Week 2: Protecting groups Flashcards
Explain if the kinetic or thermodynamic product will form
Initially a reaction will follow the kinetic pathway. But if there is enough energy for the kinetic product to get back to the starting material, then there is enough energy for the thermodynamic product to be formed.
Kinetic formed reversibly
Thermodynamic formed irreversibly
What is kinetic and thermodynamic chemoselectivity
Kinetic chemoselectivity: Where one functional group reacts quicker than the other
Thermodynamic chemoselectivity: Where the most stable product predominates
Outline the staggered and eclipsed conformations
Eclipsed: higher in energy, substituents in same place in Newman projection
Staggered: low in energy, substituents are as far away from the substituents on next carbon
What are anti- and syn- periplanar
Anti-periplanar: where large substituents are furthest away between 2 carbons
Syn-periplanar: where the large substituents are in same position between 2 carbons
What does a ring invert/flip do
Switches all axial to equatorial and vice versa
Protecting a carbonyl group
Acetyl protecting groups
protects a ketone or aldehyde by forming an acetal (dioxolane)
Unstable in acidic conditions but stable in basic. So acid removes
List the protecting groups for protecting a hydroxyl
Silyl
THP
Benzyl ether
Methyl ether
Explain Silyl protecting group
Leaving group leaves to bond to O of OH as O forms strong bond with Si.
Could use a trialkylsilyl but TMS is too labile and can be easily removed with methanol or water in the reaction. TBDMS is best as it is bulkier.
Imidazole is also needed to deprotonate the O on bonding to Si.
Remove by either using F- as F forms stronger bond with Si or with acid in solution as it protonates the O causing it to leave the Si.
Explain THP protecting group
Acts basically as an acetal (O-C-O) so is stable in base but not in acid.
Made by reacting dihydropyran in acid to form a conjugated molecule with O+ allowing the O of the hydroxyl to react.
Explain benzyl ether protecting group
A benzyl with a C-halide attachment forms a benzyl ether with the hydroxyl (when in the presence of a base).
Removed by catalytic hydrogenation which must be a Pd/C catalyst as Pt would catalyse the aromatic ring.
Could also be removed by acid if the acid has a nucleophilic conjugate base (if not acid sensitive)
Explain methyl ether protecting group
Protect only a phenolic OH because ArOH is a much better leaving group than ROH.
Removed by a strong acid.
Explain Burgi-Dunitz trajectory
Angle of nucleophilic attack on aldehydes and ketones is 107º.
This is because the HOMO of the nucleophile needs to overlap with the LUMO of the carbon which is the pi* orbital (which are already on an angle)
Explain the conformations of nucleophilic addition to a cyclic carbonyl group
Big substituents: prefer to be equatorial, lock chair structure so mostly equatorial forms
Big nucleophiles (hydride sources): can only fit into reduce carbonyl from equatorial direction so H will end up axial. A small nucleophile will do the opposite.
Difference between stereospecific and stereoselective reactions
Stereospecific: stereochemistry of reactant determines stereochemistry of product, no choice.
Stereoselective: one stereoisomer is formed predominantly, reaction has a choice of pathways
Explain prochirality and diastereotoppc and enantiotopic faces
Prochirality: trigonal carbons that can be made into a chiral centre
Diastereotoppc faces: starting material where there are 2 chiral centres in the product, thus can form diastereoisomers
Enantiotopic faces: starting materials where there is only has 1 chiral centre so only can form enantiomers
