Revision Session

Organic Chemistry

STEREOCHEMISTRY AND MECHANISM

Starter Past Paper Questions and Answers

Aromaticity
Starter Past Paper Questions and Answers

Question 1
(a) Huckels Rule Discuss

[100%]

Aromatics

Revision and Past Paper Questions and Answers

 Carbonyl

acts as both an electrophile and a nucleophile

has resonance structure

Carbonyl

Electrophile:

Formation of Enolates and Enols Removal of alpha-proton (most acidic)

Enolate Alkylation Nucleophile

Acidities of alpha and beta carbonyl protons

1,3 Dicarbonyl Compounds Why is central alpha proton more acidic? Conjugation and intramolecular H bonding

Alpha substitution reactions Reaction with an electrophile (acid catalysed)

Alpha substitution reactions Reaction with an electrophile (base catalysed)

Bases used for enolate formation Carbonyl compounds weakly acidic Strong base needed to ensure complete enolate formation LDA Lithium diisopropylamide

Deuterium Substitution of alpha protons When enriched with D2O (acid or base), all alpha protons are in equilibria with deuterium Used as an isotopic label in molecules

Racemization Stereochemistry at alpha carbon is lost during enolate formation Protonated unequally at two faces

Halogenation of Carbonyls (acid catalysed)

Halogenation of Carbonyls (lewis acid)

Unsymmetrical Ketones Two different enols are formed Occurs preferentially at the more substituted position as more stable

Enolates of Unsymetrical Ketones

Kinetic favoured due to unhindered alpha protons

1,3 Dicarbonyl Compounds Alkylate at different sites in different conditions

Decarboxylation of beta-ketoesters

Add a -CH2CO2H to an alkyl halide

Add a -CH2COCH3 to an alkyl halide

Add a -CH2CO2H then COCH3 to an acyl halide

https://learn.uea.ac.uk/webapps/portal/fram eset.jsp?tab_tab_group_id=_4_1&url=%2Fweba pps%2Fblackboard%2Fexecute%2Flauncher%3Ft ype%3DCourse%26id%3D_85894_1%26url%3D Click Vignettes Level 1 Aldol Reaction

Aldol Reaction

Mixed Aldol Reaction Use LDA (one equivalent) to convert all of aldehyde to enolate Same Ketone Aldol Reaction Use NaOEt/EtOH to convert a small proportion to enolate

Aldol Dehydration Base Catalysed

Acid Catalysed (more common)

Intramolecular Aldol Reactions Dicarbonyl compounds treated with base Leads to cyclic product

Intramolecular Aldol Reactions For Unsymmetrical Dicarbonyl Species more than one product is possible

Claisen Condensation Esters react in same fashion as aldol reaction

Intramolecular Claisen Condensations aswell

Knoevenagel Condensation

Michael Reaction Enolates react with conjugated carbonyls through terminus double bonds rather than the carbonyl itself!

Micheal reaction followed by intramolecular aldol Micheal Addition Intramolecular Aldol Aldol Condensation (Base catalysed)

Condensation with Amine Derivatives Ketone Imine

Condensation with Amine Derivatives Imine Enamine

Enamine Reactivity React simular to enolates in neutral form. Forms iminium salt, hydrolysis leads to alkylated carbonyl

Enamine Reactivity

Wittig Reaction

Introduces alkenes from ketones using phosphorus ylids.

Stage 1 Preparation of a phosphonium salt from an alkyl halide

Stage 2 Deprotonation of the phosphonium salt to form a ylid

Stage 3 Reaction of the ylid with a carbonyl group

E or Z alkenes? Ylids that have a conjugating or anionstablilizing substituent (such as a carbonyl) adjacent to negative charge give E Alkenes

Ylids without such groups are unstabilized ylids and tend to give Z Alkenes

Example of Z Alkene formation

Example of E Alkene formation

Pericyclic Reactions
Revision and Past Paper Questions and Answers

Pericyclic Reactions
Pericyclic Reaction: A concerted reaction that takes place as a result of a cyclic rearrangement of electron density Concerted: Bond making and bond breaking takes place at the same time

No intermediates are formed, proceeds through a single transition state

Cycloaddition

Cycloadditions
Diels-Alder Reaction

[4+2] cycloaddition (4 + 2 = 6 electrons)

