Migratory Insertion of Alkenes into MetalOxygen and MetalNitrogen Bonds

17 Pages·2013·1.15 MB·English

by  Anneke Runtupalit

Lawrence Berkeley National Laboratory
Recent Work
Title
Iridium-Catalyzed, Intermolecular Hydroetherification of Unactivated Aliphatic Alkenes with
Phenols
Permalink
https://escholarship.org/uc/item/5xd8s951
Journal
Journal of the American Chemical Society, 135(25)
ISSN
0002-7863
Authors
Sevov, Christo S.
Hartwig, John F.
Publication Date
2013-06-26
eScholarship.org Powered by the California Digital Library
University of California
Angew.andte
J.F. Hartwig andP.S. Hanley
Minireviews
DOI:10.1002/anie.201300134
Organometallic Reactions
Migratory Insertion of Alkenes into Metal–Oxygen and
Metal–Nitrogen Bonds
Patrick S. Hanley and John F. Hartwig*
amination·organometallicreactions·palladium·
insertion·reactionmechanisms
T
he insertion of an unsaturated ligand into a M C or M H bond
! !
proceeds through migratory insertion, a fundamental organometallic
reaction. Recent literature documents evidence of the migratory
insertion of alkenes into an M O and M N bonds for alkene alkox-
! !
ylation and alkene amination reactions, respectively. Herein we
provide an overview of the literature and a perspective on how these
recent experiments relate to classic experiments on C O and C N
! !
bond formation with alkene complexes of the late transition metals.
Introduction tionalization of alkenes,[15–18] and the olefination of aryl
halides(commonlytermedtheMizoroki–Heckreaction).[19–22]
Migratory insertion is a fundamental organometallic Inmostcases,theunsaturatedligandinsertsintoametal–
reaction. It is a concerted reaction that combines an carbon (M C) or metal–hydrogen (M H) bond. Related
! !
unsaturated ligand with an adjacent metal–ligand bond to insertions of alkenes into metal–oxygen (M O) and metal–
!
formaproductcontaininganewligandwiththeunsaturated nitrogen (M N) bonds are much less common (Scheme1).
!
group formally inserted into the original covalent metal– Overthepastdecade,however,severalpapershavedescribed
ligand bond (Scheme1). A variety of unsaturated ligands palladium-catalyzed alkene alkoxylation and alkene amina-
undergo migratory insertion, including carbon monoxide, tion reactions for which stereochemical data implies that
carbon dioxide, alkenes, alkynes, ketones, aldehydes, and migratoryinsertionofanalkeneoccursintoanM OorM N
! !
imines,andmigratoryinsertionisacommonstepinnumerous bond. Moreover, the first isolated transition metal amido
catalytic reactions, including hydroformylation,[1,2] hydroge- complexesthatinsertunactivatedalkeneshavebeenreported
nation,[3–5] polymerization,[6–9] hydroarylation,[10–14] difunc- in the past few years. These recent publications on isolated
amidocomplexesincludeinformationonthefactorscontrol-
lingtherateofinsertion.
Althoughthefirstexamplesofinsertionofanalkeneinto
a metal–heteroatom bond were reported more than two
decades ago, experiments on the insertions of alkenes into
isolatedmetalamidocomplexesarerare.Anopencoordina-
tion site is necessary for alkene coordination prior to
insertion,andmanyalkoxoandamidocomplexesformstable
multinuclear structures if the metal center is coordinatively
unsaturated. Thus, preparation of monomeric amido com-
plexes containing an open coordination site to bind and
Scheme1. MigratoryinsertionofanalkeneoralkyneintoM Rand
! subsequently insert alkenes is difficult, and the absence of
M Xbonds.
! such complexes has meant that the factors which control
insertionsofalkenesintometal–heteroatombondshavebeen
poorlyunderstood.
[*] Dr.P.S.Hanley,Prof.J.F.Hartwig
Many alkene complexes have been prepared and react
DepartmentofChemistry,UniversityofIllinoisUrbana-Champaign
withnucleophilesbyattackontothecoordinatedalkene.As
Urbana,IL61801(USA)
discussed below, the classic Wacker reaction has been
Prof.J.F.Hartwig
proposed to occur by this elementary reaction, rather than
UniversityofCalifornia,DepartmentofChemistry
718LatimerHall,Berkeley,CA94720(USA) migratory insertion. Although the product of migratory
E-mail:[email protected] insertion and nucleophilic attack on a coordinated alkene
8510 !2013Wiley-VCHVerlagGmbH&Co.KGaA,Weinheim Angew.Chem.Int.Ed.2013,52,8510–8525
Angewandte
MigratoryInsertion Chemie
the section on this topic is divided into three subsections:
1)The description of catalytic reactions involving insertions
of alkenes into bonds between nitrogen and lanthanide,
actinide, alkaline earth, and early transition metals, 2)the
description of catalytic reactions involving the insertion of
alkenesintolate-transition-metal–nitrogenbonds,and3)the
description of reactions of discrete amido complexes with
alkenes that likely occur by a migratory insertion of the
alkeneintotheM Nbond.
!
Scheme2. MigratoryinsertionofanalkeneintoM Xbondsversus
!
nucleophilicattackofXontoacoordinatedalkene.
