TopHeterocyclChem(2013)32:39–76 DOI:10.1007/7081_2013_104 #Springer-VerlagBerlinHeidelberg2013 Publishedonline:19April2013 Synthesis of Saturated Heterocycles via Metal-Catalyzed Alkene Diamination, Aminoalkoxylation, or Dialkoxylation Reactions SherryR.ChemlerandDavidA.Copeland Abstract The development of metal-catalyzed additions of nitrogen and oxygen moieties across alkenes to form saturated nitrogen and oxygen heterocycles is described herein. This chapter covers the most recent advances in osmium and palladium-catalyzedalkeneoxidationandaminationreactionsandalsosummarizes the emerging areas of copper, iron, and gold-catalyzed alkene oxidations and aminations.Inmostexamples,moderatetoexcellentlevelsofdiastereoselectivity, either by stereospecific addition across the alkene or substrate-directed diastereocontrol, have been achieved. This enables the synthesis of nitrogen and oxygen-containingheterocycleswithpredictablecontrolofstereogeniccenters.Ina few cases, asymmetric catalysis has been achieved, allowing for the synthesis of chiral nitrogen and oxygen-containing heterocycles from achiral substrates. In manyoftheseoxidationreactions,useofpre-oxidizedsubstratesorstoichiometric amounts of added oxidants are required to achieve the catalytic cycles, which frequentlyinvolvehigheroxidationstatesofthemetalcatalysts. Keywords Alkenes (cid:1) Aminohydroxylation (cid:1) Asymmetric catalysis (cid:1) Copper (cid:1) Diamination (cid:1) Dihydroxylation (cid:1) Gold (cid:1) Indolines (cid:1) Iron (cid:1) Osmium (cid:1) Palladium (cid:1) Pyrolidines(cid:1)Saturatedheterocycles(cid:1)Tetrahydrofurans Contents 1 AlkeneDiamination.......................................................................... 40 1.1 Palladium-CatalyzedAlkeneDiaminations........................................... 40 1.2 Copper-CatalyzedAlkeneDiaminations.............................................. 44 1.3 Nickel-CatalyzedAlkeneDiaminations............................................... 47 1.4 Gold-CatalyzedAlkeneDiaminations................................................. 49 S.R.Chemler(*)andD.A.Copeland DepartmentofChemistry,TheStateUniversityofNewYorkatBuffalo,Buffalo,NY14260,USA e-mail:[email protected] 40 S.R.ChemlerandD.A.Copeland 2 AlkeneAminoalkoxylation.................................................................. 51 2.1 Osmium-CatalyzedAlkeneAminoalkoxylation...................................... 51 2.2 Palladium-CatalyzedAlkeneAminoalkoxylation..................................... 53 2.3 Gold-CatalyzedAminoalkoxylation................................................... 56 2.4 Copper-CatalyzedRing-FormingAlkeneAminoalkoxylation....................... 57 2.5 Iron-CatalyzedAlkeneAminoalkoxylation........................................... 64 3 AlkeneDialkoxylation....................................................................... 65 3.1 PalladiumandCopper-CatalyzedAlkeneDialkoxylationReactions................ 65 3.2 Cobalt-CatalyzedAlkeneDialkoxylationReactions.................................. 68 3.3 Osmium-CatalyzedAlkeneandDieneDialkoxylations.............................. 68 3.4 Ruthenium-CatalyzedDieneDialkoxylations......................................... 69 References........................................................................................ 