Hydroamination: Direct Addition of Amines to Alkenes and Alkynes

98 Pages·2008·3.68 MB·English

Chem.Rev.2008,108,3795–3892 3795
Hydroamination: Direct Addition of Amines to Alkenes and Alkynes
Thomas E. Mu¨ller,*,† Kai C. Hultzsch,*,‡,§ Miguel Yus,|,§ Francisco Foubelo,|,§ and Mizuki Tada⊥,§
CATCatalyticCenter,ITMC,RWTHAachen,Worringerweg1,52074Aachen,Germany,DepartmentofChemistryandChemicalBiology,Rutgers
University,610TaylorRoad,Piscataway,NJ08854-8087,DepartamentodeQu´ımicaOrga´nica,UniversidaddeAlicante,E-03080Alicante,Spain,
andDepartmentofChemistry,GraduateSchoolofScience,TheUniversityofTokyo,Hongo,Bunkyo-ku,Tokyo113-0033,Japan
Received January 22, 2008
Contents 4.2.4. Dienes and Trienes 3853
4.3. Nonactivated Alkynes 3855
1. Introduction 3796
4.3.1. Synthesis of N-Heterocycles 3855
2. Hydroamination Reactions Involving Rare-Earth 3798
4.3.2. Synthesis of Complex Molecules in 3856
Metals, Actinides and Alkaline Earth Metals
Sequential Reactions
2.1. Mechanistic Aspects 3798
4.4. Hydroamination of Alkenes with Weaker 3857
2.2. Catalysts and Scope of Reaction 3801 Nucleophiles
2.3. Intermolecular Hydroamination Using 3807 4.5. Catalysis in Aqueous Phase and Ionic Liquids 3857
Rare-Earth Metal Catalysts
4.6. Hydroamination Using Homogeneous Zinc 3858
2.4. Post-Metallocene Rare-Earth Metal Based 3811 Catalysts
Hydroamination Catalysts
5. Heterogeneous Hydroamination Catalysts and 3859
2.5. Alkaline-Earth Metal Based Hydroamination 3814 Immobilized Early and Late Transition Metal
Catalysts Complexes
2.6. Asymmetric Synthesis of Amines Using 3815 5.1. Inorganic Solid Catalysts 3859
Rare-Earth Metal Catalysts
5.2. Metal-Ion Exchanged Zeolites and Clays 3859
2.7. Chiral Rare-Earth Metal Catalysts Based on 3818
5.3. Supported Complexes on Oxide Surfaces 3860
Non-Cyclopentadienyl Ligands
5.4. Polymer-Supported Organolanthanide 3862
2.8. Kinetic Resolution of Chiral Aminoalkenes 3824
Catalysts
3. Group 4/5 Metal Based Catalysts 3824
6. Brønsted Acid Catalyzed Hydroamination of 3862
3.1. Mechanistic Aspects 3824 Alkenes and Alkynes
3.2. Catalysts and Scope of Reaction 3826 6.1. Intermolecular Brønsted Acid Catalyzed 3862
3.3. Applications of Hydroamination Reactions in 3834 Hydroamination of Alkenes and Alkynes
Multistep Reaction Sequences 6.2. Intramolecular Brønsted Acid Catalyzed 3864
3.4. Hydroamination of Alkenes 3837 Hydroamination of Alkenes
3.5. Asymmetric Hydroamination Using Group 4 3840 7. Base-Catalyzed Hydroamination of Alkenes and 3865
Metal Catalysts Alkynes
3.6. One-Pot Reaction Sequences Involving 3841 7.1. Base-Catalyzed Hydroamination of Alkenes 3865
Hydroamination Products 7.1.1. Intermolecular Reactions 3865
4. Late Transition Metal Complexes as 3843 7.1.2. Intramolecular Reactions 3869
Homogeneous Hydroamination Catalysts
7.2. Base-Catalyzed Hydroamination of Alkynes 3871
4.1. Mechanistic Aspects 3844 8. Amino- and Amidomercuration-Demercuration of 3871
4.1.1. Nucleophilic Attack on Coordinated 3844 Alkenes and Alkynes
Alkene/Alkyne 8.1. Aminomercuration-Demercuration of Alkenes 3872
4.1.2. Nucleophilic Attack on Allylic Complexes 3846
8.1.1. Intramolecular Reactions 3872
4.1.3. Insertion into the M-H Bond of Metal 3850
8.1.2. Intermolecular Reactions 3873
Hydrides
8.2. Aminomercuration-Demercuration of Alkynes 3875
4.1.4. Oxidative Addition 3850
8.3. Amidomercuration-Demercuration of Alkenes 3875
4.2. Catalysts and Scope of Reaction 3852
8.3.1. Intramolecular Reactions 3875
4.2.1. Hydroamination of Ethene 3852
8.3.2. Intermolecular Reactions 3877
4.2.2. Higher Alkenes 3853
8.4. OtherAminomercuration-Demercuration 3877
4.2.3. Enantioselective Hydroamination with Late 3853
Reactions
Transition Metals
8.4.1. Sulfonamidomercuration Reactions 3878
*To whom correspondence should be addressed. Phone: [phone]
28594. Fax: [phone]. E-mail: Thomas.Mueller@ 8.4.2. Phosphoramidomercuration Reactions 3878
catalyticcenter.rwth-aachen.de. 8.4.3. Azidomercuration Reactions 3878
†RWTHAachen.
