Recent advances in stereoselective bromofunctionalization of alkenes using N-bromoamide reagents

12 Pages·2013·3.09 MB·English

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Recent advances in stereoselective
e.
c
en bromofunctionalization of alkenes using
c
AM. ed Li C4i9t,e7t9h8is5:Chem.Commun.,2013, N-bromoamide reagents
2:17 nport
4U
2:0 Chong Kiat Tan and Ying-Yeung Yeung*
3/2023 1bution 3. Bromination reactions have been made a lot more convenient since the invention of N-bromoamide
ded on 2/2mons Attri rtgeoivaigonetghnettsrh.eThmhaelosagenerneasad,gvbearnnottmsaaginreeatiminnogsroermeeaaegseiclnyatshseassn.itdRlieendcebwnethtlywe,nesecenovmecrhpallaoriremindpetooartnmadnotlieoacdudilnvaaernbocrenosmtihnineee.rneInaanccttoiivomisteyplaesrccitsaiovlene,
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013. Creati DOI:10.1039/c3cc43950j uosfeaolkfenNe-bs.roEmxaomampliedse irnecalguednetsbirnomexinpeanidniintigattehdecsyccolpiceeotfhedriasctaesrceaodseeslecatnivde nborovmelofmunuclttiicoonmalpizoanteionnt
uly 2er a www.rsc.org/chemcomm reactions(MCRs).
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ublished on 03 e is licensed un 1Br.omInintartioondrueaccttiioonnshavebeenaworkhorseinorganicsynthesis. N5b,r-5ob-mrdoiimmneoetaihcsyedmtaaomnrtieodirenea((NcDtBiBvADe)MtahnHadn).tIchnheltomerriomnreesbrouefathcltaeilsvosegre1en,a3c-rdteiiavbecrtoitvmhiatoyn-,
s Article. P This articl HcinoovnwevneetvnieoirenntohtfedNuue-sbetrooomiftsobharomigmhidinreeeraeacatsgivaeintryte,savlgoikelanettNilii-ttbsyreoalfnmidsostnouoxcitccieintnyim.tiTriehdleey oaiolfkdtyihnlebertlooemawvaiidrndegssgoerffleoecurtprhoiapgbhhiielliritcyrehoaafcltotighveietnyhattaoilwoonagreodnfssaSlikn2entdheises.p2plaIrncoedtmeurcemtnsst,
s N
cce (NBS)1 (Fig. 1) for example has greatly enhanced the utility thanalkylchlorides.Inaddition,alkylbromidesarealsomore
A
n of bromination reactions due to its safe and easy handling. stabletowardsunwantednucleophilicdisplacementwhencom-
e
Op InadditiontoNBS,anumberofcommerciallyavailableN-bromo- paredtoalkyliodides.3
amide reagents exist including N-bromophthalimide (NBP), Reactions ranging from the radical bromination of allylic4
andbenzylic5positionstoelectrophilicbrominationofcarbonyl
compounds,6 aromatic7 and heterocyclic8 compounds are
DepartmentofChemistry,NUS,3ScienceDrive3,11754,Singapore.
E-mail:[email protected];Fax:[phone];Tel:[phone] just some examples of the bromination reactions that are
ChongKiatTanisafinalyearPhD Ying Yeung Yeung received his
candidate at the Department of BSc (2001) at The Chinese
Chemistry at the National Univer- University of Hong Kong. He
sityofSingapore.Heobtainedhis continued his graduate research
BSc (Hons) from the same in the same university under the
university. His research interests supervision of Prof. Tony K. M.
include organic synthesis and Shing. After four years research
the development of asymmetric dedicated to natural product
organocatalysis. synthesis,DrYeungmovedtoUSA
to conduct postdoctoral research
with Prof. E. J. Corey at Harvard
University. In 2008, he joined
National University of Singapore,
ChongKiatTan Ying-YeungYeung
Department of Chemistry, as an
assistant professor. His research interests include asymmetric
catalysis,greenoxidation,andmethodologydevelopment.
Thisjournalis c TheRoyalSocietyofChemistry2013 Chem.Commun., 2013, 49, 7985--7996 7985
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2. PartI–recent progress inenantioselective
bromofunctionalization of alkenes
The enantioselective bromofunctionalization or more broadly
halofunctionalizationofalkeneshasbeenanareaofintensive
research in recent years. Many of the difficulties in achieving
bromofunctionalizationwithausefullevelofenantioselectivity
havebeenworkedoutmechanisticallybyBrownetal.aswellas
Denmarketal.
