Thermal azide–alkene cycloaddition reactions: straightforward multi-gram access to Δ 2-1, 2, 3

13 Pages·2017·1.53 MB·English

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Thermal azide alkene cycloaddition reactions:
nce. straightforward multi-gram access to Δ2-1,2,3-
4 AM. ed Lice C40it2e3this:GreenChem.,2018,20, triazolines in deep eutectic solvents†
2:42:1Unport FilipSebest, aLuisCasarrubios, a,bHenryS.Rzepa, aAndrewJ.P.White a
23 13.0 andSilviaDíez-González *a
oaded on 3/13/20mons Attribution RADrsecOccc.lIiee:/gip1vrt0eee.ded1n082c3t9hh9et/hJmcu8Jnugenc0e20127109817,8b TDfuhelleeppmroEudultutie-ccgttrdiacimsStrosibylvunettnihotens(DiwsEaoSsf)saitsuwrdeidipeeodrrwatenidtgh.eTaohnfee1rx,o2p,le3er-iotmrfiaeDznEotSaliln/inceosthmviisaptuartazanitdsioefo–nraamll-kaDetnFioeTncaaypscplwrooaeadlcldhai.stiothnereoarcigtiinonosfitnhea
nlm
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ugust 2018. Der a Creative I1n,3-tDriopodlaur ccytcilooandditions, also known as Huisgen reactions, Efzuovrleitnnheewsr,h8reeianscotiasndatrnoildaezsoo,9tlhinaemer hicdaeintneerbos,ec1y0cfoplerysmrr(eosdlu-,cahintadosfittnredinaozlro-eilzeaisrdr,i7annpegyser1as1)/-
7 Aund areconvergentandatom-economicalreactionsthatofferacon- are isolated instead. In consequence, the promise of 1,2,3-
n 0ed venient synthetic route for five-membered heterocyclic mole- triazolines as versatile synthons12 and biologicallyactive com-
d oens cules.1Todate,fewreactionscanmatchdipolarcycloadditions poundsremainsunfulfilled.13
ec
Publishcle is li imnotlheecuvlaarriectyomofpbleoxnidtystihnatthceanobbetaiinnveodlvepdroadnudcttsh.eHinecnrceea,sethoef twoArtehgeiormisoaml aezriidcet–railakzeonlienceysc,leoiatdhderiti1o,n4-isorex1p,5e-cdteisdubtostditeultievedr,
Article. This arti eyexaternssiisvemroesreeatrhcahncojuvsetriafgieedreacnedivehdasbynothtaebselyraelalcotwioendsuonvecorvtehre- afancdtotrhs.e14pTrohdeurmctoddiysntraibmuitciaolnly,isdimpoalianrlycdyciclotaatdedditbioyneslelcetardoinnigc
s ing alternative catalytic routes leading to broader and more to either triazoles or triazolines are virtually identical.
s
e
cc selective reactions, including enantioselective ones. A particu- However,whiletriazolesarearomaticandhighlystable,triazo-
A
n larly high-profile example of this is the copper-mediated linesaretypicallymorereactivethanthestartingmaterialsdue
e
Op azide–alkyne cycloaddition reaction,2 and this transformation tothenumerousdecompositionpathwaysavailabletothem.15
hasbecometheemblemofClickchemistry,3aconceptcoined The most commonly encountered products are then imines
by Sharpless in 2001 and closely related to that of Green (often hydrolysed into amines and carbonyl derivatives) and
chemistry. aziridines. The formation of aziridines upon nitrogen extru-
While the use of metals (mainly copper, but also ruthe- sion from the corresponding triazolines could be a simple
nium, iridium, or silver)4 has been instrumental for the study alternative to metal-mediated aziridination reactions with
and application of triazoles, the preparation of 1,2,3-triazo- azides as nitrene source.16 However, the formation of aziri-
lines from azides and alkenes remains limited to highly acti- dines from the corresponding triazolines depends stronglyon
vatedalkenes,suchasstrainedandelectron-richalkenes,5and the position and electronic nature of the substituents on the
therefore out of the scope of Click chemistry. Simple alkenes five-membered ring,12 which has led to apparently conflicting
donotreactwithazidesorreactveryslowlyandreactiontimes reportsovertheyears.17,18Unlikethereactionwithalkynes,to
of several days or even months are not overly uncommon.6 the best of our knowledge no metal-mediated version of the
azide–alkene cycloaddition has been reported and therefore
thescopeofthisreactionremainsseverelylimited.
Ontheotherhand,itwasrecognisedearlyonthatthereac-
aDepartmentofChemistry,ImperialCollegeLondon,ExhibitionRoad,
tion media could play a key role in numerous non-catalysed
SouthKensington,LondonSW72AZ,UK.E-mail:[email protected]
bDepartamentodeQuímicaOrganicaI,FacultaddeCienciasQuímicas,Universidad dipolar cycloaddition reactions.19 As part of our interest in
ComplutenseandCentrodeInnovaciónenQuímicaAvanzada(ORFEO–CINQA), developing user-friendly and greener methodologies, we
28040Madrid,Spain turned our attention to Deep Eutectic Solvents (DESs). DESs
†Electronic supplementary information (ESI) available: FAIR data for NMR
are combinations of two or three inexpensive, non-toxic and
spectra, computational and crystallographic data, see ref. 48. CCDC
1843142–1843147.ForESIandcrystallographicdatainCIForotherelectronic safe components that produce a non-flammable mixture with
formatseeDOI:10.1039/c8gc01797b a much lower melting point than any of the individual com-
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ponents. These mixtures, which are liquids at the reaction Table1 Solventscreeninga,b
temperature, are held together via hydrogen bonding inter-
actions. The interesting physico-chemical properties of DESs
are often compared to those of ionic liquids, with the
additional advantages of lower costs and much higher user-
and environment-friendliness (i.e. water tolerance).20 The
benefits of using DESs instead of ionic liquids or standard
organic solvents are obviously dependent on the actual DES Entry Solvent 1ac(%) 3aac(%) 4aac(%)
ce. components. Those made of urea, glycerol, water or choline 1 Toluene 25 5 13
13/2023 12:42:14 AM. ution 3.0 Unported Licen prfycaoelhtaiiardlromcTotentirhcsia,io,eudt2nimle3oaasnaarpa,strpneoeulDrdfcipichEapaaliSyrtssasirt,oosircxonohLualsraiezlgdavwooaeirlninlfesyesbiDcspaecEfrefaroinrSdonomsm-dmcaiaasportitnpeanrhlilggietysaerstiindceenloedaoGrdtmroDoireleexiyssteeipadelnsoslvepl–neicsrAcrh.de2alaei4dclnmdhegFcireinyrsmarcogtezlrmiooaysiac.nmtrtdaiyedsoz.t2eniih1tdpsiieaon,I2srnne2-, 4567891230 1TTDEEDMC,HBttHiM4eOOgM-FCClDSAHyNlEOcmi3oxeane 13130321290478263 <1311<5<<58010555 711117<0543015
oaded on 3/mons Attrib emmitaehdneiyraotweftatrhsaezrsaoetlieeosxn2a5amloisrpeltedrsiaetzihtoheleebsre2tn6hehrfoaicuviegahlbeetffehneecpLtreoewfpiDasrEaeScdiadisnitryDeoaEfcSto.ionInne a1112Reaction coWDnEdaSitteirons: Azide 1a17(21 mmol), sty05r5ene 2a (1.3 eq01u8iv.) in
nlm ofthecomponents,ortheformationofhydrogenbondsbetween 2 mL of solvent. bObserved trace decomposition products:
wo
oC
018. Deative eithHereroefinthewcoempreopnoernttssatnrdaitghhetfcoyrcwloaarddditaioznidpe–aartlnkeernse. cyclo- .
ugust 2er a Cr aadzodliitnioencryecalcotaiodndsucitns,DoeerpiEnutseocmticeScoalvseenstsaztoiriydieinldes1,,2w,3h-etrrie- c1H NMR yields/recovery are the average of two independent experi-
n 07 Aed und orersgualntsic.PsroellvimenitnsaroyrstiuondiicesltioquaisdcserotanilnytlheedrotoledoifsaDpEpSoiinnttinhge maseinnttserannadlswtaenredadredt.ermined with respect to 1,3,5-trimethoxybenzene
d oens azide–alkenecycloadditionreactionandtheoriginoftheaziri-
ec
Publishcle is li dineproductsarealsopresented. Capitalising on this promising result, the optimisation
Article. This arti Results and discussion stitcudsioelsvethnetsnfaoncdusdediffoenrecnytclroeaadcdtiiotinontirmeaecstioannsdintedmepeepraetuutreecs-
s were screened. At 80 °C no further conversion was observed
s
e Optimisationofthereactionconditions
cc whenthereactionmixturewasheatedfor24hinsteadof16h.
A
n 4-Trifluoromethylphenyl azide and styrene were chosen as Comparable conversions into 3aa and 4aa were observed at
e
Op model substrates and they were reacted at 80 °C overnight 90°Cafter8h,butagainthereactiondidnotproceedfurther
(Table1).Mixturesof1,5-disubstitutedtriazoline3aaandaziri- afterlongerheatingperiods.Higherreactiontemperaturesled
dine4aawereobtainedinmostreactions.Anumberofknown tosignificantformationofdecompositionproducts.
decomposition products of triazolines –an imine, aniline or Next,anumberofcommonlyencounteredDESsweretested
acetophenone (Table 1)– were evidenced by NMR in many of (Table 2). In all cases, the starting azide was fully converted
these reactions but only as traces. Disappointing NMR yields when 2 equivalents of styrene were employed and overall
were obtained in all tested organic solvents independently of similar reaction outcomes were obtained with most of the
their characteristics due to severe decomposition of cyclo- tested DESs. The original choice, choline chloride/urea (1:2),
adductsand/orthestartingazide(upto80%ofthetotalmass, led to the highest conversion into the desired triazoline 3aa.
Table 1, entries 1–10), which made it virtually impossible to When choline iodide was used instead as the Lewis base
isolate any reaction product. In stark contrast with these partner, significant formation of 4-trifluoromethylaniline
results, a clean reaction was obtained when the model sub- (∼10%) was observed and the resulting DES was only liquid
strates were heated in a mixture 1:2 of choline chloride and above70°C,whichmadeitsmanipulationcumbersome.Other
urea(DES,Table1,entry12). DESs remained valuable options, except when a more acidic
It is important to note that both reaction products are partnersuchasglycolicacidwasusedasoneofthecomponents
stable under the reaction conditions and they were recovered and only a complex mixture of decomposition products was
quantitativelywhenheatedseparatelyat80°CinDESfor16h. obtained (Table 2, entry 6).27 A similar outcome was observed
However,partialdecompositionoftriazoline3aawasobserved when a popular ionic liquid, BMIM·PF (BMIM = N-butyl-
6
when heated in standard organic solvents (i.e. DMSO, 1,4- N′-methylimidazolium),wasusedassolvent(Table2,entry7).
dioxane) at the same temperature (vide infra). We believe that After this screening, the term DES in this article will refer
this increased stability of triazolines in DES is key to explain- solelytoa1:2mixtureofcholinechlorideandurea.28Todate,
ingthesuccessofthesereactions. only a handful of 1,2,3-triazolines have been structurally
4024 | GreenChem.,2018,20,4023–4035 Thisjournalis©TheRoyalSocietyofChemistry2018
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Table2 Screeningofdeepeutecticsolventsa
Entry Solvent 3aab(%) 4aab(%)
ce. 1 Cholinechloride/urea(1:2) 67 22
n
4 AM. ed Lice 234 CCChhhooollliiinnneeeiccohhdllooidrriiedd/uee//rewetaaht(ye1lre:n(21e):g2l)ycol(1:2) 666101 111813
2:42:1Unport 56 CChhoolliinneecchhlloorriiddee//ggllyycceorliocla(1ci:d2()1:2) 6D1ecomposit1io2n
23 13.0 7 BMIM·PF6 Decomposition
13/20ution oafRseoalcvteionnt.cbo1nHdiNtiMonRs:yiAezliddsea1rae(t1hemamveorla)g,estoyrfetnweo2iand(2epeeqnudive.n)tinex2pmeriL-
oaded on 3/mons Attrib maseinnttserannadlswtaenredadredt.ermined with respect to 1,3,5-trimethoxybenzene
nlm
owCo characterised,29 and therefore single crystals were grown for
018. Deative C3araysatanlds o4faa3atoaccoonnftiarimnetdhetwaossiingndeepdesntdruecntturmesol(eFciugl.e1saanndd2in). Fig.2 Structure of aziridine 4aa (50% probability ellipsoids). Most
August 2der a Cr bmoatthioonfwthitehmC5thlyeintrgiaczao.l0in.2e0rÅinoguthaosftahesm{Na1ll,Ne2n,vNe3lo,Cp4e}dpelafonre- 6h(°0y):d.9roN(2g1),e–CnCs42–arNe11.4o–7mC72(it4t1)e,8d.3Nf(o13r–).cCl3arit1y..4S5e1l(e5c),teCd2b–oCn3dle1.n4g8t4h(s5)(Å;)Can3–dNa1n–gCle2s
n 07 ed un inmolecule3aa-A(0.18Åin3aa-B),whichatomsarecoplanar
d oens to better than 0.01 Å in both instances. In each case, the
Article. PublisheThis article is lic mwpp4-lliCaaothnnlFeee3ct-,hupawelhpehepsNni.r1loyeA–laCztcgih5hrrie–oedCsuip1nphe6ecei–lsnCsipcya2alsl1effmrdiotnooldsrwgstsiiotochanonr-eprCaelnf5saapgnrileasecmrstotobrotireoeeitnnhtcthgeeoedmc{aNNms.1u12o,c–8NnhC°2,5,itNanhbn3abodt,Coniti4dthns}, SWsccoiotppheeaooffsetthhteeorfreeoaapcctttiiioomnnisweidthcoanrdanitgioenosfianryhl/ahnedte,rowaeryelxapzloidreesdatnhde
s styrene (Table 3). In all cases, the desired 1,5-disubstituted
es thecaseof4aa,thetorsionanglebetweenthetwosubstituents
cc triazolines were the major product in these reactions and the
A is138°(Fig.2).