Reactions Occurring by Migratory Insertion of
Olefins into M O Bonds
!
contain the same connectivity, the stereochemistry of the
products of the two reactions is different. As shown in The oxidative functionalization of alkenes is the one of
Scheme2, the migratory insertion pathway leads to the the most widely used processes catalyzed by soluble transi-
oppositerelativeconfigurationsofthea-andb-carbonatoms tion-metalcomplexes.Theoxidationofethyleneinwaterwith
of the resulting alkyl complex. Ongoing work has sought to apalladiumcatalyst,commonlytermedtheWackerprocess,is
reveal what complexes and reaction conditions lead to used to produce 2!106tons of acetaldehyde annually
insertion and what complexes and reaction conditions lead
tonucleophilicattackonthecoordinatedalkene.Recentdata
that begins to address this issue are included in this Mini-
review.
To develop new, selective metal-catalyzed olefin alkox-
Scheme3. TheWackerprocess.
ylation and amination reactions, fundamental knowledge of
the factors that control the rate and stereoselectivity of the
insertion of alkenes into M O and M N bonds is needed. (Scheme3).[23] The metal-mediated formation of new C O
! ! !
Thesefactorsarejustbeginningtoberevealed.Thus,oneaim bondsbythe additionofanoxygennucleophiletoanolefin
of this Minireview is to provide a perspective on how these was thought for many years to occur exclusively by nucleo-
recentexperimentsrelatetoclassicexperimentsonC Oand philic attack of an oxygen nucleophile onto a metal-coordi-
!
C N bond formation with alkene complexes of the late nated olefin. Well-characterized metal olefin complexes had
!
transitionmetals,andtosummarizetheexistingliteratureon beenprepared,andalcoholswereshowntoaddtothealkene
chemistry involving migratory insertion of alkenes into the ofthesecomplexesatthefaceoppositethemetalcenter.[24–27]
M N and M O bonds of isolated metal amido and metal Thus, metal-catalyzed additions of oxygen nucleophiles to
! !
alkoxo complexes, respectively. We will also describe mech- olefins were typically assumed to occur by antiaddition.
anistic studies of catalytic amination and alkoxylation reac- However,alkoxometalolefincomplexesthatreactbymigra-
tions,thatofferinsightintothemigratoryinsertionstep. toryinsertionhaverecentlybeenidentified.Inthissection,we
Wehaveseparatedthisreviewintotwosections.Thefirst describecatalyticreactions,includingtheWackerprocess,for
sectionisdividedintotwosubsections:1)Thedescriptionof whichmechanisticdataimpliesthattheC Obondisformed
!
catalyticreactionsforwhichevidenceofalkeneinsertioninto byinsertionofanalkeneintoanM Obond.Stoichiometric
!
an M O bond has been gained, and 2)the description of reactionsofalkoxocomplexeswithalkeneswillbediscussed
!
stoichiometric reactions of alkoxo complexes with alkenes. indetail.
The second section describes chemistry involving migratory
insertions of alkenes into M N bonds. Because more data
!
have been published on alkene insertions into M N bonds,
!
JohnHartwigistheHenryRapoportProfes- PatrickHanleyreceivedhisB.S.fromWest
sorattheUniversityofCalifornia,Berkeley. VirginiaUniversityin2008underthedirec-
Hisgroupseekstodiscovernewreactions tionofProf.JeffreyL.Petersen.Hecom-
catalyzedbytransition-metalcomplexesand pletedhisPh.D.in2012attheUniversity
torevealnewreactionmechanisms.He ofIllinoisatUrbana-Champaignunderthe
recentlyauthoredthetextbook“Organo- directionofProf.JohnF.Hartwig,studying
transitionMetalChemistry:FromBonding newcarbon–nitrogenbond-formingreac-
toCatalysis”.Heisthe2006recipientof tionsofpalladium.Currently,heisaSenior
theACSAwardinOrganometallic ChemistatTheDowChemicalCompanyin
Chemistryandthe2013ACSH.C.Brown Michigan.
AwardinSyntheticMethods.Hewas
electedtotheNationalAcademyofScien-
cesin2012.
Angew.Chem.Int.Ed.2013,52,8510–8525 !2013Wiley-VCHVerlagGmbH&Co.KGaA,Weinheim www.angewandte.org 8511
Angew.andte
J.F. Hartwig andP.S. Hanley
Minireviews
CatalyticReactionsInvolvingAlkeneInsertionintoM OBonds
!
ThemechanismoftheWackerprocesshasbeendisputed
for the last four decades. Early kinetic data on the Wacker
oxidation were consistent with a mechanism involving
synaddition of a preformed palladium-hydroxo complex
across ethylene.[28] However, experiments conducted by
Akermark, Stille, B"ckvall, and co-workers demonstrated
thatpalladiumligatedwithsubstitutedordeuterium-labeled
alkenes formed products by antioxypalladation.[29–32] For
example, the addition of CO to the combination of bis[(cis-
[D]ethylene)PdCl]andHOinabufferedsolutionofCuCl
2 2 2 2
andNaOAcledtotheformationoflactoneproducts,andthe
configuration of the carbon atoms in the lactone indicated
thatanantiadditionoftheoxygenatomandpalladiumtothe
ethylenehadoccurred.[30]Infact,B"ckvall,Siegbahn,andco-
workers stated that a hydroxymetal olefin complex is too
unreactive to undergo cis migration of an OH ligand to
aboundalkene.[33]
Henry andco-workers correctly noted thatthese experi-
mentswereconductedunderreactionconditionsdistinctfrom
thoseofthecatalyticWackerreaction.TheWackerprocessis
typicallyconductedwithlowchlorideconcentrations.Henry
andco-workersexaminedthehydroxylationofallylicalcohols
and demonstrated that the stereochemical outcome of the
oxypalladation step is different at high and low concentra-
tions of chloride ion. At high chloride ion concentration,
productsfromantioxypalladationwereobserved,butatlow
chloride ion concentration the stereochemical configuration
of the observed products indicated that synoxypalladation,
presumablybymigratoryinsertionofanalkeneintoametal–
alkoxobond,occurred.[34–39]Becausetwosetsofproductswith
different relative configurations were observed, the hydrox-
ylation of allylic alcohols must occur by two different
mechanisms. Despite these results, the mechanism of the
Scheme4. a)Oxidativecyclizationof6-(2-hydroxy-phenyl)-3-deuterio-
Wacker process was described in leading textbooks as cyclohexene.b)MechanismforformationofproductsA–Cafter
occurring by the attack of a free water molecule on synoxypalladation.M.S.=molecularsieves,TFA=trifluoroacetate.