8.4.4. Acetamidomercuration Reactions Using 3878
‡RutgersUniversity.
|UniversidaddeAlicante. Acetonitrile
⊥TheUniversityofTokyo. 8.4.5. Nitromercuration Reactions 3878
§E-mailaddresses:[email protected];[email protected];[email protected];
[email protected]. 9. Hydroamination of Alkenes and Alkynes under 3878
Microwave Irradiation
10.1021/cr0306788CCC:$71.00 2008AmericanChemicalSociety
PublishedonWeb08/26/2008
3796 ChemicalReviews,2008,Vol.108,No.9 Mülleretal.
9.1. Hydroamination of Alkenes under Microwave 3878
Irradiation
9.2. Hydroamination of Alkynes under Microwave 3879
Irradiation
10. Radical Hydroamination of Alkenes 3880
11. Conclusions 3883
12. Abbreviations 3884
13. Acknowledgments 3884
14. References 3884
1. Introduction
Nitrogen-containing compounds, such as amines, enam-
ines, and imines, are valuable and commercially important
bulk chemicals, specialty chemicals, and pharmaceuticals.1
Amongvarioussynthesisroutes,hydroamination,thedirect ThomasE.MüllerwasborninLandshut,SouthernGermany,in1967.He
formation of a new C-N bond by addition of an amine to received his undergraduate education at LMU München and ETH Zürich.
HisDiplomarbeitledhimforthefirsttimetotheUnitedKingdom,wherehe
an unsaturated CC bond, is of particular significance. The
workedwithD.M.L.Goodgame,ICLondon,oncoordinationpolymers.After
reaction offers an atom-efficient pathway starting from returning to Switzerland, he received his Diploma in 1991. He joined the
readily accessible alkenes and alkynes. While the reaction research group of D. M. P. Mingos at IC London the following year and
is thermodynamically feasible under normal conditions receivedhisPh.D.degreein1995forstudiesonpolyaromaticphosphines
(slightly exothermic but nearly ergoneutral, because hy- andtheircoordinationtonoblemetals.In1995,hemovedtotheUniversity
ofSussextopursuepostdoctoralresearchonfullerenesandnanotubeswith
droaminationreactionsareentropicallynegative,inparticular
D. M. Walton and Sir H. K. Kroto. After working for two years as Liebig-
in the intermolecular variant),2,3 there is a high reaction
StipendiatinclosecollaborationwithM.BellerandW.A.HerrmannatTU
barrier. The 2 + 2 cycloaddition of N-H across the CC München,hestartedhishabilitationin1998inthegroupofJ.A.Lercher.In
bond, which is orbital-forbidden under thermal conditions 2003,hecontinuedatTUMünchenasPrivatdozent.Aftervisitingprofessor
butcanbepromotedwithlight,4canbeavoidedbytheuse positions at NUS Singapore (2005) and University of Tokyo (2005), he
of a catalyst opening other reaction pathways. However, acceptedthepositionasheadofCATCatalyticCenter,RWTHAachen,in
relatively low reaction temperatures (generally e200-300 2007.Hehaspublishedmorethan50papers,mainlyinthefieldofamine
°C) are required, because the conversion is limited by the synthesis, mechanistic studies on hydroamination, reductive amination,
hydrogenation of nitriles, and catalyst immobilization. His current research
reaction equilibrium at higher temperatures.5
interestisfocusedonhomogeneouscatalysiswithtransitionmetalcomplexes,
Thehydroaminationofalkenesismoredifficultcompared immobilizationofhomogeneouscatalysts,supportedionicliquidsandmetal
with that of alkynes because of the lower reactivity and nanoparticles,multiphasereactions,andbuildingblocksystemsforhetero-
electron density of CdC bonds.6 A particular challenge is geneouscatalysis.
the reversal of the regiochemistry to obtain the anti-
Markovnikov product.7 For good reason, the catalytic anti-
Markovnikov addition of H-NR to olefins was listed as
2
oneoftheso-called“TenChallengesforCatalysis”.6During
recent years, hydroamination became a widely explored
operation in the synthesis of nitrogen heterocycles and
complexmolecules.TheMarkovnikovadditionofprotected
amines to alkynes is now an established synthesis strategy.
Withthedevelopment ofa newgeneration ofcatalysts,the
additionofprotectedaminestoalkeneswillquicklybecome
a routine reaction. More challenging and, thus, demanding
furtherdevelopmenttimeistheconversionofstronglybasic
amines, such as ammonia, as well as achieving adequate
controloftheregioselectivityinanti-Markovnikovfashion.
During the last decade, the interest of the scientific
KaiCarstenHultzschstudiedchemistryattheUniversityofMainz,Germany,
communityinhydroaminationhasincreasedsharply(Figure
andToronto,Canada,from1991to1996.HefinishedisPh.D.in1999under
1).Whilemostlyalkaliandlanthanidemetalcatalystswere
the guidance of Jun Okuda in Mainz. After two years as a Feodor Lynen
used in early studies, the focus has shifted recently to the
postdoctoralfellowinthegroupofRichardR.SchrockatMIT,hebeganhis
useofzirconium,titanium,andlatetransitionmetalcatalysts. independentresearchcareerin2001asaDFGEmmyNoetherfellowatthe
Mostcatalystsareemployedashomogenouscatalysts,while UniversityofErlangen-Nu¨rnberg,Germany.Afterfinishinghishabilitationin
the development of heterogeneous catalysts lags behind. In 2006andvisitingprofessorpositionsinErlangen(2005/2006)andMu¨nster
this respect, new strategies for the immobilization of (2007), he accepted his assistant professor position at Rutgers University,
Piscataway,NJ,in2007.HeistherecipientoftheWo¨hlerYoungInvestigator
homogeneouscatalystswillgainincreasedimportance.Some
Award, the ADUC Award for Habilitands, the Lieseberg Award from the
examples are described below.