n 1H NMR conversions for the corresponding aziridines ranged
e
Op between 6 and 36%. Proportionally, the highest formation of
aziridines was observed when using azides bearing electron-
donating substituent(s) (Table 3, entries 12–15). Reactions
with heteroaryl azides as cycloaddition partners (Table 3,
entries16–18)werecarriedatlowertemperatures(60–70°C)as
substantial decomposition of the reaction products was
observedat80°C.
Even if the main purpose of this work was the preparation
of 1,2,3-triazolines, manyof the formed aziridines4 were also
isolated and fully characterised due to the inherent impor-
tance of this heterocyclic motif, both in chemistry and
biology.30 Traces of aniline derivatives were observed in many
ofthesereactions,butsuchadecompositionproductwasonly
significantwhenanitrosubstituentwaspresentinthestarting
azide (Table 3, entry 2, 23% by 1H NMR). On the other hand,
imine formation was only competitive in the reaction of
heteroaryl azide 1r (Table 3, entry18). Indeed, whereastriazo-
Fig.1 Structure of one (3aa-A) of the two independent molecules linesbearingortho-electron-donorgroupsintheir1-arylsubsti-
presentinthecrystaloftriazoline3aa(50%probabilityellipsoids).Most
tuentswerefoundrelativelystable,thiswasnotthecasewhen
hydrogensareomittedforclarity.Selectedbondlengths(Å)andangles
the ortho substituent was an electron-withdrawing one. For
(°):N1A–N2A1.380(6),N2A–N3A1.241(8),N3A–C4A1.471(8),C4A–C5A
1.538(8), N1A–C5A 1.462(7); N3A–N2A–N1A 112.2(5), C4A–C5A–C16A example, in the reaction with 2-trifluoromethylphenyl azide,
113.2(4). only traces of the desired triazoline were observed together
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Table3 Reactionscope–arylandheteroarylazidesa decomposition by-products. Finally, purification on neutral
alumina resulted in the substantial decomposition of both
products. Overall, basified silica led to the best separation of
the formed reaction products while minimising their
decompositionduringpurification.
Benzylic azides were also screened in DES (Table 4),
althoughlowerconversionsintocycloadductswereobservedin
Entry R 3:4b(%) 3c(%) 4c(%)
these reactions, particularly when no electron-withdrawing
2:42:14 AM. Unported Licence. 6725341d 4444444-------BCNCCICr(OlNFO13((O2e11(()1gE(f11c))ta)b)()1d) 76676771830021:::::::3223621170444 55556556748787 2122—1441018 fgoemorrrauoidxturetuurpdrrsetieosffw.emoeTrnrehaelnxeyitpmrlrpeeeidarssoceetdtnoiauotz.cnsitiLdsgooe,nfnwicfbgoiieictnshrav(naerteztrhiasddaicoteetinc)boo,1enmbavsurplittenoimdhgsiiettgaioshotenctrhoriaouerzfelodfatolchirbntemieeoranueatsaintoecedndtmioaiopnnnf-
13/2023 1ution 3.0 891101 4H33--,5FC(-1F((iC13)hF(1)j))(1k) 67576636::::21329001 56576846 1——253 abzeierTnihdiernepereorarintcetgdiobnteoinoygfiet1lhd-eazamidmaojoi-x2rt-ueptrrheoodoxufycetrteh(g3ai4noveiaso,wmTiatebhrliecs4tty,rrieeannztoerlyihn4ae).ss
nloaded on 3/mmons Attrib 11114523 4244-,--4OMiP,M6re-((e(1M13(ml1e)2n))3)(1o) 55556427::::33326539 54451866 22219871 toNarffiMtee1dRr,5th-odyeiiaersteluidpnb,rgsotrdinetuusecptaeeetdctathtitvrisie5al0tzyro)a°.lnCinTsefhfooiarrsmn3dra0etaaidozcitnariy,oisdnw.i3ne1ceoHo(bu4otl9wad%ienvaeealdrsn,odaw3mbh5eei%xntpu1werHree-
owCo 16e 69:15 62 14
018. Deative foofrsmtierrdining(DTEaSb,leal4b,eeitnltoryw5c)o.nOvnelryssiotanrstiwnegrmeoabtetraiianlesdwaefrteerre1c6ovh-
ust 2a Cr 17 35:6 — — ered from the reactions with other aliphatic azides (i.e. decyl
uger
Ad
n 07 ed un 18f 43:11 33 — Table4 Reactionscope–aliphaticazidesa
d oens
ec
Publishcle is li aReaction conditions: Azide 1X, styrene 2a (2 equiv.) in DES (0.5 M).
