Chapter7CyclicCompounds.
StereochemistryofReac7ons
Organic Chemistry, 5th ed. Marc Loudon
Eric J. Kantorowski California Polytechnic State University San Luis Obispo, CA
Chapter7Overview
• 7.1Rela)veStabili)esoftheMonocyclicAlkanes
• 7.2Conforma)onsofCyclohexane• 7.3Monosubs)tutedCyclohexanes.Conforma)onalAnalysis
• 7.4Disubs)tutedCyclohexanes• 7.5Cyclopentane,Cyclobutane,andCyclopropane• 7.6BicyclicandPolycyclicCompounds
• 7.7Rela)veReac)vi)esofStereoisomers• 7.8Reac)onsthatformStereoisomers
• 7.9StereochemistryofChemicalReac)ons
2
MonocyclicCompounds
• Compoundscontainingasinglering(e.g.,cyclopentane,cyclohexane)
• Rela)vestabili)esaredeterminedfromheatsofforma)on(ΔHf°)
• Allhavethesameempiricalformula:CH2
• Thus,stabili)escanbereadilycomparedonapercarbonbasis
37.1Rela7veStabili7esoftheMonocyclicAlkanes
CycloalkaneHeatsofForma<onperCH2
47.1Rela7veStabili7esoftheMonocyclicAlkanes
Cyclohexane
• Hasthesamestabilityasatypicalunbranchedalkane
• Prevalentinmanynaturallyoccurringorganiccompounds
• Itsconforma)onrevealsitsuniquestability
57.1Rela7veStabili7esoftheMonocyclicAlkanes
TheChairConforma<on
• Cyclohexaneadoptsanon‐planar,puckeredconforma)on
• Thisavoidsanglestrainandtorsionalstrain
67.2Conforma7onsofCyclohexane
TheChairConforma<on
77.2Conforma7onsofCyclohexane
DrawingChairConforma<ons
• Notethe“V”arrangement
87.2Conforma7onsofCyclohexane
DrawingChairConforma<ons
• Notetheparallellines
• Iden)fyupanddowncarbons
97.2Conforma7onsofCyclohexane
EquatorialandAxialHydrogens
107.2Conforma7onsofCyclohexane
InterconversionsofChairConforma<ons
• Commonlyreferredtoasachairflip
117.2Conforma7onsofCyclohexane
BoatConforma<on
127.2Conforma7onsofCyclohexane
BoatandTwistBoatConforma<ons
137.2Conforma7onsofCyclohexane
Rela<veEnthalpies
147.2Conforma7onsofCyclohexane
Monosubs<tutedCyclohexanes
• Subs)tuentscanoccupyanaxialorequatorialposi)on
157.3Monosubs7tutedCyclohexanes.Conforma7onalAnalysis
Monosubs<tutedCyclohexanes
• Representconforma7onaldiastereomers
• Equatorialispreferredbylargergroups• Notethatthe‘down’methylremainsdowna]erthechairinterconversion
167.3Monosubs7tutedCyclohexanes.Conforma7onalAnalysis
1,3‐DiaxialInterac<ons
177.3Monosubs7tutedCyclohexanes.Conforma7onalAnalysis
Methylcyclohexane
• Theaxialconforma)onisanalogoustogauchebutane
187.3Monosubs7tutedCyclohexanes.Conforma7onalAnalysis
tert‐Butylcyclohexane
• Theconforma)onplacingthebulkyt‐butylgroupequatorialisoverwhelminglyfavored
197.3Monosubs7tutedCyclohexanes.Conforma7onalAnalysis
Cis‐TransIsomers
• Trans:thetwogroupshaveanup‐downrela)onship
• Cis:thetwogroupshaveadown‐downrela)onship
207.4Disubs7tutedCyclohexanes
Cis‐TransIsomers
• Cisandtransspecifytherela7vestereochemicalconfigura)ons
• Cisandtranssaysnothingaboutabsoluteconfigura)on
• Forexample,therearetwoenan)omersofcis‐1‐chloro‐2‐methylcyclohexane:
217.4Disubs7tutedCyclohexanes
Conforma<onalAnalysis
• Fordisubs)tutedderiva)ves,thelargergroupwillpreferen)allyoccupytheequatorialposi)on
227.4Disubs7tutedCyclohexanes