UniversityofHeidelberg,andtheEmmy-Noether-Habilitation-Awardfromthe
SincethelastcomprehensivereviewbyMu¨llerandBeller UniversityofErlangen-Nu¨rnberg.Hismainareasofinterestsaretransition
in 1998,8 review articles covering many aspects of hy- metalcatalyzedstereoselectiveolefinheterofunctionalizationsand(co)polym-
erizationofnonpolarandpolarmonomers.
droaminationhavebeenpublished(seeTable1).Thearticle
ofAlonsoetal.deservesparticularattentionforitsthorough 1998untilJune2007isdiscussed.Thefirstpartofthisreport
coverage of the hydroamination of alkynes.9 In the review coversmechanisticaspectsofhydroaminationwithearlyand
article presented here, the development of the subject from late transition metal catalysts. The use of heterogeneous
Hydroamination ChemicalReviews,2008,Vol.108,No.9 3797
MiguelYuswasborninZaragoza(Spain)in1947andreceivedhisB.Sc. FranciscoFoubelowasborninCarren˜a-Cabrelas(Asturias)in1961.He
(1969), M.Sc. (1971), and Ph.D. (1973) degrees from the University of studied chemistry at the University of Oviedo from which he received
Zaragoza.AfterspendingtwoyearsasapostdoctoralfellowattheMax B.S.(1984),M.S.(1986),andPh.D.(1989)degrees.Afterapostdoctoral
PlanckInstitutfu¨rKohlenforschunginMu¨lheima.d.Ruhr,hereturnedto stay(1989-1991)asaFulbrightfellowatPrincetonUniversity,hemoved
SpaintotheUniversityofOviedowherehebecameassociateprofessor totheUniversityofAlicanteandjoinedtheresearchgroupofProfessor
in1977,beingpromotedtofullprofessorin1987atthesameuniversity. M.YuswherehebecameAssociateProfessorin1995andFullProfessor
In 1988, he moved to a chair in Organic Chemistry at the University of in 2002. Now he is a member of the Department of Organic Chemistry
AlicantewhereheiscurrentlytheheadoftheOrganicSynthesisInstitute andtheOrganicSynthesisInstitute(ISO)atthesameuniversity.Hehas
(ISO).ProfessorYushasbeenvisitingprofessoratdifferentinstitutions published more than 80 papers and is cofounder of the new chemical
anduniversitiessuchasETH-Zentrum,Oxford,Harvard,Uppsala,Tucson, companyMEDALCHEMY,S.L.,asaspin-offoftheUniversityofAlicante.
Okayama, Paris, Strasbourg, and Kyoto. He is coauthor of more than Hisresearchinterestsarefocusedonthedevelopmentofnewsynthetic
400papers,mainlyinthefieldofthedevelopmentofnewmethodologies methodologies for the preparation of functionalized organolithium com-
involvingorganometallicintermediates,andthreepatents.ProfessorYus poundsfromdifferentprecursorsandtheapplicationoftheseorganome-
hasbeenamemberoftheAdvisoryBoardofthejournals,amongothers, tallicintermediatesinorganicsynthesis.Heterofunctionalizationofalkenes
Tetrahedron, Tetrahedron Letters, Chemistry Letters, European Journal andthedevelopmentofnewsyntheticmethodsforasymmetricsynthesis
ofOrganicChemistry,TrendsinOrganicChemistry,andCurrentChemical relatedtochiralsulfiniminesarerecentinterests.
Biology,beingRegionalEditorofLettersinOrganicChemistryalso.He
has given more than 100 lectures, most of them abroad, and already
supervised43Ph.D.students.Amongothers,hehasreceivedtwicethe
JapanSocietyforthePromotionofSciencePrize(Okayama,1999;Kyoto,
2007),theFrench-SpanishPrizeoftheSociete´Franc¸aisedeChimie(Paris,
1999),theC.A.StiefvaterMemorialLectureAward(Nebraska,2001),the
Nagase Science and Technology Foundation fellowship (Kyoto, 2003),
the Cellchem Lectureship (Sheffield, 2005), the Singenta Lectureship
(Basel,2007),andtheFundeun-IberdrolaPrize(Alicante,2007).Hiscurrent
researchinterestisfocusedonthepreparationofveryreactivefunction-
alized organometallic compounds and their use in synthetic organic
chemistry, arene-catalyzed activation of different metals, preparation of
newmetal-basedcatalysts,includingmetallicnanoparticles,forhomoge-
neousandheterogeneousselectivereactions,andasymmetriccatalysis.
In 2002, he and other members of the ISO founded the new chemical
companyMEDALCHEMY,S.L.,tocommercializefinechemicals.
catalysts,baseandacidcatalyzedhydroamination,andsome
MizukiTadawasbornin1979inTokyo(Japan).Shestudiedandreceived
stoichiometric reactions, such as the mercuration/demercu-
her B.Sc. (2001) and M.Sc. (2003) from the Department of Chemistry,
ration protocol are described next. Recently, non-conven-
Graduate School of Science at The University of Tokyo. She obtained
tionalreactionconditions,inparticulartheuseofmicrowaves herPh.D.in2005fromTheUniversityofTokyounderthesupervisionof
and radical chemistry in solution, have been introduced in Prof.YasuhiroIwasawa.Shebecametheassistantprofessorofchemistry
hydroamination.Inthefinalpartofthisreport,thescopeof in2004-2007andwaspromotedtoassociateprofessorintheDepartment
hydroaminationreactionsasnewandhighlyexcitingaccess ofChemistry,GraduateSchoolofScience,atTheUniversityofTokyoin
2008. Her current research focuses on the catalyst surface, advanced
to complex nitrogen-containing molecules is discussed.
surfacedesignofsupportedmetal-complexcatalysts,surfacemolecular-
Hydroamination in the context of this review article is imprintedcatalystsandinsitutime-resolvedcharacterizationofcatalyst
defined as the addition of H-NR across a nonactivated surfaces.