ss Article. This arti wsbatt1eaH7rne0dN°daCMredtRfe.orcrmyIi2seio4nldlehasdt.eafdwrReieytiahtehcltedrieosas.nvpdeecrRcaaetrgraeticoetodio1fo,nt3uw,tt5iom-attireni6md=0ee°8ptChehnof.oxdeyreRbn3eet2naechzxte.ipnoeneriacmaserrinniettsderaonnuadtl Entry Azide 3:4b(%) 3c(%) 4c(%)
e
cc 1d 1s 36:34 28 29
A
n
e
Op with 30% of aziridine, 18% of imine and 6% of aniline. In 2d,e 1t 50:30 42 22
thecaseof2-nitrophenylazide,onlyformationofimine(18%)
andaniline(16%)wasevidencedby1HNMR. 3 1u 18:8 — —
While the optimisation studies were carried out using
1 mmol of aryl azide, the reactions could be easily scaled up
andthescopeofthecycloadditionwasexploredusing3to5g 4e,f 1v 9:24:42:15 6(31va) 1(44va)
20(33va)
of azide (15–27 mmol). This led to the multigram isolation of
29(34va)
1,2,3-triazolines,typicallybysimpleprecipitationandrecrystal- 5g 1w n.d. 16 5
lisation from the reaction mixture, which minimisesthe need
for volatile organic compounds. Column chromatography was aReaction conditions: Azide1X, styrene 2a (2 equiv.perazidegroup)
in DES (0.5 M). b1H NMR yields are the average of two independent
stillnecessaryinsomecases,asfortheisolationofoilytriazo-
experimentsandweredeterminedwithrespectto1,3,5-trimethoxyben-
lines and aziridines, since the latter remained in the filtrate zene as internal standard. cIsolated yields. dReaction carried out at
duringthefirstrecrystallizationstep.Whiletriazoline3aaand 85°C.eReactiontime=24h.fFourreactionproductscouldbeisolated
inthisreaction:
aziridine 4aa could be separated on silica, significant
decomposition (∼40% of the formed materials) was observed
as expected for products sensitive to acidic conditions. This
could be easily avoided using basified silica (triethylamine),
instead.Nodecompositionwasobservedwithcelluloseeither,
althoughtheseparationof3aaand4aawaspoorandrequired
severalcolumnstoobtainanacceptablepurity.Whenbasified
alumina or florisil were used as stationary phase only triazo-
line 3aa was recovered, albeit contaminated with some gReactioncarriedoutat70°C.
4026 | GreenChem.,2018,20,4023–4035 Thisjournalis©TheRoyalSocietyofChemistry2018
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azideandadamantylazide)at80°C.Whenthereactiontemp-
erature was raised to 90 °C, 8% of the desired triazoline was
observedby1HNMRwithdecylazide,buthighertemperatures
onlyledtoseveredecompositionofthereactionmixture.
Next, the generalityof the reaction in terms of alkene sub-
stitution was studied (Table 5). Two other styrene derivatives
were screened bearing either an electron-withdrawing or an
electron-donatinggroupattheparaposition(Table5,entries1
e. and2).Whileonlyformationoftriazoline3dcwasobservedin
c
2:42:14 AM. Unported Licen tftdhoreirearmizvroaealtatiiincovteeniot(nwoTaawasbzilitoerhbids54ie,-nrmveeenerdttahrtywoioxi3tywh)s.taytTshrheeanel4seo-s,ctahroulblocotrtawuoineraerendroaaflwtoiitogtruhioaefza.otAnrliianaspizemho3ltiihldnayderl
13/2023 1ution 3.0 owburaorsacdeoxsnpifgeinrrimaelnescdweberyiesXo-ubransyeurcsvureyadsltainfllooirtgsrta1hHpihsNyfM(aFmRigis.lpy3e)cobtfreuccmaoum,swephosieucvnhedriasnl. Fig.3 Structure of triazoline 3dd (50% probability ellipsoids). Most
oaded on 3/mons Attrib cI(Tnoatrebrerlesespt5oi,nnegdnliytn,rgyt4ha)ez.iTrihrdeiiasncwetiao4sndaelosofast4ht-ehvieonnymllypaypjroriodrdinrueecatcatthiffoaontrdcpoerudolddtuhbceet 11h(°1.y)53:d4.r92No9(g21(e1–),2nN)sN.2a1r–1e.C3o57m24i1t.(t41e86d)8,f1o(N1r92c)–l;aNrNi3ty3.–1SN.e22l5e–1c5Nt(e11d9)1b,1o1Nn.9d37–(le1C4n4)g,th1Cs.44(7AÅ7–)(2Ca)n,5dAC–a4nC–g1Cl6eA5s
nlm isolatedanalyticallypurefromthisreaction.
wo
oC
018. Deative
ugust 2er a Cr Table5 Reactionscope–monosubstitutedalkenesa impWaectaolsnothfoeucnydclothaadtdtithieonalolyulticcosmueb.stIintudeenedt,htahseareparcotifoonunodf
7 Aund allyltrimethylsilanedeliveredtriazoline3dgingoodyieldsand
n 0ed only traces of the corresponding aziridine. However, allylic
d oens alcoholledtotheformationof30%ofaziridine4dhandonly
ec
Publishcle is li 5fo%rmoaftitorinazo(l∼in2e5%(Tab1Hle 5N,MenRtrieysie6lda),ndin7d).icSaitginveificoafntparnoidliuncet
Article. This arti Entry Alkene 3:4b(%) 3c(%) 4c(%) ddeecriovmatpivoessi.tiEovne,nwanasalokbenseervaesdnoinn-aacltlivareteadctaiosn1s-owctietnheaclolyullidc
s 1 2b 53:31 39 — be successfully used under our reaction conditions (Table 5,
s
cce entry8).Asexpected,5electron-richeralkenesledtocompletely
A
n 2 2c 86:0 70 — selective reactions and no aziridine formation was observed
e
Op (Table 5, entries 9 and 10). These alkenes were particularly
reactive cycloaddition partners and triazoline 3dk could be
3 2d 56:25 42 14
prepared at 65 °C in high yields. This accrued reactivity was
exploited with allyl vinyl ether (Table 5, entry 11), which deli-
4 2e 31:40 — 31
vered 5-(allyloxy)triazoline 3dl with only traces of the
triazoline issue of the reaction of the allyl moiety.
5 2f 44:16 41 3 Nevertheless, the presence of an allyl group remained proble-
matic and around 30% of the overall mass could not be
6 2g 67:<5 62 — accountedforinthiscase.
7 2h 5:30 — 16 Next, the effect of introducing additional substituents on
the alkene partner was explored. In general, longer reaction
8d 2i 52:15 43 26
times and/or higher reaction temperatures were required to
9e 2j 74:0 66 — overcometheincreasedstericbulkinthesereactions(Table6).
