Chapter 6 - Stereochemistry of Fused and Bridged Ring System.pdf

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1. Stereochemistry Of Fused And
Bridged Ring System

2. •Somecycliccompoundscontainmorethanonering.
•Iftworingssharetwoormorecommonatoms,thecompoundis
calledabicycliccompound.
•Iftworingshaveasinglecommonatom,thecompoundiscalled
aspirocycliccompound.
Bicyclic Compounds
Fused And Bridged Ring System

3. •Thecarbonatomsatwhichtworingsarejoinedinabicycliccompound
arecalledbridgeheadcarbons.
Fused And Bridged Ring System
i.Whenthebridgeheadcarbonsofabicycliccompoundareadjacent,
thecompoundisclassifiedasafusedbicycliccompound:
ii.Whenthebridgeheadcarbonsarenotadjacent,thecompoundis
classifiedasabridgedbicycliccompound:

4. Bicyclic Compounds
Fused And Bridged Ring System
•Thenomenclatureofbicyclichydrocarbonsisbestillustratedby
example:
•Thiscompoundisnamedasabicyclooctanebecauseitisabicyclic
compoundcontainingatotalofeightcarbonatoms.
•Thenumbersinbracketsrepresentthenumberofcarbonatomsinthe
respectivebridges,inorderofdecreasingsize.

5. Bicyclic Compounds
Fused And Bridged Ring System
•Drawstructuresforeachofthefollowingcompounds.Identifythe
bridgeheadcarbonatomsiftheyarepresent.
a.spiro[3.5]nonane b.bicyclo[4.3.0]nonane
c.bicyclo[3.3.0]octane d.bicyclo[2.2.2]octane

6. Bicyclic Compounds
Fused And Bridged Ring System
•GivetheIUPACnameofthecompound:
(Itscommonnameisdecalin.)
•Thecompoundhastwofusedringsthatcontainatotalof10carbons,and
isthereforenamedasabicyclodecane.
•Threebridgesconnectthebridgeheadcarbons:twocontainfourcarbons,
andonecontainszerocarbons.(Thebondconnectingthebridgehead
carbonsinafusedringsystemisconsideredtobeabridgewithzero
carbons.)

7. Fused Ring System
(cisand transRing Fusion)
•Tworingsinafusedbicycliccompoundcanbejoinedinmorethan
oneway.
•Therearetwostereoisomersofdecalin:cis-decalinandtrans-decalin

8. Chair conformation
Chair conformation
Fused Ring System
(cisand transRing Fusion)

9. Fused Ring System
(cisand transRing Fusion)
•Whichoneshouldbemorestable,cis-decalinortrans-decalin?
trans-decalin cis-decalin
•trans-decalinismorestablethancis-decalinsinceallcarbons
areequatorialwhereasincis-decalin,onecarbonisequatorial
andtheotherisaxial.

10. Quiz
1.Drawtheplanarstructureofdecalinwiththenumberingofall
carbonatomsandanswerthefollowingquestions:
i.Isthecompoundafusedorabridgedringbicycliccompound?
ii.Writeanothertwonamesofthecompound.
2.Decalinexistsintwostereoisomericforms:
i.Whatarethenamesofthesetwostereoisomericformsof
decalin?
ii.Drawtheplanarstructuresandthecorrespondingchair
conformationsofthetwostereoisomericforms.
iii.Whichoneofthestereoisomericformsofdecalinismore
stable?Giveexplanationinsupportofyouranswer.

11. Fused Ring System
(chair interconversion)
•Eachcyclohexaneringincis-decalincanundergothechair
interconversion.
•However,intrans-decalin,thesix-memberedringscanassumetwist-boat
conformations,buttheycannotchangeintotheiralternativechair
conformations.
Rigid

12. cis-and trans-Decalin

13. cis-and trans-Decalin
•trans-Decalinismorestablethancis-decalin.Therearethreeextra-
annulargaucheinteractionsincis-decalin.cis-Decalin,therefore,hasa
higherenergycontentthantrans-decalin.

14. •Commentonthechiralityofthefollowingdimethylcyclohexanes:
Chiralityof Cyclic Compound
cis-1,2-isomer cis-1,3-isomer cis-1,4-isomer
•Theplanarstructuresofcis-1,2-
dimethylcyclohexanehaveinternal
mirrorplanes(planesofsymmetry).
•However,thisisnotaplaneofsymmetryinthecaseofcis-1,2-
dimethylcyclohexane,becauseeachconformationofcis-1,2-
dimethylcyclohexaneischiralandhasnosymmetryplane.