70 1 Alkene Diamination Thesynthesisofasaturated nitrogenheterocycle andconcomitantintroduction of two nitrogen functionalities across an alkene can be enabled in a very direct and efficient manner using transition metal catalysis. Alkene diamination, initially explored in the 1970s with stoichiometric metal promoters, has experienced a resurgenceofeffortinthelastdecade[1–4].Transitionmetalsemployedtocatalyze olefindiaminationreactionsforthesynthesisofsaturatedheterocycliccompounds include palladium, copper, nickel, and gold (vide infra). Methods for alkene diamination that do not use metals have also been recently developed [5–13], but these reactionsfalloutofthescopeofwhichwillbecovered inthischapter.This review will focus on contributions made in the last decade, with emphasis on stereoselectivemetal-catalyzedalkenediaminationprotocols. 1.1 Palladium-Catalyzed Alkene Diaminations The first Pd-catalyzed alkene diamination was reported in 2005 and enabled the regio- and diasteroselective synthesis of cyclic ureas from conjugated dienes (Scheme1)[14].Theregioselectivityisthoughttoresultfromtherequiredforma- tionofaπ-allylpalladiumintermediate(Scheme1).Displacementof[Pd(0)]with thesecondaminegeneratestheproductandoxidationof[Pd(0)]withbenzoquinone regeneratesthe[Pd(II)]catalyst. That same year, a Pd-catalyzed intramolecular diamination of unactivated, isolatedalkenes was reportedtooccur inthepresenceofstoichiometric PhI(OAc) 2 (2.2 equiv.) [15]. This reaction generated fused 5,5-, 6,5-, and 7,5-bicyclic ureas inhighyieldsfromunsaturatedN-tosylureas(Scheme2). Amechanisminvolvinga[Pd(II)]/[Pd(IV)]catalyticcyclewasproposed(Scheme3) [15,16].Theauthorsproposedasequenceinvolvingsyn-aminopalladation,oxida- tion of [Pd(II)] to [Pd(IV)], N–Pd disassociation and C–N bond formation via S 2 substitution at carbon. An alternative mechanism that would give the same N SynthesisofSaturatedHeterocyclesviaMetal-CatalyzedAlkeneDiamination... 41 Scheme1 Pd-catalyzeddiaminationofconjugateddienes[14] O RR11 NH NHTs PPhdI((OOAAcc))22((52m.2oel%qu)iv) R1 N ONH R2 CMHe42NCCl2,l/Nrt,a1O2Ahc(1equiv) R1 R2 SubstrateScope O O O O N NTs N NTs Ph N NTs N NTs Ph 92% 94% 95% 91% O NHTs Pd(OAc)2(25mol%) O NH PhIC(OHA2cC)l22,(2rt.,24e8qhuiv) N NTs 86% O N NHTs Pd(OAc)2(10mol%) O H PhI(OAc)2(2.2equiv) CH2Cl2,rt,12h N NTs 89% Scheme2 Pd-catalyzeddiaminationofisolatedalkenes[15] stereochemical result has been supported by density functional theory (DFT) calculations and entails anti-aminopalladation, N–Pd association, oxidation to Pd(IV)andreductiveeliminationtogivetheN–Cbond[17]. 42 S.R.ChemlerandD.A.Copeland Scheme3 ProposedPd-catalyzeddiaminationmechanism[15,16] Scheme4 Diaminationofinternalalkenes[18] Using a similar protocol, bis-amination of internal alkenes for the synthesis of bisindoles was also achieved (Scheme 4) [18]. It is noteworthy that a metal-free alkenediaminationhasbeenreportedtooccurwithsimilarsubstratesandreagents togivelargelyidenticalproducts,butintheabsenceofapalladiumcatalyst[8]. Other oxidants were subsequently explored to enable the intramolecular Pd-catalyzed alkene diamination. In 2009, a Pd-catalyzed intra/intermolecular diamination that used N-fluorobenzenesulfonamide (NFBS) as both the oxidant and external amine source was reported [19]. Both γ-unsaturated amides and carbamates underwent the exo-selective reaction in good to excellent yield. A Pd(II)/Pd(IV)catalyticcycleinvolvingtrans-aminopalladationandC–Nformation via S 2 substitution was also proposed for this alkene diamination sequence N (Scheme5)[19,20]. Copper(II) bromide has also been used as the stoichiometric oxidant for the Pd-catalyzed diamination of internal acrylates (Scheme 6) [21–23]. Complemen- tary diastereoselectivities were obtained based upon the substrate structure: ureas gavecis-substitutedcyclicureaproductsfromtrans-acrylates[23]andsulfamides gave trans-substituted cyclic sulfamide products from trans-acrylates [22]. In the urea substrate case, the proposed mechanism is cis-aminopalladation followed by S 2displacementof[Pd],activatedbyCuBr .Inthesulfamidecase,theproposed N 2 SynthesisofSaturatedHeterocyclesviaMetal-CatalyzedAlkeneDiamination... 