1,1-Disubstitutedalkenesledtotheexclusiveformationofthe
corresponding triazolines with the notable exception of 1,1-
10f 2k 90:0 85 —
diphenylethene (Table 6, entries 1–3). Norbornene yielded tri-
11g 2l 56:0 37 —
azoline3dpquantitativelyatroomtemperature(Table6,entry4),
aReaction conditions: Azide 1d, alkene 2X (2 equiv.) in DES (0.5 M). as expected for a strained substrate.5a In stark contrast,
b1HNMRyieldsaretheaverageoftwoindependentexperimentsand unstrained 1,2-disubstituted alkenes led to the stereospecific
were determined with respect to 1,3,5-trimethoxybenzene as internal formation of the corresponding aziridines (trans-aziridines
standard. cIsolated yields. dReaction carried out at 85 °C. eReaction
carriedoutat75°C.fReactioncarriedoutat65°C.gReactioncarried from E-alkenes and cis-aziridines from Z-alkenes). The crystal
outat60°C. structure of 4dq confirmed the stereospecificity of the aziri-
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Table6 Reactionscope–disubstitutedalkenesa Mechanisticstudiesandoriginoftheaziridines
(A)TheDESeffect:Asmentionedintheintroduction,nometal-
based catalysts have been reported for azide–alkene cyclo-
additionreactions.Wecouldonlyfindtworeportsevokingthe
use of organocatalysts in this reaction. Garcia-Garibayand co-
workers reported the use of dimethylurea as catalyst in the
Entry Alkene Conditions 3:4b(%) 3c(%) 4c(%) cycloaddition reaction of aryl azides and electron-poor 1,2-di-
e. 1 75°C,96h 92:0 87 — substituted alkenes.35 Alternatively, tetramethylammonium
c
13/2023 12:42:14 AM. ution 3.0 Unported Licen 234 91R00T0,°1C°C6,,1h672hh 6316000::01:07 529149 —1—1 toorhemoenbbyaedotttcdaahrntiiioieennaogssteeneeeddtnmo,tr(reTisaiipaxasucoztobcluofrlolaatrlemeiettneed7ape,st.awce3rnoon6iaanibsteWzrdsdoieuiehltressiebvoesne1ydnd–asw3sf,btti)eoeg.yornLsn1miuiHilftnybiteclNjdesdaei,iMncitasuitttfaeRepdaod.npxetoihoycdn,oieanecmttyciiocopynlfncooglosaooiurdatefirddsotudurnhecilettatisoscoiftnnwwiotteeehnorrreeesf-
oaded on 3/mons Attrib 56 110100°°CC,,4186hh 00::6402 —— 5336 tthiornoFsuugrtihnheHrDm-EboSor,ne,daininngoprigrneatvneirooacucasttiaoelnyxtsaimcbpeeltffewseeceotnfisdthipoefotlecanyrclcsoyuacgdlgodeaistditdoendi-
nlm partnersandDEScomponents.23,24,26bWhilesuchinteractions
owCo 7 90°C,32h 0:26 — 21
018. Deative 8 95°C,32h 0:26 — 21 minitgehrntalbeniterostgaebnlisahtoemd,wmitohstaonfythoergaalnkeicneaszisdcereetnherdouignhthitiss
ugust 2er a Cr aReaction conditions: Azide 1d, alkene 2X (2 equiv.) in DES (0.5 M). wneovrekrthareelesnsottesstuesdceepatcihbleoftotheforDmEiSngcohmypdorongeenntsbaosnodrsg.anWoe-
7 Aund b1HNMRyieldsaretheaverageoftwoindependentexperimentsand catalysts for cycloaddition. In these tests, THF/water mixtures
d on 0ensed wstearneddaredte.rcmIsionleadtedwiytiheldress.pect to 1,3,5-trimethoxybenzene as internal agnendevoiugsorsooulsutsitoinrrsi.ngViwrteuraellryeqiudiernedticianlorredseurltstoweenrseuroebhtaoimneod-
ec
Publishcle is li dine formation,32 which is in agreement with the expected wenitthrieesit5hearnd156)maonld%evoefnchifotlhineeccohnlvoerrisdieonorofutrreiaazo(Tlianbele3a7a,
Article. This arti conAfzigiruirdaitnioesna4ldstqa–b4idlittywoefrseinagclceotmbipraadniiceadlsb(vyiddeeicnofrma)p.3o3sition rweamsaoibnteadinmedodwehstenittshheoucyldclobaedndoittieodntwhaast ocanrlryieddecooumtpinosTitHioFn/
s products, which suggeststhat triazolines bearing substituents water in the absence of an additive. Using both DES com-
s
e
cc onthe4-positionareconsiderablylessstableandsupportsthe ponents in sub-stochiometric quantities further improved the
A
n notion of aziridines being formed from 1,4-disubstituted results, but none of these conditions were competitive when
e
Op triazolines,asdiscussedbelow. comparedtothedevelopedreactionsinDES,which ledtothe
From these results, it is clear that the product distribution highestandcleanestconversions(Table7,entries4and8).
is most strongly influenced by the alkene substitution, while Overall, it appears plausible that the observed “DES effect”
the nature of the azide has acrucial effect on the overall con- in the azide–alkene reaction is mainly due to the increased
versionintocyclisedproducts. thermal stability of the formed cycloadducts when compared
Finally, we screened a 1,2-diene under our reaction con- to standard organic solvents. However, an organocatalytic
ditions, cyclohexylallene (Scheme 1). In this case, no aziri- effect of one or both DES components cannot be completely
dine formation was observed and instead two conjugated ruledoutatthistime.
cycloadducts were obtained (together with aniline and (B) Formation and evolution of triazolines: It is well estab-
other unidentified decomposition products), triazoline 3du lishedthatthecycloadditionofarylazidesandsimplealkenes
and triazole 5du, issue of a double bond migration in proceeds through an asynchronous concerted mechanism.37
3du. The observed regioselectivity is in accordance with In comparison, the factors determining the final reaction
the few reports available on intermolecular azide–allene productdistributionarelessstudied.35,38 Accordingly, wenext
cycloadditions.34 carried out a computational mechanistic study to rationalise
No conversion of triazoline 3du into triazole 5du was the obtained experimental results and focused our efforts on
observed during its isolation/purification. However, attempts 1,2,3-triazolines as the origin of the isolated aziridines. The
togrowcrystalsof3dufromahotsolutioninmethanolledto formation of the three-membered heterocycles via a nitrene–
the characterisation of peroxide 5du′ instead. While triazole alkene cycloaddition was not considered since formation of
5du′ was not present in the reaction mixture, traces of it nitrenesfromthereportedarylazidesishighlyunlikelyatthe
could already be evidenced in the 1H NMR of triazoline 3du reactiontemperaturesemployed.39Indeed,azide1dwasquan-
after a pentane/diethyl ether wash, which shows its high titatively recovered after heating it in DES at 80 °C for 24 h or
reactivity. at 90 °C for 8 h. Hence, the formation of aziridines 4 from
4028 | GreenChem.,2018,20,4023–4035 Thisjournalis©TheRoyalSocietyofChemistry2018
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GreenChemistry Paper
e.
