MPOC Ch 6 Stereochemistry

Isomers Different compounds with the same molecularformula

Constitutional Isomers different connectivity B Br CeeHnBr Br xx

Stereoisomers identical connectivity butdifferent spatial arrangements

Br Br µ and I

Enantiomers Chirastereoisomers that are non superimposable mirror images

a moleculethat is not superimposable on its mirror image

recognized by a lack of an internalplane ofsymmetry

Br Br M and I

Diastereomers stereoisomers that are not enantiomers Br Br R and H I and I H d Br Br

ChiralCenter atom with fourdifferent attached Colderterm groups

Ein

Stereosenic Center an atom at which the interchange of two produces a groups stereoisomer Br Br

G 4 Tn in 1LHE L enantiomers diastocomers H H Stereocenter

as most

P Stereogenic unit an atom or grouping of atoms at which interchangeof twogroups produces a stereoisomer any nd

Chemistry 531 – Physical Organic Chemistry Josh Osbourn

Stereochemistry

Non carbonstecocerthfill t neitherenantiomer Low inversion and is isolable barrier

Stable e Chiral phosphineligands cBum fifths Phd isolable Canbeused for asymmetric

synthesis

ChiralmoleculeswithoutchiralcertosI

Chiral if R Rz Rie Ry C c c and

R R Rs t Ry

i H Hi KC c dk 1kC c O Hy c jH ketene ACO f f me Me J ope sp enantiomers I allere

Atropisomers stereoisomers resultingfromrestricted bondrotation

BINAP pph can'toccupythesame pith Plane as thetwoH's

would bump Hinderedrotation

AchiralMolecules Possess a plane of symmetry

mesocompound compound

Hsc with one or morechiral is centersthatis achiral ITIII achiral dueto a planofsymmetry 01T OH CHS 1 Ht 3stococentos It tf III CB

Draw allstereoisomers e identifyrelationships Chemistry 531 – Physical Organic Chemistry Josh Osbourn

Stereochemistry

SkrochemicalDescriptorst Re S for chiral centers Lone Prioritize the four around the Chiral Center Pair H C DST groups Highest AN 1 Lowest AN 4 usuallyH

Tie examine connected tie move out one atom I compare groups Point 4 to back

1oz 3

Canalso use for Elz cc H

y E config ooo CHH B g

2 Axial Chirality H H Sight down the axis Ttm PrioritizeGroups G H bI g CI LP f f Be p

Highest priority her group tohighest priorityforgroup P

to I fIipm P q

3 De L

Used in Fisher Projections

carbohydrates e amino acids Typically H It 50 Naturally 50 Convention H OH H occurring HO COOH COOH HO H H OH OH H Ho H 12N H NINH NINH Hl OH on H Hotl H Right D i CHEH CHOH CILOH L serine D Glucose L Glucose naturallyoccurring Chemistry 531 – Physical Organic Chemistry Josh Osbourn

Stereochemistry

Opticalactivityandchirality

PlanePolarized Light Chiral one enantiomer of light is

I slowed morethantheother

chiral enantiomers to

different indices ofrefraction

all electricfieldsoscillating 6

in the same detected togiveopticalrotation plane OH OH pot pot B pBr Mr Es rien achiral achiral 50 150 50 1 150 opticallyinactive opticallyinactive active active optically optically OH so so e racemic mixture t inactive optically rotation Observedrotation specific GTF pathlength dm Concentration gloms

Ex A of cocaine dissolved in 7 S ML of in a 1.20gsample Chaz 5.0cm tube had an X 1.30 What is CDD sample

G D 16 1,306.50dmt.zogf.cm

Chiral non racemic mixture of enantiomers that is not I

When a rxn produces a non 50 so mixture of enantiomers have an excess you of one enantiomer

enantiomeric excess ee x too EiEz_x 100 Infix t Et Ez Chemistry 531 – Physical Organic Chemistry Josh Osbourn