2
alkene or alkyne providing a higher substituted amine or
enamine, respectively. When ammonia or a primary amine
example, see Scheme 2), telomerization of amines with
is reacted with an alkyne, the enamine formed isomerizes
butadiene,69–74additionstoalkenesactivatedbyaneighbor-
subsequently to the corresponding imine. The addition of
amines to allenes and dienes is closely related and will be ing electron-accepting substituent, such as the aza-Michael
covered. For the latter reactions, regioselectivity is an reaction20,75–79andtheadditiontoacrylicacidoracrylonitrile
important issue, even when symmetric substrates are used, derivatives,80–84 oxidative amination using molecular oxy-
as1,2and2,1addition,andfordienes,1,4additionprovides gen85 or styrene86 as oxidant, and allylic amination of
different products (Scheme 1). 3-alkenyl-carbonates87 are generally not considered in this
Relatedreactions,suchasthereactionofnitrogennucleo- review except for cases where it seems appropriate. The
philes with cyclopropanes62–67 or cyclopropenes68 (for an hydroamination of slightly activated substrates, such as
3798 ChemicalReviews,2008,Vol.108,No.9 Mülleretal.
Scheme1
Scheme2 Scheme3. SimplifiedMechanismforRare-EarthMetal
CatalyzedHydroamination/CyclizationofAminoalkenes
norbornene, vinylethers, and, in particular, vinylarenes is,
however, included.
2. Hydroamination Reactions Involving
Rare-Earth Metals, Actinides and Alkaline Earth
Metals
Rare-earth metal complexes are highly efficient catalysts
for intramolecular hydroamination of various C-C unsat-
urations such as alkenes, alkynes, allenes, and dienes, but
reducedratesareobservedinintermolecularhydroamination
processes. Attractive features of rare-earth metal catalysts beensynthesizedforenantioselectivehydroamination.While
includeveryhighturnoverfrequenciesandexcellentstereo- therare-earthmetalcatalystsareveryefficientcatalystsfor
selectivities,renderingthismethodologyapplicabletoconcise hydroamination,theirsensitivitytooxygenandmoisturehave
synthesisofnaturallyoccurringalkaloidsandotherpolycyclic limited their use in many applications.
azacycles.Thegeneralhydroaminationmechanisminvolves Aswillbediscussedinchapter3,recentdevelopmentsin
rate-limiting C-C multiple bond insertion into the Ln-N catalytically active group 4 metal complexes have resulted
bond, followed by rapid protonolysis by other amine in significant improvements in their reactivity towards
substrates.ThegroundbreakingstudiesinthegroupsofT.J. aminoalkenes,andthefirsthighlyenantioselectiveexamples
Marks,30 some of which were summarized in the 1998 using chiral catalysts have been reported. Similar to rare-
review,8 and later G. A. Molander have utilized predomi- earth metals, group 4 metal complexes are very oxophilic,
nantly lanthanocene complexes. Since then, sterically less whichreducestheirfunctionalgrouptolerance.Nevertheless,
encumberedliganddesigns(e.g.,constrained-geometrycom- group 4 metal catalysts have been applied to the synthesis
plexes,post-metallocenes)havebeendevelopedtoimprove of a range of biologically active molecules of relevance to
reaction rates and alter catalyst stereoselectivities. Metal- pharmaceutical industry.
loceneandnon-metallocenechirallanthanidecomplexeshave
2.1. Mechanistic Aspects
The mechanism of the hydroamination/cyclization30,88,89
proceedsthrougharare-earthmetalamidospecies,whichis
formeduponprotonolysisofarare-earthmetalamidooralkyl
bond in the precatalyst (Scheme 3). The first step of the
catalyticcycleinvolvesinsertionoftheolefinintotherare-
earth metal amido bond with a seven-membered chair-like
transition state (for n ) 1). The roughly thermoneutral
insertion step88 is usually rate-determining, giving rise to a
zero-order rate dependence on substrate concentration and
first-orderratedependenceoncatalystconcentration(eq1).
