NAPS

Role of NaH when with carbonyl

deprotonates α to carbonyl

reason mCPBA doesnt react with a,b-unsaturated carbonyl

not e- rich enough

used to form epoxide on a,b-unsaturated carbonyl

HOOH / -OOH

used to reduce C=O but leave C=C alone (linear)

NaBH4

used to reduce C=O and C=C (cyclic)

NaBH4

reason for alkene being reduced by naBH4 in a cyclic compound

• increased ring strain in β position

• alkene more open to attack due to enforced planarity

LUMO for hard Nu

C=O π*

LUMO for soft Nu

C=C π*

‘Michaels reagent’

a,b-unsaturated carbonyl attacked at C=C

reason for C=O alkenes being attacked

α C is (+)

C=O IR for a,b-unsaturated carbonyl

1678

C=C IR stretch for a,b-unsaturated carbonyl

1628

IR evidence of polarisation

generally weaker/lower stretches

C NMR evidence of polarisation

β = higher (more deshielded)

α = same

carbonyl = lower (more shielded)

H NMR evidence of polarisation (carbonyl alkene)

β = (much) higher (deshielded)

α = higher (slight deshielding)

Reason for EWG facilitating 1,4-addition

HOMO is lower in energy than standard diene

effect of carbonyl conjugated to alkene

overal lowering of orbital energy

thermo product of enolate

carbonyl

kinetic product of enolate

hydroxy alkene

mechanism that establishes equilibrium between enol and carbonyl

tautomerisation

good neutral nucleophile

amine / -NH2

first step in acid catalysed process (C=O)

protonation of carbonyl

intermediate acid catalysed conjugate addition proceeds via

enol intermediate

intermediate base catalysed conjugate addition proceeds via

enolate intermediate

grignard type of Nu

hard

softens the hard Nu grignard

CuI

Role of LDA (generally)

deprotonates

should be conscious of when metals present

co-ordination

Atoms that can be chiral centres

C, S, Si

assignment of chiral centres (R or S)

• asign priority to each substituent of the chiral centre

• draw molecule with lowest priority at the back

  • moving from 1 to 3, clockwise = R, anticlockwise = S

assigning priority to substituents of chiral centre

• start immediately bonded to the centre

• compare atoms, highest atomic number is best

• if some substituents are the same, look to the atoms they are bonded to

priority of lone pairs

lower than hydrogen

cis coupling constant

large (10-13Hz)

trans coupling constant

v. large (14-18Hz)

geminal alkene coupling constant

v small (0-2Hz)

reason for trans bonds ‘communicating’ better (largest J)

good orbital overlap (APP)

something to be wary of with ester conjugate acceptors

double addition

makes a good conjugate receptor

stable anion

pKa indicates..

stability of anion

greater pKa =

less stable

test to see which EWG best stabilises anion

look at pKa if there was a H there

determines kinetic control

relative rates of reaction

determines thermodynamic control

position of an equilibrium

favoured out of kinetic and thermo

thermo, most stable

needed for thermo control to happen

kinetic product to be reversible

can effect whether the product favours kinetic or thermo

reaction conditions (i.e. temperature, reaction time)

reason for C=O attacked first in kinetic product

carries the largest (+) charge

reason for 1,4- being thermo product (more stable)

still has strong C=O bond

most common addition with acid catalyst

1,4-addition

preferred reaction for amines

1,4-addition

hard Nu are generally…

• small

• negatively charged

• basic

• low E HOMO

hard E+ are generally…

• small

• positively charged

• high E LUMO

soft Nu are generally…

• larger

• uncharged

• less electronegative

• not basic

• high E HOMO

soft E+ are generally…

• larger

• neutral

• polarisable e-

• low E LUMO

favoured reactions between hard and soft species

hard - hard, soft - soft

type of centre the carbonyl C is

hard

type of centre b-C is

soft

control of hard interactions

charge control

control of soft interactions

orbital control

reason Cu softens grignards

decreases difference in electronegativity between X and C

influence of R group on esters

large R = forced 1,4 (even w/ grignard)

needed for SnAr

EWG in ortho or para position

How -OSiMe3 starts to react

O lp forms doube bond w C and likely causes a C=C to attack another species

Thing to consider when LA and C=O are together

the LA can coordinate to C=O

Options when an amine group is present as a reagent

whether it will deprotonate or attack a protonated C=O

What a C=O can do in acid

become hydroxy alkene

how many times will amines attack

as many times as they can

can OAc be a LG?

Yes