chapter 7€¦ · chapter 7 cyclic compounds. stereochemistry of reacons organic chemistry, 5th ed....

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