Umpolung Reactivity Flashcards
What is natural polarity
- Certain functional groups have an innate polarity which dictates which synthons you can and can’t use
What is the innate polarity of ketone and what does it mean about synthons
- Delta negative on oxygen
2. So synthon which is positive on carbon matches natural polarity
What happens to natural polarity in a conjugated system
- Alternating delta + and - atoms
2. If synthon matches it is a good synthon
What does umpolung reactivity refer to and give example with ketone
- Reactivity that goes against the natural polarity
- In case of ketone this would be using a reagent corresponded to the synthon with a negative charge on the carbonyl carbon
Why is umpolung reactivity useful for ketones
- Allows you to build up any ketone by nucleophilic substitution
What is a dithiane and how can it be used
- 6 membered Cyclic with two sulfur atoms and carbon atom in between
- The carbon in between the two sulfur atoms has acidic protons on it
- So you can deprotonate and alkylate- you can do this twice
- Then unmask the ketone to give the desired product
What is used to unmask the ketone from a dithiane
- Hg(ClO4)2 + H2O
What else can dithiane be used for
- Protecting the latent carbonyl from nucleophilic attack
2. Similar to ketal but with sulfur instead of oxygen
What is the difference in reactivity between a ketal and dithiane
- The acidic position that can be deprotonated and alkylated - can’t do with acetal or ketal
- Different methods for installation and removal
What are the different methods of installation for acetal/ketal compared to dithiane
- Sulfur is much softer than oxygen, so installation and removal of a diathine is catalysed best by soft lewis acids (Hg2+)
- Installation and removal of an acetal/ketal is catalysed by Bronsted acids (H+)
Give 3 examples of Lewis acids
- TiCl4
- BF3
- Zn(OTf)2
What are the problems with using Hg and water to remove dithiane
- Mercury salts are toxic
Which methods are preferred for dithiane removal
- methods based on oxidation or alkylation of the sulfur are often used
- Silver salts
- Iodine, N-chlorosuccinimide, N-bromosuccinimide - but would add to alkenes
- Produce a ketone
What is another method of dithiane removal that doesn’t produce a ketone
- hydrogen over Raney-nickel
2. Very good at cleaving C-S bonds so doesn’t give ketone but instead removes the dithiane without trace
What is relationship between ketals and dithianes
- They are orthogonal meaning you can install or take off one without affecting the other
What does 1,3-dithiane correspond to
- It can be alkylated in the 2-position twice
2. Corresponds to a dianioninc carbonyl system
How can a dithiane be used to access a 1,2 dicarbonyl
- Add BuLi to 2 position
- Then can add ketone which adds as alcohol
- Then remove dithiane with Hg(ClO4)2
- Then oxidise alcohol
How can a dithiane be used to access a 1,4-dicarbonyl
- Michael addition to an enone
- Add nBuLi to dithiane
- Then add alpha, beta unsaturated carbonyl
- Then remove dithiane with AgNO3
How can 1,3-dicarbonyls be accessed
- Addition of base to ketone to form enolate
- Add onto different ketone which becomes alcohol
- Oxidation by TPAP, NMO to form dicarbonyl
How can 1,5-dicarbonyls be accessed
- A vinylogous aldol can be used- Michael addition of an enolate
How can you access 1,6-dicarbonyl
- Ozonize a cyclic alkene with 6 carbons in it- O3, PPh3
What would be retrosynthesis sequence from a 1,6-dicarbonyl
- 1,6-dicarbonyl (FGI, Ozonolysis) –> cyclohexene (FGI Diels-Alder)–> diene + dienophile
What is ozonolysis
- Turns alkene into two carbonyls
