CM2121: Diastereoselectivity

Reference:
Organic Chemistry, 2nd ed., by Clayden, Greeves and Warren
Chapter 33

Lecture Notes prepared by Dr. Hoang T. Giang

Outline
1. Stereospecific and Stereoselective Reactions

2. Prochirality

3. Diastereoselectivity: Addition to Carbonyl Groups

4. Diastereoselectivity: Aldol Reactions

Reference: - Clayden 2nd ed. Chapter 33

2
1. Stereospecific and Stereoselective Reactions
• Enantiomers and diastereomers
• Enantioselective reactions

O "H-" HO H H OH
+
Ph Ph Ph

• Diastereoselective reactions
O "H-" HO H H OH
+
Ph Ph Ph

3
1. Stereospecific and Stereoselective Reactions

Examples of stereospecific reactions:

4
1. Stereospecific and Stereoselective Reactions
• Making single diastereomer using stereospecific reactions

• Stereoselective reations

5
2. Prochirality
• Reacting centers that are not stereogenic (or chiral) centers but can be
made into them are called prochiral

• Carbonyl group or double bond

• Tetrahedral carbon atom

6
2. Prochirality - naming
• Tetrahedral carbon atom: pro-R or pro-S

7
2. Prochirality - naming
• Trigonal carbon center: Re face or Si face

8
3. Additions to carbonyl groups
O HO H H OH
EtMgBr +
Ph Ph Ph
H

O HO H H OH
Ph EtMgBr Ph + Ph
H

- A chiral center at the alpha carbon can influence the stereochemical

outcome of a nucleophilic addition to the carbonyl group

9
3. Additions to carbonyl groups

- Conformational analysis: stable conformation: the large group is

perpendicular to the carbonyl group

10
3. Additions to carbonyl groups
Nucleophilic addition to a carbonyl group

Bürgi-Dunitz angle

Felkin – Anh model

11
3. Additions to carbonyl groups

12
3. Additions to carbonyl groups
Felkin – Anh model:

13
3. Additions to carbonyl groups

14
3. Additions to carbonyl groups
Felkin – Anh model:
Case 2: The effect of electronegative atoms

The electronegative atom “acts” as the largest group

15
3. Additions to carbonyl groups
Felkin – Anh model:
Case 3: Chelation

16
3. Additions to carbonyl groups
Felkin – Anh model: Case 3: Chelation

17
3. Additions to carbonyl groups
Felkin – Anh model:

18
4. Aldol reactions: syn and anti aldol product
Generally, in aldol reactions:

Formation of cis- or trans-enolate

19
4. Aldol reactions: transition states

20
4. Aldol reactions: transition states

21
4. Aldol reactions: transition states

22
4. Aldol reactions: making E/Z enolate

Boron enolates

23