Nishimura,H.
Araki,Y.
MaedaandS.
Uemura,Org.
Lett.
,2003,5,2997.
9Forselectedexamples,see:(a)X.
Yu,J.
Wang,W.
Guo,Y.
TianandJ.
Wang,Organometallics,2016,35,1876;(b)E.
Ozkal,B.
CacheratandB.
Morandi,ACSCatal.
,2015,5,6458;(c)J.
R.
Bour,J.
C.
Green,V.
J.
WintonandJ.
B.
Johnson,J.
Org.
Chem.
,2013,78,1665;(d)H.
Li,Y.
Li,X.
-S.
Zhang,K.
Chen,X.
WangandZ.
-J.
Shi,J.
Am.
Chem.
Soc.
,2011,133,15244;(e)T.
Uto,M.
Shimizu,K.
Ueura,H.
Tsurugi,T.
SatohandM.
Miura,J.
Org.
Chem.
,2008,73,298;(f)M.
Nakano,T.
SatohandM.
Miura,J.
Org.
Chem.
,2006,71,8309;(g)P.
Zhao,C.
D.
IncarvitoandJ.
F.
Hartwig,J.
Am.
Chem.
Soc.
,2006,128,3124;(h)Y.
Terao,M.
Nomoto,T.
Satoh,M.
MiuraandM.
Nomura,J.
Org.
Chem.
,2004,69,6942;(i)Y.
Terao,H.
Wakui,T.
Satoh,M.
MiuraandM.
Nomura,J.
Am.
Chem.
Soc.
,2001,123,10407.
10(a)N.
Ishida,N.
Ishikawa,S.
Sawano,Y.
MasudaandM.
Murakami,Chem.
Commun.
,2015,51,1882;(b)L.
SouillartandN.
Cramer,Chem.
Sci.
,2014,5,837;(c)N.
Ishida,S.
SawanoandM.
Murakami,Chem.
Commun.
,2012,48,1973;(d)N.
Ishida,S.
Sawano,Y.
MasudaandM.
Murakami,J.
Am.
Chem.
Soc.
,2012,134,17502;(e)T.
SeiserandN.
Cramer,J.
Am.
Chem.
Soc.
,2010,132,5340;(f)T.
SeiserandN.
Cramer,Chem.
–Eur.
J.
,2010,16,3383;(g)T.
Seiser,O.
A.
RothandN.
Cramer,Angew.
Chem.
,Int.
Ed.
,2009,48,6320;(h)M.
Shigeno,T.
YamamotoandM.
Murakami,Chem.
–Eur.
J.
,2009,15,12929;(i)S.
Matsumura,Y.
Maeda,T.
NishimuraandS.
Uemura,J.
Am.
Chem.
Soc.
,2003,125,8862;(j)R.
C.
Laroc,ChandK.
Reddy,Org.
Lett.
,2000,1,3325;(k)T.
NishimuraandS.
Uemura,J.
Am.
Chem.
Soc.
,1999,121,11010.
11P.
R.
Khoury,J.
D.
GoddardandW.
Tam,Tetrahedron,2004,60,8103.
12Forareviewsee:(a)H.
YorimitsuandK.
Oshima,Bull.
Chem.
Soc.
Jpn.
,2009,82,778forselectedexamples,see:(b)M.
WaibelandN.
Cramer,Angew.
Chem.
,Int.
Ed.
,2010,49,4455;(c)R.
Wakabayashi,D.
Fuijino,S.
Hayashi,H.
YorimitsuandK.
Oshima,J.
Org.
Chem.
,2010,75,4337;(d)M.
Iwasaki,S.
Hayashi,K.
Hirano,H.
YorimitsuandK.
Oshima,J.
Am.
Chem.
Soc.
,2007,129,4463;(e)S.
Hayashi,K.
Hirano,H.
YorimitsuandK.
Oshima,J.
Am.
Chem.
Soc.
,2006,128,2210;(f)T.
Kondo,K.
Kodoi,E.
Nishinaga,T.
Okada,Y.
Morisaki,Y.
WatanbeandT.
Mitsudo,J.
Am.
Chem.
Soc.
,1999,120,5587;(g)J.
Nokami,K.
Yoshizane,H.
MatsuuraandS.
Sumida,J.
Am.
Chem.
Soc.
,1998,120,6609.
13M.
Uemura,K.
Yagi,M.
Iwasaki,K.
Nomura,H.
YorimitsuandK.
Oshima,Tetrahedron,2006,62,3523.
14(a)J.
P.
Perdew,K.
BurkeandM.
Ernzerhof,Phys.
Rev.
Lett.
,1996,77,3865;(b)C.
AdamoandV.
Barone,J.
Chem.
Phys.
,1999,110,6158.
15(a)S.
N.
SteinmannandC.
Corminboeuf,J.
Chem.
TheoryComput.
,2010,6,1990;(b)S.
N.
SteinmannandC.
Corminboeuf,Chimia,2011,65,240;(c)S.
N.
SteinmannandC.
Corminboeuf,J.
Chem.
Phys.
,2011,134,044117;(d)S.
N.
SteinmannandC.
Corminboeuf,J.
Chem.
TheoryComput.
,2011,7,3567.
16(a)Y.
ZhaoandD.
G.
Truhlar,Acc.
Chem.
Res.
,2008,41,157;(b)Y.
ZhaoandD.
G.
Truhlar,Theor.
Chem.
Acc.
,2008,120,215.
17A.
Klamt,WIREsComput.
Mol.
Sci.
,2011,1,699.
18M.
D.
Wodrich,B.
Ye,J.
F.
Gonthier,C.
CorminboeufandN.
Cramer,Chem.
Eur.
J.
,2014,20,15409.
19(a)B.
DeBoef,S.
J.
PastineandD.
Sames,J.
Am.
Chem.
Soc.
,2004,126,6556;(b)C.
P.
Langes,P.
S.
WhiteandM.
Brookhart,J.
Am.
Chem.
Soc.
,1999,121,4385.
20T.
Kang,Y.
Kim,D.
Lee,Z.
WangandS.
Chang,J.
Am.
Chem.
Soc.
,2014,136,4141.
ThisjournalisTheRoyalSocietyofChemistry2017Chem.
Sci.
,2017,8,7174–7179|7179EdgeArticleChemicalScience