apalladium-boundethylene.[40]
ThesestudiesofHenrywereconductedonallylicalcohols
todeterminewhethertheadditionoccurredbyasynoranti
oxypalladationprocess.Allylicalcoholsmightprovideresults resulted from antiaddition of the palladium and oxygen
that are biased toward one mechanism or another because acrosstheinternalalkene.
theycontaintwobindingsitesandmightisomerizeunderthe Stereochemical evidence for a synoxypalladation step
reaction conditions. Thus, other researchers more recently also has been gained by Stoltz etal. for similar palladium-
have studied the stereochemistry of different Wacker reac- catalyzed cyclizations of phenols and primary alcohols.[42]
tions. Treatment of a deuterium-labeled unsaturated alcohol with
Hayashi etal. assessed the stereochemistry of the oxy- 10mol% [(bpy)Pd(TFA)] (bpy=2,2’-bipyridine), 2equiva-
palladationstepintheoxidativecyclizationofano-allylphe- lents of Na2CO3, 1atm of O2, and 500mgmol!1 of 3#
nol.[41] Stereospecifically deuterated, racemic 6-(2-hydroxy- molecular sieves in toluene at 808C for 3hours generated
phenyl)-3-deuteriocyclohexenesunderwentcyclizationinthe cyclized productsin51%overall yield(Scheme5).Likethe
presence of [Pd(MeCN)(BF)] as a precatalyst and (S,S)- productsofHayashi$sexperiment,theproductsfromStoltz$s
4 4 2
2,2’-bis-(4-isopropyloxazolyl)-1,1’binaphthyl as a ligand with experimentarebestrationalizedasformingbyasynoxypal-
4equivalentsofbenzoquinoneinMeOHat408C(Scheme4). ladation (migratory insertion of the alkene into the Pd O
!
In the absence of added LiCl, a series of cyclized products bond). However, the stereochemistry of the oxypalladation
were obtained and formed by synoxypalladation by migra- process, in this case, indicated that the reactions with or
toryinsertion,followedbyaseriesofb-hydrogenelimination without added chloride anion both occurred by a syn-oxy-
andinsertionstepstogeneratethedifferentproductisomers. palladation pathway. In addition, reactions conducted with
In the presence of added LiCl, different products formed. nonchelating ligands based on pyridine occurred by a syn-
Under these reaction conditions, the major cyclized product oxypalladationpathway.
8512 www.angewandte.org !2013Wiley-VCHVerlagGmbH&Co.KGaA,Weinheim Angew.Chem.Int.Ed.2013,52,8510–8525
Angewandte
MigratoryInsertion Chemie
Scheme5. Oxidativecyclizationofo-allylphenol.
Wolfe and co-workers published a series of reports of
alkoxyarylations of alkenes. The stereochemistry of the
products from the palladium-catalyzed reaction of aryl
bromides with g-hydroxy alkenes indicated that these reac-
tions also occur by a synaddition of the palladium and the
oxygen atom across the alkene (Scheme6).[43–45] These
Scheme7. Proposedreactionmechanismoflanthanide-catalyzed
alkynehydroalkoxylation.
withtheproposedmechanisminScheme7.Althoughlantha-
nide-catalyzed cyclizations of alkenyl alcohols have been
reported,thesereactionsdonotproceedthroughapathway
involving migratory insertion of the alkene into an Ln O
!
bond.[48] The thermodynamics of the insertion of an alkyne
andaterminalalkeneintoLn Obondshavebeenexamined
!
bycalorimetryandthesedatapredictthattheinsertionofan
Scheme6. Palladium-catalyzedreactionofarylbromideswith alkyneisexothermic(DH= 13kcalmol!1),buttheinsertion
g-hydroxyalkenes.dba=dibenzylideneacetone,dpe-phos=bis[2-(di- !
of a terminal alkene is significantly endothermic (DH=
phenylphosphino)phenyl]ether.
+22kcalmol!1).[49]
reactions are highly regio- and stereoselective, thus forming
the trans-2,5-disubstituted furan products. The selectivity of ReactionsofMetalAlkoxoComplexeswithAlkenesforwhich
these products is inconsistent with a mechanism involving DirectEvidencehasbeenGainedforMigratoryInsertionintoan
transhydroxypalladationofthealkene.Theanti-hydroxypal- M OBond
!
ladationpathwaywouldgeneratesyn-1’,2-disubstitutedprod-
ucts, which are not observed. The proposed mechanism for Althoughanalysisofcatalyticolefinalkoxylationsystems
these reactions begins with oxidative addition of the aryl provided stereochemical and kinetic evidence for a syn-
bromide to a Pd0 species ligated by a bis(phosphine) and oxypalladationstepbymigratoryinsertionofanalkeneligand
subsequent transmetalation to generate a [Pd(Ar)(OR)] into a M O bond, the metal alkoxo complexes that were
!
