March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th Edition (2013)

Chapter 6. Mechanisms and Methods of Determining Them

6.E. The Baldwin Rules For Ring Closure¹⁷

In previous sections, the kinetic and thermodynamic aspects of ring-closure reactions were discussed in a general way. J.E. Baldwin¹⁸ supplied a more specific set of rules for certain closings of three seven-membered rings. These rules distinguish two types of ring closure, called exo and endo, and three kinds of atoms at the starred positions: Tet for sp³, Trig for sp², and Dig for sp. The following are Baldwin's rules for closing rings of 3–7 members.

Rule 1. Tetrahedral systems

a. 3-7-Exo–Tet are all favored processes

b. 5-6-Endo–Tet are disfavored

Rule 2. Trigonal systems

a. 3-7-Exo–Trig are favored

b. 3-5-Endo–Trig are disfavored¹⁹

c. 6-7-Endo–Trig are favored

Rule 3. Digonal systems

a. 3-4-Exo–Dig are disfavored

b. 5-7-Exo–Dig are favored

c. 3-7-Endo–Dig are favored

“Disfavored” does not mean it cannot be done, only that it is more difficult than the favored cases. These rules are empirical and have a stereochemical basis. The favored pathways are those in which the length and nature of the linking chain will enable the terminal atoms to achieve the proper geometries for reaction. The disfavored cases require severe distortion of bond angles and distances. Many cases in the literature are in substantial accord with these rules, and they are important in the formation of five- and six-membered rings.²⁰

Although Baldwin's rules can be applied to ketone enolates,²¹ additional rules were added to make the terminology more specific.²² The orientation of the orbital as it approaches the reactive center must be considered for determining the correct angle of approach. Diagrams that illustrate the enolate rules are shown.

The rules are

a. 6–7 enolendo–exo–tet reactions are favored

b. 3–5 enolendo–exo–tet reactions are disfavored

c. 3–7 enolexo–exo–tet reactions are favored

d. 3–7 enolexo–exo–trig reactions are favored

e. 6–7 enolendo–exo–trig reactions are favored

f. 3–5 enolendo–exo–trig reactions are disfavored