When an aldehyde and a hydroxide react, an ____ is established

Equilibrium

Why is there no quantitative deprotonation on aldehydes and hydroxides reacting?

Water and alpha-hydrogens are similarly acidic

When aldehyde and hydroxide react, what form exists in basic solution?

Both Keto and Enol

What happens when an enol (or enolate) reacts w/ its own keto form? What is the rxn called?

- Substrate is both nucleophile and electrophile - Self-addn rxn

What are the products of self-addn rxns called?

Beta-hydroxy aldehydes (or ketone) - Aldol

Under basic conditions, what is the nucleophile and electrophile?

- Enolate (Nu) will add into carbonyl carbon of aldehyde/ketone (E+)

What happens when basic aldol conditions are heated up?

Loss of beta-hydroxyl group = alpha,beta-unsaturated aldehyde/ketone

Is the elimination step after heating reversible or irreversible?

Irreversible

What is usually the product under normal acidic conditions for aldol formation?

Alpha,beta-unsaturated aldehyde

What happens when you use ketones for aldol chemistry?

Products are sterically hindered tertiary alcohols - Unstable

With basic conditions, hindered substrates favour ______

Retro aldol rxn

With acidic conditions, ________ is promoted and ketones can be used to access alpha,beta-unstaurated ketones

Elimination

Describe the claisen-schmidt rxn

Combining aldehyde w/ no alpha-hydrogens w/ a ketone to get only ONE product

What should be used during a directed aldol rxn?

- LDA, THF, -78 against ketone - Aldehyhde + H2O against enolate

When Nu and E+ are n same substrate, ____________ will occur

intramolecular cyclization

What does the claisen condensation produce?

beta-ketoester from esters

What must the base be in a claisen condensation?

Alkoxide base that matches alkoxy portion of ester

Is the final step of claisen condesnation reversible or irreversible? What is the final step?

- Irreversible - Deprotonation

Esters that only have ___________ will NOT undergo claisen condensation

One alpha hydrogen

Why cant esters with one alpha hydrogen undergo claisen condensation?

Once the addn occurs, there will be no potential for formation of second enolate

What are alpha,beta-electrophiles?

Compounds that have a DB in conjugation w/ C=O

How many places of attack are there for alpha,beta-E+?

2

What is regioselectivity?

Preference for a rxn (bond formation) to take place at one reactive site over another

When charges are closer together, resonance is a _______ contributer

Stronger

For a Nu, what are strong bases?

RMgX, RLi, Hydrides (H-)

For Nu, what are the weak bases?

H2O, ROH, RSH, RPH2, stabilized enolates

Nu with a negative charge will react w/ most ____ charged E+

Positively - 1,2 addn

Neutral Nu will react w/ ____ E+

Weaker - 1,4 Addn

What are the weakest bases?

RNH2, R2NH, CN, unstabilized enolates

Describe kinetic products

- Low temps - Formed quickest - Lowest activation energy - 1,2 addn

Describe thermodynamic products

- High temps - Formed most stable products - 1,4 addn

Describe the michael addn

1,4 addn of enolate (Nu) anion to alpha,beta-unsaturated E+

What is the best anion for michael addns?

1,3-dicarbonyl compounds

What are tandem rxns?

Use stable intermediates formed from one rxn as substrates in a second rxn

Describe the robinson annulation

Conjugate addn followed by intramolecular aldol condensation to form a new ring

An alpha,beta-unsaturated ketone undergoes a ______ addn using an enolate as the Nu during the robinson annulation

1,4

What cannot undergo a robinson annulation?

alpha,beta-unsaturated esters, amides, nitriles, or phenyl ketones