BaldwinsRules RAJ 3

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S. RAJKUMAR 28.02.2012 
Baldwin’s Rules 
 
• Prof. J. E. Baldwin – 1976 
 
• Qualitative set of generalization on the probability of 
a ring closure (RC) 
 
• Empirical « rules » formulated from observations and 
stereoelectronic reasoning 
 
• Describe kinetic feasibility of ring closure 
 
• Physical basis lie in stereochemical 
 
• The rules do not apply to second row elements and to 
pericyclic reactions 
Terminology/Classification (1) 
• Prefix exo when the 
breaking bond is 
exocyclic to the 
smallest ring formed. 
 
 
• Prefix endo when the 
breaking bond is 
endocyclic to the 
smallest ring formed. 
Terminology/Classification (2) 
• Numerical prefix describe the size of formed ring. 
 
• Sufixes Tet, Trig and Dig indicate the geometry of 
the carbon undergoing the RC. 
• Tetrahedral for sp3 carbon 
• Trigonal for sp2 carbon 
• Digonal for sp carbon 
 
Rules for Ring Closure (1) 
• Tetrahedral Systems 
• 3 to 7-exo-Tet are all favoured processes 
• 5 to 6-endo-Tet are disfavoured 
 
 
Rules for Ring Closure (2) 
• Trigonal systems 
• 3 to 7-exo-Trig are all favoured processes 
• 3 to 5-endo-Trig are disfavoured; 6 to 7-endo-Trig are 
favoured 
 
 
 
Rules for Ring Closure (3) 
• Digonal Systems 
• 3 to 4-exo-Dig are disfavoured processes; 5 to 7-exo-
Dig are favoured 
• 3 to 7-endo-Dig are favoured 
 
Other Than Nucleophilic Cases 
• Radical Processes 
(homolitic): 
 
 
 
 
• Cationic Processes: 
Attack Trajectories 
• Favoured paths to transition states are: 
Tetrahedral Systems 
Trigonal Systems 
Digonal Systems 
Favoured and Disfavoured 
• Favoured RC will be those in which length and 
nature of linking chain enables terminal atoms to 
achieve required trajectory to form final ring bond 
 
 
• Disfavoured RC would require severe bond angle 
and distances distortion, so the desired RC will be 
difficult (if available, alternative pathways will 
dominate) 
 
 
Tetrahedral carbon (1) 
• All exo-Tet cyclisations are favoured 
 
 
 
Trigonal Carbon (1) 
• All exo-Trig cyclisations are favoured 
Trigonal Carbon (2) 
• Example of disfavoured 5-endo-Trig 
Trigonal Carbon (3) 
• 5-endo-Trig versus 5-exo-Trig 
Trigonal Carbon (4) 
• 5-endo-Trig exceptions : 
Trigonal Carbon (5) 
• 5-endo-Trig versus 5-exo-Trig; Nitrogen analogue 
Trigonal Carbon (6) 
• 5-endo-Trig versus 5-exo-Trig; Nitrogen 
analogue (MO explanation) 
Digonal carbon 
• All endo-Dig cyclizations are favoured 
• 3- and 4-exo-Dig cyclisations are disfavoured 
Intramolecular Alkylations of 
Ketone Enolates (1) 
• Endocyclic alkylations 
• Exoclyclic alkylations 
• 6- to 7- membered RC 
 Favoured 
• 3- to 5- membered RC 
 Disfavoured 
• 3- to 7- membered RC 
 Favoured 
Intramolecular Aldol 
Condensations (1) 
• Endocyclic reactions 
• Exoclyclic reactions 
• 3- to 7- membered RC 
Favoured 
• 3- to 5- membered RC 
Disfavoured 
• 6- to 7- membered RC 
Favoured 
Stereoelectronic Constraints 
O
Y
O
Y
C alkylations
C alkylations
180° attack
109° attack
Intramolecular alkylations 
of ketone enolates 
Intramolecular aldol 
 condensations 
O alkylations O alkylations
Intramolecular Alkylations of 
Ketone Enolates (1) 
• Why 5-(Enolendo)-exo-tet disfavoured? 
Intramolecular Alkylations of 
Ketone Enolates (2) 
• Why 6-(enolendo)-exo-tet favoured? 
Intramolecular Aldol 
Condensations (2) 
Statistics : 4 possibilities to form a 5 membered ring 
 2 possibilities to form a 6 membered ring 
Previsions : 6 membered ring would be predominant or exclusive 
6-(enolendo)-exo-trig versus 5-(enolendo)-exo-trig 
Intramolecular Aldol 
Condensations (3) 
Formation of cyclohexanone totally dominates over even statistically 
preferred cyclopentanones production. 
Conclusion 
• Only give information about whether processes are 
favoured or disfavoured and not allowed and 
forbidden. 
 
• Nucleophilic RC feasibility strongly depends on ring 
size, geometry of reacting atom and exo or endo 
nature of reaction. 
 
• Structural modification can dramatically affect the 
cyclization mode. 
 
• If favoured trajectory of attack valid, then reaction 
will follow the Baldwin’s rules. 
 
 
Summary (1) 
Size Exo Endo 
Tet Trig Dig Tet Trig Dig 
3   X X  
4   X X  
5    X X  
6    X   
7      
Summary (2) 
Exo-Tet Exo-Trig 
Size enolendo enolexo enolendo enolexo 
3 X  X  
4 X  X  
5 X  X  
6     
7     
References 
• J. E. Baldwin, J. Chem. Soc., Chem. Commun. 1976, 734. 
• J. E. Baldwin, J. Cutting, W. Dupont, L. Kruse, L. Silberman, R. C. 
Thomas, J. Chem. Soc., Chem. Commun. 1976, 736. 
• J. E. Baldwin, R. C. Thomas, L. Kruse, L. Silberman, J. Org. Chem, 
1977, 42, 3846. 
• J. E. Baldwin, L. Kruse, J. Chem. Soc., Chem. Commun. 1977, 233. 
• J. E. Baldwin, M. J. Lusch, Tetrahedron, 1982, 38, 2939. 
• C. D. Johnson, Acc. Chem. Res. 1993, 26, 476. 
• J. Clayden, N. Greeves, S. Warren, P. Wothers, Oxford, chapter 
42, p 1140. 
• D. A. Evans, internet course. 
 
 
 
 
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