intermediate. This intermediate undergoes selective migra- predicted to insert olefins have not been isolated and fully
toryinsertionofthependantalkeneintothePd Obondover characterized. Until recently, only a single example of an
!
thePdArbond,andtheresultingalkylpalladiumarylcomplex alkoxide complex that reacts with an olefin was reported.
undergoes C C bond-forming reductive elimination to gen- Bryndza reported the reaction of [(dppe)Pt(CH)(OCH)]
! 3 3
eratethetetrahydrofuranproduct. [dppe=1,2-bis(diphenylphosphanyl)ethane] with the highly
Catalytic olefin alkoxylation reactions proposed to pro- activated alkene, tetrafluoroethylene (TFE), in [D]THF
8
ceed by a migratory insertion pathway are not limited to (THF=tetrahydrofuran) at 258C to generate [(dppe)Pt-
palladium-catalyzed reactions. Marks and co-workers has (CH)(CFCFOCH)] in almost quantitative yield.[50] The
3 2 2 3
reported the lanthanide-catalyzed hydroalkoxylation of al- reactionisfirstorderinplatinummethoxideandtetrafluoro-
kynylandallenylalcohols.[46,47]Theactivelanthanidecatalyst ethylene. At 808C, the chemical shift of the tetrafluoro-
!
is formed by rapid protonolysis of the amide ligand of the ethylene resonance in the 19FNMR spectrum was found to
[Ln{N(TMS)}] precatalyst to generate a lanthanide alkoxo varylinearlywiththequantityofaddedTFE,thusindicating
2 3
species, which undergoes turnover-limiting migratory inser- that tetrafluoroethylene interacts with the platinum meth-
tionofthetetheredalkyneintotheLn Obond.Theresulting oxidecomplex.Tetrafluoroethylenewasproposedtobindto
!
vinyletherisprotonolyzedtoreleasethecyclizedproductand the platinum methoxide to form a five-coordinate olefin
regeneratetheactivecatalyst. complex. Upon warming to 258C, the observed alkene
Thesereactionsarefirstorderincatalystandzeroorderin complex formed a product from insertion of the alkene
alkynyl or allenyl alcohol. These kinetic data are consistent ligandintothePt Obondtoformanalkylplatinumcomplex.
!
Angew.Chem.Int.Ed.2013,52,8510–8525 !2013Wiley-VCHVerlagGmbH&Co.KGaA,Weinheim www.angewandte.org 8513
Angew.andte
J.F. Hartwig andP.S. Hanley
Minireviews
In addition, a labeling experiment showed that the dppp- cyclizationbyamigratoryinsertionpathway.Thus,thisstudy
ligatedplatinumcomplexreactstoformanewalkylcomplex provided the first evidence for reaction of an alkene with
in the presence of 10equivalents of CDOD and perfluor- adirectlyobservedmetalalkoxocomplextoformanewC O
3 !
ocyclopentenewithlessthan8%incorporationoftheOCD bondbymigratoryinsertionofthealkeneintoaM Obond.
3 !
group (Scheme8). This result indicates that the methoxide More important, the modest activation barrier for insertion
ligand does not dissociate from the platinum complex and intoaRh Obondimpliesthatmanycatalyticolefinoxidation
!
subsequently attack a coordinated olefin by an anti-oxy- reactions believed to occur by nucleophilic attack of an
platinationpathway. alkoxide onto a metal-coordinated olefin might occur,
instead, by migratory insertion of a an alkene into a metal–
alkoxidebond.
Aseriesofcomputationalstudiesontherelativeratesfor
migratory insertion of alkenes into square-planar methyl,
amido, and hydroxo complexes of rhodium have also been
published.[52] The calculated free-energy barriers for migra-
tory insertion of the alkene into the M X bond of the
!
rhodium complexes [(PMe)Rh(h2-CH=CH)(X)] (X=
3 2 2 2
CH, NH, OH) follow the trend Rh NH < Rh OH !
3 2 ! 2 !
Rh CH (Scheme10). This trend was attributed to the
! 3
Scheme8. Reactionsofplatinummethoxidecomplexeswithperfluoro-
natedalkenes.
More recently, the first well-characterized alkoxo com-
plexesthatundergomigratoryinsertionofunactivatedolefins
were reported.[51] A series of triethylphosphine-ligated rho-
dium alkoxide complexes, formed by the reaction of the
rhodium(I)silylamidocomplex[(PEt)RhN(SiMe)]witha,
3 2 3 2
w-enolsatroomtemperatureorbelow,ledtoHN(SiMe) and
3 2
the alkoxorhodium olefin complex in Scheme9. A crystal
Scheme10. Optimizedground-stateandtransition-stateenergiesfor
ethyleneinsertionintorhodium–alkyl,rhodium–amido,andrhodium–
hydroxybonds.
Scheme9. Reactionsofalkoxorhodiumalkenecomplexes.
presence of an M X dative bond in the transition state and
!
structure of the olefin complex of a more stable analogue, immediateinsertionproduct.TheM NorM Obondofan
! !
whichdoesnotundergoinsertion,wasobtained.Thiscomplex X-typeligandinthestartingcomplexbecomesanM NorM
! !
adopts a square-planar geometry, and the alkene moiety of ObondofanL-typeligandduringtheinsertionstep.Because
the homoallylic alkoxide ligand is bound perpendicular to theM X(X=NH,OH)bondistransformedintoadifferent
! 2
squareplane.Uponwarmingto258Cinthepresenceofadded type of bond during this process, rather than cleaved, the
PEt,aseriesofalkoxo-olefincomplexesformedfunctional- barriertomigratoryinsertionislowerwhenX=NH andOH
3 2
ized tetrahydrofurans and [(PEt)RhH] in good yields by thanwhenX=CH.WhenX=CH,theM Xbondisbroken
3 4 3 3 !
sequential migratory insertion of the alkene into the Rh O intheproduct,andtheM Xbondorderinthetransitionstate
! !
bondandb-hydrogenelimination(Scheme9). islower.