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n Brown and co-workers were the first to demonstrate that a
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AM. ed Li rbarpoimdoannidumdegioennearnatdivfereoeleafilnk-etno-eosleifninNtMraRnssfeturdeixeissts(Sbcehtewmeeen2t)h.1e2
2:17 nport Therateofthisolefin-to-olefintransferprocesswasalsofound
2:40 U tobecompetitivewiththenucleophiliccaptureofthebromonium
n 2/23/2023 1Attribution 3. pFiog.s1sibElexamwpitlehsosfuNch-brroemaogaemnidtse.reHagoewnetsv.er, this feature article will imamonneecc.ehhnWaaannniiittsshimmoet,nhtohreniucehsexecmidasntaebknrreacostemiothononefailuidszumeevcethhilooenapp.morTeashnpsiiitbsdiolpfibtoytrshosoemifbeorleanncaireunammctieiozmsateritlazieoancntstiifovoenerf
ded omons only review selected examples from the recent advances of bromofunctionalizationofalkeneachallengingtask.
oam the electrophilic bromofunctionalization of alkenes starting Thenextimportantmechanisticrationalizationoftheproblem
ownle Co from2005. of enantioselective bromofunctionalization was demonstrated
013. DCreativ withThtehgeenfoerrmalalytiaocnceopftetdhembercohmanoinsmiumofisounchornecaecttihonesebleecgtirnos- ianndacsoe-rwieosrkoefrsa.1c3etTohlyesiesxpexepriemriemnetsntssimcounladtuectthede ebnyviDroennmmaenrkt
uly 2er a philicbrominesourcecomesintocontactwiththealkene.Such where the configurational stability of both bromonium and
ublished on 03 Je is licensed und sbcdtaruuopcSdmttuuiseobrsetnshdepiauqetbmuryfceooinarontmnlctyaseo,idmwnthebpirayasentOoirbeablalansehcteitrn-ievrvuteeecldaalbleti.irn9ooopnlmihsqiohulneiipdiu(SSbmcOeht2iewoimneneeancs1aetn)h.riebSeisebnorcffouemNrtpMhirdeoRer- ci(cnnEahu)nl-cso4tlrger-ooooecnnnptigeheulrniymaleetieo(aivonntinhiadzseioenclrxegaecfnseimpnsbes-etcedooti-ildaovee.elfetiTnefbhir.nrmeoTtmrhirnaaeotenenbdss-ifhuioenamrf,ltroShaacscenhuedpemlfmroceiznhseaeal2otnti)erocoscnena1noibaufytmahbenuoxdictsohe1bnsbaess
s Article. P This articl abneldBiervnoemudcoltefouoonppchteiilnoentahalreiezbatrgioeomnneoornafilaluylkmeonrbeitnsagigneienndea,rnatlhlSyeNa2ffnfouarcsdlhesiooppnrho.1id0leuctiss cthoemThphaaelryoenddiiustcomotvhieoernerd.attehoatftihneteardmdoilteiocnuloafr4n-uocclteeonpehiinlitcocaaspotluurteioonf
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cc ofhighdiastereoselectivity,assuggestedbytheproposedmecha- ofbromotosylate1aresultedintheerosionofenantiospecificity
A
n nisminScheme1. in the highly polar hexafluoroisopropyl alcohol (HFIP) solvent
e
Op In recent years a renewed focus has been cast on the long medium(Scheme3).Themainfactorsaffectingtheerosionof
standingchallengeofenantioselectivebromofunctionalization enantiospecificity were identified to be the concentration of
of alkenes. More broadly, the solving of this long standing theolefin(4-octene)andthecountercationoftheacetate.The
problem should be addressed under the umbrella of enantio- observation for bromotosylate stands in complete contrast to
selective halofunctionalization of alkenes. Several reviews on theanalogouscaseofchlorotriflate1b,whereenantiospecificity
thistopicarealreadyintheliterature.11 was preserved even in the presence of 4-octene. These results
This article will only limit its coverage to the electrophilic establishedtherelativestabilityofthechloroniumioncompared
bromofunctionalization of alkenes using N-bromoamide tothebromoniumion.
reagents.Thearticleconsistsoftwoparts:partonewillreview Theabovetwoobservationssuggesttheinherentdifficultyof
therecentprogressinthecatalyticenantioselectivebromofunc- formingastableandchiralbromoniumionduetothepresence
tionalizationofalkenesusingN-bromoamidereagents,andthe ofarapidanddegenerateolefin-to-olefintransfermechanism.
second part will address the other significant progress in Nonetheless,somesolutionstothisproblemhavebeenunravelled
diastereoselective bromofunctionalization of alkenes. Efforts inrecentyearsandwillbedescribedinthefollowingsections.
from our own laboratory in these two fields will be described It is noteworthy that breakthroughs in chloro-14 and
aswell.