UseofPlanarStructures
• Althoughcyclicstructureshavenon‐planarconforma)ons,planarrepresenta)onsares)lluseful
237.4Disubs7tutedCyclohexanes
StereochemistryandtheChairConformer
• Cis‐1,2‐dimethylcyclohexaneconformerscanbeshowntobechiral
• …butachairinterconversionconvertsoneenan)omerintotheother:
247.4Disubs7tutedCyclohexanes
StereochemistryandtheChairConformer
• Cis‐1,3‐dimethylcyclohexanehastwoasymmetriccarbons
• …yetneitherconformerischiral
257.4Disubs7tutedCyclohexanes
StereochemistryandtheChairConformer
• Therefore,planarrepresenta)onscanbeusedtomorereadilyevaluatechirality
267.4Disubs7tutedCyclohexanes
StereochemistryandtheChairConformer
• Trans‐1,2‐dimethylcyclohexanerepresentsadifferentsitua)on
• Theplanarstructuresrevealittobechiral
277.4Disubs7tutedCyclohexanes
StereochemistryandtheChairConformer
• Hence,eachenan)omercanexistindependentlyandcanbeisolatedinop)callyac)veform
287.4Disubs7tutedCyclohexanes
Cyclopentane
• Existsintheenvelopeconforma<on• Eachcarbonrapidlyalternatesasthe“point”oftheenvelope
297.5Cyclopentane,Cyclobutane,andCyclopropane
Cyclobutane
• Suffersfromanglestrain• Existsinapuckeredconforma)on
• Puckeringhelpsrelievesomeeclipsing
307.5Cyclopentane,Cyclobutane,andCyclopropane
Cyclopropane
• Suffersfromanglestrainandeclipsingstrain• Cannotpuckertorelievethesestrains• C‐Cbondsaresome)mesreferredtoasbananabonds
317.5Cyclopentane,Cyclobutane,andCyclopropane
• Notethatbondingprimarilyoccursoutsideoftheinternuclearaxis
Classifica<onandNomenclature
• Bicyliccompounds:Tworingssharetwoormorecommonatoms
• Spirocycliccompounds:Tworingshaveasinglecommonatom
327.6BicyclicandPolycyclicCompounds
Classifica<onandNomenclature
• Fusedandbridgedbicycliccompounds
337.6BicyclicandPolycyclicCompounds
Classifica<onandNomenclature
• Polycycliccompounds• Possessfascina)ngmoleculararchitecturecommonlywithinteres)ngphysicalproper)es
• Canbesynthe)callychallenging
347.6BicyclicandPolycyclicCompounds
CisandTransRingFusion:Decalin
357.6BicyclicandPolycyclicCompounds
• Ringfusioncausestrans‐decalintobeconforma)onallylocked
Trans‐Decalin
367.6BicyclicandPolycyclicCompounds
• Bicycliccompoundswithsmallringsarerestrictedtocisringfusion
• Transfusionwouldincurtoomuchringstrain
RingFusionwithSmallRings
377.6BicyclicandPolycyclicCompounds
Trans‐Cycloalkenes
• Smallrings(≤7)cannothavetrans(orE)stereochemistry
• Trans‐cyclooctenehasbeenprepared,butitsignificantlylessstablethantheZisomer
• Largerrings(≥9)cancomfortablyexistaseithercisortrans
• Trybuildingmodelsforthesecycloalkenes
387.6BicyclicandPolycyclicCompounds
Bredt’sRule
• Adoublebondcannotbeatabridgeheadposi)onunlessoneoftheringshas≥8atoms
397.6BicyclicandPolycyclicCompounds
Steroids
407.6BicyclicandPolycyclicCompounds
Steroids
417.6BicyclicandPolycyclicCompounds
Rela<veReac<vi<esofEnan<omers
• Enan)omersreactatthesameratewithanachiralreagent
• Forexample,boththeRandSenan)omersofthefollowingalkenereactatthesamerate:
427.7Rela7veReac7vi7esofStereoisomers