d[subst]
rate)- )k[subst]0[catalyst]1 (1)
dt
The resting state of lanthanocene catalysts is an amido
Figure1. Numberofarticlespublishedonhydroamination. amine species of the general form Cp* Ln(NHR)(NH R)
2 2
Hydroamination ChemicalReviews,2008,Vol.108,No.9 3799
Table1. ReviewArticlesonHydroaminationReactionsa
substrates
no.of covering
ref authors citedrefs until topicsinorderofimportance alkenes alkynes dienes allenes
10 Andrea,Eisen 118 09/2007 thoriumanduraniumcatalysts X X
11 Aillaud,Collin,Hannedouche,Schulz 61 07/2007 asymmetrichydroamination X X X X
12 Brunet,Chu,Rodriguez-Zubiri 122 04/2007 platinumcatalyzedhydroamination X
promotedwithhalideanions
13 Lee,Schafer 135 04/2007 groupIVamidatecomplexes X X X
14 Severin,Doye 40 10/2006 recentdevelopmentsin X
hydroaminationofalkynes
15 Hunt 169 01/2007 computationalaspectsofhydroamination X X X X
withorganolanthanides
16 Liu,Bender,Han,Widenhoefer 78 10/2006 platinumcatalysts X
17 Widenhoefer,Han 116 05/2006 goldcatalysts X X X X
18 Mitsudo,Ura,Kondo 94 02/2006 zerovalentrucomplexes X
19 Rowlands 55 2006 freeradicalreactions X
20 Hii 30 2006 palladiumcatalysts,enantioselective
21,22 Gottfriedsen,Edelmann 308,285 05/2005 chemistryoforganolanthanidesandactinides X X
23 Hultzsch 53 12/2004 rare-earthandgroupIVmetalcatalysts X
24 Doye 93 12/2004 titaniummetallocenecatalysts X
25 Hultzsch,Gribkov,Hampel 87 11/2004 non-metallocenesrare-earthcatalysts, X
enantioselective
26 Odom 92 10/2004 titaniumdiamidecomplexes X
27 Rosenthal,Burlakov,Arndt,Baumann, 76 09/2004 zirconiumandtitanium X
Spannenberg,Shur metallocenecomplexes
28 Arndt,Okuda 94 08/2004 cationicalkylcomplexesofrare-earthmetals X
29 Hultzsch 120 08/2004 asymmetrichydroamination X X X X
30 Hong,Marks 24 02/2004 organolanthanidecatalysts X X X X
31 Brunet,Poli 16 2004 selectedaspectsofRu,Pdcatalysis X
32 Beller,Tillack,Seayad 118 2004 greenaspects X X
33 Barbaro,Bianchini,Giambastiani, 148 11/2003 enantioselectivehydroaminationwith X
Parisel iridiumandnickelcomplexes
9 Alonso,Beletskaya,Yus 456 10/2003 comprehensivereviewonalkynes X
34 Buffat 148 08/2003 synthesisofpiperidines X X
35 Hartwig 40 07/2003 palladium,nickel,andrhodiumcatalysts X X
36 Leung 57 07/2003 vinyl-andalkynylphosphines X X
37 Beller,Seayad,Tillack,Jiao 34 06/2003 regioselectivity X X
38 Roesky,Mu¨ller 24 04/2003 enantioselectivehydroamination X X
39 Salzer 55 11/2002 arene(tricarbonyl)chromiumcomplexes X
40 Bytschkov,Doye 44 08/2002 groupIVmetalcomplexes X X
41 Pohlki,Doye 38 07/2002 recentresultsin2002 X
42 Gibson,Ibrahim 67 02/2002 asymmetriccatalysisusing[(arene)Cr(CO)] X
3
complexesasligands
43 Duncan,Bergman 55 2002 imidozirconocenecomplexes
44 Seayad,Tillack,Hartung,Beller 142 2002 basecatalyzedhydroaminationreactions X X X
45 Taube 22 2002 microreview
46 Molander,Romero 130 09/2001 lanthanocenecatalysts X X X
47 Nobis,Drie(cid:1)en-Ho¨lscher 26 05/2001 recentresultsin2002 X X X
48,49 Mu¨ller 55,56 02/2001 homogeneousandheterogeneous X X X
catalysts,respectively
50 Siebeneicher,Doye 37 11/2000 chemistryof[CpTiMe] X
2 2
51 Togni,Bieler,Burckhardt,Kollner, 21 07/1999 iridiumcatalysts,protectedamines X
Pioda,Schneider,Schnyder
52 Haak,Doye 37 1999 microreview X X
53 Yamamoto,Radhakrishnan 36 08/1998 PdIIcatalyzedadditionofpronucleophiles X
54 Eisen,Straub,Haskel 46 1998 organoactinidecatalyzedtelomerisation X
55 Johannsen,Jørgensen 165 1998 synthesisofallylicamines X
56 Merola 93 1997 iridiumcatalysts
8 Mu¨ller,Beller 239 07/1997 comprehensivereview,mechanisticaspects X X X X
57 Brunet 56 1997 rhodiumcatalyst,hydroamination X
withlithiumphenylamide
58 Simpson,Cole-Hamilton 200 01/1996 reactionscatalyzedwithrhodium X
trialkylphosphinecomplexes
59 Anwander 115 1996 homogeneouslanthanidecatalysts
60 Taube 21 1996 microreview
61 Marks,Gagne,Nolan,Schock, 49 1989 thermodynamicaspects X
Seyam,Stern
aImportantarticleswithparticularfocusonhydroaminationaremarkedinbold.
based on spectroscopic and crystallographic evidence.88 inhibition.Forexample,stericallyopenansa-lanthanocenes
However, lanthanocene catalysts are only slightly inhibited and constrained-geometry catalysts have displayed product
bythepresenceofexternalbases,suchasn-propylamineor inhibition (apparent first-order kinetics),88,90–92 while self-
THF,butdependingonthestericcongestionaroundthemetal accelerationhasbeenobservedinthecyclizationofamino-
center and substrate structure, significant deviations from hexene derivatives using sterically more encumbered cata-
zero-orderratekineticshavebeenobserved,andthesehave lysts.91 Metal centers in non-metallocene-type catalysts are
been attributed to substrate self-inhibition and product often more accessible to amine bases, as evidenced by
3800 ChemicalReviews,2008,Vol.108,No.9 Mülleretal.
Scheme4. ProposedAmineParticipationintheOlefin andreleasingtheheterocyclicproduct.Surprisingly,kinetic
InsertionTransitionStateoftheHydroamination/ studiesusingN-deuteratedaminoalkenes88b,95haverevealed
Cyclizationa alargeprimarykineticisotopeeffectwithk /k intherange
H D
of2.3-5.2,althoughnoN-Hbondbreakingisinvolvedin
the rate-determining olefin insertion step. A plausible
explanation involves partial proton transfer from a coordi-
natedaminetotheR-carboninthefour-memberedinsertion
step (Scheme 4). However, some experimental data, in
aRR′NH)substrateorhydroaminationproduct. particular the observation of sequential hydroamination/
bicyclizationsequences(Videinfra),isinconflictwiththese
coordinating solvents (e.g., THF) found in the precatalysts, findings, because the latter requires a finite lifetime for the
andkineticdeviationshavebeenobservedmorefrequently.93–95 rare-earth metal alkyl intermediate.