Reversible reaction but driven to product due to loss of 2 pi bonds and formation of 2 sigma bonds Diene must be Z (cis)

Cycloaddition

Stereochemistry of Diels Alder

Cycloaddition

Stereochemistry of Diels Alder

Cycloaddition

Hetero Diels-Alder Reactions

Examples

Cycloaddition

Other Cycloadditions
Example: [8 + 2] Thermal Conditions

Cycloaddition

Other Cycloadditions

Cycloaddition

Other Cycloadditions
How to tell if a cycloaddition under thermal conditions work? If Aromatic Intermediate (4n+2) then yes If Antiaromatic Intermediate (4n) then no [2+2] Antiaromatic No [4+2] Aromatic Yes [4+4] Antiaromatic No [6+4] Aromatic Yes [8+2] Aromatic Yes Etc

Cycloaddition

Photochemical [2+2]
By exciting the HOMO to a higher energy state (HOMO*) the phases are changed to allow orbital overlap

Cycloaddition

Thermal [2+2] Cycloaddition

Special Case where photochemical activation is not needed, use Ketene.

Why? Central carbon atom is sp hybridised and overlaps antiarafacial

Cycloaddition

Antarafacial Overlap for Ketene [2+2]

Sigmatropic Rarrangement

Sigmatropic Rearrangements

Example [3,3]-sigmatropic rearrangement

Driving Force Enol Keto tautomerisation C=O stronger than C=C

Sigmatropic Rarrangement

Claisen Rearrangement
First sigmatropic rearrangement
Phenyl allyl ether is heated to give ortho-substituted phenol

Sigmatropic Rarrangement

Sigmatropic Rearrangement
Proceed via a chair-like transition state

For Substituted Allyl Ethers (on sp3 next to oxygen) the resulting alkene is always E (trans)!

Sigmatropic Rarrangement

Cope Rearrangement

Use Carbon instead of oxygen. Note with no substituents; no overall reaction. Again only E (trans) alkenes formed

Sigmatropic Rarrangement

[2,3]-Sigmatropic Rearrangements
Proceeds via a 5 membered transition state Requires negative charge for 6 electron movement

Sigmatropic Rarrangement

[2,3]-Sigmatropic Rearrangements

Again E (Trans) favoured due to nature of transition state (not going to cover here)

Sigmatropic Rarrangement

[1,5]-Sigmatropic Hydrogen Shifts

Electrocyclic Reactions

Electrocyclic Reactions
Only one sigma bond formed across conjugated system, loss of one pi bond.

Electrocyclic Reactions

Exceptions
Expect Anti-Aromatic transition state so this should not happen?

Electrocyclic Reactions

Nazarov Cyclisation

Carbocation Rearrangements

Carbocation Rearrangements

More Alkyl Substituents = More Stable

Carbocation will rearrange to give an alternative more thermodynamic cation by adding substituents wherever possible

Carbocation Rearrangements

Carbocation Rearrangements

Driven by thermodynamics

Wagner-Meerwein Rearrangements

Carbocation Rearrangements

Carbocation Rearrangements

Pinacol Rearrangement

Carbocation Rearrangements

Choice of Migrating Group

Carbocation Rearrangements

Unsymmetrical Diols

Carbocation Rearrangements

Dienone-Phenol Rearrangement

Again, phenyl has right of way against methyl.

Carbocation Rearrangements

Beckmann Rearrangement

Carbocation Rearrangements

Beckmann Rearrangement

Carbocation Rearrangements

Beckmann Rearrangement

Anionic Rearrangements

Benzillic Acid Rearrangement

Related to Pinacol Rearrangement

Anionic Rearrangements

Favorskii Rearrangement
Similar to Benzillic Acid Rearrangement

Anionic Rearrangements

Favorskii Rearrangement

Ring Contraction method

Anionic Rearrangements

Baeyer-Villiger Reaction
Very Important Migration to Oxygen

Anionic Rearrangements

Baeyer-Villiger Reaction
Preference of Migrating Group

The group that is more able to stabilise a positive charge has right of way. Phenyl has right of way due to cyclopropane intermediate Stereochemistry is retained during reaction