Themechanismoftheoxypalladationstepwasassessedby
aseries of kineticand stereochemicalexperiments. The rate
of the reaction was first order in rhodium and zero order in Reactions Involving Migratory Insertion of Olefins
PEt.Inaddition,thereactionwasslightlyfasterinless-polar into M N Bonds
3 !
solvents than in more-polar solvents. This solvent effect is
inconsistentwithamechanisminvolvingformationofanionic Catalyticreactionsthatproceedbymigratoryinsertionof
intermediatebydissociationofthealkoxideandsubsequent an alkene into an M N bond are much more common than
!
nucleophilicattackofthealkoxideonarhodium-coordinated thosethatproceedbymigratoryinsertionsintoM Obonds.
!
olefin. Finally, the reaction of an alkoxo olefin complex Moreover,aseriesofpalladiumamidocomplexeshavebeen
containingadeuterium-labeled,dimethyl-substitutedalkenyl isolatedandinsertolefinswithmoderateactivationbarriers.
alcohol generated a single isomer of the trans-deuterio In addition, thermochemical analysis of the bond enthalpies
tetrahydrofuran. The isomer formed is consistent with of bis(pentamethylcyclopentadienyl) samarium complexes
8514 www.angewandte.org !2013Wiley-VCHVerlagGmbH&Co.KGaA,Weinheim Angew.Chem.Int.Ed.2013,52,8510–8525
Angewandte
MigratoryInsertion Chemie
shows that insertions into a samarium amide should be
considerablylessendothermicthaninsertionsintosamarium
alkoxides,[49] and multiple reports describe lanthanide- and
actinide-catalyzed hydroamination reactions, which are pro-
posed to occur by migratory insertion of an alkene into the
M N bond. In addition, several published reports hypothe-
!
size that GroupIV transition-metal-catalyzed hydroamina-
tionscanproceedbyamigratoryinsertionpathway,although
themechanismoftheinsertionstepisstillbeingdebated.This
section describes examples of catalytic reactions for which
experimentalevidencehasbeengainedinsupportofmigra-
toryinsertionasastepofthecatalyticcycle.Inaddition,we Scheme11. Proposedreactionmechanismoflanthanide-catalyzedhy-
describe in detail the reactions of well-characterized metal droamination.
amidocomplexeswithalkenes.
1HNMR spectroscopy and X-ray crystallography confirmed
CatalyticReactionsInvolvingInsertionsintotheMetal–Nitrogen the presence of an additional coordinated amine. Eyring
BondsofLanthanide,Actinide,Alkaline-Earth,andEarly analysis of the rate of cyclization of 1-aminopent-4-ene
TransitionMetalComplexes catalyzed by [Cp*LaCH(TMS)] over a 25–608C temper-
2 2
ature range revealed an activation barrier for migratory
The mechanism of lanthanide-catalyzed hydroamination insertion of DH!=(12.7 1.4)kcalmol!1 and DS!=
"
is typically believed to occur by migratory insertion of an ( 27.0 4.6)calmol!1. These values are consistent with
! "
alkeneintoaLn Nbond.[53–57]However,closerevaluationof a highly ordered transition state. Reactions conducted with
!
thekineticdataobtainedfrommanyofthesesystemssuggests N-deuterium-labeled aminoalkenes revealed a primary KIE
that a reevaluation of some of the steps of the reaction of 2.7–5.2. If migratory insertion by a concerted pathway
mechanism is appropriate. A large kinetic isotope effect involving a four-membered transition state were turnover
(KIE) is observed for reactions of N-deuterated amino- limiting,aprimaryKIEwouldnotbeobserved.Therefore,the
alkenes in many cases, and these data are inconsistent with authors propose that a proton on the coordinated amine
a simple migratory insertion reaction being the turnover- ligandstabilizesthetransitionstateformigratoryinsertionby
limiting step. Assistance by a coordinated amine was pro- protonatingtheformingLn Cbondasthealkeneinsertsinto
!
posedinitiallytoaccountforthekineticisotopeeffect.Recent theLn Nbond(Scheme12).
!
resultsfromSadowandothers[53]showthathydroaminations
by alkaline-earth- and early-transition-metal systems also
occurwithalargekineticisotopeeffect.Sadowproposedthat
thesesystemsreactthroughasix-memberedtransitionstate,
notthroughasimplemigratory-insertionpathway.
In this section, we present examples of lanthanide- and
actinide-catalyzedhydroaminationreactions.Althoughthese
reactionswereproposedtooccurbymigratoryinsertionofan Scheme12. Proposedproton-assistedmechanismofalkeneinsertion
alkeneintoaM Nbond,itispossiblethatthesesystemsreact intoanLn Nbond.