Coordinativesaturationofthemetalcenterthroughstrong From a thermodynamic point of view, rare-earth metal
aminebindingresultsinreducedelectrophilicityandtherefore catalyzedhydroamination/cyclizationofaminoalkenesdiffers
reducedcatalyticactivity.Therefore,ifbindingofeitherthe
significantly from reactions involving aminoalkynes, ami-
substrate (Ksubst) or the product azacycle (Kprod) to the
noallenes, and conjugated aminodienes. For terminal ami-
catalyst is substantial, the rate of the reaction is reduced to noalkenes, the olefin insertion step of the Ln-amide into
the same extent as the reservoir of the more reactive, the carbon-carbon double bond is approximately thermo-
coordinatively unsaturated species is diminished with in-
neutral, and it is only slightly exothermic for an internal
creasing amine (substrate/product) concentration (eq 2).
aminoalkenewithan1,2-disubstitutedalkene(Scheme5,step
d[subst] k[catalyst] A).88,92Thefollowingprotonolysisoftheprimaryrare-earth
rate)- )
dt 1+Ksubst[subst]+Kprod[prod] metal alkyl species is quite exothermic, to a lesser extent
also for the secondary rare-earth metal alkyl species. In
(2)
markedcontrast,insertionofanalkyne,allene,or1,3-diene
Inmanyinstancesthebindingconstantsofthesubstrate(e.g., intotheLn-amidebondisveryexothermic(Scheme5,steps
primary aminoalkene) and product azacycle are similar or B-D).91,96,97Protonolysisoftheresultingvinyl(incaseof
virtuallyidentically(Ksubst≈Kprod≡K ),resultinginapparent alkynesandallenes)orη3-allyl(incaseofconjugateddienes)
eq
zero-orderratedependenceonsubstrateconcentration,because rare-earth metal species is about thermoneutral (for the
the overall amine concentration remains constant throughout vinylic species) to slightly endothermic (for the allylic
thereaction(eq3;[L])[subst]+[prod]). species)duetothesignificantstabilizationofthesespecies.
Despite these significant differences, it was proposed that
d[subst] k[catalyst]
rate)- ) (3) in all these cyclization reactions the insertion step is
dt 1+K [L]
eq rate-determining,89a,bfollowedbyarapidprotonolysisstep.
The rare-earth metal alkyl species formed in the insertion However, recent DFT analyses of the catalytic cycle of the
process is prone to rapid protonolysis with a second amine rare-earth metal catalyzed hydroamination of dienes and
molecule, regenerating the rare-earth metal amido species allenessuggestthatprotonolysisoftherare-earthmetalη3-
Scheme5. ThermodynamicsoftheElementaryStepsinRare-EarthMetalCatalyzedHydroamination/Cyclization88,91,92,96,97
Hydroamination ChemicalReviews,2008,Vol.108,No.9 3801
Table2. ComparisonofActivationParametersforHydroamination/CylizationReactions.
Scheme6. 5-endo-dig-Hydroamination/Cyclizationofa Scheme7. Lanthanocene-CatalyzedHydroamination/
Homopropargylamine.100 CyclizationofAminoalkenes88
allylspecies(inhydroaminationofdienes)orvinylicspecies
(inhydroaminationofallenes)istherate-limitingstep.89c–e
Theactivationparametersassociatedwiththerate-determin-
ingstepofthecatalyticcycleindicatethatthehydroamination/
Scheme8. Lanthanocene-CatalyzedHydroamination/
cyclizationinvolvesahighlyorderedtransitionstate(Table2). CyclizationofAminoalkynes96
Thehighestenthalpicbarrierisobservedforthecyclizationof
theinternalaminoalkenes,originatingfromstericandelectro-
staticrepulsionofthe1,2-disubstitutedolefin.
Quitegenerally,rare-earthmetalcatalyzedcyclizationsof
aminoalkenes, aminoalkynes, and aminodienes produce
exclusivelytheexocyclichydroaminationproducts.However,
cyclizationofhomopropargylaminesleadstotheformation
of the endocyclic enamine product via a 5-endo-dig-
hydroamination/cyclization (Scheme 6),100 most likely due
to steric strain in the four-membered ring exocyclic hy-
increasingionicradiusoftherare-earthmetalion(Table3,
droaminationproduct.Interestingly,the5-endo-digcycliza- entries 1-3 and 7-9).88 Better accessibility of the metal
tionisevenpreferredinthepresenceofanolefingroupthat
center also results in increased rates of cyclization, as
would lead to a 6-exo hydroamination product.
observable in the tied-back ansa-lanthanocene precatalysts
Initialstudiesonintermolecularhydroaminationofalkynes Me Si(C Me ) LnE(SiMe ) (2a,b-Ln; E ) CH (a), N (b))
withprimaryamines101suggestedfororganoactinidecatalysts 2 5 4 2 3 2
incomparisontothestericallymorehinderedpermethyllan-
amechanismcloselyrelatedtothatfoundforneutralgroup thanocenesCp* LnE(SiMe ) (1a,b-Ln;E)CH(a),N(b))
4 metal catalysts (Vide infra), involving a [2 + 2] cycload- (Figure 2 and T2able 3, ent3rie2s 3-6). A further increase in
dition pathway proceeding via reactive L AndNR imido
2 catalystactivitywasobservedwhenstericallymoreopenand
species. This proposal was put forth based on kinetic and
less electron-donating constrained-geometry catalysts
structuralevidence.101However,theobservationofactinide-
catalyzed hydroamination of an alkyne with a secondary
amine,102aswellashydroamination/cyclizationreactionsof
primary and secondary aminoalkenes,103 provide strong
evidencethatasecondmechanisticpathwaymustbeopera-
tive.Thereactionproceedsviainsertionoftheolefinicdouble
bond into an actinide-amide σ-bond in a polar and highly
orderedfour-centeredinsertiontransitionstate,analogousto
the lanthanide-mediated reaction.
