Stereocontrolled Synthesis Flashcards
Give an overview of organo-boron reagents.
Give an overview of organo-silicon reagents.
Give an overview of organo-sulfur reagents.
- Sulfur can exist in a number of oxidation states.
What is the Julia reaction?
Draw a reaction scheme for the formation of the product.
The formation of an E-alkene from a sulfone.
The E-alkene is always formed in a Julia reaction. Why?
An anion intermediate is formed which lives long enough for rotation about the C-C bond. Elimination takes place from the least sterically hindered anti-periplanar alignment to give the E-alkene.
What is the Kocienski modification and why was it developed?
Conditions of the Julia reaction are harsh therefore this method was developed, using a tetrazole functionalised sulfone.
What is the Peterson reaction?
Name two ways that the starting material can be made.
Formation of E or Z alkenes using a beta-hydroxy silane.
A beta-hydroxyl silane can be formed from:
- Vinyl silanes
- Metal-halogen exchange
Show how beta-hydroxyl silanes can be formed from vinyl silanes.
Show how beta-hydroxyl silanes can be formed from metal-halogen exchange.
Beta-hydroxy silanes can be converted into alkenes by acid or base in the Peterson reaction.
Draw the mechanism for the acid-promoted reaction.
Beta-hydroxy silanes can be converted into alkenes by acid or base in the Peterson reaction.
Draw the mechanism for the base-promoted reaction.
Draw the mechanism for the conversion of an E-vinyl silane / Z-vinyl silane to an alkene via electrophilic substitution.
Substitution occurs with retention of double bond geometry.
Draw the mechanism for electrophilic additions to allyl silanes.
This forms a beta-carbocation which undergoes loss of Me3Si+.
The electrophile attacks ANTI to silicon.
Draw the reaction between an allyl silane and an aldehyde via electrophilic addition.
There is very little stereocontrol at the new hydroxyl stereocentre.
What can be used in place of an allyl silane when adding to an aldehyde to allow for stereocontrol?
Allyl boranes.
As the lone pairs on the carbonyl oxygen can donate into the empty p-orbital on boron, a closed cyclic transition is possible and this leads to excellent levels of stereocontrol.
Draw the mechanism for the addition of an E/Z-allyl borane to an aldehyde.
- E-allyl boranes give anti-homoallylic alcohol products
- Z-allyl boranes give syn-homoallylic alcohol products
Why are homoallylic alcohol product useful?
They can be converted into aldol products.
What can be used to generate aldol products directly?
Boron enolates.
They allow for control over syn/anti-diastereoselectivity.
Draw the mechanism for the reaction of an E-boron enolate with an aldehyde.
Draw the mechanism for the reaction of a Z-boron enolate with an aldehyde.
Draw the mechanism for the formation of a 1,2,3-stereotriad from an E-boron enolate.
The enolate attacks the aldehyde over the smallest group, i.e. Felkin-Anh addition.
Draw the mechanism for the formation of a 1,2,3-stereotriad from a Z-boron enolate.
How does the mechanism for the formation of a 1,2,3-stereotriad from a Z-boron enolate change when there’s a syn-pentane interaction?
Draw the mechanism for the formation of an anti-1,3-diol.
Draw the mechanism for the formation of syn-1,3-diol.
Explain axial vs. equatorial preference in hydride reductions for cyclohexane.
Draw how the two types of sulfur ylides are formed.
What is formed from the addition of a sulfur ylide to a ketone?
What differentiates the two types of sulfur ylides upon addition to a cyclic ketone?
Addition of the sulfonium ylide reflects the preference of axial addition for small nucleophiles. Addition of sulfoxonium ylide is reversible and fast compared to the ring closing step, leading to the formation of the thermodynamic product.
Describe the chemoselectivity of sulfur ylide addition to enones.
Harder, unstabilised sulfonium ylide reacts with the hard C=O.
Softer, stabilised sulfoxonium ylide reacts with softer C=C.