Rela<veReac<vi<esofEnan<omers
• Enan)omersreactatthedifferentrateswithachiralreagent
• Diastereomericproductsandtransi)onstateshavedifferentfreeenergies
437.7Rela7veReac7vi7esofStereoisomers
Rela<veReac<vi<esofEnan<omers
• Enzymesareenan)omericallypurechiralmolecules(reagents)
• Theycatalyzethereac)onofonlyoneenan7omerofapair
447.7Rela7veReac7vi7esofStereoisomers
Rela<veReac<vi<esofEnan<omers
457.7Rela7veReac7vi7esofStereoisomers
Rela<veReac<vi<esofDiastereomers
• Diastereomersgenerallyhavedifferentreac)vi)estowardanyreagent(chiralorachiral)
• Boththestar)ngmaterialsandtransi)onstatesarediastereomeric
• Consequently,theirstandardfreeenergiesofac)va)on,andhencetheirreac)onrates,differ
467.7Rela7veReac7vi7esofStereoisomers
Reac<onsThatGiveEnan<omericProducts
• Consideranachiralcompoundyieldingachiralproduct
477.8Reac7onsthatformStereoisomers
ChiralEnvironments
487.8Reac7onsthatformStereoisomers
Reac<onsThatGiveDiastereomericProducts
• Somereac)onscouldleadtodiastereomericproducts
• Ingeneral,whendiastereomericproductscanbeformed,theyareformedatdifferentrates
• Byconven)on,onlyoneoftheenan)omersisnormallydrawn
497.8Reac7onsthatformStereoisomers
StereochemistryofAddi<onReac<ons
• Syn‐addi<on:
• An/‐addi<on:
507.9StereochemistryofChemicalReac7ons
StereochemistryofSubs<tu<onReac<ons
• Reten<onofconfigura)on:
• Inversionofconfigura)on:
517.9StereochemistryofChemicalReac7ons
Overview
• Inordertoobservewhetherreten)onorinversionhasoccurred,thecarbonundergoingsubs)tu)onmustbeastereocenter
527.9StereochemistryofChemicalReac7ons
StereochemistryofBromineAddi<on
• Addi)onofbrominetoanalkeneisahighlystereoselec7vereac)on
• Threestereoisomersarepossibleforthefollowingreac)on:
537.9StereochemistryofChemicalReac7ons
StereochemistryofBromineAddi<on
547.9StereochemistryofChemicalReac7ons
Stereospecificity
• Reac)onsinwhichdifferentstereoisomersofastar)ngmaterialgivedifferstereoisomersofaproductarecalledstereospecificreac<ons
557.9StereochemistryofChemicalReac7ons
StereochemistryofHydrobora<on‐Oxida<on
• Hydrobora)onisastereospecificsyn‐addi)on
567.9StereochemistryofChemicalReac7ons
StereochemistryofHydrobora<on‐Oxida<on
• Theoxida)onoforganoboranesisastereospecificsubs7tu7onreac)on
577.9StereochemistryofChemicalReac7ons
StereochemistryofHydrobora<on‐Oxida<on
• Thetwostepsofhydrobora)on‐oxida)onresultinnetsyn‐addi)onofH‐OHtothealkene
• Notethatthetransdesigna)onofthenamehasnothingtodowiththewayH‐OHadded
587.9StereochemistryofChemicalReac7ons
StereochemistryofHydrogena<on
• Cataly)chydrogena)onisastereospecificsyn‐addi)on
597.9StereochemistryofChemicalReac7ons
StereochemistryofOxymercura<on‐Reduc<on
• Oxymercura)onofalkenesisastereospecifican7‐addi)on
• Recallthatthisproceedsviaacyclicmercuriniumion
607.9StereochemistryofChemicalReac7ons
StereochemistryofOxymercura<on‐Reduc<on
• Thereduc)onstepvariesfromcasetocase
• Overall,theoxymercura)on‐reduc)onreac)onisnotstereospecific
• Itishighlyregioselec7ve,however
617.9StereochemistryofChemicalReac7ons