15. StereochemicalConsequences of the Chair Interconversion
Non-congruent mirror images of each other
•cis-1,2-dimethylcyclohexane
is chiral
•However,thechairinterconversionconvertsoneenantiomerintotheother:
•By turning structure B 120°
about a vertical axis :

16. •cis-1,2-dimethylcyclohexaneisamixtureofchiral(andenantiomeric)
conformationsinrapidequilibrium.
•Becausetheseenantiomersareinterconvertedveryrapidly,theycannot
beseparatedatordinarytemperatures.
•Althoughitdoesnotexhibitopticalactivityatordinarytemperatures,ata
temperaturesolowthattherateofthechairinterconversionwouldbe
negligible,itcouldinprinciplebeseparatedintoenantiomers,eachof
whichwouldbeopticallyactive.
Chair
interconversion
Chirality of cis-1,2-
Dimethylcyclohexane

17. Chirality of cis-1,3-Dimethylcyclohexane
•cis-1,3-dimethylcyclohexane,anothermoleculewithtwoasymmetric
carbons,isamixtureofconformationaldiastereomers:
•Yet, even though each conformation has two asymmetric carbons, neither
conformation is chiralbecause each has an internal plane of symmetry.

18. Chirality of cis-1,3-Dimethylcyclohexane
•Bothconformationsofcis-1,3-dimethylcyclohexanearemeso.
•cis-1,3-dimethylcyclohexaneisthusarapidlyinterconverting
mixtureoftwodifferentmesocompounds,eachadiastereomerof
theother.
•Likeanymesocompound,cis-1,3-dimethylcyclohexaneisachiral
i.e.opticallyinactive.
diastereomer

19. •Wecanseefromitsplanarstructuresthattrans-
1,2-dimethylcyclohexaneischiral.
•Eachenantiomeriscapableofindependent
existenceandcanbeisolatedinopticallyactive
form.
Chirality of trans-1,2-Dimethylcyclohexane
•Thechairinterconversionconvertseachenantiomerintoaconformational
diastereomer.

20. Chirality of trans-1,3-Dimethylcyclohexane
•trans-1,3-dimethylcyclohexanedoesnothaveaplaneofsymmetryand
existsasapairofenantiomers.
•Theringflipintrans-1,3-dimethylcyclohexanedoesnotracemizethis
compoundbutregeneratethesameenantiomer.
Chiral

21. Chirality of cis-and trans-1,4-Dimethylcyclohexane
•cis-andtrans-1,4-dimethylcyclohexanecontainaninternal
symmetryplane,onlytwostereoisomersappear.Therefore,they
arebothmesocompounds(opticallyinactive)
meso compounds
(optically inactive)
meso compounds
(optically inactive)

22. Chirality of trans-Decalin
•Thesymmetrypointgroupoftrans-decalinisC
2h.
•trans-Decalinisnotopticallyactive,itisamesocompound.H
H

23. Chirality of cis-Decalin
•cis-Decalinischiralandexistsasapairofnon-resolvableenantiomers.
•Sincethechairinterconversionconvertsoneenantiomerintotheother,
theycannotbeseparatedatordinarytemperatures.

24. Stereochemistry Of Fused And
Bridged Ring System

25. Fused Ring System
(Hydrindane)
•Hydrindane(octahydro-1H-indene)isaninterestingmoleculebecauseit
resultsfromthefusionoftworingsofdifferentsize,andalsobecauseit
representsaportion(ringsCandD)ofthesteroidnucleus.
bicyclo[4.3.0]nonane

26. Chirality of cis-and trans-Hydrindanes
•Thetrans-hydrindanesareconformationallyrigidmoleculesand
occursastwostabletrans-enantiomers.
trans-(R,R)- trans-(S,S)-trans-Hydrindane
•Thecis-hydrindanesisflexibleandoccursasapairof
enantiomericconformers.
cis-Hydrindane(meso)

27. •Ofthemanynaturallyoccurringcompoundswithfusedrings,the
steroidsareparticularlyimportant.
•Asteroidisacompoundwithastructurederivedfromthefollowing
tetracyclicringsystem.
Steroids
Cholesterol

28. Cholesterol
•Important cell component

29. Cholesterol
•Precursorofallothersteroidsincludingvertebratesexhormones.
Cholesterol →Sex Hormones
big difference

30. •Twostructuralfeaturesareparticularlycommoninnaturallyoccurring
steroids:
i.Thefirstisthatinmanycasesallringfusionsaretrans.
➢Becausetrans-fusedcyclohexaneringscannotundergothechair
interconversion,all-transringfusioncausesasteroidtobe
conformationallyrigidandrelativelyflat.
ii.Manysteroidshavemethylgroups,calledangularmethyls,at
carbons10and13.
Steroids

