Silver mediated functionalization of (3.2.1) bicyclic systems obtained from tetrahalocyclopenes

248 Pages·2003·8.2 MB·English

by  Orugunty, Ravi Shankar

SILVERMEDIATEDFUNCTIONALIZATIONOF[3.2.1]BICYCLICSYSTEMS
OBTAINEDFROMTETRAHALOCYCLOPROPENES
By
RAVISHANKARORUGUNTY
ADISSERTATIONPRESENTEDTOTHEGRADUATESCHOOL
OFTHEUNIVERSITYOFFLORIDAINPARTIALFULFILLMENT
OFTHEREQUIREMENTSFORTHEDEGREEOF
DOCTOROFPHILOSOPHY
UNIVERSITYOFFLORIDA
2003
“Intryingtounderstandthemysteryoflife,manhasfollowedmanydifferentapproaches.
Amongthemtherearethewaysofthescientistandmystic,buttherearemanymore;the
waysofthepoets,children,clowns,shamans,tonameafew. Thesewayshaveresulted
indifferentdescriptionsoftheworld,bothverbalandnon-verbal,whichemphasize
differentaspects. Allarevalidandusefulinthecontexttheyarose. Allofthem,
however,areonlydescriptions,orrepresentations,ofrealityandarethereforelimited.
Nonecangiveacompletepictureoftheworld.”
TheTaoofPhysics,FritjofCapra
Thisworkisdedicatedtoallmyteacherswhohaveeducatedme
ACKNOWLEDGMENTS
Iwouldliketothankmyparents,brothersandsisterfortheirenduringfaithinme
throughoutthecourseofmygraduatestudies. Theirpatience,love,support,and
encouragementwerevitaltomysuccess. SpecialacknowledgmentsareduetoDr.
DennisWright,whoshowedgreatenthusiasmandencouragedmetopursuethisproject
andotherprojectswithindependence. Hisabilitytoteachtheartofviewingmolecules,
disconnection,andinsightintoanysyntheticproblemhashadadeepimpactonmy
thinking. Hisdiscussionsthroughoutthecourseofthisworkwereveryhelpfuland
encouraging. Ithasbeenapleasuretoworkwithhim. IwouldalsoliketothankMs.
LoriClarkforhelpingmeattheoffice,registeringmeeverysemesterandhelpingmefill
outalltherequiredpaperwork. Herhelphasmademystayatthisdepartmentvery
uneventfulandpleasant. Withouther,Iwouldhavebeensurelylostinadministrative
procedures. IwouldalsoliketoacknowledgeDr.MerleBattiste,whotookgreatinterest
inmyresearch,hementored,andeducatedmeintheartandscienceoforganicchemistry
especiallythevalueofelementalanalysisasaninvestigativetool. Hisabilitytomentor
graduateandundergraduatestudentshasleftadeepimpactonme. Specialthanksare
duetoDrIonGhiviriga,whosehelpwithNMRstudieswerevitalforthiswork. Thanks
areduetoDr.TomasHudlicky,whowaseverpresentwithhishelpfuldiscussionsand
encouragement. IwasveryfortunateinhavinghadmanydiscussionswithDr.Hudlicky,
whogivesauniqueandrefreshingperspectiveontheartoforganicchemistryandlife.
Withouthispositiveaswellasnegativemotivation,thisdocumentwouldnothaveseen
m
thelightofday. IwouldalsoliketothankallmygroupmembersespeciallyMs.Lynn
UsherandMs.MariaEstrellawithwhomIhadtoworkonadailybasis.Theyhadthe
patienceandkindnesstooverlookmyfaultsandhelpmeduringthecourseofthiswork.
SpecialthanksgotoClaudeRobothamforbeingtherewhenever1neededhishelp. I
wouldalsoliketothankDr.KanikaSharmaandDr.CherianZachariah,foralltheirhelp
andsupport.
IV
TABLEOFCONTENTS
Page
ACKNOWLEDGMENTS
iii
ABSTRACT vii
CHAPTER
1 CHEMISTRYOFHALOGENATEDCYCLOPROPENES 1
Introduction 1
CycloadditionReactionsofTetrahalocyclopropenes 3
SynthesisofCycloproparenesusingHalogenatedCyclopropenes 10
HalogenatedCyclopropenesin1,3-DipolarReactions 13
ThermalRearrangementsofTetrahalocyclopropenes 16
ReactionsInvolvingCyclopropeniumionsfromHalogenatedCyclopropenes 20
NucleophilicSubstitutionswithTetrahalocyclopropenes 28
Conclusion 33
2 DIELSALDERREACTIONOFTETRABROMOCYCLOPROPENEAND2,5-
DIMETHYLFURAN STRUCTUREANDREARRANGEMENTSTUDIES 34
:
Introduction 34
KineticData,ResultsandDiscussion 38
Experimental 42
3 FUNCTIONALIZATIONOFTETRAHALOCYCLOPROPENE
CYCLOADDUCTSBYSILVERPROMOTEDREACTIONS 45
Introduction 45
ResultsandDiscussion 48
SilverPromotedAdditionofOxygenNucleophiles 48
SilverMediatedAdditionofCarbonNucleophiles 50
AdditionofOrganometallicReagentstoDihaloenones103aand103c 58
SilverMediatedIntramolecularCyclizationofTetrabromooxa[3.2.1]bicyclic
Systems 66
ConclusionsandFutureWork 77
