stereoselective synthesis

what is stereospecificity

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

stereoselectivity

the reaction can produce either stereoisomer but one is preferred

diastereocontrol

controlling which diastereomer is produced

enantiocontrol

controlling which enantiomer is produced

major way of producing alkenes

the Wittig reaction

ylid + aldehyde → alkene + Ph₃P=O

what drives the wittig reaction

the carbonyl is more stable than the alkene but the P=O bond is very strong/stable, driving the reaction

how are ylids formed for the wittig reaction

phosphonium bromide salt + BuLi

wittig reaction mechanism including intermediate

intermediate = betane

collapses into products due to ring strain

possible intermediates of the wittig reaction

how does this first step happen

cis and trans betane

O and P come together at right angles then turn to be parallel in order to form a bond

cis betane structure + newman projection

trans betane structure + newman projection

which betane forms fast/slow and which is reversible (+ when?)

cis = fast + reversible (when R1 is electron withdrawing group so stabilises ylid)

trans = slow

show route to betane transition states and give relative stabilities

cis’s transition state more stable as R groups are on opposite sides

trans’s TS has steric clash from overlapping R groups

wittig product formed from cis betane + speed of formation

Z isomer only - no bond rotation

slow formation

wittig product formed from trans betane + speed of formation

E isomer

fast formation

which of E and Z isomers from wittig is kinetic or thermodynamic product and why

Z isomer (from cis betane) is kinetic product as initial step quicker

E isomer (from trans betane) is thermodynamic product as betane is much more stable

overall wittig reaction to form E and Z isomers with transition states

R groups end up with opposite stereochemistry to what they have in the transition state

the reaction is controlled by the energies of the betane

what does the pathway followed depend on

if R1 is EWG, the reaction initially forms the cis-betane but then goes back to the reactants and eventually follows the trans-betane pathway to form the E isomer

if R1 is not EWG, the reaction simply proceeds to form the Z isomer

dihydroxylation mechanism and stereospecificity

diastereospecific - forms cis diol only

epoxidation mechanism and stereospecificity

diastereospecific - forms cis epoxide only

explain the stereospecificty of the alkene dihydroxylation and epoxidation mechanisms

both diastereospecific - the alkene reacts at both ends at the same time in a concerted mechanism so the stereochemistry of the alkene is preserved

show mechanisms

show mechanisms