Stereochemistry

ee 20 60 80 R 2 80 100 123 1 12,0 801 20 160 er 80.20 4 1 71 1 Racemic excess of R denatiomericratio

OH Ex CDF the7 You prepare the molecule t record

Et CiHas pure en CABO t5.10 What is ee t

ee too 76 t ee 6.7

Enantiomers most interaction strong Interact with achiralentities in an identical manner Common racemiccompound i heat same Same Mp bp 0 Same refractiveindex light Mp silica gel can't be separated conglomerate i Enantiomerssmell differently our body is chiral R S separation

1 Direct resolution Ph Ph ph Gt Ph Ph B 1tgN E I Nb ip TOO f B t T B ipr OH iPrXO t O n h

Arechiral 0 o.o of base p

2 Kinetic Resolution

Takingadvantage of the fact that enantiomers will react w chiral reagents

through diaster transitionstates

unequal ratedifference energy BuOH O O t flow1 yeast IOB Lh OI Br lipase Br 96 ee easilyseparate 454Conversion Chemistry 531 – Physical Organic Chemistry Josh Osbourn

Stereochemistry

Jacobsen HydrolyticKinetic Resolution JACS 2002,124 1307

PostDoc w Sharpless

Yz of 2001 Nobel Prize for asymmeticepoxidation

Nu epoxide opering OH OH t OH r r r I L Jacobsen destroy OH R o M sales E OH t f 1 t tho p r 7991 ee T r keep M sales M

for

sis will the in give f Ny other epoxide

enantiomer OF Her r X OAC F F I F CES 3 Chiral Shift Reagent Ao Lanthanide metal w chiral ligand EuChfd3 Xx O Ev y

Amein Enid T Agim

4 Chromatography

HPLC GC TLC etc ominimally destructive

Highselectivity ChiralstPhag R t S Low detection limit puts mix different Limit no universal chiralstationery

retention plase

times Limit Chiralcolumn 51 Chemistry 531 – Physical Organic Chemistry Josh Osbourn

Stereochemistry

TopicityRelationships

Br Br Br Br and Br Br w homotopicprotons Identical

have same NMR signal

and B B Br B B

entatiotopicprotons enantiomers

have same NMRsignal unless a shift reagent is used

OH OH OH AH M D M t and l T l 779 l 779S diasterotopic protons diastocomers

havedistinct 1H Nmr signals

I OH S µ pro D or Br Bite diaslerotopic Gtsgroups

Prochiralface

the 3 like Rts Assign groups O si face y µ Brmsop

MSBr H j IBC 010 Si 11 Re attack attack H Re face lit Enantiomers

Chemistry 531 – Physical Organic Chemistry Josh Osbourn

Stereochemistry

Rxn of an achiral molecule w a chiral reagent

CIMB Blank t BC p off t Kg H g H H Hsc

di isopinocampheylborane Diastercomers

formed in different Ipc amounts H Bm

he

StereospecificandstocoselectiveRXI

Stereospecific rxn Sterochem of the material dictates the starting stereochemof the product

Stereoselective an rtn that produces an excess of one stereoisomer

SNZ Rin

stereospecific AnyStereospecific I A e rxn is CN OTS stereoselective stereoselective

me Stereospecific t e Ph Ph mI Ph µ 15 stereoselective 67 33

M to sole OAC Bison product Sakurai Rin 11

Stereoselective rn

OAC not stereospecific

Chemistry 531 – Physical Organic Chemistry Josh Osbourn

Stereochemistry Diels Alder

Regioselective e stereoselective

09 1 NotFormed one Home if one Iem Timpone of regioisomers Correct alignment regioselective part

Use endo rule to predict stereoisomers

t it i'ten

Rome skpggsekd.ve en 11 phone K

TimescaleImplicationI Time scale is important for all stereochemical concepts

But is achiral because the

ii as i i is

enantiomers

achiral because a fast ringflip interconverts the enantiomericforms

enantiomers

Chemistry 531 – Physical Organic Chemistry Josh Osbourn