Scheme1 Generalmechanismoftheelectrophilicbromofunctionalizationofalkene. Scheme2 Degenerateolefin-to-olefintransferofbromonium.
7986 Chem.Commun., 2013, 49, 7985--7996 Thisjournalis c TheRoyalSocietyofChemistry2013
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quinuclidine of the quinine scaffold. This proposed mechanism
wasalsosupportedbythechangeinenantioselectivitiesofthe
bromolactonization with various halogen sources especially
betweenNBSandtetrabromocyclohexadienone.16b
Another competent chiral organocatalyst came in the form
oftheC -symmetrictrisimidazoline4reportedbyFujiokaetal.
3
(Scheme 5).18 Using their protocol, a variety of 5-aryl-substituted
hexenoicacidsareamendabletoenantioselectivebromolactoniza-
e. tion. Their substrate scope includes 1,1-disubstituted, trisub-
c
n stituted, and tetrasubstituted hexenoic acids. Mechanistically,
e
c
M. d Li they found the presence of the three imidazoline units to be
Ae crucialtoachievinghighenantioselectivity.Theuseofboththe
2:17 nport mono- and di-imidazoline variants of catalyst 4 resulted in
2:40 U much lower enantioselectivities. Additionally, NMR studies
n 2/23/2023 1Attribution 3. Sthceheemroesio3noEfffeenctanotfiohsapleocgifeicni,tyc.ountercation,andconcentrationofalkeneon ctinhornmeAdenououdctnteheliedtAsrodb(Sfyiffchhteehrexeemenngetors5oioc)ul.uapctiisodunsgwtgoeasostnoetffheuernepidtrobofbyacoabutlraellyatsbetmo4rpaaltasotrsiynhwgowitonhf
ded omons iodofunctionalization15 of alkenes were also achieved concur- aclassofamino-thiocarbamatecatalysts.Thefirstofthisclass
ownloae Com rentlyinrecentyears. o(Sfcahmemineo-6th).ioAcfatrebraemxtaetnesciavme estwuidtihesa,ctiwncohcoantaalaylsktaltouindinscgaffsiotelds
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013. Creati 2.1 Enantioselectiveintramolecularbromofunctionalization
uly 2er a ofalkenes
Jd Onesuccessfulreportofthe enantioselectivebromofunctiona-
ublished on 03 e is licensed un bqlcioruzo-aiwnmtioionornkleaeodcrfteso.ar1nil6vkiezTedanhtetieoosirnswysloaoufslurdZet-iia1soc,3n3lo-atesosnettydhhnebiesyscpht(hrSiorceabhllleaeombmrogerawa4nta)oo.scrtyahtoaeflyuTssatenfoogrfattnhhdee
s Article. P This articl f1r,o4m-Tdhiaethzdaebiersicilgyacnblooor-[fa2tc.o2ar.ty2a]lwoycshttiac3nhewd(aDesmABporCneOscte)rdaaetsedadbbtryhoeamcpoolrmaecvptiooentueisnzacwteoioronkf
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ce catalyst.17Inthisreporttheyproposedadualactivationmode
c
A
n where NBS is activated via a hydrogen bonding with the NH
e
Op groups of the urea and the carboxylate anion is bound to the
Scheme4 EnantioselectivebromolactonizationofZ-1,3-enynes. Scheme5 EnantioselectivebromolactonizationwithC3-symmetrictrisimidazoline.
Thisjournalis c TheRoyalSocietyofChemistry2013 Chem.Commun., 2013, 49, 7985--7996 7987
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oam
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s Article. P This articl Scheme8 Synthesisof(R)-(+)-boivinianinAfromchiralbromolactone.
s
e
cc The enantioenriched bromolactones can be converted into
A Scheme6 Enantioselective bromolactonization with amino-thiocarbamate
en catalysts. valuable intermediates. In one example, we were able to perform
p
O the debromination of a bromolactone into (R)-(+)-boivinianin A
(Scheme8).24Theenantiomerof(R)-(+)-boivinianinAcanreadilybe
were discovered. These are the N-aryl substituent indicated as accessedbyusingtheenantiomeroftheprolinebasedcatalyst7.