! !
throughthesamesix-memberedtransitionstateproposedfor
reaction of the alkaline-earth- and early-transition-metal Fragal%, Marks, and co-workers have also studied the
systems. We will summarize the mechanistic data collected mechanism of these hydroamination reactions by computa-
foreachsysteminlightoftherecentproposals. tionalmethods.Theycalculatedtheenthalpicandfree-energy
A seminal report on hydroamination by Marks and co- activation barriers for intramolecular hydroamination of
workersdescribedintramolecularreactionsofaminoalkenes aminoalkenes. The computed barriers indicate that the
catalyzed by a series of bis(pentamethylcyclopentadienyl) migratoryinsertionstepisturnoverlimiting.[58]Theactivation
lanthanide complexes, including those of lanthanum, neo- parameters computed for the cyclization of 1-aminopent-4-
dymium,samarium,yttrium,andlutetium.[53]Reactionswith ene were DH!=11.3kcalmol!1, DG!=12.5kcalmol!1, and
catalysts containing the larger lanthanides occurred faster DS!= 14.6calmol!1.Becausethecatalytichydroamination
!
than those with catalysts containing the smaller lanthanides. requires temperatureshigher thanroomtemperature,either
Thesehydroaminationswerefoundtobefirstorderincatalyst the free energy is calculated incorrectly, or migratory
andzeroorderinaminoalkene.Thisresultisconsistentwith insertion is not the turnover-limiting step. In addition, the
rapid proton transfer to generate a lanthanide amide, computedtransitionstateforthemigratoryinsertionstepdid
followed by turnover-limiting migratory insertion of the notincludetheproposedprotonassistancefromacoordinated
pendantalkeneintotheLn Nbond(Scheme11). amineligandtoaccountfortheprimaryisotopeeffect.
!
Amido complexes lacking a pendant alkene were pre- Marksandco-workersalsoinvestigatedhydroaminations
pared by the reaction of [Cp*LaCH(TMS)] (Cp*=penta- catalyzed by actinide complexes ligated by constrained-
2 2
methylcyclopentadienyl, TMS=trimethylsilyl) and HNR. geometryligands(Scheme13).Theactivityoftheseorgano-
2
Angew.Chem.Int.Ed.2013,52,8510–8525 !2013Wiley-VCHVerlagGmbH&Co.KGaA,Weinheim www.angewandte.org 8515
Angew.andte
J.F. Hartwig andP.S. Hanley
Minireviews
Scheme14. Proposedmechanismofcalcium-catalyzedhydroamination
Scheme13. Actinide-catalyzedhydroaminationofaminoalkenes. ofaminoalkenes.
actinide catalysts is similar to that of the most active aminations catalyzed by d0 systems. They reported the
lanthanide catalysts and exceeds that of most GroupIV hydroamination of aminoalkenes catalyzed by a magnesiu-
transition-metalsystems.Thescopeofthesesystemsincludes m(II) amido complex ligated by tris(4,4-dimethyl-2-oxazoli-
aminoalkenes,aminoalkynes,aminoallenes,andaminodienes. nyl)phenylborate([ToM]).[68]Thereactionof[ToM]MgMeand
The catalytic reaction was proposed to occur by migratory aminoalkenesoccurswithalargeprimaryKIE,liketheKIE
insertionofapendantalkeneintoanAn Nbond.[59,60] Marks and co-workers[53] obtained for the hydroamination
!
A series of GroupIV complexes that catalyze the catalyzed by lanthanide metallocene complexes. However,
cyclization/hydroamination of secondary amines also has theratesofthesehydroaminationsarefirstorderinMgand
beenreportedrecently.Typically,hydroaminationscatalyzed firstorderinaminoalkene,thussuggestingthatbindingofthe
by early-transition-metal complexes occur by [2+2] cyclo- substrateoccursreversiblypriortocyclization.However,the
additions of an alkene across a metal–imido bond.[61,62] isolated[ToM]Mg primaryamidocomplex containinga teth-
However, hydroamination by this mechanism can only lead ered alkene did not undergo cyclization in the absence of
totheadditionofprimaryaminestoalkenes;ametalimido added amine. The complex underwent cyclization in the
complexcannotformfromasecondaryamine. presenceofacatalyticamountofprimaryaminetoforman
Yet, Gribkov and Hultzsch reported the intramolecular amido complex containing the cyclized product bound
hydroamination of secondary aminoalkenes catalyzed by through the secondary amine function (Scheme15). Thus,
[Cp2ZrMe]+[MeB(C6F5)3]!,[63] and Stubbert and Marks re- an additional amine ligand is necessary to promote cycliza-
portedintramolecularhydroaminationsofsecondaryamino- tion.
alkenesandaminoalkynescatalyzedbyzirconiumcomplexes
ligated by the same constrained-geometry ligand shown in
Scheme13.[64]BothauthorsproposedthatthenewC Nbond
!
forms by migratory insertion. In addition, Majumder and
Odom reported the intramolecular hydroamination of pri-
mary aminoalkenes catalyzed by titanium and zirconium
dipyrrolylmethane complexes.[65] Based on the competitive
formation of products from hydroamination and oxidative
amination, these reactions likely occur by insertion of an
alkeneintoanM Nbond.
! Scheme15. Reactionsof[ToM]Mgamidocomplexesinthepresence
Hillandco-workersreportedthefirsthydroaminationof
andabsencesofaddedamine.
aminoalkenes catalyzed by alkaline-earth-metal complexes,
andthesereactionsalsoareproposedtoproceedbymigratory
insertion of the alkene into the M N bond. Hill and co- On the basis of these data, Sadow and co-workers[68]
!
workers examined the intramolecular hydroamination of proposed that cyclization of the [ToM]Mg amido complex
aminoalkenes catalyzed by calcium amido and magnesium occurs by substitutionof one arm of the [ToM] ligand for an
amido complexes ligated by bdiketiminates amine, followed by concerted rate-limiting C N and C H
! !