2.2. Catalysts and Scope of Reaction
As reviewed earlier,8,30 rare-earth metal catalysts are
among the most active and most versatile catalysts for the
intramolecular hydroamination of (terminal) aminoalkenes
(Scheme7)88,104andaminoalkynes(Scheme8),96producing
pyrrolidines, piperidines, indolines, and azepanes. The rate
of cyclization generally decreases with increasing ring size
(5 > 6 . 7).88,96
Figure 2. Dependence of catalytic activity in hydroamination/
Catalyticactivityinrare-earthmetalcatalyzedhydroami- cyclizationofaminoalkenesonstericdemandofthecatalystligand
nation/cyclizationofaminoalkenesgenerallyincreaseswith frameworkforrare-earthmetalandactinidecatalysts.
3802 ChemicalReviews,2008,Vol.108,No.9 Mülleretal.
Table3. RateDependenceonIonicRadiusandStericDemandoftheAncillaryLigandintheRare-EarthMetalCatalyzedCyclization
ofAminoalkenes
entry catalyst ionic radius,107 Å T,°C TOF,h-1 ref
1 Cp*LaCH(SiMe) (1a-La) 1.160 25 95 88
2 32
2 Cp*SmCH(SiMe) (1a-Sm) 1.079 60 48 88b
2 32
3 Cp*LuCH(SiMe) (1a-Lu) 0.977 80 <1 88b
2 32
4 MeSi(CMe)LuCH(SiMe) (2a-Lu) 0.977 80 75 88b
2 5 42 32
5 MeSi(CMe)(CH)LuCH(SiMe) 0.977 80 200 88b
2 5 4 5 4 32
6 meso-[(ebi)YbN(SiMe)]a 0.985 25 0.6b 108
32
7 MeSi(CMe)(tBuN)NdN(SiMe) (3b-Nd) 1.109 25 200 105
2 5 4 32
8 MeSi(CMe)(tBuN)SmN(SiMe) (3b-Sm) 1.079 25 181 105
2 5 4 32
9 MeSi(CMe)(tBuN)LuCH(SiMe) (3a-Lu) 0.977 25 90 105
2 5 4 32
10 MeSi(CMe)(tBuN)Th(NMe) (6-Th) 1.09 25 15 103a,b
2 5 4 22
11 MeSi(CMe)(tBuN)U(NMe) (6-U) 1.05 25 2.5 103a,b
2 5 4 22
aebi)ethylene-bis-(η5-indenyl).bEstimatedvalue(2mol%catalyst,70h,79%isolatedyield).
Table4. RateDependenceonIonicRadiusandStericDemand
oftheAncillaryLigandintheRare-EarthMetalandActinide
CatalyzedHydroaminationCyclizationofAminoalkynes
ionic TOF, Figure3. Proposedstabilizationoftheolefininsertiontransition
entry catalyst radius,107 Å h-1 ref statethroughintramolecularchelation.
1 Cp*LaCH(SiMe) (1a-La) 1.160 135 96b
2 32
2 Cp*NdCH(SiMe) (1a-Nd) 1.109 207 96b Scheme10. LanthanoceneCatalyzedIntramolecular
2 32
3 Cp*2SmCH(SiMe3)2(1a-Nd) 1.079 580 96b Hydroamination/BicyclizationofAminodialkenes
4 Cp*LuCH(SiMe) (1a-Lu) 0.977 711 96b
2 32
5 MeSi(CMe)NdCH(SiMe) 1.109 78 96b
2 5 42 32
(2a-Nd)
6 Cp*UMe (4-U) 1.05 26 103a,b
2 2
7 MeSi(CMe)(tBuN)Th(NR) 1.09 7.8 103a,b
2 5 4 22
(6-Th)
8 MeSi(CMe)(tBuN)U(NR) 1.05 1210 103a,b
2 5 4 22
(6-U)
significantly slower and under much more forcing reaction
Scheme9
conditions (Vide infra). Interestingly, the reactivity pattern
in rare-earth metal catalyzed hydroamination/cyclization
reactions of aminoalkynes with respect to ionic radius size
andstericdemandoftheancillaryligandfollowstheopposite
trend to that observed for aminoalkenes, for example,
generally decreasing rates of cyclization with increasing
ionicradiusoftherare-earthmetalandmoreopencoordina-
tion sphere around the metal (Table 4).96
Me Si(C Me )(tBuN)LnE(SiMe ) (3a,b-Ln; E ) CH (a),
2 5 4 3 2
N(b))wereutilized.105Electroniceffectsalsoplayapivotal Thehydroaminationreactionsusingoxophiliclanthanide
role for catalytic activity. Thus, decreased reactivity of a catalystsarebestperformedinnon-polaraliphaticoraromatic
constrained-geometry indenyl lutetium complex containing solvents, whereas slight rate depressions are noticeable in
an electron-donating pyrrolidinyl substituent was observed polar solvents, such as THF (ktoluene/kTHF ≈ 5).88b Interest-
in comparison to 3a-Lu.106 ingly, the ansa-yttrocene 9,
Thestereoelectroniccharacteristicsoftheancillaryligand
are significantly more pronounced for organoactinide cata-
lysts. The constrained-geometry complexes Me Si(C Me )-
2 5 4
(tBuN)An(NR ) (6-An;An)Th,U;NR )NMe ,NMeEt,
2 2 2 2
NEt )103 are highly active hydroamination catalysts for
2
essentiallythesamesetofsubstratesasappliedtolanthanide
catalysts. In contrast, the sterically more encumbered and
electronically more saturated ansa-actinocenes
Me Si(C Me ) AnR (5-An; An ) Th, U; R ) CH SiMe , withanetherfunctionalitytetheredtothesiliconbridge,was
2 5 4 2 2 2 3