R1andtheO-alkoxysubstituentatthequinolineunitindicated Theamino-thiocarbamatecatalystswerealsofoundtobeable
as R2. The tuning of these sites allowed a number of alkenoic toperformtheenantioselectivebromoaminocyclizationofavariety
acids to be accommodated into this protocol. These include ofolefinicamides(Scheme9).Intheseriesofstudies,amides9,11
1,1-disubstituted pentenoic acid,19 both E and Z-pentenoic and 13 were found to be possible substrates for achieving high
acid,20,21andthestyrenetypecarboxylicacid.22 enantioselectivities.25 One of the essential requirements for this
Whiletheaboveexampledemonstratedtheessentialityofusing reactionisthepresenceofthenosylsubstituents.TheNHofthe
O-alkylthiocarbamateonacinchonaalkaloidscaffold,subsequent 4-nosyl amide is then sufficiently acidic for the reaction to take
workshownthatS-alkylthiocarbamatesarealsocompetentchiral place smoothly in an enantioselective fashion. The resulting
organocatalystsonaprolinebackbone(Scheme7).23Inoneof enantioenriched bromo-pyrrolidine and piperidine products are
ourstudies,S-alkylthiocarbamatecatalyst6wasabletoserveas usefulbuildingblocksofvariouspharmaceuticals.
a chiral catalyst for the bromolactonization of hexenoic acids. Mechanistically, the above reactions catalyzed by amino-
On the other hand, O-alkyl thiocarbamate 7 could catalyze thiocarbamateswereproposedtoproceedviaadualactivation
the enantioselective bromolactonization of pentenoic acids. mode. The sulfur atom in the catalyst is believed to act as a
Anadditionalmotivationforcarryingouttheworkonaproline Lewisbaseactivatorofbromine,26whiletheaminemayinteract
scaffold is that both enantiomers of proline are available. In with the nucleophile via an acid–base interaction (Model B,
contrast,onlypseudo-enantiomericpairsofcinchonaalkaloids Scheme10).19
arecommerciallyavailable.Themagnitudesofenantioselectivityof Sulfur or more broadly chalcogens have been known to form
some bromolactones are not equal when a pseudo-enantiomeric stable1:1molecularadductswithbromine.27Denmarketal.have
pairofcinchonaalkaloidderivedthiocarbamateswereusedin alsodemonstratedthecompetenceofsulfur-containingcompounds
somespecificstudies.21,22 asbothbromolactonizationandbromoetherificationcatalysts.28
7988 Chem.Commun., 2013, 49, 7985--7996 Thisjournalis c TheRoyalSocietyofChemistry2013
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e.
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M. d Li
Ae
2:17 nport
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3/2023 1bution 3. Scheme11 Enantioselectivebromoaminocyclizationwithcyclicdialkylselenide.
n 2/2Attri
ded omons to be unstable for long term storage as well as during the
oam reaction.29
wnlCo Building up from d-mannitol, cyclic selenide catalyst 15 was
oe
013. DCreativ coalepfaibnliecoafmeffiedcetsin.3g0thIneteenreasnttiinosgelyle,ctiinveccoycnltizraatsitontooftthrie-sucbinstcihtuotneda
uly 2er a alkaloid based amino-thiocarbamates, the 3-nosyl amide was
Jd foundtobetheoptimalsubstituentforthesubstrate.
ublished on 03 e is licensed un abanbrooTmovheleoecfeiaantbhtaoealvryneitf-diimccaesatnyisotstiunoeffinmsecswdi.eeeInrnxtealsymtnepaaocldtei,dsreisecnhpaononwruttciesoludesboepsbltehyrcaitltegiev.rseoEcubonprnaostnmatuiinoosiesinnetghlgeebcrttoiihvfthiee-
s Article. P This articl caactidiHonednsernwieveacrkteievreeasp.nodrtecdo-bwyosrkeveerrsalregproourtpesdutshinegdcehsiyrmalmpheotrsipzahtoiorinc
s
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cc of 1,8-oct-4-ene-diols with the chiral phosphate catalyst 18
A Scheme9 Enantioselectivebromoaminocyclizationwithamino-thiocarbamates.
n (Scheme 12).31 While modest enantioselectivity was achieved
e
Op with NBS, much higher enantioselectivity was reported with
N-iodo-2-pyrrolidone.
Later, more highly enantioselective bromoetherifications
werereportedindependentlybyDenmarkandShi.InDenmark’s
case, the use of a co-catalyst triphenylphosphine sulfide was
foundtobeanessentialrequirement(Scheme13).32Anumber
ofsubstratesincluding5-aryl-4-pentenolsareapplicabletotheir
protocol.Intheirstudy,theyobservedthattheZ-pentenolsgave
Scheme10 Proposed mechanism of the amino-thiocarbamate catalyzed
enantioselectivebromocyclization.