(Scheme14).[66,67] Kinetic analysis of the reaction catalyzed bond formation through a six-centered transition state
bythemagnesiumsystemrevealedafirst-orderdependence (Scheme16).Bythisproposedmechanism,hydroaminations
on catalyst concentration and an inverse first-order depend- would not proceed through the typical pathway involving
ence on the concentration of aminoalkene. Although pre- migratoryinsertionofthealkeneintoaM Nbond.
!
liminary,thesedataareconsistentwithamechanisminvolv- In addition, Sadow and co-workers reported that zirco-
ingturnover-limitinginsertionofalkeneintotheM Nbond, nium[69] and yttrium[70] complexes coordinated by similar
!
which occurs after dissociation of one substrate from the ligand frameworks catalyze hydroamination, and the mech-
metalcenter. anistic data in this study imply that these reactions occur
Morerecently,Sadowandco-workersgainedevidencefor through the same six-membered transition state as that
an alternative pathway for C N bond formation in hydro- proposed for reactions of the alkaline earth systems. Sub-
!
8516 www.angewandte.org !2013Wiley-VCHVerlagGmbH&Co.KGaA,Weinheim Angew.Chem.Int.Ed.2013,52,8510–8525
Angewandte
MigratoryInsertion Chemie
Additional studies are clearly needed to delineate the
relationshipsbetweentheexperimentaldataandmechanisms
ofhydroaminationcatalyzedbyalkalineearth,groupIV,and
lanthanidecomplexes.
CatalyticReactionsInvolvingInsertionsintoPd NBonds
!
Most published literature on palladium-catalyzed oxida-
tive amination reactions of alkenes with amides, commonly
termed the aza-Wacker reaction, state that the mechanism
involves nucleophilic attack of a nitrogen nucleophile onto
ametal-coordinatedolefin.Anumberofearly,elegantstudies
demonstrated that the addition of nitrogen nucleophiles to
Scheme16. Proposedreactionmechanismof[ToM]Mg-catalyzedhydro- a palladium-coordinated alkene formed new C N bonds by
aminationofaminoalkenes. antiaminopalladation.[75–77]Hegedusandco-wor!kersreported
the first catalytic oxidative amination of alkenes with
benzoquinoneasanoxidanttoregeneratethepalladium(II),
sequently, Schafer and co-workers proposed a similar tran- andproposedthatthesereactionsoccurredbyantiadditionof
sitionstateforthehydroaminationofprimaryandsecondary thepalladiumandthenucleophileacrossthealkene.[78]Over
aminoalkenes catalyzed by zirconium complexes ligated by the next two decades, several studies described palladium-
atetheredbis(ureate).[71] catalyzed amination reactions, but none contained evidence
Theproposedsix-memberedtransitionstateaccountsfor for a synaminopalladation by migratory insertion of the
the kinetic data obtained on the systems described by the alkeneintoaPd Nbond.[79–82]Thus,migratoryinsertionwas
!
groupsofSadowandSchaferandisapossibletransitionstate not thought to be part of the mechanism of palladium-
forC NbondformationbytheLnandAnsystemsdescribed catalyzedaminationsofalkenes.
!
by the group of Marks.[53,58–60] The orders in substrate, when During the past ten years, however, this view of the
combinedwithinformationontherestingstate,andtheKIE mechanism has changed. Palladium-catalyzed amination re-
values suggest parallels between these systems. The large actions now thought to occur by a migratory insertion step
KIEsobservedformanyofthereactionssuggestthatcleavage include carboaminations,[83–86] oxidative aminations,[87–89]
of the N H bond occurs in the turnover-limiting step. chloroaminations,[90] aminoacetoxylations,[91] diaminations,[92]
!
Although the computed barriers for alkene insertion are and hetero-Heck-type transformations.[93] In some cases,
moderate,theydonotaccountforcleavageofanN Hbond stereochemical evidence for synaminopalladation by migra-
!
during the transition state. Thus, it seems possible that the tory insertion has been gained. Because reviews detailing
mechanism of lanthanide-catalyzed hydroamination occurs known examples of palladium-catalyzed reactions involving
througharelatedsix-memberedtransitionstate.Atthesame an aminopalladation step are available,[94,95] this review
time, the lanthanide systems described by Marks and co- focusesonthemigratoryinsertionstep.
workers.[72]havebeenshowntocatalyzetandemC NandC Stahl and co-workers reported the first palladium-cata-
! !
Cbond-formingadditionstoalkenes.AsshowninScheme17, lyzed intermolecular oxidative amination of unactivated
these data imply that the reactions, at least those of the alkenes with amides.[91] The stereochemistry of the product
secondary N-allylamines, form an intermediate containing that arose from the oxidative amination of norbornene was
aM Cbond.Analternateexplanationfortheprimarykinetic consistentwithamechanisminvolvingsynaminopalladation.
!
isotope effect and zero-order dependence on substrate The oxidative coupling of two norbornenes and p-toluene-
concentration is reaction by a mechanism involving turn- sulfonamideinthepresenceof5mol%[(CHCN)PdCl]in
3 2 2
over-limiting formation of a metal imido intermediate.[73,74] DMEunder1atmofO and5mol%CuCl at608Cformed
2 2
a cyclic product with relative configurations in the product
thatareconsistentwithnorborneneinsertionintothePd N
!
bond(Scheme18).[96]
Stahlandco-workerssubsequentlyinvestigatedthemech-
anism of palladium-catalyzed oxidative amination reactions
with several palladium catalysts under varied reaction con-
ditions.[88] In most cases, the relative configuration of the
products from the oxidative cyclization of a deuterium-
labeled,sulfonamide-substituted aminoalkeneareconsistent
withamechanisminvolvingsynaminopalladation(migratory
insertion;Table1).Aminationofsubstratescontaininganosyl
group instead of a tosyl group formed products exclusively
Scheme17. Bicyclizationofanaminodiene,thussuggestingthepres- derived from synaminopalladation.Because the NH proton
enceofaM Cbondandamigratoryinsertionstep. ofthenosylgroupismoreacidicthantheNHprotonofthe
!
