201K: To Alkenes, Arenes and Beyond - Olefinations

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