In addition to the bifunctional amino-thiocarbamate
catalyst, we later discovered that dialkyl cyclic selenides
arealsocapablechiralcatalystfortheenantioselectivebromo-
aminocyclization of olefinic amides (Scheme 11). The motiva-
tion for designing such dialkyl selenides is to overcome
the low reactivity of certain olefinic amides towards catalysis
byamino-thiocarbamates.Whilehigherreactivitywasobserved
with amino-selenothiocarbamates, however, they were found Scheme12 Desymmetrizationof1,8-oct-4-enediolswithachiralphosphate.
Thisjournalis c TheRoyalSocietyofChemistry2013 Chem.Commun., 2013, 49, 7985--7996 7989
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e.
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2:17 nport Scheme15 Enantioselectivesemi-pinacolrearrangement.
4U
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3/2023 1bution 3. ecantaanlytisot,sethleecytiwvietyre(Sacbhleemtoea1ff5o).r3d5T(2hRe,3enS)a-n21tioweinthricghoeodd(y2iSe,l3dRa)-n2d1
n 2/2Attri was obtainable by switching to (DHQ)2Pyr and N-Boc-D-phenyl-
ded omons glycine(NBDP)catalyst.
Downloave Com Sanchdetmripeh1e3nylpEhnoasnptihoisneelescutlipvehidberocmo-oceatthaelyrsifti.cation with chiral phosphoric acid 2o.f2alkEennaenstioselectiveintermolecularbromofunctionalization
013. Creati Incomparisontoenantioselectiveintramolecularbromofunctiona-
ublished on 03 July 2e is licensed under a apIewhnxneiagonsthateceldrymnemecnotloseliasszcnotegttefdaeidvoxebecsnfrleaoauolnremsmctitviithoxoietevesuityetrheilieneeeeldcosrdts.foibvOobciofyunttyctht,hltimhehezxeeiuoegdxochahotbnhe-rdcreeoyeremcwdnlhudiaozaosceenetcddhddyece,btelreitrnszhoc.eatemdendEobti-erocaotosmhmenelooferinescgtgtuhwivertihierttshdey. ltsccdioehozuulauieergtlcaidthtoloienvbprtehheopeiofrnooscatbpbaelthkrltaeameoimlnnryoiesecltstdeo,caautt(cchaSiltdaccienkrhgiclenebama.rtteosaIenrlmaym1saocto6oerl)e2sme.3tc2ce6epu,rneliTpafttihrricroteaeifmvoptiyerooiimsenrnitlnu,adwgctaslahepewsoarneopsdarmhniepsitriclishoeloiovonsisenewgenldeeoevc.tpnoteeUiarvnnbsiltitieoinnieowggas-
s Article. P This articl athpepSlhsicoialebanlcedastuaclboy-sswttroa(rStkeceshrwesmituhetigl1io4zoe).dd33ec5nh-aiArnlaktliyolps-4he-lopesecptnihtveoitnryio.clIsnacwaidedrde1it9aiolsanos, ethsteeArbnifroioctmahteioornniouwrmgaasnirnoetcceaertnmatllyeytdicrieaptaeop.rpterdoabcyhTtaonginatnedrmcoo-lwecourlkaerrsb.rUosminog-
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Acce tphheiylewtoertehealscoataalbylteictporoaptopcloyl.substrates with nitrogen nucleo- (DHQD)2PHALwith(+)-camphorsulfonicacid(CSA)asanadditive,
n they were able to obtain the highly enantioselective bromoester-
Ope In another recent study, Toste et al. reported a highly enantio- ificationofarangeofallylicsulfonamides(Scheme17).37
selective bromocyclization using chiral phosphoric acids together
withaspecializedDABCOderivedtricationicbrominatingreagent.34
ThefinalexampleofN-bromoamideinducedenantioselective
intramolecular bromofunctionalization in this section is the
N-bromoacetamideinducedsemi-pinacolrearrangementoftertiary
alcohol20tobromoketones21.Usingacombinationofcinchona
alkaloid based (DHQD)2Pyr and N-Boc-L-phenylglycine (NBLP)
Scheme16 Enantioselective intermolecular bromoesterification with chiral
Scheme14 Enantioselectivebromoetherificationwithchiralphosphoricacidcatalyst. phosphoricacid.
7990 Chem.Commun., 2013, 49, 7985--7996 Thisjournalis c TheRoyalSocietyofChemistry2013
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Scheme17 Enantioselectiveintermolecularbromoesterificationwith(DHQD)2PHAL.
e.
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2:17 nport Scheme19 Tin(IV)chloridecatalyzedhaloamidationofolefin.
