Wk1: Chiral method 3

What is organocatalysis?

Use of a substoichiometric amount of an organic molecule (no metal) to increase reaction rate.

What does substoichiometric mean?

Less than 1 equivalent of catalyst (e.g., 0.2 equiv = 5 turnovers).

What is the most famous organocatalyst for aldol reactions?

(S)-proline.

What yield and ee are achieved in the proline-catalysed aldol with acetone?

97% yield, 96% ee.

What is the key feature of a chiral auxiliary strategy?

Attach chiral auxiliary to starting material, do diastereoselective reaction, then remove auxiliary to get single enantiomer. Can be recycled.

What natural products are chiral auxiliaries often derived from?

Amino acids.

In Evans auxiliary, why does the electrophile attack from the top face?

Bottom face is shielded by the isopropyl group.

What is the difference between enantiocontrol and diastereocontrol?

Enantiocontrol = ee (one enantiomer over other). Diastereocontrol = de (one diastereomer over other).

Why are epoxides reactive with nucleophiles?

Ring strain (60° bond angles instead of 109°).

What reagent is most commonly used for epoxidation of alkenes?

m-CPBA (meta-chloroperoxybenzoic acid).

Is peracid epoxidation stereospecific or stereoselective?

Stereospecific: cis-alkene → cis-epoxide, trans-alkene → trans-epoxide.

What is the stereochemical outcome of Sₙ2 attack on an epoxide?

Inversion (nucleophile attacks from rear, trans product).

Who won the 2001 Nobel Prize for stereoselective oxidations?

Barry Sharpless.

What three reactions did Sharpless win the Nobel Prize for?

Epoxidation, dihydroxylation, aminohydroxylation.

What type of alcohol is required for Sharpless Epoxidation?

Allylic alcohol (C=C–CH₂OH).

What are the three components of Sharpless Epoxidation catalyst system?

Ti(OiPr)₄ (titanium tetraisopropoxide), diethyl tartrate (DET), TBHP (oxidant).

How does the choice of DET enantiomer control epoxidation face?

(–)-DET → epoxidation from top face. (+)-DET → epoxidation from bottom face.

What does Sharpless Dihydroxylation do?

Converts alkene to a vicinal diol (two OH groups) with high enantioselectivity.

What metal is used in Sharpless Dihydroxylation?

Osmium tetroxide (OsO₄) – catalytic with chiral ligand.

What are the two common chiral ligands in Sharpless Dihydroxylation?

DHQ and DHQD (dihydroquinine / dihydroquinidine).

What does DHQ ligand do in Sharpless Dihydroxylation?

Directs dihydroxylation from below the alkene face.

Name four methods to obtain a single enantiomer from the past 3 lectures.

Asymmetric hydrogenation (BINAP + Ru/Rh), Mitsunobu inversion, organocatalysis (proline), Sharpless epoxidation/dihydroxylation, kinetic resolution, diastereomeric salts, Evans auxiliary.

What is the difference between stereospecific and stereoselective?

Stereospecific: different stereoisomers of starting material give different stereoisomers of product (e.g., cis/trans alkene → cis/trans epoxide). Stereoselective: one product stereoisomer is favoured over another from a single starting material.