isomers and conformations

what are configurational isomers?

stereoisomers that cannot interconvert

what are conformational isomers?

spatial arrangements of molecules through rotations of bonds

what are the features of enantiomers? (3)

non super imposable mirror images of each other

both rotate plane polarised light in equal but opposite directions

other physical and chemical properties are the same

how do chiral amines behave?

not configurationally stable

inversion of lone pair is fast at room temp

why can phosphines and sulfoxides be isolated as single enantiomers?

they interconvert slower

what is planar vs axial chirality?

planar = planar system with a perpendicular substituent

axial = non planar arrangement of 4 groups about an axis

is this planar or axial chirality?

planar (perpendicular substituent)

is this planar or axial chirality?

axial

what is atropisomerism? what is type of chirality is this?

restricted rotation around a chiral axis

a type of axial chirality

what are diastereoisomers?

how do their properties compare?

stereoisomers with different configurations at one or more stereo centres

• different chemical and physical properties

what is the difference between syn and anti (diastereoisomers)

syn = groups on the same face

anti = groups on the opposite face

for compounds with n stereocentres…

how many stereoisomers are there? how many diastereomers?

what are meso isomers?

stereoisomers with identical substituents show diastereomers and one is achiral due to a symmetry plane or point of inversion

what is the top molecules’ relationship to each other

how are the top and bottom molecules meso isomers?

are there any diastereomers?

top two molecules are enantiomers

not enantiomers to each other as they are achiral

the top and bottom would be diastereomers, except that the bottom molecule is not chiral and has no stereocentres

how to decide whether a geometrical isomer of an alkene is E or Z (Cahn-Ingold)?

assign which end of the double bond is highest in priority

on each carbon, assign the priorities of each group

E = two higher priority groups on opposite sides

Z = two higher priority groups on same side

how to decide whether an enantiomer is R or S (Cahn-Ingold)?

priorities the substituents on the molecules from highest to lowest

redraw the molecule to look down the bond of lowest priority

determine if substituents 1,2,3 are in clockwise or anticlockwise order

R = clockwise

S = anticlockwise

how can the substituents on a molecule be prioritised?

higher atomic number > lower

greater number of higher priority atoms

multiple bonds = 2 or 3 bonds to atom of that atomic mass

if above doesn’t work, move to next atom in ring or chain

how to determine if a molecule is eclipsed or staggered?

rotate C-C bond so groups with same orientation are both up/down

look down bond

staggered = as far apart as possible

eclipsed = groups line up

staggered Newman projection

bond angle?

eclipsed Newman projection

why are staggered and eclipsed conformations different energies?

eclipsed = higher due to repulsion of coplanar bonds

staggered = groups as far apart as possible, also hyper conjugative stabilisation

how does the staggered conformation of ethane show hyper conjugative stabilisation?

what is the energy diagram as ethane moves through staggered and eclipsed?

staggered conformation of butane?

gauche conformation of butane?

eclipsed conformation of butane?

draw butane’s conformations as it rotates

what is the energy diagram as butane moves through its conformations?

explain the shape compared to ethane

methyl groups have larger steric effect than hydrogens

gauche = groups as far apart as possible, also hyper conjugative stabilisation so lower in energy

minimum when methyl groups are antiperiplanar

what is the difference between axial and equatorial in 6 membered rings?

axial = atoms above or below the ring

equatorial = atoms to the side of the ring

what do chair and boat conformations look like?

which is more stable

chairs are more stable than boats

where is there a steric clash?

1,3-diaxial

how do chairs change after ring inversion?

orientation of substituents change

• all equatorial become axial and all axial become equatorial

which position are larger groups more stable in (chairs)?

more stable in equatorial

in axial there are 1,3-diaxial, and gauche interactions

which conformation is favoured in disubstituted cyclohexanes?

largest group or more groups equatorial

draw in chair and decide which conformation is more favoured

draw in chair and decide which conformation is more favoured

why are smaller rings less stable that cyclohexanes?

rings are more strained

eclipsing interactions = torsional strain

show ring strain in cyclopropane

torsional strain? orbital overlap?

each C-C angle is 60

show ring strain in cyclobutane

how is it better than cyclopropane?

relieves some torsional strain by adopting puckered conformation

show ring strain in cyclopentane

confirmation?

adopt envelope conformation - sawn off chair

eclipsed = more strain on right hand carbon

how does ring strain chain as ring gets bigger?

strain decreases

carbons become more staggered rather than eclipsed

what conformation does cyclohexene adopt?

hybridisation?

contains two sp² carbons = trigonal planar

adopts half chair conformation

= more strained

are double bonds attached to cyclohexane ring axial or equatorial?

draw angle

neither

C=O bond intersects axial-equatorial bond ange

show cyclohexene chair ring flip

what is a decalin?

fused cyclohexanes

how do trans decalins exist?