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ded omons areavcatriioenty. of nitriles and olefins could be subjected to this
oam
wnlCo Themechanismwasproposedtoproceedviaabromonium
Dove ion ring intermediate which was opened by acetonitrile to
uly 2013. er a Creati gnineittnroeilrtehateceobuirnlodtmerromeasemudlitidaitenepCirnot(deSurcmchtee.mdieat2e0D). Awthtaicchk bcoyuwldatiesromonertihzee
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ublished on 03 e is licensed un ScheAmheig1h8lyEennaanntiotisoesleeclteivcetiivneteirnmtoelremcuolalercburolamrobamroinmatoiofunnocftciohanlacolinzea.tion btchoreouHymldaodjarfeuaffmnoeocrtdtnisoaatnlr.saaetlrierezidpeastoitrohotnefadt1o,fw5aa-idltskhieseurnZibeensss(t.OiotITunftfte)m2hdeeattfesaitlrrstahttzreooiffllecatsahtete2ai7lrcyasrwttea,iptlhoythzraetesndy,
s Article. P This articl mcwaaetsatalyrlesctpooamrntdepdlelixbgaycnaFtdaelnyssgytste(eStmcah,l.etmhweietyh1w8ae).r3se8caUanbsdileniugtmojuastctrhi0fil.ea0vt5ee–mNth,oeNl%0e-dnoiaofnxttiihdoee- oanptein-rienlgatioofnsthheipbtroomthoenbiurommiidnete(rSmchedemiatee2b1y).4t3hFeolalzoiwdiengfrothme
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c selectivebromoaminationofchalconewithNBSandTsNH.High
c 2
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n yields and high diastereoselectivities were also achieved. It is also
e
Op worth noting that successful chloro-39 and iodoamination40 of
chalconeswerereportedbythesamegroup.
3. Part II – recent progress in diastereose-
lective bromofunctionalization of alkenes
AlthoughitismentionedinScheme1thattheopeningofarigid
bromonium intermediateleadstoananti-relationshipbetween
thebromineandnucleophile,therehasbeenmuchroomforthe
developmentofnoveldiastereoselectivebromofunctionalization
ofalkenes.Inmanycases,aLewisacidoraLewisbasecatalyst
is needed to activate the brominating reagent towards such Scheme20 Proposedmechanismofhaloamidationofolefin.
reactions.Nevertheless,recentlydiscoveredNBS-initiatedcascades
andmulticomponentreactions(MCRs)havebeenfoundtoproceed
without the need for an additional catalyst. The Lewis acid
catalyzedandcatalyst-freeMCRswillbeaddressedaccordingly
inthissection.
3.1 Diastereoselectivebromofunctionalizationofalkeneswith
aLewisacidcatalyst
InCorey’sconcisesynthesisofoseltamivirphosphate(Tamiflu),41
they disclosed a novel Lewis acid catalyzed haloamidation of Scheme21 NBSinducedsynthesisof1,5-disubstitutedtetrazolesfromalkenes.
Thisjournalis c TheRoyalSocietyofChemistry2013 Chem.Commun., 2013, 49, 7985--7996 7991
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toCorey’shaloamidation,thebromoamideswereabletoconvert
intooxazolinesinthepresenceofNaHCO andwater.
3
3.2 NBSinitiatedcyclicetheropeningcascades
In Braddock and co-workers’ study of model obtusallene sys-
tems, they discovered that NBS can be utilized to initiate a
Scheme22 NBS induced bromoazidation of a,b-unsaturated carboxylic acid transannular oxonium ion formation–fragmentation reaction
derivatives. (Scheme25).47Whenthemacrocycliccompound33wastreated
ce. withNBS, the reaction proceeded inthe presence of a nucleo-
n
e
c phile, for example acetic acid. Addition of 1 mol% of tetra-
M. d Li methylguanidine(TMG)wasfoundtobenecessary.Inaddition,
Ae
42:17 Unport intuwcalesoaplhsoilifcopuanrdtntehrastfborrotmhiisnereaancdtiowna.tercanalsoserveasthe
3/2023 12:bution 3.0 esypnoItxhniedaseils-aotpoefernseitnnut-gddyico,axJseacpmaadinsedoetnoheyadtffraool.trhdfoyrpusrniofeddruothlcat(stScNlehBaedSmicneagn2t6io)n.4ti8htieaWtteohtaeannl
n 2/2Attri the poly epoxide 35 with an OBoc terminal group was treated
oaded ommons w(HitFhIP)N,BthSeidnesairehdigbhrloympinoalaterdspoolvlyecnytclehewxaasfluaoffrooridseodprionp3an6%ol
wnlCo Scheme23 NBSpromotedFriedel–Craftsalkylationofalkene. yield. The polycycle 36 was further elaborated tocomplete the
Dove totalsynthesis.