Angew.Chem.Int.Ed.2013,52,8510–8525 !2013Wiley-VCHVerlagGmbH&Co.KGaA,Weinheim www.angewandte.org 8517
Angew.andte
J.F. Hartwig andP.S. Hanley
Minireviews
into a Pd N bond formed the product with low enantio-
!
selectivity.However,amidocyclizationreactionsthatoccured
primarily by transamidopalladation formed products with
excellentenantioselectivity(96%).
Ney and Wolfe investigated the stereochemistry of
palladium-catalyzed carboamination of N-arylaminoalkenes
witharylbromides.ThereactionofN-arylaminoalkeneswith
aryl bromides in the presence of 1mol% [Pd(dba)],
2 3
2mol%dppbligand,and1.2equivalentsNaOtBu,intoluene
at 608C generated carboaminated products (see Scheme19
Scheme18. Proposedreactionmechanismofthepalladium-catalyzed
oxidativeaminationofnorbornene.DME=dimethoxyethane,Ts=
4-toluenesulfonyl.
Table1: Oxidativeaminationofasulfonamide-substitutedaminoalkene.
Scheme19. Palladium-catalyzedcarboaminationofN-arylaminoalkenes
witharylbromides.
Entry Pdcatalyst[a] t Yield Productratio
[h] [%] synamino- antiamino- forarepresentativeexample).[99]Byconductingthereaction
palladation palladation withasubstratecontainingacyclicalkene,theygainedstrong
1 Pd(OAc)/DMSO 15 70 100:0 – evidence that the C N bond-forming step of these multi-
2 !
2 Pd(OAc)/py 15 84 98:2 – component reactions occurs by migratory insertion of the
2
3 Pd(O2CCF3)2/py 15 85 88:12 – alkeneintoaPd Nbond.Carefulselectionofthephosphine
!
4 Pd(IMes)(O2CCF3)2/BzOH 72 60 43:8 37:12 ligandresultedinselectivesynthesisofeitherthe5-arylor6-
5 Pd(OCCF)/sp 72 72 59:41 –
2 32 arylcarboaminatedproducts(Scheme20).[84]Reactionscata-
[a]IMes=1,3-di(2,4,6-trimethylphenyl)imidazolin-2-ylidene,py=pyri-
dine,sp=sparteine.
tosyl group, the palladium amido species is formed more
readily with a nosylamide than with a tosylamide. Lower
stereoselectivity from the oxidative cyclization of tosyl-
substituted carboxamide substrates was observed with most
catalystcombinations,althoughtheoriginoftheselectivityis
notwellunderstood.
Further mechanistic investigation on the intramolecular Scheme20. Palladium-catalyzedcarboaminationofN-arylamino-
amidationofalkenescatalyzedby[(IMes)Pd(OCCF)HO], alkenestoformeither5-arylor6-arylproducts.dppf=1,1’-bis(diphe-
2 3 2 2
nylphosphino)ferrocene.
whichformsproductsfrombothsyn-andanti-amidopallada-
tion pathways (Table1; entry4), revealed that reactions
conducted in the presence of NaCO exclusively formed lyzed by the combination of [Pd(dba)] and the chelating
2 3 2 3
products from a syn-amidopalladation pathway.[97] In the phosphinedppf-iPrprovidedprimarilythe6-aryloctahydro-
absence of base, reaction by both synamidopalladation by cyclopenta[b]-pyrroleproduct.However,analogousreactions
formation of a palladium sulfonamidate complex and sub- conducted with the combination of [Pd(dba)] and
2 3
sequentmigratoryinsertionandanantiamidopalladationby P(tBu)Me·HBF generated the 5-aryl isomer with high
2 4
a nucleophilic attack on a coordinated alkene occur. In the diastereoselectivity.
presence of NaCO, a threefold rate enhancement was In addition, the group of Wolfe reported examples of
2 3
observed.Inthepresenceofbase,theproductfromthesyn- asymmetricpalladium-catalyzedcarboaminationreactionsto
amidopalladation pathway presumably forms exclusively form enantiomerically enriched 2-(arylmethyl)- and 2-(alke-
becausethebasepromotesformationofapalladiumsulfon- nylmethyl)pyrrolidines, which likely occur by migratory
amidatecomplex. insertion into a Pd N bond.[85] In contrast to the amidocyc-
!
Recently, Weinstein and Stahl investigated the enantio- lizationreactions,reportedbyStahlandco-workers,[98]which
selectivity of both the syn and anti-amidopalladation path- formtheproductwithlowenantioselectivitywhentheyoccur
ways catalyzed by a palladium complex ligated by chiral, bymigratoryinsertion,thecyclizationsreportedbyMaiand
nonracemicpyridineoxazolineligands.[98]Intheseexamples, Wolfe,whichoccurbymigratoryinsertion,formtheproducts
reactions that occurred by migratory insertion of an alkene withupto94%ee.
8518 www.angewandte.org !2013Wiley-VCHVerlagGmbH&Co.KGaA,Weinheim Angew.Chem.Int.Ed.2013,52,8510–8525