c
n
4 AM. ed Lice
2:42:1Unport
23 13.0
13/20ution
oaded on 3/mons Attrib
nlm
wo
oC
018. Deative
ust 2a Cr
uger
Ad
7 un
n 0ed Scheme1 Intermolecularazide–allenecycloadditionreactioninDES.Structuresofone(5du’-A)ofthetwoindependentmoleculespresentinthe
d oens crystaloftriazoles5du’(left)andtriazole5du(right)are50%probabilityellipsoids.Mosthydrogensareomittedforclarity.
ec
Publishcle is li
Article. This arti Table7 Organocatalytictestsa
s
s
e
c
c
A
n
e
p
O
Entry Conditions(R=–COOEt) 1d(%) 3da(%) 4da(%) ArNH (%)
2
1 Dimethylurea(10mol%),toluene,80°C,16h 12 23 12 —
2 [NBu ][HSO ](20mol%),toluene,80°C,16h 58 — — 7
4 4
3 [NBu ][HSO ](20mol%),DMF,80°C,16h 42 9 5 10
4 4
4 Standardconditions:DES,80°C,16h 5 63 24 7
Entry Conditions(R=–CF ) 1a(%) 3aa(%) 4aa(%) ArNH (%)
3 2
5 Urea(15mol%),THF/water,80°C,16h 20 19 11 6
6 ChCl(15mol%),THF/water,80°C,16h 16 22 10 6
7 Urea(30mol%),ChCl(15mol%),THF/water,80°C,16h 0 42 16 5
8 Standardconditions:DES,80°C,16h <5 72 24 <5
a1H NMR yields/recoveries are the average of two independent experiments and were determined with respect to 1,3,5-trimethoxybenzene as
internalstandard.
transient 1,4-disubstituted triazolines seems to be the most only minor decomposition was observed in other solvents
likelyoption. However, we could not prepare such atriazoline such as DMSO and dioxane (Table 8, entries 2 and 3). At
evenwhenfollowingliteratureprocedures(videsupra,Table4, 100 °C, only 58% of the starting triazoline was recovered but
entry 5). On the other hand, we observed that triazoline 3aa the main decomposition product was the corresponding
wasstableunderourreactionconditions(Table8,entry1)and aniline and only small amounts of aziridine were formed in
Thisjournalis©TheRoyalSocietyofChemistry2018 GreenChem.,2018,20,4023–4035 | 4029
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Paper GreenChemistry
Table8 Thermalstabilityoftriazoline3aaa Calculations40 were performed at the B3LYP41+GD3BJ42/
6-311++G(d,p)43 (triple-ζ) SCRF continuum solvation level,
using the CPCM44 model and N-methylformamide mixture
level parameters (ε = 181.56) to simulate the high polarity of
the eutectic solvent used experimentally. Calculations using
the alternative ωB97XD45 functional and/or the Def2-QZVPP46
quadruple-ζ basis set are reported for selected systems. All
3aa 4aa 6aa 7a ArNH
2 transitionstateswerecharacterisedbynormalcoordinateana-
Entry Conditions (%) (%) (%) (%) (%)
13/2023 12:42:14 AM. ution 3.0 Unported Licence. maa123456s1eHinntNtseMrannRDD1DD1ad,,lEMEM44ys--SSiwtDDSSe,,alOOeii81dnoor,,00esdxx810/aaa°rd00erCnn°0edcC°ee,to.C,,°e,1vC81r,16em00,16rh0i16°ihen6C°sheC,had,1r61ew6htihthheraev>985—sep9398ra5egcCteoto———69mofp1twl,e3ot,e5i—1573-ndt20rdeicmeopemet——n—7<hp5dooexsnyitbtieoe———2<nnx95pzeenrie- ptlicUΔmynoornsGgateniele‡3l-seficn5t,izs3ohrdesmmre(edkerdsepvcttdweoalareaelitaxtleatmih.dhcnretoeFgIiloRloua−tnitClo1hdil.)vneeaeIfcenrRonowftrCiroiiimetmas4rye7edasa,eicttagninaanaoianlenlndctlrdaeusgasrelysyaarnydntofneiofmdorscrg0nthooaysrkadttoehlcoevlnaenaoilrltfccuthmoidh1eteryaeosratsletas−eoamst1pfaratetfror(ioate0nohnrf.ndra0estevai4hienatr1eriygieoleMraannepbcta)eotosl,ciretiontagnatnvtiohtneeissraesst-.,
oaded on 3/mons Attrib tahFeATcIhRoemdrpaetauacttariteoipononsbaieltotswrtyue.ed4n8y.aIznidtehi1sdreaancdtiostny,resnmeawllaqsucahnotsiteinesfoorf
nlm imine 6da and the corresponding anilinewere also formed as
wo
oC
018. Deative mstaintioornabryy-pprooindtuscatsnd(Stcrhanemsiteio2n).staAtnesoavnedrvtiheweirocfortrheesplooncdaitnedg
ugust 2er a Cr eneArtgiethseisBsh3oLwYPn+iGnDS3cBhJe/m6-3e131.++G(d,p)/SCRF level, two con-
7 Aund certed asynchronous cycloaddition transition states resulting
n 0ed in the formation of regioisomeric triazolines 3da and 3da′
ed ocens werelocatedasTS11,5andTS11,4,respectively(Scheme3).The
Publishcle is li Scheme2 Completeproductdistributioninthemodelreaction. benaseirsgiseestΔeΔffGec‡3t53(fBoSrE6)-3o1n1+th+Ge(ddi,ffp)ervesn.cDeefi-nQZthVePPacwtiavsatfioounndfretoe
Article. This arti comparison (Table 8, entry 4). No triazoline was recovered at bitebiyn∼si2gnkicfaiclamnto,l−w1h.iTlshtethreegieoffseecletcotnivitthyeΔbΔaGrr‡3i5e3rwiasstomionrceresaesne-
s 100 °C in either DMSO or dioxane, with imine 6aa being the sitive to the DFT functional, ranging from 1.3 for the B3LYP
s
cce majorthermolysisproductinthelattercase(Table8,entries5 method with no dispersion included, to 2.2 for the ωB97XD
A
n and6). method which includes a built-in second generation D2 dis-
e
p
O
Scheme3 CompletereactionprofilewithΔG‡ calculatedattheB3LYP+GD3BJ/6-311++G(d,p)/SCRFlevel.
