Synthesis of Saturated Heterocycles via Metal-Catalyzed Alkene Diamination, Aminoalkoxylation ...

38 Pages·2017·1.76 MB·English

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]