draw both conformations

both groups equatorial

how do cis decalins exist?

draw conformations

can have two - one substituent equatorial and one axial

is a trans or cis decalin more stable?

trans is more stable than cis

cis has 1,3-diaxial clash

what conformations do epoxides form?

draw conformations - which is most stable?

half chair

pseudo equatorial is most stable

• epoxide stays the same even after ring flip

what conformations do bromoniums form?

show for both points forwards and points away

half chair

how can enantiomers be described?

as either + or - depending on how they rotate plane polarised light

how to calculate specific rotation of molecule

units?

how to calculate optical purity?

what is a disadvantage of this?

you must know the rotation of a pure sample - may not have been prepared before

what are the two ways of referring to a ratio of mixture of enantiomers?

enantiomeric ratio

enantiomeric excess

how to calculate enantiomeric excess?

i

if there is 95:5 ratio of two enantiomers, what is the enantiomeric excess?

95 - 5 = 90% e.e.

5:5 racemic so 90% not cancelled out

how is chiral chromatography performed? what type of chromatographic techniques are used

gas chromatography or high performance liquid chromatography

stationary phase is modified with chiral molecules

diastereomeric environment = one enantiomer is more strongly retained than the other = separated

what is the difference between achiral and chiral chromatography?

achiral = enantiomers have same affinity for stationary phase and so pass through at same rate

chiral = different affinity for stationary phase, different chemical environments so pass through at different rates

what are the different H environments in this molecule?

no rotation so not in same environment

what is trans, cis and geminal coupling constants?

proton environments near a stereocentre are what?

diastereotopic = non equivalent

show how these environments are different

show bond angles of these H’s

what is the karplus relationship?

show graph

coupling constants (3 bond H-C-C-H) depends on dihedral angle

protons opposite each other means higher coupling constant

120 = 8-12Hz

60 = 3-4Hz

180 = 10-12Hz

using karplus relationship, what are the J values?

how to draw Newman projections?

draw intermediate sawhorse projection

draw 2D of Newman projection

draw intermediate sawhorse projection

what are the 4 potential isomers that could be formed

what is stereospecificity?

only a certain stereoisomer can be produced due to how the reaction proceeds

what is stereoselectivity?

the reaction has a choose but one stereoisomer is preferred

what is diastereocontrol?

controlling which diastereomer is produced

what is enantiocontrol?

controlling which enantiomer is produced

what is a ylid?

what is the wittig reaction?

ylid + aldehyde = alkene + Ph₃P=O

how is ylid formed?

phosphonium bromide salt + BuLi

what is the reaction mechanism for wittig reaction?

intermediate?

betane intermediate = collapses into products as ring strain

what are the two possible intermediates?

cis and trans betane

draw cis betane and Newman projection

draw trans betane and Newman projection

which betane forms fast and slow?

which is reversible?

cis = fast and reversible

trans = slow

when is the cis betane formation reversible?

if R₁ is electron withdrawing group so stabilises ylid

what are the cis and trans betane formation transition states?

which is more stable and why?

cis transition state is more stable - R groups on opposite sides

trans transition state has R groups overlapping = steric clash

what is the product from the cis betane intermediate? is it fast or slow?

Z isomer only - concerted reaction as no bond rotation

slow formation

what is the product from the trans betane intermediate? is it fast or slow?

E isomer only

overall ,which is the kinetic and which is the thermodynamic product? why?

Z isomer (from cis betane) is the kinetic as quicker pathway

E isomer (from trans betane) is the thermodynamic product as the trans betane is much more stable and lower energy

which isomer is formed?

if the R group doesn’t have a stabilising group (EWG), then Z isomer as proceeds through cis route

if there is a stabilising group, it goes to Z and then reverses to make E

draw the two reaction pathways and show transition states and intermediates

show an example of EWG stabilising ylid

if R₁ is ester

electrons delocalised onto C-C bond

stabilises and withdraws electron density

what is the dihydroxylation reaction?

what is special about it

alkene + water using OsO₄ catalyst

it is diastereospecific

draw mechanism

which isomer is formed?

cis diol only formed as O is on same face of alkene

what is special about the epoxidation reaction?

it is diastereospecific

draw mechanism of cyclohexene + mCBPA

which isomer is formed?

cis epoxide formed (bonds on same face)

what is mCBPA?

meta-chlorobenzoperacid

what is a peracid?

carboxylic acid with an extra O

why is alkene dihydroxylation and epoxidation diastereospecific?

alkene reacts at both ends at the same time (concerted) so stereochemistry of alkene is preserved

what are the products when OsO₄ reacts on the top and on the bottom?

what are the products when mCPBA reacts on the top and on the bottom?

what is the product when OsO₄ reacts?

cis has high steric clash so rotates to be trans

what is the product when mCPBA reacts?

cis product