353
4030 | GreenChem.,2018,20,4023–4035 Thisjournalis©TheRoyalSocietyofChemistry2018
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GreenChemistry Paper
persion correctionand2.8 kcalmol−1 usingB3LYPwithexpli- mentally observed regioselectivity favouring the formation of
cit inclusion of the third generation GD3BJ correction 3daasthemajor product (57%isolatedyield). Thereactionis
(Table 9). These differences qualitatively match the experi- predicted exoenergic by >10 kcal mol−1 but only if dispersion
isincludedinthemodel,sincethisaffectsboththeinteraction
energies and the entropies, both of which propagate to the
Table9 CalculatedvaluesofΔG‡ forTS1a freeenergies.
353
To understand the origin of the minor products shown in
Method TS1 TS1 ΔΔG‡ ΔΔG c Scheme2,we next modelledthenitrogenextrusion processes.
1,4 1,5 353 353
ce. B3LYP/6-311++G(d,p) 30.8 29.5 1.27 −4.9,−4.1 That from 1,5-disubstituted triazoline was investigated just at
oaded on 3/13/2023 12:42:14 AM. mons Attribution 3.0 Unported Licen awB3ωpaQv1)B3BhZa1Li9Veim+Yl7nPa+PXoPbG+Dlcle(Geobd/c6rDvau,r-pis3el3a)aic1Bsrat1Je/+esdd6e+na-tGet.faro(gdcrreΔ,etptiΔhcoGesbi32(2ta520o493r6...rr570.yip7ea)rrMbotsdDΔueOGcxItp‡3:22(152e,16134r4,0..i76.am.01pr)e4rebo4nrd6teau9dl/cuht(2(3(cc1022p..,eo20...5c927dn.98/5254cFb)))3ebbbu2ynl5tl1r.a.F7tAiok−−−−InRc1111a.1178ld....b1753maD,,taoelf−2is1- ts(ldagb“doThthraiiacpoaffpeirtadburoreetoiBdllpreeeece3edretnnnsL1mosotfY0srwt(o)iPiohT.mntm+mheaNtGiebaebnoerDtn3lememetdita3snrealBeai1s6grn.dnJo0gd/Iis6iaantniith-ta(tnhs3egHientvoe1”eopd)n14ral9rea+dvpisgn+Fem,triiGsidasooigattd(nt.e8rdshuwydh,f4eocpaoaco)ft)sar(.mwPttalchinThoieoozgevfh)inmrerbeavtilvypirttd,aihiaupioatnnetThtrnhrseeeSeeiedsot2ffleiiaorf1ortnlet,rosa5neifcmtv-reiHeeegtrsahvleetraytooeaneinolrfthaicvednncieeagatc(TichriF(HonSeordineea2gutisoons1.plt,edre5io43tn-rwPlbPdbgiaghhn)oaeyr).,
nlm Table10 CalculatedvaluesofΔG‡ forTS2a As previously stated, prolonged heating at 80 °C of a pure
wo 353
oC
018. Deative Method ΔG‡353 ΔΔG353b spaomndpilnegofimain1e,5-adsisuthbestitountelyd dtreicaozomlipnoesitlieodntoprothdeucctor(rseese-
n 07 August 2ed under a Cr TTTTSSSS22221111,,,,5544--abHPh 33220010....1289 −−−−54463921....0443(−13.9)c TeCuxanopbmsltlaaepibne8lt)ei.ttPiphvareeortdTidauSelc2tthe1yc,t5hdt-iParohotnlwywsoooiusfulolddafnctphoilrmiiosndpeimulsectieeninleyadlhtduhyirdemirniorngleyeawsceo8tridioknan-t,uopacarwnumoidluoienlrsdee.
Published ocle is licens kar1a0cAda.t1ilc4tmah4l6eo.9l−BF/h1u3.pLlblcYO/P4Fv+3AeG2IrR6aD.l3ldBraeJta/a6c-t3iio1sn1+af+vraeGie(ldaeb,nplee)rglveiievaesl.,acrEednlaaettriagvyeroetfopion3stdietaormroyerda3itadtaDe′ObiIni-: ainsnoedwuasntnrdoaenlrigptlhyhaeetxiorceeaanlcedtrieoghnicyd.ceo,nwdhitiicohnsin. Ttuhrenoisvelrikaelllyretoacotiloignosmaerre-
Article. This arti
s
s
e
c
c
A
n
e
p
O
Fig.4 Computedpropertiesalonganintrinsicreactioncoordinate(IRC)for(a)energyprofileforTS2 ,(b)dipolemomentresponseforTS2 ,
1,5-H 1,5-H
(c)energyprofileforTS2 and(d)dipolemomentresponseforTS2 .
1,4-b 1,4-b
Thisjournalis©TheRoyalSocietyofChemistry2018 GreenChem.,2018,20,4023–4035 | 4031
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Paper GreenChemistry
Two diastereomeric transition states (TS2 and TS2 ) and the alkene and might also be dynamically controlled.
1,4a 1,4b
were located for the loss of dinitrogen from 1,4-disubstituted FurtherstudiesonDESapplicationsanddynamiccalculations
triazoline 3da′. The activation free energies are now low areunderwayinourlaboratories.