43 Scheme5 Pd-catalyzeddiaminationwithNFBSasoxidant[19,20] Ph Pd(OAc)2(10mol%) Ph Ph NH CO2Me CDNuMaB3FrP2,O(4040.(7°25Ce,eq1qu5uivivh)) Ph N CO2Me NTs O NHTs 92% O dr>15:1 Ph Pd(OAc)2(10mol%) Ph Ph O2NSHNHCCOO2M2Mee DCCMsu2FCB,Or42830(32(%°2Ceeq,qu1ui2viv)h) Ph NSO2NCCOO2M2Mee dr=11:1 Scheme6 Pd-catalyzeddiaminationofacrylates[22,23] mechanism is cis-aminopalladation, displacement of [Pd] with bromide and subsequentC–Nbondformationviabromidedisplacement. Thecatalyticasymmetricalkenediaminationhasbeenalongsought-aftergoal in asymmetric catalysis. The first catalytic enantioselective diamination was reportedin2007.ThisreactionformscyclicureasviaPd-catalyzedintermolecular diaminationofconjugateddienesusingdi-tert-butyldiaziridinoneasapre-oxidized diamine source [24]. The reaction is general for alkyl and aryl-substituted dienes and was regioselective for diamination at the more substituted, internal alkene of the diene (Scheme 7). Yields were good to excellent and enantioselectivity levels weregenerallyhigh.Chiralphosphoramiditeligandsprovedsuperiorinimparting enantioselectivity to the products. The mechanism involves oxidative addition of 44 S.R.ChemlerandD.A.Copeland Scheme7 Pd-catalyzedenantioselectivediaminationofdienes[24,25] Scheme8 CatalyticenantioselectiveC–Hdiamination[26] Pd(0)intotheN–Nbondofthediaziridinone,additionoftheN–Pd(II)complexto the internal alkene of the diene and concomitant π-allyl Pd formation and finally C–NbondformationviaPd(0)displacement(Scheme7)[25]. Thismethodwasfurtheradvancedbythedemonstrationthatthedienecouldbe formed in situ from terminal alkenes (Scheme 8) [26]. This C–H diamination reactioncouldbeperformedneatandprovidedsimilarproductstothoseshownin Scheme7(videsupra). 1.2 Copper-Catalyzed Alkene Diaminations Since2005,thediaminationofalkeneshasbeensimilarlypursuedusinglessexpen- sive copper complexes as reaction promoters and catalysts [27]. Highly diastereo- selective intra/intramolecular and intra/intermolecular copper(II)-promoted alkene diaminations have enabled the synthesis of pyrrolidines and indolines from SynthesisofSaturatedHeterocyclesviaMetal-CatalyzedAlkeneDiamination... 45 Scheme9 Copper(II)-promotedalkenediaminations[27–29] unsaturatedsulfamides,sulfonamides,amides,andureas(Scheme9)[27–29].Some examples of tetrahydroisoquinoline-forming diaminations have also been reported (Scheme9).ThereactionswereperformedwithCu(OAc) [27],Cu(neodecanoate) 2 2 [28], and Cu(2-ethylhexanoate) [29] as reaction promoter. Reactions with 2 Cu(2-ethylhexanoate) inPhCF generallyprovedmostefficient[29]. 2 3 The intra/intermolecular alkene diamination was rendered catalytic in [Cu(II)] withsulfonamidesastheintermolecularaminecomponentandMnO (3equiv.)as 2 thestoichiometricoxidant(Scheme10)[29].Apromisingcatalyticenantioselective intra/intermolecular alkene diamination using [Cu((R,R)-Ph-box)](OTf) as the 2 catalystwasalsoreported(Scheme10). The reaction mechanism, based on reaction diastereoselectivity and isotopic labeling studies [29], is thought to involve cis-aminocupration, homolysis of the resulting C–[Cu(II)] bond, addition of the resulting carbon radical to [Cu(II)], amine coordination and reductive elimination of the [Cu(III)] intermediate to form the new C–N bond and [Cu(I)] (Scheme 11). In the catalytic reactions, MnO isthoughttooxidizetheextruded[Cu(I)]backto[Cu(II)][29]. 