Studied by 0 people
Looks like no one added any tags here yet for you.
Conjugated molecule
When 2 (or more) double bonds are separated by a single bond → uninterrupted chain of p-orbs on adjacent C atoms
Stereospecific reaction
When stereoisomers of a compound react under identical conditions to give different products.
e.g. Sn2, E2, Diels-Alder, hydroboration of alkenes and alkynesDraw
Stereoselective reaction
When a substrate is non-stereoisomeric but its reaction leads to different stereoisomers in unequal amounts.
Draw the Wittig reaction
Olefination (turning something into an alkene) mediated by an alpha-phosphorus carbanion.
Put these bases in order of strongest to weakest:
ⁿBuLi
tBuOK
NaH
PhLi
NaNh₂
NaOMe/NaOCl
When do we need a strong base in Wittig reaction (+ modifications)?
When R₃ is an alkyl group
When do we need a weak base in Wittig reaction (+ modifications)?
When R₃ is something that stabilised the -ve charge (definitely not an alkyl group)
What's an unstabilised ylide?
Which product does it stereoselectively give?
- Has an alkyl group next to -ve charge.
- Gives predominantly or only Z-alkenes.
What's an stabilised ylide?
Which product does it stereoselectively give?
- Has an EWG next to -ve charge - stabilises anion via resonance (-M)
- Gives E alkenes as major product
4 examples of EWGs
CO₂R (ester)
COH
COR
CN
Why are unstabilised ylides Z selective?
Irreversible formation of cis oxaphosphetane
- no steric clashes
Why are stabilised ylides E selective? (1st explanation)
Reversible formation of cis and trans oxaphosphetane; → minor trans oxaphosphetane closes faster + irreversibly to the E alkene
(The 2 groups are trans in the TS - don't have to become eclipsed → lower barrier of elimination so forms faster + irreversibly.)
i.e. Equilibration of oxaphosphetanes to more stable trans diastereomer → eliminates more rapidly than cis isomer
Why are stabilised ylides E selective? (2nd explanation)
Preferential irreversible stereoselective formation of trans oxaphosphetane, via perpendicular approach between. aldehyde + ylides
→ minimises steric clashes AND repulsion between electroneg. groups
Stabilised ylides are so stable that they're sluggish to react with ketones. How can we overcome this limitation?
Use the HWE reaction: phosphonate ester used instead of phosphonium ylide.
→ phosphonate-stabilised carbanions are more nucleophilic (+ more basic) than p. ylides
→ ester group lowers pKa
→ major E alkene (when conditions favour equilibration)
Mechanism + reagents for Horner-Wadsworth-Emmons Reaction
1) NaH or EtONa (base), DME (aprotic solvent)
2) Ketone or formaldehyde?
Show mechanism + reagents for preparation of phosphonates for HWE
What is the Julia olefination?
State 3 steps + reagents
Olefination mediated by alpha-sulfonyl carbanion (SO₂Ph).
→ Forms E alkenes.
3 steps:
1) Deprotonation at the α carbon by n-BuLi or EtMgBr
2) Acylation to add a LG (RCHO)
3) Elimination using Na/Hg + MeOH
Show mechanism + reagents for the Julia olefination.
What can the Julia olefination be used to prepare? Show the mechanism for it.
Dienes!! (diene = an unsaturated hydrocarbon containing two double bonds between carbon atoms)
Is the Julia olefination stereospecific or stereoselective for a certain alkene? Give a plausible explanation for your answer.
Stereoselective for E alkene.
→ Equilibration of an intermediate anion via tunnelling
→ adopts a conformation from which rapid elimination occurs (antiperiplanar - best orb overlap, lower TS = faster elimⁿ)
What are the two single-step variants of the Julia olefination which eliminate the need for reducing agents? Show reagents.
1) J.olefination w/ benzothiazole sulfone
→ 1) LDA (base to deprotonate), 2) R'CHO
2) Julia-Kocienski olefination w/ phenyl tetrazole sulfone
→ 1) KHMDS, 2) R'CHO
Show mechanism for J.olefination w/ benzothiazole sulfone
Show mechanism for Julia-Kocienski olefination w/ phenyl tetrazole sulfone
(Add from pg 897 of Clayden)
What is the Peterson olefination? (Silly!!!)
Show general reaction scheme
Olefination mediated by an alpha-silyl carbanion
1) addition - requires addition of Grignard reagent first
2) elimination
Show mechanism + reagents of Peterson olefination addition step with an aldehyde.
Reagents: Mg, Et₂O or THF → aldehyde → quench w/ H₂O
What determines the stereochemical outcome of the Peterson elimination?
STEREOSPECIFIC: produces specific alkenes based on stereochemistry of the Beta-silyl alcohol undergoing elimination
Show Peterson olefination elimination step in acid-mediated conditions for the anti diastereomer.
H₂SO₄, H₂O/THF, rt is 18h
Gives major E alkene if R = n-Pr
Show Peterson olefination elimination step in acid-mediated conditions for the syn diastereomer.
H₂SO₄, H₂O/THF, rt is 18h
Gives major Z alkene if R = n-Pr
Show Peterson olefination elimination step in base-mediated conditions for the anti diastereomer.
KH (v. reactive base), THF, rt is 1h
Gives major Z alkene if R = n-Pr
Show Peterson olefination elimination step in base-mediated conditions for the syn diastereomer.
KH (v. reactive base), THF, rt is 1h
Gives major E alkene if R = n-Pr
Which olefinations can be used to make E alkenes?
- Wittig w/ stabilised ylides
- HWE reaction
- Julia reaction
- Peterson elimination
Which olefinations can be used to make Z alkenes?
- Wittig w/ unstabilised ylides
- Peterson elimination