enoughtoexplaintheabsenceofreactant3da′inthereaction
products(Table10).TheIRCforTS2 revealedtheformation
1,4a
ofasingletdipolarbiradicalfollowedbyarelativelylowenergy Experimental section
(e.g.ΔG‡ =2.6kcalmol−1)forelectrocyclicringclosureto
353trans
Generalprocedureforthedipolarcycloadditions
thecorrespondingaziridinescis-4daandtrans-4da.Incontrast,
e. TS21,4b was found to evolve into imine 8da upon a migration Azide (1.0 equiv.) and alkene (2.0 equiv.) were stirred in deep
c
13/2023 12:42:14 AM. ution 3.0 Unported Licen ohatelehxgfyapeadadOeirdnsrohviielpymhyrdtosaoaerellsoenl,gitttmnaheroatlnoeuonmrrasteftihecosoenaeunrmlmtltcctruso(aceF.lrtasaiirtpgoteAiioo.nsopnn4ntos)his,ocenefwdraacmhhrlitoneiawacngrlhioagnacdwtnthrgeioieperolugioonI(illRFdodeaii.CrgsbaT.o.egchm4ryeeeccxee)lprtomiraeacascedntndrestterdiittiviaiwetoozoainnotlheelisdasntsttaeheibtlspeeyy. efcpaoboouzveyreiortderfl1mineecl6d)ttimigracahhdnotst,iodl,oowuonlstvnnhft,eolianwestrzoestaiwsdds(rcheaoash)settoaodam−ttlnrei1itnddth8tueerp°rmoeceaCtehnthpeoltetedoavirrmrneawiartedeintu/sesEirer/getu.owh2,roOTitedmt.hahi(Ile3fu=tit:tecrre11meeid;aa:pczc12woote;imrlliod0iatnnh.Lt5ueppwmreMpeenar,ir)texteacctmaruonitprlme(lei82/etEo0acwlmttt2°eeaoOCddLsf
oaded on 3/mons Attrib Wcoanhlllyyersermealsaalttlihvqeeuly1a,ns5tt-aidtbiiesleusboasfttiittmhuetiendreeatbrcyit-aipozronolditnueemct3spdeaartawmtuooruesltd,antbhdeerk1ei,nn4d-edteiir-- aOsanctdcioansiroewncearrylelsyt,aftullhrisethewdearshpfruionrmgifsieadnbdob/iyolirncgfoillutrmeatthneafncrohomrlomtihfaitsorngerecacrpeyhssstyaalralyis-.
nlm substituted regioisomer 3da′ readily reacts to form either the described next, either to improve the triazoline recovery, or to
wo
018. Doeative C cWoerrhesapveonedxpinegrimazeinritdailnlyesohrowimnitnheastwthiethprdoidnuitcrtogdeisntreibvoultuiotinonis. i−s1o8lat°eC,thtehecomrriexstpuorendwiansgeaxztirraicdtiende.wIifthnoEtsOoAlicd,pthreecicpoimtatbeidneadt
ugust 2er a Cr atulstoionhsi.ghTlhyisdiespceonndseinsttenotnwtihthetahreylinaslikgehntereavnedaleadzibdyethsuebcsatil-- oMrggSaOni4c,fpilhtearseeds,wcoernecewnatsrhateeddwuintdhewraretedruacenddpbrreisnseu,rderaineddpovuerr-
7 Aund culations for nitrogenextrusionin particular, which show sig- ifiedbycolumnchromatographyonbasifiedsilica(eluent:pet-
n 0ed nificant dipolar/ionic character localised in the region of the roleum ether/EtOAc 0 → 25% gradient basified with 2% v/v
ed ocens transition state for this step. It has indeed been established NEt3 unless stated otherwise; reaction crude was dry-loaded
Publishcle is li tchhaatnvgaersiaitnionreainctitohnesmuebcshtiatuneisnmtss.m50ayAinfudlelesdtuidnyduocfethdreaminafltuic- oafntetor csotalutimonnarcyhrpohmaasteo).grOapchcaysrioenqualilrye,dthweashprinodguwctithreiccoev-ecroeldd
Article. This arti ewnilclebeofrespuocrhtesdusbesptiatruaetneltys.upon the reactions described here pen3taaan:e/EFot2lOlow(1in:1g).the general procedure from 1-azido-4-
s trifluoromethylbenzene (5.00 g, 26.7 mmol) and styrene
s
e
c (6.18 mL, 53.4 mmol), the title compound was isolated as a
c
A
n Conclusions white solid (3.68 g after recrystallisation, 0.82 g after column:
e
Op 58% overall). From this reaction, aziridine 4aa was also iso-
Arangeofdi-andtri-substitutedΔ2-1,2,3-triazolineshavebeen lated as a white solid (1.28 g, 18%) after column chromato-
prepared and fully characterised. The studied azide–alkene graphyandrecrystallisationfrompentaneat−18°C.
cycloadditions in DES typically led to mixtures of 1,2,3-triazo-
linesandaziridines,althoughtheoverallproductdistributions
were largely influenced by the alkene substitution. The
benefits of DES in this context are twofold. First, the DES
employed herein is non-flammable and it is composed of two
safe and inexpensive components, urea and choline chloride.
Secondly, much cleaner reaction crudes were obtained in DES
when compared to standard organic solvents, and typically 3aa:SinglecrystalsforX-raydiffractionweregrownfromEt O,
2
severalgramsofthedesiredtriazolinescouldthenbeisolated CCDC1843142;†Mp88.0–90.0°C;R =0.49(petroleumether/
f
analyticallypureafterasimplerecrystallisationstep. EtOAc = 80:20); IR: ν 1612 (m), 1523 (m), 1502 (m), 1458,
max
Furthermore, a mechanism for the reaction between aro- 1431, 1365 (m), 1316 (m), 1193, 1153 (m), 1111 (s), 1067 (s),
matic azides and olefins to yield triazolines and/or aziridines 1010 (m), 990 (m), 963 (m), 926 (m), 841 (m), 820 (s), 751 (s),
has been proposed. All our calculations have shown that this 698 (s) cm−1; 1H NMR (CDCl , 400 MHz) δ 7.45 (d, J = 8.5 Hz,
3
interesting process can proceed through two divergent path- 2H, H2), 7.35–7.24 (m, 5H, HAr), 7.15 (d, J = 8.5 Hz, 2H, H3),
ways, cycloaddition followed by simple loss of dinitrogen to a 4.94 (dd, J = 12.5; 8.0 Hz, 1H, H6), 4.88 (dd, J = 17.5; 12.5 Hz,
biradical intermediate and then cyclization to the corres- 1H, H5), 4.37 (dd, J = 17.5; 8.0 Hz, 1H, H5); 13C NMR (CDCl ,
3
ponding aziridines or loss of dinitrogen together with conco- 101MHz):δ142.9(C4),139.5(C7),129.5(C9),128.4(C10),126.5
mitant groupmigrationto formimines.The processseemsto (q,J=3Hz,C2),125.9(C8),124.3(q,J=269Hz,C11),124.0(q,
be highly dependent on the nature of both the starting azide J=33Hz,C1),114.4(C3),76.1(C5),57.4(C6);19FNMR(CDCl ,
3
4032 | GreenChem.,2018,20,4023–4035 Thisjournalis©TheRoyalSocietyofChemistry2018