Aldehydes & Ketones Continued (Chapter 18)

The reversible conversion of an aldehyde/ketone to an enol via α-Hydrogen rearrangement and π-electron transfer.

Tautomerization This reversible tautomerization process can occur in acidic conditions and basic conditions.

Base-Catalyzed Deprotonation Removal of the α-Hydrogen and subsequent π-electron transfer (C=O→C=C) yields the enolate ion.

A compound containing an alcohol group (—OH) adjacent to an alkene group (C=C). One carbon atom of the alkene is bonded to the alcohol group subsituent.

An anionic compoundcontaining an alkoxide group (—O–) adjacent to an alkene group (C=C). One carbon atom of the alkene is bonded to the alkoxide group subsituent.

The α-Hydrogen is highly acidic (i.e. pKa = 16–21) Resonance stabilization of the deprotonated aldehyde/ketone compound (i.e. an enolate ion) promotes the dissocation of the C—Hα bond.

LDA Lithium Diisopropylamide

• Kinetic Control: At low temperatures, the base deprotonates the Iess hindered/substituted α-Hydrogen (to form the less stable enolate ion). • Thermodynamic Control: At room/high temperatures, the base deprotonates the more hindered/substituted α-Hydrogen (to form the more stable enolate ion). While the base is still more likely to initially depronate the less hindered/substituted α-Hydrogen at room/high temperatures (i.e. thermodynamic control), the reversibility of the deprotonation leads to the more stable enolate ion being the predominant product.

• Low Temperatures • Short Reaction Times • Unreversible The less stable product isomer is the major product.

• Room/High Temperatures • Long Reaction Times • Reversible The more stable product isomer is the major product.

An enol is the less stable isomer of an aldehyde/ketone. In the presence of acid or base, the enol will tauteromize to the more stable aldehyde/ketone isomer.

2°/3° Enol Tautomerization

0°/1° Enol Tautomerization

Hg(II)-Catalyzed Hydration An enol intermediate is formed (but NOT observed) following alcohol-addition and prior to ketone-yielding tautomerization.

Hydroboration Oxidation An enol intermediate is formed (but NOT observed) following alcohol-addition and prior to aldehyde-yielding tautomerization.

HgSO4, H2O, H2SO4

• BH3 • H2O2, NaOH

• Deprotonation of the α-Hydrogen (and subsequent π-electron transfer) to yield the Enolate ion. • Protonation of the aldehydic/ketonic Oxygen to yield the Enol. Product = Enol

• Protonation of the aldehydic/ketonic Oxygen to yield the oxocarbenium ion. • Deprotonation of the α-Hydrogen (and subsequent π-electron transfer) to yield the Enol. Product = Enol

• Deprotonation of the enolic alcohol group (—OH) to yield the enolate ion. • π-electron rearrangement to yield the anionic α-Carbon aldehyde/ketone. • Protonation of anionic α-Carbon to yield the (nonionic) aldehyde/ketone. Product = Aldehyde/Ketone

• Protonation of the enolic alkene group (at the α-Carbon) AND transfer of π-electrons from Oxygen lone pair to Carbon-Oxygen bond (C=O) to yield the oxocarbenium ion. • Depronation of oxocarbenium Oxygen yield the (nonionic) aldehyde/ketone. Product = Aldehyde/Ketone

All α-Hydrogens of an aldehyde/ketone are replaced with Deuterium isotopes. The acidic α-Hydrogens are the ONLY hydrogen atoms replaced with Deuterium isotopes.

D2O (Excess), OD–

Isomerization of Aldehydic/Ketonic α-Stereoisomer The isomerization reaction yields (1) the* reagent α-Isomer* and (2) its α-Stereoisomer.