16 - WITTING REACTION AND REAGENTS Flashcards
why are witting reactions used?
make an alkene from an aldehyde or a ketone and control the stereochemistry (E or Z)
what is an ylide?
a species with opposite formal charges on adjacent atoms
what drives wittig reactions forward?
the highly stable P=O bond formed as a side product drives the reaction forward
how were alkenes formed before wittig?
how are simple ylides prepared?
what is the ylide form and what is the phosphorane form?
what are the characteristics of non stabilized vs stabilized ylides?
non stabilized ylides:
R=simple alkyl
reacts with aldehydes and ketones
good nucleophile
stabilized ylides:
R=aryl, alkenyl, CO2R, or anything that stabilizes the anion (EWG)
react with aldehydes only
not reactive enough for ketones
lower pKa
what are the characteristics of phosphonate stabilized anions
react with aldehydes and ketones
W= CO2- CO2R, CN, aryl, vinyl, SO2R, SR, OR, NR2
phosphonate stabilized carbanions are more nucleophilic and more basic than the corresponding stabilized phosphonium ylides
why are aldehydes more reactive than ketones?
- sterics: ketone has more alkyl groups, gives hindrance
- inductive effect: delta + on C is greater in aldehydes which makes them more reactive to nucleophiles
what is the mechanism of an ylide reaction?
the arrows go to make the P=O bond
how is wittig a thermal concerted [2+2] cycloaddition that allows to form?
the ylide and carbonyl approach approach each other perpendicularly
the large substituents are kept apart, and the P-C bond is long enough so that the ring can form
when we break the ring, we make a Z alkene
what happens if you use the sulfur ylide and how does the S=O bond compare to the P=O bond?
if you use a sulfur ylide you get an epoxide, if you use a phosphorus ylide you get the alkene
the P=O bond is is stronger than the S=O bond
the driving force is weaker in the sulfur analogue
what stereochemistry does a non stabilized ylide give?
Z stereochemistry
if there is a ketone and an aldehyde on the same molecule, how can you select for one?
get one equivalent only and put the ylide into the reactant not the opposite
why is the puckered ring conformation preferred for non stabilized ylides
minimizes angle strain and ecliping bond interactions that occur if the ring was planar
this transition state will lead to the Z alkene
why is the E alkene not favored for non stabilized ylides?
more steric interaction, when it’s puckered
when it’s planar, less sterics but more angular strain
what do stabilized ylides give?
more E than Z
what do CisTS and transTS yield?
what is (Z)-tricos-9-ene?
commonly available pheromone for control of the housefly in indoor areas
what are the two ways you can make this pheromone with a wittig reaction?
how is vitamin A industrially synthesized with a wittig reaction?
why is a normal ylide not used for the synthesis of juvenile hormone?
gives a very poor yield
what kind of ylide can be used for the synthesis of juvenile hormone?
Horner-Wadsworth-Emmons modification
phosphonate stabilized carbanion
more nucleophilic and more basic
mechanism to make juvenile hormone
makes the E alkene so that there is the least amount of steric effects between the CO2Me and the largest group
how does Horner-Wadsworth-Emmons work and what does it favor?
allows for E alkene on ketones
favours the E alkenes
the more equilibration amongst the intermediates, the higher the selectivity for the (E) alkene formation
with Horner-Wadsworth-Emmons, what determines the ratio between E and Z alkenes?
depends on the stereochemical outcome of the initial carbanion addition and the ability of the intermediates to equilibrate
how is the phosphonate reagent made for the synthesis of the juvenile hormone? (Arbusov reaction)
summary table