CH Ph)orthepermethylactinoceneCp* AnR (4-An)react shown to display increased reactivity (up to 5-fold) in the
2 2 2
rather sluggishly with aminoalkene substrates. cyclizationofaminoalkenesrelativetothenonfunctionalized
Cyclizationofaminoalkynescommonlyproceedssignifi- ansa-yttroceneMe Si(C Me ) YCH(SiMe ) (2a-Y),though
2 5 4 2 3 2
cantlyfasterthancyclizationofaminoalkenes.96Furthermore, the effect on diastereoselectivity was minimal to negligible
terminal as well as internal alkynes react with comparable (Scheme9).109Itwassuggestedthatthiseffectresultsfrom
rates, while internal double bonds in aminoalkenes react a stabilization of the polar olefin insertion transition state
Hydroamination ChemicalReviews,2008,Vol.108,No.9 3803
Table5. StereoselectiveRare-EarthMetalCatalyzedHydroamination/BicyclizationofAminodialkenesUsingCp*LnCH(SiMe) (Ln)
2 32
Nd(1a-Nd),Sm(1a-Sm)111
aGeneral conditions: 10 mol % catalyst in CD, 4 d. Substrates were generated in situ from their corresponding hydrochloride salts. bThe
6 6
stereochemistryoftheseproductshasnotbeenreported.
Table6. PreparationofTricyclicAromaticAzacyclesthrough
through an intramolecular chelation of the tethered donor
Rare-EarthMetalMediatedHydroamination/Bicyclization112
group (Figure 3).
Hydroamination/bicyclizationofaminodialkenes,amino-
dialkynes, and aminoalkeneynes allows facile access to
pyrrolizidinesandindolizidinesinatandemC-NandC-C
bond-forming process (Scheme 10).110 This process has entry R n m Ln T,°C dr yield,%
significant synthetic potential in the synthesis of complex 1 H 1 1 Sm rt <5.5:1b 79
naturally occurring alkaloidal skeletons. An important pre- 2 OMe 1 1 Sm 45-50 4.7:1b 84
requisite for the success of this reaction sequence is a 3 OMe 1 2 Sm 45-50 >50:1b 59a
sufficientlifetimeoftherare-earthmetalalkylintermediate 4 H 2 1 Nd 9-rt 1.7:1b 76
5 OMe 2 1 Nd 9-rt 1.4:1b 82
formed in the initial insertion process of the alkene/alkyne 6 H 2 2 Nd rt 26:1c >73
in the Ln-amide bond to permit the carbocyclization step. 7 OMe 2 2 Nd 45-50 16:1c 69
However,thissequenceisinconflictwiththelargeprimary
aIsolatedasHClsaltinthepresenceofBHT,butreadilyoxidized
kinetic isotope effect observed for primary aminoalkenes,
insolution.bStereochemistrynotestablished.cThemajorisomerhas
whichsuggestspartialN-Hbondbreakinginthecourseof a 1,3-cis relationship of the two stereocenters according to an X-ray
the olefin insertion step (Vide supra). crystallographicanalysis.
A more detailed study extended the hydroamination/
bicyclizationmethodologyalsotoquinolizidinesandprobed
whentheinitialhydroaminationstepinvolvedformationof
theinfluenceofalkylsubstituentsinvariouspositionsofthe
a five-membered ring.
substrate backbone on the sense and magnitude of diaste-
A further extension of this methodology gave access to
reoselection.111Whilemethylsubstitutioninthe(cid:1)-position
tricyclic (Table 6) and tetracyclic (eq 4) alkaloidal skel-
tothesecondaryaminenitrogeneffectedhighstereoselection
(Table 5, entries 2, 5, and 6), more remote positions closer
to the olefinic group (Table 5, entries 3, 4, 7, and 8) gave
poor selectivities. Possibly because of stereoelectronic
reasons, the larger neodymium catalyst performed better in
the formation of quinolizidines and indolizidines involving
six-membered ring formation in the initial hydroamination
(4)
step,whereasthesmallersamariumionwasmoreeffective
3804 ChemicalReviews,2008,Vol.108,No.9 Mülleretal.
Scheme11. ProposedMechanismofLanthanocene-CatalyzedInter-andIntramolecularHydroamination/Tricyclization.110b
Table7. Rare-EarthMetalCatalyzedHydroamination/CyclizationofHinderedGem-DisubstitutedAminoalkenesUsing
[(CHSiMe)Ln(µ-Me)] (Ln)Nd,Sm)
5 4 32 2
aReactioninneatsolution.
etons.112Particularlyhighdiastereoselectivitieswereachieved systems.Remarkably,electron-donatingmethoxysubstitution
in the formation of the pyrido[2,1-a]isoindolizine (Table 6, of the aromatic ring did not sequester catalyst activity and
entry 3) and benzo[a]quinolizine (Table 6, entry 6) ring selectivity to a significant extent.