2 In 2012, more electron-rich unsaturated amidine substrates were shown to undergo copper-catalyzed intramolecular alkene diamination to form bi- and 46 S.R.ChemlerandD.A.Copeland Scheme10 Cu(II)-catalyzedintra/intermoleculardiamination[29] NH Cu(OR)2 N [Cu(II)] N [Cu(II)] [Cu(II)] Ts R=2-ethylhexanoate Ts Ts NTs NHPh -[Cu(I)] [Cu(II)] [Cu(III)] -[Cu(I)] NHPh N N N Ts PhNH2 Ts Ts Scheme11 ProposedmechanismoftheCu(II)-promotedalkenediamination[29] tricyclicamidines(Scheme12)[30].Bothterminalandinternalalkenesunderwent thereactionefficiently. Theproposedmechanism,consistentwithproductdiastereoselectivity,involves two-electronoxidationoftheamidinefollowedbyaconcerted[3+2]-typeannula- tion(Scheme13)[30]. The copper-catalyzed intermolecular diamination of terminal alkenes and con- jugateddieneshasbeenreportedforthesynthesisofcyclicureas,sulfamides,and guanidines, where diaziridinones, thiadiaziridines, and (cyanimino)-diaziridines, respectively,wereusedasbothdiaminesourceandoxidant(Scheme14)[31–34]. Acatalytic,enantioselective diamination(upto74%ee)oftheterminal alkeneof conjugated dienes was achieved [35, 36], making the method complementary to analogousPd-catalyzeddienediaminations(videsupra,Sect.1.1). Itwasfurtherfoundthatdependinguponthesubstrateandcatalyststructure,the regioselectivityinthediaminationofconjugateddienescanbetunedforeitherthe internal or terminal alkene of the diene (compare Schemes 14 and 15) [33, 38]. Mechanistically, it was determined that the diamination can occur via a more SynthesisofSaturatedHeterocyclesviaMetal-CatalyzedAlkeneDiamination... 47 Scheme12 Cu-catalyzeddiaminationofunsaturatedamidines[30] Ph Ph Ph CuI(40mol%) Ph Ph 2,2'-bipyridine(40mol%) H DMF,60°C,O2(1atm),23h N Ph NH N 61% Ph Ph NH [Cu(II)] -H+ Ph Ph Ph PhPh -[Cu(I)] PhPh [Cu(II)] Ph Ph N [Cu(II)] N -[Cu(I)],-H+ N N Ph NH Ph NH Ph Scheme13 Proposedmechanismfortheunsaturatedamidinediamination[30] radical-type mechanism, selective for the terminal alkene, or via a more electro- philic,Cu(III)-typemechanism,selectivefortheinternalalkene(Scheme15)[33]. 1.3 Nickel-Catalyzed Alkene Diaminations Nickel complexes have been used to catalyze the intramolecular diamination of unsaturated sulfamides, ureas, and guanidines (Scheme 16) [4, 39]. Terminal and 1,1-disubstitutedalkenesunderwentthereactionwithgoodefficiency,andPhI(OAc) 2 wasusedasthestoichiometricoxidant. 48 S.R.ChemlerandD.A.Copeland O O CuCl(cid:129)P(OPh)3(10mol%) tBuN C6D6,rt,6h NtBu tBuN NtBu + R R (1.5equiv) R=Ph,75% R=CO2Me,50% O O CuCl(10mol%) (R)-DTBM-SEGPHOS(5.5mol%) tBuN tBuN NtBu + Ph C6D6,toluene,0°C,20h Ph NtBu (1.5equiv) 69% 65% ee O (R)-DTBM-SEGPHOS = O PAr2 Ar=3,5-(tBu)2-4-MeOC6H2 O PAr2 O O CuCl(cid:129)PPh3(5mol%) tBuN O tBuN NtBu + Ph CDCl3,65°C,9h NtBu 91% Ph (2equiv) NCN NCN 10mol%CuCl(cid:129)PPh3(1:2) tBuN CDCl3,65°C,24h NtBu tBuN NtBu + 74% (2equiv) S S OS2 + CuCClD(cid:129)PC(nl3-,B5u0)3°C(2,02m4ohl%) tBuN SNOt2Bu tBuN NtBu (1.5equiv) NTs 80% NTs Scheme14 Copper-catalyzeddiaminationofalkenesanddienes[31,32,34,35,37] O O CuBr(5mol%) tBuN NtBu + CDCl3,0°C,20h tBuN NtBu 95% (1.1equiv) O Ph Ph Ph tBuN -[Cu(I)] tBuN tBuN NtBu N CuIIL NtBu O X CuLII O tBu X O [Cu(I)] tBuN NtBu O O O tBuN tBuN NtBu tBuN NtBu NtBu CuIII Cu X L X Scheme 15 Regioselectivity and mechanism of the copper-catalyzed diamination of dienes [33,38]
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