1. Baldwin’s Rules
Nadia Fleary-Roberts
02/05/12

2. Baldwin’s rules for ring closure
Proposed in 1976 by Sir Jack Baldwin
Guidelines for ring closing reactions of 3- to 7-membered rings-
empirical rules derived from experimental observations
J. Chem. Soc. Chem. Commum., 1976,
Advanced organic chemistry, March p 212
Clayden 1st Edn p nd Edn p 810
Dr. F. Pradaux, Sheffield University

3. Nomenclature 1. Ring size 3, 4,......7
Number Indicates the size of the ring being formed

4. Nomenclature
2. Bond
The bond broken as the ring is formed is outside the new ring
The bond broken as the ring is formed is inside the ring

5. Nomenclature 3. Geometry
geometry of the carbon undergoing the ring closing can be describes as:
sp tetrahedral carbon tet
sp2 trigonal carbon trig
sp digonal carbon dig

6. For example.....

7. Reactions can be favoured or disfavoured
kinetic favourability of a reaction
A disfavoured reaction does not mean that the reaction will not occur -just that it is more difficult
Disfavoured cases require severe distortion of bond angles and distances

8. Ideal bond angles
Favoured cyclisations enable terminal atoms to achieve proper geometries
Trigonal carbons
(Bürgi-Dunitz)
Tetrahedral carbons
(Walden inversion)
Digonal carbons

9. Tetrahedral systems
all exo-tet cyclisations are favoured

10. Trigonal systems All exo-trig cyclisatons are favourable
5-endo trig are disfavoured!

12. Favoured exo-tet and exo-trig

13. Disfavoured 5-Endo-trig

14. Disfavoured 5-Endo-trig...iodocyclisation
Iodocyclisation forms the disfavoured “anti-Baldwin” endo-trig product
WHY?
Overwhelming attraction between nucleophile and electrophile
No kinetically favoured alternative pathways- 4-exo-tet would be too strained
Knight et.al. Tetrahedron Lett. 1998, 39, 8909

15. however
5-exo-trig strongly favoured over the 5-endo-trig

16. Digonal systems
All endo-dig are favoured

17. Endo-dig rationale
Alkyne has two π* orbitals-one in the plane of the ring

18. Disfavoured 3- and 4-exo-dig
Nucleophile cannot attack at the required 120° angle

19. Exceptions to the Baldwin’s rules
second row elements
Why?
Long C-S bond
Sulfur has empty 3d orbitals
cations

20. Summary
Size
Exo
Endo
Tet
Trig
Dig 3  X 4 5 6 7

21. Intramolecular endocyclic alkylation of ketone enolates
Nomenclature
enolexo or enolendo orientation of the enolate C-C bond
exo-tet or exo-trig with respect to the C-Y terminus
6 to 7 Favoured
3 to 5 Disfavoured
3 to 7 Favoured
Baldwin, Kruse, JACS Chem Commun. 1977, 233

22. Oxygen alkylation vs. Carbon alkylation
(Compare with disfavoured 5-endo trig)
(Compare with favoured 6-endo-trig)

23. Oxygen alkylation vs. Carbon alkylation
Oxygen alkylation -electrophile approaches in plane of the enolate
Carbon alkylation in 6-enolendo possible
Perpendicular approach to the enolate

24. Intramolecular aldol condensations
Favoured 3 to 7
disfavoured 3 to 5
favoured 6 to 7
Baldwin, Tetrahedron, 1982, 38, 2939

25. 5-enolendo-exo-trig vs. 6-enolendo exo-trig
6-enolendo-exo-trig exclusively formed.

26. Summary
Exo-Tet
Exo-Trig
Size
enolendo
enolexo 3 X  4 5 6 7

27. 1. Exo-tet and endo-trig favoured 2. 5-endo trig disfavoured*
Just remember.....
1. Exo-tet and endo-trig favoured
2. 5-endo trig disfavoured*
3. Endo-dig favoured
1. Enolexo endo-tet and trig are favoured
Endocyclic reactions

30. Other Than Nucleophilic Cases
Radical Processes (homolitic):
Cationic Processes: