P-based Alkene Formation Flashcards
Give the name of the reaction shown
The Wittig Olefination
What alkenes are unstabilised ylides selective for?
Z alkenes
What alkenes are stabilised ylides selective for?
E alkenes
What is the driving force of the Wittig reaction?
P=O bond formation
- P=O bond is strong
What’re the drawbacks of the Wittig Olefination?
O=PPh3 byproduct is often difficult to remove
Stabilised ylide not very reactive
- reacts poorly with ketones
Why is PPh3 used instead of Et3N in the Wittig reaction?
Because the lone pair in PPh3 is in a more diffuse and polarisable orbital than Et3N
Hence, Ph3P is a better nucleophile despite being less basic
What is the name of the intermediate formed in the Wittig reaction?
Why do unstabilised ylides form Z alkenes?
Sterics, groups move as far away as possible to minimise repulsive forces
Why are stabilised ylides selective for E alkenes?
For stabilised ylides, electronic effects outweigh steric effects
Hence, electronegative groups are remote to each other to minimise repulsion
Why must the reagents approach each other in this orientation in the Wittig reaction?
To facilitate entry into the 4-membered (puckered) ring transition state
Give the mechanism of the given reaction
Give the name of the following reaction
The HWE Olefination
Give the mechanism for the HWE Olefination
Why is the HWE Olefination superior to the Wittig Olefination?
Stabilised ylide reacts well with ketones
Dialkyl phosphate by-product is water soluble
- easily removed
How is E/Z selectivity achieved in HWE Olefination?
How is the HWE ylide prepared?
Why are alpha-Haloketones unsuitable for HWE ylide preparation?
Because of the competing Perkow side reaction
Doesn’t occur when using esters - like in HWE - as Perkow reaction would break resonance of ester
What alkene is selectively made using HWE Olefination with an aldehyde?
HWE is highly selective for E-alkenes for aldehydes
What part of the HWE Olefination determines what alkene is produced preferentially?
E-selectivity is determined by the relative stability of the oxphosphetane intermediate
- not the 1,2-addition products like in Wittig
What factors affect E-selectivity in HWE Olefination?
E-selectivity is finely balanced and can depend on the structure of:
- R1
- the phosphonate ester
- the ethyl ester
How can the HWE Olefination be improved? What impact does this have?
By modifying -OR to make P-centre more electrophilic
- phosphate becomes a better LG, final step is faster
- oxaphosphetane formation is faster and becomes less reversible
- step 1 now determine product selectivity
Give the name of the reaction shown
Ando modification (of HWE)
What’s the role of Na in the Ando modification?
To chelate to the carbonyl groups, locking the enolate geometry
It also aligns the approaching carbonyl
- electrostatic attraction between carbonyl O and Na
What provides the selectivity in the Ando modification?
Due to electrostatic interaction between aldehyde O and Na, 2 possible orientations are available
The bottom approach is favoured because R1 is far away from the big -OPh groups
Hence, Z-alkene is formed preferentially
Give the name of the reaction shown
The Still-Gennari modification (of HWE)
Why are esters inert under HWE and other P-based olefinations?
Because they are not good enough electrophiles due to resonance
What additional benefit does HWE Olefination have?
Give the name of the reaction shown
The Corey-Fuchs alkynylation
Converting aldehydes to terminal alkynes over a 2 step sequence
Give the mechanism for step 1
(Blue arrow route preferred/more accepted)
Give the mechanism of step 2, followed by the rearrangement
Give the Fukui orbital analysis for the migration of H
What key points about carbenes should be remembered?
Carbenes have 6 valence electrons, is sp2 hybridised and is a V good electrophile
- bearing a free p-orbital
They can behave as Nuc or Elec
- with carbene lone pair or with free p-orbital respectively
Why is H the best migrating group? Can other groups migrate?
Because of its non-directional s-orbital
Other groups can migrate so long as they can access the vinyl carbene
Give the name of the following reaction
The Seyferth-Gilbert alkynylation
Converting aldehydes or ketones to alkynes over a 1 step sequence
Give the mechanism of the following reaction
What advantages does the Seyferth-Gilbert alkynylation have over Corey-Fuchs alkynylation?
Wider scope - aldehydes AND ketones
Only 1 step - additional step in C-F alkynylation
Mild conditions used
- C-F uses strong bases (typically n-BuLi) whereas S-G uses potassium carbonate
What is the original Seyferth-Gilbert reagent used that can react with ketones?
How are alkynes reduced to alkenes cis-selectively?
Using Lindlar’s catalyst - producing Z-isomer ONLY
Why is the alkene product not reduced further when using Lindlar’s catalyst?
Pb(OAc)2 and quinoline poison the Pd and make it less active, thereby preventing reduction of the alkene
How do you reduce alkynes trans-selectively?
Birch type conditions
Directed reduction using LiAlH4 (usually on propargylic alcohols)
Give the mechanism of alkyne reduction using LiAlH4
Give the names of these functional groups
Give the names of these functional groups
Give the name of this reaction
The Staudinger reaction
Converts azide to amine
What is typically used to reduce azide? How does this differ to what’s used in the Staudinger reaction and what drives this process?
LiAlH4 or cat. Pd/C, H2
Staudinger reaction uses PPh3 and H2O which are much milder reagents
- Process is driven by loss of N2 and formation of strong P=O bond
Give the mechanism of the Staudinger reaction
Give a mechanism for the following reaction
Predict the structure of the product of the reaction given
Predict the structure of the product of the following aza-Wittig reaction
What is the name of the following reaction
The Appel reaction
Conversion of alcohols to alkyl halides
- with clean inversion of stereochem
Give the mechanism of the Appel reaction
Why is the Appel reaction not stereospecific when using tertiary alcohols?
Because SN2 at tertiary centre is not feasible
- too bulky
Hence the process occurs via SN1
Predict the structure of both product of the following Appel reactions
What’s a limitation of the Appel reaction?
Azides can be made (useful) but the process is not general for other nucleophiles
What’s an alternative, more general appproach, to the Appel reaction?
The Mitsunobo reaction
Give the name of the following reaction
The Mitsunobo reaction
What must the pKa of NuH be below for the Mitsunobo reaction to work?
Give the mechanism of the Mitsunobo reaction
Predict the structure of the product following the Mitsunobo reaction shown
The Mitsunobo reaction offers a way to invert alcohols on a molecule