uly 2013. er a Creati sToMlvSeNn3t,.aTshseemrebalcatgioeninwtoastefotruanzodletoenbesuaepdpwlicitahbltehetoaacertaonngiteriolef nJaomtOibsneosnti’emsthcpealersered4s8ytsaotnetdmhoes,theBperoradxeidadroelc-icekoranrnetadpioncroitn-swg,4o9mrtkhoeelresncfuuolcuelsne.od50pthhSiialmetsuilnnarleiektdoe
Jd olefinsaswellasanumberofnitrilesources.
ublished on 03 e is licensed un aaabu,bxlW-eiulintiatosrhaieatYsuchbrsai(ueOtevcTdehf)ca3aasrhabsio(g2xhtRyhll)yei-cbdcoaiaracntisadatlenydrseeet,orsisvHueallatteaijcvrmaetisvaeawnnibdtdhroc(tmo2h-Sewo,a5aozSirdi)kd-edoariftspicohwhneienrorayefll NbtfhrrBaeogiSmrmaoeneaendrtlthiaaeetcrrieosstnit3cu,8dataychniedodynw3foit9thuhienn1dtarmat1nhos:ala1%tnmtnoruiefxlaTatturMmroeGexnwoatniftfiohuofrmadecepiodoomnxtihbdfeoienrisme3od7amtywiieoeirntlihd–c
ss Article. P This articl pSmyr(ArOonlToifdt)h3ineares(itSnhcteherecemasttaeinly2gs2t)fe.4ox4ramapNleBSwparsomaoctheidevFerdiedveial–Ctrhaeftsuaslekyloaf-
cce tion of alkenes (Scheme 23).45 With electron-rich aromatic rings
A
n including toluene, o-xylene, anisole, 1,2-dimethoxy benzene, and
e
Op 1,2,3-trimethoxybenzene,theywereabletoachievethistransforma-
tionwithanumberofolefinicpartners.
Lastly, with Cu(OTf) or Zn(OTf) Hajra and co-workers were
2 2
abletoachievethestereoselectiveone-potsynthesisofoxazolines
viaabromoamideintermediate(Scheme24).46Inaprocesssimilar Scheme25 NBSinitiatedtransannularoxoniumionformation–fragmentation.
Scheme24 NBSpromotedstereoselectiveone-potsynthesisofoxazolines. Scheme26 NBSinitiatedepoxideopeningcascade.
7992 Chem.Commun., 2013, 49, 7985--7996 Thisjournalis c TheRoyalSocietyofChemistry2013
View Article Online
ChemComm FeatureArticle
e.
c
n
e
c Scheme27 NBSinitiatedepoxideopeningwithanexternalnucleophile.
M. d Li
Ae
2:17 nport of 43% (Scheme 27). While the yield of such NBS-initiated
4U
2:0 epoxide cascades was moderate, Snyder and co-workers have
3/2023 1bution 3. rtievpeoErtte2dSBhri(cid:2)SgbhBerrCyli5el(dBiDngSBe)proexaidgeencta.5s1cadeswiththemorereac-
n 2/2Attri
ded omons 3.3 CatalystfreeNBSinitiatedMCRs
oam In contrast to the above-mentioned examples, our laboratory
ownle Co discovered a range of catalyst-free NBS-initiated multicompo-
013. DCreativ neleencttrorpeahciltiiconMsC(RMsCaRres)lewssithrepaovrtaerdie,tpyaortflyodleufeintso.iSnuccohmkpiantidbsiliotyf
uly 2er a of the reagents.52 In our initial conception, we envisaged the Scheme29 Synthesis of pharmaceutically relevant molecules via the NBS
ublished on 03 Je is licensed und cfoaeymxacoslTininicbhieuieelmsittrohyeueairornccsftteeiyoartimcnoetliedygvdiieaenintlaigdnetergtianhFltoeleylredcmwfoeisnuoeirlsdrdkeiadtsottwhewaemeaEnlrlidn(wbsSoeicatahlhkfeunomNruxtseychNllaee2Htro8iop)a.nhattTisaplhicrtcekhoedeardutentcsaubtuccyklGtlie.na5bo3ngy- iainnffittioraartedmdoMthlCeeRc.urelasrpedcitsipvelacbermomenotamofidtehse(bScrohmemidees30i)n. Sthuebsberqoumenot-
s Article. P This articl pb(Mheialtreokloaennradikteoadvv-.tayTrpihee)teyaposfrowodeluellfcitanssssoatbnetdraeiocny-escdelilcehcetaitdvhietirgesos2o.wdIenrepaofsodiuteinmodnoantlo-- atghmueaindbierdsoimnaenosda.mciydcelisz)atlieodnt(oeitthheerfoinrmsiattuioonrobfyimfuirdthaezorlirnefelsuxainndg
s
cce strationoftheusefulnessofthereaction,theone-potassembly Oxygen nucleophiles in the form of carboxylic acids were
A alsofoundtobefeasiblereactionpartnersinthistypeofMCR.