4 EXPERIMENTAL 78
v
APPENDIX
A KINETICSOFREARRANGEMENT:EXPERIMENTALDATA 123
B SPECTRAOFSELECTEDCOMPOUNDS 127
C X-RAYCRYSTALLOGRAPHICDATA 197
LISTOFREFERENCES 233
BIOGRAPHICALSKETCH 240
vi
AbstractofDissertationPresentedtotheGraduateSchool
oftheUniversityofFloridainPartialFulfillmentofthe
RequirementsfortheDegreeofDoctorofPhilosophy
SILVERMEDIATEDFUNCTIONALIZATIONOF[3.2.1]BICYCLICSYSTEMS
OBTAINEDFROMTETRAHALOCYCLOPROPENES
By
RAVISHANKARORUGUNTY
August2003
Chair: DennisL.Wright
MajorDepartment: Chemistry
Thetetrahalobicyclo[3.2.1]octa-2,6-dienesareobtainedbytheDielsAlderreaction
offuranandcyclopentadienewithtetrabromoortetrachlorocyclopropene. These
oxabicyclicandcarbocyclicsystemsareversatilesyntheticintermediatesthatare
analogoustothecompoundsobtainedfrom [4+3]oxyallyladditiontofuranor
cyclopentadiene. Treatingthesecompoundswithcationicsilveraffordsthe
perhalogenatedoxabicycliccationthatcanbeefficientlytrappedbyelectronrich
aromaticsystems. Furtherinvestigationswithregardstothereactivityofthesecations
werestudiedandthegeneralityofthissilverpromotedarylationwasexplored. Reaction
ofthesecationswithwaterproducesthecorrespondingdihaloenones. Thebicyclic
ketonesthatarethusobtainedareversatilesynthonsinthattheycanbetreatedwith
variousnucleophilestoaffordhighlysubstitutedbicycliccompoundsingoodyields.
AdditionofGrignardreagentsgivessolelythe1,2additionproductsinhighyieldswhile
theadditionofcupratesgives1Aadditionproducts. PalladiumcatalyzedSuzuki
Vll
couplingsofthesedibromoenoneshavealsobeeninvestigatedandfoundtoundergo
Suzukicouplingsspecificallyatthebetapositionformingtheproductinveryhighyields
thusmakingtheseoxabicyclicsystemsveryusefulsynthons. Theintramolecularcationic
cyclizationshavealsobeenstudied. Duringthecourseoftheseinvestigationsthe
reactionbetween2,5-dimethylfuranandtetrabromocyclopropeneaffordedtheprimary
unrearrangedadduct. Thiscompoundwasusedtostudytheratesofrearrangement,in
varioussolvents,byNMRandtheimplicationsoftheseresultstothemechanismof
rearrangementhavebeendiscussed.
vm
CHAPTER
1
CHEMISTRYOFHALOGENATEDCYCLOPROPENES
Introduction
Thesynthesisofhalogenatedcyclopropanesandcyclopropeneswasfirstreported
inaseriesofpapersbyTobeyandWest.lad Theseauthorsshowedthatthethermal
decarboxylationofsodiumtrichloroacetateindimethoxyethaneproduces
dichlorocarbene,whichreactswithtrichloroethylenetoaffordpentachlorocyclopropane
(1). Pentachlorocyclopropanewassubsequentlyconvertedtotetrachlorocyclopropene(2)
bytreatmentwithaqueouspotassiumhydroxide.
Sodiumtrichloracetate 18MAqKOH
1,2-Dimethoxyethane
80°C
Scheme1.1.SynthesisofHalogenatedcyclopropenes
Tetrachlorocyclopropenewasreadilyconvertedtotetrabromocyclopropene(3)by
treatmentwithstoichiometricamountsofborontribromide. Thesehalogenated
1
2
cyclopropenes,2and3,wererespectivelyconvertedtol,2-dichloro-3,3-
difluorocyclopropene(4)andl,2-dibromo-3,3-difluorocyclopropene(5)bytreatment
withSbF3(Schemel.l). Theformationofthevarioushalogenatedcyclopropenes,3,4
and5,wereexplainedontheformationofthecorrespondingcyclopropeniumcationthat
undergoeshalogensubstitution. Thel,2-dichloro-3,3-difluorocyclopropene(4)and1,2-
dibromo-3,3-difluorocyclopropene(5)havebeenconvertedtothemonoanddiiodo
cyclopropenesrespectivelyusingpotassiumiodideinDMF.2a
—
ClX^/F l)(CF3),PF-,/120C XFvv,F Zndust.Ethanol
Cl
Cl ci
Scheme1.2.Synthesisofmono,diiodocyclopropenes.andtetrafluorocyclopropenes.
TetrafluorocyclopropenewasfirstsynthesizedbyCamaggietal.2b Thesynthesis
involvedthereactionofdifluorocarbeneand1,2-dichlorodifluoroethylenetoproduce1.2-
dichlorotetrafluorocyclopropane(9). Reductivedechlorinationofthiscyclopropanewith
zincdustaffordedtetrafluorocyclopropene(10). Thetetrafluorocyclopropenewasfound
tohavesimilarreactionsasotherhalogenatedcyclopropenes.
TetraiodocyclopropenehasbeenreportedbyWeissetal.2c Thecompoundwas
synthesizedbytreatingtetrachlorocyclopropenewithtrimethylsilyliodideat0°Corboron