31. Common Steroid Conformations

32. Alkaloids
•Strychnineinjectionsareused
tokillstraydogs/seedstokill
animals,nowfoundin
pesticides(killrats).
• isenough
tobefatal .
•Strychnineismostcommonly
derivedfromtheseeds
ofStrychnosnux-vomica,a
nativetreeofSouthIndia.
William Taylor’s death had been slow and
agonizing due to Strychnine poisoning.
1888 -the Eastern Shore of Virginia

33. Alkaloids
Strychnine
ConformationofStrychnine:
i.Ring4isinchairconformation,thus
forcingthebridgingofring6withit
viacis-diaxialbonds.
ii.Thismakesthefusionofring5with6
viaoneaxialandoneequatorialbond
i.e.cis-fusion.
iii.Ring2isalsocis-fusedwithring4i.e.,
itsbondwithnitrogenisequatorial.
iv.Ring7isalsocis-fused,and
v.Thefusionofring3and4istrans.N
N
O
O
1
2
3
4
5 6 7

34. Alkaloids
•Theconformationformulaofmorphineisdrawnasfollows:
MorphineN
CH
3
O
OH
HO O
NCH
3
H
H
HO
HO
1
2
3
4
5
7
6
8
9
10
11
12
13
14
15 16

35. Bridged Ring Systems
•Thesmallestbridgedringsystemis
bicyclo[1.1.1]pentane.
•Twobridgeheadcarbonsarebroughttoclose
proximitybecauseofverysmallendocyclic
valencyangles(72.5).
•Itisunstableandconvertedinto1,4-pentadieneon
heatingat300C.
1,4-Pentadiene

36. Bridged Ring Systems
•Themostcommonbridgedringsystemisbicyclo[2.2.1]heptaneor
norbornane.
•Inthissystem,C-1andC-4ofcyclohexanearejoinedbyamethylene
bridgeforcingittoadoptaboatconformation.
•Thesmallestendocyclicvalencyangleis93.0.
•Thesystemisconsiderablystrainedbecauseoftwoeclipsedbutaneunits
intheboat.
Bicyclo[2.2.1]heptane ornorbornane

37. Bridged Ring Systems
Exo-EndoIsomerism
•Exo–endoisomerismisaspecialtypeofstereoisomerismfound
inorganiccompoundswithasubstituentonabridgedringsystem.
•Theprefixendoisreservedfortheisomerwiththesubstituentlocated
closest,or"syn",tothelongestbridge.
•Theprefixexoisreservedfortheisomerwiththesubstituentlocated
farthest,or"anti",tothelongestbridge.

38. Bridged Ring Systems
•TheDiels-Alderreactionusually
proceedswithendoselectivity.

39. Bridged Ring Systems
Exo-EndoIsomerism
•In the Diels-Alder reaction, the stereochemistry of addition, besides
being endo,is also cis.
CyclopentadieneMaleic anhydride

40. Bridged Ring Systems
•Theendosideofthenorbornanesystemismorestericallycrowdedthan
exosidesotheexosideismoreaccessibletoavarietyofreagents
thantheendoside.
endo-Norborneol
Norcamphor
Norbornylene exo-Norbornadiol

41. Stereochemistry Of Fused And
Bridged Ring System

42. Bridged Ring Systems
•Theendosideofthenorbornanesystemismorestericallycrowdedthan
exosidesotheexosideismoreaccessibletoavarietyofreagents
thantheendoside.
Norbornylene exo-Norbornadiol
H
2, cat
or LiAlH
4
Norcamphor endo-Norborneol

43. Bridged Ring Systems
H
2, cat
or LiAlH
4
Norcamphor endo-Norborneol
H
–

44. Bridged Ring Systems
•Inthecamphanesystem,themoleculeisstronglyscreenedbythe
gem-dimethylgroupatC
7.
•Thissystemisgenerallyapproachedbyreagentsfromtheendo
side.

45. The BredtRule
•Therulestatesthatitisnotpossiblefordoublebondstobeformedonthe
bridgeheadcarbonatomsofabicyclicsystemifitinvolvesatransπbond
beingincorporatedinaringcomprisedoffewerthaneightatoms.

46. The BredtRule
•Duringtheβ-eliminationsinbicyclicsystems,thebridgeheadatomsare
notinvolved,providedtheringbearingtheincipienttransdoublebond
hasatleasteightatoms.