Open orefsutlrtaends-i1n-pthheenfyolr-1m-partoiopnenoef,thNesNkeHy2i,nteetrhmyleednieateo4xi0de(S,chaenmdeN2B9)S. In a demonstration, the one-pot reaction of cyclohexene,
NBS, acetic acid, and THF was found to yield the alkoxylether
With further synthetic manipulation, ((cid:3))-phenmetrazine and
BontrilTMwerebothobtainedwithgoodyields.54 product 44 in good yield (Scheme 31).57 Likewise for this
reaction,avarietyofolefins,cyclicethersaswellascarboxylic
In addition to using cyclic ethers, nitriles and cyanimides
could be used in place to afford a range of imidazoline55 and acidswerefoundtobeapplicabletothisMCRprotocol.
guanidine,56 respectively. The MCRs proceed via the one-pot
assembly ofolefin, NBS, NsNH , and nitrilesor cyanimides to
2
Scheme28 ProposedmechanismofNBSinitiatedaminoalkoxylationofolefins. Scheme30 NBSinitiatedMCRinthesynthesisofimidazolinesandguanidines.
Thisjournalis c TheRoyalSocietyofChemistry2013 Chem.Commun., 2013, 49, 7985--7996 7993
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FeatureArticle ChemComm
e.
c
n
e
c
M. d Li
Ae
2:17 nport
4U
2:0
3/2023 1bution 3. Scheme31 NBSinitiatedalkoxyetherificationofolefin. SNcBhSeimnietia3t3edMEnCaRn.tioselective synthesis of 2,2,6-trisubstituted morpholine via
n 2/2Attri
ded omons
oam
wnlCo
oe
Dv
013. Creati
uly 2er a
Jd
ublished on 03 e is licensed un
s Article. P This articl
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p
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Scheme32 ProposedmechanismofMCRwithmono-substitutedepoxide.
AmorechallengingMCRinvolvingmono-substitutedepoxides
Scheme34 NBSinitiatedphenoxyetherificationMCRanditsapplication.
wasalsotackledbyourgroup(Scheme32).58Inthisreaction,after
theformationofthebromooxoniumintermediate,thesubsequent
oxonium ring opening can proceed via the anti-Markovnikov phenols, were subjected to the reaction, no desired product
(path1)ortheMarkovnikov(path2)pathways.Inourinvestiga- was detected. This result is consistent with our previous
tion,wediscoveredthatpropyleneoxidegavenoregioselectivity observation in which the acidic proton plays a crucial role in
(H:I = 1:1) despite the high reaction yield. Other bulky the MCR, potentially acting as the NBS activator. Again,
mono-substituted epoxides (e.g. R2 = OTBDPS) resulted in low the MCR tolerates a range of olefinic partners as well as
regioselectivity as well. Nonetheless, it was found that when ether partners for a wider reaction scope. More interestingly,
electron-deficientepoxideslikeepichlorohydrinandepibromo- the dibromides on the aromatic ring can undergo a double
hydrinwereused,goodregioselectivitieswereachieved. Sonogashira coupling to generate compound 48, which may
In a demonstration of the synthetic utility, enantiopure serve as ligands to self-assembly spherical complexes that are
(R)-epichlorohydrincouldassemblewitholefin45,NBS,andNsNH potentiallyapplicabletotheconstructionofhigh-densitydata-
2
(Scheme 33). Upon treatment with base, enantiopure 2,2,6-trisub- storagematerials.60
stitutedmorpholine46wasobtainedwithgoodyield.
Morerecently,itwasalsodiscoveredthatsufficientlyacidic 4. Conclusion
phenolscouldbeusedasanucleophileinthisMCRtogenerate
aphenoxyetherificationproductlike47(Scheme34).59Crucially, Thisfeaturearticlehaschartedtherecentadvancesoftheuse
it was discovered that when relatively electron-rich phenols, of N-bromoamideinthebromofunctionalizationofalkenes.In
including 4-methyl, 4-tert-butyl, and 2,6-dibromo-4-methyl thecourseofthearticle,therecentflurryofreportsinthearea
7994 Chem.Commun., 2013, 49, 7985--7996 Thisjournalis c TheRoyalSocietyofChemistry2013